Imino nitriles

Only one example of this type has been reported. Cyclization of a-(acylmethoxy-imino)nitriles in the presence of lithium hydroxide provides a convenient synthesis... 

In 1903 Walther and co-workers recognized that imino-nitriles show parallel reactivity to that for the corresponding ketones in the presence of isatin under Pfitzinger conditions/... 

A catch and release synthesis of tetrazoles and cyclic amidines has been reported making use of solid-supported oximes [94]. When bound sulpho-nyloximes, obtained by reacting polymer supported sulfonyl chloride with oximes, were reacted with nucleophiles, tetrazoles or cychc amidines were obtained (Scheme 19). Alternatively, the use of TMS-CN affords imino nitriles, which have been used as intermediates for the preparation of indoles, 1,2,3,4-tetrahydropyridines, quinoxalines and benzimidazoles. 

If the rearrangement of oxime sulfonates is induced by organoaluminum reagents,the intermediate (71) is captured by the nucleophile originally attached to the Al. By this means an oxime can be converted to an imine, an imino thioether (R—N—C—SR), or an imino nitrile (R—N—C—In the last case, the nucleophile comes from added trimethyl si lyl cyanide. The imine-producing reaction can also be accomplished with a Grignard reagent in benzene or toluene. ... 

Mono-C-alkylation of imino nitriles and esters (Table 6.11)... 

Method A (liquiddiquid conditions) The alkylating agent (27.3 mmol) is added dropwise to aqueous NaOH (50%, 15 ml), the imino nitrile (22.7 mmol) and TEBA-Cl (0.5 g, 2.2 mmol) in PhMe (5 ml) at 0°C. The mixture is stirred at room temperature for 24 h and PhMe (100 ml) and H20 (100 ml) are then added. The aqueous phase is separated and extracted with PhMe (3 x 50 ml). The combined organic solutions are washed with H20 (50 ml) and brine (50 ml), dried (MgS04), and evaporated under reduced pressure at <60 °C to yield the alkylated product. 

Selected examples of the alkylation of imino nitriles and imino esters... 

In contrast with the reactions of the imino esters, the aldol condensation of imino nitriles and aromatic aldehydes in dichloromethane produces azabutadienes (Scheme 6.17), with the Z-isomers predominating often to the exclusion of the E-isomers [43, 44], Yields generally tend to be at least 10% lower when the reaction is conducted in acetonitrile. 

ZIEGLER METHOD. Cydization of dinitriles at high dilution in dialkyl ether in the presence of ether-soluble metal alkylamlide and hydrolysis of the resultant imino-nitril with formation of macrocyclic ketones in good yields. 

Imino nitrile A can be the intermediate producing the cis AMCPA observed. Two condensation products can arise starting from this compound amino nitrile 1 and enamino imine 10 (scheme 5) ... 

The imino-amine (51.6) reacts at room temperature with aldehydes or ketones with the formation of purines. The products obtained from aldehydes are slowly oxidized (by loss of two hydrogen atoms from the pyrimidine ring) at room temperature, but the ketone-derived purines are stable and are accompanied by smaller amounts of an imidazo[l,S-c]imidazoIe. During cyclization, the nitrile group is converted into a carboxamide. Pentane-2,4-dione, 2-furfuraldehyde and but-2-enal give the fully aromatized purine as the main or only product isolated (in 38-49% yield). Stirring an imino-nitrile for several hours or heating it for a few minutes with an anhydride converts it into a fused pyrimidine. 

Oxidation. Secondary a-amino nitriles afford a-imino nitriles upon reactin with IBX at room temperature. Tetrahydroisoquinoline is carbamoylated at C-1 and A -acylated at the same time on exposure to IBX and treatment with RCOOH and R NC." ... 

Damrauer and co-workers have shown that the nine-membered carbodiimide (77) can be formed in good yield by the treatment of the tosylate (329) with a strong base (Equation (36)) <80JOC1315> (see also <83JOCi694 . The mesylate derived from cyclooctanone oxime gives the nine-membered imino nitrile in 48% yield when treated with TMS-CN and Et2AICI <83JA283l>. 

Iminoyl chloride 17 reacted with tetrazoles 18 analogously to afford the 1,2,4-triazoles 19 in excellent yield. The electrocyclizaton of A -imino nitrile imines of the type 20 provided the key step for this general synthesis of 1,2,4-triazoles. Cyanuric chloride, as a triple aromatic imidoyl chloride, was treated with three equivalents of 5-phenyltetrazole to give 21 in 79% yield. ... 

Scheme 9.160. A Thorpe-Ziegler reaction of 2,6-dicyano-2-methylhexane. First, base treatment allows the dinitrile to undergo acyloin-type condensation (Scheme 9.145) to an imino-nitrile. Hydrolysis of the imine (Scheme 9.65) generates a P-ketonitrUe, which, on further hydrolysis (Scheme 9.46), produces a P-ketocarboxylic acid, which then undergoes decarboxylation (vide infra). Interestingly, the intermolecular version of this reaction is the Thorpe reaction, while the intramolecular version is the Thorpe-Ziegler reaction. See Baron, H. Remfry, F. G. P. Thorpe, J. F. /. Chem. Soc., 1904,85,1726, as well as Ziegler, K. Eberle, H. Ohlinger, H. Liebigs Ann. Chem., 1933,504, 94, and Ziegler, K. Chem. Ber., 1934,67,139.

The Strecker reaction of a dial with an amine and hydrogen cyanide, to produce a cyclic a,a -dicyanoamine, involves HCN addition to a cycUc imino nitrile intermediate as the final step. A highly diastereoselective synthesis of dihydro-5//-dibenz[c, ]azepines (80) from the biphenyldicarboxaldehyde exploits the chiral twist of the biaryl axis to achieve stereoselection. ... 

Next to be investigated were the members of the homologous series, namely, P-imino nitriles 133 and P-imino esters 134, existing predominantly in the conjugated enamine forms 131 and 132, which cannot be reduced with trichlorosilane (Scheme 15.27) [97d]. However, Maikov and Kocovsky found that Bronsted acids can facilitate the enamine-imine equiUbrium and provide sufficient concentration of the desired imine form, whose reduction can now be accomphshed. In the case of Sigamide 114b, acetic acid (1 equiv) was identified as an optimal additive the reduction, carried out in its presence, afforded the expected P-amino nitriles 135 and P-amino esters 136 in high yields and enantioselectivities (Table 15.12, entries 1 and 2). 

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