Nitric acid and its derivatives.

Carboxylic acid and its derivatives

Carboxylic acid (RCOOH) is the most important class of organic acids. It can be regarded as a compound formed by replacing the hydrogen atom in a hydrocarbon molecule with a carboxyl group (or written as -COOH) , which is a functional group of carboxylic acid. Carboxylic acid can undergo many chemical reactions. When the hydroxyl group in the carboxyl group is replaced by other atomic groups, carboxylic acid derivatives are formed, mainly carboxylic acid esters, acid halides, acid anhydrides and amides.

Section One Carboxylic Acid

In nature, carboxylic acids are often found in free state or in the form of salts or esters in animals and plants, and are a class of compounds closely related to medicine.

1. Classification and naming of carboxylic acids

According to the different structure of hydrocarbon groups, carboxylic acids can be divided into aliphatic carboxylic acids (saturated and unsaturated), alicyclic carboxylic acids and aromatic carboxylic acids. According to the number of carboxyl groups contained in the carboxylic acid molecule, it can be divided into monobasic acid and polybasic acid. Chain monocarboxylic acids (including saturated and unsaturated) are commonly called fatty acids. The classification of carboxylic acids is shown in Table 16-1.

Table 16-1 Classification of carboxylic acids

　　Many carboxylic acids can be obtained from natural products, so they often have common names based on their original source, such as formic acid, acetic acid, and oxalic acid. The systematic nomenclature of carboxylic acids is similar to that of aldehydes. The naming of saturated fatty acids is based on the longest carbon chain including the carboxyl carbon atoms as the main chain. It is called an acid according to the number of main chain carbon atoms, and the numbering starts from the carboxyl carbon atom. E.g:

　　When naming unsaturated fatty acids, the main chain should be the longest carbon chain including the carboxyl carbon atom and the carbon atoms of the multiple carbon-carbon multiple bonds. The numbering starts from the carboxyl carbon atom and the position of the multiple bond is indicated. E.g:

　　The name of the dibasic acid is based on the longest carbon chain including two carboxyl carbon atoms as the main chain, and is called "a certain diacid" according to the number of carbon atoms in the main chain. E.g;

When naming the carboxylic acid whose carboxyl group is directly attached to the alicyclic ring, the suffix "carboxylic acid or dicarboxylic acid" can be added after the name of the alicyclic hydrocarbon; the carboxylic acid whose carboxyl group is on the alicyclic ring is named after the alicyclic hydrocarbon name Linked with the name of the fatty acid. In addition, whether the carboxyl group is directly attached to the alicyclic ring or attached to the side chain of the alicyclic ring, the alicyclic ring can be named as a substituent. E.g;

Aromatic acids can be named as aromatic substituents of fatty acids. E.g:

　　2. The physical properties of carboxylic acid

　　Lower saturated fatty acids (formic acid, acetic acid, propionic acid) are liquids with a strong pungent odor; intermediate (C4-C9) carboxylic acids are oily liquids with unpleasant odors; C10 and above carboxylic acids are odorless oily solids , Very low volatility, both aliphatic dicarboxylic acid and aromatic carboxylic acid are solid.

　　Lower fatty acids are easily soluble in water, but as the relative molecular weight increases, the solubility in water decreases, and is even insoluble or insoluble in water, but soluble in organic solvents.

　　The boiling point of carboxylic acids is higher than that of alcohols with similar molecular weights. For example, the relative molecular masses of formic acid and ethanol are the same, but the boiling point of ethanol is 78.5°C, while that of formic acid is 100.5°C. This is because carboxylic acid molecules can associate with hydrogen bonds to form dimers, and this hydrogen bond between carboxylic acid molecules is more stable than that between alcohol molecules. For example, the hydrogen bond energy between ethanol molecules is 25.94kJ·mol ^-1 , and the hydrogen bond energy between formic acid molecules is 30.12kJ·mol ^-1 . Even in the gaseous state, the lower carboxylic acid exists in the form of a di-associative body.

The melting point of saturated fatty acids changes in a zigzag shape with the increase of the number of carbon atoms in the molecule (Figure 16-1). The melting point of a carboxylic acid with an even number of carbon atoms is higher than the melting point of two adjacent carboxylic acid molecules with an odd number of carbon atoms. This may be due to the fact that even-numbered carbon carboxylic acid molecules are more symmetrical and arranged more closely in the crystal. The physical constants and pKa values &ZeroWidthSpace&ZeroWidthSpaceof some carboxylic acids are shown in Table 16-2.

Table 16-2 The physical constants and pKa of some carboxylic acids

　　Three, the chemical properties of carboxylic acid

　　Carboxylic acid is composed of carboxyl group and hydrocarbyl group. The carboxyl group includes two parts, carbonyl group and hydroxyl group, and thus reflects certain properties of carbonyl group and hydroxyl group to varying degrees. However, the nature of the carboxyl group is not a simple addition of the two groups. Due to the mutual influence of the carbonyl group and the hydroxyl group, it exhibits many new properties.

　　The C=O bond length in formic acid was determined by physical method to be 0.1245nm, which is slightly longer than the bond length of ordinary carbonyl group (0.122nm); the carbon-oxygen bond length in C-OH bond is 0.131nm, which is longer than the bond length in alcohol ( 0.143nm) is much shorter. This indicates that the carbonyl group and the hydroxyl group in the carboxylic acid interact with each other.

　　In a carboxylic acid molecule, one of the three sp2 hybrid orbitals of the carbon atom of the carbonyl group forms a bond with oxygen, one forms a bond with hydroxyl oxygen, and the other forms a bond with hydrogen or a hydrocarbon group. These three orbitals are on a plane with a bond angle of about 120°; a p orbital on the carbon atom that is not involved in the hybridization and the p orbital of the oxygen atom form a π bond. However, the -OH oxygen in the carboxyl group has a pair of unshared electrons, which can form a p-π conjugated system with the π bond.

　　In this way, on the one hand, the atomic group loses the typical carbonyl properties, on the other hand the electron cloud of -OH oxygen atom moves to the carbonyl group, and the electron cloud density of oxygen decreases, which is conducive to the dissociation of hydrogen. Therefore, the acidity of carboxylic acid is stronger than that of alcohol. .

　　The X-ray measurement of formate ion shows that the bond length of its two carbon-oxygen bonds is 0.127 nm. This shows that after hydrogen leaves the carboxyl group in the form of protons, the p-π conjugation is more complete, and the bond is evened. In this way, the negative charge on -COO- is no longer concentrated on one oxygen atom, but is evenly distributed on two oxygens, so the carboxylate ion is more stable.

According to the structure of carboxylic acid, it can react as follows.

　　(1) Acidity

　　Carboxylic acid can dissociate protons in water and become acidic, and its pKa value is generally 4-5, which is a weak acid.

Although the acidity of carboxylic acid is much weaker than mineral acids such as hydrochloric acid and sulfuric acid, it is stronger than carbonic acid (pKa=6.35) and general phenols (pKa-10). Therefore, carboxylic acid can decompose carbonate and bicarbonate to release carbon dioxide.

　　2RCOOH+Na ₂ CO ₃ →2RCOONa+CO ₂ ↑+H ₂ o

RCOOH+NaHCO ₃ →RCOONa+CO ₂ ↑+H ₂ o

The reaction of carboxylic acid and sodium bicarbonate can distinguish carboxylic acid from phenols. Since carboxylic acids are soluble in sodium bicarbonate solution and emit carbon dioxide, general phenols and sodium bicarbonate have no effect.

　　The potassium, sodium and ammonium salts of low- and intermediate-grade carboxylic acids are soluble in water, so some carboxyl-containing drugs are made into carboxylates to increase their solubility in water, which is convenient for making liquids or injections.

　　In the carboxylic acid (RCOOH) molecule, the atomic group directly or indirectly connected to the carboxyl group has varying degrees of influence on the acidity of the carboxylic acid (Table 16-3).

Table 16-3 The ionization constants of some carboxylic acids

Among fatty acids, the alkyl group connected to the carboxyl group has a power induction effect (+I), which makes the hydrogen on the carboxyl group more difficult to dissociate, and the acidity is weaker than that of formic acid (1 and 2 in Table 16-3). When the halogen replaces the hydrogen on the hydrocarbon group in the carboxylic acid molecule, the acidity increases due to the electron withdrawing effect (-I) of the halogen atom (3, 6, 7, 8 in Table 16-3). The more the number of halogen atoms introduced on a carbon of the hydrocarbon group, the stronger the acidity (3, 4, 5 and 8, 9 in Table 16-3). When the halogen atoms are the same, the closer the halogen atom is to the carboxyl group, the stronger the acidity. (11, 12, 13 in Table 16-3). When the types of halogen atoms are different, their influence on acidity is F>CL>Br>I. Therefore, the acidity of fluoroacetic acid>chloroacetic acid>bromoacetic acid>iodoacetic acid (3, 6, 7, 8 in Table 16-3).

　　(2) The reaction in which the hydroxyl group is substituted

　　The hydroxyl group in the carboxylic acid can be substituted by other atoms or groups of atoms to form carboxylic acid derivatives. E.g:

　　After removing the hydroxyl group on the carboxyl group in the carboxylic acid molecule, the remaining atomic group is called the acyl group.

　　1. Esterification reaction

　　The reaction of acid and alcohol dehydration to form ester is called esterification.

The esterification reaction of carboxylic acid and alcohol is reversible, and the reaction rate is very slow, requiring acid as a catalyst. E.g:

　　2. Formation of acyl halide

　　Carboxylic acid (except formic acid) can react with phosphorus trihalide, phosphorus pentahalide or thionyl chloride (SOCL2), and the hydroxyl group in the carboxyl group is replaced by halogen to form the corresponding acid halide.

E.g:

When SOCL2 is used to prepare acid halides, the by-products are all gases, which is convenient for processing and purification.

　　3. Formation of acid anhydride

　　Except for formic acid, when monocarboxylic acid and dehydrating agent are heated together, two molecules of carboxylic acid can remove one molecule of water to form acid anhydride.

4. Formation of amide

　　Ammonia gas or ammonium carbonate is added to the carboxylic acid to obtain the ammonium salt of the carboxylic acid. When the solid ammonium carboxylate is heated , one molecule of water is lost in the molecule to form an amide.

　　(3) Decarboxylation reaction and heating reaction of dicarboxylic acid

　　The decarboxylation reaction of carboxylic acid is called decarboxylation. The result of this reaction is the removal of CO2 from the carboxyl group.

Except for formic acid, monocarboxylic acids are relatively stable and difficult to decarboxylate when heated directly. It can only occur under special conditions and generate hydrocarbons with one less carbon. E.g:

Many important decarboxylation reactions in organisms are carried out under the action of decarboxylase.

　　Some dibasic acids are not stable to heat. Under heating or co-heating with dehydrating agent, decarboxylation reaction or dehydration reaction occurs with the difference of the distance between two carboxyl groups. This is the characteristic of dicarboxylic acid.

　　1. Oxalic acid and malonic acid

　　Oxalic acid or malonic acid is heated to decarboxylate to generate monocarboxylic acid.

2. Succinic acid, glutaric acid and phthalic acid

　　These three acids lose water when heated together with the dehydrating agent and generate cyclic anhydrides.

3. Adipic acid

　　When adipic acid, pimelic acid and barium hydroxide are heated together, they both lose water and decarboxylate, forming cyclic ketones.

　　(4) Halogenation of α-H

　　Similar to the carbonyl group, the carboxyl group can also activate α-H, but its activating effect is much smaller than that of the carbonyl group. Therefore, the reaction of α-H in carboxylic acid being substituted by halogen is slow, and it is easy to proceed only by adding red phosphorus, sulfur or iodine as a catalyst or under light.

　　Four, important carboxylic acids

　　(1) Formic acid

　　Formic acid was originally found in red ants, so it is commonly known as formic acid. It is a colorless and irritating liquid with a boiling point of 100.5°C and is easily soluble in water. Formic acid is very corrosive and can make skin foam.

　　The structure of formic acid is special. The carboxyl group in the molecule is connected to the hydrogen atom. It has both a carboxyl group structure and an aldehyde group structure. Therefore, it is acidic and reductive, and can cause silver mirror reaction or fade the potassium permanganate solution.

　　(2) Acetic acid

　　The common name of acetic acid is acetic acid, which is the main component of vinegar. Acetic acid is a colorless liquid with a pungent odor, with a melting point of 16.6°C and a boiling point of 118°C. Since acetic acid can condense into an ice-like solid below 16.6°C, anhydrous acetic acid is often referred to as glacial acetic acid. Acetic acid is easily soluble in water, but also soluble in many organic substances. Acetic acid is also an important industrial raw material.

　　(Three) oxalic acid

　　The common name of oxalic acid is oxalic acid, and it often exists in the form of salt in most plants, especially herbs. Oxalic acid is a colorless crystal. Common oxalic acid contains two molecules of crystal water. Anhydrous oxalic acid has a melting point of 189°C. When heated to above 150°C, it will begin to decompose to form formic acid and carbon dioxide. Formic acid then decomposes into carbon monoxide and water.

Oxalic acid has reducing properties and is commonly used in analytical chemistry to calibrate the concentration of KMnO ₄ solution.

　　(4) Benzoic acid

　　The common name of benzoic acid is benzoic acid. The ester formed by it and alcohol exists in natural resin and

　　Inside the benzoin gum. Benzoic acid is a white solid with a melting point of 121°C, slightly soluble in water, and easy to sublimate when heated. Benzoic acid has antibacterial and antiseptic effects. It can be used as a preservative and also for external use.