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 A substance is anhydrous if it contains no water. Many processes in chemistry can be impeded by the presence of water; therefore, it is important that water-free reagents and techniques are used. In practice, however, it is very difficult to achie ...

form, but rather as the hemiacetal (ClCH₂CH(OH))₂O. Chloroacetaldehyde is a useful intermediate in the synthesis of 2-aminothiazole including the pharmaceuticals

altizide Altizide is a thiazide diuretic. In combination with spironolactone it is sold under the brand name of ''Aldactacine'' and ''Aldactazine'' by Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation ...

, polythiazide,

brotizolam Brotizolam (marketed under brand name Lendormin) is a sedative-hypnotic thienotriazolodiazepine drug which is a benzodiazepine analog. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties, and is con ...

and

ciclotizolam CiclotizolamDE Patent 2445430 (WE-973) is a drug which is a thienotriazolodiazepine derivative. It is a partial agonist for the benzodiazepine site of the GABAA receptor, with similar binding affinity In biochemistry and pharmacology, a li ...

. Another use is to facilitate bark removal from tree trunks. Chloroacetaldehyde is a metabolite of the antineoplastic ifosfamide and believed to be responsible for some of the toxicity observed with ifosfamide.

Synthesis and reactions

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 Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the mos ...

. The related bromoacetaldehyde is prepared via bromination of vinyl acetate. It also rapidly forms an acetals in the presence of alcohols. Being bifunctional, chloroacetaldehyde is a versatile precursor to many

heterocyclic compound A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

s. It condenses with thiourea derivatives to give aminothiazoles. This reaction was important as a precursor to

sulfathiazole Sulfathiazole is an organosulfur compound used as a short-acting sulfa drug. Formerly, it was a common oral and topical antimicrobial, until less toxic alternatives were discovered. Sulfathiazole exists in various forms ( polymorphs). The imine ...

, one of the first sulfa drugs.

Anhydrous

Water free chloroacetaldehyde is prepared from the hydrate by azeotropic distillation with

chloroform Chloroform, or trichloromethane, is an organic compound with chemical formula, formula Carbon, CHydrogen, HChlorine, Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to ...

, toluene or

carbon tetrachloride Carbon tetrachloride, also known by many other names (such as tetrachloromethane, also IUPAC nomenclature of inorganic chemistry, recognised by the IUPAC, carbon tet in the cleaning industry, Halon-104 in firefighting, and Refrigerant-10 in HVAC ...

. Anhydrous chloroacetaldehyde reversibly converts to

polyacetals Polyoxymethylene (POM), also known as acetal, polyacetal, and polyformaldehyde, is an engineering thermoplastic used in precision parts requiring high stiffness, low friction, and excellent dimensional stability. As with many other synthetic po ...

. 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.

Hemihydrate

Hemihydrate is formed as below. It has a melting point of 43–50 °C, boiling point of 85.5 °C. Chloroacetaldehyde reaction01

Environmental aspects

Chloroacetaldehyde is a

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

in the degradation of

1,2-dichloroethane The chemical compound 1,2-dichloroethane, commonly known as ethylene dichloride (EDC), is a chlorinated hydrocarbon. It is a colourless liquid with a chloroform-like odour. The most common use of 1,2-dichloroethane is in the production of vinyl ...

, which initially converts to

chloroethanol 2-Chloroethanol (also called ethylene chlorohydrin or glycol chlorohydrin) is an organic chemical compound with the chemical formula HOCH2CH2Cl and the ''simplest'' beta-halohydrin (chlorohydrin). This colorless liquid has a pleasant ether-like od ...

. This metabolic pathway is topical because 1,2-dichloroethane is produced on a large 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.CDC - NIOSH Pocket Guide to Chemical Hazards
/ref>

References

{{reflist Aldehydes Organochlorides