Chloroacetaldehyde

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.

Synthesis and occurrence
Hydrated chloroacetaldehyde is produced by the chlorination of aqueous vinyl chloride:
 * ClCH=CH2 +  Cl2  +  H2O   →   ClCH2CHO  +  2 HCl

It can also be prepared from vinyl acetate or by careful chlorination of acetaldehyde. The related bromoacetaldehyde is prepared via bromination of vinyl acetate. It also rapidly forms an acetals in the presence of alcohols.

Water free chloroacetaldehyde is prepared from the hydrate by azeotropic distillation with chloroform, toluene, or carbon tetrachloride. Anhydrous chloroacetaldehyde reversibly converts to polyacetals. 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 instead of polymerizing.

Relevant to its occurrence in humans, it arises via the isomerization of chloroethylene oxide, a metabolite of vinyl chloride.

Reactions
Chloroacetaldehyde readily hydrates:
 * Chloroacetaldehyde reaction01.svg

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. Chloroacetaldehyde is a building block in the synthesis of the pharmaceuticals altizide, polythiazide, brotizolam, and ciclotizolam. 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.

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.

Safety
Chloroacetaldehyde is corrosive to mucous membranes. It irritates eyes, skin and respiratory tract.

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. The Occupational Safety and Health Administration established a permissible exposure limit at a ceiling of 1 ppm (3 mg/m3) for exposures to chloroacetaldehyde.