Phosgene substitute triphosgene

H Eckert, B Forster. Triphosgene, a crystalline phosgene substitute. Angew Chem Int Ed Engl 894, 1987... 

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] ... 

In the first group, primary amines are reacted with carbonyl insertion compounds such as phosgene [727, 729], and sometimes phosgene substitutes such as triphosgene [507], various carbonates [503, 730, 731], bis(4-nitrophenyl)carbonate [503], di-ferf-butyl dicarbonate [664], S,S-dimethyl thiocarbonate [577], and N,N -carbonyldiimidazole [732], l,l-carbonylbis(benzotriazole) [728], and trihaloacetyl chlorides. Most of these compounds have been utilized as safer reagents that can be stored and handled without special precautions. 

The traditional use of phosgene in Scheme 4 can be avoided by substituting it with the less toxic triphosgene, which gives comparable yields of the M-car-boxyanhydrides. Diphosgene may also be used to form the NCA, but the reaction requires the use of charcoal and is not as reliable. Free amino acids have also been converted to their corresponding NCAs by the use of benzyl chloroforma-te with thionyl chloride. 

This is a modification of a synthetic method reported by Sahu. This method can be adapted for the synthesis of the isocyanides prepared in Section 6. A. Substitution of triphosgene for phosgene provides a safer alternative for the synthesis of isocyanides, in general. On the other hand, phosgene is less expensive and the phosgene reaction is easier to scale up. p-H2N(CgH2(CH3)2)NH2 is converted to the corresponding formamide by the procedure outlined in Section 6.A. 

At the present time, one crucial question still remains what is the industrial value of Diphosgene and Triphosgene as liquid and solid substitutes for phosgene Are the two reagents really safer than phosgene ... 

Both reagents have proved to be useful substitutes for phosgene in all its main applications. Indeed, they are sold commercially as the efficient equivalents of 2 and 3 phosgene molecules respectively in processes yielding chloro-formates, carbonates, carbamates, ureas and isocyanates, as well as in chlorinations, carboxylations and dehydrations (For a recent review of Triphosgene use in organic synthesis, see Ref. 33). 

Triphosgene (CC1,0)2C=0, is a readily available1 substitute for phosgene.2 OxidationThis combination (1) is comparable to DMSO-oxalyl chloride for both small- and large-scale Swcrn oxidations. 

Suitable substituted triazole derivatives can be cyclized with phosgene or some of its substitutes (e.g., diphosgene, triphosgene, carbonyl diimidazole) to form the corresponding triazolotriazole derivatives. This approach can be demonstrated by reactions in Scheme 81 <77CB1691,84JOC1703>. 

Triphosgene, a safe and stable crystalline solid substitute for phosgene [53, 148], is successfully utilized in the sequential synthesis of unsymmetrical ureas also bearing chiral amino acid derivatives, without any need to purify the intermediates [507]. 

Phosgene equivalents and their substitutes have found many applications in the synthesis of polycarbonates. Table 5.4 lists some examples employing triphosgene. 

The development of phosgene equivalents and substitutes is still not at an end. Phosgene equivalents with lower vapor pressures and higher TLVs remain a desirable aim, and a furtherance in the use of triphosgene for the same applications as phosgene is likely. 

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