4-Cyanopyridines salts

Diazo coupling involves the N exocyclic atom of the diazonium salt, which acts as an electrophilic center. The diazonium salts of thiazoles couple with a-naphthol (605). 2-nitroresorcinol (606), pyrocatechol (607-609), 2.6-dihydroxy 4-methyl-5-cyanopyridine (610). and other heteroaromatic compounds (404. 611) (Scheme 188). The rates of coupling between 2-diazothicizolium salts and 2-naphthol-3.6-disulfonic acid were measured spectrophotometrically and found to be slower than that of 2-diazopyridinium salts but faster than that of benzene diazonium salts (561 i. The bis-diazonium salt of bis(2-amino-4-methylthiazole) couples with /3-naphthol to give 333 (Scheme 189) (612). The products obtained from the diazo coupling are usuallv highly colored (234. 338. 339. 613-616). 

In order to illustrate the application of LSV in mechanistic analysis we can look at the redox behavior of the formazan-tetrazolium salt system which we studied some years ago [17], 1,3,5-Triphenyl formazane was oxidized at controlled potential in CH3CN-Et4NC104 solution to 2,3,5-triphenyl tetrazolium perchlorate which was then isolated in quantitative yield. Coulometry showed that the overall electrode reaction was a two-electron oxidation. It has been shown that the rate of variation of Ep with log v was 30 mV per decade of sweep rate and that there was no variation of the peak potential with the concentration of 1,3,5-triphenylformazan. According to Saveant s diagnostic criteria (Table 1), four mechanistic schemes were possible e-C-e-p-p, e-C-d-p-p, e-c-P-e-p and e-c-P-d-p. If cyclization is the rate-determining step, then the resulting e-C-e-p-p and e-C-d-p-p mechanisms would not imply variation of Ep with the concentration of base. However, we have observed the 35 mV shift of Ep cathodically in the presence of 4-cyanopyridine as a b e. These observations ruled out the first two mechanisms. The remaining possibilities were then e-c-P-e and e-c-P-d, as shown in Scheme 3. 

The acid-catalyzed cyclization of salts (188 Scheme 101) prepared from 2-cyanopyridine by quaternization with a benzyl halide provides the only method yet developed for the synthesis of 11-aminoacridzinium salts (189). The prototype quaternary salt (188 R = H) was cyclized in sulfuric acid in an overall yield of 25% (73JOC4167). A better yield (59%) was obtained when the point of electrophilic attack was activated by a para methoxy group. 

The first fully aromatic 2-azaquinolizinium salts were prepared by Krohnke et al. (64CB3566), who examined three approaches to the l-hydroxy-3-phenyI-2-azaquinoIizinium ion (262 Scheme 130). The first involved the reaction of picolinamide (261) with phenacyl bromide which produced (262) in unspecified yield. Most effective was refluxing 2-cyanopyridine (263) in moist acetonitrile with phenacyl bromide. Finally, it was shown that 2-ethoxycarbonyl-l-phenacylpyridinium ion (265) could serve as a starting material if ammonium acetate were present in the solvent. 

Cyanopyridine-4-carboxylate salts can be reduced to give dihydrofuro[3,4-f]pyridines (Equation 51) <2005RJ0279>. Under acidic conditions, the imine fragment can be hydrolyzed to generate lactone product. 

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). 

Alkoxypyridinium and 1-methoxypyridazinium salts yield cyanopyridines and cyanopyridazines, respectively, on treatment with potassium cyanide the cyano group enters the a-position with respect to the /V-oxide of the starting material. 

It is known that 3-aminobenzo[6]furan can be prepared from o-cyanophenols and a-halogenocarbonyl compounds with subsequent Thorpe cyclization (73JPR779). The extension of this synthesis to heteroatom substituted benzo[6]furans is straightforward (76JPR313). The reaction of potassium salts of 3-cyano-2-pyridones (e.g. 27) with a-halogenocarbonyl compounds (esters, ketones) yields 2-alkoxy-3-cyanopyridines which can be cyclized in the presence of sodium ethoxide to give 3-aminofuro[2,3-6]pyridines (Scheme 6). 

Metal complexes of several zinc, cadmium and mercury salts with 2-, 3- and 4-cyanopyridine have been reported.495 In none of the complexes was cyanide coordination observed. Zinc halides react with 3- and 4-cyanopyridine, but not with 2-cyanopyridine, to give 1 2 complexes which are assigned a monomeric tetrahedral structure on the basis of IR evidence. The cadmium halides also form 1 2 complexes with all the cyanopyridines, except cadmium chloride, which reacts with 2-cyanopyridine to give a 1 1 complex. The former contain... 

Cyanopyridine (pAfa 1.45) yields a trace of tetramethyl 9-cyano-9a77-quinolizine-l,2,3,4-tetracarboxylate (cf. 5) with DMAD the only product isolable from the 4-cyano isomer was the trimethyl 7-cyanoin-dolizine-l,2,3-tricarboxylate (cf. 35), whereas 2-methoxypyridine yielded 9 and ll.238 Cyclization in one direction to give 8 followed by a [1,5] sigmatropic shift, and pericyclic ring opening would lead to 9. The alternative cyclization to 10, followed by ionization and recombination, or a [1,5] shift, gives a second product 11, which has also been obtained from the quinolizinium salt 12. 

Cobalt(II) salts are effective catalysts for the oxidation of 1,2-glycols with molecular oxygen in aprotic polar solvents such as pyridine, 4-cyanopyridine, benzonitrile, DMF, anisole, chlorobenzene and sulfolane. Water, primary alcohols, fatty acids and nitrobenzene are not suitable as solvents. Aldehydic products are further oxidized under the reaction conditions. Thus, the oxidative fission of rram-cyclo-hexane-l,2-diol gives a mixture of aldehydes and acids. However, the method is of value in the preparation of carboxylic acids from vicinal diols on an industrial scale for example, decane-1,2-diol is cleaved by oxygen, catalyzed by cobalt(II) laurate, to produce nonanoic acid in 70% yield. ... 

The more flexible tether embodied in bispyridocarbazoles 321 and 322 was synthesized by Roques and colleagues (779) as shown in Scheme 50. The bischloro tether 319 was prepared from 4-bromopyridine (316) by halogen-metal exchange, condensation with 4-cyanopyridine, and Wolff-Kishner reduction of the resulting ketone 317. Catalytic hydrogenation, chlorination, and then alkylation of 320 with 319 gave the desired bispyridocarbazoles (321, 322). An important discovery in this research is that the methosulfate salts impart excellent water solubility to the bispyridocarbazoles. 

CPB2044). However, much more interesting are two further technical syntheses of the important nucleophilic catalyst DMAP (228) and related 4-aminopyridines. Treatment of 4-cyanopyridine (274), produced on a technical scale by ammonoxidation of y-picoline, with 2-vinylpyridine (275) in the presence of hydrochloric acid gives the crystalline quaternary salt 276. This salt is readily aminated by an aqueous solution of dimethyla-mine at room temperature with liberation of cyanide. The resulting aminated quaternary salt is finally cleaved by 40% NaOH to DMAP (228) and 2-vinylpyridine (275), which is recycled after separation of228 and 275 by distillation (79USP4I58093). 

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... 

Dihydropyridines generated from pyridinium salts carrying electron-withdrawing substituents at the 3 position by borohydride reduction are generally resistant to further reduction. The dihydro derivatives of 1-methyl-3-cyanopyridine, 68, 69, and 70, were recovered unchanged when treated with borohydride in water. Only 1,2-dihydro-l-methyl-3-cyano-pyridine (68) was converted to the tetrahydropyridine 71 when trimethyl borate was added to the reaction medium. Diborane/water achieved the same conversion, while added boric acid returned the starting materials. ... 

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