Nitriles, from

Reaction of 2 hloro-3-cyano-5,6-diphenylpyrazine with hydrazine hydrate is reported to give 2 hloro-3-hydrazinocarbonyl-5,6-diphenylpyrazine (848). 

Freifelder, Practical Catalytic Hydrogenation, Wiley Interscience, New York (1971), Chpt 12 M. Freifelder, Catalytic Hydrogenation in Organic Synthesis Procedures and Commentary, J. Wiley Sons, New York (1978), Chpt 6 

Rylander, Hydrogenation Methods, Academic Press, New York (1985), Chpt 7 

Resowsky, The Chemistry of Heterocyclic Compounds, Interscience, New York (1964), Vol 19, Part 1 (epoxides) 

Houben-Weyl, Methoden der Organischen Chemie, 4th ed, Vol VI/3, G. Thieme, Stuttgart (1965) ethers, p 1 epoxides, p 367 oxetanes, p 489 tetrahydrofurans, p 517 

diglyme LiBtti, Me3SiQ NaBHi, A1Q3 NaBHU, Me3SiCl NaBR,. CoClr6H20 

One of the first-known synthetic preparations of 1,2-dihydro-l,3,5-triazines involves trimerization of benzonitrile in the presence of alkali metals or organometallic reagents. 

In 1896, Lottermoser reported243 that in the presence of sodium, benzonitrile in refluxing benzene produces 2,2,4,6-tetraphenyl- 1,2-dihydro-1,3,5-triazine (157), sodium cyanide, and 2,4,6-triphenyl-1,3,5-triazine (153) [Eq (71)]. 

In support of this structure for 157, it was found that alkaline hydrolysis of the compound gives two molecules of benzoic acid and one molecule of 

The optimization of reaction conditions used by Swamer et al.246 enabled us to prepare 154 in 80% yield.247 A spectroscopic study has shown that in 

Researchers in Japan have claimed to produce l,2-dihydro-l,3,5-triazines by high-pressure reactions between aromatic or heteroaromatic nitriles and formaldehyde,249 acetaldehyde,250 or ketones251 in the presence of ammonia. 

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From nitriles by treatment with anhydrous Stannous chloride dissolved in ether saturated with hydrogen chloride the resulting crystaUine aldimine stannichloride, [(RCH=NHj)2] SnCl, or (RCH=NH,HCl)2SnCl4, is hydrolysed by warm water, and the aldehyde is isolated by distillation with steam or by extraction with a solvent (Stephen reaction), for example, for R = CH3(CH2)4, i.e., n-amyl ... 

From nitriles by Stephen s reaction (see under Aliphatic Aldehydes and Section 111,64), for example ... 

Besides a-halocarbonyl compounds, a-mercaptoketones and acids are also used for the preparation of thiazoies from nitriles and aldehydes oximes. 

HYDROXYTHIAZOLE DERTVATIVES FROM NITRILES AND a-MERCAPTO ACIDS... 

Ketenimines are usually prepared from carboxyHc acid derivatives such as amides and imino chlorides via elimination and from nitriles via alkylation with alkyl haHdes under strong basic conditions (21,64). 

Hi) Preparation of isoxazoles from nitrile N-oxides The reaction between a nitrile //-oxide and an alkyne is so facile that it is usually sufficient to leave an ether solution of the reactants at room temperature to obtain the desired isoxazole in good yield. The reaction is in general sensitive to the size of the substituent on the alkyne but not on the nitrile -oxide. In the case of poorly reactive alkynes, the difficulty may be overcome by generating the nitrile -oxide in situ and keeping its concentration low. 

Table 13 Isoxazoles from Nitrile iV-Oxides and Alkynes...

Table 14 Isoxazoles from Nitrile N-Oxides and C=C Dipolarophiles...

Synthesis o( S-amlnoacryiic acids or derivatives from nitriles by aldol type condensation... 

REFORMATSKY BLAISE Zincahyiallon Synthesis of -hydrexyesters from cartxinyl derivatives arxl a-haloesters via a zmc reagent (Reformatsky). Synthesis ol eloesleis from nitriles and a-haloesters via a zinc reagent (QIaise). 

Finally, the condensation of unsaturated compounds with fulminates known as the fulminic synthesis represents the simplest case of synthesis from nitrile oxides. Barnes has reviewed in detail the work carried out up to 1953 thus we shall be concerned here only wdth more recent publications or those of general interest. 

The experimental conditions for the syntheses starting from acid chlorides of hydroxamic acids and from nitrile oxides are somewhat different. In the former case the other component of the reaction is organometallic, usually an organomagnesium derivative of an acetylene or, less frequently, a sodium enolate of a /8-diketone. Nitrile oxides condense directly with unsaturated compounds. 

The general synthetic scheme starting from nitrile oxides, which condense with acetylenes to yield isoxazoles and with olefins to yield A -isoxazoIines may be represented by Eqs. (1) and (2). The forma-... 

The value of AG° at various reaction temperatures and corresponding Kp values are reported in Table 2. It can be understood from Table 2 that the formation of hydrogenated nitrile rubber from nitrile rubber is thermodynamically feasible. 

Carboxylic acids can be prepared from nitriles by reaction with hot aqueous acid or base by a mechanism that we ll see in Section 20.9. Since nitriles themselves are usually made by Sts 2 reaction of a primary or secondary7 alkyl halide with CN , the two-step sequence of cyanide displacement followed by nitiile hydrolysis is a good way to make a carboxylic acid from an alkyl halide (RBr —> RC=N RC02H). 

The mechanism is thought to be analogous to that suggested for the formation of 1,3,5-benzoxadiazepines from nitrile oxides and 2-phenylbenzazete (see Section 4.2.1.4.2.1.). 

The imidazole nucleus is often found in biologically active molecules,3 and a large variety of methods have been employed for their synthesis.4 We recently needed to develop a more viable process for the preparation of kilogram quantities of 2,4-disubstituted imidazoles. The condensation of amidines, which are readily accessible from nitriles,5 with a-halo ketones has become a widely used method for the synthesis of 2,4-disubstituted imidazoles. A literature survey indicated that chloroform was the most commonly used solvent for this reaction.6 In addition to the use of a toxic solvent, yields of the reaction varied from poor to moderate, and column chromatography was often required for product isolation. Use of other solvents such as alcohols,7 DMF,8 and acetonitrile9 have also been utilized in this reaction, but yields are also frequently been reported as poor. 

The addition of dry HCl to a mixture of a nitrile and an alcohol in the absence of water leads to the hydrochloride salt of an imino ester (imino esters are also called imidates and imino ethers). This reaction is called the Pinner synthesisThe salt can be converted to the free imino ester by treatment with a weak base such as sodium bicarbonate, or it can be hydrolyzed with water and an acid catalyst to the corresponding carboxylic ester. If the latter is desired, water may be present from the beginning, in which case aqueous HCl can be used and the need for gaseous HCl is eliminated. Imino esters can also be prepared from nitriles with basic catalysts. ... 

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