Acetylation

Acetylation Meaning

The process where an acetyl group gets added to a compound because of its replacement with that of an active Hydrogen atom is called acetylation. Here, the acetyl group consisting of carbonyl atoms or a carbon atom bonded in double pairs with oxygen, as well as a CH₃ or methyl group on end, gets attached to yield CH₃CO is often represented as 'R.' 


Such a reaction takes place because of a good leaving group (R) and a needy nucleophile (NP) having extra electrons, to form acetate. The chemical representation of the acetylation reaction is: 


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In the above reaction, we can see the hydrogen atom from the alcohol group undergoes replacement from the acetyl group to form an ester. 


What Is Acetylation?

There can be many examples of strong acetylation reactions that can enhance the general understanding of the acetylation. For example: In the acetylation of glucose, the simple bonding between the acetyl group with the extra electrons present in nucleophilic Oxygen, helps in easy substitution of the Hydrogen Atoms present in the phenol group.


Since the acetyl group would require a robust leaving group to undergo acetylation, it would need a strong acetylating agent such as acetic anhydride to undergo successful acetylation. Used across multiple synthesis procedures like that of aspirin, proteins, and other useful medicinal purposes, the acetylation process widely occurs in nature and artificially in laboratories. 


One such example of the acetylation of salicylic acid is mentioned below: 


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Mechanism of Acetylation of Salicylic Acid

In the above example, you can see how acetylation takes place in salicylic acid in an acidic medium. Let's have a closer look.


The acetylation of salicylic acid gets facilitated because of the presence of a few drops of concentrated sulfuric acid, that enables the detachment process of the acetate ion present in the agent acetic anhydride. Once the acetate ion establishes a stable bond with that of the nucleophilic oxygen atom (because of its free electrons) present in the salicylic acid, it undergoes dehydrogenation (the process of removal of a Hydrogen atom) in the process to yield acetic acid and aspirin. 


Acetylation with Acetic Acid

Another smooth and strong acetylation reaction of alcohols and phenols would be the use of zirconium oxide and boron as a catalyst. The process of acetylation occurs when the alcohols are introduced to acetic acid, at high temperature, with toluene as a solvent, generating an acetylated compound that takes heavily from the strength of borated zirconia. 


The chemical process involved is: 


ROH (CH₃COOH as a catalyst) (Toluene, 110℃) ➝ CH₃COOR + H₂O


Acetylation of Amines

There are several methods that allow acetylation of amines with the usage of several amines using catalytic acetic acid, ethyl/butyl acetate for the acylating agent. Used generally in the formation of formamides at lower room temperatures (20°C), the chemical reaction involved in the process of synthesis for broad-spectrum amines is: 


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There are several other examples of acetylation reactions, including:


N-acetylation of amines from N,N-dimethylacetamide


Dimethylacetamide can act as an efficient storehouse for the synthesis of acetyl and dimethylamine gas. It can deliver easy acetylation of several amines when treated at 120-125°C and can serve as an alternative to the rest of the acetylation equations. The reaction would look like: 


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N - Alpha - Acetyltransferases

These intermediate compounds enable mediation in a variety of acetylation reactions. Named after the standard variables used in the transfer of molecules, these compounds are known to occur inside cells for regulation protein formation.


The Histone Acetylation and Deacetylation

Here the proteins that copy the DNA to heal the damaged genetic material need to be engineered via acetylation, which helps in understanding the energy and accuracy of the copying of genes. Used in lysine and other gene regulation activities, these chemical reactions may include removing acetyl groups from an equation. 


What Kind of a Reaction is Acetylation?

These reactions fall under the ethanoylation under the IUPAC standards and regulations. It often comprises introducing an acetyl functional group in an acidic base to undergo replacement of the hydroxyl group. The opposite chemical reaction that results in the complete removal of the acetyl group in an equation, otherwise called as deacetylation, also comes under the same IUPAC nomenclature. These are instrumental in drug biotransformation that involves the ways the body processes and excretes drugs, with the help of acetylation reaction. It can also be helpful to conduct acetyltransferases for the treatment of any cancer or other autoimmune diseases.

FAQ (Frequently Asked Questions)

Q1. What is the Difference Between Acetylation and Methylation?

In acetylation, the addition of the acetyl group to any nucleophilic hydroxyl group takes place; however, in methylation, the addition of a methyl group to another molecule occurs like that of DNA protein synthesis. Since both, the groups contain different amounts of Carbon atoms in them that undergo the replacement. Therefore it affects the overall charge of the molecule and thus changes its affinity, size, and shape, among other properties, crucial to take part in the intermediate chemical reactions.

Q2. What Type of Amino Acids Undergo Acetylation?

The proteins with a higher concentration of serine and alanine termini are among the amino acids that undergo easy acetylation in several scenarios. These proteins generally occur in nature or can be artificially synthesized in laboratories that get involved in the process of lysine generation and its functionalities. Acetylation is found frequently in several eukaryotic proteins and regulatory peptides like that of α-tubulin, threonine, and other lysine residues.