Phosgene isocyanides from

Isocyanide dichlorides, formally imines derived from phosgene, react in a manner similar to that of phosgene (above) except that 2-amino-l,3,4-oxadiazole derivatives, instead of oxadiazolin-5-ones, are produced (Scheme 15) (71CC1223,81AP193,73CHE1216). 

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... 

Isocyanides can be prepared by elimination of water from N-alkylformamides with phosgene and a tertiary amine. Other reagents, among them TsCl in quino-... 

Syntheses from Acid Hydrazides with Phosgene, Thiophosgene, Carbon Disulfide, or Isocyanide Dichlorides... 

This phenomenon of these molecules was first discovered through derivatives of 1,3-4,6-tetraphosphahexa-l,5-diene. These derivatives can be synthesized from organyltrimethylsilylphosphanes and phosgene or isocyanide dichlorides. Primarily 1,3-diphosphapropenes, which can be isolated, are formed and then react further with phosgene or isocyanide dichlorides, eliminating CO or isocyanide, respectively, and halosilane, and through oxidative combination of the two phos-... 

Amidines with a more complicated substitution pattern have been prepared from amidines by alkylation—either at nitrogen or at nitrogen substituents. - Variations at these positions have been achieved by heteroarylation, acylation,vinylation or carboxylation with phosgene, thio-phosgene, isocyanide dichlorides or isothiocyanates. Some interesting amidines, e.g. (347)-(3S2) (Scheme 59), have been prepared in this manner. The amidine skeleton can also be varied by halogen-ation, - hydrolysis, isomerization or catalytic hydrogenation or other addition reactions if there are C=—C double bonds present as in (353 equation 173) for example. ... 

Preparation of cyanides.1 An attractive route to cyanides involves as the first step dehydration of alkylformamides with phosgene-tricthylamine (1,857) or phosphoryl chloride-diisopropylamine (13,249) to form isocyanidcs followed by isocyanidc-cyanide rearrangement. This rearrangement traditionally was conducted in the gas phase, but proceeds in almost quantitative yield when carried out by flash pyrolysis at 600°. This route to cyanides is attractive because allyl isocyanides rearrange without allylic rearrangement. Moreover, optically active carboxylic acids can be obtained from optically active amines without raccmization. 

Various vinyl isocyanides 1521-1525 are prepared from oximes (for example, 1519) by reductive formylation and dehydration of the resulting vinyl formamides (for example, 1520) with phosgene in 40-97% yield [1167]. For the dehydration step, DABCO proved to be the most effective base among acid scavengers (EtsN, pyridine, and quinoline were also used). 

Multicomponent reactions (MCRs) have, as a matter of principle, an enormous synthetic value in saving several reaction steps compared with a sequence of one-or two-component reactions. This is demonstrated in the total synthesis of the marine hexachlorinated amino acids f+J-demethyldysidenin 1531 and (-)-demethyl-isodysidenin [1169]. The key step of the synthesis is a U4CR (Ugi fourcarboxylic acid 1530, and thia-zol-2-ylmethyl isocyanide 1527, which is prepared from the corresponding form-amide 1526 by dehydration with phosgene under mild conditions in 67% 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]. 

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. 

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