2.8: Acid Halides for Ester Synthesis

Please Note: The terms "acid halide" and "acyl halide" are synonymous and are both used in this text. In biochemistry, the term "acyl" is used more frequently.

Acid Halides

An acyl halide (also known as an acid halide) is a chemical compound derived from a carboxylic acid by replacing a hydroxyl group with a halogen:

The general formula for such an acyl halide can be written RCOX, where R may be, for example, an alkyl group, CO is the carbonyl group, and X represents the halide, such as chloride.

Acid Halide Synthesis

Carboxylic acids react with thionyl chloride (SOCl₂) or oxalyl chloride (C₂O₂Cl₂) to form acid chlorides. Typically the reactions occur in the presence of a proton scavanger like pyridine to minimize unwanted side reactions. During the reaction the hydroxyl group of the carboxylic acid is converted to a chlorosulfite intermediate making it a better leaving group. The chloride anion produced during the reaction acts a nucleophile.

Analogous to the reactions of primary and secondary alcohols with PBr₃ to produce the corresponding alkyl bromide, acid bromides can be formed from the reaction of phosphorous tribromide with carboxylic acids.

 

Ester Synthesis from Acyl Chlorides

 

Acid chlorides react with alcohols for form esters are shown in the reaction below. The benefit of using acyl chlorides instead of carboxylic acid is that the reaction becomes irreversible. 

The synthesis of ethyl benzoate from benzoyl chloride and ethanol is shown as an example.

Example: Ester Synthesis from Acid Chlorides

Acid Halide Hydrolysis

Acid halides are quite reactive and therefore very unstable. They react with water (even moisture) in a hydrolysis reaction as shown below:

The hydrolysis of butonyl chloride is shown below as an example.

 

Example: Acyl Chloride Hydrolysis

Because of this reaction, it is very important to work with glassware that has been dried, and also solvents that are free from moisture. Volatile acyl halides are lachrymatory because they can react with water at the surface of the eye producing hydrohalic and organic acids irritating to the eye. Similar problems can result if one inhales acyl halide vapors. 

Contributors and Attributions

• Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)

• Prof. Steven Farmer (Sonoma State University)

• Acid Halide Chemistry. (2020, May 30). Retrieved May 22, 2021, from https://chem.libretexts.org/@go/page/45951
• Wikipedia contributors. (2021, April 28). Acyl halide. In Wikipedia, The Free Encyclopedia. Retrieved 22:06, May 22, 2021, from https://en.wikipedia.org/w/index.php?title=Acyl_halide&oldid=1020318981