In organic chemistry, an acyl halide (also known as an acid halide) is a chemical compound derived from an oxoacid by replacing a hydroxyl group (−OH) with a halide group (−X, where X is a halogen).
If the acid is a carboxylic acid (−C(=O)OH), the compound contains a −C(=O)X functional group, which consists of a carbonyl group (C=O) singly bonded to a halogen atom. 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. Acyl chlorides are the most commonly encountered acyl halides, but acetyl iodide is the one produced (transiently) on the largest scale. Billions of kilograms of acyl halides, mostly acyl chloride, are generated annually in the production of acetic acid as a by-product. Acyl halides have a wide range of uses, having significant applications in organic synthesis, pharmaceuticals, and materials science. [1] Due to this, they are readily made in many different forms and the functional group is present in many molecules.
Reactions edit
Acyl halides are rather reactive compounds often synthesized to be used as intermediates in the synthesis of other organic compounds. For example, an acyl halide can react with:
- water, to form a carboxylic acid. This hydrolysis is the most heavily exploited reaction for acyl halides as it occurs in the industrial synthesis of acetic acid. [1]
- an alcohol to form an ester. This reaction is mainly used in industry to make fragrances, flavours, plastics, and can be done on a large scale due to the reactivity of acyl halides. [1]
- an amine to form an amide. This reaction is called amidation and is used in the pharmaceutical industry due to the importance of amides in the synthesis of pharmaceuticals.
- an aromatic compound, using a Lewis acid catalyst such as AlCl3, to form an aromatic ketone.[2] This is one of the most common reactions involving acyl halides. See Friedel-Crafts acylation.
- carboxylic acids to form an organic acid anhydrides. This reaction is used in biochemistry due to the importance of anhydrides in the synthesis of peptides and other biomolecules. [1]
In the above reactions, HX (hydrogen halide or hydrohalic acid) is also formed. For example, if the acyl halide is an acyl chloride, HCl (hydrogen chloride or hydrochloric acid) is also formed.[3]
Acyl halides can also react with:
- Gilman reagents to form a ketone.[3] The Gilman reagent undergoes a coupling reaction with the acyl halide, this results in the formation of a C-C bond between the central carbon in the acyl halide and the R group in the reagent. This results in the formation of a ketone and the organocuprate with the halogen attached to it. [4]
- Grignard reagents to form an ketone intermediate then an alcohol[3] Grignard reagents undergo a coupling reaction with the acyl halide, similar to that of the Gilman reagents. One equivalent of the reagent will result in the formation of a ketone, and another equivalent will result in a tertiary alcohol.
- Lithium aluminum hydride (LAH) to form an aldehyde then a primary alcohol.[3] The reaction between LAH and the acyl halide is an SN1 reaction, where the hydrogen on LAH attacks the the central carbon while lithium acts as a catalyst by pulling electrons away from the carbon. 1 equivalent of LAH results in the formation of an aldehyde, and a second equivalent results in the formation of a primary alcohol.
Acyl halides can also polymerize with itself. This results in the formation of high molecular weight polymers like polyesters, polycarbonates, and polyamides. This is important in the production of plastics and fibres. [1]
General hazards edit
Volatile acyl halides cause tears to form, this is because they can react with water at the surface of the eye producing hydrogen halides, a strong acid, and organic acids which cause eye irritation. Similar problems can result if one inhales acyl halide vapors. Acyl halides are corrosive, can cause severe burns to the skin and severely damage the eyes. This is because the acyl group is replaced with another functional group, listed above in reactions. The process through which this happens is known as nucleophilic acyl substitution. This reaction releases flammable, acidic hydrogen halide gas. In general, acyl halides (even non-volatile compounds such as tosyl chloride) are irritants to the eyes, skin and mucous membranes.
References edit
- ^ a b c d e "What is the physical property of Acid Halides and their significance? by lobachemie2021 - Issuu". issuu.com. 2023-03-13. Retrieved 2024-04-15.
- ^ Allen, C. F. H.; Barker, W. E. (1932). "Desoxybenzoin". Organic Syntheses. 12: 16. doi:10.15227/orgsyn.012.0016.
- ^ a b c d "21.4: Chemistry of Acid Halides". Chemistry LibreTexts. 2015-08-26. Retrieved 2024-04-15.
- ^ "what kind of reaction does a gilman reagent undergo - Google Search". www.google.com. Retrieved 2024-04-15.