Isocyanides, reduction

A one-step synthesis o( mtnles from carbonyls by a reductive cyanation with tosylmethyl isocyanide (TosMIC), also synthesis of 1,3-azole or of ketones... 

The common impurities found in amines are nitro compounds (if prepared by reduction), the corresponding halides (if prepared from them) and the corresponding carbamate salts. Amines are dissolved in aqueous acid, the pH of the solution being at least three units below the pKg value of the base to ensure almost complete formation of the cation. They are extracted with diethyl ether to remove neutral impurities and to decompose the carbamate salts. The solution is then made strongly alkaline and the amines that separate are extracted into a suitable solvent (ether or toluene) or steam distilled. The latter process removes coloured impurities. Note that chloroform cannot be used as a solvent for primary amines because, in the presence of alkali, poisonous carbylamines (isocyanides) are formed. However, chloroform is a useful solvent for the extraction of heterocyclic bases. In this case it has the added advantage that while the extract is being freed from the chloroform most of the moisture is removed with the solvent. 

The easy cleavage by reduction of the N—C bond in isocyanides, which was recently observed by I. Ugi and F. Bodesheim [Chem. Ber. 94, 1167 (1961)], stimulated this experiment. 

Substitution at the SiH moiety has been carried out with alkylthio groups, such as MeS and i-PrS. Tn s(alkylthio)silanes, (RSlsSiH, are radical-based reducing agents which can effect the reduction of bromides, iodides, xanthates, phenylselenides, and isocyanides in toluene, using AIBN as the initiator at 85... 

Isocyanides [RNC] (174, 175) are isoelectronic with CO and have been extensively used as CO analogs in studies of heme proteins (176-180). W-Butyl isocyanide (N-BIC) behaves as a CO analog at both the CODH and ACS active sites (181). N-BIC competes with CO in the CO oxidation reaction, is a sluggish reductant, and causes EPR spectral changes at Clusters A, B, and C similar to those elicited by CO. 

The reactions of nucleophilic reagents with cationic and uncharged metal carbonyl complexes have received much attention in the past, and it is not surprising that these studies have now been extended to isocyanide metal complexes. Different products in these reactions can arise by three general routes these include ligand substitution, reactions involving attack at a ligand, and reduction of the metal complex. All have been observed in reactions with metal isocyanide complexes. 

Virtually all work on nickel isocyanide complexes centers on nickel(O) species. Malatesta and Bonati 90) describe complexes of the formula NiL4 and Ni(CO) L4 jj. The former are formed in a variety of reactions, including reductions of nickel(II) in the presence of isocyanides, and by the replacement of other ligands by isocyanides. The latter are, of course, derivatives of Ni(CO)4. In addition, a few ill-defined nickel(II) complexes are reported, as is the formally nickel(I) species (C5H5NiCNC6Hj)2. 

Liquid crystals based on aliphatic isocyanides and aromatic alkynyls (compounds 16) show enantiotropic nematic phases between 110 and 160 °C. Important reductions in the transition temperatures, mainly in clearing points (<100 °C), areobtained when a branched octyl isocyanide is used. The nematic phase stability is also reduced and the complexes are thermally more stable than derivatives of aliphatic alkynes. Other structural variations such as the introduction of a lateral chlorine atom on one ring of the phenyl benzoate moiety or the use of a branched terminal alkyl chain produce a decrease of the transition temperatures enhancing the formation of enantiotropic nematic phases without decomposition. 

The oxidative addition of (ArS) 2 to Pd(0) and coordination of 73 to the resultant Pd(II) both lower the total energy [state (C) from (A) via (B)]. Both the insertion of isocyanide into Pd-S of 78 giving state (D) and the reductive elimination of 74 from 79 affording state (E) are reversible. The equilibrium of the insertion and de-insertion of the isocyanide favors the formation of the product of the de-insertion reaction. [State (C) is lower than state (D).] Although state (C) is more stable than state (E), the short-lived Pd(0) can be trapped by (ArS)2 to give 77 [state (E) from state (E)]. 

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... 

Lippard et al. have demonstrated a reductive C—C coupling between the carbon donor atoms of terminal isocyanide ligands [Eq. (11)] (48,49). 

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