Phosgene substitute chloroformates

Chloroform (trichloromethane). [CAS 67-66-3], Although chloroform can be prepared by various means it is almost exclusively produced by the chlorination of methane. It can be oxidized to phosgene, substituted with various halogens, nitrated to chloropicnn (CljCNOi). hydrolyzed lo formic O... 

Chlorination of methyi chloroformate and dimethyl carbonate affords useful phosgene substitutes chloromethyi chioroformate [I], trichioromethyl chloroformate [II] also called Diphosgene and bis(trichloromethyi) carbonate [III] known as Triphosgene [see scheme 33] ... 

Processes for the continuous production of chloro-substituted chloroformates, CHjClCHROCOCl (R = H, Me, CH OCH 2CH=CH or CHjOPh) from the reaction of phosgene with 1,2-epoxides have been disciosed, in which activated carbon is used as a catalyst, and the reaction is conducted at an operating temperature of 75-115 C in a circulating stream of pre-formed chloroformate [229]. 

Such substitution also allows the chemical industry to eliminate the problems in removal and disposal of polluting byproducts, such as hydrochloric acid and chlorides, generated from the use of phosgene or chloroformates. DMC is produced by EniChem s patented process based on the oxidation of carbon monoxide with oxygen in methanol according to the following reaction ... 

Another method used to remove phosgene substitutes from the desired products is to destroy them with appropriate nucleophiles such as water or alcohols. This method can, of course, only be applied when the product is insensitive to these nucleophiles, as is the case for carbamates, carbonates, ureas, cyanides, isocyanides, and alkyl chlorides. Chloroformates, carbamoyl chlorides, isocyanates, acyl chlorides, N-carboxylic anhydrides, and carbodiimides, on the other hand, cannot be purified by this method. Consequently, a synthesis of these compounds using phosgene is worthy of consideration. 

Trichloromethyl chloroformate is useful in synthesis as a substitute for phosgene, which, owing to its high volatility and toxicity, presents a severe hazard in the laboratory. Although trichloromethyl chloroformate is toxic, it is a dense and less volatile liquid, b.p. 128°, d l 1.65, having a vapor pressure of only 10 mm. at 20°. Consequently it is more easily handled in a safe manner than phosgene. 

Trichloromethyl chloroformate (diphosgene) is used as a safe substitute for highly toxic phosgene gas. The latter is generated in situ by addition of catalytic amounts of tertiary amines or amides, or active carbon. Diphosgene also disproportionates to 2 equivalents of phosgene on heating above 250°C. 

Kempter and co-workers prepared benzodiazocines 134 (R = R1 = H R2 = H, Me) from 135 (R = H, Me) by reduction and subsequent cyclo-condensation with the appropriate carbonyl compound (75MI7 87ZC36). For example, these workers condensed 3-(o-aminophenyl)propylamine with either phosgene or alkyl chloroformate to obtain 134 (R = R1 = R2 = H, X = O). Reaction of the same diamine (77MI5 87ZC36) and substituted derivatives (77MI5) with carbon disulfide afforded thio-... 

A 2- or 6-hydroxy-substituted purine can be prepared from the corresponding 4,5-diamino-pyrimidinol by cyclization with an acid, ester, ortho ester, or amide. If the ring closure is performed with reagents such as urea, alkyl chloroformates, urethanes, phosgene, and alkyl isocyanates, the 8-hydroxypurines are formed. Various xanthine and uric acid derivatives have been prepared by the condensation of 5,6-diaminopyrimidine-2,4-diols with formic acid. Purin-2-ol (1) was prepared by this route from 4,5-diaminopyrimidin-2-ol and ethyl orthoformate. ... 

As with conventional phenols, silicon-substituted phenols are unreactive towards phosgene at room temperature [1408]. In the presence of NEt 3, HMe jSW-CjH OH and HMe2Si-4-CgH,OH were converted into the expected chloroformate derivatives. 

However, reaction of substituted silylated phenols with phosgene does not always give the chloroformate product, owing to the faster reaction represented below [1102] ... 

The reaction of (15) with an arylisocyanate was obviously the most convenient method, however other routes involving either the synthesis of 3-isocyanobenodiazepines (16), by reaction with phosgene, or the synthesis of carbamate (17), by reaction with phenyl chloroformate [18], proved to be useful when the required substituted arylisocyanates were not commercially available. 

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