They are derivatives of hydrocarbons, in the molecules of which two hydrogen atoms, located at one carbon atom, are replaced by an oxygen atom. The group >C=O obtained in this way is called a carbonyl group, or an oxo group. If the carbonyl group is bonded to one hydrogen atom and a hydrocarbon radical (or to two hydrogen atoms), then such compounds are called aldehydes, and the group is called an aldehyde group; if the carbonyl group is bonded to two hydrocarbon radicals, the compounds are called ketones, and the group is called a keto group. Thus, aldehydes and ketones are one class of organic substances - oxo compounds.

The atomic orbitals of carbon of the carbonyl group are in a state of sp 2 hybridization. Three hybrid orbitals located in the same plane at an angle of » 120 ° with respect to each other participate in the formation of three s- connections. The non-hybrid p-orbital of the carbon atom, located perpendicular to the plane in which they lie s- bonds, participates in the formation of a p-bond with an oxygen atom. The carbon-oxygen double bond is polar, the electron density is shifted to the more electronegative oxygen atom, on which a partial negative charge arises, and on the carbon atom of the carbonyl group, a partial positive charge:

It follows from this that the reaction characteristic of the carbonyl group must be a nucleophilic attack on the carbon atom. In the molecules of carbonyl compounds, in addition to the electrophilic center - the carbon atom of the oxo group - there are other reaction centers. The oxygen atom, due to the lone pair of electrons, acts as the main center in reactions, reacting with acids. Aldehydes and ketones are weak bases, the concentration of the protonated form of the carbonyl compound reaches values ​​\u003e 0.1-1% only in 60-80% sulfuric acid.

As a result of the addition of a proton due to the formation s-bonds О-Н increases the electrophilicity of the carbon atom of the oxo group and facilitates the addition of a nucleophilic particle.

Hydration of ketones is possible only in the presence of acids or alkalis as catalysts.

Mechanism of the hydration reaction in acid catalysis:

At the first stage, the proton is attached to the oxygen atom of the carbonyl group (due to the lone pair of oxygen electrons) with the formation of the oxonium cation, which at the next stage turns into a carbocation, which is easily (due to the whole positive charge on carbon) subjected to nucleophilic attack by a water molecule. The resulting oxonium cation is stabilized by proton elimination (catalyst recycle).

Mechanism of hydration reaction in basic catalysis:

When hydration is carried out in an alkaline environment, the hydroxide ion attacks the electrophilic carbon atom of the carbonyl group to form the oxonium anion, which is further stabilized by the elimination of a proton from the water molecule.

Unlike most carbonyl compounds, 2,2,2-trichloroethanal (chloral) easily reacts with water, forming a stable hydration product - chloral hydrate, used in medicine and veterinary medicine as a sedative and hypnotic. The increased reactivity of this compound is explained by the strong electron-withdrawing effect of the trichloromethyl group, which increases the effective positive charge on the carbonyl carbon atom and also stabilizes the reaction product.

Alcohol addition reactions

In the presence of dry hydrogen chloride, aldehydes react with alcohols to form acetals. In most cases, intermediately formed hemiacetals cannot be isolated in free form. It should be noted that the conversion of hemiacetals to acetals does not occur without acid catalysts.

The conversion of aldehydes to hemiacetals occurs by the mechanism of nucleophilic addition A N , and the subsequent conversion of hemiacetal to acetal is a nucleophilic substitution.

The need to use acid catalysis in the conversion of hemiacetals to acetals is due to the fact that the OH group is poorly leaving. To convert it into a good leaving group - the H 2 O molecule - acids are used as catalysts.

In the case of reactions of ketones with alcohols, the positive charge on the carbon atom of the carbonyl group is insufficient for a direct attack by the alcohol molecule, and ketals of monohydric alcohols cannot be obtained in this way. They are obtained using orthoesters of formic acid.

The reactions of formation of hemiacetals and acetals are characteristic of natural heteropolyfunctional compounds - carbohydrates. Monosaccharides are, as a rule, polyhydroxy aldehydes or polyhydroxy ketones, inside the molecules of which an interaction occurs between the hydroxyl and carbonyl groups, leading to the formation of a heterocycle:

The cyclic forms of monosaccharides are cyclic hemiacetals or cyclic hemiketals. The formation of oligosaccharides and polysaccharides is an acetal formation reaction that is repeated many times:

Polysaccharides, like acetals, undergo hydrolysis only in an acidic environment.

The addition of RSH mercaptans to aldehydes and ketones leads to the formation of thioacetals, respectively. The ability of mercaptan molecules to effectively attack the carbon atom of the carbonyl group of ketones reflects the greater tendency of RSH (compared to ROH) to form effective nucleophiles RS - , i.e. the greater acidity of thiols compared to alcohols.

The chemistry of aldehydes and ketones is determined by the presence of a carbonyl group. This group, firstly, is the site of nucleophilic attack and, secondly, increases the acidity of the hydrogen atoms associated with the -carbon atom. Both of these effects are quite consistent with the structure of the carbonyl group, and in fact both are due to the ability of oxygen to take on a negative charge.

(In this chapter, only the simplest types of nucleophilic addition reactions are considered. In Chapter 27, reactions of -hydrogen atoms will also be discussed.)

The carbonyl group contains a carbon-oxygen double bond; since the mobile -electrons are strongly attracted to oxygen, the carbonyl group carbon is an electron-deficient center, and the carbonyl group oxygen is electron-rich. Since this part of the molecule is flat, it is relatively accessible to attack from above or below this plane in a direction perpendicular to it. Not surprisingly, this available polarized group is highly reactive.

What kind of reagents will attack such a group? Since the most important stage in these reactions is the formation of a bond with an electron-deficient (acidic) carbonyl carbon, the carbonyl group is most prone to interact with electron-rich nucleophilic reagents, i.e., with bases. Typical reactions of aldehydes and ketones would be nucleophilic addition reactions.

As expected, the most accurate picture of the reactivity of the carbonyl group can be obtained by considering the transition state for the addition of a nucleophile. The carbon atom in the reagent is trigonal. In the transition state, the carbon atom begins to assume the tetrahedral configuration it will have in the product; thus, the groups associated with it converge somewhat. Therefore, some spatial difficulties can be expected, i.e., large groups will prevent this approach to a greater extent than smaller groups. But the transition state in this reaction will be relatively less difficult than the transition state for, say, a -reaction in which carbon is bonded to five atoms. It is this relative ease that is meant when the carbonyl group is said to be available for attack.

In the transition state, oxygen begins to acquire electrons and the negative charge that it will have in the final product. It is the tendency of oxygen to acquire electrons, or rather its ability to carry a negative charge, that is the real reason for the reactivity of the carbonyl group towards nucleophiles. (The polarity of the carbonyl group is not the cause of reactivity, but only another manifestation of the electronegativity of oxygen.)

Aldehydes tend to undergo nucleophilic addition more easily than ketones. This difference in reactivity is consistent with the nature of the intermediate state of the reaction and, apparently, is explained by the combined action of electronic and spatial factors. The ketone contains a second alkyl or aryl group, while the aldehyde contains a hydrogen atom. The second aryl or alkyl group of the ketone is larger than the hydrogen atom of the aldehyde and will therefore be more resistant to increasing steric hindrance in the transition state. The alkyl group donates electrons and thereby destabilizes the transition state by increasing the negative charge on the oxygen.

One might expect that the aryl group, with its electron-retracting inductive effect (problem 18.7, p. 572), would stabilize the transition state and thereby speed up the reaction; however, apparently, this effect stabilizes the initial ketone to an even greater extent due to resonance (contribution of structure I) and, as a result, deactivates the ketone in the reaction under consideration.

protonated form

The basicity of aldehydes and ketones is low, but it plays a significant role in nucleophilic addition reactions, since the electrophilicity of the carbon atom in the protonated form is much higher. Therefore, the AdN reactions typical of aldehydes and ketones can be catalyzed by acids.

2.2. Nucleophilic addition reactions

The interaction of aldehydes and ketones with nucleophilic agents is carried out according to the following general mechanism:

The Z-H nucleophile (very often there is a hydrogen atom at the nucleophilic center) is attached to the electrophilic carbon atom of the carbonyl group due to the lone pair of electrons of the nucleophilic center, forming a product in which the former carbonyl oxygen has a negative charge, and the former nucleophilic center is positively charged. This bipolar ion is stabilized by the transfer of a proton from the positively charged Z atom (Brønsted's acid) to the negatively charged oxygen atom (base). The resulting product often undergoes further transformations, for example, elimination of water.

Various compounds can act as nucleophiles, in which oxygen atoms (O-nucleophiles), sulfur atoms (S-nucleophiles), nitrogen (N-nucleophiles), carbon atoms (C-nucleophiles) act as nucleophilic centers.

The reactivity of aldehydes and ketones in nucleophilic addition reactions depends on the electrophilicity of the car-

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bonyl group: the greater the partial positive charge on the carbon atom, the easier it is to attach the nuc-

leophila. Since the molecules of aldehydes at the carbonyl carbon atom contain only one hydrocarbon residue that exhibits electron-donating properties, and the molecules of ketones have two such residues, it is natural to assume that in the general case in nucleophilic addition reactions, aldehydes are more reactive than ketones. Electron-withdrawing substituents, especially near the carbonyl group, increase the electrophilicity of the carbonyl carbon and therefore increase reactivity. The steric factor is also of certain importance: since the addition of the carbon atom of the carbonyl group changes the hybridization (sp2 → sp3), the more bulky the substituents at the carbonyl carbon atom, the greater the steric difficulties that arise during this transition. For example, in the series: formaldehyde, acetaldehyde, acetone, tert-butyl methyl ketone, the reactivity decreases.

(CH3 )3 C

a) Reactions with O-nucleophiles

Hydration

When aldehydes and ketones interact with water in a reversible process, a hydrate is formed - geminal diol, which in most cases is a very unstable compound, therefore this equilibrium is strongly shifted to the left.

However, for some carbonyl compounds, this equilibrium can be shifted to the right. Thus, in an aqueous solution, formaldehyde is almost completely in the hydrated form (unlike, for example, acetone, in which the hydrated form is extremely small in an aqueous solution), and trichloroacetic aldehyde (chloral), when interacting with water, turns into a very stable chloral hydrate even in crystalline form. .

CH2 \u003d O H 2 O CH2 (OH) 58 2

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Cl3 CCH=O + H2 O Cl3 CCH(OH)2

chloral chloral hydrate

Interaction with alcohols (acetalization reaction)

The product of addition of one alcohol molecule to an aldehyde or ketone molecule, the so-called hemiacetal, is unstable. When an aldehyde or ketone interacts with 2 equivalents of alcohol in an acidic environment, a stable product is formed -

acetal.

Let us give the mechanism of the last reaction using the example of the interaction of acetaldehyde with methyl alcohol (1:2) in the presence of a strong Bronsted acid.

Protonation of the carbonyl group of acetaldehyde leads to the formation of a cation in which the positive charge is delocalized. Compared to acetaldehyde, this cation is more electrophilic, and the nucleophilic addition of a methanol molecule to it occurs much more easily. The addition product (oxonium cation) is a strong acid, and when a proton is removed from it, hemiacetal (1-methoxyethanol) is formed.

		CH3 CH=O H
CH3 CH=O			HOCH3	CH3CHOH		CH3CHOH
		CH3CHOH		H O CH3		OCH3

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Further, through the protonated form of this hemiacetal, water is split off with the formation of a carbocation, to which the next methanol molecule is attached. Upon deprotonation of the addition product, acetaldehyde dimethyl acetal(1,1-dimethoxyethane).

							HOCH3
	CH3CHOH		CH3 CHOH			CH3CH
	OCH3			OCH3		OCH3
	CH3CH		OCH3		CH3 CH OCH3
		OCH3			OCH3

The entire reaction process described, which is called acetalization, is reversible, therefore, it is possible to effectively carry out the interaction of an aldehyde or ketone with an alcohol to an acetal only by shifting the equilibrium to the right, for example, by removing the resulting water from the reaction sphere. The reverse reaction is the acid hydrolysis of the acetal. Consequently, acetals are unstable in an acidic aqueous medium, since they undergo hydrolysis.

			OCH3 + H2O						CH3CH=O + 2CH3OH
	OCH3

IN acetals are stable in an alkaline environment, since hydrolysis

V these conditions cannot occur.

b) Reactions with S-nucleophiles

The sulfur atom in analogues of alcohols - thiols (mercaptans) - is a stronger nucleophile, so mercaptans are more easily attached to aldehydes and ketones. In this case, products similar to hemiacetals and acetals are formed, for example, when benzaldehyde reacts with two equivalents of methanethiol (methyl mercaptan) in an acidic medium, benzaldehyde dimethylthioacetal is formed.

		2CH3SH		CH(SCH3 )2

(reactions of addition-cleavage).

Reactions of nucleophilic substitution involving - hybridized carbon atom. Let us consider the mechanism of reactions of this type using the example of the interaction of carboxylic acids with alcohols ( esterification reaction). In the carboxyl group of the acid, p, -conjugation, since a pair of electrons of the oxygen atom of the OH hydroxyl group enters conjugation with a carbon-oxygen double bond (-bond):

Such conjugation is the cause, on the one hand, of increased acidity of carboxyl compounds, and on the other hand, a decrease in the partial positive charge () on the carbon atom of the carboxyl group (-hybridized atom), which greatly complicates the direct attack of the nucleophile. In order to increase the charge on the carbon atom, additional protonation is used - acid catalysis (stage I):

At stage II, the attack of the nucleophile (alcohol molecule), the protonation of the hydroxyl group with the formation of a well-leaving group occurs, at stage III - its elimination and at stage IV - proton regeneration - return of the catalyst with the formation of the final product - an ester. The reaction is reversible, which is observed during the hydrolysis of esters, the hydrolysis of fats in biosystems.

Reactions of nucleophilic addition. The most characteristic reactions of nucleophilic addition () for oxo compounds - aldehydes and ketones. The mechanism of these reactions has common features; it is a two-stage ionic process. The first stage (limiting) is a reversible attack by the nucleophile Nu : with the formation of the so-called tetrahedral intermediate. The second stage is a fast electrophile attack:

The reactivity of the oxo compound is influenced by the nature of the R and groups. Thus, the introduction of electron-donating substituents reduces the reactivity, while the introduction of electron-withdrawing substituents enhances it. Therefore, aldehydes are more reactive than ketones. In addition, the reactivity depends on the nature of the nucleophile. For example, RSH thiols, being stronger nucleophiles than ROH alcohols, react with both aldehydes and ketones, forming thioacetals that are resistant to hydrolysis, while acetals, the products of addition of alcohols to aldehydes, are not resistant to hydrolysis:

Please note that the last stages of the process represent the attack of the nucleophile (alcohol molecule) on the electrophilic reaction center (carbocation) and follow the mechanism of nucleophilic substitution. The resulting intermediate compounds - hemiacetals - are unstable. Their stabilization is possible only in a cyclic form during the formation of cyclic hemiacetals, for example, 5-hydroxypentanal:

Another example of a biologically important reaction of this type is the addition of amines and some other nitrogen-containing compounds to carbonyl compounds - aldehydes and ketones. The reaction goes along the mechanism of nucleophilic addition-elimination (-E), or nucleophilic addition-cleavage:

Other nitrogen-containing compounds that act as nucleophiles in these reactions: hydrazine, hydroxylamine, phenylhydrazine .

The products of the -E reactions in these cases are compounds of the general formula

called hydrazones (X = ), oximes (X = OH), phenylhydrazones (X = ), imines (X = R), which will be discussed in more detail in the relevant sections.

In addition to the indicated addition reactions, reactions are possible Ad R- free radical addition and polymerization or polycondensation.

Ad R - free radical addition

An example of a reaction polycondensation is the polycondensation of phenol with aldehydes, in particular, with formaldehyde, which results in the formation of polymeric reaction products - phenol-formaldehyde resins and solid polymers.

The interaction of phenol with formaldehyde can be described by the scheme:

In the course of further steps, a polymer is formed, and the by-product of the polycondensation reaction, in this case, is water.

CHAPTER 4. OXO COMPOUNDS (ALDEHYDES AND KETONES).

Questions for the lesson.

1. Electronic structure of the carbonyl group (>C=0) in oxo compounds.

2. Effect of substituents on the reactivity of >C=0-bonds in oxo compounds.

3. Mechanism of nucleophilic addition at the >C=0 bond.

4. Reactions of nucleophilic addition (for example, water, alcohols, sodium bisulfite, HCN).

5. Reactions of addition-elimination on the example of hydroxylamine, hydrazine, amines.

6. Disproportionation reaction using benzylaldehyde as an example.

7. Aldol condensation reaction mechanism.

8. Oxidation of aldehydes and ketones.

9. Polymerization of aldehydes.

Depending on the nature of the substituents associated with the carbonyl group, carbonyl compounds are divided into the following classes: aldehydes, ketones, carboxylic acids and their functional derivatives.