Nitrile imides, cyclization

The cyclization of nitrile imides, having a nitro group attached to the o-position of the phenyl ring attached to carbon was already observed by Chattaway and Walker ( 2.23 structure of the isolated products LI was established recently by Gibson... 

Of course, this cyclization occurs via the intermediate nitrile imide. The hydrazidoyl bromide, obtained from benzaldehyde 4-quinazolyl-hydrazone and bromine, could not be isolated, and only the cyclization product has been obtained in good yield... 

Further work related to the cyclization of the nitrile imides, generated from N-o-nitroarylhydrazidoyl bromides, has appeared ( ), and the reaction of hydrazidoyl halides with azide ion and phenylhydrazine has been studied. Lozinskii et al. have shown that chlorooxalylarylhydrazidoyl chlorides (see Chapter 7) react with azide ion preferentially on the halo group attached to the carbonyl group. 

From a secondary amide, formation of a nitrile ylid because of plausible elimination of trimethylsilanol prior to cyclization might be expected. However, it is possible that this elimination occurs after cyclization. Thus, the true 1,3-dipole would be the imidate methylide. In any case, the final product will be a A -pyrroline.458... 

In a diastereoselective modification of this reaction, the imidates 7 were prepared starting from primary allylic and homoallylic alcohols and the nitrile 6 following a standard procedure1 sfi. By cyclization of 7 with A -iodosuccinimide in chloroform at 20 °C, diastereomeric mixtures were obtained with one diastereomer predominating, which was easily separated. The configuration of the diastereomer was assigned on the basis of X-ray analysis. 

The reaction is believed to proceed via the imidate anion, as formed from the nitrile, which then adds to dicyanodiamide and finally cyclizes by another addition.372... 

Triazines of type 3 are also accessible by an acid-catalysed cyclocondensation of imidic esters with elimination of alcohol [see (1)]. The joining of the three imidic ester molecules that function as activated nitriles probably takes place by an electrophilic addition-elimination mechanism involving immonium ions as intermediates. Cyclization of nitriles in the presence of NH3, catalysed by lanthanum(ni) ions, with initial formation of amides, is also effective [171]. 

Add hydrolysis of l,3-dicyano-3-(2-pyridyl)hexane (Xl-151) resulted in cyclization to the imide XI-1S2. Lactam XI-1S4 was isolated from the hydrolysis of nitrile XI-1S3 followed by treatment with thionyl chloride. The... 

Scheme 5 are suggested. Benzothiazepine derivatives (33) and (34) result when the acids (31) are cyclized with dicyclohexylcarbodi-imide or the nitriles (32) with ethanolic hydrogen chloride. 

The first step in the mechanism is the reaction of DICY with epoxy to form the alkylated DICY. This was confirmed by the imide IR peak at 1570 cm The second step involves further alkylation of the nitrogen that reacted in step 1, to form the AA(-dialkyldicyandiamide. No alkylation of the other amino group was suggested. The third step is the intramolecular cyclization step to form a zwitteri-onic five-membered intermediate. This involves the intramolecular reaction of the secondary alcohol formed in step 2 with the imide functionality (—C=N—). This is in contrast with the Zahir mechanism (112) where the intramolecular cyclization involves the hydroxy and the nitrile groups. The fourth step involves the elimination of ammonia and the formation of 2-cyanimidooxazolidine. The formation of this heterocycle is consistent with the observed bathocromic IR shift from 1570 cm to 1650 cm The ammonia that is eliminated can then react with epoxy to form a trifimctional cross-hnk. The last step involves the hydrolysis of the oxa-zolidine to form the oxazoUdone and cyanamide. The hydrolysis step accounts for the formation of the carbonyl group. 

The syntheses of chiral C2-symmetric methylene-bis(oxazolines) and bi-oxazolines of type 6 and 8 are summarized in Schemes 10 and 11 [25]. Using the well-established three-step sequence - amide formation, conversion to the bis(2-chloroalkyl)amide, and subsequent base-induced cyclization [26] - various derivatives were prepared in good overall yields. Alternatively, these ligands may be synthesized in one step from the corresponding amino alcohols and readily available bis-imidates derived from malonate or oxalate [25, 27] or, as described by Masamune et al [28], by amide formation with diethyl malonate and subsequent reaction with dimethyltin dichloride, or by metal-catalyzed condensation of amino alcohols with nitriles [29]. 

Dicarboxylic acid imides e.g. (189) were prepared in high yield by cyclization of carboxylic acid amides (190) with trifluoroacetic acid this technique avoided dehydration to the nitrile (191), which was easily achieved with acetic anhydride. This work is part of a total synthesis of maleimycin. ... 

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