Functional derivatives of carboxylic acids. Dibasic carboxylic acids.a , b -Unsaturated acids
Carboxylic acid derivatives
1. Acid halides.
When exposed to phosphorus halides or thionyl chloride, the formation of halides occurs:
CH 3 COOH + PCl 5 ® CH 3 COCl + POCl 3 + HCl
The halogen in acid halides is highly reactive. A strong inductive effect determines the ease of substitution of halogen with other nucleophiles: - OH, - OR, - N.H.2, - N3, - CN etc.:
CH 3 COCl + CH 3 COOAg® (CH3CO)2O acetic anhydride + AgCl
1. Anhydrides.
Anhydrides are formed by the reaction of acid salts with their acid halides:
CH 3 COONa + CH 3 COCl ® NaCl + (CH 3 CO) 2 O
Acid anhydrides are highly chemically active and, like acid halides, are good acylating agents.
2. Amides.
Amides are obtained via acid halides
CH 3 COCl +2 NH 3® CH 3 CONH 2acetamide+NH4Cl
or from ammonium salts of acids, during dry distillation of which water is split off and an acid amide is formed. Also, acid amides are formed as a by-product during the hydrolysis of nitriles. Amidation processes are important industrially for the production of a number of valuable compounds ( N, N-dimethylformamide, dimethylacetamide, ethanolamides of higher acids).
4. Nitriles. The most important representatives of nitriles are acetonitrile CH 3 CN(used as a polar solvent) and acrylonitrile CH 2 = CHCN(monomer for the production of synthetic neuron fiber and for the production of divinylnitrile synthetic rubber, which is oil and gasoline resistant). The main method for producing nitriles is the dehydration of amides on acid catalysts:
CH 3 CONH 2 ® CH 3 C- CN + H 2 O
5. Esters. Esters of carboxylic acids are of important practical importance as solvents, hydraulic fluids, lubricating oils, plasticizers and monomers. They are obtained by esterification of alcohols with acids, anhydrides and acid halides or by the reaction of acids and alkenes:
CH 3 -CH=CH 2 + CH 3 COOH® CH 3 COOCH(CH 3) 2
Many esters are used as aromatic substances:
| CH 3 COOCH 2 CH 3 | pear essence |
| CH 3 CH 2 CH 2 COOCH 2 CH 2 CH 2 CH 2 CH 3 | pineapple essence |
| HCOOCH 2 CH 3 | rum essence |
Dibasic saturated acids
Dibasic saturated (saturated) acids have the general formula CnH 2 n(COOH) 2 . Of these, the most important are:
NOOS-SOUN- oxalic, ethanedicarboxylic acid;
NOOS-CH 2 -COOH- malonic, propanedicarboxylic acid;
NOOS-CH 2 -CH 2 -COOH- succinic, butanedicarboxylic acid;
NOOS-CH 2 -CH 2 -CH 2 -COOH- glutaric, pentanedicarboxylic acid.
Methods of obtaining
General methods the production of dibasic acids is similar to the methods for producing monobasic acids (oxidation of glycols, hydrolysis of dinitriles, Kolbe synthesis - see Lecture No. 27).
1. Oxidation of hydroxy acids:
OH-CH2CH2COOH® HOCCH 2 COOH® HOOC-CH2-COOH
2. Oxidation of cycloalkanes.
This is an industrial method for producing adipic acid HOOC- CH 2 CH 2 CH 2 CH 2 - COOH from cyclohexane.
Succinic and oxalic acids are also formed as by-products. Adipic acid is used for fiber synthesis nylon 6.6 and plasticizers.
Dibasic acids are stronger than monobasic acids. This is explained by the mutual influence of carboxyl groups that facilitate dissociation:
In general, the reactions of dicarboxylic acids and their monocarboxylic analogues are almost the same. The reaction mechanism for the formation of diamides, diesters, etc. from carboxylic acids is the same as for monocarboxylic acids. The exception is dicarboxylic acids, which contain fewer than four carbon atoms between the carboxyl groups. Such acids, the two carboxyl groups of which are capable of reacting with the same functional group or with each other, exhibit unusual behavior in reactions proceeding with the formation of five- or six-membered closed activated complexes or products.
An example of the unusual behavior of carboxylic acids is the reactions that occur when heated.
At 150 o C, oxalic acid decomposes into formic acid and CO 2:
HOOC-COOH® HCOOH + CO2
2. Cyclodehydration.
When heated g-dicarboxylic acids, in which the carboxyl groups are separated by carbon atoms, undergo cyclodehydration, resulting in the formation of cyclic anhydrides:
3. Syntheses based on malonic ester.
Dibasic acids with two carboxyl groups on one carbon atom, i.e. malonic acid and its mono- and disubstituted homologues, when heated slightly above their melting temperatures, decompose (are subjected to decarboxylation) with the elimination of one carboxyl group and the formation of acetic acid or its mono- and disubstituted homologues:
HOOCCH 2 COOH® CH 3 COOH + CO 2
HOOCCH(CH3)COOH® CH3CH2COOH + CO 2
HOOCC(CH 3) 2 COOH® (CH3) 2 CHCOOH + CO 2
The hydrogen atoms of the methylene group located between the acyl groups of malonic acid diethyl ester ( malonic ester), have acidic properties and give a sodium salt with sodium ethoxide. This salt sodium malonic ester– alkylate by mechanism nucleophilic substitution S N2 . Based on sodium malonic ester, mono- and dibasic acids are obtained:
-Na++RBr® RCH(COOCH 2 CH 3) 2 + 2 H 2 O ®
R-CH(COOH)2 alkylmalonic acid ® R-CH2COOHalkylacetic acid+CO2
4. Pyrolysis of calcium and barium salts.
During pyrolysis of calcium or barium salts adipic (C 6), pimeline (C 7) And cork (From 8) acids are eliminated CO 2 and cyclic ketones are formed:
Unsaturated monobasic carboxylic acids
Unsaturated monobasic acids of the ethylene series have the general formula CnH 2 n -1 COOH, acetylene and diethylene series - CnH 2 n -3 COOH. Examples of unsaturated monobasic acids:
Unsaturated monobasic acids differ from saturated ones by large dissociation constants. Unsaturated acids form all the usual derivatives of acids - salts, anhydrides, acid halides, amides, esters, etc. But due to multiple bonds they enter into addition, oxidation and polymerization reactions.
Due to the mutual influence of the carboxyl group and the multiple bond, the addition of hydrogen halides to a,b-unsaturated acids occurs in such a way that hydrogen is directed to the least hydrogenated carbon atom:
CH 2 = CHCOOH + HBr ® BrCH 2 CH 2 COOH b-bromopropionic acid
Ethylene acids such as acrylic acid and their esters undergo polymerization much more easily than the corresponding hydrocarbons.
individual representatives
Acrylic acid obtained from ethylene (via chlorohydrin or ethylene oxide), by hydrolysis of acrylonitrile or oxidation of propylene, which is more efficient. In technology, derivatives of acrylic acid are used - its esters, especially methyl ( methyl acrylate). Methyl acrylate easily polymerizes to form transparent glassy substances, so it is used in the production of organic glass and other valuable polymers.
Methacrylic acid and its esters are prepared on a large scale by methods similar to those for the synthesis of acrylic acid and its esters. The starting product is acetone, from which acetone cyanohydrin is obtained, subjected to dehydration and saponification to form methacrylic acid. By esterification with methyl alcohol, methyl methacrylate is obtained, which, upon polymerization or copolymerization, forms glassy polymers (organic glasses) with very valuable technical properties.
acids - mesotartaric acid is not an optically active substance. The homologue of oxalic acid is adipic acid HOOC(CH 2) 4 COOH, which is obtained by the oxidation of certain cyclic compounds. It is included in cleaning products for removing rust, and also serves as a starting material for the production of polyamide fibers (see the article “Giants organic world. Polymers").
CARBOXYLIC ACIDS AND THEIR DERIVATIVES
Although the carboxyl group consists of carbonyl and hydroxyl groups, carboxylic acids have very different properties from both alcohols and carbonyl compounds. The mutual influence of OH- and -groups leads
to the redistribution of electron density. As a result, the hydrogen atom of the hydroxyl group acquires acid properties, i.e., it is easily split off when the acid is dissolved in water. Carboxylic acids change the color of indicators and exhibit all the properties characteristic of solutions of inorganic acids.
All monobasic acids that do not contain substituents (for example, formic and acetic acids) are weak - only slightly dissociated into ions. The strength of the acid can be changed by introducing a halogen atom into the a-position of the functional group. Thus, trichloroacetic acid, formed during the chlorination of acetic acid CH 3 COOH + 3Cl 2 ®CCl 3 COOH + 3HCl, in an aqueous solution largely dissociates into ions.
Carboxylic acids can form functional derivatives, the hydrolysis of which again produces the original acids. Thus, when carboxylic acids are exposed to phosphorus(V) chloride and oxide, acid chlorides and anhydrides are formed, respectively; under the action of ammonia and amines - amides; alcohols - esters.
Crystals of monochloroacetic acid CH 2 ClCOOH.
Graph of the dependence of the boiling point of alkanes, alcohols, aldehydes and straight-chain carboxylic acids on the number of carbon atoms in the molecule.
Educational response esters is called esterification(from Greek"ether" - "ether"). It is usually carried out in the presence of a mineral acid, which acts as a catalyst. When heated, the ester (or water, if the ether boils at a temperature above 100 ° C) is distilled off from the reaction mixture, and the equilibrium shifts to the right. So, from acetic acid and ethyl alcohol get ethyl acetate - a solvent that is part of many types of glue:
Many esters are colorless liquids with a pleasant odor. Thus, isoamyl acetate smells like pear, ethyl butyrate smells like pineapple, isoamyl butyrate smells like apricot, benzyl acetate smells like jasmine, and ethyl formate smells like rum. Many esters are used as
flavoring additives in the manufacture of various drinks, as well as in perfumery. Derivatives of 2-phenylethyl alcohol have a particularly delicate odor: the ester of this alcohol and phenylacetic acid smells like honey and hyacinths. And the aroma of formic acid ester makes you remember the fragrance of a bouquet of roses and chrysanthemums. In the presence of alkali, esters can be hydrolyzed - decomposed into the original alcohol and a carboxylic acid salt. The hydrolysis of fats (esters of glycerol and higher carboxylic acids) produces the main components of soap - palmitate and sodium stearate,
NAMES OF SOME CARBOXYLIC ACIDS AND THEIR SALTS
*Ethyl acetate is a colorless, water-insoluble liquid with a pleasant ethereal odor ( t kip =77.1 °C), miscible with ethyl alcohol and other organic solvents.
**The names of esters are derived from the names of the corresponding alcohols and acids: ethyl acetate - an ester of ethyl alcohol and acetic acid (ethyl acetyl ester), isoamyl formate - an ester of isoamyl alcohol and formic acid (formic isoamyl ester).
GLACIC ACID
Vinegar, which is formed when wine sours, contains about 5% acetic acid (table vinegar is called a 3-15% solution). By distilling such vinegar, vinegar essence is obtained - a solution with a concentration of 70-80%. And pure (100 percent) acetic acid is released as a result of the action of concentrated sulfuric acid on acetates: CH 3 COOHNa + H 2 SO 4 (conc.) = CH 3 COOH + NaHSO 4.
Such pure acetic acid, which does not contain water, turns into transparent crystals resembling ice when cooled to 16.8 ° C. That's why it is sometimes called icy.
The similarity is not only external: in the crystals there are molecules of acetic acid,
Liquid at room temperature, glacial acetic acid, when cooled below 1–7 °C, turns into colorless crystals that really look like ice.
like water molecules, they form a system hydrogen bonds. The intermolecular interaction turns out to be so strong that even acetic acid vapor contains not individual molecules, but their agglomerates.
Many salts of acetic acid are unstable to heat. Thus, the decomposition of calcium acetate produces acetone:
And when a mixture of sodium acetate and alkali is heated, methane is released:
For many centuries, the main method for the synthesis of acetic acid was fermentation. Edible vinegar is still produced this way. And for the production of esters and artificial fibers, acid is used as a raw material, which is obtained by the catalytic oxidation of hydrocarbons, for example butane:
CH 3 -CH 2 -CH 2 -CH 3 +2.5O 2 ®2CH 3 -COOH+H 2 O.
CHAPTER 6. REACTIVITY OF CARBOXYLIC ACIDS AND THEIR FUNCTIONAL DERIVATIVESCHAPTER 6. REACTIVITY OF CARBOXYLIC ACIDS AND THEIR FUNCTIONAL DERIVATIVES
6.1. Carboxylic acids
6.1.1. General characteristics
Carboxylic acids are compounds whose functional group is the carboxyl group -COOH.
Depending on the nature of the organic radical, carboxylic acids can be aliphatic(saturated or unsaturated) RCOOH and aromatic ArCOOH (Table 6.1). Based on the number of carboxylic groups, they are divided into monocarboxylic, dicarbonic and tricarboxylic. This chapter deals only with monocarboxylic acids.
The systematic nomenclature of acids is discussed above (see 1.2.1). For many acids, their trivial names are used (see Table 6.1), which are often preferable to systematic ones.
Carboxylic acids, due to the carboxyl group, are polar and can participate in the formation of intermolecular hydrogen bonds (see 2.2.3). Such bonds with water molecules explain the unlimited solubility of lower acids (C 1 -C 4). In carboxylic acid molecules, a hydrophilic part (carboxyl group COOH) and a hydrophobic part (organic radical R) can be distinguished. As the proportion of the hydrophobic part increases, solubility in water decreases. Higher carboxylic acids of the aliphatic series (starting from C 10) are practically insoluble in water. Carboxylic acids are characterized by intermolecular association. Thus, liquid carboxylic acids, such as acetic acid, exist in the form of dimers. IN aqueous solutions dimers break down into monomers.
Table 6.1.Monocarboxylic acids
An increase in the ability to associate when moving from aldehydes to alcohols and then to acids is reflected in the change in boiling points of compounds of these classes with similar molecular weights.
6.1.2. Reaction centers in carboxylic acids
The chemical properties of carboxylic acids are determined primarily by the carboxyl group, which, unlike previously studied functional groups(alcoholic, carbonyl) has a more complex structure. Within the group itself there is a p,l conjugation as a result of the interaction of the p orbital of the oxygen atom of the OH group with the π bond of the C=O group (see also 2.3.1).
The carbonyl group in relation to the OH group acts as an electron acceptor, and the hydroxyl group, due to the +M effect, acts as an electron donor, supplying electron density to the carbonyl group. Features of the electronic structure of carboxylic acids determine the existence of several reaction centers(diagram 6.1):
OH-acidic center due to strong polarization of the O-H bond;
The electrophilic center is the carbon atom of the carboxyl group;
N- basic center - oxygen atom of the carbonyl group with a lone pair of electrons;
A weak CH-acid center, which appears only in derivatives of acids, since the acids themselves have an incomparably stronger OH-acid center.
Scheme 6.1.Reaction centers in a carboxylic acid molecule
6.1.3. Acid properties
The acidic properties of carboxylic acids are manifested in their ability to abstract a proton. The increased mobility of hydrogen is due to the polarity of the O-H bond due to p,p- connections (see diagram 6.1). The strength of carboxylic acids depends on the stability of the carboxylate ion RCOO, resulting from the abstraction of a proton. In turn, the stability of an anion is determined primarily by the degree of delocalization of the negative charge in it: the better the charge in the anion is delocalized, the more stable it is (see 4.2.1). In the carboxylate ion, the charge is delocalized along a p,π-conjugated system involving two oxygen atoms and is distributed equally between them
(see 2.3.1).
For carboxylic acids, the values of pl a lie in the range of 4.2-4.9. These acids are significantly more acidic than alcohols (pK a 16-18), phenols (pK a ~ 10) and thiols (pK a 11-12) (see Table 4.5).
The length and branching of the saturated alkyl radical does not significantly affect the acidic properties of carboxylic acids. In general, aliphatic monocarboxylic acids have almost the same acidity (pK a 4.8-5.0), with the exception of formic acid, whose acidity is an order of magnitude higher.
The higher acidity of formic acid can be explained with the involvement of another factor affecting the stability of the anion, namelysolvation. IN aquatic environment the charge in the small HCOO formate ion is better delocalized with the participation of polar solvent molecules than in larger carboxylate ions.
It should be noted that aromatic acids are slightly higher than aliphatic acids in acidity (pK a of benzoic acid 4.2). In the delocalization of the charge in the benzoate ion, the benzene ring acts as a weak electron acceptor, without participating in conjugation with electrons that determine the negative charge.
The acidity of carboxylic acids is significantly influenced by the substituents introduced into the hydrocarbon radical. Regardless of the mechanism
transferring the electronic influence of a substituent in a radical (inductive or mesomeric), electron-withdrawing substituents contribute to the delocalization of the negative charge, stabilize anions and thereby increase acidity. Electron-donating substituents, on the contrary, reduce it.
In aqueous solutions, carboxylic acids are weakly dissociated.
Acidic properties are manifested by the interaction of carboxylic acids with alkalis, carbonates and bicarbonates. The salts formed in this process are hydrolyzed to a noticeable extent, so their solutions have an alkaline reaction.
6.1.4. Nucleophilic substitution
Nucleophilic substitution at the sp 2 -hybridized carbon atom of the carboxyl group represents the most important group of reactions of carboxylic acids.
The carbon atom of the carboxyl group carries a partial positive charge, i.e. it is an electrophilic center (see diagram 6.1). It can be attacked by nucleophilic reagents, resulting in the replacement of the OH group with another nucleophilic species.
The hydroxide ion is a poor leaving group, so nucleophilic substitution reactions at the carboxyl group are carried out in the presence of acid catalysts, especially when weak nucleophilic reagents such as alcohols are used.
Most important reactions monocarboxylic acids are shown in Scheme 6.2.
Scheme 6.2.Some nucleophilic substitution reactions in carboxylic acids
The esterification reaction is catalyzed by strong acids.
Mechanism of esterification reaction. The catalytic effect of sulfuric acid is that it activates a carboxylic acid molecule, which is protonated at the main center - the oxygen atom of the carbonyl group (see Scheme 6.1). Protonation leads to an increase in the electrophilicity of the carbon atom. Mesomeric structures show delocalization of the positive charge in the resulting cation (I).
Next, the alcohol molecule, due to the lone pair of electrons of the oxygen atom, joins the activated acid molecule. Subsequent migration of the proton leads to the formation of a good leaving group - a water molecule. At the last stage, a water molecule is split off with the simultaneous release of a proton (catalyst return).
Esterification is a reversible reaction. Shifting the equilibrium to the right is possible by distilling off the resulting ether from the reaction mixture, distilling off or binding water, or using an excess of one of the reagents. The reverse reaction of esterification results in hydrolysis of the ester to form a carboxylic acid and an alcohol.
Formation of amides. When carboxylic acids are exposed to ammonia (gaseous or in solution), direct substitution of the OH group does not occur, but an ammonium salt is formed. Only with significant heating do dry ammonium salts lose water and turn into amides.
Formation of acid anhydrides. Heating carboxylic acids with phosphorus(V) oxide leads to the formation of acid anhydrides.
6.2. Functional derivatives of carboxylic acids
6.2.1. General characteristics
Functional derivatives of carboxylic acids contain a modified carboxyl group, and upon hydrolysis they form a carboxylic acid.
The most important functional derivatives of carboxylic acids are salts, esters, thioesters, amides, and anhydrides (Table 6.2). Acid halides are the most reactive derivatives that are widely used in organic chemistry, however, they do not participate in biochemical transformations due to their extreme sensitivity to moisture, i.e., ease of hydrolysis.
Nomenclature.The names of derivatives of carboxylic acids are based on the relationship of their structures with the structure of the carboxylic acid itself, in which the common fragment is acyl radical RC(O)-. These radicals are called by substitution combination -oic acid on -oil. Trivial names of acyl radicals are given in table. 6.3.
Saltsacids are named by listing the names of the acid's anion and cation (in the genitive case), for example, potassium acetate. The names of acid anions are, in turn, formed by replacing the suffix -il in the name of the acyl radical on -at.
Estersare called similarly to salts, only instead of the name of the cation they use the name of the corresponding alkyl or aryl, which is placed before the name of the anion and written together
Table 6.2.Some functional derivatives of carboxylic acids
with him. The ester group COOR can also be expressed descriptively, for example, “R-ester of such and such acid.”
Table 6.3.Trivial names of acyl radicals and acid derivatives
Symmetrical anhydrides acids are named by replacing the word acid in the name acid on anhydride, for example benzoic anhydride.
Titles amides with an unsubstituted NH group 2 derived from the names of the corresponding acyl radicals by replacing the suffix -oil (or-il) on -amide. In N-substituted amides, the names of the radicals at the nitrogen atom are indicated before the name of the amide with the symbol N-(nitrogen).
6.2.2. Comparative characteristics reactivity
Derivatives of carboxylic acids, like the acids themselves, are capable of undergoing nucleophilic substitution reactions at the sp 2 -hybridized carbon atom to form other functional derivatives. The mechanism of such substitution differs from the mechanism of nucleophilic substitution at the sp 3 -hybridized carbon atom in haloalkanes and alcohols discussed above (see 4.3).
Tetrahedral mechanism of nucleophilic substitution. First, a nucleophile attaches to the carbon atom of the C=O group to form an unstable intermediate anion. The reaction mechanism is called tetrahedral, since the carbon atom is transferred from sp 2 - in sp 3 is a hybrid state and takes on a tetrahedral configuration.
At the second stage, the Z particle is split off from the intermediate and the carbon atom again becomes sp 2 hybridized. Thus, this substitution reaction involves the steps accession And splitting off.
According to this mechanism, the reaction proceeds in the presence of a sufficiently strong nucleophile and a good leaving group Z, for example, in the case of alkaline hydrolysis of esters and other functional derivatives of carboxylic acids. The ease of nucleophilic attack depends on the magnitude of the partial positive charge δ+ on the carbon atom of the carbonyl group. In functional derivatives of carboxylic acids, it increases with increasing -I-effect of the Z substituent and decreases with increasing its M-effect. As a result of these effects, the amount of charge and therefore the ability to undergo nucleophilic attack in the compounds in question decreases in the following sequence. An analysis of the stability of the leaving groups Z -, which are highlighted in color, leads to the same conclusion (see 4.2.1).
Carboxylic acid derivatives are less susceptible to nucleophilic attack than aldehydes and ketones, since the electrophilicity of the carbonyl carbon atom is usually reduced
due to the +M effect of the Z substituent. For this reason, in nucleophilic reactions of functional derivatives of carboxylic acids, acid catalysis is often necessary by protonation of the oxygen atom of the carbonyl group. An example of such activation is the esterification reaction already discussed (see 6.1.3).
As a result of the interaction of carboxylic acids and their functional derivatives with alcohols or amines, an acyl residue is introduced into the molecules of these compounds. In relation to such reactions, the general name is used - acylation reactions. From this position, the esterification reaction can be considered as the acylation of an alcohol molecule.
Functional acid derivatives have different reactivity in acylation reactions. The most active are acid chlorides and anhydrides; Almost any acid derivatives can be obtained from them. Acids and esters themselves (with aliphatic alcohol residues) are much less active acylating agents. Substitution reactions involving them are carried out in the presence of catalysts. Amides undergo acylation reactions even more difficult than acids and esters.
Salts of carboxylic acids do not have acylating ability, since the carboxylic acid anion cannot be attacked by a negatively charged nucleophile or molecule with a lone pair of electrons.
6.2.3. Esters
Esters are derivatives of acids widespread in nature. Many drugs contain ester groups in their structure.
In addition to the esterification reaction, esters are formed, much more easily, by acylation of alcohols or phenols with acid anhydrides.
Some ester reactions are shown in Scheme 6.3.
Scheme 6.3.Ester reactions
Esters are capable of hydrolysis in both acidic and alkaline environments. As already mentioned (see 6.1.3), acid hydrolysis of esters is the reverse reaction of esterification. Although this reaction is reversible, acid hydrolysis can easily be made irreversible by using a large excess of water.
In the alkaline hydrolysis of esters, alkali acts as a reagent (1 mole of alkali is consumed per 1 mole of ester).
Alkaline hydrolysis of esters is an irreversible reaction, since the resulting carboxylate ion is not able to interact with the alkoxide ion (particles with the same charges). This hydrolysis is also called saponification esters. This term is due to the fact that salts of higher acids formed during alkaline hydrolysis of fats are called soaps.
6.2.4. Thioesters
Thioesters - sulfur analogues of esters - find very limited use in classical organic chemistry, but play an important role in the body. It is known that in order to exhibit catalytic activity, most enzymes of a protein nature require participation coenzymes, which are low-molecular organic compounds of non-protein nature, diverse in structure. One of the groups of coenzymes is
acyl coenzymes that act as acyl group carriers. Of these, the most common acetyl coenzyme A.
Despite the complexity of the structure of the acetyl coenzyme A molecule, from the standpoint of a chemical approach, it can be determined that this coenzyme functions as a thioester.
The thiol involved in its formation is coenzyme A(abbreviated CoASH), the molecule of which is built from the residues of three components - 2-aminoethanethiol, pantothenic acid and adenosine diphosphate (additionally phosphorylated at position 3 in the ribose fragment). Adenosine diphosphate (ADP) is discussed further as a representative of another important group of coenzymes - nucleoside polyphosphates (see 14.3.1). Pantothenic acid forms, on the one hand, an amide bond with 2-aminoethanethiol, and on the other, an ester bond with the ADP residue.
In terms of acylating ability, all acyl coenzymes A, including acetyl coenzyme A, being thioesters, occupy the “golden mean” between highly reactive anhydrides and low-active carboxylic acids and esters. Their rather high activity is due, in particular, to the increased stability of the leaving group - the CoA-S - anion - compared to the hydroxide and alkoxide ions of acids and esters, respectively.
Acetyl coenzyme A in vivo is a carrier of acetyl groups to nucleophilic substrates.
In this way, for example, acetylation of hydroxyl-containing compounds is carried out.
Using acetyl coenzyme A, the conversion of choline into acetylcholine occurs, which is an intermediary in the transmission of nervous excitation to nerve tissues(neurotransmitter) (see 9.2 1).
In addition, we can note the important participation in metabolic processes of coenzyme A itself, functioning as a thiol. In the body, any carboxylic acids are activated by conversion into reactive derivatives - thioesters.
6.2.5. Amides and hydrazides
Along with esters, an important group of acid derivatives are amides of carboxylic acids, which are also widespread in nature. It is enough to mention peptides and proteins, the structure of which contains numerous amide groups.
Depending on the degree of substitution at the nitrogen atom, amides can be monosubstituted or disubstituted (see 6.2.1).
Amides are formed by the acylation of ammonia and amines with anhydrides or esters.
Amides have the lowest acylating ability and are much more difficult to hydrolyze than other acid derivatives. Hydrolysis of amides is carried out in the presence of acids or bases.
The high resistance of amides to hydrolysis is explained by the electronic structure of the amide group, which is in many ways similar to the structure of the carboxyl group. The amide group is a p,l-conjugated system in which the lone pair of electrons of the nitrogen atom is conjugated with the π-electrons of the C=O bond. Due to the strong +M effect of the amino group, the partial positive charge on the carbonyl carbon of amides is less than that of other functional acid derivatives. As a result, the carbon-nitrogen bond in amides is partially double in nature.
A consequence of conjugation is also the extremely low basicity of the nitrogen atom of the amide group. On the contrary, amides develop weak acidic properties. Consequently, amides have amphoteric properties.
Amidas are related hydrazides- derivatives of carboxylic acids containing a hydrazine H residue 2 NNH 2. Quite a few medicinal
agents are hydrazides in nature, for example, the antituberculosis drug isoniazid (see 13.4.1). Like amides, hydrazides undergo hydrolysis under fairly harsh conditions with cleavage of the C-N bond.
6.2.6. Anhydrides
Acid anhydrides are more common in vivo in the form mixed anhydrides, including acyl residues of various acids, one of the acids being inorganic (most often phosphoric).
Acyl phosphates are good acyl group carriers because phosphate groups are good leaving groups in nucleophilic substitution reactions.
Substituted acyl phosphates are metabolites with the participation of which the body transfers acyl residues to hydroxyl, thiol groups and amino groups of various compounds.
6.3. Sulfonic acids
and their functional derivatives
Sulfonic acids RSO 3 H can be considered as derivatives of hydrocarbons in which the hydrogen atom is replaced by a sulfo group SO 3 H. The best known are sulfonic acids of the aromatic series; their simplest representative is benzenesulfonic acid. Like sulfuric acid, sulfonic acids are highly acidic.
Sulfonic acids, like carboxylic acids, form functional derivatives - salts, esters, amides, etc.
N-substituted amides have acquired great importance in medical practice. sulfanyl(n-aminobenzenesulfonic) acid - sulfonamide agents (see 9.3).
Functional derivatives are derivatives of carboxylic acids in which the OH group is replaced by a nucleophilic particle Z.
Table No. 3 Functional derivatives of carboxylic acids R─ C(O)Z
6.1. Nomenclature.
The nomenclature of carboxylic acid derivatives is very simple and is based on the names of the carboxylic acids themselves. Acid anhydrides, for example, are named by adding the word " anhydride " to the name of the corresponding acid.
To name mixed anhydrides, you need to list both acids that form the anhydride.
To denote acyl halides, the acid ending “-” new " is replaced by "- oil " with the addition of the name of the halogen.
To designate amides the ending "-ova ", characteristic of acids, is replaced by "- amide ", or the ending " carboxylic acid " is replaced by " carboxamide ».
Nitrogen-substituted amides have a prefix indicating these substituents.
The name of esters is constructed in such a way that the first part of the name is occupied by the designation of the alkyl group attached to the oxygen atom. The second part of the name is the designation of carboxylic acid, in which the ending “- new " replaced with ending "- at ».
There are several naming systems for nitriles. According to the IUPAC nomenclature, they are called alkanenitriles, i.e. the ending “-” is added to the name of the alkane nitrile " The carbon atom of the nitrile group is always numbered first.
In another naming system, the ending “- new " is replaced by "- onitrile " or the phrase " carboxylic acid " is replaced by "- carbonitrile ».
To conclude this section, we present the names of some typical functional groups of derivatives of the carboxyl group: COOR - the group is called « alkoxycarboxyl» , CONH 2 – « carbamoyl» , COCl – « chloroformyl» ,CN – « cyano» . This is the name given to these groups in polyfunctionally substituted cycloalkanes and alkanes.
6.2. Chemical properties of carboxylic acid derivatives.
Functional derivatives, like carboxylic acids, are capable of undergoing acylation reactions, and therefore can be considered as acyl derivatives various nucleophiles. Acylation reactions lead to the formation of other functional derivatives of carboxylic acids.
For a nucleophilic substitution reaction sp 2-hybrid acyl carbon atom, a two-stage addition-elimination mechanism is realized. In the first step, a nucleophilic agent adds to a carboxylic acid derivative to form a charged (for an anionic nucleophilic agent) or betaine (for a neutral nucleophilic agent) tetrahedral intermediate. In the second stage, the leaving group Z is split off from this intermediate in the form of an anion or neutral molecule and the final substitution product is formed.
In general, the reaction is reversible, but if Z And Nu differ greatly in their basicity and nucleophilicity, it becomes irreversible. Driving force leaving group elimination Z is the formation of a π bond between oxygen and the carbonyl carbon atom from an anionic tetrahedral intermediate. In principle, both stages can influence the rate of the reaction, however, as a rule, the first stage of addition of the nucleophilic agent is slow and determines the rate of the entire process. Both steric and electronic factors are important in quantifying the reactivity of carboxylic acid derivatives. Steric hindrance to the attack of a nucleophilic reagent at the carbonyl carbon atom causes a decrease in reactivity in the series:
The reactivity of functional derivatives in acylation reactions (acylation ability) depends on the nature of the Z particle and correlates with the stability of the leaving Z - anion:
the more stable the anion, the higher reactivity acyl derivative.
Acyl halides and anhydrides have the greatest acylating activity, since their acyl residues are combined with good leaving groups - halide ions and anions of carboxylic acids. Esters and amides exhibit lower acylating ability because the alkoxide and amide ions, respectively, are not stable anions and are not good leaving groups. This approach to assessing the acylating ability is shown below using the example of a comparison of the most important functional derivatives of carboxylic acids:
6.3. Acid halides.
Acid halides are functional derivatives of carboxylic acids. general formula RC(O)Hal.
Acid halides are liquids or solids with a strong, intrusive odor and are highly irritating to the skin and mucous membranes. Practical significance have acyl chlorides and acyl bromides.
It can be noted that the introduction of even one chlorine atom into the acetic acid molecule increases the acidity by two orders of magnitude, and trichloroacetic acid is comparable in strength to inorganic derivatives.
The change in acidity upon transition from a- to g-butyric acid illustrates the previously stated statement that the inductive effect (both donor and acceptor) is most noticeable on the neighboring atom. The further away the chlorine atom is located, the less effect it has on acidity.
In the aromatic series, the stability of the carboxylate anion is increased due to conjugation with the aromatic ring. Thus, benzoic acid is approximately 3.6 times stronger than acetic acid. Acceptors at positions of the 2,4,6-benzene ring increase acidity, and donors decrease it. Moreover, substituents at positions 2- and 6- have a particularly strong effect, which is caused by their proximity to the carboxy group. For example, pair-chlorobenzoic acid only 1.6 times, in ortho-chlorobenzoic acid is 19 times stronger than benzoic acid.
Lecture No. 35
Carboxylic acids and their derivatives
Monocarboxylic acids.
· Chemical properties. Preparation of derivatives of carboxylic acids: salts, anhydrides, halides, esters, amides, nitriles. Decarboxylation, reduction and halogenation of acids. Substitution reactions in the ring of aromatic carboxylic acids. The main ways of using carboxylic acids.
Derivatives of carboxylic acids.
· Salts. Receipt. Chemical properties: decarboxylation, Kolbe anodic synthesis, preparation of carbonyl compounds.
· Anhydrides. Preparation: dehydration of acids using P 2 O 5; acylation of carboxylic acid salts with acid chlorides. Chemical properties: reactions with nucleophiles (acylation, esterification).
· Acid chlorides. Receipt. Chemical properties: reactions with nucleophiles (acylation, esterification, interaction with water, ammonia, amines, phenols), reduction to aldehydes, reactions with organomagnesium compounds. Benzoyl chloride and benzoylation reactions.
· Esters. Preparation: esterification of carboxylic acids (mechanism), acylation of alcohols and their alcoholates with acyl halides and anhydrides, alkylation of carboxylate ions. Chemical properties: hydrolysis (mechanism of acid and base catalysis), transesterification; ammonolysis, catalytic hydrogenation, reduction with complex metal hydrides and metals in the presence of proton sources.
Monocarboxylic acids.
Chemical properties. Carboxylic acid derivatives
Salts
Obtaining salts – simplest reaction carboxylic acids.
The production of hydrocarbons by decarboxylation of carboxylic acid salts and Kolbe anodic synthesis is discussed in the “Alkanes” section.
Anhydrides
Carboxylic acid anhydrides can be prepared by intermolecular dehydration or acylation of carboxylic acids with acid chlorides. The acylation reaction is the introduction of an acyl group (a carboxylic acid residue, but not an aldehyde).
The first method produces symmetrical anhydrides, the second - symmetrical and unsymmetrical anhydrides.
Carboxylic acid anhydrides themselves are not of particular chemical interest. Like anhydrides of any acids, carboxylic acid anhydrides are a hidden and more reactive form of acids. They are often used instead of acids in acylation reactions (see below).
Anhydrides are easily hydrolyzed by water to the corresponding acid.
Acid halides
Acyl halides are derivatives of carboxylic acids that contain a halogen atom instead of an OH group. In the vast majority of cases, the molecule contains a chlorine atom, much less often bromine, and never fluorine. When people talk about acid halides, they almost always mean acid chlorides.
Acid chlorides are obtained by reacting phosphorus halides (PCl 3, POCl 3, PCl 5) or thionyl chloride (SOCl 2) with acids. The reaction mechanism is similar to the previously described replacement of the OH group in alcohols with a halogen atom.
The stability of formic acid chlorides is so low that they cannot be obtained.
Acid chlorides, like anhydrides, are used as reagents in many reactions for the production of carboxylic acid derivatives.
Esters
The interaction of carboxylic acids with alcohols in the presence of a mineral acid (esterification reaction) leads to esters.
Esterification reaction mechanism:
In the resulting neutral intermediate, the rates of the forward and reverse reactions are close. In general, reaction yields do not exceed 70% of theory. To increase yield, the ester is usually removed from the reaction sphere.
The mechanism of the esterification reaction was proven using isotopically labeled alcohol.
No isotopic tracer was detected in the water. Therefore, ester oxygen is from alcohol.
The esterification reaction is completely reversible. The reverse reaction is hydrolysis (acidic or alkaline). The mechanism of acid hydrolysis is shown above.
Mechanism of hydrolysis in the presence of alkalis (saponification reaction):
Acid hydrolysis, like esterification, is completely reversible. Alkaline hydrolysis produces a carboxylic acid salt and is therefore irreversible.
Transesterification
Esters can also be obtained by transesterification reaction.
The mechanism of the transesterification reaction is very similar to hydrolysis (instead of H-OH - R-OH).
Since the reaction is completely reversible, it is carried out in a large excess of alcohol (R”-OH) to shift the equilibrium to the right. In some cases, transesterification even gives best results than esterification.
The advantage of esterification and transesterification is the simplicity of the reaction and the availability of starting materials, the disadvantage is the reversibility of the reaction. In irreversible reactions, esters are produced from anhydrides or acid chlorides of carboxylic acids.
Preparation of esters from anhydrides.
Preparation of esters from acid chlorides.
