O-Aminonitriles

By condensing carbon oxysulfide with o-aminOnitriles the corresponding 2-hydroxy-5-aminothiazoles can be obtained. In the presence of benzaldehyde or its substituted derivatives the reaction leads to 5-benzy-lideneaminothiazole derivatives (218) in good yields (Scheme 114 and Table 11.35) (393, 442). However, the reaction fails with or-amino acetonitrile (206), R = H (317). The 2-alkoxy analogs (220), R = Me, Et, Pr, Bu, vinyl, were similarly obtained from 219 and benzylideneamino acetonitrile (Scheme 115a) (393). 

TABLE 11-35 2-HYDROXV-5-AMINOTHIAZOLES DERIVATIVES FROM o-AMINONITRILE AND CARBON OXYSULnOE-... 

The use of guanidine for cyclization gives amino substituted derivatives (e.g. 212) (52CB1012), and in this case o-aminonitriles may be used to furnish diamines (e.g. 8UOC1394). An unusual reaction involving nitriles occurred during the preparation of nicotinonitrile from the amide and ammonium sulfamate, when a 60% yield of the dimeric by-product (213) was formed via the nitrile (69BSB289). Similar products have been obtained from... 

E. C. Taylor and his co-workers have demonstrated an important principle in the ring-opening of pyridopyrimidines and other fused pyrimidine systems to o-aminonitriles. They have demonstrated that based-catalyzed cleavage of a 4-substituted pyrimidine will occur provided that (a) the anion formed by the attack by the base at the 2-position can be stabilized by appropriate structural features in the remainder of the molecule and (b) that the substituent attached to the 4-position is capable of departure with its bonding pair of electrons in... 

Organometallic Addition/Reduction Sequence on Chiral o -Aminonitriles... 

Thiazolopyridopyrimidines such as 259-263 are prepared by formation of the pyrimidine ring as the final step either from an o-aminonitrile (Equation 80) <2002PS( 177)293, 2004PS( 179) 1279, 2005PS(180)19,... 

The use of o-aminonitriles as ring precursors in this field is illustrated by Equation (85) <2003PS(178)649>, although the nitrile functionality is not always directly involved in the ring synthesis <2005JHC169>, for example, as in Equation (86). 

Anodic oxidations can produce cationic species that react with nucleophiles. For example, the oxidation of Af-phenylpiperi-dine performed in the presence of cyanide ions affords an o -aminonitrile according to an ECEC mechanism (Scheme 12) [17]. 

Reaction of the carbonyl group of pi peri done with cyanide and aniline leads to formation of a cyanohydrin-like function known as an o-aminonitrile (37) hydrolysis under... 

Reaction of o-aminonitriles with guanidine is a widely used and efficient method for the preparation of condensed 2,4-diaminopyrimidines, 1 2. This procedure was adopted with a... 

E.C. Taylor and A. McKillop, The Chemistry of Cyclic Enaminonitriles and o-Aminonitriles (Interscience, New York, 1970). 

For a description of the utility of this exchange/cyclization to synthesize other heterocyclic o-aminonitriles, see [40] and M. Lang and J.-P. Fleury, Tetrahedron Lett., (1974) 3967. 

Thieno[3,2-i]pyridines 162 and 163 were prepared starting from o-aminonitrile 160 and methylene-active compounds 161 (1996M955). 

E. C. Taylor and A. McKillop (Eds.), The Chemistry of Cyclic Enaminonitriles and o-Aminonitriles, in Advances in Organic Chemistry (Ed. E. C. Taylor), Vol. 7, Wiley-Inter-science, New York, 1970. 

Alkaline dimerization of o-aminonitriles is exemplified by the compound (82) formed by heating 2-amino-3-cyanopyridine in aqueous ammonia.33... 

Mercapto-4-(79-aIkyl-2-benzimida2olyl)-thiazoles, from ammonium dithio-caibamate and, At-alkyl-2-benzimid-azolyl chloromethylketones, 265 2-Meicapto-5-aminothiazoles, from o-aminonitriles and carbon disulfide,... 

Reactions were carried out by condensing o-aminonitriles [NCCH(R,)NH2] with carbon disulfide in the presence at aldehydes (R CHO) or ketones (R2COR3) in these solvents. 

Isothiocyanates of general formula 221 condensed with o-aminonitriles lead to 2-substituted 5-aminothiazoles (223) (Table 11-36) through an acyclic intermediate (222) (Scheme 116). 

In contrast to that, nucleophilic substitution in a-position to nitrogen by cyanide or methoxide predominates, if the electrolysis is carried out in acetonitrile or methanol in presence of cyanide [49], respectively, in basic methanol [50,51]. This reaction, which is supposed to occur via the iminium ion, is interesting for application in organic synthesis. The formation of synthetically valuable o -aminonitriles from 7V,7V-dialkylani-lines has been reported by Andreades and Zahnow [49]. More recently, a series of papers was published by Hurvois, Moinet, Tallec, et al. on the anodic a-cyanation of A-sub-stituted 1-benzazepines, tetrahydroquinolines, and piperidines [Eq. (9)] [52]. The reactions were performed in a special flow-through cell. In the case of the 3-methyl-substituted benzazepines the reaction is stereospecific, leading only to the trans-a-cyano diastereomer. 

The reduction of a-aminocarbonyl compounds [184-187] or o -aminonitriles [188] is similar to the reductive cleavage of the a-hydroxy compounds the loss of amine occurs at a potential less negative than the reduction of the activating group. 

A high yield of a 1, S-benzodiazepine is obtained under chemically mild conditions by refluxing the malononitrile derivative (13.6) in ethanol. The product, being an o-aminonitrile, would be expected to react with guanidine to form a new 2,4-diaminopyrimidine ring (cf. Part 1, p. 78), but this reaction failed. 

---