Decarboxylation. Decarboxylation of aromatic carboxylic acids as an electrophilic substitution reaction Decarboxylation of salts of benzoic acid

Decarboxylation

The decarboxylation reaction of carboxylic acids consists in the elimination of a carboxyl group from a carboxylic acid molecule, proceeding according to the following general scheme:

R-C(O)OH --> R-H + CO 2

The most well-known reactions are the decarboxylation of acetic and benzoic acids, which are carried out by heating a mixture of a salt of a carboxylic acid and an alkali to a high temperature:

H 3 C-C (O) ONa + NaOH --> CH 4 + Na 2 CO 3

Ph-C(O)ONa + NaOH --> PhH + Na 2 CO 3

A number of acids decarboxylate very easily with slight heating, in general, the presence of electroacceptor substituents in the organic radical of the carboxylic acid facilitates the decarboxylation reaction, for example, nitromethane and trinitrobenzene are obtained from nitroacetic and trinitrobenzoic acids, respectively:

O 2 N-CH 2 -C (O) OH --> O 2 N-CH 3 + CO 2

2,4,6-(NO 2) 3 C 6 H 2 -C(O)OH ---> 1,3,5-(NO 2) 3 C 6 H 3 + CO 2.

Decarboxylation at relatively low temperatures is a feature of aromatic carboxylic acids, in the aromatic ring of which hydroxyl groups are in the ortho- or para-position, for example, gallic acid easily turns into trihydric phenol - pyrogallol with slight heating.

Acetoacetic and malonic acids are very easily decarboxylated:

H 3 C-C(O)-CH 2 -C(O)OH --> H 3 C-C(O)-CH 3 + CO 2

HO-C(O)-CH 2 -C(O)OH --> H 3 С-C(O)OH + CO 2

The latter reaction is the basis of convenient preparative synthesis methods, called "Synthesis based on malonic and acetoacetic esters".

Decarboxylation of dicarboxylic acids is used to obtain cyclic ketones, for example, heating adipic acid with a small amount of barium oxide allows cyclopentanone to be obtained in good yield:

HO-C (O) - (CH 2) 4 -C (O) OH --> cyclo-C 4 H 8 C \u003d O + CO 2

The decarboxylation reaction is a key step in reactions such as the Kolbe (electrolysis of salts of carboxylic acids), Simonini, Marquewald, Dakin-West and Borodin-Hunsdieker reactions.

Oxidative decarboxylation. When heated to 260-300 o With the copper salt of benzoic acid, it decomposes with the formation of phenyl benzoate, carbon dioxide and copper:

2 Cu --> C 6 H 5 -C (O) O-C 6 H 5 + CO 2 + Cu

The reaction proceeds through a cyclic intermediate state. One option for oxidative decarboxylation is the reaction of carboxylic acids with lead tetraacetate (oxidant) in the presence of calcium or lithium chloride (source of chloride anions). The reaction proceeds in boiling benzene and leads to the formation of halogen derivatives of hydrocarbons:

R-C(O)-OH + Pb 4 + 2 LiCl --> R-Cl + Pb 2 + CH 3 C(O)OLi + CH 3 C(O)OH

Decarboxylation reactions are integral and important stages of such biochemical processes as alcoholic fermentation and tricarboxylic acid cycle.

Literature

K. V. Vatsuro, Mishchenko “Nominal reactions in organic chemistry”, M .: Chemistry, 1976.
J. J. Lee, Nominal reactions. Mechanisms of organic reactions, M.: Binom., 2006.

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Synonyms:

See what "Decarboxylation" is in other dictionaries:

Cleavage of CO2 from the carboxyl group of carboxylic acids to t. Enzymatic D. can be reversible (for example, D. of oxaloacetate with the formation of pyruvate) and irreversible (for example, oxidative D. of amino acids catalyzed by decarboxylases, coenzyme to ryh ... Biological encyclopedic dictionary

Cleavage of CO2 from the carboxyl group of carboxylic acids is usually with the participation of decarboxylase enzymes. Enzymatic D. can be reversible (D. oxaloacetate to pyruvate) and irreversible (oxidative D. amino acids). Special meaning in the cell ... ... Dictionary of microbiology

- [de ... + lat. carbo charcoal + gr. sour] - cleavage from organic acids of the COOH group; is essential in the process of metabolism and during decay. A large dictionary of foreign words. Publishing house "IDDK", 2007 ... Dictionary of foreign words of the Russian language

Exist., Number of synonyms: 1 split (8) ASIS Synonym Dictionary. V.N. Trishin. 2013 ... Synonym dictionary

The process of splitting off carbon dioxide from the carboxyl group (see Carboxyl) of acids. In the absence of other non-hydrocarbon gr. in the D. molecule leads to the formation of hydrocarbons. Many hypotheses of the origin of oil attach great importance to participation in ... ... Geological Encyclopedia

decarboxylation- The reaction of splitting off the CO2 group from the carboxyl group of carboxylic acids or the carboxylate group of their salts. [Arefiev V.A., Lisovenko L.A. English Russian explanatory dictionary of genetic terms 1995 407s.] Topics genetics EN decarboxylation ... Technical Translator's Handbook

Decarboxylation- * decarboxylation * decarboxylation movement or loss by organic compounds of carboxyl groups, from which CO2 is formed. D. occurs under the action of decarboxylase enzymes that catalyze the roar of 51 positions to deoxyribose instead of ... ... Genetics. encyclopedic Dictionary

Decarboxylation decarboxylation. The reaction of elimination of the CO2 group from the carboxyl group of carboxylic acids or the carboxylate group of their salts. (

The reactions of carboxylic acids can be divided into several large groups:

1) Recovery of carboxylic acids

2) Decarboxylation reactions

3) Substitution reactions at the -carbon atom of carboxylic acids

4) Reactions of nucleophilic substitution at the acyl carbon atom.

We will consider each of these groups of reactions in turn.

18.3.1. Recovery of carboxylic acids

Carboxylic acids are reduced to primary alcohols with lithium aluminum hydride. The reduction takes place under more severe conditions than is required for the reduction of aldehydes and ketones. Recovery 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 in some cases is preferable.

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-Hunsdiecker reaction, in which the silver salt of a carboxylic acid is converted to an alkyl halide when heated with a solution of bromine in CCl 4 .

Successful carrying out of this reaction requires the use of carefully dried silver salts of carboxylic acids, and the yield of the alkyl halide varies widely depending on the degree of purification and dehydration of the salt. This drawback is devoid of modification, where mercury salts are used instead of silver. The mercury salt of a carboxylic acid is not isolated individually, but a mixture of carboxylic acid, yellow mercury oxide and halogen is heated in an indifferent solvent. This method generally results in a higher and more reproducible output.

A radical chain mechanism has been established for the Borodin-Hunsdiecker reaction. The acyl hypobromite 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 turns into an alkyl radical, which then regenerates the chain by splitting off a bromine atom from the acyl hypobromite.

Circuit 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, decarboxylation occurs and, depending on the conditions, alkanes, alkenes or acetic acid esters are obtained as reaction products. 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 proton elimination or acetate ion capture. The introduction of a halide ion into the reaction mixture almost completely suppresses both 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 oxidation with lead tetraacetate in the presence of lithium chloride gives the highest yields of alkyl halides for carboxylic acids with a secondary radical.

Another reaction of decarboxylation of carboxylic acids, which is of great preparative importance, is the electrolytic condensation of salts of carboxylic acids, discovered in 1849 by G. Kolbe. He carried out the electrolysis of an aqueous solution of potassium acetate in the hope of obtaining a free radical CH 3 , but instead of it, ethane was obtained at the anode. Similarly, during the electrolysis of an aqueous solution of the sodium salt of valeric acid, n.octane was obtained instead of the butyl radical. The 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 are sharply reduced and rarely exceed 10%.

This reaction proved to be particularly useful for the synthesis of diesters of dicarboxylic acids ROOC(CH 2) n COOR with n from 2 to 34 in the electrolysis of alkali salts of half-esters of dicarboxylic acids.

In modern organic electrosynthesis, cross electrolytic condensation is widely used, which consists in the electrolysis of a mixture of carboxylic acid salts and a dicarboxylic acid monoester.

The 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 straight-chain carboxylic acid salts and dicarboxylic acid half-ester salts. 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 a high current density, a high concentration of alkyl radicals at the anode promotes their dimerization; at a low current density, 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. Once upon a time, pyrolysis of calcium or barium salts of carboxylic acids was the main method for obtaining ketones. In the 19th century, the “dry distillation” of calcium acetate was the main method for producing acetone.

Subsequently, the method was improved in such a way that it does not include the stage of obtaining salts. Vapors of carboxylic acid are passed over the catalyst - oxides of manganese, thorium or zirconium at 380-400 0 . The most efficient and expensive catalyst is thorium dioxide.

In the simplest cases, acids with two to ten carbon atoms are converted into symmetrical ketones with a yield of about 80% when boiled with powdered iron at 250-300 . This method finds application in industry. The pyrolytic method is most successfully used and 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 , 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 not very suitable for obtaining cycloalkanones with a large number of carbon atoms.

Lecture No. 12

carboxylic acids

Plan

1. Methods of obtaining.

2. Chemical properties.

2.1. acid properties.

2.3. Reactions for 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. acid properties.

2.2. Reactions of nucleophilic substitution.
Functional derivatives of carboxylic acids.

2.3. Reactions for a -carbon atom.

2.5. Recovery.

2.6. dicarboxylic acids.

1. Methods of obtaining

2. Chemical
properties

Carboxylic acids contain a carboxyl group which is directly bonded between
is a carbonyl group and a hydroxyl. Their mutual influence causes a new
a set of properties that are different from those of carbonyl compounds and
hydroxyl derivatives. Reactions involving carboxylic acids proceed according to
following main directions.

Substitution of hydrogen of the COOH group under
action of bases ( acid properties).
Interaction with nucleophilic reagents
at the carbonyl carbon atom ( the formation of functional derivatives and
recovery)
Reactions for a -carbon atom
(halogenation)
Decaboxylation

2.1. Acidic
properties

Carboxylic acids are one of the strongest organic acids. Their water
solutions are acidic.

RCOOH + H 2 O \u003d RCOO - +
H3O+

Causes of high acidity of carboxylic acids and
its dependence on the nature of the substituents in the hydrocarbon radical were
discussed earlier (see Lec. No. 4).

Carboxylic acids form salts when
interaction with active metals and most bases.

When interacting with strong inorganic
carboxylic acids can exhibit basic properties by adding
proton at 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 Lec. No. 2).

2.2. Reactions of nucleophilic substitution.
Functional derivatives of carboxylic acids.

The main type of reactions of carboxylic acids -
interaction with nucleophiles with the formation of 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 interconversions, it passes unchanged from one compound to
another 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 as
the next diagram.

So acylation is
the process of nucleophilic substitution at the carbonyl carbon atom.

Consider the reaction mechanism in general terms and
compare it with Ad N -reactions
aldehydes and ketones. As in the case of carbonyl compounds, the reaction begins
from the attack of the nucleophile on the carbonyl carbon atom bearing the effective
positive charge. At the same time it breaks p -bond carbon-oxygen and formed tetrahedral
intermediate. Ways of further transformation of the intermediate in carbonyl and
acyl compounds are different. If carbonyl compounds give a product accession, then the acyl compounds cleave off the X group and give the product substitution.

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 carboanion R — , which, due to their high basicity, are
extremely poor leaving groups. In the case of acyl compounds X
a significantly more stable leaving group (Cl — ,
RCOO - , RO - , NH 2 - ), which makes it possible to eliminate it as an anion
X — or conjugate acid
NH.

Reactivity with respect to
nucleophiles in carboxylic acids and their functional derivatives is less than in
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
a positive charge on the carbon atom and facilitates its attack
nucleophile.

Derivatives according to their acylating ability
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 converted into them
during hydrolysis.

Acid chlorides and anhydrides

Acquisition Methods

Acid chlorides are obtained by interaction
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
the action of phosphorus (V) oxide.

Mixed anhydrides can be obtained
acylation of salts of carboxylic acids with acid chlorides.

acid chlorides and anhydrides.

X loranhydrides and anhydrides are the most reactive derivatives
carboxylic acids. Their reactions with nucleophiles proceed under mild conditions, without
catalyst and is practically irreversible.

When using mixed anhydrides with
the nucleophile combines the rest of the weaker acid, and the anion of the stronger
acid plays the role of a leaving group.

AT
mixed anhydrides play an important role in biochemical acylation reactions
carboxylic acids and phosphoric acid - acyl phosphates and substituted acyl phosphates. FROM
the nucleophile combines the residue of organic acids, and the acyl phosphate anion
plays the role of a good leaving group.

Esters

Acquisition Methods

RCOO— Na+ + RCl ® RCOOR + NaCl The most important method for obtaining 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. Use of the strong
nucleophiles, which are also strong bases (for example,
basic catalysis), in this case it is impossible, since they transfer carboxylic
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, in increasing the effective positive charge on the carbon atom
carboxyl group, and, in addition, the protonation of the OH group at the stage
splitting off turns it into a good leaving group - H 2 O.

All steps 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 sphere.

Nucleophilic substitution reactions in
alkoxycarbonyl group.

Esters are weaker acylating
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
interesterification .

Hydrolysis.

Esters are hydrolyzed to form carboxylic acids by the action of
acids or alkalis.

Acid hydrolysis of esters is a reverse esterification reaction.

The mechanism of acid hydrolysis includes the same steps 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
provided by low reactivity towards nucleophiles
hydrolysis product - carboxylate anion.

Interesterification.

In the transesterification reaction, the role of the nucleophile
performs an alcohol molecule. The process is catalyzed by acids or
grounds.

The reaction mechanism is similar to the hydrolysis of complex
ethers. Interesterification is a reversible process. To shift the balance to the right
it is necessary to use a large excess of the initial alcohol. Reaction
interesterification finds application in the production of fatty acid esters
from triacylglycerides (see lek. 18)

Aminolysis.

Esters acylate ammonia and amines with
formation of amides of carboxylic acids.

Amides of carboxylic acids

The structure of the amide group

BUT 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 -adjoint system in which
additional overlapping of the p-orbital of the nitrogen atom with p -communication orbital
carbon-oxygen.

Such a distribution of electron density
leads to an increase in the energy barrier of rotation around the C-N bond to 60 -
90 kJ/mol. As a result, the amide bond has a planar structure, and the bond lengths
C-N and C \u003d O have values \u200b\u200brespectively less and more than their usual
quantities.

Lack of free rotation around the C-N bond
leads to the existence of amides cis- and trance-isomers. For
most amides is preferred trance-configuration.

The peptide bond also has trance-configuration in which the side radicals of amino acid residues
most distant from each other

Acquisition Methods

Nucleophilic substitution reactions in
carboxamide group.

Amides are the least reactive derivatives of carboxylic acids. For them
hydrolysis reactions are known that proceed under harsh conditions under the action of
aqueous solutions of acids or alkalis.

The reaction mechanisms are similar to the hydrolysis of complex
ethers. However, in contrast to the hydrolysis of esters, acid and alkaline hydrolysis
amides proceed irreversibly.

2.3. Reactions for a -carbon
atom

carboxylic acids containing a - hydrogen atoms,
react with bromine in the presence of phosphorus to form exclusively a - bromo derivatives
(Gell-Forgald-Zelinsky reaction )

Halogen in a -halo-substituted acids are easily substituted under
action of nucleophilic reagents. That's why a -halogenated acids
are starting materials in the synthesis of a wide range of substituted 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, as
As a rule, the carboxyl group is replaced by a hydrogen atom.

Unsubstituted monocarboxylic acids
decarboxylated under harsh conditions.

Decarboxylation is facilitated by the presence
electron-withdrawing substituents in a-position.

The importance of enzymatic
decarboxylation of keto-, amino- and hydroxy acids in the body (see lek. No. 14 and
16).

Decarboxylation by heating (dry
distillation) of calcium and barium salts of carboxylic acids - a method for obtaining
ketones.

2.5.
Recovery.

Carboxylic acids, acid chlorides, anhydrides and esters
are restored LiAlH 4 to primary
alcohols.

Acid chlorides can be reduced to
aldehydes (see Lec. No. 11).

In the reduction of amides of carboxylic acids
amines are formed.

3. Dicarboxylic acids

Dicarboxylic acids contain two carboxyl groups. most affordable
are linear acids containing from 2 to 6 carbon atoms. Them
the structure and methods of obtaining 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 the carboxyl group. At the same time, one can obtain
functional derivatives (acid chlorides, anhydrides, complex, esters, amides) as
one by one and 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
specific properties, which are determined by the presence in the molecule of two
carboxyl groups.

The ratio of dicarboxylic acids to
heating.

Transformations of dicarboxylic acids upon heating
depend on the length of the chain that separates the carboxyl groups, and are determined
the possibility of forming thermodynamically stable five- and six-membered
cycles.

When heated oxalic and malonic acids
decarboxylation occurs.

Succinic, glutaric and maleic acids at
when heated, they easily split off water with the formation of five- and six-membered cyclic
anhydrides.

Adipic acid when heated
decarboxylated to form a cyclic ketone, cyclopentanone.

Polycondensation reactions

D icarboxylic acids interact with diamines and diols with
the formation of polyamides and polyesters, respectively, which are used in
production of synthetic fibers.

Biologically important dicarboxylic
acids.

Oxalic acid forms insoluble salts, for example,
calcium oxalate, which are deposited as kidney and bladder stones.

succinic acid participates in the metabolic processes taking place in
body. It is an intermediate in the tricarboxylic acid cycle.

fumaric acid, as opposed to maleic , widely distributed in nature, is involved 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. acid properties.

2.3. Reactions for 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. acid properties.

2.2. Reactions of nucleophilic substitution.
Functional derivatives of carboxylic acids.

2.3. Reactions for a -carbon atom.

2.5. Recovery.

2.6. dicarboxylic acids.

1. Methods of obtaining

2. Chemical
properties

Substitution of hydrogen of the COOH group under
action of bases ( acid properties).
Interaction with nucleophilic reagents
at the carbonyl carbon atom ( the formation of functional derivatives and
recovery)
Reactions for a -carbon atom
(halogenation)
Decaboxylation