To nitrile

This method has the great advantage over method (A) in that it can be applied in particular to those aromatic nitriles in which the aryl group is readily sulphonated clearly, it can also be applied to nitriles in which the alkyl or aryl portion contains groups which are in any other way affected by concentrated sulphuric acid, or by concentrated aqueous alkalis. 

Ketones can be converted to nitriles with an additional carbon atom with the aid of the TosMIC reagent (J.R. BuU, 1975 O.H. Oldenziel, 1973). 

Thiazole carboxamides are readily dehydrated to nitriles in good yields by heating with phosphorus oxychloride (91), phosphorus pentoxide (87, 71), or phosphoryl chloride (16) (Scheme 19). 

Alkylthiazoles can be oxidized to nitriles in the presence of ammonia and a catalyst. For example, 4-cyanothiazole was prepared from 4-methylthiazole by a one-step vapor-phase process (94) involving reaction with a mixture of air, oxygen, and ammonia at 380 to 460°C. The catalyst was M0O3 and V Oj or M0O3, VjOj, and CoO on an alumina support. 

Amides react ia certain cases to form ammonium salts of sulfonated amides (22). For example, treatment with ben2amide yields ammonium A/-ben2oylsulfamate [83930-12-5] C H CONHSO NH, and treatment with ammonium sulfamate yields dianmioiiiumimidodisulfonate [13597-84-17, HN(S020NH 2 Ammonium sulfamate or sulfamic acid and ammonium carbonate dehydrate Hquid or soHd amides to nitriles (27). 

Eatty amines are made by dehydration of amides to nitriles at 280—330°C, followed by hydrogenation of the nitrile over nickel or cobalt catalysts ... 

U/ .f-dimethylhydrazine is employed as a fuel in space appHcations. /V,/V-r)ichloroalkylamines can be converted to nitriles in basic media or by treatment with CsF in acetonitrile (69). 

Pyridazinecarboxamides are prepared from the corresponding esters or acid chlorides with ammonia or amines or by partial hydrolysis of cyanopyridazines. Pyridazinecarboxamides with a variety of substituents are easily dehydrated to nitriles with phosphorus oxychloride and are converted into the corresponding acids by acid or alkaline hydrolysis. They undergo Hofmann degradation to give the corresponding amines, while in the case of two ortho carboxamide groups pyrimidopyridazines are formed. 

Nitrile A-oxides, under reaction conditions used for the synthesis of isoxazoles, display four types of reactivity 1,3-cycloaddition 1,3-addition nucleophilic addition and dimerization. The first can give isoxazolines and isoxazoles directly. The second involves the nucleophilic addition of substrates to nitrile A-oxides and can give isoxazolines and isoxazoles indirectly. The third is the nucleophilic addition of undesirable nucleophiles to nitrile A-oxides and can be minimized or even eliminated by the proper selection of substrates and reaction conditions. The fourth is an undesirable side reaction which can often be avoided by generating the nitrile A-oxide in situ and by keeping its concentration low and by using a reactive acceptor (70E1169). 

On the whole, the cycloaddition of alkynes to nitrile N-oxides is one of the most important routes to isoxazoles, but in spite of its potentially wide application, its synthetic utility is less than that of the corresponding reaction with alkenes for the following reasons. (1)... 

The thermal or photolytic fragmentation of furazans to nitriles and nitrile Af-oxides has been reported (73JOC1054, 75JOC2880). The irradiation of dimethylfurazan (419) in the presence of cyclopentene, and benzofurazan (420) in the presence of dimethyl acety-lenedicarboxylate, gave isoxazoline (421) and isoxazole (422), respectively, in good yields. The thermolysis of acenaphtho[l,2-c]furazan (423) in the presence of phenylacetylene gave isoxazole (424) in 55% yield. 

Isoxazolin-5-imines were produced by nitrile oxide addition to cyanoacetates (62HC(17)l,p.7), by the reaction of nitrones with phenylacetonitrile (74CB13), and by base addition of nitrosobenzene to nitriles (Scheme 148) (72LA(762)154). 

The 1-azirines obtained from the vapor phase pyrolysis of 4,5-disubstituted 1-phthalimido-1,2,3-triazoles (157) have been found to undergo further thermal reactions (71CC1S18). Those azirines which contain a methyl group in the 2-position of the ring are cleaved to nitriles and phthalimidocarbenes, whereas those azirines which possess a phenyl substituent in the 2-position rearrange to indoles. 

Thermolysis of tertiary and secondary alcohols with (caitxsmethoxysulfamoyi) trtethylammonium Inner salt 5 to give olefins also conversion ol amides to nitriles... 

However, when the addition is performed 111 a nucleopliilic solvent such as methanol, cleavage of the imine linkage occurs to give difliioroamino compounds [78] (equation 12) W, At-Difluorotrifluoromethylamine can be prepared from or from thiocyanates, as shown in equation 13 [79, 80] Another way to produce difluoroamino compounds is the addition of fluorine to nitriles by means of AgFj [Sf ] or C0F3 [S/]... 

Asymmetric cycloaddition of functionalized alkenes to nitrile oxides and nitrones 98YGK11. 

Nitronates derived from primary nitroalkanes can be regarded as a synthetic equivalent of nitrile oxides since the elimination of an alcohol molecule from nitronates adds one higher oxidation level leading to nitrile oxides. This direct / -elimination of nitronates is known to be facilitated in the presence of a Lewis acid or a base catalyst [66, 72, 73]. On the other hand, cycloaddition reactions of nitronates to alkene dipolarophiles produce N-alkoxy-substituted isoxazolidines as cycloadducts. Under acid-catalyzed conditions, these isoxazolidines can be transformed into 2-isoxazolines through a ready / -elimination, and 2-isoxazolines correspond to the cycloadducts of nitrile oxide cycloadditions to alkenes [74]. 

Chain extension by means of the reaction of alkyl halides with cyanide is frequently alluded to but rarely employed, mainly because of the long reaction times and poor yields usually encountered. The use of DMSO as a solvent has greatly simplified the procedures and improved the yields of many ionic reactions, and the conversion of alkyl chlorides to nitriles is a good example. 

Methyl-17/-l,5-benzodiazepin-2(37/)-one undergoes addition to nitrile imines at the 4,5-bond, e.g. formation of 33.-10 1... 

This fact gives enough reason to suppose that the reaction of hydrogen sulfide addition to nitrile groups starts with the attack of the nucleophilic mercapto anion... 

Cyano-de-diazoniations of the Sandmeyer type have been used for the synthesis of aromatic nitriles for many decades (example Clarke and Reed, 1964), as cyanide ions are comparable to bromide and iodide in many respects. A homolytic cyano-de-diazo-niation that does not use metal ions as reductant or ligand transfer reagent was described by Petrillo et al. (1987). They showed that substituted diazosulfides (XC6H4 — N2 — SC6H5), either isolated or generated in situ from arenediazonium tetrafluoroborates and sodium benzenethiolate, react with tetrabutylammonium cyanide in dimethylsulfoxide under photon stimulation, leading to nitriles (XC6H4CN). The method worked well with eleven benzenediazonium ions substituted in the 3- or 4-position, and was also used for the synthesis of phthalo-, isophthalo-, and tere-... 

Heterocyclic sulphoxides of general structure 185,186 and 187 have been prepared by cycloaddition of diarylsulphines 173b to nitrile oxides 188226, nitrile ylides 189227 and nitrones 190228, respectively (equation 100). 

The conversion of secondary a-nitro sulfones (257) upon treatment with 20% aqueous titanium(III) chloride in THF to nitriles has been reported (equation 157)146. 

Iminocarbene complexes of chromium and tungsten are useful isolable synthetic equivalents to nitrile ylides having the advantage that the range of 1,3-dipo-larophiles is not limited to electron-acceptor substrates and can be extended to electronically neutral as well as to electron-rich systems [56] (Scheme 18). 

Giacomelli et al. constructed 3-propylisoxazole-5-yl-methanol via a [3-1-2] cycioaddition (Fig. 15) [158]. Nitrobutane was converted to nitrile oxide in the presence of 4-(4,6-dimethoxy [1,3,5]triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) and catalytic 4-dimethylaminopyridine (DMAP). Trityl chloride resin-bound propargyl alcohol was employed as the dipolarophile to trap the nitrile oxide, forming the cyclo adduct isoxazole ring under unusually mild conditions (i.e., microwave irradiation at 80 °C for five times 1 min). Disappearance of the starting material was monitored by FT-IR. 

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