Chloroacetaldehyde is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon- hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

with the formula ClCH₂CHO. Like some related compounds, it is highly electrophilic reagent and a potentially dangerous

alkylating agent Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting ...

. 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 achi ...

form, but rather as the

hemiacetal A hemiacetal or a hemiketal has the general formula R1R2C(OH)OR, where R1 or R2 is hydrogen or an organic substituent. They generally result from the addition of an alcohol to an aldehyde or a ketone, although the latter are sometimes called hemike ...

(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 Polythiazide is a thiazide diuretic. A diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are ...

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 to related compounds like brotizolam, but a ...

. Another use is to facilitate bark removal from tree trunks. Chloroacetaldehyde is a metabolite of the antineoplastic

ifosfamide Ifosfamide (IFO), sold under the brand name Ifex among others, is a chemotherapy medication used to treat a number of types of cancer. This includes testicular cancer, soft tissue sarcoma, osteosarcoma, bladder cancer, small cell lung cancer, ce ...

and believed to be responsible for some of the toxicity observed with ifosfamide.

Synthesis and reactions

Hydrated chloroacetaldehyde is produced by the

chlorination Chlorination may refer to: * Chlorination reaction, a halogenation reaction using chlorine * Water chlorination Water chlorination is the process of adding chlorine or chlorine compounds such as sodium hypochlorite to water. This method is us ...

of aqueous

vinyl chloride Vinyl chloride is an organochloride with the formula H2C=CHCl. It is also called vinyl chloride monomer (VCM) or chloroethene. This colorless compound is an important industrial chemical chiefly used to produce the polymer polyvinyl chloride (PVC ...

: :ClCH=CH₂ + Cl₂ + H₂O → ClCH₂CHO + 2 HCl It can also be prepared from

vinyl acetate Vinyl acetate is an organic compound with the formula CH3CO2CH=CH2. This colorless liquid is the precursor to polyvinyl acetate and ethene-vinyl acetate copolymers, important industrial polymers. Production The worldwide production capacity of ...

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 ...

. The related bromoacetaldehyde is prepared via bromination of

. It also rapidly forms an acetals in the presence of alcohols. Being bifunctional, chloroacetaldehyde is a versatile precursor to many heterocyclic compounds. It condenses with

thiourea Thiourea () is an organosulfur compound with the formula and the structure . It is structurally similar to urea (), except that the oxygen atom is replaced by a sulfur atom (as implied by the '' thio-'' prefix); however, the properties of ur ...

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 t ...

, one of the first sulfa drugs.

Anhydrous

Water free chloroacetaldehyde is prepared from the hydrate by

azeotropic distillation In chemistry, azeotropic distillation is any of a range of techniques used to break an azeotrope in distillation. In chemical engineering, ''azeotropic distillation'' usually refers to the specific technique of adding another component to gener ...

with

chloroform Chloroform, or trichloromethane, is an organic compound with formula C H Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to PTFE. It is also a precursor to various re ...

toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) ...

carbon tetrachloride Carbon tetrachloride, also known by many other names (such as tetrachloromethane, also recognised by the IUPAC, carbon tet in the cleaning industry, Halon-104 in firefighting, and Refrigerant-10 in HVACR) is an organic compound with the chemi ...

. 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 pol ...

. 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, ...

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 vin ...

, 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

Safety

Chloroacetaldehyde is corrosive to

mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It i ...

s. 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 The Occupational Safety and Health Administration'' (OSHA ) is a large regulatory agency of the United States Department of Labor that originally had federal visitorial powers to inspect and examine workplaces. Congress established the agenc ...

established a

permissible exposure limit The permissible exposure limit (PEL or OSHA PEL) is a legal limit in the United States for exposure of an employee to a chemical substance or physical agent such as high level noise. Permissible exposure limits are established by the Occupational ...

at a ceiling of 1 ppm (3 mg/m³) for exposures to chloroacetaldehyde.CDC - NIOSH Pocket Guide to Chemical Hazards
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References

{{reflist Aldehydes Organochlorides