Phosgene isocyanide chemistry

H.E. writes - Thirty years ago, I started my doctoral thesis with a preparation of 2-chloroethyl chloroformate from phosgene on a 600 g scale. My supervisor was Ivar Ugi, an expert in phosgene chemistry, and Ugi s tradition in this field has been continued, particularly in isocyanide chemistry. In 1986, I rediscovered tri-pho ene and realized its potential, in principal, as a substitute for phosgene in... 

Synthetic routes that access appropriately substituted thienobenzazepines are also quite important for medicinal chemistry stracture activity relationship studies, and many involve similar bond connectivity strategies. One notable example employs the use of conunercially available 4-methyl-3-nitrophenol (Scheme 6.3). Methylation of the phenol followed by bromination, hydrolysis, and oxidation of the benzylic alcohol afforded aldehyde 9 in quantitative yield. Treatment of this aldehyde with 5-lithio-2-methylthiophene provided, after dehydroxylation, nitro intermediate A in good overall yield. Reduction of the nitro functionality and treatment with phosgene presented the corresponding isocyanide which upon cychzation using aluminum trichloride in a Friedel-Crafts fashion afforded the... 

The use of phosgene in the presence of triethylamine has become an often applied method since Ugi s extensive works in this field [1157]. As a prelude to preparative isonitrile chemistry, Ugi s 1971 procedure for the production of tert-butyl isocyanide is presented [1165]. tert-Butyl formamide is dehydrated with phosgene to afford fert-butyl isocyanide in 82% yield. 

Reviews on the synthesis and chemistry of carbodiimides are given in [1248-1250]. Carbodiimides are mainly synthesized in one of three ways from ureas or thioureas, from isocyanates, or from isocyanides. Several reagents have been employed in carbodiimide synthesis phosgene [1252, 1253], dimethylphosgenimi-nium chloride [1254], tiiphosgene [561, 562], phosphorus pentoxide [1255], phos-phoryl chloride [1256], triphenylphosphine dibromide [758, 1257-1261], triphenylphosphine/tetrahalomethanes [1262, 1263], iminophosphoranes [1264-1277], Mitsunobu reagent [1278, 1279], p-tosyl chloride [1280, 1281], and CDC [1137] oxidative additions have also been used [1282-1284]. 

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