Isonitriles phosgene

Isocyanides (Isonitriles). Phosgene in combination with triethylamine dehydrates monosubstituted alkylformamides to isocyanides (yields 60-80%). The mechanism... 

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. " ... 

Guanidines have been prepared by the reaction between an amine, or an amine salt, and a host of other reagents, such as a thiourea in the presence of lead or mercuric oxide [83, 157, 158], carbodi-imides [140, 174, 175],calcium cyanamide [176, 177], isonitrile dichlorides [178—180], chloroformamidines [181], dialkyl imidocarbonates [182], orthocarbonate esters [183], trichloro-methanesulphenyl chloride [184], and nitro- or nitroso-guanidines [185-188]. Substituted ureas can furnish guanidines, either by treatment with amines and phosphorus oxychloride [189], or by reaction with phenylisocyanate [190] or phosgene [191]. 

Phosgene, as well as the easier to handle diphosgene (chloroformic acid trichloromethyl ester) or triphosgene (carbonic acid bis(trichloromethyl) ester) transform primary, secondary and tertiary amides and thioamides to chloromethyleneiminium chlorides (25 equation 15), whereby the reaction with thioamides is of broader scope and proceeds with fewer side reactions. The amide chlorides derived from primary and secondary amides can lose HCl, giving nitriles or imidoyl halides, respectively. /V-Sub-stituted formamides can be converted to isonitriles via amide halides. ... 

Metal carbamoyl complexes can readily be converted into isonitrile complexes with phosgene (in the presence of NEtj), a procedure which can be utilized to prepare complexes of isonitriles which do not exist in the free state [635] ... 

Using this method, the complex [Fe(cp)(CO) j C(0)NHMe ] has been converted into [Fe(cp)(CO) j(CNMe)]Cl, and cis-[Pt(PPh3)j C(0)NHMe Cl] has been used to prepare cj s-[Pt(PPh3)(CNMe)CIj] [635]. In an interesting variation on this procedure, the reaction of phosgene with unsymmetrical carbodiimide adducts of iron has been used to prepare iron(II) complexes containing two different isonitrile ligands at a now chiral centre [636] ... 

The reaction of COClj with methanamide, HCONH, at 0 C in CHCl 3/1,4-dioxane solution gave a compound with an empirical formula of CjH ClNjOj, claimed to be (HC0NH2)2.HC1 [237]. The reaction of a series of Af-(hydroxyalkyl)methanamides with phosgene results in their dehydration to the corresponding isonitriles [634a] ... 

In general, these two reactions are definitely not suitable for the preparation of appreciable quantities of pure isonitriles indeed, they have been largely replaced by the more widely applicable dehydration method [lc,d,fj. This was first discovered by Hagedorn in 1956 and entails transformation of primary amines into for-mamides, followed by dehydration either with phosgene (or its precursors) and triethylamine, or phosphorus oxychloride and di-wo-propylamine [If]. 

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. 

Temocillin [66148-78-5], fi-lactam antibiotic (penicillin derivative), 224. In one method, phosgene is employed to generate the isonitrile function of the penicillanic add ester 223 [160-162]. 

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