Nitrile sulfides

3-dipolar additions with dipolarophiles. Alkynes yield isothiazoles (40) in a regiospecific reaction, and with nitriles 1,2,4-thiadiazoles (41) are produced.43 47 Nitrile sulfides also react with ketones, forming 1,3,4-oxathia-zoles (39), or with activated alkenes, yielding isothiazolines.47,48 There are clearly many other reactions of nitrile sulfides still to be discovered. 

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Thermal reactions of 1,4,2-dioxa-, 1,4,2-oxathia- and 1,4,2-dithia-azoles are summarized in Scheme 1. The reactive intermediates generated in these thermolyses can often be trapped, e.g. the nitrile sulfide dipole with DMAD. 

C. Wenti up and P. Kamhouris, N-Sulfides Dinitrogen Sulfide, Thiofulminic Acid and Nitrile Sulfides, Chem. Rev., 91, 363 (1991). 

Nitrile sulfides (37) have some, admittedly slight, structural affinity with the other nitrogen-sulfur reagents discussed in Section IV. They are unstable reactive intermediates that can be generated by the thermolysis of 1,3,4-oxathiazol-2-ones (38) or of 1,3,4-oxathiazoles (39).41 42 An alternative preparation is by the elimination of 2 moles of hydrogen fluoride from imini-sulfur difluorides (Scheme 5).43 Nitrile sulfides (37) are capable of undergoing... 

Type G syntheses are typified by the 1,3-dipolar cycloaddition reactions of nitrile sulfides with nitriles. Nitrile sulfides are reactive 1,3-dipoles and they are prepared as intermediates by the thermolysis of 5-substituted-l,3,4-oxathiazol-2-ones 102. The use of nitriles as dipolarophiles has resulted in a general method for the synthesis of 3,5-disubstituted-l,2,4-thiadiazoles 103 (Scheme 11). The thermolysis is performed at 190°C with an excess of the nitrile. The yields are moderate, but are satisfactory when aromatic nitrile sulfides interact with electrophilic nitriles. A common side reaction results from the decomposition of the nitrile sulfide to give a nitrile and sulfur. This nitrile then reacts with the nitrile sulfide to yield symmetrical 1,2,4-thiadiazoles <2004HOU277>. Excellent yields have been obtained when tosyl cyanide has been used as the acceptor molecule <1993JHC357>. 

An alternative route to C-linked derivatives involves the 1,3-dipolar cycloaddition reaction of nitrile sulfides with nitriles which yields 3,5-disubstituted-l,2,4-thiadiazoles of unequivocal structure (see Section 5.08.9.8). 

Entry Nitrile Sulfide Product 76 Yield (%)° Isomer ratio b... 

In contrast, the reaction of SchifFs bases (276) with aryl nitrile sulfides yields 1,2,4-thiadiazolines (277) in very low yields (2-5%) (Equation (42)) <86JCR(S)156>. 

As reported before (see Section 4.14.5.2), 1,3,4-oxathiazolone (112) undergoes ring fragmentation readily on heating to give nitrile sulfides, a very unstable class of 1,3-dipoles. A considerable part... 

Azolines of type (13) undergo thermal decomposition in an analogous way to that already discussed for azolones (see Section 4.14.5.2) (Scheme 19). Path (i) is followed by those azolines having Z = S and path (ii) by those with Z = O. Path (i) is a typical retro-1,3-dipolar cycloaddition process, via an intermediate nitrile sulfide, while path (ii) might involve an acyl (Y = Z = O) or thioacyl (Y = S, Z = O) nitrene intermediate (136), which in turn rearranges to iso(thio)cyanate. However, no systematic attempts to trap this possible nitrene intermediate seem to have been made, and so a concerted pathway for the fragmantation cannot be ruled out. 

As reported before (see Section 4.14.6.1, Scheme 19), thermolysis of oxathiazolines (169) proceeds via a retro 1,3-dipolar cycloaddition to produce the carbonyl compound and the nitrile sulfide intermediate. Trapping reactions have been carried out with DMAD, ECF (ethyl cyano formate), and benzonitrile to give respectively isothiazoles (170) and thiadiazoles (171) and (172). However in two particular cases (R = 4-MeOC6H4, 4-ClCgH4, thermolysis in the presence of benzonitrile gives (172) and the thiadiazole (173) in very low yields. It has been suggested that the latter arises... 

Dipolar cycloaddition is one of the most important methods in assembling five-membered ring heterocycles. For the 1,4-(oxa/thia)-2-azole system, nitrile oxides, and nitrile sulfides have the correct sequence of atoms for the 47t 1,3-dipolar component and the 2n component can be a either a C=0 or a C=S heterodipolarophile (Scheme 41). Nitrile oxides, usually generated in situ from the corresponding hydroximoyl chlorides and a base, add to various types of (3=0 bond affording 1,4,2-dioxazole derivatives. 

Phenylthiazirene (34) was considered to be the most reasonable nitrile sulfide precursor but no spectral peak could be assigned unambiguously to this otherwise unknown compound <78JCS(P1)746>. 

When compared with the results of Holm et al. the lack of benzonitrile sulfide (35) bands may be explained by a change in the photochemical pathway due to the microscopic environment (argon matrix at 11 K Wentrup et al. versus PVC/EPA Holm et al.) or to rephotolysis of benzonitrile sulfide (35) under the experimental conditions into benzonitrile (28) and sulfur. A dependence of the photochemical pathways due to the microscopic environments are known from other cases <76TL873>. For a further discussion of the generation and reaction of nitrile sulfides see the review by Wentrup and Kambouris <91CRV363>. 

Phenyl nitrile sulfide, from the thermolysis of an oxathiazolone (34) (R = Ph), adds with the same orientation as the nitrile oxides to Bu C P (Scheme 10) <87S689, 88AG1541>. More 1,2,4-thiazaphospholes are produced with phosphaalkenes, R = Ph, 2- and 4-tolyl, R = Ph, SiMe3 <88TL4535> for side products of this reaction see Chapter 3.15 and Section 4.22.11.2. 

The anhydro-5-hydroxy-l,3,2-oxathiazolylium hydroxide system (83) and DMAD thermally yielded an intermediate 1 1 cycloadduct (84) which lost C02 forming dimethyl 2-phenylisothiazole-3,4-dicarboxylate (85) (72CB196). Irradiation of (83) in neat DMAD formed the valence tautomer (82) which lost C02 to give the nitrile sulfide dipole (81) captured by DMAD to form dimethyl 3-phenylisothiazole-4,5-dicarboxylate (80) (75JA6197) (see also CHEC 4.17). 

Phenylthiazirine (9) could be a yet undetected precursor for the nitrile sulfide when generated from the thiatriazole or 8. Its possible formation from the thiatriazole system has attracted other investigators15,29 with regard to certain thermal reactions. However, as a cyclic conjugated 4-n electron-system it should be antiaromatic,30 and therefore thermally unstable. It could possibly be generated in photochemical reactions. 

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