General structural formula of esters:
where R and R’ are hydrocarbon radicals.
Hydrolysis of esters
One of the most characteristic abilities of esters (besides esterification) is their hydrolysis - splitting under the influence of water. In another way, the hydrolysis of esters is called saponification. Unlike the hydrolysis of salts, in this case it is practically irreversible. A distinction is made between alkaline and acid hydrolysis of esters. In both cases, alcohol and acid are formed:
a) acid hydrolysis
b) alkaline hydrolysis
Examples of problem solving
Alkaline hydrolysis - ester
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Alkaline hydrolysis of esters, like acid hydrolysis, proceeds through the addition-elimination mechanism.
Alkaline hydrolysis of esters, sometimes called a specific base catalysis reaction, is actually a displacement reaction (see Sect.
Alkaline hydrolysis of esters by the Bac2 mechanism proceeds through nucleophilic addition at the carbonyl group to form a tetrahedral intermediate (see section. This is a common reaction of nucleophiles with the carbonyl group of an ester, and various examples of its application will be discussed below in this section. Interaction with hydride ions leads to to reduction, so this reaction will be discussed together with other reduction reactions (see Sect.
Alkaline hydrolysis of esters occurs with a thermal effect equal to the heat of neutralization of the resulting acid. The reactions of esterification of alcohols with acid chlorides, as well as the first stage of esterification with acid anhydrides, are also exothermic.
Alkaline hydrolysis of esters is an irreversible reaction, since the final reaction product (carboxylate anion) does not exhibit the properties of a carbonyl compound due to complete decalcification of the negative charge.
Alkaline hydrolysis of esters occurs with a thermal effect equal to the heat of neutralization of the resulting acid. The reactions of esterification of alcohols with acid chlorides, as well as the first stage of esterification with acid anhydrides, are also exothermic.
Alkaline hydrolysis of esters is called saponification. The rate of hydrolysis of esters also increases with heating and in the case of using excess water.
Alkaline hydrolysis of esters is characteristic of a large number of reactions in which a negatively charged nucleophile attacks the carbonyl carbon of a neutral substrate.
Alkaline hydrolysis of esters is called saponification. The rate of hydrolysis of esters also increases with heating and in the case of using excess water.
Practically alkaline hydrolysis of esters is carried out in the presence of caustic alkalis KOH, NaOH, as well as hydroxides of alkaline earth metals Ba (OH) 2, Ca (OH) 2 - The acids formed during hydrolysis are bound in the form of salts of the corresponding metals, so the hydroxides have to be taken at least in equivalent ratio with the ester. Typically, excess base is used. The separation of acids from their salts is carried out using strong mineral acids.
The reaction of alkaline hydrolysis of esters is called the saponification reaction.
The reaction of alkaline hydrolysis of esters is called the saponification reaction.
The method of alkaline hydrolysis of esters is included as part of various multi-stage processes of organic synthesis. For example, it is used in the industrial production of fatty acids and alcohols by the oxidation of paraffins (chap.
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4.6. Esters
Esters can be obtained by reacting carboxylic acids with alcohols ( esterification reaction). The catalysts are mineral acids.
Video experiment "Preparation of ethyl acetate ether".
The esterification reaction under acid catalysis is reversible.
The reverse process - the cleavage of an ester under the action of water to form a carboxylic acid and alcohol - is called ester hydrolysis. RCOOR’ + H2O (H+) RCOOH + R’OH Hydrolysis in the presence of alkali is irreversible (since the resulting negatively charged carboxylate anion RCOO– does not react with the nucleophilic reagent – alcohol).
This reaction is called saponification of esters(by analogy with alkaline hydrolysis of ester bonds in fats when producing soap).
Esters of lower carboxylic acids and lower monohydric alcohols have a pleasant smell of flowers, berries and fruits. Esters of higher monobasic acids and higher monohydric alcohols are the basis of natural waxes. For example, beeswax contains an ester of palmitic acid and myricyl alcohol (myricyl palmitate):
CH(CH)–CO–O–(CH)CH
Chemical properties - section Chemistry, GENERAL REGULARITIES OF THE STRUCTURE AND CHEMICAL BEHAVIOR OF OXO COMPOUNDS 1. Hydrolysis of Esters (Acid and Alkaline Catalysis). ...
1. Hydrolysis of esters (acid and alkaline catalysis). The ester is a weak acylating agent and can be hydrolyzed in the presence of catalysts (acids or bases).
1.1 Alkaline hydrolysis:
Mechanism of alkaline hydrolysis:
Alkaline hydrolysis has a number of advantages over acid hydrolysis:
- proceeds at a higher speed, since the hydroxide anion is a stronger and smaller nucleophile compared to a water molecule;
- in an alkaline environment, the hydrolysis reaction is irreversible, since an acid salt is formed that does not have acylating ability.
Therefore, in practice, the hydrolysis of esters is often carried out in an alkaline medium.
1.2 Acid hydrolysis:
2. Transesterification reaction. Interaction with alkoxides in a solution of the corresponding alcohol leads to the exchange of alkyl groups of the ester; the reaction is reversible:
3. Ammonolysis reaction:
Esters in nature, their importance in industry. The least reactive derivatives of carboxylic acids - esters, amides, nitriles - are widely used as solvents.
Industrial and preparative significance are ethyl acetate, dimethylformamide And Acetonitrile. Dimethylformamide is an aprotic solvent for both polar (even salts) and non-polar substances and is currently widely used in industry as a solvent for polyamides, polyimides, polyacrylonitrile, polyurethanes, etc., used for the formation of fibers and films, the preparation of glue, etc. etc., as well as in laboratory practice.
Esters of lower carboxylic acids ( C1 – C5) and lower alcohols (CH3OH, C2H5OH) They have a fruity smell and are used to flavor soaps and confectionery products. Acetates, butyrates of citronellol, geraniol, linalool, which have a pleasant floral odor, are included, for example, in lavender oil and are used to make soaps and colognes.
Diphenylacetic acid esters, e.g. diethylaminoethyl ester (spasmolitin), known as antispasmodics - drugs that relieve spasms of the smooth muscles of internal organs and blood vessels. Anestezin – ethyl ether n-aminobenzoic acid, novocaine – diethylaminoethyl ether n-aminobenzoic acid, paralyzing nerve endings, causes local anesthesia and pain relief. More powerful than novocaine is xycaine (N- 2,6-dimethylphenylamide N,N'-diethylaminoacetic acid).
Ethyl acetate – colorless liquid, is used as a solvent for dissolving nitrocellulose, cellulose acetate and other polymeric materials, for the manufacture of varnishes, as well as in the food industry and perfumery.
Butyl acetate – colorless liquid with a pleasant odor. Used in the paint and varnish industry as a solvent for nitrocellulose and polyester resins.
Amyl acetates– good solvents for nitrocellulose and other polymeric materials. Isoamyl acetate is used in the food industry (pear essence).
Artificial fruit essences. Many esters have a pleasant odor and are used in the food industry and perfumery.
All topics in this section:
GENERAL REGULARITIES OF THE STRUCTURE AND CHEMICAL BEHAVIOR OF OXO COMPOUNDS
Multiple bonds between carbon and oxygen are found in aldehydes, ketones, carboxylic acids, as well as their derivatives. For compounds containing a carbonyl group, the most characteristic properties are
OXO COMPOUNDS
Aldehydes and ketones are hydrocarbon derivatives that contain a functional group in the molecule called a carbonyl or oxo group. If a carbonyl group is bonded to one
Technical methods for producing formaldehyde
3.1 Catalytic oxidation of methanol: 3.2 Ka
Specific methods for aromatic series
11.1 Oxidation of alkylarenes. Partial oxidation of the alkyl group associated with the benzene ring can be accomplished by the action of various oxidizing agents. Methyl group – MnO
Nucleophilic addition reactions
1.1 Addition of magnesium alkyls: where
Oxidation reactions of aldehydes and ketones
5.1 Oxidation of aldehydes. Aldehydes oxidize most easily, turning into carboxylic acids with the same number of carbon atoms in the chain:
Oxidation-reduction reactions (disproportionation)
6.1 The Cannizzaro reaction (1853) is characteristic of aldehydes that do not contain hydrogen atoms in the α-position, and occurs when they are treated with concentrated p
CARBOXYLIC ACIDS AND THEIR DERIVATIVES
Carboxylic acids are derivatives of hydrocarbons containing a carboxyl functional group (–COOH) in the molecule. This is the most “oxidized” functional group, which is easy to see
MONOCARBOXYLIC ACIDS
Monocarboxylic acids are hydrocarbon derivatives containing one functional carboxyl group in the molecule - COOH. Monocarboxylic acids are also called monobases
Isomerism
Structural: · skeletal; · metamerism Spatial: · optical. Synthesis methods. Monocarbon
Reactions of carboxylic acids with nucleophilic reagents
1.1 Formation of salts with metals:
DERIVATIVES OF CARBOXYLIC ACIDS
Carboxylic acids form a variety of derivatives (esters, anhydrides, amides, etc.), which participate in many important reactions. General formula of derivatives
Methods of obtaining
1. Interaction with phosphorus (V) chloride:
Chemical properties
1. Use of anhydrides as acylating agents.
Anhydrides, like acid halides, have high chemical activity and are good acylating agents (often
Methods for preparing amides
1. Ammonia acylation:
Chemical properties
1. Hydrolysis of amides 1.1 In an acidic environment:
Methods of obtaining
1. Esterification reaction: Esterification mechanism
DICARBOXYLIC ACIDS
The class of dicarboxylic acids includes compounds containing two carboxyl groups. Dicarboxylic acids are divided depending on the type of hydrocarbon radical: ·
General methods for preparing dicarboxylic acids
1. Oxidation of diols and cyclic ketones:
Isomerism
Structural: · skeletal; positional isomerism; · metamerism. Spatial: · geometric. Unlimited
Chemical properties of fats
1. Hydrolysis. Among the reactions of fats, hydrolysis, or saponification, which can be carried out with both acids and bases, is of particular importance:
FEATURES OF PHYSICAL PROPERTIES OF HOMO-FUNCTIONAL HYDROCARBONS DERIVATIVES
The presence of a functional group associated with a hydrocarbon substituent significantly affects the physical properties of the compounds. Depending on the nature of the functional group (atom) e
HYDROCARBONS
Among the many different functional derivatives of hydrocarbons, there are compounds that are highly toxic and hazardous to the environment, moderately toxic and completely harmless, non-toxic, widely
When esters are heated with alcohols, a double exchange reaction occurs, called transesterification. Both acids and bases have a catalytic effect on this reaction:
To shift the equilibrium in the desired direction, a large excess of alcohol is used.
Methacrylic acid butyl ester (butyl methacrylate) can be obtained in 94% yield by heating methyl methacrylate with n-butanol with continuous removal of methanol as it is formed:
Alcoholysis of esters of carboxylic acids under the influence of alkaline catalysts is of particularly great preparative importance for the synthesis of esters of thermally unstable carboxylic acids with a long side chain (for example, esters b-keto acids) and alcohol esters, unstable in acidic environments, which cannot be obtained by conventional esterification methods. Sodium alcoholates, sodium hydroxide and potassium carbonate are used as catalysts for such reactions.
Alcoholysis of esters b-keto acids are easily carried out at 90-100°C without a catalyst. For example, the octyl ester of acetoacetic acid was synthesized from acetoacetic ester using this method:
This makes it possible to exchange a primary alcohol with another primary or secondary alcohol with a higher boiling point, but this method is not suitable for obtaining esters from tertiary alcohols. Esters of tertiary alcohols are obtained in another way - by mutual transesterification of two different esters of carboxylic acids, for example, an ester of formic acid and some other acid:
The reaction is carried out in the presence of catalytic quantities rubs-sodium butoxide at 100-120°C.
In this case, the lowest boiling component of the equilibrium mixture is slowly distilled off, in this case the methyl ester of formic acid (methyl formate, bp 34°C).
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Hydrolysis - ether
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Hydrolysis of ethers in a strongly acidic environment (Sect.
Subsequently, the hydrolysis of ethers began to be of interest from the point of view of the theory of chemical structure, namely as a reaction by which the relative strength of the carbon-oxygen bond can be determined depending on the structure of the radical. In the 1930s, a practical need arose to develop a technically acceptable method for the hydrolysis of diethyl ether; This need was dictated by the fact that in the process of producing synthetic rubber using Lebedev’s method, ether was formed as a by-product, which it was advisable to convert into alcohol. In this regard, in the USSR, the hydrolysis of diethyl ether was studied by Vanscheidt and Lozovskaya and Kagan, Rossiyskaya and Cherntsov, using oxides of aluminum, titanium, thorium, chromium and manganese as catalysts.
The patent literature describes the hydrolysis of ethers to form alcohols by the action of dilute sulfuric acid at high temperature and pressure; the process was carried out at 272 C and 130 atm for 25 minutes. This method is used only when it is necessary to dispose of excess ethyl ether.
The patent literature describes the hydrolysis of ethers with the formation of alcohols under the action of dilute sulfuric acid at high temperature and pressure [22J; the process was carried out at 272 C and 130 atm for 25 minutes. This method is used only when it is necessary to dispose of excess ethyl ether.
Removal of acetaldehyde from the reaction sphere in the form of an oxime determines the completeness of the hydrolysis of the ether. Water, alcohols, and hydrocarbons do not interfere with the determination.
The hydrolysis of peptides, amides and phosphate esters and the hydration of pyridine aldehydes are catalyzed similarly. Hydrolysis of ethers is not catalyzed by metal ions because no chelates are formed and the intermediate cannot be stabilized.
General acid-base catalysis is very common, but there are a few cases in which specific catalysis by hydrogen or hydroxyl ions occurs; in this case, the rate constant varies linearly with [H3O] and [OH -] and is independent of the presence of other acidic and basic substances. For example, specific catalysis was discovered in the hydrolysis of ethers (see p.
The cleavage of phenol esters with aluminum chloride provides a ready-made method for obtaining phenol derivatives that are difficult to synthesize; Some characteristic transformations of phenol esters into the corresponding phenols are listed here. Despite the fact that the cleavage of alkoxy groups is so easily catalyzed by aluminum chloride, there is no methodological study on the effect of substituents on aluminum chloride-catalyzed hydrolysis of ethers.
However, for the reaction to be successful, it is necessary to have two, for example, methoxyl groups in the molecule of the azo component or the use of a very active diazo component. It is interesting that during azo coupling of phenol esters, hydrolysis of the ester group often occurs, so that the result is the formation of an azo dye, which is a derivative of the phenol itself. Let us recall that in general the hydrolysis of ethers is very difficult. The mechanism of this reaction has not been studied.
In conclusion, we can say that saponification under MPA conditions is synthetically advantageous in the case of sterically hindered esters. In this case, a solid potassium hydroxide/toluene system and crown ethers or cryptands should be used as catalysts. In addition, the rate of hydrolysis of carboxylic acid ethers with concentrated aqueous sodium hydroxide is significantly higher for hydrophilic carboxylates. Good catalysts are quaternary ammonium salts, especially Bu4NHSO4 and some anionic and nonionic surfactants. This indicates that any of three possible mechanisms may occur: surface reactions, micellar catalysis, or a true MPA reaction. Depending on the conditions, each of these mechanisms can be realized.
As a result, we will obtain the following values of DN srVn: 311 for HI, 318 for HBg, 329 for HC1, 334 for water and 334 for ROH. Thus, we can predict that HI will have the greatest reactivity, in full agreement with experiment, although in practice concentrated aqueous solutions are used, whereas our calculations were made for reactions in the gas phase. It is well known that at room temperature ethers are practically incapable of reacting with water and alcohols. In addition, it is customary to say that the hydrolysis of ethers is accelerated by hydrogen rather than hydroxyl ions, which is in agreement with the nucleophilic properties established for ethers by our approximate calculations, Addition of hydrogen halides to olefins. The first step is to determine whether the rate-determining step is the electrophilic attack of the hydrogen ion or the nucleophilic attack of the halide ion on the carbon atom of the olefin.
Ethers are neutral liquids that are poorly soluble in water. They do not react with sodium metal, which makes it possible to remove residual water and alcohol from them using sodium metal. Ethers are very durable.
Weak acids and alkalis have no effect on them. Alkalis do not promote hydrolysis of ethers. Along with this resistance to hydrolysis, ethers are quite easily oxidized by atmospheric oxygen, especially under the influence of light, forming peroxides (p. Esters, as a rule, are sparingly soluble in water, but are easily soluble in most organic solvents. Many of the esters have a specific, a pleasant fruity smell, which allows them to be used for the production of artificial fruit essences in confectionery or perfumery, as well as for identifying certain acids or alcohols by the smell of their esters.
Ethers are neutral liquids that are poorly soluble in water. They do not react with sodium metal, which makes it possible to remove residual water and alcohol from them using sodium metal. Ethers are very durable. Weak acids and alkalis have no effect on them. Hydrolysis of ethers occurs with difficulty when heated with water in the presence of acids. Alkalis do not promote hydrolysis of ethers. Along with this resistance to hydrolysis, ethers are quite easily oxidized by atmospheric oxygen, especially under the influence of light, forming peroxides (p. Esters, as a rule, are sparingly soluble in water, but are easily soluble in most organic solvents. Many of the esters have a specific, a pleasant fruity smell, which allows them to be used for the production of artificial fruit essences in confectionery or perfumery, as well as for identifying certain acids or alcohols by the smell of their esters.
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Esters are called functional derivatives of carboxylic acids of the general formula RC(O)OR" .
Esters of carboxylic acids (as well as sulfonic acids) are named similarly to salts, only instead of the name of the cation, the name of the corresponding alkyl or aryl is used, which is placed before the name of the anion and written together with it. The presence of an ester group -COOR can also be reflected in a descriptive way, for example, “R-ester of (such and such) acid” (this method is less preferable due to its cumbersomeness):
Esters of lower alcohols and carboxylic acids are volatile liquids with a pleasant odor, poorly soluble in water and well soluble in most organic solvents. The odors of esters resemble the odors of various fruits, so in the food industry they are used to prepare essences that imitate fruit odors. The increased volatility of esters is used for analytical purposes.
Hydrolysis. The most important of the acylation reactions is the hydrolysis of esters with the formation of alcohol and carboxylic acid:
The reaction takes place in both acidic and alkaline environments. Acid-catalyzed hydrolysis of esters - the reverse reaction to esterification, proceeds according to the same mechanism A AC 2:
The nucleophile in this reaction is water. A shift in equilibrium towards the formation of alcohol and acid is ensured by the addition of excess water.
Alkaline hydrolysis is irreversible; during the reaction, a mole of alkali is consumed per mole of ether, i.e., the alkali in this reaction acts as a consumable reagent and not a catalyst:
Hydrolysis of esters into alkaline environment proceeds via a bimolecular acyl mechanism B AC 2 through the stage of formation of tetrahedral intermediate (I). The irreversibility of alkaline hydrolysis is ensured by the practically irreversible acid-base interaction of carboxylic acid (II) and alkoxide ion (III). The resulting carboxylic acid anion (IV) is itself a fairly strong nucleophile and therefore is not subject to nucleophilic attack.
Ammonolysis of esters. Amides are obtained by ammonolysis of esters. For example, when aqueous ammonia reacts with diethyl fumarate, complete fumaric acid amide is formed:
When ammonolysis of esters with amines with low nucleophilicity, the latter are first converted into amides of alkali or alkaline earth metals:
Amides of carboxylic acids: nomenclature; structure of the amide group; acid-base properties; acid and alkaline hydrolysis; splitting with hypobromites and nitrous acid; dehydration to nitriles; chemical identification.
amides are called functional derivatives of carboxylic acids of the general formula R-C(O)-NH 2- n R" n , where n = 0-2. In unsubstituted amides, the acyl residue is connected to an unsubstituted amino group; in N-substituted amides, one of the hydrogen atoms is replaced by one alkyl or aryl radical; in N,N-substituted amides, by two.
Compounds containing one, two or three acyl groups attached to a nitrogen atom are generically called amides (primary, secondary and tertiary, respectively). The names of primary amides with an unsubstituted group - NH 2 are derived from the names of the corresponding acyl radicals by replacing the suffix -oil (or -yl) with -amide. Amides formed from acids with the suffix -carboxylic acid receive the suffix -carboxamide. Sulfonic acid amides are also named after the corresponding acids, using the suffix -sulfonamide.
The names of the radicals RCO-NH- (like RSO 2 -NH-) are formed from the names of amides, changing the suffix -amide to -amido-. They are used if the rest of the molecule contains a higher group or the substitution occurs in a more complex structure than the R radical:
In the names of N-substituted primary amides RCO-NHR" and RCO-NR"R" (as well as similar sulfonamides), the names of the radicals R" and R" are indicated before the name of the amide with the symbol N-:
These types of amides are often referred to as secondary and tertiary amides, which are not recommended by IUPAC.
N-Phenyl-substituted amides are given the suffix -anilide in their names. The position of substituents in the aniline residue is indicated by numbers with primes:
In addition, semi-systematic names have been preserved, in which the suffix -amide is combined with the base of the Latin name for the carboxylic acid (formamide, acetamide), as well as some trivial names such as "anilides" (acylated anilines) or "toluidides" (acylated toluidines).
Amides are crystalline substances with relatively high and distinct melting points, which allows some of them to be used as derivatives for the identification of carboxylic acids. In rare cases, they are liquids, for example, formic acid amides - formamide and N,N-dimethylformamide - known dipolar aprotic solvents. Lower amides are highly soluble in water.
Amides are one of the most resistant to hydrolysis functional derivatives of carboxylic acids, due to which they are widely distributed in nature. Many amides are used as medicines. For about a century, paracetamol and phenacetin, which are substituted amides of acetic acid, have been used in medical practice.
Structure of amides. The electronic structure of the amide group is largely similar to the structure of the carboxyl group. The amide group is a p,π-conjugated system in which the lone pair of electrons of the nitrogen atom is conjugated with the electrons of the C=O π bond. Delocalization of electron density in the amide group can be represented by two resonance structures:
Due to conjugation, the C-N bond in amides has partially bilinked character, its length is significantly less than the length of a single bond in amines, while the C=O bond is slightly longer than the C=O bond in aldehydes and ketones. Amide group due to conjugation has a flat configuration . Below are the geometric parameters of the N-substituted amide molecule, established using X-ray diffraction analysis:
An important consequence of the partially doubly bonded nature of the C-N bond is the rather high energy barrier for rotation around this bond; for example, for dimethylformamide it is 88 kJ/mol. For this reason, amides having different substituents on the nitrogen atom can exist in the form of π-diastereomers. N-Substituted amides exist predominantly as Z-isomers:
In the case of N,N-disubstituted amides, the ratio of E- and Z-isomers depends on the volume of radicals connected to the nitrogen atom. Amide stereoisomers are configurationally unstable; their existence has been proven mainly by physicochemical methods; they have been isolated in individual form only in isolated cases. This is due to the fact that the rotation barrier for amides is still not as high as for alkenes, for which it is 165 kJ/mol.
Acid-base properties. Amides have weak both acidic and basic properties . The basicity of amides lies within the range of Pk BH + values from -0.3 to -3.5. The reason for the reduced basicity of the amino group in amides is the conjugation of the lone pair of electrons of the nitrogen atom with the carbonyl group. When interacting with strong acids, amides are protonated at the oxygen atom in both dilute and concentrated acid solutions. This kind of interaction underlies acid catalysis in amide hydrolysis reactions:
Unsubstituted and N-substituted amides exhibit weak NH-acid properties , comparable to the acidity of alcohols and remove a proton only in reactions with strong bases.
Acid-base interactions underlie the formation of amides intermolecular associates , the existence of which explains the high melting and boiling temperatures of amides. The existence of two types of associates is possible: linear polymers and cyclic dimers. The predominance of one type or another is determined by the structure of the amide. For example, N-methylacetamide, for which the Z-configuration is preferred, forms a linear associate, and lactams with a rigidly fixed E-configuration form dimers:
N, N-Disubstituted amides form dimers due to the dipole-dipole interaction of 2 polar molecules:
Acylation reactions. Due to the presence of a strong electron-donating amino group in the conjugated amide system, the electrophilicity of the carbonyl carbon atom, and therefore the reactivity of amides in acylation reactions, is very low. Low acylating ability of amides is also explained by the fact that the amide ion NH 2 - is a bad leaving group. Of the acylation reactions, the hydrolysis of amides is important, which can be carried out in acidic and alkaline media. Amides are much more difficult to hydrolyze than other functional derivatives of carboxylic acids. The hydrolysis of amides is carried out under more stringent conditions compared to the hydrolysis of esters.
Acid hydrolysis amides - irreversible reaction leading to the formation of carboxylic acid and ammonium salt:
In most cases, acid hydrolysis of amides proceeds according to the mechanism bimolecular acid acylation A AC 2 , i.e., similar to the mechanism of acid hydrolysis of esters. The irreversibility of the reaction is due to the fact that ammonia or amine in an acidic environment is converted into ammonium ion, which does not have nucleophilic properties:
Alkaline hydrolysis Same irreversible reaction; as a result, a carboxylic acid salt and ammonia or amine are formed:
Alkaline hydrolysis of amides, like the hydrolysis of esters, proceeds according to tetrahedral mechanism IN AC 2 . The reaction begins with the addition of a hydroxide ion (nucleophile) to the electrophilic carbon atom of the amide group. The resulting anion (I) is protonated at the nitrogen atom, and then a good leaving group is formed in the bipolar ion (II) - an ammonia or amine molecule. It is believed that the slow stage is the decomposition of the tetrahedral intermediate (II).
For anilides and other amides with electron-withdrawing substituents at the nitrogen atom, the decomposition of the tetrahedral intermediate (I) can proceed through the formation of a dianion (II):
Nitrous acid digestion. When interacting with nitrous acid and other nitrosating agents, amides are converted into the corresponding carboxylic acids with yields of up to 90%:
Dehydration. Unsubstituted amides under the influence of phosphorus(V) oxide and some other reagents (POC1 3, PC1 5, SOCl 2) are converted into nitriles:
47. Carboxylic acids: halogenation according to Gell-Volhard-Zelinsky, use of the reaction for synthesis a -hydroxy and a -amino acids.
Halogenation of aliphatic carboxylic acids.
Aliphatic carboxylic acids are halogenated to the α-position by chlorine or bromine in the presence of catalytic quantities red phosphorus or phosphorus halides (Gell-Volhard-Zelinsky reaction ). For example, when hexanoic acid is brominated in the presence of red phosphorus or phosphorus(III) chloride, 2-bromohexanoic acid is formed in high yield, for example:
It is not the carboxylic acid itself that undergoes bromination, but the acid chloride formed from it in situ. The acid chloride has stronger CH-acid properties than the carboxylic acid and forms the enol form more easily.
Enol (I) adds bromine to form a halogen derivative (II), which subsequently eliminates hydrogen halide and turns into an α-halogenated acid halide (III). At the last stage, the acid halide of the unsubstituted carboxylic acid is regenerated.
From the resulting α-halogen-substituted acids, other heterofunctional acids are synthesized using nucleophilic substitution reactions.
Esters are typical electrophiles. Due to the +M effect of the oxygen atom associated with the hydrocarbon radical, they exhibit a less pronounced electrophilic character compared to acid halides and acid anhydrides:
The electrophilicity of ethers increases if the hydrocarbon radical forms a conjugated system with the oxygen atom, the so-called. activated esters:
Esters undergo nucleophilic substitution reactions.
1. Hydrolysis of esters occurs in both acidic and alkaline environments.
Acid hydrolysis of esters is a sequence of reversible transformations opposite to the esterification reaction:
The mechanism of this reaction involves protonation of the oxygen atom of the carbonyl group to form a carbocation, which reacts with a water molecule:
Alkaline hydrolysis. Hydrolysis in the presence of aqueous solutions of alkalis is easier than acidic because the hydroxide anion is a more active and less bulky nucleophile than water. Unlike acidic, alkaline hydrolysis is irreversible:
Alkali does not act as a catalyst, but as a reagent. Hydrolysis begins with a nucleophilic attack by the hydroxide ion on the carbon atom of the carbonyl group. An intermediate anion is formed, which splits off the alkoxide ion and turns into a carboxylic acid molecule. The alkoxide ion, as a stronger base, abstracts a proton from the acid molecule and turns into an alcohol molecule:
Alkaline hydrolysis is irreversible because the carboxylate anion has a highly delocalized negative charge and is not susceptible to attack by the alcohol hydroxyl.
Alkaline hydrolysis of esters is often called saponification. The term comes from the name of the products of alkaline hydrolysis of fats - soap.
2. Interaction with ammonia (immonolysis) and its derivatives proceeds by a mechanism similar to alkaline hydrolysis:
3. The transesterification reaction (alcoholysis of esters) is catalyzed by both mineral acids and shells:
To change the equilibrium, the more volatile alcohol is distilled to the right.
4. Claisen ester condensation is characteristic of esters of carboxylic acids containing hydrogen atoms in the α-position. The reaction occurs in the presence of strong bases:
The alkoxide ion abstracts a proton from the α-carbon atom of the ether molecule. A mesomerically stabilized carbanion (I) is formed, which, acting as a nucleophile, attacks the carbon atom of the carbonyl group of the second ether molecule. The addition product (II) is formed. It splits off the alkoxide ion and turns into the final product (III). Thus, the entire scheme of the reaction mechanism can be divided into three stages:
If two esters containing α-hydrogen atoms react, a mixture of four possible products is formed. The reaction is used for the industrial production of acetoacetic ester.
5. Reduction of esters:
Primary alcohols are formed by the action of hydrogen gas in the presence of a skeletal nickel catalyst (Raney nickel).
6. The action of organomagnesium compounds followed by hydrolysis leads to the formation of tertiary alcohols.
The hydrolysis of esters is catalyzed by both acids and bases. Acid hydrolysis of esters is usually carried out by heating with hydrochloric or sulfuric acid in an aqueous or aqueous-alcoholic medium. In organic synthesis, acid hydrolysis of esters is most often used for mono- and dialkyl-substituted malonic esters (Chapter 17). Mono- and disubstituted derivatives of malonic ester, when boiled with concentrated hydrochloric acid, undergo hydrolysis followed by decarboxylation.
For base-catalyzed hydrolysis, an aqueous or aqueous-alcoholic solution of NaOH or KOH is usually used. Best results are achieved by using a thin suspension of potassium hydroxide in DMSO containing a small amount of water.
The latter method is preferred for the saponification of hindered acid esters; another modification of this method is the alkaline hydrolysis of hindered esters in the presence of 18-crown-6-polyester:
For preparative purposes, base-catalyzed hydrolysis has a number of obvious advantages over acid hydrolysis. The rate of basic hydrolysis of esters is usually a thousand times higher than with acid catalysis. Hydrolysis in an acidic environment is a reversible process, in contrast to hydrolysis in the presence of a base, which is irreversible.
18.8.2.A. Mechanisms of ester hydrolysis
Hydrolysis of esters with pure water is in most cases a reversible reaction, leading to an equilibrium mixture of the carboxylic acid and the parent ester:
This reaction is greatly accelerated in acidic and alkaline media, which is associated with acid-base catalysis (Chapter 3).
According to K. Ingold, the mechanisms of ester hydrolysis are classified according to the following criteria:
(1) Type of catalysis: acidic (symbol A) or basic (symbol B);
(2) Type of cleavage, indicating which of the two C-O -bonds in the ester is cleaved as a result of the reaction: acyl oxygen (AC index) or alkyl oxygen (AL index):
(3) Molecularity of the reaction (1 or 2).
From these three criteria, eight different combinations can be made, which are shown in diagram 18.1.
These are the most common mechanisms. Alkaline saponification almost always belongs to type B AC 2. Acid hydrolysis (as well as esterification) in most cases has a mechanism A AC 2.
The A AC 1 mechanism is usually observed only in strongly acidic solutions (for example, in concentrated H 2 SO 4), and especially often for sterically hindered aromatic acid esters.
The mechanism of AC 1 is still unknown.
The B AL 2 mechanism was found only in the case of exceptionally strong spatially shielded acyl groups and neutral hydrolysis of β-lactones. The mechanism of A AL 2 is still unknown.
According to the A AL 1 mechanism, tertiary alkyl esters usually react in a neutral or acidic environment. The same substrates under similar conditions can react according to the B AL 1 mechanism, however, when moving to a slightly more alkaline environment, the B AL 1 mechanism is immediately replaced by the B AC 2 mechanism.
As can be seen from Scheme 18.1, reactions catalyzed by acids are reversible, and from the principle of microscopic reversibility (Chapter 2) it follows that esterification catalyzed by acids also proceeds by similar mechanisms. However, with base catalysis, the equilibrium is shifted towards hydrolysis (saponification), since the equilibrium shifts due to ionization of the carboxylic acid. According to the above scheme, in the case of mechanism A, AC 1 groups COOR and COOH are protonated at the alkoxy or hydroxyl oxygen atom. Generally speaking, from the point of view of thermodynamics, protonation of the carbonyl oxygen, the C=O group, is more favorable, because in this case, the positive charge can be delocalized between both oxygen atoms:
Nevertheless, the solution also contains a tautomeric cation in small quantities - a necessary intermediate in the A AC 1 mechanism. Both B1 mechanisms (of which B AC 1 is unknown) are in fact not catalytic at all, because at the beginning the dissociation of the neutral ester occurs.
Of the eight Ingold mechanisms, only six have been experimentally proven.
Esters are functional derivatives of carboxylic acids with the general formula RC(0)0R."
Methods of obtaining. The most significant way to obtain esters is the acylation of alcohols and phenols with various acylating agents, for example, carboxylic acid, acid chlorides, anhydrides. They can also be obtained by the Tishchenko reaction.
Esters are prepared in high yields by alkylation of carboxylic acid salts with alkyl halides:
Esters are formed by the electrophilic addition of carboxylic acids to alkenes and alkynes. The reaction is often used to produce tertiary alcohol esters, e.g. rubs-butyl ethers:
The addition of acetic acid to acetylene produces an industrially important monomer vinyl acetate, Zinc acetate on activated carbon is used as a catalyst:
Hydrolysis. The most important of the acylation reactions is the hydrolysis of esters with the formation of alcohol and carboxylic acid:
The reaction takes place in both acidic and alkaline environments. Acid-catalyzed hydrolysis of esters - the reverse reaction of esterification, proceeds by the same mechanism Als 2
Alkaline hydrolysis is irreversible; during the reaction, a mole of alkali is consumed per mole of ether, i.e., the alkali in this reaction acts as a consumable reagent and not a catalyst:
Hydrolysis of esters in an alkaline medium proceeds via a bimolecular acyl mechanism VAS2 through the stage of formation of tetrahedral intermediate (I). The irreversibility of alkaline hydrolysis is ensured by the practically irreversible acid-base interaction of carboxylic acid (I) and alkoxide ion (III). The resulting carboxylic acid anion (IV) is itself a fairly strong nucleophile and therefore is not subject to nucleophilic attack.
Transesterification. Using this reaction, the interconversion of esters of the same acid is carried out according to the following scheme:
Transesterification is a reversible process, catalyzed by both acids and bases, and proceeds by the same mechanisms as the reactions of esterification and hydrolysis of esters. The equilibrium is shifted by well-known methods, namely by using an excess of the reagent alcohol (R"OH in the diagram above - for a shift to the right) or by distilling off one of the reaction products if it is the lowest boiling component. By transesterification, for example, a well-known anesthetic is obtained novocaine(base) from l-aminobenzoic acid ethyl ester:
Ester condensation. When two ester molecules condense in the presence of a basic catalyst, β-oxo acid esters are formed:
The ethyl acetate molecule has weak CH-acid properties due to the inductive effect of the ester group and is able to interact with a strong base - the ethoxide ion:
Amides of carboxylic acids. Methods of obtaining. Structure of the amide group. Acid-base properties of amides. Acid and alkaline hydrolysis. Cleavage of amides by halogens in an alkaline medium and nitrous acid. Dehydration to nitriles.
Amides are functional derivatives of carboxylic acids of the general formula R-C(O)-NH2_nR"„, where n = 0-2.
Methods of obtaining. The most important method for preparing amides is the acylation of ammonia and amines with acid halides, anhydrides and esters.
Acylation of ammonia and amines with acid halides. The acylation reaction of ammonia and amines with acid halides is exothermic and is carried out upon cooling:
Acylation of ammonia and amines with anhydrides. For the acetylation of amines, the most accessible anhydride, acetic anhydride, is most often used:
Ammonolysis of esters. Amides are obtained by ammonolysis of esters. For example, when aqueous ammonia reacts with diethyl fumarate, complete fumaric acid amide is formed:
Structure of amides. The electronic structure of the amide group is largely 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 electrons of the C=0 bond. Delocalization of electron density in the amide group can be represented by two resonance structures:
Due to conjugation, the C-N bond in amides is partially double-linked; its length is significantly less than the length of a single bond in amines, while the C=0 bond is slightly longer than the C=0 bond in aldehydes and ketones. The amide group has a flat configuration due to conjugation. Below are the geometric parameters of the iV-substituted amide molecule, determined using X-ray diffraction analysis:
Acid-base properties. Amides have weak acidic and basic properties. The basicity of amides lies within the range of pA"in+ values from -0.3 to -3.5. The reason for the reduced basicity of the amino group in amides is the conjugation of the lone pair of electrons of the nitrogen atom with the carbonyl group. When interacting with strong acids, amides are protonated at the oxygen atom as in dilute and concentrated solutions of acids. This kind of interaction underlies acid catalysis in the hydrolysis reactions of amides:
Acylation reactions. Due to the presence of a strong electron-donating amino group in the conjugated amide system, the electrophilicity of the carbonyl carbon atom, and therefore the reactivity of amides in acylation reactions, is very low. The low acylating ability of amides is also explained by the fact that the amide ion NH2- is a poor leaving group. Among the acylation reactions, the hydrolysis of amides, which can be carried out in acidic and alkaline media, is of practical importance. Amides are much more difficult to hydrolyze than other functional derivatives of carboxylic acids. The hydrolysis of amides is carried out under more stringent conditions compared to the hydrolysis of esters.
Acid hydrolysis of amides is an irreversible reaction leading to the formation of carboxylic acid and ammonium salt:
Alkaline hydrolysis is also an irreversible reaction; as a result, a carboxylic acid salt and ammonia or amine are formed:
Nitrous acid digestion. When interacting with nitrous acid and other nitrosating agents, amides are converted into the corresponding carboxylic acids with yields of up to 90%:
Carbonic acid and its functional derivatives; phosgene, chlorocarbon ethers, carbamic acid and its esters (urethanes). Urea (urea), basic and nucleophilic properties. Hydrolysis of urea. Acylureas (ureids), ureidic acids. Interaction of urea with nitrous acid and hypobromites. Guanidine, basic properties.
Carbonic acid traditionally does not belong to organic compounds, but it itself and its functional derivatives have a certain similarity with carboxylic acids and their derivatives, and therefore are discussed in this chapter.
Dibasic carbonic acid is an unstable compound that easily breaks down into carbon dioxide and water. In an aqueous solution of carbon dioxide, only 0.1% of it exists in the form of carbonic acid. Carbonic acid forms two series of functional derivatives - complete (medium) and incomplete (acidic). Acid esters, amides and other derivatives are unstable and decompose to release carbon dioxide:
Complete carbonic acid chloride - phosgene COC1 2 - is a low-boiling liquid with the smell of rotten hay, very toxic, causes pulmonary edema, and is formed as a harmful impurity during the photochemical oxidation of chloroform as a result of improper storage of the latter.
In industry, phosgene is produced by radical chlorination of carbon (II) monoxide in a reactor filled with activated carbon:
Phosgene, like acid chlorides of carboxylic acids, has a high acylating ability; many other functional derivatives of carbonic acid are obtained from it.
When phosgene reacts with alcohols, two types of esters are formed - complete (carbonates) and partial (carbon chloride esters, or chloroformates), the latter being both esters and acid chlorides. Tertiary amines or pyridine are used as a hydrogen chloride acceptor and a nucleophilic catalyst.
Carbamic acid- incomplete carbonic acid amide - an unstable compound, decomposes to form ammonia and carbon dioxide:
Esters of carbamic acid - carbamates, or urethanes, - stable compounds obtained by adding alcohols to isocyanates or by acylating ammonia and amines with the corresponding chloroformate:
Urea(carbamide) - a complete amide of carbonic acid - was first isolated from urine by I. Ruel (1773). It is the most important end product of protein metabolism in mammals; an adult excretes 25-30 g of urea per day. Urea was first synthesized by F. Wöhler (1828) by heating ammonium cyanate:
This synthesis was the first example of obtaining an organic substance from an inorganic compound.
In industry, urea is produced from ammonia and carbon dioxide at elevated pressure and temperature (180-230 °C, 150-200 atm):
Urea has weak basic properties (p.iHvn + 0.1) and forms salts with strong acids. Salts of nitric and oxalic acids are insoluble in water.
Urea is protonated at the oxygen atom rather than the nitrogen atom. This is probably due to the delocalization of lone pairs of electrons of nitrogen atoms due to p,π conjugation.
In boiling water, urea hydrolyzes to form ammonia and carbon dioxide; acids and bases catalyze this reaction:
The primary products formed when urea is heated are ammonia and isocyanic acid. Isocyanic acid can trimerize to cyanuric acid or condense with a second urea molecule to form biuret. Depending on the heating rate, one or another path of urea decomposition dominates:
The action of hypohalites also leads to the decomposition of urea. Depending on conditions, nitrogen or hydrazine may be formed; This is exactly how the latter is obtained in industry:
Urea also exhibits nucleophilic properties in alkylation and acylation reactions. Alkylation of urea, depending on the alkylating agent, can lead to O- and TV-alkyl derivatives:
Guanidine, or iminourea (H 2 N) 2 C=NH, is produced industrially by fusing urea with ammonium nitrate or by heating orthocarbonic acid esters with ammonia:
Guanidine is a colorless crystalline substance with strong basic properties. High basicity at the level of alkali metal hydroxides is due to the complete delocalization of the positive charge in the symmetrical guanidinium cation:
Guanidine and biguanidine residues are found in some natural compounds and medicinal substances.