2-Cyanopyridine, reaction with

Starting from readily available cyanopyridines, reaction with alkynes leads to substituted bipyridyls. Polynuclear pyridine derivatives can also be synthesized [42]. Substituted alkynes give two positional isomers. 

Interestingly, the same authors [13b] have isolated the l,2-dihydro-l,2,4,5-tetra-zine intermediate 21 by condensation of 2-cyanopyridine 20 with hydrazine hydrate in presence of flower of sulfur (Scheme 8.9 b). The reaction time is reduced under the action of microwave irradiation (125 W) protic solvents also promote the transformation. 

Like 2,2 - and 2,3 -bipyridines, 2,4 -bipyridine is formed by a number of reactions where one of the pyridine rings is built up from simpler components. Thus 4-(aminomethyl)pyridine with acetylene or acetaldehyde at 450"C affords 2,4 -bipyridine and 4-cyanopyridine reacts with acetylene at 120 C under pressure in the presence of a cobalt catalyst to give 2,4 -bipyridine in over 90% yield. 4-Acetylpyridine with acrolein and ammonia in the presence of dehydrating and dehydrogenating catalysts also gives 2,4 -bipyridine. A number of minor routes to 2,4 -bipyridine are worthy of... 

Table 26 Reaction of 2-chloro-3-cyanopyridine 136 with excess hydrazines (Equation 48) <2004TL2389>...

Cyanides can react with 1-aminopyridinium salts to give 2-substituted triazolopyridines, possibly via the pyridinium ylide. With 1-aminopyridinium iodide and cyanide ion the intermediate 4-cyanopyridine reacts with the aminopyridinium salt to give 2-(4-pyridyl)triazolopyridine (45).51 When acetonitrile or benzonitrile are used, 2-methyl- and 2-phenyltriazolo-pyridines are obtained.58 60 The reaction is thought to involve a dipolar cycloaddition of the N- mi nopyridine with the nitrile, as shown in Eq. (4). 

A new process for the homolytic acylation of protonated heteroaromatic bases has been developed by Minisci et al. An A-oxyl radical generated from iV-hydroxyphthalimide by oxygen and Co(ll) abstracts a hydrogen atom from an aldehyde. The resulting nucleophilic acyl radical adds to the heterocycle which is then rearomatized via a chain process. Under these conditions, quinoline and benzaldehyde afford three products (Equation 108) <2003JHC325>. A similar reaction with 4-cyanopyridine gives 2-benzoyl-4-cyanopyridine in 96% yield. 

The treatment of 3-chloro-4-cyanopyridine (454) with hydroxyamine hydrochloride in methanol in the presence of sodium methoxide at 40°C for 10 min afforded 3-aminoisoxazolo[5,4-c]pyridine (455) (59%) (Equation (37)) (87ZC337). This reaction did not proceed at 0°C. 

Furan underwent photocyclization reactions with 2-alkoxy-3-cyanopyridines <1999J(P1)171> and 2-alkoxynico-tinic acid esters <2002TL6103>, forming cage-like adducts, as shown in Scheme 44, that presumably resulted from a singlet [4-f4] cycloaddition followed by a triplet [24-2] cycloaddition. Reaction of 2-cyanofuran, however, provided the [44-4] product as the major isomer <2004TL4437>. 

Tsujimoto et al., 1977). Pyridines and 4-cyanopyridine react with triethyl-amine, but in these cases secondary photolysis reactions do not play a dominant role, and the amines [75a,b] (Bryce-Smith et al., 1977) and [76] (Caronna et ah, 1978) are produced (Scheme 12). The cyano group is obviously effective in making the reaction regio-selective. 2,3-Dicyanopyridines suffer decyana-tion upon irradiation in the presence of tertiary amines in acetonitrile solution (Tada et al., 1980). 2-Cyanopyridine and 4-cyanopyridine also undergo photoreactions with alkenes (e.g. cyclopentene) to give adducts in which the cyano group is replaced by the alkene (Bernard et al., 1981). 

In aqueous acetonitrile 2-cyanopyridine undergoes an interesting photoaddition reaction with alkenes as shown in Scheme 30 to give [133] (Saito,... 

The preceding discussion has, by implication, suggested that radical ipso-substitution reactions with heteroaromatic bases are rare. A few examples have been uncovered. For example, irradiation of 2-cyanoquinoline in acidic ethanol led to hydroxyethylation of the heterocycle with loss of the cyano-group (Scheme 24) <73BCJ942, 74BCJ942>. Similarly, 2-cyanopyridine has been transformed into 2-(l-hydroxyethyl)-pyridine in 30% yield by this method when run under conditions of high dilution <75CC241>. 

It is interesting to contrast this substitution reaction with a complementary method for achieving the hydroxyalkylation of pyridines and quinolines developed by Minisci et al. <85T617>. They found that addition of hydroxylamine-(9-sulfonic acid to an acidic solution of 4-cyanopyridine in methanol containing catalytic iron(Il) sulfate, gave 2-(hydroxymethyl)-4-cyanopyridine 70 on work-up (Scheme 25). No products derived from ipso-substitution of the cyano-fiinction were observed. 

Reaction of quaternary salt 226 with 4-melhylpiperidine gives rise to 4-(4-methylpiperidino)pyridine (277), which is a liquid, in contrast to the crystalline DMAP (228) and PPY (184) (83EUP74837). The reaction of 4-cyanopyridine (274) with acrylamide in the presence of HCI furnishes the crystalline quaternary salt 278, in quantitative yield, which is readily aminated with dimethylamine. Subsequent cleavage of the aminated quaternary salt by heating with strong alkali solution gives monomeric or... 

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