Trimerization of nitriles

Triazines can be obtained either by condensation methods using the fluorinated anhydride (89IZV928) or by trimerization of nitriles, e.g., per-... 

Swamer et a/.246 described the formation of l,2-dihydro-2,4,6-triphenyl-1,3,5-triazine (154b) (yield 14%) from benzonitrile in the presence of sodium hydride and proposed a detailed mechanism (Scheme 8), which is, presumably, valid for all trimerizations of nitriles in the presence of organometallic reagents.243-246... 

Trimerization of nitriles is an especially valuable synthetic method for forming symmetrically substituted 1,3,5-triazincs. 

The reaction conditions are similar to those used in the trimerization of nitriles. 

Trimerization of nitriles, isocyanates, isothiocyanates, imidates, and carbodiimides all lead to symmetrical 2,4,6-trisubstituted 1,3,5-triazines (see Section 6.12.9.5). The use of lanthanide trifluoromethanesulfonate and ammonia as cocatalysts is claimed as a big improvement. The trisaminal of 2,4,6-triformyl-l,3,5-triazine is also useful for further derivatization to unusual structures (see Section 6.12.7.1). Treatment of a 1 1 pyridine/conc. ammonia solution of an aromatic aldehyde with excess Fremy s salt is another development. Separation of the amide coproduct was claimed to be easy. The synthesis fails with aliphatic aldehydes (see Section 6.12.9.5.4). Aminolysis of 2,4,6-triaryl-1,3,5-oxadiazinium salts gives symmetrical 1,3,5-triazines but the reactions are limited in that electron-withdrawing groups in the aromatic rings lead to instability and difficulty in separation of products (see Section 6.12.10.4). 

Trisubstituted 1,3,5-triazines 3 are obtained by acid-, Lewis acid-, or base-catalyzed cyclo-trimerization of nitriles ... 

Acetylacetonates of zinc Trimerization of nitriles, epoxy/cyanate ester... 

Another example of the remarkable reactivity of Mg actuated by our procedure is its reaction with nitriles. In this respect, the Mg resembles an alkali metal more than an alkaline earth. Benzonitrile reacts with Mg overnight, in refluxing DME, to give 2,4,6-triphenyl-l,3,5-triazine and 2,4,5-triphenylimidazole in 26 and 27% yield, respectively, based on magnesium. Jhe imidazole was shown to arise, at least in part, from the action of Mg on the triazine. The trimerization of aromatic nitriles to give symmetrical triazines is not unknown, but generally the reactions are... 

In this approach the C(2)-N(3) and C(6)-N(l) components are usually the same. Formamide or nitriles are common C-N components. A classical example is the trimerization of acetonitrile to give 2,6-dimethyW-pyrimidinamine <1994HC(52)1 >, while a modern example involves a similar trimerization of a variety of alkyl and benzylic nitriles 707 under microwave conditions <2005JC0483>. 

Trimerization of imidates is a valuable route to 1,3,5-triazines. Imidates can be considered as activated nitriles and cyclotrimerize more readily. Most symmetrical 2,4,6-trialkyl-1,3,5-triazines are easily formed, although large alkyl substituents may give rise to steric hindrance (61JOC2778). Symmetrical isocyanurates (525) are readily available from isocyanates, RNCO catalysts include tertiary amines, phosphines and sodium methoxide. Aldehydes RCHO and ammonia give hexahydro-1,3,5-triazines (526), known as aldehyde ammonias (73JOC3288). 

Probably the cyclotrimerization of nitriles is the best known route to 1,3,5-triazines. The reaction has the obvious limitation that it is of value for preparing the symmetrical derivatives only. Nevertheless, many important triazines, such as cyanuric chloride, are made in this way. There are a number of other cyclotrimerization reactions which are also useful, in particular the trimerization of imidates. An easy route to 1,3,5-triazine from ammonium acetate has been developed. 

Phenylsodium is formed initially in the reaction between benzonitrile and sodium (Scheme 79) (59JOC208). Trimerizations of aryl or heterocyclic nitriles catalyzed by amines or alkoxides resemble the reactions of the perfluoronitriles described above (Schemes 77 and 78 respectively). Kurabayashi et al. (71BCJ3413) studied the trimerization of benzonitrile under pressure in methanol, and have shown that the rate determining step is the reaction of the benzimino ether with benzonitrile. Steric factors exert an important influence in the trimerizations of aryl cyanides. The cyclizations of ort/zo-substituted aryl cyanides need more severe conditions than either the corresponding meta or para derivatives (Table 14). 

The preparation of 1,3,5-triazine 1,3,5-trioxides by trimerization of a nitrile oxide was reported (09CB803) however, the structure of the product has been reassigned as a polymer (65LA(687)191>. 

Baxendale and Ley [60] employed the Smith Synthesizer as well as the Emrys Optimizer from Biotage [59] for conducting neat KOf-Bu mediated trimerizations of various liquid nitriles to give aryl- and alkyl-substituted 4-... 

Hydroboration of nitriles has also been used in syntheses of N-halo-organoborazines (see II.2.4.). Furthermore, a hydrogen-transfer reaction has been described by which borazines are formed through the reaction of trimeric aminoboranes with dimethylaminoborane in high yield 26> [Eq. (5)]. The latter method, however, is primarily of theoretical interest. 

Table 6 A Summary of the Various Methods Used in the Trimerization of Aromatic Nitriles...

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