Chloroacetaldehyde is an organic compound with the formula ClCH2CHO. Like some related compounds, it is highly electrophilic reagent and a potentially dangerous alkylating agent. The compound is not normally encountered in the anhydrous form, but rather as the hemiacetal (ClCH2CH(OH))2O.
Chloroacetaldehyde is a metabolite of the antineoplastic ifosfamide and believed to be responsible for some of the toxicity observed with ifosfamide.
It can also be prepared from vinyl acetate[5] or by careful chlorination of acetaldehyde.[1] The related bromoacetaldehyde is prepared via bromination of vinyl acetate. It also rapidly forms an acetals in the presence of alcohols.[6]
Water free chloroacetaldehyde is prepared from the hydrate by azeotropic distillation with chloroform, toluene, or carbon tetrachloride. Anhydrous chloroacetaldehyde reversibly converts to polyacetals.[7][1] Less reactive chloroacetaldehyde derivatives might be used instead to obtain chloroacetaldehyde or bypass its intermediate formation completely: e.g. chloroacetaldehyde dimethyl acetal (2-chloro-1,1-dimethoxyethane) hydrolyzes in acidic conditions to give chloroacetaldehyde, which may then quickly react with the other reagents[7] instead of polymerizing.
Being bifunctional, chloroacetaldehyde is a precursor to many heterocyclic compounds. It condenses with thiourea derivatives to give aminothiazoles. This reaction was once used in the preparation of sulfathiazole, one of the first sulfa drugs.[5] Chloroacetaldehyde is a building block in the synthesis of the pharmaceuticals altizide, polythiazide, brotizolam, and ciclotizolam.[7] Chloroacetaldehyde is an alkylating agent. It reacts with adenosine and cytidine to give cyclic products containing a fused imidazole group. This reaction is related to the possible mutagenic properties of chloroacetaldehyde.[9]
Environmental aspects
Chloroacetaldehyde is a metabolite in the degradation of 1,2-dichloroethane, which initially converts to chloroethanol. This metabolic pathway is topical because 1,2-dichloroethane is produced on a large scale as a precursor to vinyl chloride.[10]
Safety
Chloroacetaldehyde is corrosive to mucous membranes. It irritates eyes, skin and respiratory tract.[1]
Based on data collected from human studies in 1962, exposures to 45 ppm of chloroacetaldehyde were found to be disagreeable and caused conjunctival irritation to the subjects.[11] The Occupational Safety and Health Administration established a permissible exposure limit at a ceiling of 1 ppm (3mg/m3) for exposures to chloroacetaldehyde.[12]
↑S. M. McElvain and D. Kundiger "Bromoacetal" Organic Syntheses 1943, volume 23, p. 8. doi:10.15227/orgsyn.023.0008.
123Keiji, T (1992-10-30). "α-Chlorocarbonyl Compounds: Their Synthesis and Applications (Commemoration Issue Dedicated to Professor Shigeo Tanimoto On the Occasion of His Retirement)". Bulletin of the Institute for Chemical Research, Kyoto University. 70 (3): 341. hdl:2433/77455. ISSN0023-6071.
↑Singer, B. (1996). "DNA Damage: Chemistry, Repair, and Mutagenic Potential". Regulatory Toxicology and Pharmacology. 23 (1 Pt 1): 2–13. doi:10.1006/rtph.1996.0002. PMID8628915.
↑Janssen, D. B.; van der Ploeg, J. R. and Pries, F., "Genetics and Biochemistry of 1,2-Dichloroethane Degradation", Biodegradation, 1994, 5, 249-57.doi:10.1007/BF00696463
