1-Chloroethyl Chloroformate1

[50893-53-3]  · C3H4Cl2O2  · 1-Chloroethyl Chloroformate  · (MW 142.97)

(reagent for the N-dealkylation of tertiary amines1,2)

Alternate Names: a-chloroethyl chloroformate; ACE-Cl.

Physical Data: bp 118-119 °C; d 1.325 g cm-3; nD20 1.4230.

Form Supplied in: commercially available liquid.

Preparative Method: by stirring phosgene and acetaldehyde in the presence of benzyltributylammonium chloride, followed by distillation (96% yield).2

Purification: purified by vacuum distillation.

N-Dealkylation of Tertiary Amines.

1-Chloroethyl chloroformate (1) introduced by Olofson and co-workers, effects the selective, high yielding dealkylation of tertiary amines (eq 1).2 Heating the amine (2) at reflux in 1,2-dichloroethane with 1 equiv of (1) for one hour results in formation of the ACE-piperidine (3). Evaporation of the solvent followed by heating the residue in methanol gives the hydrochloride salt of the secondary amine (4). Reagent (1) is preferred over the related reagent Vinyl Chloroformate for this application as the overall reaction conditions are milder and yields are higher.

Ease of cleavage of N-substituents is observed to occur in the order ArCH2 > allyl, t-alkyl >> s-alkyl > methyl > primary alkyl >> piperidine ring opening.3 Dealkylation of aromatic amines can be achieved, but this requires higher temperatures. Acetoxy and alkoxycarbonyl groups are stable to the reaction conditions.

1. Olofson, R. A. PAC 1988, 60, 1715.
2. Olofson, R. A.; Martz, J. T.; Senet, J.-P.; Piteau, M.; Malfroot, T. JOC 1984, 49, 2081.
3. Olofson, R. A.; Abbott, D. E. JOC 1984, 49, 2795.

Alan Armstrong

University of Bath, UK

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