TriChloromethyl chloroformate preparation

The mechanism of the condensation in Part D probably involves thioformylation of the metallated isocyanoacetate followed by intramolecular 1,1-addition of the tautomeric enethiol to the isonitrile. This thi2izole synthesis is analogous to the formation of oxazoles from acylation of metallated isonitriles with acid chlorides or anhydrides. " Interestingly, ethyl formate does not react with isocyanoacetate under the conditions of this procedure. Ethyl and methyl isocyanoacetate have been prepared in a similar manner by dehydration of the corresponding N-formylglycine esters with phosgene and trichloromethyl chloroformate, respectively. The phosphoryl chloride method described here was provided to the submitters by Professor U. Schollkopf and is based on the procedure of Bohme and Fuchs. The preparation of O-ethyl thioformate in Part C was developed from a report by Ohno, Koi/.uma, and Tsuchihaski. " ... 

The chlorination of methyl chloroformate in sunlight was first reported by Hentschel, but without a detailed description of either the procedure or the results. The first step of the present procedure for the preparation of trichloromethyl chloroformate utilizes an ultraviolet light source and affords a simple and reproducible way to obtain this reagent. Although trichloromethyl chloroformate may also be synthesized by photochemical chlorination of methyl formate,the volatility of methyl formate causes losses during the reaction and increases the hazard of forming an explosive mixture of its vapor and chlorine gas. The preparation of trichloromethyl chloroformate by chlorination of methyl chloroformate in the dark with diacetyl peroxide as initiator has been reported. However, the procedure consists of several steps, and the overall yield is rather low. 

Trichloromethyl chloroformate has proven effective in the preparation of N-carboxy-a-amino acid anhydrides from amino acids, and various compounds having isocyanate, acid chloride, and chloroformate groups.For example, trichloromethyl chloroformate may be used instead of phosgene in the preparation of 2-tert-butoxycarbonyloxyimino-2-phenylacetonitrile. The use of this reagent is illustrated here by the synthesis of 3-isocyanato-propanoyl chloride from 3-aminopropanoic acid hydrochloride. 

Trichloromethyl-chloroformate is produced by exhaustive photochlorination of methyl-chloroformate (Eq. 29) [39], and, although so far never observed, phosgene could be an additional hazard in case of an equipment breakdown. In up-scaling the preparative procedure, care has to be taken that... 

It is obtained as a by-product in the preparation of trichloromethyl chloroformate when methyl chloroformate which is impure with dimethyl carbonate is employed. 

Identification of trichloromethyl chloroformate may also be made by using dimethyl amino benzaldehyde and diphenylamine paper, prepared as described on p. 81. In presence of trichloromethyl chloroformate this turns yellow as in the presence of phosgene. 

Oxazolidinones are commonly prepared from amino alcohols by incorporation of a carbonyl unit. Additions to the list of reagents that effect the transformation are bis(trichloromethyl)carbonate <89S875> and trichloromethyl chloroformate <89JOC323l>, which offer the advantages of easier handling and reduced risk of exposure compared to phosgene. As a further step in that direction,... 

A disadvantage of the present procedure is that it requires the use of the relatively foul-smelling substance, ethyl isocyanoacetate. Although this material is commercially available (from, e g., Aldrich Chemical Company, Inc.), it is moderately expensive. The authors have found that the existing preparative procedure (Hartman, G. D. Weinstock, L. M. Org. Synth., Coll. Vol V11988, 620) can be improved by the use of trichloromethyl chloroformate (Kurita, K. Iwakura, Y. Org. Synth., Coll. Vol. VI 1988, 715) rather than phosphoryl chloride. This substitution simplifies purification of the isocyanoacetate by eliminating the aqueous portion of the workup. 

Analogous to amino acids, a-hydroxy acids form cyclic anhydrides when treated with phosgene. However, a much more efficient reagent for this transformation with lactic acid is trichloromethyl chloroformate. By this method, L-lactic acid O-carboxyanhydride (3) is prepared as a crystalline solid in 46% yield [2]. Although 3 has found application in polymer chemistry, its use in asymmetric synthesis has been limited. Reaction of 3 with 4-bromo-benzaldehyde methylthio(thiocarbonyl)hydrazone in the presence of TFA gives a mixture of 4 (25%) and 5 (56%), which is separable by column chromatography [3]. 

Sigurdsson, S.T., Seeger, B., Kutzke, U. and Eckstein, F. (1996) A mild and simple method for the preparation of isocyanates from aliphatic amines using trichloromethyl chloroformate. Synthesis of an isocyanate containing an activated disulfide. The Journal of Organic Chemistry, 61, 3883-3884. 

Diphosgene (Trichloromethyl chloroformate), CICOOCCI0, Mol. wt. 197.85, b.p. 128°, 49°/50 mm. toxic, asphyxiating gas used in the first world war as a poison gas. This reagent is generally prepared by chlorination hv) of methyl formate or methyl chloroformate. 

The preparative route to [l,5-f][l,3,5]thiadiazine-2-ones 312 is outlined in Scheme 65. Thus, 5-amino-3-methyl-pyrazole-l-carbothioamides 313, obtained from the reaction of 5-amino-3-methylpyrazole (314) with isothiocyanates, react smoothly with trichloromethyl chloroformate to afford 312 (Scheme 65) <2004JFA1898>. 

Oxazolidinones 593, which represent potential chiral auxiliaries, have been prepared with diphosgene (trichloromethyl chloroformate) [418, 419). 

Trichloromethyl chloroformate is a useful substitute for phosgene in the preparation of isocyanates from amines, amino-acids, and amino-alcohols (Scheme 10). 

Preparative Methods by treatment of N-Hydroxysuccinimide (HOSu) with Trichloromethyl Chloroformate (TCF, CI3COCOCI) or using trimethylsilylated N-hydroxysuc-cinimide and phosgene, both giving DSC in good yield (eq 1 ). ... 

Polymers prepared with the trichloromethyl-functional initiators648 or with chloroform or carbon tetrachloride as a transfer agent649 have been used as macroinitiators for ATRP. The method has been used to make PVAc-block-PS... 

Readily available allylic and benzylic trichloromethyl sulfoxides undergo an unusual base-induced / -elimination of chloroform, with formation of the corresponding y.,(l-unsaturated sulfine, under mild conditions at room temperature the procedure has been applied to form vinylthioaldehyde 5-oxides and vinylthioketone 5-oxides.89 N-Sulfinylamines (115) have likewise been prepared by / -elimination of chloroform from trichloromethanesulfinamides (114).90 The reaction is promoted rapidly at room temperature by pyrrolidine and Et3N and the sulfinylamines (115) can be trapped by o-phenylenediamine (116), to give benzothiadiazole, before desulfonative hydrolysis occurs. 

Isolation of novel free carbenes is not always trivial, mainly due to difficulties with decomposition and the need to handle free NHCs under inert atmosphere conditions. In this context, the use of protected forms of free NHC carbenes has appeared as a useful alternative to the preparation of NHC complexes. N-Heterocyclic rings containing alkoxide or trichloromethyl groups, such as shown in Scheme 7, can be considered as NHC-adducts in the sense that they can readily eliminate alcohol or chloroform to unmask the carbene, which would then coordinate to the metal. 

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