A-Chloroethyl chloroformate

Deall lation. Chloroformates such as vinyl chloroformates (40) are used to dealkylate tertiary amines. Chloroformates are superior to the typical Von Braun reagent, cyanogen bromide, because of increased selectivity producing cleaner products. Other chloroformates such as aHyl, methyl, phenyl, and trichloroethyl have also been used in dealkylation reactions. Although the dealkylation reaction using chloroformates is mostiy carried out on tertiary amines, dealkylation of oxygen or sulfur centers, ie, ethers or thioethers, can also be achieved. a-Chloroethyl chloroformate [50893-53-3] (ACE-Cl) (41,42) is superior to all previously used chloroformates for the dealkylation reaction. ACE-Cl has the advantage that the conditions requked for ACE... 

Tertiary aliphatic amines are also cleaved by HI, but useful products are seldom obtained. Tertiary amines can be cleaved by reaction with phenyl chloroformate R3N -h ClCOOPh —> RCl 4- R2NCOOPh. a-Chloroethyl chloroformate behaves similarly.Alkyl halides may be formed when quaternary ammonium salts are heated R4N+X" R3N -)- RX. ... 

A,r-Benzyl groups can be removed by reaction of amines with chloroformates. This can be a useful method for protecting-group manipulation if the resulting carbamate is also easily cleaved. A particularly effective reagent is a-chloroethyl chloroformate, which can be removed by subsequent solvolysis.78... 

On a laboratory scale, one of the favored catalyst is the benzyl tri-n-butyl ammonium chloride (BTBAC). The most important reagent, a-chloroethyl chloroformate ( ACE-CI ), typically is isolated in 96% yield by stirring acetaldehyde with phosgene (1.1 eq.) neat for an hour in the presence of 3 mol. % BTBAC. Even chloromethyl chloroformate can be prepared using this process, but it is essential to introduce the monomeric gaseous formaldehyde into the... 

Thus, in the initial test system (N-deethylation of N-ethylpiperidine), the use of a-chloroethyl chloroformate (acronym ACE-CI) surpassed the yield obtained with vinyl chloroformate (I) -> (IV), 99% w 90% as shown in scheme 132 (Ref. 189). 

Ethynylation of azaaromatics. After activation of the system by a chlorofor-mate ester, pyridine, quinoline, pyridazine, and analogous heterocycles are attacked by the tin compound. a-Chloroethyl chloroformate is particularly effective as the... 

Tertiary amines 657 are cleaved by reaction with chloroformate (for example, a-chloroethyl chloroformate, or phenyl chloroformate, 658), resulting in carbamates 659 (for an extended discussion, see Section 4.7). 

The large-scale synthesis of a-chloroethyl chloroformate (ACE-Q) by the above method (stirring acetaldehyde with 1.1 equiv. of neat pho ene for 1 h in the presence of 3.0% benzyl tri-n-butylammonium chloride (BTBAC), giving an isolated yield of 96%) has a particular value since its ethanolysis product, a-chloroethyl ethyl carbonate, is a commercial alkylating agent used to mask carboxyls in penicillins and cephalosporins. 

Alternatively, in cases where the unlabeled O- or A-methyl target compound is available, the requisite starting material may be prepared from it by either ether cleavage (e.g., HI, HBr, BBrs, TMSI, thiolates) or A-demethylation (e.g., BrCN, vinyl chlorofor-mate, a-chloroethyl chloroformate, MCPBA-FeS04). 

With tertiary amines, phosgene-amine complexes can be formed. Warming results in decomposition to an N,N-dialkylchloroformamide by elimination of alkyl chloride. This has been utilized for the mild and high yielding deprotection of A-methyl amines (eq 8). a-Chloroethyl chloroformate, prepared... 

---