N X+ R3 Y Z N N2 – N X R3 N Z– Y N2 + 3 4 (X = NPh, O, S) N S R3 R4 N3 a R3 = Me, R4 = H b R3 = Me, R4 = CN c R3 = Me, R4 = CHO d R3 = Me, R4 = NO2 e R3 = Ph, R4 = CN f R3 = MeS, R4 = CN g R3 = MeSO2, R4 = CN 5 N S N O Me 6 N S N O N+ Me 7 O– N S Me N N N 8 Me N S C N 9 226 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 226 J. Chem. Research (M), 1997, 1631–1650 Rates and Products of the Thermal Decomposition of 5-Azidoisothiazoles (The late) Gerrit L’abb�e, Leonard K.Dyall, Kathleen Meersman and Wim Dehaen* Department of Chemistry, University of Leuven, Celestijnenlaan 200F, 3001 Leuven (Heverlee), Belgium 5-Azidoisothiazoles have been thermolysed in p-xylene solutions to yield bicyclic products; there are appreciable neighbouring group effects on the reaction rates. Both azidobenzenes and the a-azides of five-membered heteroaromatics thermolyse when heated in solution, but there are important differences in both reaction products and rates.Whereas simple azidobenzenes thermolyse slowly,1 the heterocyclic a-azides normally undergo ring opening.3,4 A further important difference between azidobenzenes and these heterocyclic a-azides relates to neighbouring group effects from such ortho substituents as nitro and formyl. In the azidobenzenes, an ortho nitro group is known to increase the thermolysis rate by 1060-fold, and an ortho formyl one by 29-fold.11 In both cases, a cyclic product results.1 The stabilization provided by the ring hetero-atom (represented by 3) places a high negative charge on the inner azido nitrogen atom, which must inhibit the formation of the bridging bond represented in the transition state 4.In this paper we explore the possibility that suitable 4-substituents in 5-azidoisothiazoles might exert large neighbouring group effects. We have synthesized the azides 5a–g, which were fully characterized by 1H and 13C NMR and IR spectroscopy, as well as by mass spectroscopy.The decay of the azido band in the IR spectrum was monitored, and all the decompositions were smoothly first-order. Rate constants are presented in Table 1, and the activation parameters for 5a in Table 2 (for both Tables see full text). The four 5-azido-4-cyano compounds 5b, 5e, 5f and 5g were chosen in order to see what effect substituents at position 3 in the ring might exert on the rate. The methyl, phenyl and methylsulfanyl groups had virtually no effect, whereas the strongly electron-withdrawing methylsulfonyl group reduced the rate by about 30%. An interesting feature of the reaction rates is the seven-fold increase when a 4-cyano group is introduced into 5-azido-3-methylisothiazole.In our studies of other a-azido heterocycles the cyano group has generally had the opposite effect on rates.5,11,12,14 With the 5-azidoisothiazoles, we must assume that 4-substituents such as formyl and nitro, which have similar inductive and resonance properties to cyano, will cause a rate increase of similar magnitude.In fact, these two groups do cause moderately large rate enhancements. These two neighbouring group effects are larger than those observed with 5-azidoisoxazoles, 12 but substantially smaller than those measured for azidobenzenes.11 As expected, 5c furnished 4-methylisothiazolo[5,4-c]- isoxazole 6 and 5d yielded 6-methylisothiazolo[4,5-c]-1,2,5- oxadiazole 1-oxide 7 upon thermolysis. Thermolysis of 5-azido-3-methylisothiazole 5a in 2,3-dimethylbutadiene as solvent yielded the triazoline 8; we did not obtain any derivative of the expected ring-opened cyano thione 9.Thermolyses of the azides 5f and 5g in the diene did not lead to isolation of triazolines, but moderately good yields of the corresponding primary amine were identified. This result appeared to demonstrate that a nitrene intermediate had been formed in the unimolecular decomposition of the azide. Techniques used: IR, 1H and 13C NMR, low- and high-resolution mass spectrometry References: 21 Schemes: 2 Table 1: First-order rate constants for thermal decomposition of 5-azidoisothiazoles in p-xylene solution Table 2: Arrhenius data for thermolysis of 5a in p-xylene solution Received, 17th March 1997; Accepted, 7th April 1997 Paper E/7/01866E References cited in this synopsis 1 L.K. Dyall, in The Chemistry of Functional Groups, ed. S. Patai and Z. Rappoport, Wiley, Chichester, 1983, Supplement D, p. 287. 3 M. Funicello, P. Spagnolo and P. Zanirato, Acta Chem. Scand., 1993, 47, 231. 4 W. Dehaen and J. Becher, Acta Chem. Scand., 1993, 47, 244. 5 G. L’abb�e, L. Dyall, K. Meersman and W. Dehaen, J. Chem. Soc., Perkin Trans. 2, 1994, 2401. 11 L. K. Dyall and P. A. S. Smith, Aust. J. Chem., 1990, 43, 997. 12 G. L’abb�e, L. Dyall, K. Meersman and W. Dehaen, J. Chem. Soc., Perkin Trans. 2, 1996. 14 L. K. Dyall, P. M. Suffolk, W. Dehaen and G. L’abb�e, J. Chem. Soc., Perkin Trans. 2, 1994, 2215. *To receive any correspondence (e-mail: wim.dehaen@chem. kuleuven