Acylation reaction, also known as (acylation reaction), is a reaction in organic chemistry in which hydrogen or other groups are replaced by acyl groups, and the compound that provides the acyl group is called an acylating agent. The acylation reaction can be expressed by the following general formula: RCOZ+SH → RCOS+HZ. In the general formula, RCOZ is the acylating agent, Z represents OCOR, OH, ORˊ, etc.; SH is the acylate, and S represents RO, R″NH, Ar, etc. .

reaction mechanism

1. The mechanism of O-acylation, N-acylation, and C-acylation at the α position of the carbonyl group is a nucleophilic process;

2. The mechanism of C-acylation of aromatics and C-acylation of alkenes is an electrophilic process.

Acylation reaction on oxygen atom

Definition: The acylation reaction on the oxygen atom refers to the reaction in which the hydroxyl hydrogen atom in the alcohol or phenol molecule is replaced by an acyl group to form an ester, so it is also called esterification reaction.
Rule: The ease of the reaction depends on the nucleophilicity, steric hindrance and activity of the acylating agent of the alcohol or phenol.
(1) The general rule for O-acylation of alcohols is that primary alcohols are easier to react, followed by secondary alcohols, and tertiary alcohols are the most difficult to acylate.
(2) Although benzyl alcohol and allyl alcohol among primary alcohols are not tertiary alcohols, they also show similar properties to tertiary alcohols because they are easy to dehydroxylate to form stable carbocations.
(3) The nucleophilicity of the hydroxyl oxygen atom of the phenolic hydroxyl group is reduced due to the influence of aromatic hydrocarbons, and its acylation is more difficult than that of alcohol.
Acylating agent: Commonly used acylating agents for O-acylation of alcohols and phenols include carboxylic acids, carboxylic acid esters, acid anhydrides, acid chlorides, ketenes, etc.
Carboxylic acid as acylating agent
Since carboxylic acid is a weak acylating reagent, its acylation of alcohol is a reversible equilibrium reaction. The reaction formula is as follows:
The reaction mechanism is generally a bimolecular reaction of acyl oxygen cleavage under acid catalysis.

catalyst

For many esterification reactions, the reaction rate can double for every 10°C increase in temperature.
High-boiling point alcohols and high-boiling point acids usually require the addition of catalysts and reaction at higher temperatures.
(1) Protonic acids mainly include inorganic acids such as concentrated sulfuric acid, perchloric acid, tetrafluoroboric acid, and hydrogen chloride gas, and organic acids such as benzenesulfonic acid and p-toluenesulfonic acid.
① Concentrated sulfuric acid is the most widely used due to its good catalytic activity and water absorption.
②For some alcohols that are sensitive to inorganic acids, organic acids such as benzenesulfonic acid and p-toluenesulfonic acid can be used as catalysts. For example, in the following two reactions, alcohol molecules contain acid-sensitive chemical bonds and functional groups, so benzenesulfonic acid and p-toluenesulfonic acid can be used as catalysts, of which (8) is the central stimulant drug Meclofenoxate. The biggest advantage of protonic acid catalysis is simplicity, but it is easy to dehydrate acids and tertiary alcohols with large steric hindrance.
(2) Lewis acid commonly used Lewis acid catalysts include boron trifluoride (BF3), aluminum trichloride (AlCl3), zinc dichloride (ZnCl2) and silica gel. Lewis acid as a catalyst has the advantages of high yield, good product purity, and can avoid the decomposition or rearrangement of double bonds and side reactions. like:
(3) Strong acidic ion exchange resin. Since strong acidic ion exchange resin can dissociate H+, it can be used as a catalyst for esterification reaction. The main advantages of using ion exchange resin as a catalyst are: fast reaction speed, mild reaction conditions, good selectivity, and high yield; simple product post-processing, no need for neutralization and water washing; the resin can be recycled and can be produced continuously; The equipment has no corrosion and less waste water is discharged.
For example, in the preparation of methyl acetate, in the presence of ion exchange resin and calcium sulfate desiccant, the reaction only takes 10 minutes, and the yield can reach 94%. After the preparation of benzyl acetate was changed from the original sulfuric acid catalysis to the ion exchange resin catalysis, the yield and other aspects have also been greatly improved. Commonly used ion exchange resins are sulfonic acid type (R—SO3H) macroporous (such as D72, D61) resins.
(4) Dicyclohexylcarbodiimide (DCC) and its analogs are dehydrating agents
DCC (Dicyclohexylcarbodiimide,9) is a good acylating dehydrating agent. It is carried out under the catalysis of excess acid or organic base. First, it reacts with carboxylic acid to produce intermediate (10) with greater acylation activity and acid anhydride. Intermediate (10) and acid anhydride react with alcohol to form ester. The process is as follows:
Similar to DCC are the following compounds: N,N'-diisopropylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, molecular sieves, etc.