Electrophilic substitution reactions- replacement reactions in which the attack is carried out electrophile- a particle that is positively charged or has a deficiency of electrons. When a new bond is formed, the outgoing particle is electrofuge splits off without its electron pair. The most popular leaving group is the proton H+.
All electrophiles are Lewis acids.
General view of electrophilic substitution reactions:
(cationic electrophile)
(neutral electrophile)
There are aromatic (widespread) and aliphatic (less common) electrophilic substitution reactions. The nature of electrophilic substitution reactions specifically for aromatic systems is explained by the high electron density of the aromatic ring, which can attract positively charged particles.
For aromatic systems, there is actually one mechanism of electrophilic substitution - S E Ar. Mechanism S E 1(similar to the mechanism S N 1) - is extremely rare, but S E 2(corresponding by analogy S N 2) - does not occur at all.
Reactions S E Ar
Reaction mechanism S E Ar or aromatic electrophilic substitution reactions is the most common and most important among the substitution reactions of aromatic compounds and consists of two stages. At the first stage, the electrophile is added, and at the second stage, the electrofuge is separated:
During the reaction, a positively charged intermediate is formed (in Figure 2b). It bears the name Ueland intermediate, aronium ion or σ-complex. This complex is generally very reactive and is easily stabilized, quickly eliminating the cation.
Limiting stage in the vast majority of reactions S E Ar is the first stage.
The attacking particles are usually relatively weak electrophiles, so in most cases the reaction S E Ar occurs under the influence of a catalyst - Lewis acid. The most commonly used are AlCl 3, FeCl 3, FeBr 3, ZnCl 2.
DECARBOXYLATION, elimination of CO 2 from the carboxylic group of carboxylic acids or the carboxylate group of their salts. This is usually carried out by heating in the presence of acids or bases. Aromatic acids are decarboxylated, as a rule, under harsh conditions, for example, when heated in quinoline in the presence of a metallic acid. powders By this method, in the presence of Cu, furan is obtained from pyroslitic acid. DECARBOXYLATION of aromatic acids is facilitated in the presence of electrophilic substituents, for example, trinitrobenzoic acid is decarboxylated when heated to 40-45 °C. D. vapors of carboxylic acids over heated catalysts (Ca and Ba carbonates, Al 2 O 3, etc.) - one of the methods for the synthesis of ketones:
2RCOOH: RCOR + H 2 O + CO 2.
DECARBOXYLATION of sodium salts of carboxylic acids during electrolysis of their conc. aqueous solutions is an important method for the preparation of alkanes. Halogendecarboxylation - replacement of the carboxyl group in a molecule with a halogen, occurs under the action of LiCl and Pb tetraacetate on carboxylic acids, as well as free halogens (Cl 2, Br 2, I 2) on salts of carboxylic acids, for example:
RCOOM RHal (M = Ag, K, Hg, T1).
Silver salts of dicarboxylic acids under the action of I 2 are easily converted into lactones: 
Oxidative DECARBOXYLATION also plays an important role - the elimination of CO 2 from carboxylic acids, accompanied by oxidation. Depending on the oxidizing agent used, such DECARBOXYLATION leads to alkenes, esters, and other products. Thus, during DECARBOXYLATION of phenylacetic acid in the presence of pyridine-N-oxide, benzaldehyde is formed: 
Similar to DECARBOXYLATION of salts of carboxylic acids, DECARBOXYLATION of organoelement derivatives and esters occurs, for example: 
The decarboxylation reactions of carboxylic acids are an energetically favorable process, because as a result, a stable CO 2 molecule is formed. Decarboxylation is typical for acids that have an electron-withdrawing substituent in the ά-position. Dibasic acids are the easiest to decarboxylate.
Oxalic and malonic acids are easily decarboxylated when heated, and when succinic and glutaric acids are heated, cyclic anhydrides are formed, which is due to the formation of five- or six-membered heterocycles having stable “half-chair” and “chair” conformations.
In biological systems, decarboxylation reactions occur with the participation of enzymes - decarboxylases. Decarboxylation of amino acids leads to the formation of biogenic amines.
Decarboxylation of amino acids leads to the formation of biogenic amines.
In saturated aliphatic acids, as a result of the EA influence of the carboxyl group, CH appears - an acidic center at the α-carbon atom. This is clearly demonstrated in halogenation reactions.
Halide-substituted acids are widely used for the synthesis of biologically important compounds - hydroxy and amino acids.
Lecture No. 12
CARBOXYLIC ACIDS
Plan
1. Methods of obtaining.
2. Chemical properties.
2.1. Acidic properties.
2.3. Reactions by a -carbon atom.
2.5. Recovery.
2.6. Dicarboxylic acids.
Lecture No. 12
CARBOXYLIC ACIDS
Plan
1. Methods of obtaining.
2. Chemical properties.
2.1. Acidic properties.
2.2. Nucleophilic substitution reactions.
Functional derivatives of carboxylic acids.
2.3. Reactions by a -carbon atom.
2.5. Recovery.
2.6. Dicarboxylic acids.
1. Methods of obtaining
2. Chemical
properties
Carboxylic acids contain a carboxyl group in which they are directly linked
a carbonyl group and a hydroxyl. Their mutual influence determines a new
a complex of properties different from the properties of carbonyl compounds and
hydroxyl derivatives. Reactions involving carboxylic acids proceed according to
the following main directions.
- Substitution of hydrogen of the COOH group under
action of grounds ( acid properties). - Interaction with nucleophilic reagents
at the carbonyl carbon atom ( formation of functional derivatives and
recovery) - Reactions by a -carbon atom
(halogenation) - Decaboxylation
2.1. Acidic
properties
Carboxylic acids are among the strongest organic acids. Their water
solutions are acidic.
RCOOH + H 2 O = RCOO - +
H3O+
Reasons for the high acidity of carboxylic acids and
its dependence on the nature of substituents in the hydrocarbon radical was
discussed earlier (see lecture No. 4).
Carboxylic acids form salts when
interaction with active metals and most bases. 
When interacting with strong inorganic
acids, carboxylic acids can exhibit basic properties by adding
proton on the carbonyl oxygen atom. 
Protonation of carboxylic acids is used
to activate the carboxyl group in nucleophilic substitution reactions.
Due to the presence in the molecule at the same time
acidic and basic centers, carboxylic acids form intermolecular
hydrogen bonds and exist mainly in the form of dimers (see lecture No. 2).
2.2. Nucleophilic substitution reactions.
Functional derivatives of carboxylic acids.
The main type of reactions of carboxylic acids is
interaction with nucleophiles to form functional derivatives.
Interconversions linking carboxylic acids and their functional
derivatives are shown in the diagram.
The connections shown in the diagram contain
acyl group During
their mutual transformations, it passes unchanged from one compound to
the other by combining with a nucleophile. Such processes are called acylation,
and carboxylic acids and their functional derivatives – acylating
reagents. In general terms, the acylation process can be represented
the following diagram. 
Thus, acylation is
the process of nucleophilic substitution at the carbonyl carbon atom.
Let us consider the reaction mechanism in general form and
compare it with Ad N -reactions
aldehydes and ketones. As with carbonyl compounds, the reaction begins
from a nucleophile attack on the carbonyl carbon atom bearing an effective
positive charge. At the same time it breaks p -carbon-oxygen bond is formed tetrahedral
intermediate. Paths for further transformation of the intermediate at carbonyl and
acyl compounds are different. If carbonyl compounds give the product accession, then acyl compounds eliminate group X and give the product substitutions.
The reason for the different behavior of acyl and
carbonyl compounds - in different stability of the potential leaving group X.
In the case of aldehydes and ketones, this is the hydride anion H — or carbonanion R — , which, due to their high basicity, are
extremely poor leaving groups. In the case of acyl compounds X
much more stable leaving group (Cl — ,
RCOO - , RO - , NH 2 - ), which makes it possible to eliminate it in the form of an anion
X — or conjugate acid
NH.
Reactivity towards
carboxylic acids and their functional derivatives have less nucleophiles than
aldehydes and ketones, since the effective positive charge on the carbonyl
their carbon atom is lower due to the + M- effect of the X group.
The activity of the acyl group increases under conditions
acid catalysis, since protonation increases the effective
positive charge on the carbon atom and makes it easier to attack
nucleophile. 
According to the acylating ability of derivatives
carboxylic acids are arranged in the next row in accordance with the decrease
+M-effect of group X.
In this series, the previous terms can be obtained from
subsequent acylation of the corresponding nucleophile. The process of getting more
there are practically no active acylating reagents from less active ones due to
unfavorable equilibrium position due to higher basicity
leaving group compared to the attacking nucleophile. All functional
derivatives can be obtained directly from acids and are converted into them
during hydrolysis.
Acid chlorides and anhydrides
Receipt methods
Acid chlorides are prepared by reacting
carboxylic acids with phosphorus and sulfur halides.
RCOOH + SOCl 2 ® RCOOCl + SO 2 +
HCl
RCOOH + PCl 5 ® RCOOH + POCl 3 +
HCl
Anhydrides are formed from carboxylic acids under
action of phosphorus oxide (V).
Mixed anhydrides can be prepared
acylation of carboxylic acid salts with acid chlorides.
acid chlorides and anhydrides.
X acid chlorides and anhydrides are the most reactive derivatives
carboxylic acids. Their reactions with nucleophiles occur under mild conditions, without
catalyst and is practically irreversible.
When using mixed anhydrides with
the nucleophile connects the residue of a weaker acid, and the anion of a stronger one
acid plays the role of a leaving group. 
IN
mixed anhydrides play an important role in biochemical acylation reactions
carboxylic acids and phosphoric acid - acyl phosphates and substituted acyl phosphates. WITH
a nucleophile combines with an organic acid residue, and the acylphosphate anion
acts as a good leaving group. 
Esters
Receipt methods
RCOO— Na+ + R Cl ® RCOOR + NaCl The most important method for preparing esters is esterification reaction. The reaction proceeds as a nucleophilic substitution in
carboxyl group.
Carboxylic acids are weak acylating
reagents due to the significant +M effect of the OH group. Using strengths
nucleophiles, which are also strong bases (for example,
main catalysis), in this case is impossible, since they convert carbon
acids into even less reactive salts of carboxylic acids. The reaction is carried out
under conditions of acid catalysis. The role of the acid catalyst is, as already
said to increase the effective positive charge on the carbon atom
carboxyl group, and, in addition, protonation of the OH group at the stage
elimination turns it into a good leaving group - H 2 O. 
All stages of the esterification reaction
reversible. To shift the equilibrium towards the esterification process, use
excess of one of the reactants or removal of products from the reaction area.
Nucleophilic substitution reactions in
alkoxycarbonyl group.
Esters are weaker acylating agents.
reagents than anhydrides and acid chlorides. S N -reactions in the alkoxycarbonyl group proceed in more
harsh conditions and require acid or base catalysis. The most important
reactions of this type are hydrolysis, aminolysis and
transesterification
.
Hydrolysis.
Esters hydrolyze to form carboxylic acids under the influence of
acids or alkalis.
Acid hydrolysis of esters is the reverse reaction of esterification. 
The mechanism of acid hydrolysis includes the same stages as
and the esterification process, but in reverse order.
Alkaline hydrolysis of esters requires
equimolar amounts of alkali and proceeds irreversibly.
RCOOR + NaOH ® RCOO - Na + + R OH
The essence of alkaline catalysis is to use
instead of a weak nucleophile - water, a stronger nucleophile -
hydroxide ion. 
Irreversibility of the process
ensured by low reactivity towards nucleophiles
hydrolysis product – carboxylate anion.
Transesterification.
The role of the nucleophile in the transesterification reaction
performed by an alcohol molecule. The process is catalyzed by acids or
reasons. 
The reaction mechanism is similar to the hydrolysis of complex
ethers. Transesterification is a reversible process. To shift balance to the right
it is necessary to use a large excess of the starting alcohol. Reaction
transesterification is used to produce fatty acid esters
from triacylglycerides (see lec. 18)
Aminolysis.
Esters acylate ammonia and amines with
formation of amides of carboxylic acids. 
Amides of carboxylic acids
Structure of the amide group
A the mid group is found in many biologically important compounds,
primarily in peptides and proteins (peptide bond). Her electronic and
spatial structure largely determines their biological
functioning.
The amide group is p-p - the conjugate system in which it occurs
additional overlap of the p-orbital of the nitrogen atom with p -communication orbital
carbon-oxygen.
This electron density distribution
leads to an increase in the energy barrier for rotation around the C-N bond to 60 –
90 kJ/mol. As a result, the amide bond has a flat structure, and the bond lengths
C-N and C=O have values less and more than their usual values, respectively.
quantities
No free rotation around the C-N bond
leads to the existence of amides cis- And trance-isomers. For
most amides, it is preferred trance-configuration.
The peptide bond also has trance-configuration in which the side radicals of amino acid residues
farthest from each other
Receipt methods
Nucleophilic substitution reactions in
carboxamide group.
Amides are the least reactive derivatives of carboxylic acids. For them
hydrolysis reactions are known that occur under harsh conditions under the influence of
aqueous solutions of acids or alkalis. 
The reaction mechanisms are similar to the hydrolysis of complex
ethers. However, unlike ester hydrolysis, acid and alkaline hydrolysis
amides proceed irreversibly.
2.3. Reactions by a -carbon
atom
Carboxylic acids containing a -hydrogen atoms,
react with bromine in the presence of phosphorus to form exclusively a -bromo derivatives
(Gell–Forhald–Zelinsky reaction
)
Halogen in a -halogenated acids are easily replaced by
action of nucleophilic reagents. That's why a -halogenated acids
are starting materials in the synthesis of a wide range of substituted compounds a -position
acids, including a -amino- and a -hydroxy acids.
2.4.
Decarboxylation
Decarboxylation is the elimination of CO 2 from carboxylic acids or their salts. Decarboxylation
carried out by heating in the presence of acids or bases. At the same time, how
As a rule, the carboxyl group is replaced by a hydrogen atom.
Unsubstituted monocarboxylic acids
decarboxylate under harsh conditions.
Decarboxylation is facilitated by the presence of
electron-withdrawing substituents in a-position.
Enzymatic is important
decarboxylation of keto-, amino- and hydroxy acids in the body (see lecture No. 14 and
16).
Decarboxylation by heating (dry
distillation) of calcium and barium salts of carboxylic acids - method of obtaining
ketones.
2.5.
Recovery.
Carboxylic acids, acid chlorides, anhydrides and esters
are reduced by LiAlH 4 to primary
alcohols 
Acid chlorides can be reduced to
aldehydes (see lecture No. 11).
When reducing amides of carboxylic acids
amines are formed.
3. Dicarboxylic acids
Dicarboxylic acids contain two carboxyl groups. Most accessible
are acids of linear structure containing from 2 to 6 carbon atoms. Their
the structure and methods of preparation are presented in Table 9. bacteria
Chemical properties of dicarboxylic acids in
basically similar to the properties of monocarboxylic acids. They give all the reactions
characteristic of a carboxyl group. In this case, it can be obtained
functional derivatives (acid chlorides, anhydrides, esters, amides) as
one or both carboxyl
groups. Dicarboxylic acids are more acidic than monocarboxylic acids.
due to the –I effect of the carboxyl group. As the distance between
carboxyl groups, the acidity of dicarboxylic acids decreases (see table.
9).
In addition, dicarboxylic acids have a number of
specific properties that are determined by the presence in the molecule of two
carboxyl groups.
The ratio of dicarboxylic acids to
heating.
Transformations of dicarboxylic acids when heated
depend on the length of the chain separating the carboxyl groups and are determined
the possibility of forming thermodynamically stable five- and six-membered
cycles.
When heating oxalic and malonic acids
decarboxylation occurs.
Succinic, glutaric and maleic acids at
when heated, water is easily split off to form five- and six-membered cyclic
anhydrides.
Adipic acid when heated
decarboxylates to form a cyclic ketone, cyclopentanone.
Polycondensation reactions
D icarboxylic acids react with diamines and diols with
formation of polyamides and polyesters, respectively, which are used in
production of synthetic fibers.
Biologically important dicarbonates
acids.
Oxalic acid
forms sparingly soluble salts, for example,
calcium oxalate, which are deposited as stones in the kidneys and bladder.
succinic acid
participates in metabolic processes occurring in
body. It is an intermediate compound in the tricarboxylic acid cycle.
Fumaric acid,
unlike maleic ,
widespread in nature, participates in the process
metabolism, in particular in the tricarboxylic acid cycle.
Lecture No. 12
CARBOXYLIC ACIDS
Plan
1. Methods of obtaining.
2. Chemical properties.
2.1. Acidic properties.
2.3. Reactions by a -carbon atom.
2.5. Recovery.
2.6. Dicarboxylic acids.
Lecture No. 12
CARBOXYLIC ACIDS
Plan
1. Methods of obtaining.
2. Chemical properties.
2.1. Acidic properties.
2.2. Nucleophilic substitution reactions.
Functional derivatives of carboxylic acids.
2.3. Reactions by a -carbon atom.
2.5. Recovery.
2.6. Dicarboxylic acids.
1. Methods of obtaining
2. Chemical
properties
Carboxylic acids contain a carboxyl group in which they are directly linked
a carbonyl group and a hydroxyl. Their mutual influence determines a new
a complex of properties different from the properties of carbonyl compounds and
hydroxyl derivatives. Reactions involving carboxylic acids proceed according to
the following main directions.
- Substitution of hydrogen of the COOH group under
action of grounds ( acid properties). - Interaction with nucleophilic reagents
at the carbonyl carbon atom ( formation of functional derivatives and
recovery) - Reactions by a -carbon atom
(halogenation) - Decaboxylation
2.1. Acidic
properties
Carboxylic acids are among the strongest organic acids. Their water
solutions are acidic.
RCOOH + H 2 O = RCOO - +
H3O+
Reasons for the high acidity of carboxylic acids and
its dependence on the nature of substituents in the hydrocarbon radical was
discussed earlier (see lecture No. 4).
Carboxylic acids form salts when
interaction with active metals and most bases.
When interacting with strong inorganic
acids, carboxylic acids can exhibit basic properties by adding
proton on the carbonyl oxygen atom.
Protonation of carboxylic acids is used
to activate the carboxyl group in nucleophilic substitution reactions.
Due to the presence in the molecule at the same time
acidic and basic centers, carboxylic acids form intermolecular
hydrogen bonds and exist mainly in the form of dimers (see lecture No. 2).
2.2. Nucleophilic substitution reactions.
Functional derivatives of carboxylic acids.
The main type of reactions of carboxylic acids is
interaction with nucleophiles to form functional derivatives.
Interconversions linking carboxylic acids and their functional
derivatives are shown in the diagram.
The connections shown in the diagram contain
acyl group During
their mutual transformations, it passes unchanged from one compound to
the other by combining with a nucleophile. Such processes are called acylation,
and carboxylic acids and their functional derivatives – acylating
reagents. In general terms, the acylation process can be represented
the following diagram.
Thus, acylation is
the process of nucleophilic substitution at the carbonyl carbon atom.
Let us consider the reaction mechanism in general form and
compare it with Ad N -reactions
aldehydes and ketones. As with carbonyl compounds, the reaction begins
from a nucleophile attack on the carbonyl carbon atom bearing an effective
positive charge. At the same time it breaks p -carbon-oxygen bond is formed tetrahedral
intermediate. Paths for further transformation of the intermediate at carbonyl and
acyl compounds are different. If carbonyl compounds give the product accession, then acyl compounds eliminate group X and give the product substitutions.
The reason for the different behavior of acyl and
carbonyl compounds - in different stability of the potential leaving group X.
In the case of aldehydes and ketones, this is the hydride anion H — or carbonanion R — , which, due to their high basicity, are
extremely poor leaving groups. In the case of acyl compounds X
much more stable leaving group (Cl — ,
RCOO - , RO - , NH 2 - ), which makes it possible to eliminate it in the form of an anion
X — or conjugate acid
NH.
Reactivity towards
carboxylic acids and their functional derivatives have less nucleophiles than
aldehydes and ketones, since the effective positive charge on the carbonyl
their carbon atom is lower due to the + M- effect of the X group.
The activity of the acyl group increases under conditions
acid catalysis, since protonation increases the effective
positive charge on the carbon atom and makes it easier to attack
nucleophile.
According to the acylating ability of derivatives
carboxylic acids are arranged in the next row in accordance with the decrease
+M-effect of group X.
In this series, the previous terms can be obtained from
subsequent acylation of the corresponding nucleophile. The process of getting more
there are practically no active acylating reagents from less active ones due to
unfavorable equilibrium position due to higher basicity
leaving group compared to the attacking nucleophile. All functional
derivatives can be obtained directly from acids and are converted into them
during hydrolysis.
Acid chlorides and anhydrides
Receipt methods
Acid chlorides are prepared by reacting
carboxylic acids with phosphorus and sulfur halides.
RCOOH + SOCl 2 ® RCOOCl + SO 2 +
HCl
RCOOH + PCl 5 ® RCOOH + POCl 3 +
HCl
Anhydrides are formed from carboxylic acids under
action of phosphorus oxide (V).
Mixed anhydrides can be prepared
acylation of carboxylic acid salts with acid chlorides.
acid chlorides and anhydrides.
X acid chlorides and anhydrides are the most reactive derivatives
carboxylic acids. Their reactions with nucleophiles occur under mild conditions, without
catalyst and is practically irreversible.
When using mixed anhydrides with
the nucleophile connects the residue of a weaker acid, and the anion of a stronger one
acid plays the role of a leaving group.
IN
mixed anhydrides play an important role in biochemical acylation reactions
carboxylic acids and phosphoric acid - acyl phosphates and substituted acyl phosphates. WITH
a nucleophile combines with an organic acid residue, and the acylphosphate anion
acts as a good leaving group.
Esters
Receipt methods
RCOO— Na+ + R Cl ® RCOOR + NaCl The most important method for preparing esters is esterification reaction. The reaction proceeds as a nucleophilic substitution in
carboxyl group.
Carboxylic acids are weak acylating
reagents due to the significant +M effect of the OH group. Using strengths
nucleophiles, which are also strong bases (for example,
main catalysis), in this case is impossible, since they convert carbon
acids into even less reactive salts of carboxylic acids. The reaction is carried out
under conditions of acid catalysis. The role of the acid catalyst is, as already
said to increase the effective positive charge on the carbon atom
carboxyl group, and, in addition, protonation of the OH group at the stage
elimination turns it into a good leaving group - H 2 O.
All stages of the esterification reaction
reversible. To shift the equilibrium towards the esterification process, use
excess of one of the reactants or removal of products from the reaction area.
Nucleophilic substitution reactions in
alkoxycarbonyl group.
Esters are weaker acylating agents.
reagents than anhydrides and acid chlorides. S N -reactions in the alkoxycarbonyl group proceed in more
harsh conditions and require acid or base catalysis. The most important
reactions of this type are hydrolysis, aminolysis and
transesterification
.
Hydrolysis.
Esters hydrolyze to form carboxylic acids under the influence of
acids or alkalis.
Acid hydrolysis of esters is the reverse reaction of esterification.
The mechanism of acid hydrolysis includes the same stages as
and the esterification process, but in reverse order.
Alkaline hydrolysis of esters requires
equimolar amounts of alkali and proceeds irreversibly.
RCOOR + NaOH ® RCOO - Na + + R OH
The essence of alkaline catalysis is to use
instead of a weak nucleophile - water, a stronger nucleophile -
hydroxide ion.
Irreversibility of the process
ensured by low reactivity towards nucleophiles
hydrolysis product – carboxylate anion.
Transesterification.
The role of the nucleophile in the transesterification reaction
performed by an alcohol molecule. The process is catalyzed by acids or
reasons.
The reaction mechanism is similar to the hydrolysis of complex
ethers. Transesterification is a reversible process. To shift balance to the right
it is necessary to use a large excess of the starting alcohol. Reaction
transesterification is used to produce fatty acid esters
from triacylglycerides (see lec. 18)
Aminolysis.
Esters acylate ammonia and amines with
formation of amides of carboxylic acids.
Amides of carboxylic acids
Structure of the amide group
A the mid group is found in many biologically important compounds,
primarily in peptides and proteins (peptide bond). Her electronic and
spatial structure largely determines their biological
functioning.
The amide group is p-p - the conjugate system in which it occurs
additional overlap of the p-orbital of the nitrogen atom with p -communication orbital
carbon-oxygen.
This electron density distribution
leads to an increase in the energy barrier for rotation around the C-N bond to 60 –
90 kJ/mol. As a result, the amide bond has a flat structure, and the bond lengths
C-N and C=O have values less and more than their usual values, respectively.
quantities
No free rotation around the C-N bond
leads to the existence of amides cis- And trance-isomers. For
most amides, it is preferred trance-configuration.
The peptide bond also has trance-configuration in which the side radicals of amino acid residues
farthest from each other
Receipt methods
Nucleophilic substitution reactions in
carboxamide group.
Amides are the least reactive derivatives of carboxylic acids. For them
hydrolysis reactions are known that occur under harsh conditions under the influence of
aqueous solutions of acids or alkalis.
The reaction mechanisms are similar to the hydrolysis of complex
ethers. However, unlike ester hydrolysis, acid and alkaline hydrolysis
amides proceed irreversibly.
2.3. Reactions by a -carbon
atom
Carboxylic acids containing a -hydrogen atoms,
react with bromine in the presence of phosphorus to form exclusively a -bromo derivatives
(Gell–Forhald–Zelinsky reaction
)
Halogen in a -halogenated acids are easily replaced by
action of nucleophilic reagents. That's why a -halogenated acids
are starting materials in the synthesis of a wide range of substituted compounds a -position
acids, including a -amino- and a -hydroxy acids.
2.4.
Decarboxylation
Decarboxylation is the elimination of CO 2 from carboxylic acids or their salts. Decarboxylation
carried out by heating in the presence of acids or bases. At the same time, how
As a rule, the carboxyl group is replaced by a hydrogen atom.
Unsubstituted monocarboxylic acids
decarboxylate under harsh conditions.
Decarboxylation is facilitated by the presence of
electron-withdrawing substituents in a-position.
Enzymatic is important
decarboxylation of keto-, amino- and hydroxy acids in the body (see lecture No. 14 and
16).
Decarboxylation by heating (dry
distillation) of calcium and barium salts of carboxylic acids - method of obtaining
ketones.
2.5.
Recovery.
Carboxylic acids, acid chlorides, anhydrides and esters
are reduced by LiAlH 4 to primary
alcohols
Acid chlorides can be reduced to
aldehydes (see lecture No. 11).
When reducing amides of carboxylic acids
amines are formed.
3. Dicarboxylic acids
Dicarboxylic acids contain two carboxyl groups. Most accessible
are acids of linear structure containing from 2 to 6 carbon atoms. Their
the structure and methods of preparation are presented in Table 9. bacteria
Chemical properties of dicarboxylic acids in
basically similar to the properties of monocarboxylic acids. They give all the reactions
characteristic of a carboxyl group. In this case, it can be obtained
functional derivatives (acid chlorides, anhydrides, esters, amides) as
one or both carboxyl
groups. Dicarboxylic acids are more acidic than monocarboxylic acids.
due to the –I effect of the carboxyl group. As the distance between
carboxyl groups, the acidity of dicarboxylic acids decreases (see table.
9).
In addition, dicarboxylic acids have a number of
specific properties that are determined by the presence in the molecule of two
carboxyl groups.
The ratio of dicarboxylic acids to
heating.
Transformations of dicarboxylic acids when heated
depend on the length of the chain separating the carboxyl groups and are determined
the possibility of forming thermodynamically stable five- and six-membered
cycles.
When heating oxalic and malonic acids
decarboxylation occurs.
Succinic, glutaric and maleic acids at
when heated, water is easily split off to form five- and six-membered cyclic
anhydrides.
Adipic acid when heated
decarboxylates to form a cyclic ketone, cyclopentanone.
Polycondensation reactions
D icarboxylic acids react with diamines and diols with
formation of polyamides and polyesters, respectively, which are used in
production of synthetic fibers.
Biologically important dicarbonates
acids.
Oxalic acid
forms sparingly soluble salts, for example,
calcium oxalate, which are deposited as stones in the kidneys and bladder.
succinic acid
participates in metabolic processes occurring in
body. It is an intermediate compound in the tricarboxylic acid cycle.
Fumaric acid,
unlike maleic ,
widespread in nature, participates in the process
metabolism, in particular in the tricarboxylic acid cycle.
DECARBOXYLATION, elimination of CO 2 from the carboxylic group of carboxylic acids or the carboxylate group of their salts. This is usually carried out by heating in the presence of acids or bases. DECARBOXYLATION of saturated monocarboxylic acids usually occurs under harsh conditions. Thus, calcination of Na acetate with an excess of soda lime leads to the elimination of CO 2 and the formation of methane: CH 3 COONa + NaOH CH 4 + Na 2 CO 3 . DECARBOXYLATION is facilitated for acids containing a -position of electronegative groups. Easy DECARBOXYLATION of acetoacetic (formula I) and nitroacetic acids (II) is due to the occurrence of a cyclic transition state:
Chemical encyclopedia. Volume 2 >>
D. homologues of nitroacetic acid - a preparative method for obtaining nitroalkanes.
Naib. DECARBOXYLATION of acids is easily carried out, the carboxyl group of which is directly bonded to another electroph. in groups. For example, heating pyruvic acid with conc. H 2 SO 4 easily leads to acetaldehyde:
When DECARBOXYLATING oxalic acid under the same conditions, in addition to CO 2, H 2 O and CO are formed.
D. is also facilitated if the carboxyl group is connected to an unsaturated C atom; Thus, DECARBOXYLATION of the monopotassium salt of acetylenedicarboxylic acid is a convenient method for the synthesis of propiolic acid:
D. acetylene carboxylic acid is carried out at room temperature in the presence of. Cu salts: HCCCOOH HC=CH + CO 2 . Aromatic acids are decarboxylated, as a rule, under harsh conditions, for example, when heated in quinoline in the presence of a metallic acid. powders By this method, in the presence of Cu, furan is obtained from pyroslitic acid. DECARBOXYLATION of aromatic acids is facilitated by the presence of electroph. substituents, for example, trinitrobenzoic acid is decarboxylated when heated to 40-45 °C.
D. vapors of carboxylic acids over heated catalysts (Ca and Ba carbonates, Al 2 O 3, etc.) - one of the methods for the synthesis of ketones: 2RCOOH:
RCOR + H 2 O + CO 2. When DECARBOXYLATING a mixture of two acids, a mixture of unsymmetrical and symmetrical ketones is formed. DECARBOXYLATION of sodium salts of carboxylic acids during electrolysis of their conc. aqueous solutions (see Kolbe reactions) are an important method for the preparation of alkanes.
DECARBOXYLATION reactions that have preparative significance include halogendecarboxylation - the replacement of a carboxyl group in a molecule with a halogen. The reaction occurs under the influence of LiCl (or N-bromosuccinimide) and Pb tetraacetate on carboxylic acids, as well as free halogens (Cl 2, Br 2, I 2) on
salts of carboxylic acids, for example: RCOOM RHal (M = Ag, K,
Hg, T1). Silver salts of dicarboxylic acids under the action of I 2 are easily converted into lactones:
Oxidation also plays an important role. DECARBOXYLATION - elimination of CO 2 from carboxylic acids, accompanied by oxidation. Depending on the oxidizing agent used, such DECARBOXYLATION leads to alkenes, esters, and other products. Thus, during DECARBOXYLATION of phenylacetic acid in the presence of pyridine-N-oxide, benzaldehyde is formed:
Similar to DECARBOXYLATION of salts of carboxylic acids, DECARBOXYLATION of organoelement derivatives and esters occurs, for example:
The degeneration of esters is also carried out under the action of bases (alcoholates, amines, etc.) in an alcohol (aqueous) solution or Li and Na chlorides in DMSO.
Enzymatic DECARBOXYLATION is of great importance in various metabolic processes. There are two types of such reactions: simple DECARBOXYLATION (reversible reaction) and oxidative DECARBOXYLATION, in which first DECARBOXYLATION occurs and then dehydrogenation of the substrate. According to the latter type, enzymatic DECARBOXYLATION of pyruvic and a -ketoglutaric acids are intermediate products of the breakdown of carbohydrates, fats and proteins (see Tricarboxylic acid cycle). Enzymatic DECARBOXYLATION of amino acids in bacteria and animals is also widespread.
Reactions of carboxylic acids can be divided into several large groups:
1) Reduction of carboxylic acids
2) Decarboxylation reactions
3) Substitution reactions at the -carbon atom of carboxylic acids
4) Nucleophilic substitution reactions at the acyl carbon atom.
We will consider each of these groups of reactions in turn.
18.3.1. Reduction of carboxylic acids
Carboxylic acids are reduced to primary alcohols using lithium aluminum hydride. Reduction occurs under more severe conditions than are required for the reduction of aldehydes and ketones. Reduction is usually carried out by boiling in a solution of tetrahydrofuran.
Diborane B 2 H 6 also reduces carboxylic acids to primary alcohols. The reduction of the carboxyl group to CH 2 OH by the action of diborane in THF is carried out under very mild conditions and does not affect some functional groups (NO 2 ; CN; 
), so this method is preferable in some cases.
18.3.2. Decarboxylation
This term combines a whole group of diverse reactions in which CO 2 is eliminated and the resulting compounds contain one carbon atom less than the original acid.
The most important of the decarboxylation reactions in organic synthesis is the Borodin-Hunsdicker reaction, in which the silver salt of a carboxylic acid, when heated with a solution of bromine in CCl 4, is converted into an alkyl halide.
To successfully carry out this reaction, it is necessary to use carefully dried silver salts of carboxylic acids, and the yield of alkyl halide varies widely depending on the degree of purification and dehydration of the salt. The modification, where mercury salts are used instead of silver, does not have this drawback. The mercury salt of a carboxylic acid is not isolated in individual form, but a mixture of carboxylic acid, yellow mercuric oxide and halogen is heated in an indifferent solvent. This method generally results in higher and more reproducible yield.
A chain radical mechanism has been established for the Borodin-Hunsdicker reaction. The acylhypobromite formed in the first stage undergoes homolytic cleavage with the formation of a carboxyl radical and a bromine atom. The carboxyl radical loses CO 2 and becomes an alkyl radical, which then regenerates the chain by eliminating a bromine atom from the acyl hypobromite.
Chain initiation:
Chain development:
The original method of oxidative decarboxylation of carboxylic acids was proposed by J. Kochi in 1965. Carboxylic acids are oxidized with lead tetraacetate, during which decarboxylation occurs and alkanes, alkenes or acetic acid esters are obtained as reaction products, depending on the conditions. The mechanism of this reaction has not been established in detail; the following sequence of transformations is assumed:
The alkene and ester appear to be formed from the carbocation, respectively, by abstraction of a proton or capture of an acetate ion. The introduction of a halide ion into the reaction mixture almost completely suppresses both of these processes and leads to the formation of alkyl halides.
These two decarboxylation methods complement each other well. Decarboxylation of Ag or Hg salts gives the best results for carboxylic acids with a primary radical, while during oxidation with lead tetraacetate in the presence of lithium chloride, the highest yields of alkyl halides are observed for carboxylic acids with a secondary radical.
Another reaction of decarboxylation of carboxylic acids that has important preparative significance is the electrolytic condensation of salts of carboxylic acids, discovered in 1849 by G. Kolbe. He carried out electrolysis of an aqueous solution of potassium acetate in the hope of obtaining the free radical CH 3, but instead ethane was obtained at the anode. Similarly, by electrolysis of an aqueous solution of the sodium salt of valeric acid, n.octane was obtained instead of the butyl radical. Electrochemical oxidation of carboxylate ions turned out to be historically the first general method for the synthesis of saturated hydrocarbons. During the electrolysis of sodium or potassium salts of saturated aliphatic acids in methanol or aqueous methanol in an electrolyzer with platinum electrodes at 0-20°C and with a sufficiently high current density, alkanes are formed with a yield of 50-90%.
However, in the presence of an alkyl group in the -position, the yields decrease sharply and rarely exceed 10%.
This reaction has proven to be particularly useful for the synthesis of diesters of dicarboxylic acids ROOC(CH 2) n COOR with n from 2 to 34 during the electrolysis of alkaline salts of half-esters of dicarboxylic acids.
In modern organic electrosynthesis, cross-electrolytic condensation is widely used, which consists of the electrolysis of a mixture of carboxylic acid salts and dicarboxylic acid monoester.
Electrolysis of a solution of these two salts results in the formation of a mixture of three very different reaction products, which can be easily separated by distillation into their individual components. This method allows you to lengthen the carbon skeleton of a carboxylic acid by any number of carbon atoms in almost one operation.
Electrolytic condensation is limited to salts of carboxylic acids with a straight radical and salts of half-esters of dicarboxylic acids. Salts of ,- and ,-unsaturated acids do not undergo electrochemical condensation.
For the Kolbe reaction, a radical mechanism was proposed, including three successive stages: 1) oxidation of carboxylate ions at the anode to carboxylate radicals 
; 2) decarboxylation of these radicals to alkyl radicals and carbon dioxide; 3) recombination of alkyl radicals.
At high current densities, a high concentration of alkyl radicals at the anode promotes their dimerization; at low current densities, alkyl radicals either disproportionate to form an alkene or alkane or abstract a hydrogen atom from the solvent.
Salts of carboxylic acids also undergo decarboxylation during pyrolysis. Pyrolysis of calcium or barium salts of carboxylic acids was once the main method for producing ketones. In the 19th century, “dry distillation” of calcium acetate was the main method for producing acetone.
Subsequently, the method was improved in such a way that it eliminates the stage of obtaining salts. Carboxylic acid vapors are passed over a catalyst - oxides of manganese, thorium or zirconium at 380-400 0. The most effective and expensive catalyst is thorium dioxide.
In the simplest cases, acids with a number of carbon atoms from two to ten are converted into symmetrical ketones with a yield of about 80% when boiled with powdered iron at 250-300 . This method is used in industry. The most successful pyrolytic method is currently used for the synthesis of five- and six-membered cyclic ketones from dibasic acids. For example, from a mixture of adipic acid and barium hydroxide (5%) at 285-295°C, cyclopentanone is obtained with a yield of 75-85%. Cyclooctanone is formed from azelaic acid when heated with ThO 2 with a yield of no more than 20%; this method is of little use for the preparation of cycloalkanones with a large number of carbon atoms.
