625-36-5

3-Chloropropionyl chloride is an important bifunctional reagent. It is capable of acylation and possesses a 2-chloro-ethyl fragment (CH2CH2Cl), which can be subjected to nucleophilic substitution and serves as a masked vinyl group. It can be used as a starting material in many reactions to construct a variety of (hetero)cyclic compounds.

Clear colorless to dark brown liquid

3-Chloropropionyl chloride is a reagent used in the synthesis of Beclamide (B119400), which is a chlorinated benzylpropanamide used as an anticonvulsant drug. It is used in the treatment of tonic-clonic seizyres and has sedative properties.

3-Chloropropionyl chloride (1) is commercially available and can be prepared from β-propiolactone (2) and thionyl chloride.1 Other standard methods available for the preparation of acyl chlorides can also be applied: the reaction of acrylic acid (3) or 3-chloropropionic acid (4) with thionyl chloride, phosphoryl chloride, phosgene, or phosphorus trichloride.

(1) The Friedel¨CCrafts acylation of tert-butylbenzene (5) with 3-chloropropionyl chloride (1) followed by cyclization provid- ed indanone 6, which was further transformed into urea derivative 7, a potent TRPV1 antagonist.

(2) A novel high-yielding one-pot microwave-assisted synthesis of condensed 5-substituted pyranoisoquinoline-1,6-diones 9 from 2-substituted isoquinoline-1,3-diones 8 and 3-chloropropionyl chloride (1) was reported.

(3) Acylation of 2-aminophenol (12) with 3-chloropropionyl chloride (1), followed by cyclization in the presence of polyphosphoric acid (PPA), gave benzoxazole 13, which was further reacted with 4-chlorophenyl-1-piperazine to yield the target benzo[d]oxazole analogue 14, a selective dopamine D4 receptor ligand.

Nonflammable

3-Chloropropionyl chloride is produced by reaction of acrylic acid with hydrogen chloride and phosgene in the presence of, for example, dimethylformamide as catalyst, or by reaction of propiolactone with thionyl chloride.

[1] Patent: WO2005/92842, 2005, A1. Location in patent: Page/Page column 18-19
[2] Angewandte Chemie, 1960, vol. 72, # 22, p. 836 - 845
[3] Patent: US2013/317248, 2013, A1. Location in patent: Paragraph 0061; 0062
[4] Patent: US2013/317252, 2013, A1. Location in patent: Paragraph 0091