(Fisher projection), a method of depicting space on a plane. org structures connections, having one or several. chiral centers. When projecting a molecule onto a plane (Fig.) asymmetric. the atom is usually omitted, retaining only the crossing lines and substituent symbols; in this case, the substituents located in front of the plane are located on the right and left, and behind the plane - at the top and bottom (dotted line).

Fischer formulas for a molecule with one asymmetric. atom (I), as well as a scheme for constructing such a formula for compounds with two asymmetric. atoms (P) HOWORTH FORMULAS

HOWORTH FORMULAS

(Haworth f-ly), image on the plane of spaces. cyclic structures conn. When constructing X. f. the cycle is conventionally considered flat (in fact, the molecule could be in the conformation of a chair or a bathtub) and is projected onto the plane at a certain angle; in this case, the part of the ring closest to the observer in the drawing is located below and is usually highlighted with a thicker line (Fig.). In monosaccharides, the oxygen atom of the ring is usually located at the top. away from the observer (in the case of the pyranose cycle - on the right).

The formulas of Fischer (a) and Haworth (b) give the monosaccharides - -D-glucopyranose (I) and -L-galactofuranose (II).

Atoms or groups of atoms depicted in Fischer's f-lahs on the left and right, in X. f. are located accordingly. above and below the cycle plane. The side chains at the C-5 atom in pyranoses or at C-4 in furanoses are depicted above the plane of the ring for the D-configuration of the carbon atom and below the plane for the L-configuration (see Fig. Stereochemical nomenclature).
Proposed by W. Haworth (Haworth) in 1926.

55. Compounds with a hydroxyl group.

Hydroxyl group (hydroxyl) is the OH functional group of organic and inorganic compounds, in which the hydrogen and oxygen atoms are linked by a covalent bond. In organic chemistry it is also called " alcohol group».

Phenols are derivatives of aromatic hydrocarbons whose molecules contain one or more hydroxyl groups directly connected to the benzene ring.

The names of phenols are compiled taking into account the fact that for the parent structure, according to IUPAC rules, the trivial name “phenol” is retained. The numbering of the carbon atoms of the benzene ring starts from the atom directly bonded to the hydroxyl group (if it is the senior function), and continues in such a sequence that the existing substituents receive the lowest numbers.

The simplest representative of this class is phenol itself, C 6 H 5 OH.

The structure of phenol. One of the two lone electron pairs of the oxygen atom is drawn into the -electron system of the benzene ring (+M-EFFECT of the OH group). This leads to two effects: a) the electron density in the benzene ring increases, and the electron density maxima are in the ortho and para positions relative to the OH group; b) the electron density on the oxygen atom, on the contrary, decreases, which leads to a weakening of the O–H bond. The first effect is manifested in the high activity of phenol in electrophilic substitution reactions, and the second - in the increased acidity of phenol compared to saturated alcohols.

Mono-substituted phenol derivatives, for example methylphenol (cresol), can exist in the form of three structural isomers - ortho-, meta- and para-cresols:

Physical properties. Phenols are mostly crystalline substances (meta-cresol is liquid) at room temperature. They have a characteristic odor, are quite poorly soluble in cold water, but well soluble in hot water and especially in aqueous solutions of alkalis. Phenols form strong hydrogen bonds and have fairly high boiling and melting points. Thus, phenol itself is colorless crystals with t pl = 41 °C and t bp = 182 °C. Over time, the crystals turn red and darken.

56. Five-membered heterocyclic compounds.

Five-membered heterocycles- organic cyclic compounds, which contain at least one heteroatom.

The most famous representatives:

Representative	Structural formula	Related compounds
Furan		Furfural, Pyroslitic acid, Cumparone, Isobenzfuran, Tetrahydrofuran, 1,3-dioxolane
Thiophene		Thionaphthene, Thiophthene, Tetrahydrothiophene, Thiolane, Thiolane dioxide, Biotin
Pyrrole		Indole, Oxindole, Indoxyl, Isatin, Carbazole, Pyrrolidine, 2-pyrrolidone, N-methylpyrrolidone, Proline
Oxazole		Benzoxazole, 2-oxazoline
Isoxazole

57.Alcohols called aliphatic compounds containing a hydroxyl group (alkanols, alkenols, alkynols); hydroxyarenes or aromatic hydroxy derivatives are called phenols . The name of an alcohol is formed by adding the suffix -ol to the name of the corresponding hydrocarbon or based on the hydrocarbon radical. Depending on the structure of the hydrocarbon radical, alcohols are distinguished:

primary:

secondary:

tertiary:

Monohydric phenols:

Phenols are characterized by stronger acidic properties than alcohols; the latter do not form carbonium ions AIk – O – in aqueous solutions, which is associated with a lesser polarizing effect (electroacceptor properties of acyl radicals compared to aromatic ones).

Alcohols and phenols, however, readily form hydrogen bonds, so all alcohols and phenols have higher boiling points than the corresponding hydrocarbons.

If the hydrocarbon radical does not have pronounced hydrophobic properties, then these alcohols are highly soluble in water. Hydrogen bonding determines the ability of alcohols to transform into a glassy rather than crystalline state upon hardening.

Compounds with two or more hydroxyl groups are called polyhydric alcohols and phenols:

58. Lewis acids and bases.

J. Lewis proposed a more general theory of acids and bases.

Lewis bases – these are electron pair donors (alcohols, alcoholate anions, ethers, amines, etc.)

Lewis acids - these are electron pair acceptors , those. compounds having a vacant orbital (hydrogen ion and metal cations: H +, Ag +, Na +, Fe 2+; halides of elements of the second and third periods BF 3, AlCl 3, FeCl 3, ZnCl 2; halogens; tin and sulfur compounds: SnCl 4, SO 3).

Thus, Bronsted and Lewis bases are the same particles. However, Brønsted basicity is the ability to attach only a proton, while Lewis basicity is a broader concept and means the ability to interact with any particle that has a low-lying unoccupied orbital.

A Lewis acid-base interaction is a donor-acceptor interaction, and any heterolytic reaction can be represented as a Lewis acid-base interaction:

There is no single scale for comparing the strength of Lewis acids and bases, since their relative strength will depend on what substance is taken as the standard (for Bronsted acids and bases, the standard is water). To assess the ease of acid-base interactions according to Lewis, R. Pearson proposed a qualitative theory of “hard” and “soft” acids and bases.

Rigid bases have high electronegativity and low polarizability. They are difficult to oxidize. Their highest occupied molecular orbitals (HOMO) have low energy.

Soft bases have low electronegativity and high polarizability. They oxidize easily. Their highest occupied molecular orbitals (HOMO) have high energy.

Hard acids have high electronegativity and low polarizability. They are difficult to recover. Their lowest unoccupied molecular orbitals (LUMO) have low energy.

Soft acids have low electronegativity and high polarizability. They are easily restored. Their lowest unoccupied molecular orbitals (LUMO) have high energy.

The hardest acid is H +, the softest is CH 3 Hg +. The hardest bases are F - and OH - , the softest are I - and H - .

59. .Ethers.

Ethers- organic substances having the formula R-O-R 1, where R and R 1 are hydrocarbon radicals. It should, however, be taken into account that such a group may be part of other functional groups of compounds that are not ethers. Methods of preparation]

• According to Williamson

In laboratory conditions, ethers are prepared according to Williamson by the interaction of halogen derivatives capable of reacting with Sn2 and alkoxide and phenoxide ions. The reaction proceeds smoothly with halomethane and primary haloalkanes. In the case of secondary haloalkanes, the reaction may be complicated by a side elimination reaction.

Physical properties

Ethers are mobile, low-boiling liquids, slightly soluble in water, and very flammable. They exhibit weakly basic properties (they attach a proton at the O atom).

Ethers form peroxide compounds under the influence of light:

As a result, when distilling ethers in laboratory conditions, it is prohibited to distill them to dryness, since in this case a strong explosion will occur as a result of the decomposition of peroxides.

The most important ethers

Name	Formula	Melting temperature	Boiling temperature
Dimethyl ether	CH 3 OCH 3	−138.5 °C	−24.9 °C
Diethyl ether	CH 3 CH 2 OCH 2 CH 3	−116.3 °C	34.6 °C
Diisopropyl ether	(CH 3) 2 CHOCH(CH 3) 2	−86.2 °C	68.5 °C
Anisole		−37 °C	154 °C
Oxiran		−111.3 °C	10.7 °C
Tetrahydrofuran		−108 °C	65.4 °C
Dioxane		11.7 °C	101.4 °C
Polyethylene glycol	HOCH 2 (CH 2 OCH 2) n CH 2 OH	−	−

biological significance

Aryl ethers are preservatives, antioxidants, used in the perfume industry. Some ethers have an insecticidal effect.

60. Substitute nomenclature (IUPAC) for organic compounds.

In the IUPAC substitutive nomenclature, the name of an organic compound is determined by the names of the main chain (the root of the word), the carbon atoms in which are numbered in a certain order, as well as substituents and functional groups (designated as prefixes or suffixes). Any atom or group of atoms that replace hydrogen is considered as a substituent. A functional group is an atom or group of non-hydrocarbon atoms that determine whether a compound belongs to a particular class. If there are several groups, then the oldest one is selected:

IUPAC is a generally accepted nomenclature and is now a standard in chemistry.

61. Oxidation of C-H and C=C bonds.

62. Covalent bonds. Hybridization.

Covalent bond(atomic bond, homeopolar bond) - a chemical bond formed by the overlap (sharing) of a pair of valence electron clouds. The electronic clouds (electrons) that provide communication are called shared electron pair. A covalent bond is formed by a pair of electrons shared between two atoms, and these electrons must occupy two stable orbitals, one from each atom.

A + + B → A: B

As a result of socialization, electrons form a filled energy level. A bond is formed if their total energy at this level is less than in the initial state (and the difference in energy will be nothing more than the bond energy).

According to the theory of molecular orbitals, the overlap of two atomic orbitals leads, in the simplest case, to the formation of two molecular orbitals (MO): linking MO And anti-binding (loosening) MO. The shared electrons are located on the lower energy bonding MO. Orbital hybridization- a hypothetical process of mixing different (s, p, d, f) orbitals of the central atom of a polyatomic molecule with the appearance of identical orbitals that are equivalent in their characteristics.

Types of hybridization

To depict molecules with asymmetric carbon atoms on the i-plane, projections proposed in 18E1 by E. Fischer are often used.

Let us consider the principle of their construction using the example of a bromofluorochloromethane molecule. The starting point for constructing Fischeoa projections is the spatial model of the molecule or its wedge-shaped projection.
Let's position the molecule in such a way that only the carbon atom of the bromofluorochloromethane molecule remains in the plane of the drawing, as shown in the figure:

Let us project all the atoms onto the drawing plane (Br and CL from bottom to top, since they are located under the drawing plane, and F and H from top to bottom). In order for the resulting projection to differ from the structural formula, we agree not to depict the asymmetric carbon atom. He implied in the Fisher projection at the intersection of the vertical and horizontal lines:

As can be seen from the above example, the Fischer projection is constructed in such a way that the bonds of an asymmetric atom with substituents are depicted by vertical and horizontal (but not inclined!) lines.

When using Fisher projections, it is important to remember that the vertical line in them depicts connections moving away from us, and the horizontal line - connections directed towards us. This leads to the following rules for using Fischer projections:

IT IS FORBIDDEN:
1) You cannot remove the projection from the drawing plane (for example, view it “in the light”, that is, from the other side of the sheet).
2) You cannot rotate the projection in the drawing plane by 90° and 270°.
3) You cannot swap any two substituents on an asymmetric atom.

CAN:
1) You can rotate the projection in the flatness of the drawing by 180°. With this rotation, the vertical lines remain vertical, and the horizontal ones - horizontal.
2) It is possible to perform an even number of pairwise permutations of substituents on an asymmetric atom.
3) It is possible to perform a circular rearrangement of three substituents on an asymmetric atom. The fourth deputy remains in his place.

Asymmetric the carbon atom is bonded to four non-equivalent groups in the glucose molecule; such atoms include carbon atoms with numbers from 1 to 5

Antipodes

a substance characterized by opposite in sign and equal in magnitude rotations of the plane of polarization of light with the identity of all other physical and chemical properties (except for reactions with other optically active substances and physical properties in a chiral medium)

Racemate- an equimolar mixture of two enantiomers( Enantiomers(ancient Greek ἐνάντιος + μέρος - opposite + part, measure) - a pair of stereoisomers, which are mirror images of each other, not compatible in space). Racemates do not have optical activity and also differ in properties from the individual enantiomers. They are products of non-stereoselective reactions

Types of Retzamat

· Racemic conglomerate is a mechanical mixture of crystals of two enantiomers in a 1:1 ratio, with each crystal consisting of molecules of only one enantiomer.

· Racemic compound(true racemate) consists of crystals, each of which contains molecules of both enantiomers and their ratio is 1:1. This ratio of enantiomers in racemic compounds is maintained up to the level of the crystal lattice.

· Pseudoracemate is a solid solution of two enantiomeric compounds, that is, it is a homogeneous disordered mixture of enantiomers in a 1:1 ratio.

Physical properties

· Optical activity. Racemates do not exhibit optical activity, that is, they do not rotate the plane of polarization of light. This phenomenon is explained by the fact that for enantiomers the optical rotation is opposite in sign, but equal in magnitude. Since rotation is an additive quantity, in the case of a racemate, due to compensation of the contributions of enantiomers, it is equal to zero.

· Crystal Shape. Since enantiomers form enantiomorphic crystals, racemic conglomerates exist as two types of crystals, which are mirror images of each other in shape. It was this fact that allowed L. Pasteur to manually separate crystals of racemic tartrates.

· Density. According to Wallach's rule, formulated in 1895, crystals of racemates have a higher density than crystals of the individual enantiomers. This is associated both with thermodynamic factors and with the kinetics of nucleation and crystal growth of the racemic compound. This rule was confirmed by analysis of a crystallographic database.

· Melting temperature. For a racemic conglomerate, the melting point is always lower than the melting point of the individual enantiomers, as can be seen from its phase diagram. For example, enantiomerically pure hexagelicene melts at 265-267 °C, and the racemate melts at 231-233 °C.

If the racemate is true, which is typical for most organic racemates, then its melting point can be either higher or lower than the melting point of the enantiomers. Thus, in the case of dimethyl tartrate, the melting points of the pure enantiomer and the racemate are 43.3 °C and 86.4 °C, respectively. Mandelic acid racemate, on the contrary, melts at a lower temperature than the enantiomerically pure substance (118.0 °C and 132.8 °C, respectively). Addition of an individual enantiomer to a true racemate always results in a lower melting point, unlike what is observed for conglomerates.

In rare cases, when racemates exhibit the properties of solid solutions, they melt at the same temperature as the individual enantiomers (for camphor - ≈178 ° C).

· Solubility. Most chiral compounds are characterized by differences in solubility between the racemate and the individual enantiomers. The solubility of racemic conglomerates is higher than the solubility of pure enantiomers. Meyerhoffer's rule of thumb, applicable to non-dissociating organic compounds, states that the solubility of the racemate is twice that of the enantiomers. For true racemates, the solubility may be greater or less than the solubility of the enantiomers

Reactions of monosaccharides

Glucose, or grape sugar, or dextrose(D-glucose), C 6 H 12 O 6 - found in the juice of many fruits and berries, including grapes, which is where the name of this type of sugar comes from. It is a monosaccharide and six-hydroxy sugar (hexose). The glucose unit is part of polysaccharides (cellulose, starch, glycogen) and a number of disaccharides (maltose, lactose and sucrose), which, for example, are quickly broken down into glucose and fructose in the digestive tract.

D-Fructose

Obtained as β-form. Very hygroscopic colorless prisms or needles. tmelt 103-105 (decomposes).
Specific optical rotation for the sodium D line at a temperature of 20°C: [α] D 20 -132.2 → -92.4 (c=4 in H 2 O).
Solubility: 375 20, 740 55 in H 2 O; soluble in MeOH, EtOH, pyridine, acetone, glacial acetic acid.
The anhydrous form is stable at temperatures > 21.4 °C. Capable of hydration to form hemihydrate (and dihydrate) at temperatures< 20°С. Перекристаллизовать из МеОН. Положительная реакция Селиванова. Кристаллический сахар - β-D-пираноза, но в растворе содержится ≥ 15% фуранозной формы и значительное количество открытой линейной формы. В составе соединений найдена только фуранозная форма. Сладкий вкус.

Ascorbic acid(from ancient Greek ἀ - non- + lat. scorbutus- scurvy) - an organic compound with the formula C 6 H 8 O 6, is one of the main substances in the human diet, which is necessary for the normal functioning of connective and bone tissue. Performs the biological functions of a reducing agent and coenzyme of some metabolic processes, and is an antioxidant. Only one of the isomers is biologically active - L- ascorbic acid, which is called vitamin C . Ascorbic acid is naturally found in many fruits and vegetables.

Glycosides- organic compounds whose molecules consist of two parts: a carbohydrate (pyranoside or furanoside) residue and a non-carbohydrate fragment (the so-called aglycone). In a more general sense, carbohydrates consisting of two or more monosaccharide residues can also be considered as glycosides. Mostly crystalline, less often amorphous substances, highly soluble in water and alcohol.

Glycosides are a large group of organic substances found in the plant (less often in the animal) world and/or obtained synthetically. During acid, alkaline, or enzymatic hydrolysis, they are split into two or more components - an aglycone and a carbohydrate (or several carbohydrates). Many of the glycosides are toxic or have strong physiological effects, for example, glycosides of digitalis, strophanthus and others.

Fructose(fruit sugar), C 6 H 12 O 6 - monosaccharide, ketone alcohol, ketohexose, glucose isomer.

Physical properties

White crystalline substance, highly soluble in water. The melting point of fructose is lower than the melting point of glucose. 2 times sweeter than glucose and 4-5 times sweeter than lactose.

Chemical properties

In aqueous solutions, fructose exists as a mixture of tautomers, in which β-D-Fructopyranose predominates and contains, at 20 °C, about 20% β-D-Fructofuranose and about 5% α-D-Fructofuranose

Unlike glucose and other aldoses, fructose is unstable in both alkaline and acidic solutions; decomposes under conditions of acid hydrolysis of polysaccharides or glycosides

Modern ideas about the structure of organic compounds. Fundamentals of stereochemistry of organic compounds. Asymmetric carbon atom. Chirality. Fischer projection formulas.

Theory of chemical structure A.M. Butlerov

In 1861 A.M. Butlerov proposed a theory of the chemical structure of organic compounds, which consists of the following basic principles.

1) In the molecules of substances there is a strict sequence of chemical bonding of atoms, which is called a chemical structure.

2) The chemical properties of a substance are determined by the nature of its elementary components, their quantity and chemical structure.

3) If substances with the same composition and molecular weight have different structures, then the phenomenon of isomerism occurs.

4) Since in specific reactions only some parts of the molecule change, studying the structure of the product helps determine the structure of the original molecule.

5) The chemical nature (reactivity) of individual atoms in a molecule changes depending on the environment, i.e. depending on which atoms of other elements they are connected to.

Butlerov's theory provides the fundamental possibility of knowing the geometry of a molecule (microscopic properties) through knowledge of chemical properties (macroscopic properties). The basic principles of the theory of structure retain their significance to this day.

Electronic theories of chemical bonding.

The electronic structure of organic compounds is depicted using Lewis electron formulas. They use dots to indicate the position of all valence electrons: electrons of chemical bonds and lone pairs of electrons. It is believed that lone pairs of electrons form part of the outer shell of only one atom, and the electrons involved in the formation of a covalent bond are part of the outer shell of both atoms. For example, in the Lewis formula for carbon tetrachloride below, all atoms have an octet of electrons.

For each atom in a Lewis structure, a formal charge is determined. It is believed that the atom owns all the unshared electrons and half of the electrons in covalent bonds. An excess of electrons belonging to an atom in a molecule compared to a free atom causes a negative charge, and a deficiency causes a positive charge. The sum of the formal charges of all atoms gives the charge of the particle as a whole.

Basic principles of quantum organic chemistry.

Modern theories of covalent bonds are based on the concepts of quantum mechanics. According to the principles of quantum mechanics, the state of an electron in an atom is determined by a wave function called an atomic orbital. The formation of a chemical bond between atoms is considered as a result of the interaction of two orbitals, each of which contains one electron. In this case, the formation of molecular orbitals (MOs) occurs. From two atomic orbitals two molecular orbitals are formed, one of which ( connecting) has lower energy, and the other ( loosening) – higher energy than the original AO.

The bonding electrons occupy the lower energy bonding orbital, so the interaction of the orbitals results in an energy gain.

Depending on the type of atomic orbitals that combine, different types of MOs are formed. The symmetry and nodal properties of orbitals play a decisive role in this. Nuclear s -orbitals have spherical symmetry and do not have nodal surfaces passing through the center of the atom. Nuclear p -orbitals have cylindrical symmetry and three states p x , p y and p z . Every p -orbital has a nodal plane passing through the center of the atom and perpendicular to the axis, respectively x, y or z.

The nodal surface is the place where the probability of finding an electron is zero and the wave function changes sign. The more nodes, the higher the energy of the orbital. Thus, p -orbital consists of two parts in which the signs of the wave functions are opposite.

When considering the electronic structure of polyatomic molecules, it is necessary to use a set of orbitals that achieves their maximum overlap. In this regard, there is a concept hybridization orbitals. A carbon atom in an excited state contains four unpaired electrons in its outer energy level and is capable of forming four covalent bonds.

Hybrid orbitals participate in the formation of bonds.

The first valence state is sp 3 hybridization . As a result of hybridization with the participation of one s and three p orbitals of the carbon atom, four equivalent sp 3 -hybrid orbitals are formed, directed to the vertices of the tetrahedron at angles of 109.5 o:

In the state of sp 3 hybridization, the carbon atom forms fours-bonds with four substituents and has a tetrahedral configuration with bond angles equal to or close to 109.5 o:

Methane

The second valence state is sp 2 hybridization . As a result of hybridization with the participation of one s- and two p-orbitals of a carbon atom, three equivalent sp 2 -hybrid orbitals are formed, lying in the same plane at angles of 120 o, and the p-orbital not participating in hybridization is located perpendicular to the plane of the hybrid orbitals.

In the state of sp 2 hybridization, the carbon atom forms threes-bonds due to hybrid orbitals and onep-bond due to the p-orbital not participating in hybridization and has three substituents.

The third valence state of carbon is sp-hybridization . As a result of hybridization with the participation of one s- and one p-orbital, two equivalent sp-hybrid orbitals are formed, lying at an angle of 180 0, and the p-orbitals not participating in hybridization are located perpendicular to the plane of the hybrid orbitals and to each other. In the sp-hybridization state, the carbon atom forms twos-bonds due to hybrid orbitals and twop-bond due to p-orbitals not participating in hybridization and has two substituents:

Acetylene

Basics of stereochemistry.

Stereochemistry is a part of chemistry devoted to the study of the spatial structure of molecules and the influence of this structure on the physical and chemical properties of a substance, on the direction and rate of their reactions.

Conformations (rotational isomerism).

The transition from the simplest organic hydrocarbon, methane, to its closest homologue, ethane, poses problems of spatial structure, for the solution of which it is not enough to know the previously discussed parameters. 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) . The energy of different conformers is not the same, but the energy barrier separating the different rotary isomers is small for most organic compounds. Therefore, under ordinary conditions, as a rule, it is impossible to fix molecules in one strictly defined conformation. Typically, several rotational forms that easily transform into each other coexist in equilibrium.

Let's consider ways of graphically representing conformations and their nomenclature. For an ethane molecule, one can predict the existence of two conformations that differ maximally in energy. They are shown below as perspective projections (1) (“sawmill goats”), lateral projections (2) and Newman's formulas .

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.

As the molecule becomes more complex, the number of possible conformations increases. Yes, for n-butane can already be depicted in six conformations, differing in the relative arrangement of CH 3 groups, i.e. rotation around the central connection C-C. 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.

The various eclipsed and inhibited conformations of butane are not the same in energy. Corresponding energies of all conformations formed during rotation around the central C-C bond.

So, conformations are different spatial forms of a molecule that has a certain configuration. Conformers are stereoisomeric structures that correspond to energy minima on the potential energy diagram, are in mobile equilibrium and are capable of interconversion by rotation around simple bonds.

Sometimes the barrier to such transformations becomes high enough to separate stereoisomeric forms (for example, optically active biphenyls). In such cases, they no longer talk about conformers, but about actually existing stereoisomers .

Geometric isomerism.

An important consequence of the rigidity of a double bond (the absence of rotation around it) is the existence geometric isomers . The most common of them are cis-, trans-isomers compounds of the ethylene series containing unequal substituents on unsaturated atoms. The simplest example is the isomers of butene-2.

Geometric isomers have the same chemical structure, differing in the spatial arrangement of atoms, i.e. By configurations . This difference creates a difference in physical (as well as chemical) properties. Geometric isomers, unlike conformers, can be isolated in pure form and exist as individual stable substances. For their mutual transformation, an energy of the order of 125–170 kJ/mol is required, which can be provided by heating or irradiation.

In the simplest cases, the nomenclature of geometric isomers does not present any difficulties: cis- forms are geometric isomers in which identical substituents lie on the same side of the pi bond plane, trance- isomers have identical substituents on different sides of the pi bond plane. In more complex cases it is used Z,E-nomenclature . Its main principle: to indicate the configuration indicate cis-(Z, from German Zusammen - together) or trance-(E, from German Entgegen - opposite) location senior deputies with a double bond.

In the Z,E system, substituents with a higher atomic number are considered senior. If the atoms directly associated with unsaturated carbons are the same, then they move on to the “second layer”, if necessary - to the “third layer”, etc.

3. Optical isomerism (enantiomerism).

Among organic compounds there are substances that can rotate the plane of polarization of light. This phenomenon is called optical activity, and the corresponding substances are called optically active . Optically active substances occur in pairs optical antipodes - isomers, the physical and chemical properties of which under normal conditions are the same, with the exception of one thing - the sign of rotation of the plane of polarization. (If one of the optical antipodes has, for example, a specific rotation of +20 o, then the other has a specific rotation of -20 o).

Projection formulas.

To conventionally depict an asymmetric atom on a plane, use projection formulas of E. Fisher . They are obtained by projecting onto a plane the atoms to which the asymmetric atom is associated. In this case, the asymmetric atom itself is usually omitted, retaining only the intersecting lines and substituent symbols. To remember the spatial arrangement of substituents, a broken vertical line is often preserved in projection formulas (the upper and lower substituents are removed beyond the plane of the drawing), but this is often not done. left model in the previous figure:

Here are some examples of projection formulas:

(+)-alanine(-)2-butanol(+)-glyceraldehyde

The names of substances show their rotation signs. This means, for example, that the left-handed antipode of butanol-2 has spatial configuration, expressed precisely by the above formula, and its mirror image corresponds to dextrorotatory butanol-2. Configuration Definition optical antipodes is carried out experimentally.

In principle, each optical antipode can be depicted by twelve (!) different projection formulas - depending on how the model is located when constructing the projection, from which side we look at it. To standardize projection formulas, certain rules for writing them have been introduced. Thus, the main function, if it is at the end of the chain, is usually placed at the top, the main chain is depicted vertically.

In order to compare “non-standard” written projection formulas, you need to know the following rules for transforming projection formulas. In order to compare “non-standard” written projection formulas, you need to know the following rules for transforming projection formulas.

1. Formulas can be rotated 180° in the drawing plane without changing their stereochemical meaning:

2. Two (or any even number) rearrangements of substituents on one asymmetric atom do not change the stereochemical meaning of the formula:

3. One (or any odd number) permutations of substituents at the asymmetric center leads to the formula for the optical antipode:

4. A 90° rotation in the drawing plane turns the formula into an antipodeal one, unless at the same time the condition for the location of the substituents relative to the drawing plane is changed, i.e. do not consider that now the lateral substituents are located behind the drawing plane, and the upper and lower ones are in front of it. If you use a formula with a dotted line, then the changed orientation of the dotted line will directly remind you of this:

5. Instead of permutations, projection formulas can be transformed by rotating any three substituents clockwise or counterclockwise; the fourth substituent does not change its position (this operation is equivalent to two permutations):

6. Projection formulas cannot be derived from the drawing plane.

Racemates.

If the formula of a substance contains an asymmetric atom, this does not mean that such a substance will have optical activity. If an asymmetric center arises during a normal reaction (substitution in the CH 2 group, addition at a double bond, etc.), then the probability of creating both antipodean configurations is the same. Therefore, despite the asymmetry of each individual molecule, the resulting substance turns out to be optically inactive. This kind of optically inactive modification, consisting of an equal amount of both antipodes, is called racemates.

Other types of optically active substances.

This section lists some other classes of organic compounds that also exhibit optical activity (i.e., existing as pairs of optical antipodes).

The carbon atom does not have a monopoly on the creation of chiral centers in the molecules of organic compounds. The center of chirality can also be silicon, tin, and tetracovalent nitrogen atoms in quaternary ammonium salts and tertiary amine oxides:

In these compounds, the center of asymmetry has a tetrahedral configuration, like the asymmetric carbon atom. There are, however, also compounds with a different spatial structure of the chiral center.

pyramidal the configuration is chiral centers formed by atoms of trivalent nitrogen, phosphorus, arsenic, antimony, and sulfur. In principle, the center of asymmetry can be considered tetrahedral if the lone electron pair of the heteroatom is taken as the fourth substituent:

Optical activity can also occur without chiral center, due to the chirality of the structure of the entire molecule as a whole ( molecular chirality or molecular asymmetry ). The most typical examples are the presence chiral axis or chiral plane .

The chiral axis appears, for example, in allenes containing various substituents at sp 2-hybrid carbon atoms. It is easy to see that the compounds below are incompatible mirror images, and therefore optical antipodes:

Another class of compounds having a chiral axis are optically active biphenyls, which have ortho-positions have bulky substituents that hinder free rotation around the C-C bond connecting the benzene rings:

Chiral plane characterized by the fact that it can be distinguished between “top” and “bottom”, as well as “right” and “left” sides. An example of compounds with a chiral plane is the optically active trance- cyclooctene and optically active ferrocene derivative:

Diastereomerism.

Compounds with several asymmetric atoms have important features that distinguish them from the previously discussed simpler optically active substances with one center of asymmetry.

Let us assume that in a molecule of a certain substance there are two asymmetric atoms; Let's call them conditionally A and B. It is easy to see that molecules with the following combinations are possible:

	((-)	((-)		((-)	((+)
Molecule 1	F A		Molecule 3	AA	BB
	((+)	((+)		((+)	((-)
Molecule 2	AA	BB	Molecule 4	AA	BB

Molecules 1 and 2 are a pair of optical antipodes; the same applies to a pair of molecules 3 and 4. If we compare molecules from different pairs of antipodes - 1 and 3, 1 and 4, 2 and 3, 2 and 4 - with each other, then we will see that the listed pairs are not optical antipodes: the configuration of one asymmetric atom is the same, the configuration of the other is not the same. These are couples diastereomers , i.e. spatial isomers, Not constituting optical antipodes with each other.

Diastereomers differ from each other not only in optical rotation, but also in all other physical constants: they have different melting and boiling points, different solubilities, etc. Differences in the properties of diastereomers are often no less than the differences in properties between structural isomers.

An example of a compound of this type is chloromalic acid

Its stereoisomeric forms have the following projection formulas:

erythro-forms threo- forms

Titles erythro- And treo- come from the names of the carbohydrates erythrose and threose. These names are used to indicate the relative position of substituents in compounds with two asymmetric atoms: erythro -isomers they are those for which two identical lateral substituents appear in the standard projection formula on one side (right or left); treo -isomers have identical lateral substituents on different sides of the projection formula. Two erythro- isomers are a pair of optical antipodes; when they are mixed, a racemate is formed. A pair of optical isomers are and threo- forms; they also produce a racemate when mixed, which differs in properties from the racemate erythro- forms. Thus, there are a total of four optically active isomers of chloromalic acid and two racemates.

With a further increase in the number of asymmetric centers, the number of spatial isomers increases, and each new asymmetric center doubles the number of isomers. It is determined by the formula 2 n, where n is the number of asymmetric centers.

The number of stereoisomers may decrease due to partial symmetry appearing in some structures. An example is tartaric acid, in which the number of individual stereoisomers is reduced to three. Their projection formulas:

Formula I is identical to formula Ia, since it transforms into it when rotated by 180° in the plane of the drawing and, therefore, does not represent a new stereoisomer. This optically inactive modification is called meso form . Meso- All optically active substances have forms with several identical (i.e., associated with identical substituents) asymmetric centers. Projection formulas meso- forms can always be recognized by the fact that they can be divided by a horizontal line into two halves, which, when written on paper, are formally identical, but in reality are mirrored:

Formulas II and III depict the optical antipodes of tartaric acid; when they are mixed, an optically inactive racemate is formed - grape acid.

Nomenclature of optical isomers.

The simplest, oldest, but still in use system of nomenclature of optical antipodes is based on comparison of the projection formula of the called antipode with the projection formula of a certain standard substance chosen as the “key”. Yes, fora-hydroxy acids and a-amino acids, the key is the upper part of their projection formula (in standard notation):

L-hydroxy acids (X = OH) D- hydroxy acids (X = OH)

L-amino acids (X = NH 2) D- amino acids (X = NH 2)

Configuration of alla-hydroxy acids that have a hydroxyl group on the left in the standard written Fischer projection formula are designated by the sign L; if the hydroxyl is located in the projection formula on the right - sign D

The key to designate the configuration of sugars is glyceraldehyde:

L-(-)-glyceraldehyde D-(+)-glyceraldehyde

In sugar molecules the designation D- or L- refers to configuration lower asymmetric center.

System D-,L- designation has significant drawbacks: firstly, the designation D- or L- indicates the configuration of only one asymmetric atom; secondly, for some compounds different symbols are obtained, depending on whether the glyceraldehyde or hydroxyacid key is taken as the key, for example:

These shortcomings of the key system limit its use at present to three classes of optically active substances: sugars, amino acids and hydroxy acids. Designed for general use R,S-system Kahn, Ingold and Prelog.

To determine the R- or S-configuration of the optical antipode, it is necessary to arrange the tetrahedron of substituents around the asymmetric carbon atom in such a way that the lowest substituent (usually hydrogen) has the direction “away from the observer”. Then, if the movement during the transition in a circle of the three remaining substituents from the eldest to the average in seniority and then to the youngest occurs counterclock-wise - ThisS -isomer (associated with the same hand movement when writing the letter S), if clockwise - This R- isomer (associated with the movement of the hand when writing the letter R).

To determine the seniority of substituents on an asymmetric atom, the rules for calculating atomic numbers are used, which we have already discussed in connection with the Z,E nomenclature of geometric isomers.

To select R, S-notations according to the projection formula, it is necessary, by an even number of permutations (which, as we know, do not change the stereochemical meaning of the formula), to arrange the substituents so that the youngest of them (usually hydrogen) is at the bottom of the projection formula. Then the seniority of the remaining three substituents, falling clockwise, corresponds to the designation R, counterclockwise - the designation S:

5. Methods for obtaining stereoisomers

Obtaining pure stereoisomers is an important task, since, as a rule, only one of the stereoisomeric forms is biologically active. Meanwhile, under normal conditions, as a rule, mixtures of stereoisomers are formed - diastereomers or optical antipodes. To obtain pure stereoisomeric forms, these mixtures.

Projection of a three-dimensional molecule onto a plane

Fischer projection (Fischer projection formula, Fischer formula) - a method of depicting a three-dimensional molecule in the form of a projection, in which vertical bonds are removed beyond the projection plane, and horizontal bonds protrude in front of this plane. These formulas were proposed by E. Fischer in 1891 to depict the structures of carbohydrates. The use of Fischer projections for non-carbohydrate molecules can be misleading and is not recommended by IUPAC.

Construction

In the Fischer projection, chemical bonds are depicted as horizontal and vertical lines, at the crosshairs of which there are stereocenters. The carbon skeleton is depicted vertically, with the carbon atom on top, from which the numbering of the skeleton begins (for example, the aldehyde atom for aldoses). In addition, in the Fisher projection, all horizontal connections are directed towards the observer, and vertical connections are removed from the observer. This condition is important for the correct construction of the Fischer projection, as well as for reconstructing the three-dimensional structure of a molecule from its projection. For this reason, the Fischer projection cannot be rotated by 90° or 270°, as this will lead to a change in the configuration of the stereocenters. According to IUPAC guidelines, hydrogen atoms should be depicted explicitly, but structures without hydrogen atoms are also considered acceptable.

Restoring a 3D recording

To restore the spatial shape of a molecule from the Fischer projection, it is necessary to depict horizontal bonds directed towards the observer (thick wedges), and vertical bonds - going beyond the image plane (dashed wedges). Next, you can depict the molecule in any three-dimensional representation.

Usage

Fischer projections are most widely used to construct structural formulas of monosaccharides, as well as amino acids. They also form the basis of the d/l nomenclature used to distinguish the enantiomers of these natural compounds.

CHAPTER 7. STEREOCHEMICAL BASICS OF THE STRUCTURE OF MOLECULES OF ORGANIC COMPOUNDS

CHAPTER 7. STEREOCHEMICAL BASICS OF THE STRUCTURE OF MOLECULES OF ORGANIC COMPOUNDS

Stereochemistry (from Greek. stereos- spatial) is “chemistry in three dimensions”. Most molecules are three-dimensional (threedimentional, abbreviated as 3D). Structural formulas reflect the two-dimensional (2D) structure of a molecule, including the number, type, and bonding sequence of atoms. Let us recall that compounds that have the same composition but different chemical structures are called structural isomers (see 1.1). The broader concept of the structure of a molecule (sometimes figuratively called molecular architecture), along with the concept of chemical structure, includes stereochemical components - configuration and conformation, reflecting the spatial structure, i.e., the three-dimensionality of the molecule. Molecules that have the same chemical structure can differ in spatial structure, i.e., exist in the form of spatial isomers - stereoisomers.

The spatial structure of molecules is the relative arrangement of atoms and atomic groups in three-dimensional space.

Stereoisomers are compounds in which the molecules have the same sequence of chemical bonds of atoms, but different locations of these atoms relative to each other in space.

In turn, stereoisomers can be configuration And conformational isomers, i.e. vary accordingly configuration And conformation.

7.1. Configuration

Configuration is the order in which atoms are arranged in space, without taking into account differences resulting from rotation around single bonds.

Configuration isomers can transform into each other by breaking some and forming other chemical bonds and can exist separately in the form of individual compounds. They are classified into two main types - enantiomers And diastereomers.

7.1.1. Enantiomerism

Enantiomers are stereoisomers that are related to each other, like an object and an incompatible mirror image.

They can only exist as enantiomers chiral molecules.

Chirality is the property of an object to be incompatible with its mirror image. Chiral (from Greek. cheir- hand), or asymmetrical, objects are the left and right hand, as well as gloves, boots, etc. These paired objects represent an object and its mirror image (Fig. 7.1, a). Such items cannot be completely combined with each other.

At the same time, there are many objects around us that are compatible with their mirror image, i.e. they are achiral(symmetrical), such as plates, spoons, glasses, etc. Achiral objects have at least one plane of symmetry, which divides the object into two mirror-identical parts (see Fig. 7.1, b).

Similar relationships are also observed in the world of molecules, i.e. molecules are divided into chiral and achiral. Achiral molecules have planes of symmetry; chiral molecules do not.

Chiral molecules have one or more chirality centers. In organic compounds, the center of chirality most often acts asymmetric carbon atom.

Rice. 7.1.Reflection in a mirror of a chiral object (a) and a plane of symmetry cutting an achiral object (b)

An asymmetric carbon atom is one that is bonded to four different atoms or groups.

When depicting the stereochemical formula of a molecule, the symbol "C" for the asymmetric carbon atom is usually omitted.

To determine whether a molecule is chiral or achiral, there is no need to depict it with a stereochemical formula; it is enough to carefully consider all the carbon atoms in it. If there is at least one carbon atom with four different substituents, then this carbon atom is asymmetric and the molecule, with rare exceptions (see 7.1.3), is chiral. Thus, of the two alcohols - propanol-2 and butanol-2 - the first is achiral (two CH 3 groups at the C-2 atom), and the second is chiral, since in its molecule at the C-2 atom all four substituents are different ( N, OH, CH 3 and C 2 H 5). The asymmetric carbon atom is sometimes marked with an asterisk (C*).

Consequently, the 2-butanol molecule is capable of existing as a pair of enantiomers that are not compatible in space (Fig. 7.2).

Rice. 7.2.Enantiomers of chiral butanol-2 molecules are not compatible

Properties of enantiomers. Enantiomers have the same chemical and physical properties (melting and boiling points, density, solubility, etc.), but exhibit different optical activity, i.e., the ability to deflect the plane of polarized light*.

When such light passes through a solution of one of the enantiomers, the polarization plane deviates to the left, and the other to the right by the same angle α. The value of the angle α, reduced to standard conditions, is a constant of the optically active substance and is called specific rotation[α]. Left-hand rotation is indicated by a minus sign (-), right-hand rotation by a plus sign (+), and the enantiomers are called left- and right-handed, respectively.

Other names for enantiomers are associated with the manifestation of optical activity - optical isomers or optical antipodes.

Each chiral compound can also have a third, optically inactive form - racemate For crystalline substances, it is usually not just a mechanical mixture of crystals of two enantiomers, but a new molecular structure formed by the enantiomers. Racemates are optically inactive because the left-hand rotation of one enantiomer is compensated by the right-hand rotation of an equal amount of the other. In this case, a plus or minus sign (?) is sometimes placed before the name of the compound.

7.1.2. Relative and absolute configurations

Fischer projection formulas. To depict configurational isomers on a plane, you can use stereochemical formulas. However, it is more convenient to use simpler to write Fischer projection formulas(simpler - Fischer projections). Let us consider their construction using the example of lactic (2-hydroxypropanoic) acid.

The tetrahedral model of one of the enantiomers (Fig. 7.3) is placed in space so that the chain of carbon atoms is in a vertical position, and the carboxyl group is on top. Bonds with non-carbon substituents (H and OH) at the chiral center should

* See tutorial for details Remizov A.N., Maksina A.G., Potapenko A.Ya. Medical and biological physics. 4th ed., revised. and additional - M.: Bustard, 2003.- P. 365-375.

Rice. 7.3.Construction of the Fischer projection formula of (+)-lactic acid

We should be directed to the observer. After this, the model is projected onto a plane. The symbol of the asymmetric atom is omitted; it is understood as the point of intersection of the vertical and horizontal lines.

The tetrahedral model of a chiral molecule before projection can be positioned in space in different ways, not only as shown in Fig. 7.3. It is only necessary that the connections forming a horizontal line on the projection be directed towards the observer, and the vertical connections - beyond the plane of the drawing.

The projections obtained in this way can, with the help of simple transformations, be brought to a standard form, in which the carbon chain is located vertically, and the senior group (in lactic acid this is COOH) is on top. Transformations allow two operations:

In the projection formula, it is allowed to swap places of any two substituents at the same chiral center an even number of times (two permutations are sufficient);

The projection formula can be rotated 180 in the drawing plane? (which is equivalent to two permutations), but not by 90?.

D.L-Configuration designation system. At the beginning of the twentieth century. a system for classifying enantiomers was proposed for relatively simple (from the standpoint of stereoisomerism) molecules, such as α-amino acids, α-hydroxy acids, and the like. Behind configuration standard glyceraldehyde was taken. Its levorotatory enantiomer was arbitrarily attributed to formula (I). This configuration of the carbon atom was designated by the letter l (from lat. laevus- left). The dextrorotatory enantiomer was accordingly assigned formula (II), and the configuration was designated by the letter d (from the Latin. dexter- right).

Note that in the standard projection formula l -glyceraldehyde has an OH group on the left, and d -glyceraldehyde - on the right.

Classification as d- or l - a number of other optically active compounds related in structure are produced by comparing the configuration of their asymmetric atom with the configuration d- or l -glyceraldehyde. For example, in one of the enantiomers of lactic acid (I) in the projection formula the OH group is on the left, as in l -glyceraldehyde, therefore enantiomer (I) is classified as l -row. For the same reasons, enantiomer (II) is classified as d -row. Thus, from a comparison of Fisher projections, we determine relative configuration

It should be noted that l -glyceraldehyde has left rotation, and l -lactic acid - right (and this is not an isolated case). Moreover, the same substance can be either left- or right-handed, depending on the conditions of determination (different solvents, temperature).

The sign of rotation of the plane of polarized light is not associated with belonging to d- or l -stereochemical series.

Practical determination of the relative configuration of optically active compounds is carried out using chemical reactions: either the substance under study is converted into glyceraldehyde (or another substance with a known relative configuration), or, conversely, from d- or l -glyceraldehyde produces the test substance. Of course, during all these reactions the configuration of the asymmetric carbon atom should not change.

The arbitrary assignment of left- and right-handed glyceraldehyde to conventional configurations was a forced step. At that time, the absolute configuration was not known for any chiral compound. The establishment of the absolute configuration became possible only thanks to the development of physicochemical methods, especially x-ray diffraction analysis, with the help of which in 1951 the absolute configuration of a chiral molecule was first determined - it was a salt of (+)-tartaric acid. After this, it became clear that the absolute configuration of d- and l-glyceraldehydes is indeed what was originally assigned to them.

The d,l-System is currently used for α-amino acids, hydroxy acids and (with some additions) for carbohydrates

(see 11.1.1).

R,S-Configuration designation system. The d,L-System is of very limited use, since it is often impossible to correlate the configuration of any compound with glyceraldehyde. The universal system for designating the configuration of chirality centers is the R,S-system (from lat. rectus- straight, sinister- left). It is based on sequence rule, based on the seniority of substituents associated with the center of chirality.

The seniority of substituents is determined by the atomic number of the element directly associated with the center of chirality - the larger it is, the older the substituent.

Thus, the OH group is older than NH 2, which, in turn, is older than any alkyl group and even COOH, since in the latter a carbon atom is bound to an asymmetric center. If the atomic numbers are the same, the group whose atom next to carbon has a higher atomic number is considered senior, and if this atom (usually oxygen) is connected by a double bond, it is counted twice. As a result, the following groups are arranged in descending order of precedence: -COOH > -CH=O > -CH 2 OH.

To determine the configuration, the tetrahedral model of a compound is placed in space so that the lowest substituent (in most cases this is a hydrogen atom) is furthest away from the observer. If the seniority of the three remaining substituents decreases clockwise, then the center of chirality is assigned the R-configuration (Fig. 7.4, a), if counterclockwise -S-configuration (see Fig. 7.4, b), as seen by the driver behind the wheel (see Fig. 7.4, V).

Rice. 7.4.Determination of the configuration of lactic acid enantiomers by R,S- system (explanation in text)

To indicate the configuration according to the RS system, you can use Fisher projections. To do this, the projection is transformed so that the junior deputy is located on one of the vertical links, which corresponds to its position behind the drawing plane. If, after transformation of the projection, the seniority of the remaining three substituents decreases clockwise, then the asymmetric atom has an R-configuration, and vice versa. The application of this method is shown using the example of l-lactic acid (the numbers indicate the seniority of the groups).

There is a simpler way to determine the R- or S-configuration using the Fischer projection, in which the minor substituent (usually the H atom) is located on one of horizontal connections. In this case, the above-mentioned rearrangements are not carried out, but the seniority of the deputies is immediately determined. However, since the H atom is “out of place” (which is equivalent to the opposite configuration), the drop in precedence will now mean not the R-, but the S-configuration. This method is illustrated using l-malic acid as an example.

This method is especially convenient for molecules containing several chiral centers, where rearrangements would be required to determine the configuration of each of them.

There is no correlation between the d,l and RS systems: these are two different approaches to designating the configuration of chiral centers. If in the d,L-system compounds with similar configurations form stereochemical series, then in the RS-system the chiral centers in compounds, for example, of the l-series, can have both R- and S-configuration.

7.1.3. Diastereomerism

Diastereomers are stereoisomers that are not related to each other, like an object and an incompatible mirror image, i.e., they are not enantiomers.

The most important groups of diastereomers are σ-diastereomers and π-diastereomers.

σ -Diastereomers. Many biologically important substances contain more than one chirality center in a molecule. In this case, the number of configuration isomers increases, which is defined as 2n, where n- number of chirality centers. For example, if there are two asymmetric atoms, the compound can exist as four stereoisomers (2 2 = 4), making up two pairs of enantiomers.

2-Amino-3-hydroxybutanoic acid has two centers of chirality (C-2 and C-3 atoms) and therefore must exist as four configurational isomers, one of which is a natural amino acid.

Structures (I) and (II), corresponding to l- and d-threonine, as well as (III) and (IV), corresponding to l- and d-allothreonine (from the Greek. alios- other), relate to each other as an object and a mirror image incompatible with it, i.e. they are pairs of enantiomers. When comparing structures (I) and (III), (I) and (IV), (II) and (III), (II) and (IV), it is clear that in these pairs of compounds one asymmetric center has the same configuration, and the other is the opposite. Such pairs of stereoisomers are diastereomers. Such isomers are called σ-diastereomers, since the substituents in them are connected to the chirality center by σ bonds.

Amino acids and hydroxy acids with two centers of chirality are classified as d- or l -row according to the configuration of the asymmetric atom with the lowest number.

Diastereomers, unlike enantiomers, differ in physical and chemical properties. For example, l-threonine, which is part of proteins, and l-allothreonine have different specific rotation values ​​(as shown above).

Mesoconnections. Sometimes a molecule contains two or more asymmetric centers, but the molecule as a whole remains symmetrical. An example of such compounds is one of the stereoisomers of tartaric (2,3-dihydroxybutanedioic) acid.

Theoretically, this acid, which has two chirality centers, could exist in the form of four stereoisomers (I)-(IV).

Structures (I) and (II) correspond to d- and l-series enantiomers (assignment is based on the “upper” chirality center). It would seem that structures (III) and (IV) also correspond to a pair of enantiomers. In fact, these are formulas of the same compound - optically inactive mesotartaric acid. It is easy to verify the identity of formulas (III) and (IV) by rotating formula (IV) by 180°, without taking it out of the plane. Despite two centers of chirality, the mesotartaric acid molecule as a whole is achiral, since it has a plane of symmetry passing through the middle of the C-2-C-3 bond. In relation to d- and l-tartaric acids, mesotartaric acid is a diastereomer.

Thus, there are three (not four) stereoisomers of tartaric acids, not counting the racemic form.

When using the R,S system, there are no difficulties in describing the stereochemistry of compounds with several chiral centers. To do this, determine the configuration of each center according to the R, S-system and indicate it (in parentheses with the appropriate locants) before the full name. Thus, d-tartaric acid will receive the systematic name (2R,3R)-2,3-dihydroxybutanedioic acid, and mesotartaric acid will have the stereochemical symbols (2R,3S)-.

Like mesotartaric acid, there is a meso form of the α-amino acid cystine. With two centers of chirality, the number of stereoisomers of cystine is three due to the fact that the molecule is internally symmetrical.

π -Diastereomers. These include configurational isomers containing a π bond. This type of isomerism is characteristic, in particular, of alkenes. Relative to the plane of the π bond, identical substituents on two carbon atoms can be located one at a time (cis) or in different directions (trance) sides. In this regard, there are stereoisomers known as cis- And trance-isomers, as illustrated by cis- and trans-butenes (see 3.2.2). π-Diastereomers are the simplest unsaturated dicarboxylic acids - maleic and fumaric.

Maleic acid is thermodynamically less stable cis-isomer compared to trance-isomer - fumaric acid. Under the influence of certain substances or ultraviolet rays, an equilibrium is established between both acids; when heated (~150?C) it is shifted towards a more stable trance-isomer.

7.2. Conformations

Free rotation is possible around a simple C-C bond, as a result of which the molecule can take on different shapes in space. This can be seen in the stereochemical formulas of ethane (I) and (II), where the color-coded CH groups 3 located differently relative to another group of SNs 3.

Rotating one CH group 3 relative to the other occurs without disturbing the configuration - only the relative arrangement in space of the hydrogen atoms changes.

The geometric shapes of a molecule that transform into each other by rotating around σ bonds are called conformations.

According to this conformational isomers are stereoisomers, the difference between which is caused by the rotation of individual parts of the molecule around σ bonds.

Conformational isomers usually cannot be isolated in their individual state. The transition of different conformations of the molecule into each other occurs without breaking the bonds.

7.2.1. Conformations of acyclic compounds

The simplest compound with a C-C bond is ethane; Let's consider two of its many conformations. In one of them (Fig. 7.5, a) the distance between the hydrogen atoms of two CH groups 3 the smallest, so C-H bonds that are opposite each other repel each other. This leads to an increase in the energy of the molecule and, consequently, to less stability of this conformation. When looking along the C-C bond, it is clear that the three C-H bonds on each carbon atom “eclipse” each other in pairs. This conformation is called obscured.

Rice. 7.5.Occluded (a, b) and inhibited (in, G) ethane conformation

In another conformation of ethane, resulting from the rotation of one of the CH groups 3 at 60? (see Fig. 7.5, c), the hydrogen atoms of the two methyl groups are as far apart as possible. In this case, the repulsion of electrons from C-H bonds will be minimal, and the energy of such a conformation will also be minimal. This more stable conformation is called inhibited. The difference in energy of both conformations is small and amounts to ~12 kJ/mol; it defines the so-called energy barrier of rotation.

Newman's projection formulas. These formulas (simpler - Newman projections) are used to depict conformations on a plane. To construct a projection, the molecule is viewed from the side of one of the carbon atoms along its bond with the neighboring carbon atom, around which rotation occurs. When projecting, three bonds from the carbon atom closest to the observer to hydrogen atoms (or in the general case to other substituents) are arranged in the form of a three-rayed star with angles of 120?. A carbon atom removed from the observer (invisible) is depicted as a circle, from which it is also at an angle of 120? three connections depart. Newman projections also provide a visual representation of the eclipsed (see Fig. 7.5, b) and inhibited (see Fig. 7.5, d) conformations.

Under normal conditions, ethane conformations easily transform into each other, and we can talk about a statistical set of different conformations that differ slightly in energy. It is impossible to isolate even a more stable conformation in individual form.

In more complex molecules, replacing hydrogen atoms at neighboring carbon atoms with other atoms or groups leads to their mutual repulsion, which affects the increase in potential energy. Thus, in a butane molecule, the least favorable conformation will be the eclipsed conformation, and the most favorable will be the inhibited conformation with the most distant CH 3 groups. The difference between the energies of these conformations is ~25 kJ/mol.

As the carbon chain lengthens in alkanes, the number of conformations rapidly increases as a result of increased possibilities of rotation around each C-C bond, so long carbon chains of alkanes can take on many different shapes, such as zigzag (I), irregular (II) and claw-shaped (III). ).

A zigzag conformation is preferred, in which all C-C bonds in the Newman projection form an angle of 180°, as in the hindered conformation of butane. For example, fragments of long-chain palmitic C 15 H 31 COOH and stearic C 17 H 35 COOH acids in a zigzag conformation (Fig. 7.6) are part of the lipids of cell membranes.

Rice. 7.6.Skeletal formula (a) and molecular model (b) of stearic acid

In the claw-shaped conformation (III), carbon atoms that are distant from each other in other conformations come together. If there are functional groups at a sufficiently close distance, for example X and Y, that are capable of reacting with each other, then as a result of an intramolecular reaction this will lead to the formation of a cyclic product. Such reactions are quite widespread, which is associated with the advantage of the formation of thermodynamically stable five- and six-membered rings.

7.2.2. Conformations of six-membered rings

The cyclohexane molecule is not a flat hexagon, since with a flat structure the bond angles between the carbon atoms would be 120°, i.e., they would significantly deviate from the normal bond angle of 109.5°, and all the hydrogen atoms would be in an unfavorable occluded position. This would lead to cycle instability. In fact, the six-membered cycle is the most stable of all cycles.

The different conformations of cyclohexane result from partial rotation around σ bonds between carbon atoms. Of the several nonplanar conformations, the most energetically favorable conformation is armchairs(Fig. 7.7), since in it all bond angles between the C-C bonds are equal to ~110?, and the hydrogen atoms at neighboring carbon atoms do not obscure each other.

In a non-planar molecule, one can only conditionally speak of the arrangement of hydrogen atoms “above and below the plane.” Instead, other terms are used: bonds directed along the vertical axis of symmetry of the cycle (in Fig. 7.7, A shown in color) are called axial(a), and connections oriented away from the cycle (as if along the equator, by analogy with the globe) are called equatorial(f).

If there is a substituent in the ring, a conformation with an equatorial position of the substituent is more favorable, such as conformation (I) of methylcyclohexane (Fig. 7.8).

The reason for the less stability of conformation (II) with the axial arrangement of the methyl group is 1,3-diaxial repulsion CH groups 3 and H atoms in positions 3 and 5. In this

Rice. 7.7.Cyclohexane in chair conformation:

A- skeletal formula; b- ball-and-rod model

Rice. 7.8.Ring inversion of a methylcyclohexane molecule (not all hydrogen atoms shown)

In this case the cycle undergoes the so-called inversions, taking on a more stable conformation. The repulsion is especially strong in cyclohexane derivatives having 1- and 3-position bulk groups.

Many derivatives of the cyclohexane series are found in nature, among which hexahydric alcohols play an important role - inositols. Due to the presence of asymmetric centers in their molecules, inositols exist in the form of several stereoisomers, of which the most common is myoinositol. The myoinositol molecule has a stable chair conformation in which five of the six OH groups are in equatorial positions.