Description
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.
Chemical Properties
Clear colorless to dark brown liquid. Soluble in ethanol, ether and chloroform. Slightly soluble in water.
Uses
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.
Preparation
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.
Reactions
(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.
Flammability and Explosibility
Non flammable
Synthesis
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.
