For aldehydes and ketones, nucleophilic addition reactions are most characteristic A N .

General description of the nucleophilic addition mechanismA N

The ease of nucleophilic attack on the carbon atom of the carbonyl group of an aldehyde or ketone depends on the magnitude of the partial

positive charge on the carbon atom, its spatial availability and acid-base properties of the medium.

Taking into account the electronic effects of the groups associated with the carbonyl carbon atom, the value of the partial positive charge δ+ on it in aldehydes and ketones decreases in the following series:

The spatial availability of the carbonyl carbon atom decreases when hydrogen is replaced by bulkier organic radicals, so aldehydes are more reactive than ketones.

General scheme of nucleophilic addition reactions A N to the carbonyl group involves a nucleophilic attack on the carbonyl carbon followed by the addition of an electrophile to the oxygen atom.

In an acidic environment, the activity of the carbonyl group, as a rule, increases, since due to the protonation of the oxygen atom, a positive charge arises on the carbon atom. Acid catalysis is usually used when the attacking nucleophile has low activity.

According to the above mechanism, a number of important reactions of aldehydes and ketones are carried out.

Many reactions characteristic of aldehydes and ketones occur in the body, these reactions are presented in the subsequent sections of the textbook. This chapter will discuss the most important reactions of aldehydes and ketones, which are summarized in Scheme 5.2.

addition of alcohols. Alcohols, when interacting with aldehydes, easily form hemiacetals. Hemiacetals are not usually isolated due to their instability. With an excess of alcohol in an acidic environment, hemiacetals turn into acetals.

The use of an acid catalyst in the conversion of hemiacetal to acetal is clear from the reaction mechanism below. The central place in it is occupied by the formation of a carbocation (I), stabilized due to the participation of the lone pair of electrons of the neighboring oxygen atom (+M effect of the C 2 H 5 O group).

The reactions of formation of hemiacetals and acetals are reversible; therefore, acetals and hemiacetals are easily hydrolyzed by excess water in an acidic medium. In an alkaline environment, hemiacetals are stable, since the alkoxidion is a more difficult leaving group than the hydroxide ion.

The formation of acetals is often used as a temporary protection of the aldehyde group.

Water connection. Adding water to a carbonyl group - hydration- reversible reaction. The degree of hydration of an aldehyde or ketone in an aqueous solution depends on the structure of the substrate.

The product of hydration, as a rule, cannot be isolated by distillation in a free form, since it decomposes into its original components. Formaldehyde in an aqueous solution is hydrated by more than 99.9%, acetaldehyde is approximately half, and acetone is practically not hydrated.

Formaldehyde (formaldehyde) has the ability to coagulate proteins. Its 40% aqueous solution, called formalin, used in medicine as a disinfectant and preservative of anatomical preparations.

Trichloroacetic aldehyde (chloral) is fully hydrated. The electron-withdrawing trichloromethyl group stabilizes chloral hydrate to such an extent that this crystalline substance splits off water only during distillation in the presence of dehydrating substances - sulfuric acid, etc.

The pharmacological effect of CC13CH(OH)2 chloral hydrate is based on the specific action of the aldehyde group on the body, which determines the disinfectant properties. Halogen atoms enhance its action, and hydration of the carbonyl group reduces the toxicity of the substance as a whole.

Addition of amines and their derivatives. Amines and other nitrogen-containing compounds of the general formula NH2X (X = R, NHR) react with aldehydes and ketones in two stages. First, nucleophilic addition products are formed, which then, due to instability, split off water. In this regard, this process is generally classified as a reaction attachment-detachment.

In the case of primary amines, substituted imines(also called Schiff bases).

Imines are intermediates in many enzymatic processes. The preparation of imines proceeds through the formation of amino alcohols, which are relatively stable, for example, in the reaction of formaldehyde with α-amino acids (see 12.1.4).

Imines are intermediates in the production of amines from aldehydes and ketones by reductive amination. This general method consists in the reduction of a mixture of carbonyl compound with ammonia (or amine). The process proceeds according to the addition-cleavage scheme with the formation of an imine, which is then reduced to an amine.

When aldehydes and ketones react with hydrazine derivatives, hydrazones. This reaction can be used to isolate aldehydes and ketones from mixtures and their chromatographic identification.

Schiff's bases and other similar compounds are easily hydrolyzed by aqueous solutions of mineral acids to form the starting products.

In most cases, the reactions of aldehydes and ketones with nitrogenous bases require acid catalysis, which accelerates the dehydration of the addition product. However, if the acidity of the medium is increased too much, the reaction will slow down as a result of the conversion of the nitrogenous base into the non-reactive conjugate acid XNH3+.

polymerization reactions. These reactions are characteristic mainly of aldehydes. When heated with mineral acids, aldehyde polymers decompose into the starting products.

The formation of polymers can be viewed as the result of a nucleophilic attack by an oxygen atom of one aldehyde molecule on the carbonyl carbon atom of another molecule. So, when formalin is standing, a polymer of formaldehyde, paraform, precipitates in the form of a white precipitate.

Nucleophilic addition to alkynes is initiated under the influence of a negatively charged particle - nucleophile. In general, bases are the catalyst for such reactions. General scheme of the first stage of the nucleophilic addition reaction:

Typical nucleophilic addition reactions

A typical example of a nucleophilic addition reaction is the Favorsky reaction - the addition of alcohols in the presence of alkalis to form alkenyl esters:

Primary amines under the action of bases add to alkynes to form imines:

By analogy, acetylene reacts with ammonia to form ethylideneimine:

At high temperature in the presence of a catalyst, the imine dehydrogenates and turns into acetonitrile:

In an environment of very strong bases (for example: KOH + DMSO), acetylene reacts with hydrogen sulfide, forming divinyl sulfide:

Radical addition reactions

In the presence of peroxides or other conditions that promote the formation of free radicals, the addition to alkynes proceeds according to a radical mechanism - against the Markovnikov rule (Harash effect):

According to the free radical mechanism*, the reaction of alkynes with thiols can proceed:

* - In the presence of bases, the reaction proceeds according to the nucleophilic mechanism.

Similarly, the addition of carbenes occurs:

Ethynylation reactions

Ethynylation reactions are called reactions of increasing the carbon skeleton of alkynes with the preservation of the triple bond. They can proceed by both electrophilic and nucleophilic mechanisms, depending on the medium and reaction conditions, the nature of the substrate, and the type of catalyst used.

Obtaining acetylenic alcohols

In the presence of strong bases, alkynes with a terminal triple bond are able to add carbonyl compounds to form alcohols (Favorsky reaction):

The most important reaction from this group is the addition of formaldehyde to acetylene with the formation of propargyl alcohol and then butyn-2-diol-1,4 *:

Obtaining acetylenic esters and acids

Acetylene acids or their esters can be obtained by the Zuzhi reaction:

Catalysts: PdCl 2 , CuCl.

Hydrogenation reactions

Heterogeneous hydrogenation

Hydrogenation of alkynes with hydrogen on heterogeneous catalysts, as a rule, leads to the formation cis- connections. Hydrogenation catalysts are Ni, Pd, Pt, as well as oxides or complexes of Ir, Ru, Rh and some other metals.

At the first stage, an alkene is formed, which is almost immediately hydrogenated to an alkane:

To stop the reaction at the stage of alkene production, Lindlar catalysts (Pd/PbO/CaCO 3) or nickel boride are used.

When acetylene is hydrogenated on a nickel-cobalt catalyst, isobutylene can be obtained:

Homogeneous hydrogenation

Homogeneous hydrogenation is carried out with sodium amide in liquid ammonia or lithium aluminum hydride in tetrahydrofuran. During the reaction, trance-alkenes.

Hydroboration

Alkynes easily add diborane against Markovnikov's rule, forming cis-alkenylboranes:

or oxidize H 2 O 2 to an aldehyde or ketone.

Nucleophilic addition reactions - addition reactions in which the attack at the initial stage is carried out by a nucleophile - a particle that is negatively charged or has a free electron pair.

In the final step, the resulting carbanion undergoes electrophilic attack.

Despite the commonality of the mechanism, addition reactions are distinguished by carbon-carbon and carbon-heteroatom bonds.

Nucleophilic addition reactions are more common for triple bonds than for double bonds.

Nucleophilic addition reactions at carbon-carbon bonds

Multiple bond nucleophilic addition is usually a two-step Ad N 2 process - a bimolecular nucleophilic addition reaction:

Nucleophilic addition at the C=C bond is quite rare, and, as a rule, if the compound contains electron-withdrawing substituents. The Michael reaction is of the greatest importance in this class:

Attachment at the triple bond is similar to attachment at the C=C bond:

Nucleophilic addition reactions at a carbon-heteroatom bond Nucleophilic addition at a multiple carbon-heteroatom bond has the Ad N 2 mechanism

As a rule, the rate-limiting stage of the process is a nucleophilic attack, electrophilic addition occurs quickly.

Sometimes the addition products enter into an elimination reaction, thereby collectively giving a substitution reaction:

Nucleophilic addition at the C=O bond is very common, which is of great practical, industrial and laboratory importance.

Acylation of unsaturated ketones

This method involves treating the substrate with an aldehyde and cyanide ion in a polar aprotic solvent such as DMF or Me 2 SO. This method is applicable to a,b-unsaturated ketones, esters and nitriles.

Condensation of esters with ketones

When esters are condensed with ketones, the yield of α-diketone is low, about 40%, this is due to the side reaction of ester self-condensation.

Hydrolysis of nitro compounds (Nef reaction)

The Nef reaction is a reaction of acid hydrolysis of nitro compounds with the formation of carbonyl compounds. Discovered in 1892 by the Russian chemist M.I. Konovalov and J. Nef in 1894. The Nef reaction consists in the hydrolysis of acyl forms of nitro compounds (nitronic acids), and therefore primary and secondary aliphatic and alicyclic nitro compounds can enter into it.

The Nef reaction makes it possible to obtain dicarbonyl compounds with a yield of up to 80-85%. To do this, the reaction is carried out at pH=1, since in a less acidic medium, nitronic acids isomerize back into a nitro compound with a decrease in the conversion of the nitro compound, and in a more acidic one, the formation of by-products increases. This reaction is carried out at t=0-5 0 C .

Interaction of ketones with acid chlorides in the presence of piperidine

Acid chlorides are easily reduced to primary alcohols under the action of lithium aluminum hydride. But if the enamine obtained from the ketone under the action of piperidine is reacted with acid chlorides, then after the hydrolysis of the initially obtained salt, b-diketones are formed.

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.

a) Interaction with alcohols. Aldehydes can react with one or two alcohol molecules to form hemiacetals and acetals, respectively.

Hemiacetals are compounds containing both hydroxyl and alkoxyl (OR) groups at one carbon atom. Acetals are compounds containing two alkoxy groups at one carbon atom:

hemiacetal acetal

The reaction for obtaining acetals is widely used in organic syntheses to "protect" the active aldehyde group from undesirable reactions:

Such reactions are of particular importance in the chemistry of carbohydrates.

b) Accession of hydrosulfites serves to isolate aldehydes from mixtures with other substances and to obtain them in pure form, since the resulting sulfo derivative is very easily hydrolyzed:

R-CH \u003d O + NaHSO 3 → R-CH (OH) -SO 3 Na.

in) reaction with theoli. aldehydes and ketones react with thiols in an acidic environment, dithioacetal is formed:

G) Accession of hydrocyanic(hydrocyanic) acid:

CH 3 -CH \u003d O + H-CN → CH 3 -CH (CN) -OH.

The resulting compound contains one carbon atom more than the original aldehyde or ketone, so these reactions are used to lengthen the carbon chain.

e) Attachment of the Grignard reagent. In organic synthesis, the Grignard reagent is extremely often used - one of the simplest organometallic compounds.

When a solution of a haloalkane in diethyl ether is added to magnesium shavings, an exothermic reaction easily occurs, magnesium goes into solution and a Grignard reagent is formed:

R-X + Mg → R-Mg-X,

where R is an alkyl or aryl radical, X is a halogen.

- The interaction of the Grignard reagent with formaldehyde, almost any primary alcohol (except methanol) can be obtained. For this, the addition product of the Grignard reagent is hydrolyzed with water.

H 2 CO + RMgX → R-CH 2 -O-MgX → R-CH 2 -OH.

- When using any other aliphatic aldehydes, secondary alcohols can be obtained:

- Tertiary alcohols are obtained by the interaction of Grignard reagents with ketones:

(CH 3) 2 C \u003d O + R-MgX → (CH 3) 2 C (R) -O-MgX → (CH 3) 2 C (R) -OH

16. Aldehydes and ketones. Chemical properties: condensation reaction, reactions with nitrogen-containing compounds. Individual representatives and their application.

Organic compounds in the molecule of which there is a carbonyl group C=O are called carbonyl compounds or oxo compounds. They are divided into two related groups - aldehydes and kwtons.

Condensation reaction:

Aldol condensation

with compounds with CH acidic properties, aldehydes and ketones are able to enter into various condensation reactions. compounds containing mobile hydrogen in these reactions acts as a nucleophilic reagent and is called the mytelin component, and aldehydes and ketones are called the carbonyl component. the reaction of aldol condensation proceeds under the action of dilute alkalis on the aldehyde or ketone. while one aldehyde molecule is a methylene component, the other is a carboxylic component.

Under the action of a base, the aldehyde removes a proton from the α CH acid center and turns into a carbanion. The carbanion is a strong nucleophile and attaches to another aldehyde molecule. the stabilization of the resulting anion occurs due to the elimination of a proton from a weak acid.

Mechanism:

If the aldol condensation is accompanied by the elimination of water (at high temperature), then such a condensation is called crotonic condensation:

The reaction of aldol or cratonic condensation is often carried out in a mixed substance. when the methylene and carboxylic components are different compounds. the selection of partners for this reaction is based on the fact that the carbonyl component must be highly reactive in nucleophilic addition reactions. basically it's an aldehyde. at the same time, the methylene component must have a high CH-acidity - various aldehydes or ketones having an α-hydrogen atom.