From Isocyanides

The addition of ethyl hypochlorite to isocyanides has been used by Nef to synthesize 1-haloformimidates. 

Similarly, addition of reactive halides, such as acyl halides, to isocyanides is feasible, and Nef has synthesized a variety of formimidoyl chlorides by this method Recently, Havlik and Wald ( ) have 

The reaction of the formimidoyl chlorides XV, which are generated from monosubstituted formamides and thionyl chloride, with sulfenyl chloride may actually proceed by addition of sulfenyl chloride to isocyanide. 

This reaction is a general synthetic method for 1-chlorothioformimidates, and good yields are reported ( ). 

If formamide is used instead of the monosubstituted derivatives, thiocyanates XVI are obtained in good yield ( ). 

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Other functional groups that are easily differentiated are cyanide (5c =110-120) from isocyanide (5c = 135- 150), thiocyanate (5c =110-120) from isothiocyanate (5c = 125 - 140), cyanate (5c = 105- 120) from isocyanate (5c = 120- 135) and aliphatic C atoms which are bonded to different heteroatoms or substituents (Table 2.2). Thus ether-methoxy generally appears between 5c = 55 and 62, ester-methoxy at 5c = 52 N-methyl generally lies between 5c = 30 and 45 and. S-methyl at about 5c = 25. However, methyl signals at 5c = 20 may also arise from methyl groups attached to C=X or C=C double bonds, e.g. as in acetyl, C//j-CO-. 

Isocyanides lose HCN + H2CN more readily, and this may help differentiate cyanides from isocyanides. 

In addition to a-additions to isocyanides, copper oxide-cyclohexyl isocyanide mixtures are catalysts for other reactions including olefin dimerization and oligomerization 121, 125, 126). They also catalyze pyrroline and oxazoline formation from isocyanides with a protonic a-hydrogen (e.g., PhCH2NC or EtOCOCHjNC) and olefins or ketones 130), and the formation of cyclopropanes from olefins and substituted chloromethanes 131). The same catalyst systems also catalyze Michael addition reactions 119a). 

Mo(NO)2L2Cl2, from isocyanide ligand addition to [Mo(NO)2Cl2]. These complexes are, in general, analogous to many known complexes of these metals with other ligands. 

Several other complexes, M(CNBu )jL (L = an activated olefin), have also been reported recently (110). This group of complexes, with the ligands (L) including maleic anhydride, fumaronitrile, and tetracyano-ethylene, arises from isocyanide ligand substitution by the olefin. Less active olefins such as ethylene and diphenylacetylene, and azobenzene did not react. 

In this period, the most important reactions of the isocyanides were the formations of tetrazole derivatives from isocyanides and hydrazoic acid, a process introduced in 1910 by Oliveri-Mandala and Alagna, and then in 1921 Passerini introduced the reaction (P-3CR), which was the first 3-component reaction of the isocyanides. In the 1940s Baker,and later Dewar, proposed mechanisms of the P-3CR. The important role of the intermediate hydrogen bond between the carboxylic acid and the carbonyl compound in suitable solvents was mentioned. ... 

El Kaim L, Gageat M, Gaultier L, Grimaud L (2007) New Ugi/Pictet-Spengler multicomponent formation of polycyclic diketopiperazines from isocyanides and alpha-keto acids. Synlett 2007(03) 0500-0502... 

Oxidation of the a-hydroxy-/ -acylamino amides obtained by this strategy constitutes an easy access to a-ketoamides. The Banfi group [28] reported the synthesis of a-ketoamides such as 37 and 38 starting from isocyanides and acid components... 

Structures of type XVIII or XIX as proposed for the diazodicyanomethane complex (Table 12) may also apply to the complexes of diphenyldiazomethane and 9-diazo-fluorene. The formation of the ketenimine complex (45) from the reaction of (CN)2CN2 and Ni(t-BuNC)4 probably occurs via attack of the complexed dicyano-methylene carbene on the isocyanide ligand113 The observation that these complexes112 113 catalyze the formation of ketenimines from isocyanides and diazo compounds, a reaction which does not proceed under same conditions without the transition metal, may be of preparative value 113 ... 

Ugi I, From isocyanides by four-component condensation to antibiotic syntheses, Angew. Chem., 94 826-835, 1982. 

One of the most prominent class of multicomponent reactions involves the use of isocyanides [5] and many synthetic methods have been developed to access heterocycles from isocyanide-based chemistry [6, 7]. There are a number of reviews covering the applications of isocyanide-based MCRs in drug discovery [8, 9]. fii this review, we will focus on the most recent developments in the field. 

Lithiation occurs at the carbon syn to the nitroso oxygen. From isocyanides, e.g. ... 

Four-membered N-heterocycles, synthesis from isocyanides 85S1083. 

Scheme 11 Redox active ligand participation in catalytic formation of carbodiimides from isocyanides and organic azides...

In 1957, Ugi et al. compared the spectroscopic data of comparable tetrazole and penta-zole derivatives [56], and noted that the 1-substituted tetrazoles were easily produced from isocyanides and hydrogen acid [29], but that the desired isocyanides were less easily prepared. Ugi then successfully investigated the formation of isocyanides by dehydrating... 

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