Aromaticity is a special property of some chemical compounds, due to which the conjugated ring of unsaturated bonds exhibits abnormally high stability; greater than what would be expected with only one conjugation. Aromaticity is not directly related to the smell of organic compounds, and is a concept that characterizes the totality of structural and energetic properties of certain cyclic molecules containing a system of conjugated double bonds. The term "aromaticity" was proposed because the first representatives of this class of substances had a pleasant odor. The most common aromatic compounds contain six carbon atoms in the ring; the ancestor of this series is benzene C 6 H 6 . X-ray diffraction analysis shows that the benzene molecule is flat, and the length of the C-C bonds is 0.139 nm. It follows that all six carbon atoms in benzene are in sp 2-hybrid state, each carbon atom forms σ bonds with two other carbon atoms and one hydrogen atom lying in the same plane, bond angles are 120º. Thus, the σ-skeleton of the benzene molecule is a regular hexagon. Moreover, each carbon atom has a non-hybrid p-orbital located perpendicular to the flat skeleton of the molecule; all six are non-hybrid p-electrons interact with each other, forming π-bonds, not localized in pairs, but combined into a single π-electron cloud. Thus, circular conjugation occurs in the benzene molecule. Graphically, the structure of benzene can be expressed by the following formula:
Circular conjugation gives an energy gain of 154 kJ/mol - this value is conjugation energy - the amount of energy that must be expended to destroy the aromatic system of benzene.
To form a stable aromatic system it is necessary that p-electrons were formally grouped into 3, 5, 7, etc. double bonds; mathematically this is expressed Hückel's rule : cyclic compounds that have a flat structure and contain (4n + 2) electrons in a closed conjugation system, where n is a natural series of numbers, have increased thermodynamic stability.
31 . Electrophilic substitution reactions in benzene (halogenation, nitration, sulfonation, alkylation, acylation). An idea of the mechanism of electrophilic substitution reactions in the aromatic series, σ- and π-complexes.
Halogenation
To introduce a halogen into the aromatic ring, complexes of halogens with Lewis acids are used as reagents. The role of the latter is to polarize the halogen-halogen bond, as a result of which one of the atoms acquires a positive charge, while the other forms a bond with the Lewis acid due to its vacant d-orbitals.
Nitration
Benzene and its homologues are converted into nitro compounds by the action of a nitrating mixture, which consists of concentrated sulfuric and nitric acids (2:1). The nitrating particle (electrophile) is the nitronium cation NO 2 +, the existence of which in the nitrating mixture is proven by the cryoscopic method: measurements of the freezing temperatures of nitric and sulfuric acids and their mixture indicate the presence of four particles in the solution.
Sulfonation
The sulfonation reaction of arenes is believed to occur in oleum under the action of sulfur trioxide, and in sulfuric acid with the participation of the HSO 3 + cation. Sulfur trioxide exhibits electrophilic character due to the polarity of the S–O bonds.
Friedel-Crafts alkylation
One of the ways to obtain benzene homologues is the alkylation reaction. The transformation is named after S. Friedel and J. M. Crafts, who discovered it. As a rule, haloalkanes and aluminum halides are introduced into the reaction as catalysts. It is believed that the catalyst, a Lewis acid, polarizes the C-halogen bond, creating a deficiency of electron density on the carbon atom, i.e. the mechanism is similar to the halogenation reaction
Friedel-Crafts acylation
Similar to the alkylation reaction is the acylation reaction of aromatic compounds. Anhydrides or halides of carboxylic acids are used as reagents; aromatic ketones are the products. The mechanism of this reaction involves the formation of a complex between the acylating reagent and the Lewis acid. As a result, the positive charge on the carbon atom increases incomparably, making it capable of attacking the aromatic compound.
It should be noted that, unlike the alkylation reaction, in this case it is necessary to take an excess of the catalyst relative to the amount of reagents, because the reaction product (ketone) is itself capable of complexation and binds a Lewis acid.
Electrophilic substitution reactions of σ- and π-complexes characteristic of aromatic carbocyclic and heterocyclic systems. As a result of the delocalization of p-electrons in the benzene molecule (and other aromatic systems), the p-electron density is distributed evenly on both sides of the ring. Such shielding of the ring carbon atoms by p-electrons protects them from attack by nucleophilic reagents and, conversely, facilitates the possibility of attack by electrophilic reagents. But unlike the reactions of alkenes with electrophilic reagents, the interaction of aromatic compounds with them does not lead to the formation of addition products, since in this case the aromaticity of the compound would be disrupted and its stability would decrease. Preservation of aromaticity is possible if an electrophilic particle replaces a hydrogen cation. The mechanism of electrophilic substitution reactions is similar to the mechanism of electrophilic addition reactions, since there are general patterns of reactions.
General scheme of the mechanism of electrophilic substitution reactions S E:
The formation of a pi complex is due to the pi bond in the compound, and the sigma complex is formed due to the sigma bond.
Formation of a π-complex. The resulting electrophile X+ (for example, a Br+ ion) attacks the electron-rich benzene ring, forming a π-complex.
Transformation of a π-complex into a σ-complex. The electrophile takes 2 electrons from the π-system, forming a σ-bond with one of the carbon atoms of the benzene ring. Difference between pi and sigma bonds: A sigma bond is stronger, a sigma bond is formed by hybrid orbitals. A pi bond is formed by unhybridized pi orbitals. A pi bond is more distant from the centers of the atoms being connected, so it is less strong and easier to break.
32. Aromatic hydrocarbons. The influence of substituents in the benzene ring on the isomeric composition of the products and the reaction rate. Activating and deactivating substituents. Ortho-, para- and meta-orientators. Radical substitution and oxidation reactions in the side chain.
An essential feature of the reactions for the production and transformation of aromatic hydrocarbon derivatives is that new substituents enter the benzene ring in certain positions relative to existing substituents. The patterns that determine the direction of substitution reactions in the benzene ring are called orientation rules.
The reactivity of a particular carbon atom in the benzene ring is determined by the following factors: 1) the position and nature of the existing substituents, 2) the nature of the active agent, 3) the reaction conditions. The first two factors have a decisive influence.
Substituents on the benzene ring can be divided into two groups.
Electron donors (of the first kind) are groups of atoms capable of donating electrons. These include OH, OR, RCOO, SH, SR, NH 2, NHR, NR 2, NHCOR, -N=N-, CH 3, CH 2 R, CR 3, F, CI, Br, I.
Electron-withdrawing substituents (of the second kind) are atomic groups capable of withdrawing and accepting electrons from the benzene nucleus. These include S0 3 H, N0 2, CHO, COR, COOH, COOR, CN, CC1 3, etc.
Polar reagents acting on aromatic compounds can be divided into two groups: electrophilic and nucleophilic. The most common processes for aromatic compounds are alkylation, halogenation, sulfonation and nitration. These processes occur during the interaction of aromatic compounds with electrophilic reagents. Reactions with nucleophilic reagents (NaOH, NH 2 Na, etc.), for example, hydroxylation and amination reactions, are also known.
Substituents of the first kind facilitate reactions with electrophilic reagents, and they orient the new substituent in ortho- And pair- provisions.
Substituents of the second kind complicate reactions with electrophilic reagents: they orient the new substituent to the meta position. At the same time, these substituents facilitate reactions with nucleophilic reagents.
Let us consider examples of reactions with different orienting effects of substituents.
1. Deputy of the first kind; electrophilic reagent. The reaction-facilitating effect of the substituent, o-, p-orientation:
2. Deputy of the second kind; electrophilic reagent. The action of a substituent that hinders the reaction; m-orientation:
3. Deputy of the first kind; nucleophilic reagent; m-orientation. Obstructive action of the deputy. Examples of such reactions with an indisputable mechanism are unknown.
4. Deputy of the second kind; nucleophilic reagent, o-, p-orientation:
Orientation rules for electrophilic substitution in the benzene ring are based on the mutual influence of the atoms in the molecule. If in unsubstituted benzene C 6 H 6 the electron density in the ring is distributed evenly, then in substituted benzene C 6 H 5 X, under the influence of substituent X, a redistribution of electrons occurs and areas of increased and decreased electron density appear. This affects the ease and direction of electrophilic substitution reactions. The entry point of a new substituent is determined by the nature of the existing substituent.
Orientation rules
The substituents present on the benzene ring direct the newly introduced group to certain positions, i.e. have an orienting effect.
According to their directing action, all substituents are divided into two groups: orientants of the first kind And orientants of the second kind.
Orientants of the 1st kind ( ortho-para ortho- And pair- provisions. These include electron-donating groups (electronic effects of the groups are indicated in parentheses):
R ( +I); -OH( +M,-I); -OR ( +M,-I); -NH2( +M,-I); -NR 2 (+M,-I)+M-effect in these groups is stronger than -I-effect.
Orientants of the 1st kind increase the electron density in the benzene ring, especially on the carbon atoms in ortho- And pair-positions, which favors the interaction of these particular atoms with electrophilic reagents. Example:
Orientants of the 1st kind, increasing the electron density in the benzene ring, increase its activity in electrophilic substitution reactions compared to unsubstituted benzene.
A special place among the 1st kind orientants is occupied by halogens, which exhibit electron-withdrawing properties: - F (+M<–I ), -Cl (+M<–I ), -Br (+M<–I ).Being ortho-para-orientants, they slow down electrophilic substitution. Reason - strong –I-the effect of electronegative halogen atoms, which reduces the electron density in the ring.
Orientants of the 2nd kind ( meta-orientators) direct subsequent substitution predominantly to meta-position. These include electron-withdrawing groups:
NO 2 ( –M, –I); -COOH( –M, –I); -CH=O ( –M, –I); -SO3H ( –I); -NH 3 + ( –I); -CCl 3 ( –I).
Orientants of the 2nd kind reduce the electron density in the benzene ring, especially in ortho- And pair- provisions. Therefore, the electrophile attacks carbon atoms not in these positions, but in meta-position where the electron density is slightly higher. Example:
All orientants of the 2nd kind, generally reducing the electron density in the benzene ring, reduce its activity in electrophilic substitution reactions.
Thus, the ease of electrophilic substitution for the compounds (given as examples) decreases in the order:
toluene C 6 H 5 CH 3 > benzene C 6 H 6 > nitrobenzene C 6 H 5 NO 2.
Side chain radical substitution and oxidation reactions
The second most important group of reactions of alkyl aromatic hydrocarbons is free radical substitution side chain hydrogen atom in a-position relative to the aromatic ring.
Preferential substitution in a-position is explained by the high stability of the corresponding alkyl aromatic radicals, and therefore the relatively low strength a-C-H-bonds. For example, the energy of breaking the C-H bond in the side chain of the toluene molecule is 327 kJ/mol - 100 kJ/mol less than the energy of the C-H bond in the methane molecule (427 kJ/mol). This means that the stabilization energy of the benzyl free radical C 6 H 5 -CH 2 · is equal to 100 kJ/mol.
The reason for the high stability of benzyl and other alkyl aromatic radicals with an unpaired electron is a-carbon atom is the possibility of distributing the spin density of the unpaired electron in a non-bonding molecular orbital covering carbon atoms 1", 2, 4 and 6.
As a result of distribution (delocalization), only 4/7 of the spin density of the unpaired electron remains with the non-ring carbon atom, the remaining 3/7 of the spin density is distributed between one pair- and two ortho- carbon atoms of the aromatic nucleus.
Oxidation reactions
Oxidation reactions, depending on the conditions and nature of the oxidizing agent, can proceed in different directions.
molecular oxygen at a temperature of about 100 o C, it oxidizes isopropylbenzene via a radical chain mechanism to a relatively stable hydroperoxide.
33. Condensed aromatic hydrocarbons: naphthalene, anthracene, phenanthrene, benzopyrene. Their structural fragments in natural and biologically active substances (steroids, alkaloids, antibiotics).
Naphthalene - C 10 H 8 solid crystalline substance with a characteristic odor. Insoluble in water, but soluble in benzene, ether, alcohol, chloroform. Naphthalene is similar in chemical properties to benzene: it is easily nitrated, sulfonated, and interacts with halogens. It differs from benzene in that it reacts even more easily. Naphthalene is obtained from coal tar.
Anthracene is colorless crystals, melting point 218° C. Insoluble in water, soluble in acetonitrile and acetone, soluble in benzene when heated. Anthracene is obtained from coal tar. Its chemical properties are similar to naphthalene (it is easily nitrated, sulfonated, etc.), but differs from it in that it more easily enters into addition and oxidation reactions.
Anthracene can photodimerize under the influence of UV radiation. This leads to a significant change in the properties of the substance.
The dimer contains two covalent bonds formed as a result of cycloaddition. The dimer decomposes back into two anthracene molecules when heated or under UV irradiation with a wavelength below 300 nm. Phenanthrene is a tricyclic aromatic hydrocarbon. Phenanthrene appears as shiny, colorless crystals. Insoluble in water, soluble in organic solvents (diethyl ether, benzene, chloroform, methanol, acetic acid). Solutions of phenanthrene glow blue.
Its chemical properties are similar to naphthalene. Benzpyrene, or benzopyrene, is an aromatic compound, a representative of the family of polycyclic hydrocarbons, a substance of the first hazard class.
Formed during the combustion of hydrocarbon liquid, solid and gaseous fuels (to a lesser extent during the combustion of gaseous fuels).
In the environment it accumulates mainly in soil, less in water. It enters plant tissues from the soil and continues its movement further in the food chain, while at each stage the BP content in natural objects increases (see Biomagnification).
It has strong luminescence in the visible part of the spectrum (in concentrated sulfuric acid - A 521 nm (470 nm); F 548 nm (493 nm)), which allows it to be detected in concentrations up to 0.01 ppb by luminescent methods.
34. Halogen derivatives of hydrocarbons. Classification, nomenclature, isomerism.
Halogen derivatives can be classified in several ways:
1. in accordance with the general classification of hydrocarbons (i.e. aliphatic, alicyclic, aromatic, saturated or unsaturated halogen derivatives)
2. by the quantity and quality of halogen atoms
3. according to the type of carbon atom to which the halogen atom is attached: primary, secondary, tertiary halogen derivatives.
According to IUPAC nomenclature, the position and name of the halogen is indicated in the prefix. Numbering begins from the end of the molecule to which the halogen atom is closest. If a double or triple bond is present, then it is this that determines the beginning of the numbering, and not the halogen atom: The so-called “rational nomenclature” for compiling the names of halogen derivatives. In this case, the name is constructed as follows: hydrocarbon radical + halide.
Some halogen derivatives have trivial names, for example, the inhalation anesthetic 1,1,1-trifluoro-2-bromo-2-chloroethane (CF 3 -CBrClH) has the trivial name fluorotane. 3. Isomerism
3.1. Structural isomerism 3.1.1. Isomerism of substituent positions
1-bromobutane 2-bromobutane
3.1.2. Isomerism of the carbon skeleton
1-chlorobutane 2-methyl-1-chloropropane
3.2. Spatial isomerism
Stereoisomerism can occur when there are four different substituents on one carbon atom (enantiomerism) or when there are different substituents on a double bond, for example:
trans-1,2-dichloroethene cis-1,2-dichloroethene
35. Reactions of nucleophilic substitution of the halogen atom, their use in the synthesis of organic compounds of various classes (alcohols, ethers and esters, amines, thiols and sulfides, nitroalkanes, nitriles). - makes it possible to obtain representatives of almost all classes of organic compounds (alcohols, ethers, amines, nitriles, etc.), therefore these reactions are widely used in the synthesis of medicinal substances. Basic reaction mechanisms
Substitution of a halogen at an sp 3 -hybrid carbon atom can be carried out by both S N 1 and S N 2 mechanisms. The substitution of the halogen at the sp 2 -hybrid carbon atom (in aryl and vinyl halides) occurs either by the type of addition-elimination or by the type of elimination-addition and is much more difficult than for the sp 3 -hybrid. - S N 1 mechanism includes two stages: a) dissociation of alkyl halide into ions; b) interaction of a cation with a nucleophile Nucleophilic attack of a contact ion pair, in which the asymmetry is largely preserved, leads to a reversal of the configuration. In a solvate-separated ion pair, one side of the cation is shielded by the solvated halide ion and nucleophile attack is more likely on the other side, resulting in preferential configuration reversal, but selectivity is reduced and racemization is increased. Complete racemization is possible only with the formation of a free cation (c). However, complete racemization is not usually observed for optically active halides via the S N 1 mechanism. Racemization ranges from 5 to 20%, therefore, practically no solvated cation is formed.
The stage of carbocation formation is limiting, and, therefore, the stability of the cation determines the speed of the process. The rate of the process also depends on the concentration of the alkyl halide and is independent of the concentration of the nucleophile.
The formation of a carbocation can cause a number of side processes: isomerization of the carbon chain, elimination (EI), etc.
Nucleophile Nu - attacks the substrate from the side opposite to the leaving group. In this case, the reaction proceeds in one stage with the formation of a transition state in which sp 3 -hybridization of the central carbon atom changes to sp 2 - with a p-orbital perpendicular to the plane of location of the hybrid orbitals. One lobe of the etor orbital overlaps with the nucleophile, and the second with the leaving group. The C-Nu bond is formed simultaneously with the cleavage of the C-Y bond.
The rate of conversion of starting substances into reaction products depends on: 1) the magnitude of the positive charge on the carbon atom of the substrate, 2) spatial factors, 3) the strength of the nucleophile and 4) in the kinetic region, the concentration of both the nucleophile and the alkyl halide. With a large excess of nucleophile, the reaction can proceed in the first or fractional order. (The terms S N 1 and S N 2 indicate only molecularity, not the order of the reaction.)
The reaction is always accompanied by a reversal of the configuration. A side reaction may be the elimination of E2.
The S N Ar (addition-elimination) mechanism is usually realized in the presence of electron-withdrawing substituents that create d+ (direct the nucleophile) and stabilize the s-complex. In heterocycles, their role is played by the heteroatom. In contrast to the S N 2 mechanism for alkyl halides, the nucleophile forms a new bond before the old one breaks.
Pyridine and quinoline can be considered as analogues of nitrobenzene. As in nitrobenzene, the position of the halogen in the ring is of great importance. 3-Halopyridines are similar to halobenzenes, 2-,4-substituted ones are similar to nitrohalobenzenes, while 4-halopyridine is more active than 2-substituted. The reactivity of alkyl halides in nucleophilic substitution reactions in protic solvents decreases (the ability of groups to leave decreases) in the following order: RI > RBr > RCl > RF.
In the case of activated haloarenes, the appearance of a positive charge at the reaction center depends not only on the number, location and nature of other substituents in the nucleus, but also on the nature of the replaced halogen. Therefore, halogen atoms can be replaced with increasing ease in row I< Br < Cl < F .Катализ замещения галоген в аренах медью – один из важных технологических приемов, позволяющий ускорить реакцию замещения неактивированного галогена в аренах, снизить температуру реакции (~ на 100 о С), увеличить селективность процесса и выход продукта. Предполагают, что реакция идет через стадию образования медь-органических комплексов
Aromatic substrates (aryl halides) must be activated, otherwise the yield of the target product (ester) may be low due to side processes. The replacement of halogen in primary and secondary alkyl halides with an amino group is carried out by heating them with an alcoholic, aqueous or aqueous-alcoholic solution of ammonia, a primary or secondary amine under pressure (in an autoclave). This produces a mixture of salts of primary, secondary, tertiary amines and quaternary ammonium salts
1. The molecule has a flat cyclic structure.
2. All atoms in the cycle are in a state of sp2 hybridization (hence the s-skeleton is flat and all sp-orbitals are parallel.
3. In the molecule there is a delocalized p-electron system containing 4n + 2 p-electrons, where n = 0,1,2, is a natural series of numbers. This rule is called Hückel's rule
Heterocyclic compounds also have an aromatic character. When replacing –CH= in a benzene molecule with –N=, the heterocyclic compound pyridine is formed.
Mesomeric effect. Electron-donating and electron-withdrawing substituents. Resonance theory as a qualitative way to describe the delocalization of electron density.
The mesomeric effect or effective conjugation is the transfer of the electronic influence of substituents through a conjugated system. Unlike the I (inductive) effect, the M (mesomeric) effect is transmitted through the conjugation system without attenuation. Deputy lower electr. density in conjugation system (displacement of the ED in its direction) manifested. - M-effect and phenomenon. electron acceptor. (substituents contain multiple bonds of a carbon atom with more negative heteroatoms).
Deputy increased electr. density in conjugation system (displacement of the EF from itself towards the conjugate system) manifested. +M-effect and phenomenon. electron donor. (substituents containing a heteroatom with an unshared pair of electrons)
M-effect (hydroxy, amino, OR, halogens). - M-effect (nitro, sulfo, carboxyl, carbonyl).
Resonance theory- the theory of the electronic structure of chemical compounds, according to which the distribution of electrons in molecules is a combination (resonance) of canonical structures with different configurations of two-electron covalent bonds.
Resonance structures of cyclopentadienide ion
Configuration and conformation are the most important concepts in stereochemistry. Configuration. Elements of symmetry of molecules (axis, plane, center) and operations of symmetry (rotation, reflection). Chiral and achiral molecules. Asymmetric carbon atom as a center of chirality.
Steriochemistry– section of chemistry, study space. built molecules and their influence. on physical and chemical properties, as well as on direction. and the speed of their reaction. It is based on three fundamental concepts: chirality, configuration and conformation.
Configuration– these are spaces. inlet location into the composition of a molecule of atoms or at. groups without taking into account the differences that arose in the following. rotation around single bonds.
Axis of symmetry. If the rotation of a molecule around any axis passing through it is at an angle of 2π/ n= 360°/ n leads to a structure that does not differ from the original one, then such an axis is called the axis of symmetry n-th order C n.
Plane of symmetry (mirror plane) is an imaginary plane that passes through the molecule and divides it into two mirror-like equal parts.
In the presence of center of symmetry all atoms of a molecule that do not lie in the center of symmetry are located in pairs on one straight line passing through the center, at the same distance from the center, as, for example, in benzene.
Conformations molecules - various spatial forms of molecules that arose when the relative orientation of its individual parts changed in the res. internal rotation of atoms or groups of atoms around single bonds, bending of bonds, etc.
If the molecules are incompatible with their mirror image. This property is called chirality, and the molecules themselves – chiral(means that two objects relate to each other as left and right hands (from the Greek. chiros- hand) and are mirror images that do not coincide when trying to combine them in space).
Asymmetric carbon atom - an atom bonded to four different substituents.
Molecules with one center of chirality (enantiomerism). Glyceraldehyde as a configuration standard. Fischer projection formulas. Relative and absolute configuration. D-, L- and R-, S-systems of stereochemical nomenclature. Racemates.
Enantiomers are stereoisomers whose chiral molecules are related to each other as an object and an incompatible mirror image (they represent two optical antipodes and are therefore also called optical isomers).
Glyceraldehyde contains a chiral center, existing in the form of 2 stereoisomers, possessing. various opt.activity.
Projection formulas proposed E. Fischer: 1) carbon skeleton location. vertically; 2) placed at the top. senior function group; 3) the tetrahedron is oriented so that the chiral center is located in the plane, the substituents located to the right and left of the carbon chain are directed forward from the projection plane; Substituents are placed vertically, moving away from the observer beyond the projection plane; The asymmetric carbon atom is transferred to the plane at the intersection point of the horizontal and vertical lines. Relative configuration- this is the relative arrangement of substituents at different asymmetries. atoms in relation to each other; it is usually denoted by prefixes ( cis- And trans-, treo- And erythro- etc.). Absolute configuration- this is the true arrangement in space of substituents at each asymmetric atom of the molecule; most often it is denoted by letters D or L .
R,S-nomenclature.1) Determine the order of precedence of substituents at the chiral center: a) the order of precedence is first established for atoms immediately adjacent. connection with the center: “the higher the atomic number, the older the substituent.” b) if the closest. atoms are the same, then the procedure should be carried out for the atom of the next sphere. 2) Having located the youngest substituent from the observer, determine the direction of decline in the seniority of the remaining three substituents. If it occurs clockwise, it is an R-isomer; if it occurs counterclockwise, it is an S-isomer. D,L-nomenclature(Related to the Fischer projection). If the functional group at the chiral center is on the right, then it is a D-isomer, and on the left is an L-isomer. Enantiomers differ in their ability to rotate plane-polarized light: on the right (+) D, on the left (-) L.
7. The emergence of conformations as a result of rotation around σ bonds. Factors that make rotation difficult. Newman's projection formulas. Types of stress. Energy characteristics of open chain conformations. Relationship between spatial structure and biological activity
1. Conformations (rotational isomerism). Without changing either bond angles or bond lengths, one can imagine many geometric shapes of the ethane molecule, differing from each other in the mutual rotation of carbon tetrahedra around the C-C bond connecting them. As a result of this rotation, rotary isomers (conformers).
In projection Newman the molecule is viewed along the C-C bond). Three lines diverging at an angle of 120° from the center of the circle indicate the bonds of the carbon atom closest to the observer; the lines “poking out” from behind the circle are the bonds of the distant carbon atom.
The conformation shown on the left is called obscured . This name reminds us that the hydrogen atoms of both CH 3 groups are opposite each other. The eclipsed conformation has increased internal energy and is therefore unfavorable. The conformation shown on the right is called inhibited , implying that free rotation around the C-C bond is “inhibited” in this position, i.e. the molecule exists predominantly in this conformation.
The minimum energy required to completely rotate a molecule around a particular bond is called rotation barrier for this connection. The rotation barrier in a molecule like ethane can be expressed in terms of the change in potential energy of the molecule as a function of the change dihedral (torsion) angle systems. The dihedral angle (denoted by ) is shown in the figure below:
As the molecule becomes more complex, the number of possible conformations increases. Below, the conformations of n-butane are depicted as Newman projections. The conformations shown on the left (shaded) are energetically unfavorable; only inhibited ones are practically realized.
Cycloalkanes. Nomenclature. Small cycles. Electronic structure of cyclopropane. Features of the chemical properties of small cycles (addition reactions). Regular cycles. Substitution reactions. Types of stress. Energy difference between cyclohexane conformations (chair, bathtub, half-chair). Axial and equatorial connections. Receipt. Properties
Physical properties. Under normal conditions, the first two members of the series (C 3 - C 4) are gases, (C 5 - C 16) are liquids, starting from C 17 are solids.. Preparation. 1. The main method for obtaining cycloalkanes is the elimination of two halogen atoms from dihaloalkanes:
2. During the catalytic hydrogenation of aromatic hydrocarbons, cyclohexane or its derivatives are formed: t°, P, Ni C 6 H 6 + 3H 2 → C 6 H 12.
Chemical properties. In terms of chemical properties, small and ordinary cycles differ significantly from each other. Cyclopropane and cyclobutane are prone to addition reactions, i.e. similar in this respect to alkenes. Cyclopentane and cyclohexane are close in their chemical behavior to alkanes, since they undergo substitution reactions.1. For example, cyclopropane and cyclobutane are capable of adding bromine (although the reaction is more difficult than with propene or butene):
2. Cyclopropane, cyclobutane and even cyclopentane can add hydrogen, giving the corresponding normal alkanes.
The addition occurs when heated in the presence of a nickel catalyst:
3. Again, only small cycles enter into the addition reaction with hydrogen halides. The addition to cyclopropane homologues occurs according to Markovnikov’s rule:
4. Substitution reactions. Conventional cycles (C 6 and higher) are stable and only undergo radical substitution reactions like alkanes: t ° C 6 H 12 + Br 2 → C 6 H 11 Br + HBr.
5. Dehydrogenation of cyclohexane in the presence of a nickel catalyst leads to the formation of benzene: t ° Ni
C 6 H 12 → C 6 H 6 + 3H 2 .6. When strong oxidizing agents (for example, 50% nitric acid) act on cyclohexane in the presence of a catalyst, adipic (hexanedioic) acid is formed:
Structural features of cycloalkanes and their chemical behavior. Cyclopropane has a flat structure, so the hydrogen atoms of neighboring carbon atoms are located above and below the plane of the cycle in an energetically unfavorable (“obscured”) position. This is one of the reasons for the “tension” of the cycle and its instability.
Conformations of the six-membered ring: a - chair: 6 - bath. Another possible arrangement of atoms for cyclohexane corresponds to the bath conformation, although it is less stable than the chair conformation. It should be noted that in both the chair and bath conformations, the bonds around each carbon atom are in a tetrahedral arrangement. Hence the incomparably greater stability of ordinary cycles compared to small cycles, hence their ability to enter into substitution reactions, but not addition. Cycloalkanes are saturated cyclic hydrocarbons. The simplest representatives of this series: cyclopropane cyclobutane. General formula CnH2n. Structure. Isomerism and nomenclature.Cycloalkanes are saturated cyclic hydrocarbons. The simplest representatives of this series:
Alkenes. Nomenclature. Isomerism. Methods of obtaining. Electrophilic addition reactions, mechanism. Addition of halogens, hydrohalogenation, hydration and the role of acid catalysis. Markovnikov's rule. Concept of radical addition reactions. Oxidation of alkenes (ozonation, epoxidation).
Alkenes- These are not cyclic hydrocarbons, in the molecules of which 2 carbon atoms are in a state of sp 2 hybridization and are connected to each other by a double bond.
The first representative of the homologous series of alkenes is ethene (ethylene) - C 2 H 4. . The homologous series of alkenes has the general formula C n H 2n. A characteristic feature of the structure of alkenes is the presence of a double bond >C=C in the molecule<. Двойная связь образуется при помощи двух пар обобщенных электронов. Углеродные атомы, связанные двойной связью, находятся в состоянии sp²-гибридизации, каждый из них образует три σ-связи, лежащие в одной плоскости под углом 120º.
Alkenes are characterized by structural isomerism: differences in chain branching and in the position of the double bond, as well as spatial isomerism (cis and trans isomers). According to international nomenclature, alkenes are named by numbering the longest chain starting from the end to which the double bond is closest. According to rational nomenclature, they are considered derivatives of ethylene, where one or more hydrogen atoms are replaced by hydrocarbon radicals. For example, let’s name the substance according to the international (IUPAC) nomenclature: CH 3 – C(CH 3) = CH 2 Isobutylene, unsymmetrical dimethylethylene, 2-methylpropene.
Aromaticity is not directly related to the smell of organic compounds, and is a concept that characterizes the totality of structural and energetic properties of some cyclic molecules containing a system of conjugated double bonds. The term "aromaticity" was coined because the first members of this class of substances had a pleasant odor.
Aromatic compounds include a wide group of molecules and ions of various structures that meet the criteria of aromaticity.
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Aromatic compounds and Hückel's rule
Mesomeric effect (conjugation effect). Part 1.
Aromaticity. Criteria for aromaticity of organic compounds.
Aromatic heterocycles. Part 1
Hückel's rule of aromaticity
Subtitles
I have already talked about the phenomenon of aromaticity, and I will devote this video entirely to this topic. So, aromatics. First of all: why are these substances called aromatic? Obviously, from the word “aroma”. You might think that all aromatic compounds have a strong odor, but many of them have no smell at all. So why? Perhaps this is due to the fact that they are somehow related to substances that have a strong odor, so they were called aromatic. It remains a mystery. Most known aromatic compounds, 99% of such substances, are either benzene or benzene derivatives. Let's draw benzene. Typically a benzene molecule is drawn like this. A cycle of 6 atoms with three double bonds. These are the three double bonds. In the video about resonance, I said that this structural formula is not the only one. Another option is also possible. This electron can move here, this electron can move here, and this electron can move here. Let's draw what we get in the end. This is the structural formula we get. A possible configuration of the benzene molecule is where the double bonds are located differently than in the first formula. Here are the two formulas. From the video about resonance, you know that in reality everything is a little more complicated. Both formulas are correct. Benzene exists in two configurations at once, and does not change from one to another. This is shown as a cycle of six carbon atoms with a circle in the middle. This is how chemists often depict the benzene ring. This means that all the π electrons that form double bonds in the molecule are distributed between the atoms, smeared throughout the ring. It is the delocalization of π electrons in the ring that gives aromatic substances their unique properties. This configuration is much more stable than just a static alternation of single and double bonds in the ring. There is another way to draw benzene. I'll change the color and show it yellow. The delocalization of π electrons is shown as follows: dotted line here, here, here, here, here and here. This is the most popular option for displaying the delocalization of electrons in the benzene ring, that is, the presence of a conjugated system of π-electrons. I'll tell you what it is. These two formulas are also used, but the true structure of benzene lies between these configurations. We need to show you what's going on there. Surely you have heard about conjugated systems of π-electrons. I think it would be useful to show the benzene molecule in three dimensions. So, look. Here's a cycle of six carbon atoms: carbon, carbon, carbon, carbon, carbon, carbon. Each of the carbon atoms is bonded to three more atoms, two carbon atoms and a hydrogen atom. I'll draw hydrogen and its bond to carbon. Here's a hydrogen atom, here's a hydrogen atom, hydrogen, hydrogen, and two more hydrogen atoms. Each carbon atom has three hybrid orbitals, this is sp2 hybridization. In addition, each of them still has a free p-orbital. This p orbital does not form sigma bonds with neighboring atoms. And then there are p-orbitals, which look like dumbbells. Here is a p-orbital, here is a p-orbital, here, here are two more p-orbitals. In fact, there are more orbitals, but then they would cover the picture. Don't forget that the benzene molecule has double bonds. I'll highlight one of the carbon atoms. This sigma connection corresponds to, let's say, this sigma connection. For convenience, I will show another connection. Let's say this sigma bond corresponds to this bond between two carbon atoms. The double bond, which I'll show in purple, is formed by lateral overlap of the p orbitals. The p orbitals of neighboring carbon atoms overlap. An orbital is a region where an electron can end up with a certain probability. These regions are large, they overlap and the electrons form an additional π bond. What happens in the conjugated system of π-electrons. I'll write this down so you don't forget. Conjugated system of π-electrons. There may be a bond at this location if the orbitals overlap. This is how I will show the overlap of orbitals. When moving to another configuration, the orbitals will overlap here. In fact, all these π electrons are jumping around the entire ring. Electrons travel through all these p orbitals. They can be anywhere in the cycle. This is what is meant when they talk about the aromatic properties of substances. Because of this, substances acquire special stability. Most aromatic substances are just such cycles, benzene and its derivatives. But there are other substances. Any substance that has 4n + 2 π electrons in its ring, where n is an integer, is aromatic, that is, it is an aromatic compound. Let's count the electrons. Each of the six carbon atoms has one π electron. Each carbon atom has one p-orbital, and each such orbital is occupied by one electron. In total there are 1, 2, 3, 4, 5, 6. You can put it another way: each double bond is 2 π-electrons. 1, 2, 3, 4, 5, 6. This is called compliance with Hückel's rule. I think it's a German surname. Hückel's rule. Benzene corresponds to it. When n is equal to one, 4 * 1 + 2 = 6. The rule is true. With n equal to two, there should be 10 π electrons. With ten π electrons, the rule holds true. It will be a molecule like this, and it corresponds to Hückel's rule. There will be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 carbon atoms in the ring. There are 5 double bonds here: 1, 2, 3, 4, 5. So that the bonds alternate. This is also an aromatic compound. It has 10 π electrons, one for each carbon atom, or two in each double bond. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. And now the part that surprises me. 6 and 10 comply with the rule, but not 8. What's wrong with eight electrons? Why is this number inappropriate? What if there are four π electrons? Let's say the molecule looks like a quadrilateral. Or like a road sign - 1, 2, 3, 4, 5, 6, 7, 8 and alternating double bonds. Will these substances also be aromatic compounds? They also have alternating bonds, which means electrons can move from place to place and delocalize in the cycle. Move from here to here, from here to here. From here to here, from here to here. But it turns out that in such substances π electrons do not stabilize the system at all, and the cycle turns out to be less stable than a linear molecule. And these molecules do not comply with Hückel's rule. 4n + 2 is 6, 10, 14 π electrons, that is, 14, 10 or 6 carbon atoms. If the number of atoms is different, but it is a cycle with alternating bonds, the substance is anti-aromatic. Let's write down this term. They are very unstable. They are very unstable and open up, becoming linear molecules. I hope you found it interesting. Subtitles by the Amara.org community
Story
In 1959 Saul Winstein introduced the concept of “homoaromaticity” - a term used to describe systems in which a stabilized cyclic conjugate system is formed by bypassing one saturated atom.
Explanation of aromaticity
Aromaticity criteria
There is no single characteristic that allows one to reliably classify a compound as aromatic or non-aromatic. The main characteristics of aromatic compounds are:
- tendency to substitution reactions rather than addition (the easiest to determine, historically the first sign, example - benzene, unlike ethylene, does not decolorize bromine water)
- energy gain compared to a system of non-conjugated double bonds. Also called Resonance Energy (improved method - Dewar Resonance Energy) (the gain is so great that the molecule undergoes significant transformations to achieve the aromatic state, for example cyclohexadiene is easily dehydrogenated to benzene, dihydrogen and trihydric phenols exist predominantly in the form of phenols (enols) rather than ketones etc.)
- the presence of a ring magnetic current (observation requires complex equipment), this current ensures a shift of the chemical shifts of protons associated with the aromatic ring into a weak field (7-8 ppm for the benzene ring), and protons located above/below the plane of the aromatic system - in a strong field (NMR spectrum).
- the presence of the plane itself (minimally distorted), in which all (or not all - homoaromaticity) atoms forming an aromatic system lie. In this case, rings of pi-electrons formed during the conjugation of double bonds (or electrons included in the ring of heteroatoms) lie above and below the plane of the aromatic system.
- The Hückel Rule is almost always observed: only a system containing (in the ring) 4n+2 electrons (where n = 0, 1, 2, ...) can be aromatic. A system containing 4n electrons is anti-aromatic (in a simplified sense, this means an excess of energy in the molecule, inequality of bond lengths, low stability - a tendency to addition reactions). At the same time, in the case of peri-junction (there is an atom(s) belonging to 3 rings simultaneously, that is, there are no hydrogen atoms or substituents near it), the total number of pi electrons does not correspond to Hückel’s rule (phenalene, pyrene, crown). It is also predicted that if it is possible to synthesize molecules in the form of a Möbius strip (a ring of a sufficiently large size so that the twisting in each pair of atomic orbitals is small), then for such molecules a system of 4n electrons will be aromatic, and of 4n+2 electrons will be anti-aromatic.
Modern representations
In modern physical organic chemistry, a general formulation of the aromaticity criterion has been developed
AROMATICITY(from the Greek aroma, gender aromatos - incense), a concept characterizing a set of structural, energetic. properties and characteristics of the reaction. cyclical abilities structures with a system of conjugated connections. The term was introduced by F.A. Kekule (1865) to describe the properties of compounds structurally close to benzene, the founder of the class of aromatic compounds.
To the number of most important signs of aromaticity include the tendency to be aromatic. conn. to a substitution that preserves the system of conjugated bonds in the cycle, and not to an addition that destroys this system. In addition to benzene and its derivatives, such solutions are characteristic of polycyclic aromatic compounds. hydrocarbons (for example, naphthalene, anthracene, phenanthrene and their derivatives), as well as for isoelectronic heterocyclic conjugates. connections. It is known, however, that there are many connections. (azulene, fulvene, etc.), which also easily enter into substitution systems, but do not have all the other signs of aromaticity.
Reaction ability cannot serve as an accurate characteristic of aromaticity also because it reflects the properties of not only the basic. state of this compound, but also the transition state (activated complex) of the solution, in which this is the connection. enters. Therefore, more stringent criteria for aromaticity are associated with physical analysis. St. in the main electronic states cyclic. conjugated structures. The main difficulty is that aromaticity is not an experimentally determined characteristic. Therefore, there is no unambiguous criterion for establishing the degree of aromaticity, i.e. degree of similarity to St. benzene. Below are considered the most. important signs of aromaticity.
The structure of the electronic shell of aromatic systems.
The tendency of benzene and its derivatives to retain the structure of the conjugated ring in decomp. transformations means higher. thermodynamic and kinetic stability of this structural fragment. Stabilization (decrease in electronic energy) of a molecule or ion that has a cyclic structure, is achieved when all bonding molecular orbitals are completely filled with electrons and nonbonding and antibonding orbitals are vacant. These conditions are met when the total number of electrons in the cycle. polyene is equal to (4l + 2), where n = = 0,1,2... (Hückel's rule).
This rule explains the stability of benzene (form I) and cyclopentadienyl anion (II; n = 1). It made it possible to correctly predict the stability of cyclopropenyl (III; n = 0) and cycloheptatrienyl (IV; n = 1) cations. Due to the similarity of the electronic shells of the conn. II-IV and benzene, like higher cyclic ones. polyenes - , , annulenes (V-VII), are considered aromatic. systems. 
Hückel's rule can be extrapolated to a series of conjugated heterocyclics. conn. - derivatives of pyridine (VIII) and pyrilium cation (IX), isoelectronic to benzene, five-membered heterocycles of type X (pyrrole, furan, thiophene), isoelectronic to the cyclopentadienyl anion. These compounds are also classified as aromatic. systems. 
Derivatives of compounds II-X and other more complex structures obtained by isoelectronic substitution of methine groups in polyenes I-VII are also characterized by high thermodynamic properties. stability and general tendency to substitution reactions in the nucleus.
Cyclic. conjugated polyenes, which have 4n electrons in the ring (n=1,2...), are unstable and easily enter into addition reactions, because they have an open electron shell with partially filled nonbonding orbitals. Such connections, most a typical example of which is cyclobutadiene (XI), including canthiaromatic. systems.
Rules that take into account the number of electrons in a cycle are useful for characterizing the properties of monocyclics. structures, but are not applicable to polycycles. When assessing the aromaticity of the latter, it is necessary to take into account how the electronic shells of each individual cycle of the molecule correspond to these rules. They should be used with caution in the case of multi-charged cyclic batteries. ions Thus, the electronic shells of the dication and dianion of cyclobutadiene meet the requirements of Hückel’s rule. However, these structures cannot be classified as aromatic, since the dication (n = 0) is not stable in a flat form, which provides cyclic structure. conjugation, and in a bent diagonally; The dianion (n=1) is generally unstable.
Energy criteria for aromaticity. Resonance energy. To determine quantities. measures of aromaticity characterizing increased thermodynamic stability aromatic conn., the concept of resonance energy (ER), or delocalization energy, was formulated.
The heat of hydrogenation of a benzene molecule, formally containing three double bonds, is 151 kJ/mol greater than the heat of hydrogenation of three ethylene molecules. This value, associated with ER, can be considered as energy additionally expended on the destruction of the cyclic. a system of conjugated double bonds of the benzene ring that stabilizes this structure. T. arr., ER characterizes the contribution of the cyclic. conjugation into the heat of formation (total energy, heat of atomization) of the compound.
A number of theoretical methods have been proposed. ER assessments. They differ ch. arr. choosing a comparison structure (i.e. a structure in which the cyclic conjugation is broken) with the cyclic. form. The usual approach to calculating ER is to compare the electronic energies of the cycle. structure and the sum of the energies of all isolated multiple bonds contained in it. However, the calculated t. arr. ER, regardless of the quantum chemical used. method, tend to increase with increasing system size. This often contradicts experiments. data about the saints aromatic. systems. Thus, the aromaticity in the series of polyacenesbenzene (I), naphthalene (XII), anthracene (XIII), tetracene (XIV) decreases (for example, the tendency to addition increases, the alternation of bond lengths increases), and the ER (given in units = 75 kJ/ mole) grow: 
The ER values calculated by comparing the electronic energies of cyclic cycles do not have this drawback. structure and similar acyclic. conjugate full (M. Dewar, 1969). Calculated t. arr. quantities are usually called Dewar ER (ED). For example, the EDP of benzene (1.013) is calculated by comparing it with 1,3,5-hexatriene, and the EDP of cyclobutadiene by comparing it = = with 1,3-butadiene.
Connections with positive values of ERD are classified as aromatic, those with negative values are classified as anti-aromatic, and those with ERD values close to zero are classified as non-aromatic. Although the EDP values vary depending on the quantum chemical approximations. calculation method, relates. their order practically does not depend on the choice of method. Below are the ERD per electron (ER/e; in units), calculated using the modified version. Hückel molecular orbital method: 
Naib. ERD/e, that is, max. benzene is aromatic. A decrease in ERD/e reflects a decrease in aromatic. St. The data presented are in good agreement with established ideas about the manifestations of aromaticity.
Magnetic criteria for aromaticity. Cyclic. The conjugation of electrons leads to the appearance of a ring current in the molecule, which causes exaltation of the diamagnosis. receptivity. Since the values of the ring current and exaltation reflect the effectiveness of the cyclic. pairings, they may. used as quantities. a measure of aromaticity.
Aromatic compounds include compounds whose molecules support induced diamagnetic electronic ring currents (diatropic systems). In the case of annulens (n = 0,1,2...) there is a direct proportionality between the strength of the ring current and the magnitude of the electric propulsion. However, for non-alternant hydrocarbons (for example, azulene) and heterocyclic. conn. this dependence becomes more complex. In some cases, the system may simultaneously both diatropic and anti-aromatic, for example. bicyclodecapentaene.
Presence of inducers. ring current in cyclic conjugated systems characteristically manifests itself in the proton magnetic spectra. resonance (PMR), because the current creates an anisotropic magnetic field. field that significantly affects the chemical shifts of protons associated with ring atoms. Signals of protons located in the internal parts aromatic rings shift towards a strong field, and the signals of protons located on the periphery of the ring shift towards a weak field. Yes, internal protons of annulene (form VI) and annulene (VII) appear at - 60°C in the PMR spectrum, respectively. at 0.0 and -2.99m. d., and external ones at 7.6 and 9.28 ppm.
For anti-aromatic Annulene systems, on the contrary, are characterized by paramagnetic properties. ring currents leading to a shift in external protons into a strong field (paratropic systems). Yes, chem. shift ext. protons of annulene is only 4.8 ppm.
Structural criteria for aromaticity. The most important structural characteristics of the benzene molecule are its planarity and complete alignment of bonds. A molecule can be considered aromatic if the lengths of carbon-carbon bonds in it lie in the range of 0.136-0.143 nm, i.e. close to 0.1397 nm for the benzene(I) molecule. For non-cyclical of conjugated polyene structures, the lengths of the C-C bonds are 0.144-0.148 nm, and the lengths of the C=C bonds are 0.134-0.135 nm. An even greater alternation of bond lengths is typical for antiaromatics. structures. This is supported by rigorous non-empirical data. geometric calculations parameters of cyclobutadiene and exp. data for its derivatives.
Proposed various expressions for quantities. aromaticity characteristics based on the degree of alternation of bond lengths, for example. for hydrocarbons, the aromaticity index (HOMA d) is introduced:
where a = 98.89, X r is the length of the r-th bond (in A), n is the number of bonds. For benzene, HOMA d is maximum and equal to 1, for cyclobutadiene it is minimum (0.863).
Detailed program of lectures and
comments on the second part of the course
The detailed program of lectures and comments to the second part of the general course of lectures in organic chemistry (PLL) are based on the Program of the general course of organic chemistry, developed at the Department of Organic Chemistry of the Faculty of Chemistry of Moscow State University. PPLs reveal the filling of the second part of the general course of lectures with factual material on the theory and practice of organic chemistry. PPL is intended primarily for 3rd year students who want to prepare well and quickly enough for exams and colloquiums and understand how much knowledge a student must have to get an excellent grade on the exam. PPLs are prepared in such a way that the mandatory program material is printed in normal font, and the optional material is in italics, although it should be recognized that such a division is sometimes quite arbitrary.
One of the goals of this manual is to help students correctly and accurately compose lecture notes, structure the material, make the right accents in the notes, and separate mandatory material from non-essential material when working independently with notes or a textbook. It should be noted that despite the wide spread of modern teaching methods and the availability of a variety of educational material in textbooks and on the Internet, only independent persistent, if not hard, work on taking notes (lectures, textbooks, other materials), work at seminars, independent writing of the most important equations and mechanisms, and independent solution of synthetic problems can lead to success in the study of organic chemistry (and other subjects). The authors believe that listening to a course of lectures creates the basis for studying organic chemistry and covers all topics included in the exam. However, lectures listened to, as well as textbooks read, remain passive knowledge until the material is consolidated in seminars, colloquiums, when writing tests, assignments and analyzing errors. The PPL lacks equations of chemical reactions and mechanisms of the most important processes. This material is available in lectures and textbooks. Each student must obtain some knowledge on his own: write the most important reactions, mechanisms, and better yet, more than once (independent work with lecture notes, with a textbook, colloquium). Only what is acquired through independent, painstaking work is remembered for a long time and becomes active knowledge. What is easily obtained is easily lost or forgotten, and this is true not only in relation to the course of organic chemistry.
In addition to program materials, this development contains a number of auxiliary materials that were demonstrated during the lectures and which, according to the authors, are necessary for a better understanding of organic chemistry. These auxiliary materials (figures, tables, etc.), even if they are printed in normal font, are most often not intended for literal memorization, but are needed to assess trends in changes in the properties or reactivity of organic compounds. Since the auxiliary materials, figures, and tables demonstrated during lectures can be difficult to completely and accurately write down in notes, the placement of these materials in this development is intended to help course students fill in the gaps in notes and notes, and to focus during the lecture not on the shorthand recording of numbers and tables, but on perception and understanding of the material discussed by the lecturer.
AROMATICITY.
1. Aliphatic (from the Greek αλιφατικό - oil, fat) and aromatic (αρωματικόσ - incense) compounds (nineteenth century).
2. Discovery of benzene (Faraday, 1825). The structure of benzene (Kekule, 1865). o-, m-, p-isomers, ortho-xylene.
3. Other formulas proposed for benzene (Ladenburg, Dewar, Thiele, etc.). Benzene isomers (prismane, bicyclohexa-2,5-diene, benzvalene, fulven).
4. Hückel molecular orbital method. Independent consideration of σ- and π-bonds (i.e. formed by sp 2 and p-orbitals). Molecular orbitals of benzene (three bonding orbitals: one orbital has no nodes, two orbitals have one nodal plane, all of them are occupied, they have only 6 electrons; three orbitals are antibonding. Two of them have 2 nodal planes, the highest energy antibonding orbital has three nodal planes and the antibonding orbitals are not occupied.
Concept of the Frost circle for benzene, cyclobutadiene and cyclooctatetraene.
Hückel's rule. FLAT, MONOCYCLIC, CONNECTED hydrocarbons will be aromatic if the cycle contains (4n+2) π – electrons.
Anti-aromatic compounds. Non-aromatic compounds. Cyclooctatetraene.
5. Description of benzene using the “valence scheme” method, resonance theory (Pauling), mesomerism, use of limit structures.
6. Cancellations. Methanoannulens. Aromatic ions. Condensed hydrocarbons. Heterocycles.
A few comments on the stability of cancellations.
-cancelled – not flat, cannot be aromatic.
1,6-methane--cancelled- flat, (except for the bridge, of course!), it is aromatic.
Annulene is a non-aromatic polyene, stable below -70 o C.
-cancelled not flat cycles if there are no 2 bridges. Therefore - not aromatic.
Annulenes are ordinary polyenes.
-cancelled– flat, aromatic. Know the peculiarity of its PMR spectrum!
7. Detailed consideration AROMATIC CRITERIA.
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Aromaticity criteria – quantum mechanical – number of p-electrons 4n+2(Hückel's rule), see comments below. Energy (increasing thermodynamic stability due to delocalization of electrons, the so-called delocalization energy – ED). ED in benzene: (6a +8β) – (6a +6β) (for cyclohexatriene) = 2β = 36 kcal/mol or 1.56 eV is EER (empirical resonance energy). There are several more ways to calculate resonance energy: vertical resonance energy (also known as ED according to Hückel, measured in units of integral β, for benzene it is 0.333), there is also (at 5++) ERD (i.e., the Dewar resonance energy, per 1 electron, 0.145 eV for benzene), there is also (at 5+++) ERD according to Hess-Schaad, for benzene: 0.065 eV, then the same as EDNOE in the textbook by Reutov, Kurtz, Butin. There is also (at 5++++) TER (topological ER). Also, “there are many things in the world, friend Horatio, that our sages never dreamed of” (W. Shakespeare). The energy criterion is the most inconvenient and unclear of all. The energy values for this criterion are always calculated, because, as a rule, it is impossible to select the corresponding non-aromatic molecule for comparison. Therefore, one should be calm about the fact that there are many different estimates of the delocalization energy even for classical aromatic molecules, but for more complex systems these values are completely absent. You can never compare different aromatic systems based on the magnitude of delocalization energies - you cannot conclude that molecule A is more aromatic than molecule B, because the delocalization energy is greater. Structural - a very important, if not the most important, criterion, since it is not theoretical, but experimental in nature. The specificity of the geometry of molecules of aromatic compounds lies in the tendency to coplanar arrangement of atoms and alignment of bond lengths. In benzene, the alignment of bond lengths is perfect - all six C-C bonds are the same in length. For more complex molecules, the alignment is not perfect, but it is significant. The criterion is taken as a measure of the relative deviation of the lengths of conjugated bonds from the average value. The closer to zero, the better. This quantity can always be analyzed if structural information is available (experimental or from high-quality quantum chemical calculations). The tendency towards coplanarity is determined by the advantage of collinearity of the atomic axes R-orbitals for their effective overlap. The question arises: what deviation from the planar arrangement is permissible without loss of aromaticity? Examples of plane distortion in aromatic molecules are given in the lecture; they can also be found in specialized literature (see below, p. 20). Magnetic (presence of ring current - diatropic system, influence on the chemical shifts of protons outside and inside the ring, examples - benzene and -annulene). The most convenient and accessible criterion, since the 1 H NMR spectrum is sufficient for its assessment. For an accurate determination, theoretical calculations of chemical shifts are used. What is diatropy? Chemical – tendency towards substitution reactions rather than addition reactions. The most obvious criterion that clearly distinguishes the chemistry of aromatic compounds from the chemistry of polyenes. But it doesn't always work. In ionic systems (for example, in the cyclopentadienyl anion or tropylium cation), substitution cannot be observed. Substitution reactions sometimes occur in non-aromatic systems, but aromatic systems are always capable of addition reactions to some extent. Therefore, it is more correct to call the chemical criterion a SIGN of aromaticity. |
8. THE CONCEPT OF AROMATICITY. SIGNS AND CRITERIA OF AROMATICITY. - Comments
Aromaticity – a concept that characterizes a set of special structural, energetic and magnetic properties, as well as features of the reactivity of cyclic structures with a system of conjugated bonds.
Although aromaticity is one of the most important and most fruitful concepts in chemistry (not only organic), - there is no generally accepted short definition this concept. Aromaticity is understood through a set of special characteristics (criteria) inherent in a number of cyclic conjugated molecules to one degree or another. Some of these criteria are of an experimental, observable nature, but the other part is based on the quantum theory of the structure of molecules. Aromaticity has a quantum nature. It is impossible to explain aromaticity from the standpoint of classical structural theory and resonance theory.
Do not do it Confuse aromaticity with delocalization and conjugation. In the molecules of polyenes (1,3-butadiene, 1,3,5-hexatriene, etc.) there is a clear tendency towards delocalization of electrons (see 1st semester, chemistry of dienes) and the formation of a single conjugated electronic structure, which is manifested in spectra (primarily electronic absorption spectra), some changes in bond lengths and orders, energy stabilization, special chemical properties (electrophilic 1,4-addition in the case of dienes, etc.). Delocalization and conjugation are necessary but not sufficient conditions for aromaticity. Aromaticity can be defined as the property in which a conjugated ring of unsaturated bonds exhibits greater stability than would be expected from conjugation alone. However, this definition cannot be used without experimental or calculated data on the stability of the cyclic conjugated molecule.
In order for a molecule to be aromatic, it must contain at least one cycle, every from the atoms of which it is suitable for the formation of an aromatic system R-orbital. It is this cycle (ring, system of rings) that is considered aromatic in the full sense of the word (if the criteria listed below are met).
There should be 4n+2 (that is, 2, 6, 10, 14, 18, 22, etc.) electrons in this cycle.
This rule is called Huckel's rule or criterion for aromaticity. The source of this rule is highly simplified quantum chemical calculations of idealized cyclic polyenes made in the early days of quantum chemistry. Further research has shown that this simple rule fundamentally gives correct aromaticity predictions even for very complex real systems.
The rule, however, must be used correctly, otherwise the forecast may be incorrect. General recommendations are given below.
Molecule containing at least one aromatic ring has the right to be called aromatic, but this generalization should not be overused. So, it is obvious that styrene contains a benzene ring, and therefore can be called an aromatic molecule. But we may also be interested in the ethylene double bond in styrene, which has no direct relation to aromaticity. From this point of view, styrene is a typical olefin with a conjugated double bond.
Never forget that chemistry is an experimental science, and no theoretical reasoning replaces or replaces knowledge of the real properties of substances. Theoretical concepts, even ones as important as aromaticity, only help to better understand these properties and make useful generalizations.
Which orbitals are considered suitable for the formation of an aromatic system?– Any orbitals perpendicular to the plane of the cycle, and
a) belonging to included in the cycle multiple (endocyclic double or triple) bonds;
b) corresponding to lone pairs of electrons in heteroatoms (nitrogen, oxygen, etc.) or carbanions;
c) corresponding to six-electron (sextet) centers, in particular carbocations.
Please note that the listed fragments a), b), c) give an even number of electrons to the overall system: any multiple bonds - 2 electrons, lone pairs - 2 electrons, vacant orbitals - 0 electrons.
What is not suitable or does not contribute to the aroma system:
a) onium forms of cationic centers– that is, cations containing a full octet of electrons. In this case, such a center breaks the conjugated system, for example, N-methylpyrrole is aromatic (6 electrons in the ring), and N,N-dimethylpyrrolium is non-aromatic (ammonium nitrogen does not contribute to the π-system):
Attention - if the onium center is part of a multiple bond, then it is the multiple bond that participates in the formation of the aromatic system, therefore, for example, N-methylpyridinium is aromatic (6 π-electrons, two from each of the three multiple bonds).
The concept of isoelectronicity. Isoelectronic systems are usually similar in terms of aromaticity. In this sense, for example, N-methylpyridinium is isoelectronic to methylbenzene. Both are obviously aromatic.
b) lone pairs lying in the plane of the ring. On one atom, only one π orbital can contribute to the aromatic system. Therefore, in the cyclopentadienyl anion the carbanion center contributes 2 electrons, and in the phenyl anion the carbon atom of the carbanion center contributes 1 electron, as in the benzene molecule. The phenyl anion is isoelectronic to pyridine, and the cyclopentadienyl anion is isoelectronic to pyrrole.
All are aromatic.
c) Exocyclic double bond or radical center. Such structures are generally non-aromatic, although each such structure requires special consideration using real experimental data .
For example, quinones are non-aromatic, although a) they have planar, fully conjugated rings containing 6 electrons (four from the two multiple bonds in the ring plus two from the two exocyclic bonds).
The presence in a certain conjugated structure of so-called quinoid fragments, that is, bond systems with two exocyclic double bonds, is always a source of instability and favors processes that transform the system with a quinoid fragment into a normal aromatic system. Thus, anthracene is a 14-electron aromatic system containing a quinoid fragment, therefore, anthracene easily attaches bromine or dienophiles, since the products already have two full-fledged aromatic benzene rings:
Aromaticity of polycyclic structures represents a rather complex theoretical problem. From a formal point of view, if a system has at least one benzene ring, then it can be considered aromatic. This approach, however, does not make it possible to consider the properties of the molecule as a whole.
The modern approach to polycyclic systems is to find in them All possible aromatic subsystems, starting from the largest possible - the outer contour. In this sense, for example, naphthalene can be represented as a common 10-electron system (outer contour) and two identical 6-electron benzene rings.
If the outer contour is not aromatic, then smaller aromatic contours should be sought. For example, diphenylene has 12 electrons along its outer contour, which does not correspond to Hückel’s rule. However, we can easily find two practically independent benzene rings in this compound.
If bicyclic hydrocarbons are planar and have conjugated double bonds, Hückel's rule works for bi- and polycyclic hydrocarbons that have one bond in common ( naphthalene, anthracene, phenanthrene, etc., and also azulene). Hückel's rule does not work well for fused rings that have a carbon atom common to 3 rings. The rule for counting electron pairs using the “walking around the perimeter, or along one of the contours” method can help in this case, for example:
acenaphthylene pyrene perylene
sum of π-electrons: 12 16 20
including along the perimeter, 10 14 18 (along the naphthalene contour - 10 and 10)
However, for such complex cycles this rule may not always work. Moreover, it says nothing about the actual properties of the molecule. For example, acenaphthylene has a regular double bond between atoms 1 and 2.
Various examples of isoelectronic aromatic heterocycles.
PYRROL – FURAN – THIOPHENE (6π electrons) .
PYRIDINE– PYRIDINIUM– PYRILIUM (6π electrons) .
Pyridazine – PYRIMIDINE– pyrazine (6 π electrons) .
Oxazoles – thiazoles – IMIDAZOLE (6π electrons) .
INDOL– QUINOLINE (10π electrons) .
About the "nuts" . In educational literature, aromatic cycles are often denoted using a circle inside a polygon. Let us be clear that this type of designation should be avoided whenever possible. Why?
Because:
a) in complex polycyclic structures, the circles do not have a specific meaning and do not allow us to understand where aromaticity lives - in individual cycles or as a whole. If you draw, for example, anthracene with “nuts,” it will not be clear what is the reason for its “not-quite-aromatic” and pronounced diene properties
b) even the most classical aromatic systems such as benzene and its derivatives can exhibit non-aromatic polyene properties, to consider which it is necessary to see the structure of multiple bonds.
c) it is the Kekul structure that is necessary to consider the effects of substituents using an indispensable tool - resonance structures. "Nut" is completely fruitless in this regard. So, using Kekule’s formula, we will perfectly understand the reason for high acidity P-nitrophenol and bright yellow color P-nitrophenolate. What are we going to do with the “nut”?
Preferred is the simple “Kekul-Butlerov” method, which corresponds to the classical theory of structure and explicitly denotes multiple bonds. Having drawn such a classical structure, you can always talk about its aromaticity or non-aromaticity, using the appropriate rules and criteria. It is the classical Kekul structure that is accepted as a standard in all leading international chemical journals.
And when are mugs appropriate?? To designate non-benzenoid aromatic systems, especially charged ones. In this case, the classical notation is somewhat clumsy and does not show charge delocalization.
It is also difficult to do without circles in organometallic chemistry, where aromatic systems often play the role of ligands. Try to reflect the structure of ferrocene or other complexes containing a cyclopentadienyl ligand without circles!
Flatness. A cycle that claims to be aromatic and contains the required continuous system of p-orbitals must be flat(or almost flat). This requirement is one of the most unpleasant, since it is not very easy to determine “by eye” which cycle is flat and which is not. The following points can be considered as simple tips:
a) cyclic conjugated systems containing 2 or 6 electrons and satisfying the conditions considered, as a rule, planar and aromatic. Such systems are usually implemented in small and medium-sized cycles (2-8 members);
b) cyclic ionic systems with the number of electrons 2, 6, 10, 14 are almost necessarily aromatic, since aromaticity is the reason for the existence and stability of such ions;
c) neutral systems with 10, 14, 18 or more electrons in one single large-sized cycle, on the contrary, almost always require additional measures to stabilize the flat structure in the form of additional bridges, since the energy gain due to the formation of a large aromatic system does not compensate for either the stress energy generated in macrocycles, nor the entropy lost in the formation of a single planar structure.
Attention : Reading the following paragraph is strictly not recommended for persons with weak and unstable knowledge. Anyone with a rating of less than 99 points can skip this paragraph.
Anti-aromaticity. Systems that satisfy all the conditions discussed above (flat cycles with a continuous system of π-orbitals), but the number of electrons is 4n, are considered anti-aromatic - that is, really non-existent. But if in the case of aromaticity we are dealing with real molecules, then in the case of antiaromaticity the problem is more complicated. It is important to understand that a real anti-aromatic system is not at a minimum, but at a maximum of potential energy, that is, it is not a molecule, but a transition state. Antiaromaticity is a purely theoretical concept that describes why some cyclic conjugated systems are either completely unstable and could not be obtained even at the cost of enormous effort, or show clear tendencies to exist in the form of an ordinary polyene with alternating single and multiple bonds.
For example, cyclobutadiene would be anti aromatic if it existed as a square molecule with bonds of equal length. But there is no such square molecule in Nature. Therefore, the correct way to say it is: the hypothetical square cyclobutadiene is anti-aromatic, and That's why does not exist. Experimentally, at very low temperatures, substituted cyclobutadienes were isolated, but their structure turned out to be typical non-aromatic dienes - they had a clear difference between short double and long single bonds.
Really existing planar conjugated molecules with 4n electrons are always highly reactive non-aromatic polyenes. For example, benzocyclobutadiene actually exists (8 electrons in the outer circuit), but has the properties of an extremely active diene.
Anti-aromaticity – extremely important concept in the theory of aromaticity. The theory of aromaticity predicts both the existence of particularly stable aromatic systems and the instability of anti-aromatic systems. Both of these poles are important.
Antiaromaticity is a very important concept in chemistry. All unsaturated conjugated cyclic systems containing an antiaromatic number of π electrons always have very high reactivity in various addition reactions.
9. Trivial examples of the synthesis of non-benzenoid aromatic ions.
Cyclopropenylium cation, tropylium cation
Cyclopentadienylide anion. Aromatic carbocyclic anions C8, C10, C14.
10. Optional: attempts to synthesize anti-aromatic molecules – cyclobutadiene, cyclopentadienylium cation.
Development of the concept of aromaticity. Cyclobutadiene iron tricarbonyl. Volumetric, spherical aromaticity, homoaromaticity, etc.
11. Preparation of aromatic hydrocarbons.
1. Industrial sources– oil and coal.
Reforming. Chain: heptane – toluene – benzene – cyclohexane.
2. Laboratory methods:
a) Wurtz-Fittig reaction (an outdated method, which has rather historical significance, do not do it apply when solving problems),
b) catalytic trimerization of acetylene,
c) acid-catalyzed trimerization of acetone and other ketones;
d) cross-coupling, both non-catalytic using cuprates and catalytic in the presence of palladium complexes,
e) Friedel-Crafts reaction, mainly acylation with reduction according to Clemmensen (alkylaryl ketones) or Kizhner-Wolf (any ketones and aldehydes) should be used,
f) aromatization of any derivatives of cyclohexane, cyclohexene, cyclohexadiene under the action of sulfur (fusion, suitable only for the simplest compounds) or dichlorodicyanbenzoquinone (DDQ or DDQ, a general-purpose reagent).
12. Properties of the ring and aliphatic side chain in aromatic hydrocarbons.
1. Hydrogenation. When does partial ring hydrogenation occur? Hydrogenation of functional groups (C=C, C=O) without ring hydrogenation. Examples.
2. Birch reduction (Na, liquid NH 3). Why is EtOH needed? The influence of donors and acceptors in the ring on the direction of the reaction.
3. Free radical halogenation of benzene (was in school!). Halogenation of toluene and its homologues into the side chain. Selectivity of halogenation.
4. Oxidation of the side chain and polycondensed aromatic hydrocarbons. Ozonation of benzene and other aromatic compounds.
5. Diels-Alder reaction for benzene and anthracene. Conditions.
6. Reaction of alkali metals and Mg with naphthalene and anthracene (optional).
ELECTROPHILIC SUBSTITUTION IN THE AROMATIC SERIES.
1. Why electrophilic substitution (ES)?
2. What types of electrophiles are there and what EZ reactions will we examine in detail? (protonation, nitration, sulfonation, halogenation, alkylation, acylation, formylation). In a month we will consider: azo coupling, nitrosation, carboxylation).
3. Simplified mechanism of electrophilic substitution in the aromatic ring (without π-complexes). Arenonium ions. Similarity to allylic cation. Representation of arenonium ions on paper - resonance structures or “horseshoe” - be sure to learn how to draw resonance structures for s-complexes, since the “horseshoe” will lead to a dead end when we come to the influence of substituents on the direction of electrophilic substitution. Protonation of arenes.
4. Evidence of the existence of π-complexes using the example of the reaction of DCl and benzene (G. Brown 1952). Evidence for the existence of σ-complexes.
5. Generalized mechanism of EZ, including the formation of π- and σ-complexes. The rate-limiting stage of electron detonation in the benzene ring. The concept of the kinetic isotope effect. Let us remember once again what a transition state and intermediate are.
6. Orientation for electrophilic substitution: ortho-, meta, para-, ipso. Orientants of the first and second kind. Be sure to draw resonance structures for s-complexes with various substituents. Separately analyze the influence on the structure of s-complexes of substituents with inductive and mesomeric effects, as well as a combination of multidirectional effects. Partial velocity factors. Consistent and discordant orientation. Examples of different ratios of o-/p-isomers in cases where the ring contains a substituent of the 1st kind (for example, sterically hindered) or of the 2nd kind (ortho-effect). NMR of benzolonium ions and some arenes.
7. Consideration of specific electrophilic substitution reactions. Nitration. Agents. Exotic agents. Attack particle. Features of nitration of different classes of compounds - nitroarenes (conditions), halogenated benzenes (division of o- and p-isomers. How?), naphthalene and biphenyl. Nitration of aromatic amines (protecting groups, how to do O- And P- isomers? Is it possible to nitrate anilines to the m-position?). Nitration of phenol (conditions, division O- And P- isomers).
7. Sulfonation of arenes. Agents, nature of the electrophile, reversibility. Features of sulfonation of naphthalene, toluene, phenol, aniline, protection by sulfo group in EZ reactions.
8. Sulfonic acid derivatives: tosyl chloride, tosylates, sulfonamides. Restoration of the sulfo group.
9. Halogenation. A series of halogenating agents in decreasing order of activity (know at least 3 examples). The nature of the electrophile, features of the halogenation of toluene, halogenated benzenes, be able to obtain all halogenated benzenes, halogenation of naphthalene, biphenyl, aniline, phenol, anisole. Features of iodination. Chlorination of iodobenzene without electrophilic catalysts. Polyvalent iodine compounds (PhICl 2, PhI=O, PhI(OAc) 2)
10.Alkylation and acylation according to Friedel-Crafts. Alkylation – 3 disadvantages, examples of syntheses, reversibility, influence of halogen in RHal, agents, intramolecular alkylation, restrictions on substituents, features of alkylation of phenols and amines, synthesis of n-alkylbenzenes. Acylation - comparison with alkylation, reagents, cyclic anhydrides in acylation, intramolecular reactions, Fries rearrangement.
Table 1.
Table 2. Data on nitration of halobenzenes.
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Compound |
products, %* |
relative speed nitration (benzene =1)** |
Partial speed factor for O- And P- position (benzene = 1) |
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|
ortho |
meta |
pair |
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|
C 6 H 5 – F |
0,054 (O) 0,783 (P) |
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|
C 6 H 5 – Cl |
0,030 (O) 0,136(P) |
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|
C 6 H 5 – Br |
0,033 (O) 0,116(P) |
||||
|
C 6 H 5 – I*** |
0,205 (O) 0,648(P) |
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*) K. Ingold. Theoretical foundations of organic chemistry M., "Mir", 1973, p. 263;
**) ibid. 247; ***) According to the latest research, the mechanism of electrophilic substitution in aryliodides may be more complex than previously accepted.
About separation O- And P- isomers of disubstituted arenes by crystallization.
Table 3. M.p. O- And P-isomers of disubstituted arenes in o C.
COMPARISON OF ALKYLATION AND ACYLATION REACTIONS ACCORDING TO FRIEDEL-CRAFTS.
|
ALKYLATION |
ACYLATION |
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|
REAGENT |
AlkHal, AlkOH, alkenes. (No ArHal!). |
Carboxylic acid halides (CA), anhydrides CA, rarely - CA |
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|
CATALYST |
Lewis acids, especially non-ferrous halides Al, Fe, Sn, etc., BF 3, H 2 SO 4, H 3 PO 4, cation exchangers. |
AlCl 3 (no less mole per mole, better yet more), H 2 SO 4, H 3 PO 4. |
|
|
PRODUCT |
Alkyl and polyalkylarenes. |
Aromatic ketones. Only one acyl group can be introduced. |
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|
FEATURES AND DISADVANTAGES |
It is practically of little use due to many adverse reactions, namely: 1) polyalkylation, 2) isomerization of the original n-alkyl into sec- and tert-alkyl. 3) isomerization of polyalkylbenzenes into a mixture or into a more stable product. |
A very convenient reaction, practically uncomplicated by adverse reactions. As a rule, only the para isomer is formed. If P-position is occupied, then it is an ortho isomer (relative to the strongest orientation). |
|
|
REVERSIBILITY |
EAT. (see below) |
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|
APPLICATION AREA |
CANNOT BE USED for arenes containing type II substituents. Can be used for aryl halides. |
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|
FEATURES OF APPLICATION TO PHENOLS |
NOT DESIRED use AlCl 3 . CAN use catalysts - H 3 PO 4, HF with alcohols as alkylating reagents. |
CAcCl can undergo acylation on oxygen. When phenol ether is heated, FRIS regrouping(cat. – AlCl 3). Sometimes AcOH\BF 3 can be used for the Fr-Kr reaction Synthesis of phenolphthalein. |
|
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FEATURES OF APPLICATION TO AROMATICS CHESKY, AMINES |
Direct alkylation is practically impossible, since it is impossible to use AlCl 3, H 2 SO 4, H 3 PO 4, HF (attack of AlCl 3 or H + or alkyl on nitrogen - as a result, the electron-donating properties of nitrogen decrease. Under the action of RHal, N -alkylanilines). |
Nitrogen acylation occurs. Catalysts form nitrogen complexes. Acylation is possible using two equivalents. acylating agent and ZnCl 2 to form p-acyl-N-acylanilines. |
|
Note:
The reversibility of the alkylation reaction according to Friedel-Crafts leads to the fact that all possible alkylation and dealkylation reactions occur simultaneously in the system, and the meta position is also affected, since the alkyl group activates All positions of the benzene ring, although to varying degrees.
However, due to the preferential ortho-para orientation of the processes of alkylation and reverse dealkylation under the influence of an electrophile, for example, during the ipso-attack of a proton, the least reactive and more thermodynamically stable 1,3- and 1,3 accumulate in the mixture during a prolonged reaction ,5-isomers, since the alkyls in them less well orient the proton attack under other alkyls:
Similar reasons determine the formation of different regioisomers during sulfonation, with the significant difference that the sulfonic group is an orientant of the second kind, which makes polysulfonation difficult.
12. FORMATION – introduction of the SNO group.
Formylation is a special case of acylation.
Many formic acid derivatives can formylate arenes. Formylation reactions with CO, HCN, HCO(NMe 2) 2. Specifics of selecting electrophilic catalysts for formylation reactions.
GATTERMAN-KOCH(1897) – ArH + CO + HCl (AlCl 3 / Cu 2 Cl 2). Is there NS(O)S1? And NS(O)F?
GATTERMAN– HCN b\w + HCl gas. Cat. AlCl 3 or ZnCl 2.
Gutterman-Adams(optional) – Zn(CN) 2 + HCl. You can use 1.3.5. triazine,/HC1/A1C1 3 (optional), or C1 2 CHOR (at 5+++)
Guben-Gesh(acylation with RCN, HCl and ZnCl 2).
FORMATION ACCORDING TO VILSMEIER-HAACK. Only electron-enriched arena! + DMF + POC1 3 (can be SOCl 2, COCl 2).
13. Hydroxymethylation reaction, condensation of carbonyl compounds with arenes (DDT, diphenylolpropane), chloromethylation.
14.Applicability of formylation and hydroxymethylation reactions.
Gatterman-Koch - alkylbenzenes, benzene, halobenzenes.
Gatterman – activated arenes, toluene.
Vilsmeyer-Haack – only activated arenas
Chloromethylation – phenol, anisole, alkyl and halogen benzenes.
Hydroxymethylation – activated arenes.
(Activated arenes are anilines, phenol, and phenol esters.)
15. Triarylmethane dyes. Crystal violet (4-Me 2 N-C 6 H 4) 3 C + X - . Synthesis from p-Me 2 N-C 6 H 4 CHO + 2 Me 2 NPh + ZnCl 2 → LEUCO FORM (white color). Further oxidation (PbO 2 or other oxidizing agent) into tert- alcohol, then acid treatment, color appearance.
OPTIONAL MATERIAL.
1) Mercuration of benzene with Hg(OAc) 2 Hexamercuration of benzene with Hg(OAc F) 2. Preparation of hexaiodobenzene.
2) Decarboxylation of aromatic acids ArCOOH (heating with copper powder in quinoline) = ArH + CO 2. If there are electron-withdrawing groups in the ring, then you can simply heat the arenecarboxylic acid salt very strongly. If there are donors, especially in the ortho position, substitution of a carboxyl group by a proton is possible, but this is rare!
3) Exotic electrophiles in reactions with arenes: (HN 3 /AlCl 3 - gives aniline), R 2 NCl / AlCl 3 gives R 2 NAr) (SCl 2 /AlCl 3 gives Ar 2 S. Rhodanation of aniline or phenol with dirodan (SCN) 2. Formation of 2-aminobenzothiazoles.
4) There are a large number of “tricky” reactions that are impossible to remember and are not necessary, for example PhOH + TlOAc + I 2 = o-iodophenol, or PhOH + t-BuNH 2 + Br 2, -70 o C = o-bromophenol
NUCLEOPHILIC SUBSTITUTION IN THE AROMATIC SERIES.
Why does nucleophilic substitution in arenes that do not contain strong electron-withdrawing groups occur with great difficulty?
1. S N Ar– ADDING-DETACHING.
1) The nature of the intermediate. Meisenheimer complexes. (Conditions for stabilization of the intermediate.) 13 C NMR, ppm: 3(ipso), 75.8(o), 131.8(m), 78.0(p).
2) Nucleophiles. Solvents.
3) Mobility series of halogens. F (400)>>NO 2 (8)>Cl(1) ≈ Br(1.18)>I (0.26). Limiting stage.
4) Series of activating ability of substituents (in what position?) NO 2 (1)>MeSO 2 (0.05)>CN(0.03)>Ac(0.01).
5) Examples of specific reactions and specific conditions.
6) Optional: possibility of substitution of NO 2 - group. Selective substitution of NO 2 - groups. Spatial factors.
7) Nucleophilic substitution of hydrogen in di- and trinitrobenzene. Why do you need an oxidizing agent?
2. ARINE mechanism – (ABLISHMENT-ADDITION).
Labeled chlorobenzene and ortho-chlorotoluene, potassium or sodium amides in liquid NH 3 . Mechanism.
Hydrolysis of o-, m-, and p-chlorotoluene, NaOH, H 2 O, 350-400 o C, 300 atm. VERY HARD CONDITIONS!
The importance of the inductive effect. The case of o-chloroanisole.
The slow stage is proton abstraction (if Hal=Br, I) or halide anion abstraction (if Hal=Cl, F). Hence the unusual mobility series for halogens:Br>I> Cl>F
Methods for generating dehydrobenzene. The structure of dehydrobenzene - in this particle No triple bond! Dehydrobenzene recovery.
3. MechanismS RN1. Quite a rare mechanism. Generation of radical anions - electric current, or irradiation, or potassium metal in liquid ammonia. Reactivity ArI>ArBr. A few examples. What nucleophiles can be used? Application S RN1 : reactions for a-arylation of carbonyl compounds via enolates.
4. Nucleophilic substitution in the presence of copper. Synthesis of diphenyl ether, triphenylamine, hydrolysis of o-chloroanisole.
5. A few rare examples. Synthesis of salicylic acid from benzoic acid, nucleophilic substitution in hexafluorobenzene.
6. S N 1 Ar – see topic "Diazo compounds".
Further reading on the topic "Aromatic compounds"
M.V.Gorelik, L.S.Efros. Fundamentals of chemistry and technology of aromatic compounds. M., "Chemistry", 1992.
NITRO COMPOUNDS.
Minimum knowledge on aliphatic nitro compounds.
1. SYNTHESIS: a) direct nitration in the gas phase - only the simplest (1st semester, topic - alkanes).
b) RBr + AgNO 2 (ether) = RNO 2 (I) + RONO (II). The ratio of I and II depends on R: R first. 80:10; R tues. 15:30. R rubs 0:10:60 (E2, alkene). You can use NaNO 2 in DMF. Then the amount of RNO 2 is greater even for secondary R. Method b) is good for RX active in S N 2-substitution, for example ClCH 2 COONa + NaNO 2 in water at 85 o C. (topic: nucleophilic substitution and ambident anions, 1st semester).
c) NEW METHOD OF SYNTHESIS– oxidation of the amino group with CF 3 CO 3 H(from (CF 3 CO) 2 O + H 2 O 2 in CH 2 Cl 2 or MeCN). Suitable for aliphatic and aromatic amines. Sometimes you can take m-CNBA (m-chloroperbenzoic acid, m-CPBA, a commercial reagent). DO NOT TAKE KMnO 4 or K 2 Cr 2 O 7 FOR OXIDATION! Especially for aromatic amines!
2. PROPERTIES. The most important property is high CH acidity, tautomerism of nitro and aci forms (pKa MeNO 2 10.5). Equilibrium is established slowly! Both forms react with NaOH, but only the aci form reacts with soda! (Ganch).
High CH acidity makes nitro compounds analogues of enolizable carbonyl compounds. The acidity of nitromethane is close to the acidity of acetylacetone, and not simple aldehydes and ketones, so rather weak bases are used - alkalis, alkali metal carbonates, amines.
The Henri reaction (Henry) is an analogue of aldol or croton condensation. Since the Henri reaction is carried out under mild conditions, the product is often a nitroalcohol (an analogue of an aldol) rather than a nitroolefin (an analogue of a crotonic product). RСН 2 NO 2 is always a CH component!
Michael and Mannich reactions for RNO 2. Optional: halogenation in NaOH, nitrosation, alkylation of anions.
RESTORATION OF AROMATIC COMPOUNDS.
1) The most important intermediate products of the reduction of nitrobenzene in an acidic environment (nitrosobenzene, phenylhydroxylamine) and an alkaline environment (azoxybenzene, azobenzene, hydrazobenzene).
2) Selective reduction of one of the nitro groups in dinitrobenzene.
3) IMPORTANT PROPERTIES OF PRODUCTS OF INCOMPLETE RESTORATION OF NITROARENES.
3a) Benzidine rearrangement (B.P.).
YIELD 85% for benzidine. (R, R’ = H or other substituent). PAY ATTENTION TO THE POSITION OF R and R’ before and after regrouping!
Another 15% are by-products – mainly diphenyline (2,4’-diaminodiphenyl) and ortho-benzidine.
Kinetic equation: V=k[hydrazobenzene] 2– as a rule, protonation at both nitrogen atoms is necessary.
Benzidine rearrangement is an intramolecular reaction. Proof. Mechanism: concerted -sigmatropic rearrangement. Harmonized process for benzidine.
If one or both para positions of the starting hydrazobenzenes are occupied (R=Hal. Alk, AlkO, NH 2, NMe 2), a semidine rearrangement can occur to form SEMIDIN OV.
Some substituents, for example SO 3 H, CO 2 H, RC(O), located in the p-position, can be eliminated to form the products of the usual B.P.
B.P. used in the production of azo dyes, diamines, e.g. benzidine, tolidine, dianisidine. Discovered by N.N. Zinin in 1845
BENZIDINE IS A CARCINOGEN.
4) AZOBENZENE Ph-N=N-Ph. Syn-anti-isomerism.
AZOXYBENZENE Ph-N + (→О -)=N-Ph. (Task: synthesis of unsymmetrical azo- and azoxybenzenes from nitrosoarenes and aromatic amines or arylhydroxylamines, respectively, or synthesis of azoxybenzenes from nitrobenzenes and aromatic amines (NaOH, 175 o C).
5) PHENYLHYDROXYLAMINE. Rearrangement in acidic medium.
At 5 +: related rearrangements: N-nitroso-N-methylaniline (25 o C), N-nitroaniline (10 o C, was), Ph-NH-NH 2 (180 o C). The mechanism is usually intermolecular.
6) NITROSOBENZENE and its dimer.
About the reaction of nitrobenzene RMgX with the formation of alkylnitrosobenzenes and other products. This reaction shows why DO NOT make Grignard reagents from halonitrobenzenes!
METHODS FOR PRODUCING AMINES,
known from the materials of previous lectures.
1. Alkylation of ammonia and amines according to Hoffmann
2. Reduction of nitriles, amides, azides, oximes.
3. Reduction of aromatic nitro compounds.
4. Regroupings of Hoffmann, Curtius and Schmidt.
5. (Hydrolysis of amides.)
New ways.
1. Reductive amination of C=O (catalytic).
2. Leuckart (Eschweiler-Clark) reaction.
3. Gabriel synthesis,
4. Ritter reaction.
5. Catalytic arylation of amines in the presence of copper and palladium catalysts (Ullmann, Buchwald-Hartwig reactions) is the most powerful modern method for the synthesis of various amines.
Chemical properties of amines , known from previous lectures.
1. Nucleophilic substitution (alkylation, acylation).
2. Nucleophilic addition to C=O (imines and enamines).
3. Elimination according to Hoffmann and Cope (from amine oxides).
4. Electrophilic substitution reactions in aromatic amines.
5. Basicity of amines (school curriculum).
New properties .
1. Basicity of amines (new level of knowledge). What are pK a and pK b.
2. Reaction with nitrous acid.
3. Oxidation of amines.
4. Miscellaneous– Hinsberg test, halogenation of amines.
DIAZONE COMPOUNDS.
1. DIAZO and AZO compounds. DIAZONIUM SALT. Anions are simple and complex. Solubility in water. Explosive properties. Charge distribution on nitrogen atoms. Covalent derivatives.
2. Diazotization of primary aromatic amines. Diazotization mechanism (simplified scheme using H + and NO +). How many moles of acid are required? (Formally – 2, in reality – more.) Side formation of triazenes and side azo coupling.
3. Diazotizing agents in order of decreasing reactivity.
NO + >>H 2 NO 2 + >NOBr>NOCl>N 2 O 3 >HNO 2.
4. Nitrosation tues. And rubs. amines Reaction of aliphatic amines with HNO 2.
5. Diazotization methods: a) classical, b) for low-basic amines, c) reverse order of mixing, d) in a non-aqueous medium - use of i-AmONO. Features of diazotization of phenylenediamines. Monitoring the completion of the reaction.
6. Behavior of diazonium salts in an alkaline environment. Diazohydrate, syn- and anti-diazotates. Ambidity of diazotates.
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7. Reactions of diazo compounds with the release of nitrogen. 1) The thermal decomposition of aryldiazonium occurs through highly reactive aryl cations. The substitution mechanism in this case is similar to S N 1 in aliphatic chemistry. This mechanism is followed by the Schiemann reaction and the formation of phenols and their ethers. 2) Nucleophiles are reducing agents. The mechanism is electron transfer and formation of an aryl radical. According to this mechanism, a reaction with iodide ion occurs, replacing the diazo group with hydrogen. 3) Reactions in the presence of copper powder or copper(I) salts. They also have a radical nature; copper plays the role of a reducing agent. The nucleophile is transferred to the aryl radical in the coordination sphere of copper complexes. Such reactions are the majority in the chemistry of diazonium salts. Sandmeyer reaction and its analogues. 4) Nesmeyanov’s reaction. 5) Diaryliodonium and bromonium salts. |
8. Reactions of diazo compounds without nitrogen evolution. Recovery. Azo combination, requirements for azo and diazo components. Examples of azo dyes (methyl orange). |
9. Gomberg-Bachmann and Meyerwein reactions A modern alternative is cross-coupling reactions catalyzed by transition metal complexes and the Heck reaction. At 5++: cross-combination with diazonium salts and diaryliodonium salts.
10. DIAZOMETHANE. Preparation, structure, reactions with acids, phenols, alcohols (difference in conditions), with ketones and aldehydes.
PHENOLS AND QUINONES.
Most of the most important methods for the synthesis of phenols are known from the materials of previous lectures:
1) synthesis through Na-salts of sulfonic acids;
2) hydrolysis of aryl chlorides;
3) through diazonium salts;
4) cumene method.
5) hydroxylation of activated arenes according to Fenton.
PROPERTIES OF PHENOLS.
1) Acidity; 2) synthesis of esters; 3) electrophilic substitution (see topic "Electrophilic substitution in arenas");
4) Electrophilic substitution reactions not previously considered: Kolbe carboxylation, Reimer-Tiemann formylation, nitrosation; 5) tautomerism, examples; 6) Synthesis of ethers; 6a) synthesis of allyl ethers; 7) Claisen rearrangement;
8) oxidation of phenols, aroxyl radicals; Bucherer reaction;
10) conversion of PhOH to PhNR 2.
QUINONES.
1. Structure of quinones. 2. Preparation of quinones. Oxidation of hydroquinone, semiquinone, quinhydrone. 3. Chloranil, 2,3-dichloro-5,6-dicyano-1,4-quinone (DDQ). 4. Properties of quinones: a) redox reactions, 1,2- and 1,4-addition, Diels-Alder reaction.
IMPORTANT NATURAL ENOLS, PHENOLS AND QUINONES.
VITAMIN C (1): Ascorbic acid. Reducing agent. Staining with FeCl 3 . In nature, it is synthesized by all chlorophyll-containing plants, reptiles and amphibians, and many mammals. In the course of evolution, humans, monkeys, and guinea pigs have lost the ability to synthesize it.
The most important functions are the construction of intercellular substance, tissue regeneration and healing, the integrity of blood vessels, resistance to infection and stress. COLLAGEN SYNTHESIS (hydroxylation of amino acids). (Collagen is everything about us: skin, bones, nails, hair.) Synthesis of norepinephrine. Lack of vitamin C – scurvy. Vitamin C content: black currant 200 mg/100 g, red pepper, parsley – 150-200, citrus fruits 40-60, cabbage – 50. Requirement: 50-100 mg/day.
TANNIN, this is gallic acid glycoside (2). Contained in tea, has tanning properties
RESVERATROL(3) – found in RED WINE (French). Reduces the likelihood of cardiovascular diseases. Inhibits the formation of ENDOTHELIN-1 peptide, a key factor in the development of atherosclerosis. Helps promote French wine on the market. More than 300 publications over the past 10 years.
CLOVE OIL: eugenol (4).
VITAMIN E (5)(tocopherol - “I carry offspring”). Antioxidant. (It itself forms inactive free radicals). Regulates selenium metabolism in glutathione peroxidase, an enzyme that protects membranes from peroxides. With a deficiency - infertility, muscular dystrophy, decreased potency, the oxidation of lipids and unsaturated fatty acids increases. Contained in vegetable oils, lettuce, cabbage, yolk, cereals, oatmeal (rolled oatmeal, muesli). Requirement – 5 mg/day. Vitamin deficiency is rare.
VITAMINS OF GROUP K (6). Regulation of blood clotting and mineralization of bone tissue (carboxylation of the glutamic acid residue at position 4 (in proteins!)) - result: calcium binding, bone growth. Synthesized in the intestines. Requirement – 1 mg/day. Hemorrhagic diseases. Antivitamins K. Dicumarin. Reduced blood clotting during thrombosis.
UBIQINON(“ubiquitous quinone”), also known as coenzyme Q (7). Electron transfer. Tissue respiration. ATP synthesis. Synthesized in the body.
CHROMONE (8) and FLAVONE (9)– semiquinones, phenol half-esters.
QUERCETIN (10). RUTIN – vitamin P (11)(this is quercetin + sugar).
Permeability vitamin. If there is a deficiency, bleeding, fatigue, pain in the limbs. The connection between vitamins C and P (ascorutin).
ANTHOCYANINS(from Greek: coloring of flowers).
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WHAT IS LIGNIN? What does wood consist of? Why is it hard and waterproof?
"ALICYCLES", 2 lectures.
1. Formal classification of cycles(heterocycles and carbocycles, both of which can be aromatic or non-aromatic. Non-aromatic carbocycles are called alicycles.
2. Distribution in nature (oil, terpenes, steroids, vitamins, prostaglandins, chrysanthemum acid and pyrethroids, etc.).
3. Synthesis - end of the 19th century. Perkin Jr. – from natrmalonic ester. (see paragraph 13). Gustavson:
Br-CH 2 CH 2 CH 2 -Br + Zn (EtOH, 80 o C). This is 1,3-elimination.
4. BAYER (1885). Tension theory. This is not even a theory, but a discussion article: According to Bayer – all cycles are flat. Deviation from angle 109 about 28’ – voltage. The theory lived and lived for 50 years, then died, but the term remained. First syntheses of macro- and medium cycles (Ruzicka).
5. TYPES OF STRESS IN CYCLES: 1) ANGULAR (small cycles only), 2) TORSIONAL (obstructed), TRANSANNULAR (in medium cycles).
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Eg. according to Bayer |
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Eg. according to D H o f kcal/m (heat image) |
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Eg. according to D H o f kcal/m: C 9 (12.5 kcal/m), C 10 (13 kcal/m), C 11 (11 kcal/m), C 12 (4 kcal/m), C 14 (2 kcal/m). |
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Heat of combustion for CH 2 group, kcal/m |
SMALL CYCLES 166.6 (C3), 164.0 (C4) |
REGULAR 158.7 (C5), 157.4 (C6) |
MIDDLE TO FROM 12 (FROM 13) MACROCYCLES > C 13 |
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6. CYCLOPROPANE. Structure(С-С 0.151 nM, Р НСН = 114 о), hybridization ( According to calculations, for C-H it is closer to sp 2, for C-C - to sp 5), banana bonds, angle 102 o, similarity to alkenes, TORSION stress - 1 kcal/m per C-H, i.e. 6 kcal/m from 27.2 (table). Acidity CH - pKa like ethylene = 36-37, possible conjugation of the cyclopropane fragment with R-orbitals of neighboring fragments (stability of cyclopropylmethyl carbocation) .
FEATURES OF CHEMICAL PROPERTIES. 1. Hydrogenation in C 3 H 8 (H 2 /Pt, 50 o C)/ 2. with wet HBr - ring opening of methylcyclopropane according to Markovnikov, 1,5-addition to vinylcyclopropane 3. Radical halogenation. 4. Resistance to some oxidizing agents (neutral solution of KMnO 4, ozone). In phenylcyclopropane, ozone oxidizes the Ph ring to form cyclopropanecarboxylic acid.
7. CYCLOBUTANE. Structure(С-С 0.155 nM, Р НСН = 107 о) , CONFORMATION – folded, deviation from the plane is 25 o. TORSIONAL Stress.
Almost not FEATURES OF CHEMICAL PROPERTIES:Hydrogenation in C 4 H 10 (H 2 / Pt, 180 o C). Structural features of oxetanes: TORSION stress – 4 kcal/m instead of 8.
8. CYCLOPENTANE. There is almost no angular stress. In a flat one there are 10 pairs of obscured CH bonds (this could give a torsion stress of 10 kcal/m, but cyclopentane is not flat). Conformations: open ENVELOPE – half-chair – open ENVELOPE. PSEUDO-ROTATION is a compromise between angular and torsional stress.
9. CYCLOHEXANE – CHAIR. There is no angular or torsional stress. Axial and equatorial atoms. All C-H bonds of neighboring carbon atoms are in an inhibited position. Transition between two possible chair conformations via a twist shape, etc. 10 5 times per second. NMR spectrum of cyclohexane. Fast and slow metabolic processes in NMR.
MONOSUBSUBMITTED CYCLOHEXANES. Conformers. Axial and gauche-butane interactions.
Free conformational energies of substituents.– D G o, kcal/m: H(0), Me(1.74, this is ~ 95% of the e-Me conformer at equilibrium), i-Pr(2.1), t-Bu (5.5), Hal (0.2-0.5) Ph (3.1).
Tret-butyl group acts as an anchor, securing the conformation in which it itself occupies an equatorial position. IN rubs-butylcyclohexane at room temperature is more than 99.99% equatorial conformer.
Anomeric effect. Discovered on monosaccharides and will be discussed in more detail there.
10. DISUBMITTED CYCLOHEXANES. Cis-trans isomers, enantiomers for 1,2-. 1.3-. 1,4-disubstituted cyclohexanes.
11. INFLUENCE OF CONFORMATIONAL STATE on reactivity. Recall elimination in menthyl and isomenthyl chloride (1 sem). Bredt's rule.
12. The concept of conformations of middle cycles (chair-baths, crowns, etc.)Transannular tension. The concept of transannular reactions.
13. Methods for the synthesis of small cycles.
14. SYNTHESIS OF ORDINARY AND MEDIUM CYCLES.
Through malonic ether.
Pyrolysis of Ca, Ba, Mn, Th salts of a,w-dicarboxylic acids.
Dieckmann condensation.
Through a,w – dinitriles.
Acyloic condensation.
Metathesis of alkenes.
Cyclotri- and tetramerization on metal complex catalysts.
Demyanov's reaction.
15. Structural features of cycloalkenes.
16. Synthesis of cycloalkynes.
17. Bicycles. Spiranes. Adamantane.
18. Exotic. Tetrahedran, cuban, angulan, propellane.
HETEROCYCLIC COMPOUNDS.
1. Five-membered heterocycles with one heteroatom.
Pyrrole, furan, thiophene, aromaticity, their derivatives in nature (porphyrin, heme, chlorophyll, vitamin B 12, ascorbic acid, biotin).
2. Methods for the synthesis of five-membered heterocycles with one heteroatom. Paal-Knorr method. Pyrrole synthesis according to Knorr and furan according to Feist-Benary. Transformations of furan into other five-membered heterocycles according to Yuryev. Preparation of furfural from plant waste containing five-carbon carbohydrates (pentosans).
3. Physical and chemical properties of five-membered heterocycles.
1H and 13C NMR spectra data, δ ppm. (for benzene δН 7.27 and δС 129 ppm)
Dipole moments
3.1 Electrophilic substitution in pyrrole, furan and thiophene.
In terms of reactivity towards electrophiles, pyrrole resembles activated aromatic substrates (phenol or aromatic amines), pyrrole is more reactive than furan (rate factor more than 10 5), thiophene is much less reactive than furan (also approximately 10 5 times), but more reactive than benzene (rate factor 10 3 -10 5). All five-membered heterocycles are prone to polymerization and resinization in the presence of strong protic acids and highly reactive Lewis acids. Pyrrole is particularly acidophobic. FOR ELECTROPHILIC SUBSTITUTION IN FIVE-MEMBERED HETEROCYCLES, ESPECIALLY PYRROLES, STRONG MINERAL ACIDS, AlCl 3, AND STRONG OXIDIZING AGENTS CANNOT BE TAKEN! Although this rule is not absolute, and thiophene is somewhat acid-resistant, it is simpler and safer to avoid such reactions altogether for all donor heterocycles. Examples of electrophilic substitution reactions in pyrrole, furan and thiophene.
3.2. Basicity and acidity of pyrrole, alkylation of Li, Na, K and Mg derivatives of pyrrole.
3.3. Condensation of pyrrole with aldehydes (formylation, formation of porphyrins).
3.4. Features of the chemical properties of furans (reaction with bromine, Diels-Alder reaction.
3.5. Features of the chemical properties of thiophene. Desulfurization.
3.6. Reactions of C-metalated five-membered heterocycles.
4. Condensed five-membered heterocycles with one heteroatom.
4.1. Indoles in nature (tryptophan, skatole, serotonin, heteroauxin. Indigo.)
4.2 Fischer synthesis of indoles. Mechanism.
4.3 Comparison of the properties of indole and pyrrole. Similar to pyrrole indole is acidophobic and very sensitive to oxidizing agents. A significant difference from pyrrole is the orientation of the electrophilic substitution at position 3.
5. Five-membered heterocycles with two heteroatoms. Imidazole, amphotericity, tautomerism, use in acylation. Comparison with amidines. Imidazole is a hydrogen bond donor and acceptor. This is important for the chemistry of enzymes such as chymotrypsin. It is the histidine fragment of chymotrypsin that transfers the proton and ensures the hydrolysis of the peptide bond.
6. Pyridine, aromaticity, basicity ( pKa 5.23; basicity comparable to aniline (pKa = 4.8), but slightly higher). pKa of pyridine derivatives: 2-amino-Py= 6,9 , 3-amino-Py = 6,0 . 4-amino-Py = 9.2. This is a pretty strong foundation. 4-nitro-Py = 1.6; 2-cyano-Py= -0.26).
Pyridine derivatives in nature (vitamins, nicotine, NADP).
6.1. 1H (13C) NMR spectra data, δ, ppm
6.2. Methods for the synthesis of pyridines (from 1,5-diketones, three-component Hantzsch synthesis).
6.3. Chemical properties of pyridine. Alkylation, acylation, DMAP, pyridine complexes with Lewis acids. (cSO 3, BH 3, NO 2 + BF 4 -, FOTf). Mild electrophilic reagents for sulfonation, reduction, nitration and fluorination, respectively.
6.4. Electrophilic substitution reactions for pyridine. Features of reactions and examples of conditions for electrophilic substitution in pyridine.
6.5. Pyridine N-oxide, preparation and its use in synthesis. Introduction of a nitro group into the 4-position of the ring.
6.6. Nucleophilic substitution in 2-, 3-, and 4-chloropyridines. Partial rate factors compared to chlorobenzene.
A similar trend is observed for 2-, 3- and 4-haloquinolines.
6.7. Nucleophilic substitution of hydride ion:
reaction of pyridine with alkyl or aryllithium;
reaction of pyridine with sodium amide (Chichibabin reaction). Since elimination of the free hydride ion is impossible for energetic reasons, in the Chichibabin reaction the intermediate sigma complex is aromatized by reacting with the reaction product to form the sodium salt of the product and molecular hydrogen.
In other reactions, the hydride is usually removed by oxidation. So, pyridinium salts can undergo hydroxylation, leading to the formation of 1-alkylpyridones-2. The process is similar to amination, but in the presence of an oxidizing agent, for example, K 3 .
6.8. Lithium derivatives of pyridine. Reception, reactions.
6.9. Pyridine nucleus as a strong mesomeric acceptor. Stability of carbanions conjugated to the pyridine ring in 2- or 4-positions. Features of the chemical properties of methylpyridines and vinylpyridines.
7. Condensed six-membered heterocycles with one heteroatom.
7.1. Quinoline. Quinine.
1H (13C) NMR spectra of quinoline, δ, ppm.
7.1. Methods for obtaining quinolines. Syntheses of Scroup and Döbner-Miller. The concept of the mechanism of these reactions. Synthesis of 2- and 4-methylquinolines.
7.2. Isoquinolines,synthesis according to Bischler-Napieralski .
7.3. Chemical properties of quinolines and isoquinolines. Comparison with pyridine, differences in the properties of pyridine and quinoline.
Behavior of heterocyclic compounds in the presence of oxidizing and reducing agents intended to modify side chains.
Reducers:
Pyrrole is almost unlimitedly resistant to reducing agents, as well as bases and nucleophiles (for example, it can withstand hydrides, borane, Na in alcohol without affecting the ring, even with prolonged heating).
Thiophene - like pyrrole, is resistant to reducing agents, as well as bases and nucleophiles, with the exception of reducing agents based on transition metals. Any nickel compounds (Raney nickel, nickel boride) cause desulfurization and hydrogenation of the skeleton. Palladium and platinum catalysts are usually poisoned by thiophenes and do not work.
Furan is the same as pyrrole, but is very easily hydrogenated.
Indole is completely similar to pyrrole.
The pyridine ring is reduced more easily than the benzene ring. For side chains, you can use NaBH 4 , but it is undesirable (often even impossible) to use LiAlH 4 .
For quinoline, the rules are almost the same as for pyridine; LiAlH 4 cannot be used.
In quaternized form (N-alkylpyridinium, quinolinium) they are very sensitive to reducing agents (ring reduction), bases, and nucleophiles (ring opening).
Oxidizing agents.
The use of oxidizing agents for compounds of pyrrole, indole and, to a lesser extent, furan, usually leads to destruction of the ring. The presence of electron-withdrawing substituents increases resistance to oxidizing agents, however, more detailed information about this is beyond the scope of the 3rd year program.
Thiophene behaves like benzene - ordinary oxidizing agents do not destroy the ring. But the use of peroxide oxidizers in any form is strictly prohibited - sulfur is oxidized to sulfoxide and sulfone with loss of aromaticity and immediate dimerization.
Pyridine is quite stable to most oxidizing agents under mild conditions. The ratio of pyridine to heating with KMnO 4 (pH 7) to 100 o C in a sealed ampoule is the same as for benzene: the ring is oxidized. In an acidic environment, pyridine in its protonated form is even more resistant to oxidizing agents; a standard set of reagents can be used. Peracids oxidize pyridine to N-oxide - see above.
Oxidation of one of the quinoline rings with KMnO 4 leads to pyridine-2,3-dicarboxylic acid.
8. Six-membered heterocycles with several nitrogen atoms
8.1. Pyrimidine. Pyrimidine derivatives as components of nucleic acids and drugs (uracil, thymine, cytosine, barbituric acid). Antiviral and antitumor drugs - pyrimidines (5-fluorouracil, azidothymidine, alkylmethoxypyrazines - components of the smell of food, fruits, vegetables, peppers, peas, fried meat. The so-called Maillard reaction (optional).
8.2. The concept of the chemical properties of pyrimidine derivatives.
Pyrimidine can be brominated at position 5. Uracil (see below) can also be brominated and nitrated at position 5.
Mild reactions S N 2 Ar in chloropyrimidines(analogy with pyridine!): Position 4 goes faster than position 2.
Substitution of 2-C1 under the influence of KNH 2 in NH 3 l. The mechanism is not arine, but ANRORC (5+++).
10. Binuclear heterocycles with several nitrogen atoms. Purines ( adenine, guanine).
The most famous purines (caffeine, uric acid, acyclovir). Purine isosteres (allopurinol, sildenafil (Viagra™)).
Additional literature on the topic "Heterocycles"
1. T. Gilchrist “Chemistry of heterocyclic compounds” (Translated from English - M.: Mir, 1996)
2. J. Joule, K. Mills “Chemistry of heterocyclic compounds” (Translated from English - M.: Mir, 2004).
AMINO ACIDS .
1. Amino acids (AA) in nature. (≈ 20 amino acids are present in proteins, these are encoded by AAs; >200 AAs occur in nature.)
2. α-, β-, γ-amino acids. S-configuration of natural L-amino acids.
3. Amphotericity, isoelectric point(pH is usually 5.0-6.5). Basic (7.6-10.8), acidic (3.0-3.2) amino acids. Confirmation of the zwitterionic structure. Electrophoresis.
4. Chemical properties of AK– properties of COOH and NH 2 groups. Chelates. Betaines. Behavior when heating(compare with hydroxy acids). The formation of azlactones from N-acetylglycine and hydantoins from urea and AA is 5++. Ester synthesis and N-acylation are the path to peptide synthesis (see lecture on protein).
5. Chemical and biochemical deamination,(don’t teach the mechanisms!), the principle of enzymatic transamination with vitamin B 6 (was in the topic “Carbonyl Compounds” and in the course of biochemistry).
7. The most important methods of amino acid synthesis:
1) from halocarboxylic acids - two primitive methods, including phthalimide. (Both are already known!)
2) Strecker synthesis;
3) alkylation of CH acid anions – PhCH=N–CH 2 COOR and N-acetylaminomalonic ester.
4) Enantioselective synthesis of AA by:
a) microbiological (enzymatic) separation and
b) enantioselective hydrogenation using chiral catalysts.
5) β-amino acids. Synthesis according to Michael.
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Hydrophobic amino acids |
A little about the biochemical role (for general development) |
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ALANIN |
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Removal of ammonia from tissues to the liver. Transamination, transformation into pyruvic acid. Synthesis of purines, pyrimidines and heme. |
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VALINE* |
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If, as a result of a mutation, valine replaces the glutamine acid in hemoglobin, a hereditary disease occurs—sickle cell anemia. A serious hereditary disease common in Africa, but which confers resistance to malaria. |
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LEUCINE* |
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ISOLEUCINE* |
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PROLINE |
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Bends in protein molecules. No rotation where there is proline. |
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PHENYLALANINE* |
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If it is not converted into tyrosine, there will be a hereditary disease, phenylpyruvic oligophrenia. |
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TRYPTOPHAN* |
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Synthesis of NADP, serotonin. Breakdown in the intestines to skatole and indole. |
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Hydrophilic amino acids |
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GLYCINE Gly (G) |
H 2 N-CH 2 -COOH |
Participates in a huge number of biochemical syntheses in the body. |
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SERINE Ser (S) |
HO-CH 2-CH(NH2)-COOH |
Participate (as part of proteins) in the processes of acylation and phosphorylation. |
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THREONINE* Thr (T) |
CH 3 -CH(OH)-CH(NH 2)-COOH |
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TYROSINE Tyr (Y) |
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Synthesis of thyroid hormones, adrenaline and norepinephrine |
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"Acidic" amino acids |
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ASPARAGIC ACID Asp (D) |
HOOC-CH 2-CH(NH2)-COOH |
Amino group donor in syntheses. |
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GLUTAMIC ACID Glu(E) |
HOOC-C 4 H 2 -CH 2-CH(NH2)-COOH |
Forms GABA (γ-aminobutyric acid (aminalone) - a sedative. Glu removes NH 3 from the brain, turning into glutamine (Gln). 4-carboxyglutamic acid binds Ca in proteins. |
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"A M I D S" of acidic amino acids |
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ASPARAGINE Asn(N) |
H2N-CO-CH 2 -CH(NH 2)-COOH |
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GLUTAMINE Gln (Q) |
H2N-CO-CH 2 -CH 2 -CH(NH 2)-COOH |
Donoramino groups in syntheses |
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CYSTEINE Cys(C) |
HS-CH 2-CH(NH2)-COOH |
Formation of S-S bonds (tert, protein structure, regulation of enzyme activity) |
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CYSTINE |
Cys-S-S-Cys |
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METHIONINE* Met |
MeSCH 2 CH 2 - CH(NH2)COOH |
Methyl group donor |
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"Essential" amino acids |
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LYSINE* Lys (K) |
H 2 N-(CH 2) 4 -CH(NH 2)-COOH |
Forms crosslinks in collagen and elastin making them elastic. |
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ARGININE Arg(R) Contains a guanidine fragment |
H 2 N-C(=NH)-NH-(CH 2) 3 -CH(NH 2)-COOH |
Participates in the removal of ammonia from the body |
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HISTIDINE His(H) Imidazole residue |
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Histamine synthesis. Allergy. |
* - essential amino acids. Glucose and fats are easily synthesized from most amino acids. Amino acid metabolism disorders in children lead to mental disability.
PROTECTING GROUPS USED IN PEPTIDE SYNTHESIS.
N.H. 2 -protecting groups –
RC(O)- = ( HC(O)- ) CF 3 C(O) - phthalylic
ROC(O)- = PhCH 2 OC(O)- and substituted benzyls , t-BuOC(O)- and etc. rubs-groups,
Fluorenylmethyloxycarbonyl group,
Ts-group
COOH -protecting groups – ethers – PhCH 2 O- and substituted benzyls,
t-BuO- and fluorenyl methyl ethers.
Separate consideration of protective groups for other amino acid amino acids is not provided.
Methods for creating a peptide bond.
1. Acid chloride (via X-NH-CH(R)-C(O)Cl). The method is outdated.
2..Azide (according to Curtius, through X-NH-CH(R)-C(O)Y → C(O)N 3 as a soft acylating reagent.
3.Anhydrite – e.g. through mixed anhydride with carbonic acid.
4. Activated esters (for example C(O)-OS 6 F 5, etc.)
5. Carbodiimide – acid + DCC + amine
6. Synthesis on a solid support (for example, on Merrifield resin).
Biological role of peptides. A few examples .
1. Enkephalins and endorphins are opioid peptides.
for example Tyr-Gly-Gly-Phe-Met and
Tyr-Gly-Gly-Phe-Leu from pig brain. Several hundred analogues are known.
2. Oxytocin and vasopressin Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu -Gly-NH 2
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DuVigneaud, Nob.pr. 1955 Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Arg -Gly-NH 2
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3. Insulin controls the uptake of glucose by the cell. Excess glucose in the blood (diabetes) leads to glycosylation of everything (mainly proteins).
4. Peptide transformations: angiotensinogen → angiotensin I → angiotensin II. One of the main mechanisms for regulating blood pressure (BP), the site of application of many drugs (ACE blockers - angiotensin-converting enzyme. Stage 1 catalyst is the enzyme renin (isolated from the kidneys).
5. Peptide toxins. Effective against diseases - botulism, tetanus, diphtheria, cholera. Poisons of snakes, scorpions, bees, fungal toxins (phalloidin, amantine), marine invertebrates (Conusgeographus – 13 AK, two -S-S-bridges). Many are stable when boiled in an acidic solution (up to 30 minutes).
6. Peptide antibiotics (gramicidin S).
7. Aspartame Asp-Phe-OMe is 200 times sweeter than sugar. Bitter and "tasty" peptides.
8. Proteins. Four levels of organization of the native protein molecule. A protein is a unique (along with nucleic acids) type of macromolecule that has a precisely known structure, ordered down to the details of stereochemistry and conformation. All other known macromolecules, including natural ones (polysaccharides, lignin, etc.) have a more or less disordered structure - a wide distribution of molecular weights, free conformational behavior.
The primary structure is the sequence of amino acids. What is the shorthand name for primary structure?
Secondary structure - conformationally regular elements of two types (α-helices and β-layers) - this is how only part of the protein macromolecule is ordered.
Tertiary structure is a unique ordered stereochemical configuration of a complete macromolecule. The concept of “folding” a polypeptide chain into the tertiary structure of a protein. Prions.
Quaternary structure is a combination of several subunits in proteins consisting of several polypeptide chains. Disulfide bridges (reversible transformation of cysteine-cystine) as a way to fix tertiary and quaternary structures.
CARBOHYDRATES.
1. What are carbohydrates? Carbohydrates are around and inside us.
2. The concept of photosynthesis of D-glyceric acid derivatives. Only for particularly outstanding students - the formation of glyceric acid diphosphate from D-ribulose.
3. What is the D-series of carbohydrates?(Briefly about the history of the concept of D- and L-series).
4. Classification of carbohydrates: a) by the number of C atoms; b) by the presence of C=O or CHO groups; c) by the number of cyclic fragments.
5. Synthesis of carbohydrates from D-glyceraldehyde using the Kiliani-Fisher method.How did Fischer establish the formula for glucose?
6. Derivation of the formulas of all D-tetroses, -pentoses, -hexoses from D-glyceraldehyde (open structures). For all students – know the formula of glucose (open and cyclic), mannose (2-glucose epimer), galactose (4-glucose epimer), ribose. Pyranoses and furanoses.
7. Be able to move from an open form to a cyclic form according to Haworth. Be able to draw the formulas of α- and β-glucose (all substituents in the e-position except the anomeric one) in the chair conformation.
8. What are epimers, anomers, mutarotation. Anomeric effect.
9. Chemical properties of glucose as an aldehyde alcohol: a) chelates with metal ions, preparation of glycosides, full ethers and esters, isopropylidene protection; b) oxidation of the CHO group with metal ions, bromine water, HNO 3. Splitting by Will. Reaction with amines and obtaining ozazones. The most important principles and techniques for selective alkylation of various hydroxyls in glucose.
10. D-fructose as a representative of ketoses. Open and cyclic forms. Silver mirror reaction for fructose.
11. The concept of deoxy sugars, amino sugars. This also includes chitin and heparin. Septulose and octulose in avocados. Maillard reaction.
12. OLIGOSACHARIDES. Maltose,cellobiose,lactose, sucrose. Reducing and non-reducing sugars.
13. Polysaccharides – starch(20% amylose + 80% amylopectin),starch iodine test, glycogen, cellulose,hydrolysis of starch in the oral cavity (amylase) and hydrolysis of cellulose,nitro fiber, viscose fiber, paper production , blood groups and the differences between them.
IMPORTANT POLYSACCHARIDES.
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POLYSACCHARIDE |
COMPOSITION and structure |
notes |
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cyclodextrins |
α-(6), β-(7), γ-(8) Consists of glucose 1-4 connections. |
Excellent complexing agents, chelating agents |
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starch |
α-glu-(1,4)-α-glu 20% amylose + 80% amylopectin |
Amylose= 200 glu, linear polysaccharide. Amylopectin= 1000 or more glu, branched. |
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glycogen |
"branched" starch, participation of 6-OH |
Glucose reserves in the body |
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From fructose residues |
Contained in Jerusalem artichoke |
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cellulose |
β-glu-(1,4)-β-glu |
Cotton, plant fiber, wood |
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cellulose |
Xanthate at 6-position |
Production of viscose - rayon, cellophane (packaging film) |
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cellulose acetate |
Approximately diacetate |
acetate fiber |
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cellulose nitrate |
Trinitroether |
Smokeless powder |
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Making paper from wood |
Wood = cellulose + lignin. Treat with Ca(HSO 3) 2 or Na 2 S + NaOH |
Sulfation of wood - removal of lignin into water - production of cellulose pulp. |
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Poly-α-2-deoxy-2-N-Ac-aminoglucose (instead of 2-OH - 2-NH-Ac) |
If you remove Ac from nitrogen you get chitosan - a fashionable dietary supplement |
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hyaluronic acid |
– (2-AcNH-glucose – glucuronic acid) n – |
Lubrication in the body (eg joints). |
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The structure is very complex – (2-HO 3 S-NH-glucose – glucuronic acid) n – |
Increases blood clotting time |
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Chondroitin sulfate |
Glycoproteins (collagen), proteoglycans, connection through NH 2 asparagine or OH serine |
Found everywhere in the body, especially in connective tissue and cartilage. |
Note: Glucuronic acid: 6-COOH – 1-CHO
Gluconic acid: 6-CH 2 OH – 1-COOH
Glucaric acid: 6-COOH – 1-COOH
1. Chemistry and biochemistry of nucleic acids.
Nitrogen bases in RNA: U (uracil), C (cytosine) are pyrimidine derivatives. A (adenine), G (guanine) are purine derivatives. In DNA Instead of U (uracil), T (thymine) is present.
Nucleosides ( sugar+ nitrogen base): uridine, cytidine, thymidine, adenosine, guanosine.
Nucleotides( phosphate+ sugar+ nitrogenous base).
Lactim-lactam tautomerism.
Primary structure nucleic acids (connection of nucleosides through the oxygen atoms at C-3 and C-5 of ribose (deoxyribose) using phosphate bridges.
RNA and DNA.
a) Major bases and minor bases (RNA). For tRNA alone, the list of minor bases approaches 50. The reason for their existence is protection from hydrolytic enzymes. 1-2 examples of minor bases.
c) Chargaff's rules for DNA. The most important: A=T. G=C. However, G+C< А+Т для животных и растений.
Principles of DNA structure
1. Irregularity.
There is a regular sugar phosphate backbone to which nitrogenous bases are attached. Their alternation is irregular.
2. Antiparallelism.
DNA consists of two polynucleotide chains oriented antiparallel. The 3' end of one is located opposite the 5' end of the other.
3. Complementarity (complementarity).
Each nitrogenous base of one chain corresponds to a strictly defined nitrogenous base of the other chain. Compliance is determined by chemistry. Purine and pyrimidine pair together to form hydrogen bonds. There are two hydrogen bonds in the A-T pair, and three in the G-C pair, since these bases have an additional amino group in the aromatic ring.
4. Presence of a regular secondary structure.
Two complementary, antiparallel polynucleotide chains form right-handed helices with a common axis.
Functions of DNA
1. DNA is the carrier of genetic information.
The function is provided by the fact of the existence of a genetic code. Number of DNA molecules: in a human cell there are 46 chromosomes, each containing one DNA molecule. The length of 1 molecule is ~ 8 (i.e. 2x4) cm. When packaged, it is 5 nm (this is the tertiary structure of DNA, supercoiling of DNA on histone proteins).
2. Reproduction and transmission of genetic information is ensured by the process of replication (DNA → new DNA).
3. Realization of genetic information in the form of proteins and any other compounds formed with the help of enzyme proteins.
This function is provided by the processes of transcription (DNA to RNA) and translation (RNA to protein).
Repair– restoration of the damaged DNA section. This is due to the fact that DNA is a double-stranded molecule; there is a complementary nucleotide that “tells” what needs to be corrected.
What errors and damages occur? a) Replication errors (10 -6), b) depurination, loss of purine, formation of apurine sites (in each cell the loss of 5000 purine residues per day!), c) deamination (for example, cytosine turned into uracil).
Inducible damage. a) dimerization of pyrimidine rings under the influence of UV at C=C bonds with the formation of a cyclobutane ring (photolyases are used to remove dimers); b) chemical damage (alkylation, acylation, etc.). Damage repair – DNA glycosylase – apurinization (or apyrimidinization) of the alkylated base – then the introduction of a “normal” base in five stages.
Disruption of the reparation process – hereditary diseases (xeroderma pigmentosum, trichothiodystrophy, etc.) There are about 2000 hereditary diseases.
Transcription and translation inhibitors are antibacterial drugs.
Streptomycin – inhibitor of protein synthesis in prokaryotes.
Tetracyclines - “bind to the 30S subunit of the bacterial ribosome and block the attachment of aminoacyl-tRNA to the A-center of the ribosome, thereby disrupting elongation (i.e., reading of mRNA and synthesis of the polypeptide chain).”
Penicillins and cephalosporins – β-lactam antibiotics. The β-lactam ring inhibits cell wall synthesis in Gram-negative microorganisms.
Viruses – inhibitors of matrix synthesis in eukaryotic cells.
Toxins – often do the same thing as viruses. α-Amanitin– toadstool toxin, LD 50 0.1 mg per kg body weight. Inhibition of RNA polymerase. The result is irreversible changes in the liver and kidneys.
Ricin – a very strong protein poison from castor beans. This is an N-glycosylase enzyme that removes an adenine residue from the 28S rRNA of the large ribosomal subunit and inhibits protein synthesis in eukaryotes. Contained in castor oil.
Enterotoxin from the causative agent of diphtheria (protein with a mass of 60 kDa) - inhibition of protein synthesis in the pharynx and larynx.
Interferons – proteins with a size of about 160 AA are secreted by some vertebrate cells in response to infection by viruses. The amount of interferon is 10 -9 – 10 -12 g, i.e. one protein molecule protects one cell. These proteins, like protein hormones, stimulate the synthesis of enzymes that destroy the synthesis of viral mRNA.
Hereditary diseases (monogenic) and (not to be confused!) family predisposition to diseases (diabetes, gout, atherosclerosis, urolithiasis, schizophrenia are multifactorial diseases.)
Principles of nucleotide sequence analysis (optional).
DNA technology in medicine.
A. DNA extraction. B. DNA cleavage using restriction enzymes. Human DNA is 150x10 6 nucleotide pairs. They must be divided into 500,000 fragments of 300 pairs each. Next is gel electrophoresis. Next – Southern blot hybridization with a radioprobe or other methods.
Sequencing. Exonucleases sequentially cleave off one mononucleotide. This is an outdated technique.
PCR (PCR) – polymerase chain reaction. (Nobel pr. 1993: Carrie Mullis)
Principle: primers (these are DNA fragments of ~20 nucleotides - commercially available) + DNA polymerase → DNA production (amplifier) → DNA analysis (sequencer). Now everything is done automatically!
A method of DNA sequencing using labeled defective nucleotides (such as dideoxynucleotides). Now the tags are not radioactive, but fluorescent. Testing for AIDS and other STIs. Fast, but expensive. It's better not to get sick!
The success of PCR for diagnosis and widespread use is due to the fact that the enzymes involved in the process, isolated from heat-resistant hot spring bacteria and genetically engineered, can withstand heat, which denatures (dissociates the DNA strands) and prepares them for the next round of PCR.
TERPENS, TERPENOIDS AND STEROIDS.
Turpentine – volatile oil from pine resin.
Terpenes are a group of unsaturated hydrocarbons with the composition (C 5 H 8) n, where n³ 2, widely distributed in nature. Contain isopentane fragments, usually connected in a “head to tail” manner. (this is the Ruzicka Rule).
Monoterpenes C 10 (C 5 H 8) 2 Ce squee Terpenes C 15, (C 5 H 8) 3 Diterpenes C 20, (C 5 H 8) 4 Triterpenes C 30, (C 5 H 8) 6. Polyterpenes (rubber).
The degree of hydrogenation of terpenes can vary, so the number of H atoms does not have to be a multiple of 8. There are no C 25 and C 35 terpenes.
Terpenes are acyclic and carbocyclic.
Terpenoids (isoprenoids) are terpenes (hydrocarbons) + functionally substituted terpenes. An extensive group of natural compounds with a regular skeletal structure.
Isoprenoids can be divided into
1) terpenes, incl. functionally substituted,
2) steroids
3) resin acids,
4) polyisoprenoids (rubber).
The most important representatives of terpenes.
Some features of the chemistry of terpenes, bicyclic molecules and steroids.
1) non-classical cations; 2) rearrangements of the Wagner-Meyerwein type; 3) easy oxidation; 4) diastereoselective synthesis; 5) influence of remote groups.
Formally, terpenes are products of the polymerization of isoprene, but the synthesis route is completely different! Why exactly are polyisoprene derivatives so widespread in nature? This is due to the peculiarities of their biosynthesis from acetyl coenzyme A, i.e. actually from acetic acid. (Bloch, 40-60. Both carbon atoms from C 14 H 3 C 14 UN are included in the terpene.)
SCHEME FOR THE SYNTHESIS OF MEVALONIC ACID - the most important intermediate product in the biosynthesis of terpenes and steroids.
Condensation acetyl coenzyme A b acetoacetyl Coenzyme A undergoes the Claisen ester condensation process.
Synthesis of limonene from geranyl phosphate, an important intermediate both in the synthesis of a wide variety of terpenes and in the synthesis of cholesterol. Below is the transformation of limonene into camphor under the influence of HCl, water and an oxidizing agent (PP - pyrophosphate residue).
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The conversion of mevalonic acid to geranyl phosphate occurs by 1) phosphorylation of 5-OH, 2) repeated phosphorylation of 5-OH and the formation of pyrophosphate, 3) phosphorylation at 3-OH. All this happens under the influence of ATP, which is converted into ADP. Further transformations:
The most important steroid hormones.
Formed in the body from cholesterol. Cholesterol is insoluble in water. Penetrates the cell and participates in biosynthesis through complexes with sterol-transfer proteins.
BILE ACIDS . Cholic acid. Cis-joint of rings A and B. Bile acids improve lipid absorption, lower cholesterol levels, and are widely used for the synthesis of macrocyclic structures.
STEROIDS – MEDICINES.
1. Cardiotonics. Digitoxin. Found in various types of foxglove (Digitalis purpurea L. or Digitalislanata Ehrh.) Glycosides are natural compounds that consist of one or more glucose or other sugar residues, most often linked through the 1- or 4- positions to an organic molecule (AGLICONE). Substances of similar structure and action are found in the venom of some species of toads.
2. Diuretics. Spironolactone (veroshpiron). Aldosterone antagonist. Blocks the reabsorption of Na+ ions, thus reducing the amount of fluid, which leads to a decrease in blood pressure. Does not affect the content of K+ ions! It is very important.
3. Anti-inflammatory drugs. Prednisolone. 6-Methylprednisolone (see formula above). Fluorosteroids (dexamethasone (9a-fluoro-16a-methylprednisolone), triamcinolone (9a-fluoro-16a-hydroxyprednisolone. Anti-inflammatory ointments.
4. Anabolics. Promotes the formation of muscle mass and bone tissue. Methandrostenolone.
5. BRASSINOSTEROIDS- NATURAL COMPOUNDS THAT HELP PLANTS FIGHT STRESS (drought, frost, excessive moisture) HAVE GROWTH-REGULATING ACTIVITY.
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The drug "Epin-extra", NNPP "NEST-M".
METAL COMPLEX CATALYSIS (1 SEMESTER).
