Regio- and stereo-specificity of cycloaddition reactions of sulphines with diphenylnitrilimine

摘要

1218 J.C.S. Perkin I Regio- and Stereo-specificity of Cycloaddition Reactions of Sulphines with Diphenylnitriliminet By Bianca F. Bonini, Gaetano Maccagnani," and Germana Mazzanti, Laboratorio CNR dei composti del carbonio contenenti eteroatomi, lstituto di Chimica Organica dell'UniversitA, Wale Risorgimento 4, 40136 Bologna, Italy Lambertus Thijs, Gauke E. Veenstra, and Binne Zwanenburg,' Department of Organic Chemistry, University of Nijmegen, Toernooiveld, Nijmegen, The Netherlands Sulphines (thione S-oxides) undergo cycloaddition reactions with diphenylnitrilirnine to yield in a regiospecific manner 1.3.4-thiadiazoline 1 -oxides, with the exception of thiofluorene S-oxide, which gave the other regioisorner (a 1.2.3-thiadiazoline 1 -oxide) as a by-product. The products obtained from cyclisation with geometrically isomeric sulphines indicate that steric integrity is lost during the reaction.This stereomutation does not come about by sulphine isomerization prior to reaction but is caused by product equilibration afterwards. It is shown that the steric integrity is lost by ring opening-ring closure of the cycloaddition product. A ring expansion of the addition product similar to the penam-cepharn conversion is described. CYCLOADDITIONreactions of cumulenes with 1,3-dipoles serve as an important source of a great variety of hetero- cyclic compounds.l In this respect cycloadditions with sulphines (thione S-oxides) are of special interest, since these heterocumulenes have a bent structure allowing the existence of geometrical isomerism.2 This structural property of sulphines enables us to investigate the stereo- chemistry of the cyclization as well as the regiochemistry.From the synthetic point of view these cycloadditions are of interest since they lead directly to heterocyclic com- pounds containing the sulphoxide function. Previously we reported on the cycloaddition reactions of sulphines with dia~oalkanes,~ nitrile oxide^,^ nitrile ylide~,~and nitrones6 This paper gives a full account of the cycloaddition reactions of sulphines with diphenyl- nitrilimine Phb=N-NPh (DPNI). Diphenyl sulphine (la) gave with DPNI, generated * ila situ from N-(a-chlorobenzy1idene)-N'-phenylhydr-azine and triethylamine, the cycloadduct (2a) in 68 yield, The structure of this adduct was assigned on the basis of spectral data, vmax 1070 (SO) and 1535 (GN) cm-1, combustion analysis, and independent synthesis.Oxidation of 2,4,5,5-tet raphenyl- A2-1,3,4-thiadiazoline t This paper is designated Part 14 of the series ' Sulphines ' bythe Italian group (Part 13, ref. 4) and part 36 of the series ' Chemistry of Sulphines ' by the Dutch group (Part 35, G. E. Veenstra and B. Zwanenburg, Tetrahedron, 1978, in the press). H. Ulrich, ' Cycloaddition Reactions of Heterocumulenes ', Academic Press, New York, 1967. J. F. King and T. Durst, J. Amer. Chem. SOL,1963,85, 2676; Canad. J. Chem., 1966, 44, 819; B. Zwanenburg, L. Thijs, and J. Strating, Tetrahedron Letters, 1967, 3453; B. Zwanenburg and J.Strating, Quart. Reports Sulfur Chem., 1970, 5,79; B. F.Bonini, L. Lunazzi, G. Maccagnani, and G. Mazzanti, J.C.S. Perkin I, 1973, 2314; A. Tangerman and B. Zwanenburg, Tetrahedron Letters, 1973, 79; Th. W. Hummelink, J. Cryst. MoZ. Struct., 1974,4, 87, 373. (3a) (see Scheme l),obtained from the cycloaddition of thiobenzophenone and DPNI, gave the corresponding S-oxide which was identical with adduct (Za). The struc- ture of adduct (3a) was firmly established by Huisgen et aL9 Sulphines (lb and c) similarly gave the adducts (2b) (62)and (Zc) (85). The reaction of thiofluoren- one S-oxide with DPNI was reported7 to yield solely adduct (2d). However, in view of the deviant results obtained with this sulphine and benzonitrile oxide: the reaction of (Id) and DPNI was carefully re-examined.Indeed, a second product (4) was isolated in low yield (15) in addition to the predominant adduct (2d) (54). The structure of the minor product (4) was apparent from the correct elemental analysis and particularly the i.r. band at 1125 cm-l (sulphinamide lo). Chemical proof for structure (2d) was provided by the thennolytic be- haviour of the corresponding sulphone (5d). Heating in benzene (80 "C) gave quantitative liberation of sulphur dioxide while benzonitrile as well as the anil (6d) were isolated in high yields. This two-fold extrusion process B. F. Bonini, G. Maccagnani, A. Wagenaar, L. Thijs, and B. Zwanenburg, J.C.S. Perkin I, 1972, 2490; B. Zwanenburg, A. Wagenaar, L.Thijs, and J. Strating, ibid.. 1973, 73; L. Thijs, A. Wagenaar, E. M. M. van Rens, and B. Zwanenburg, Tetrahedron Letters, 1973, 3589. B. F. Bonini, G. Maccagnani, G. Mazzanti, L. Thijs,H. P. M. M. Ambrosius, and B. Zwanenburg, J.C.S. Perkin I, 1977, 1468. 5 B. F. Bonini, G. Maccagnani, G. Mazzanti, and B. Zwanen- burg, Gazetta, 1977, 107,289. 6 B. F. Bonini, G. Maccagnani, G. Mazzanti, P. Pedrini, and B. Zwanenburg, Gazetta, 1977, 107,283. 7 B. I;.Bonini, G. Maccagnani, L. Thijs, and B. Zwanenburg, Tetrahedron Letters, 1973, 3569. 8 R. Huisgen, M. Seidel, G. Wallbillich, and H. Knupfer,Tetvahedron, 1962, 17,3. Q R. Huisgen and W. Mack, Chern. Ber., 1972, 105,2815. 10 L. J. Bellamy, 'Advances in Infrared Group Frequencies ', Methuen, London, 1968.is only feasible for adduct (2d), not for (4). Similarly, the sulphone derived from (2a) gave upon heating SO,, benzonitrile, and anil (6a) (see Scheme 1). R1 0=s" R2 (1) a; R1 = R2 = Ph b; R1 = R2 = 4-MeOCgH4 C; R1 = R2 = 4-MeCgH4 d; R1 R2 = e; R1 = Ph R2 = 2-MeCsH4 f ; R1 = 2-MeCgH4 R2 = Ph g; R1 = Ph R2 = 1-naphthyl h; R1 = l-naphthyl, R2 = Ph i ; R1 = 4-MeCgHb R2 = amp;ClCgH4 j ; R1 = 4-CLC6Hb ,R2 = 4-MeCgH4 k; R1 = Ph R2 = PhS I; R1 = PhS R2 = Ph m; R1 = Ph, R2 = Me n; R1 = Me , R2 = Ph The results with the sulphines (la-d) show a high degree of regiospecificity for the cycloaddition with 0 (5 1 compensation for the x-bond energy lost is achieved in the combined energy of the two newly formed o-bonds.Ap-parently, attachment of an oxygen atom to the C=S func-tion does not affect the outcome of this energy balance. Having established the regiochemistry of the cyclo- addition, the stereochemistry was investigated by treat- ing geometrically isomeric sulphines with the 1,3-dipole. From the reaction of the isomers of phenyl o-tolyl sul- phine (le and f ) with DPNI the same predominant adduct was isolated to which tentatively the anti-structure (2e) was assigned (see Experimental section). In both cases the n.m.r. spectrum of the crude product mixture showed in addition to the methyl signal of (2e) at 6 2.38 an ab- sorption at 6 2.07 attributable to the methyl group of the syrt-adduct (2f). On the basis of integration the anti : syn ratio was 9 : 1.However, the syn-adduct (2f) could not be isolated probably because of isomerization to the anti-isomer during chromatography. Attempts to pre- pare both adducts (2d and f) by oxidation of the parent thiadiazoline also resulted in the formation of one strongly dominating isomer which turned out to be identical with the anti-adduct (2e) obtained during the cyclo- additions of (le and f). Similarly, cycloaddition of the isomers (lg and h) with DPNI gave only one adduct (2g). The sterically hindered isomers of mesityl phenyl sulphine failed to react, demonstrating that the cycloaddition with DNPI is sensitive to steric hindrance as observed4 for SCHEMEI DNPI. The regiochemistry is the same as that observed for the cycloaddition reactions of DPNI and the corres- ponding diary1 thioketones,g this in spite of the fact that the distribution 11*12 and other molecular parameters l3 differ considerably. This observation, that the orient- ation of thioketones and its S-oxides in cycloaddition reactions with DPNI is the same, is consistent with the results obtained previously with other 1,3-dipoles, vix.diazoalkanes and benzonitrile oxide.4 The orientation in cycloadditions with heterodipolarophiles usually obeys the principle of maximum gain in o-bond energy,12 mean- ing that the reactants join in such a manner that the best ~ 1972,11 J. p. snyder and D. N. H ~J.C.S.~ ,-hem.~ comm.,, 1305; F. Bernardi, G. Maccagnani, and A.Mangini, Anales de Quim., 1974, 70, 1199; J. van Lierop, A. van der Avoird, and B. Zwanenburg, Tetrahedron, 1977, 33, 359. other 1,3-dipoles with sulphines. In order to minimize the influence of steric factors the E-and Z-isomers of 9-chlorophenyl P-tolyl sulphine (li and j) were subjected to cycloaddition with DPNI. With (li) a mixture of the diastereoisomeric adducts (2i and j) was obtained in the ratio 1: 1 whereas (lj) gave the product ratio of 2 : 3. Oxidation of the parent thiadiazoline gave a ratio of (2i and j) of 1 : 2. The E-and Z-isomers of phenyl phenyl- thio sulphine (lk and 1) both yielded the same adduct (2k)-All the experiments conducted with the geometrically isomeric sulphines indicate that the steric integrity is lost during the cycloaddition.This result is surprising since 12 R. Huisgen, Angew. Chem. Internat. Edn., 1963, 2, 633. l3 J. P. Snyder, J. Org. Chem., 1973, 38, 3965. 1220 other 1,3-dipoles such as diazoalkanes l4and benzonitrile oxide4 showed a stereospecific cyclization. In view of this an explanation invoking a non-concerted cycloaddi- tion process seems rather unlikely. On the other hand, 0 SN (2d) (4) SCHEME2 both isomerization of the sulphines prior to cycloaddition and product equilibration afterwards would account for the loss of steric integrity. (2) (7) J.C.S. Perkin T Pyramidal inversion of the sulphoxide function 159 16 in the adducts (2) seems unlikely, since the configurational stability of sulphoxides is usually rather high.In this case interaction of the imine bond and/or the lone pair at N-4 with the sulphoxide function may lower the inversion barrier.15 The arrangement of atoms -N(4)-C(5)-S(=O) present in the adducts is also encountered in the five-membered ring of the penicillin skeleton. It istherefore suggested that the stereomutation of (2) bears some resemblance to the con- version of (22)-penicillin sulphoxide into the (S)-sulphox- ide,17 which is believed to proceed via the intermediacy of a ring-opened product,l* vix. a sulphenic acid. In the present case the ring opening-ring closure (2) (8) is thought to be responsible for the loss of stereospecificity in the cycloaddition. In order to provide evidence for this mechanism the (9 1 (301 SCHEME3 Isomerization of sulphines in the presence of triethyl- amine was observed equilibrium ratio 88 : 12 for (le) : (If) and 69 : 31 for (lk) : (ll).Reliable information on isomerization during cyclization can be provided by recovering sulphines from incomplete reactions. Such experiments were conducted with (le, f, k, and 1) ; in all cases the recovered sulphine had the original configur- ation. Therefore, isomerization prior to cycloaddition is not a likely explanation for the non-stereospecificity. Support for product equilibration was provided by the equilibration of mixtures of (2i and j) in the ratios 1 : 1 and 1:2, on standing or heating, to give the ratio 3 :2. Similar behaviour was found for the isomeric adducts (2k and 1).l4 L. Thijs, A. Wagenaar, E. M. M. van Rens, and B. Zwanenburg, Tetrahedron Letters, 19 7 3, 3589. 16 A. Rauk, L. C. Allen, and K. Mislow, Angew. Chem., 1970, 82, 453; A. Rauk, J. D. Andose, W. G. Frick, R. Tang, and K. Mislow, J. Amer. Chem. SOC.,1971, 93, 6507. l6 P. H. Lauer, lsquo; Steric Aspects of Sulfur Chemistry,rsquo; ed. A. Senning, Marcel Dekker, New York, 1972, vol. 3. mixture of adducts of (2m and n), obtained from the cycloaddition of E-+ 2-methyl phenyl sulphine (lm and n), was treated with trimethylsilyl chloride and hexa- methyldisilazane. Similar conditions were used to trap 19 the intermediate sulphenic acid during the equilibration of penicillin sulphoxides. However, no silylated sul- phenate was isolated but the dimer of the 1,3-dipole, vix.(7), instead. The formation of (7) is rationalized as out-lined in Scheme 3. The ring-opened sulphenate (8) can close in two fashions. Reaction of the ambident sul- phenate at the sulphur atom leads to the five-membered ring (2), whereas closure via the oxygen atom produces the six-membered ring (9), which upon fragmentation gives DPNI, the ketone R1R2C=0,and sulphur. Dimer-ization of DPNI leads to (7). Heating the adduct (2a) 17 D. H. R. Barton, F. Comer, and P. G. Sammes, J. Amer. Chem. SOC.,1969, 91,1529; R. A. Archer and P. V. De Marco, ibid., p. 1530. 18 T. S. Chou, J. R. Burgtorf, A. L. Ellis, S. R. Lammert, and S. P. Kukolja, J. Amer. Chem. SOC.,1974, 96, 1609. lo T. S. Chou, Tetrahedron Letters, 1974, 725. in the presence of thiobenzophenone provided a means to trap DPNI to yield the product (3a) in addition to benzo- phenone and sulphur.* Confirmatory evidence for the suggested equilibration via (2) (8) was obtained by treating the adduct mixture (2m and n) with acetic anhydride in benzene for 6 h at 80 "C.Thiadiazine (loa) was isolated in 70 yield. The structure of this product was established on the basis of a correct elemental analysis and spectral data (ix., n.m.r., and mass). The formation of (loa) is readily explained as outlined in Scheme 4. The primary Ph (10) All experiments were carried out under nitrogen and with dry solvents. N-(a-Chlorobenzylidene) -N'-phenylhydr- azine was prepared as described in ref.8. Sulphines were prepared as reported previously 22 by oxidation of the corres- ponding thiocarbonyl compounds with m-chloroperbenzoic acid. 2,4,5,5-Tetraphenyl-A2-1,3,4-thiadiazolinel-Oxide (2a).-A solution of triethylamine (1.00g, 10.0mmol) in benzene (5 ml) was added slowly to a stirred solution of diphenyl sulphine (la)(1.07g, 5.0 mmol) and DPNI precursor (1.15g, 5.0 mmol) in benzene (25 ml). After heating at reflux for 0.5 h, the mixture was allowed to react at 20 "C for 20 h. 0; R = Me b; R = Et SCHEME4 ring-opened product (11) cj. (8) is trapped by acetic anhydride as a mixed anhydride. The enamine function reacts in a nucleophilic fashion with the sulphur atom now bearing a good leaving group.The thiadiazine thus formed is acylated by acetic anhydride as expected for the enamine part of this molecule.20 Propionic anhydride similarly gave product (lob) in 60 yield. The formation of the six-membered ring (10) bears ana- logy with the conversion of penicillin sulphoxide to cephalosporin (penam-cepham conversion) .21 In conclusion, sulphines react with DPNI to give thiadiazoline S-oxides with a high degree of regiospeci-ficity. The cycloaddition is non-stereospecific due to equilibration of the adducts via a ring opening-ring closure mechanism. EXPERIMENTAL 1.r.spectra were recorded with a Perkin-Elmer 257grating spectrometer. N.m.r. spectra were obtained with JEOL C-6OHL or Varian HA 100 and T-60 spectrometers (Me,Si as internal standard).Mass spectra were recorded with a JEOL JMS DlOO spectrometer. * An for the formation Of (3a)from (2a)and thiobenzophenone could be a retro-1,3-dipolar cycloaddition reaction giving DPNI and (14. Preferential cyclization with thiobenzophenone would then give (2a). However, the sulphine (la)which is stable under these conditions, was notdetected. Therefore, this rationale is rejected. 2O P. W. Hickmott and H. Suschitzky, Chem. and Ind., 1970, 1188. 21 P. G. Sammes, Chem. Rev., 1976,76, 113. The precipitated Et,NHCl (0.55g) was filtered off and the filtrate concentrated in vacuo. The residue was chroma- tographed on a silica gel column. Elution with benzene gave unchanged precursor (0.20 g) ; elution with benzene-ether (1 : 1) gave the adduct (2a) (1.40g, 68), m.p.167-168 "C (from methanol) (Found: C, 76.8;HI 4.75;N, 6.8;S,7.85. C,,H,,N,OS requires C, 76.45;H, 4.9;N, 6.85; S, 7.85y0), vmx. (CCl,) 1070 cm-l (SO), 6 (CDCl,) 6.8-8.1 (m, ArH). The adduct (2a) was identical in all respects with that pre- pared by cycloaddition of diphenylnitrilimine and thio- benzophenone 23 and subsequent oxidation as follows. A solution of monoperphthalic acid (mPPA) (0.45mmol) was added at 0 "C to the adduct (3a) (0.18g, 0.46mmol) in ether (10ml). After 24 h the phthalic acid was filtered off, the filtrate was concentrated and the residue was chromato-graphed on silica. Elution with benzene afforded adduct (2a) (0.17g, 91). 2,4,5,5-Tetraphenyl-A2-l,3,4-thiadiazolinc1,l-Dioxide(5a). -Adduct (2a) (0.7g, 1.69mmol) in ether (30ml) was treated with mPPA (8.9mmol) for 60 h at 5 "C.Removal of the phthalic acid, concentration of the filtrated in vacuo, and chromatography on silica gel gave the sulphone (5a) (0.44g, 61y0), m.p. 118-119 "C from CH2C12-hexane (1 : l) (Found: C, 72.8; H, 4.9; N, 6.45; S,7.35. C2,H,,,N2SO2 22 B. Zwanenburg, L. Thijs, and J. Strating, Rec. Trav. chim., 1967, 86, 577; B. F. Bonini, s. Ghersetti, G. Maccagnani, and G. Mazzanti, Boll. sci. Fat. ind. Bologna, 1969, 27, 419; B. Zwanenburg, L*Thijs, and J-Strating, Rec. Trav. chim., I9T19 90,614; B.Zwanenburg, L.Thijs, and A. Tangerman, Tetrahedron, 1971,27, 1731; A. Tangerman and B. Zwanenburg, J.C.S. Perkin IT, 1974,1413. 23 R.Huisgen, R. Grashey, M. Seidel, H. Knupfer, and R. Schmidt, Annalen, 1962, 658, 169. 1222 requires C, 73.55; H, 4.75; N, 6.6; S, 7.55y0),v,,, (CCl,) 1125 and 1330 cm-l (SO,), 6 (CDCl,) 6.8-8.1 (m, ArH). Heating of (5a) (43.11 mg, 0.1015 mmol) for 15 min in ben- zene (5 ml) at 80 "C gave benzonitrile and N-diphenyl- methyleneaniline (6a) in quantitative yield. The yields were determined by g.1.c. analysis (column 20 SE 30; 250"). The SO, liberated during the thermolysis was trap- ped in 0.1N-NaOH (50 ml). Titration of the absorbed SO, with I, indicated a lOOyoyield. 2,4-Di~henyZ-5,5-bis-(p-methoxyphmyl)-A2-l,3,4-thiadi-azoline l-Oxide (2b) .-As described for (2a) , bis-(p-meth-oxyphenyl) sulphine (lb) (0.67 g, 2.46 mmol) gave the adduct (2b)(0.71 g, 62y0), m.p.137-138 "C (from methanol) (Found: C, 71.4; H, 4.9; N, 5.7; S, 6.9. C,,H,,N,O,Sre-quires C, 71.75; H, 5.15; N, 5.95; S, 6.85y0),vmax. (CCl,) 1070 cm-l (SO), 6 (CDC1,) 3.81 (3 H, s, OMe), 3.86 (3 H, s, OMe), and 6.5-8.1 (18 H, m, ArH). 2,4-Diphenyl-5,5-di-p-tolyl-A2-1,3,4-thiadiazoline l-Oxide (2c) .-As decribed for (Za), di-p-tolyl sulphine (lc) (1.50 g, 6.20 mmol) gave the adduct (2c) (2.30 g, 85y0), m.p. 152- 153 "C (from methanol) (Found: C, 77.6; H, 5.5; N, 6.5; S, 7.2. C,,H,,N20S requires C, 77.0; H, 5.55; N, 6.4; S, 7.35y0),vmax. (CCl,) 1070 cm-l (SO), 6 (CDCl,) 2.30 (3 H, s, Me), 2.36 (3 H, s, Me), and 6.9-8.2 (18 H, m, ArH). As described for (Za), adduct (2c) (0.20 g, 0.46 mmol) gave upon oxidation with mPPa (1.5 mmol) 2,4-diphenyl-5,5-di-(p- tolyl-A2-l,3,4-thiadiazolzne1, l-dioxide (5c) (0.03 g, 14y0), m.p.107-108 "C (Found: C, 73.2; H, 5.4; N, 6.05. C,,H2,N,0,S requires C, 74.3; H, 5.35; N, 6.2y0), vmax. (CCI,) 1 125 and 1 330 cm-l (SO,), 6 (CDCl,) 2.37 (6 H, s, Me) and 6.8-8.3 (18 HI m, ArH). During the isolation and puri- fication spontaneous fragmentation of (512) was observed. Thermolysis of (5c) gave SO,, benzonitrile, and anil (6c). Cycloaddition with Thiofluorenone S-Oxide (Id).-As described for (2a), sulphine (Id) (1.06 g, 5.0 mmol), tri- ethylamine (1.0 g, 10.0 mmol), and DPNI precursor (1.15 g, 10.0 mmol) gave after elution with benzene fluorenone (0.2 g, 22) and 2',4'-diphenylfluorene-9-sPiro-5'-A3'-1',2',3'-thiadiazoline 1'-oxide (4) (0.3 g, 15y0), n1.p.154-155 "C (from methanol) (Found: C, 76.0; H, 4.35; N, 6.95; M, 406.2061. C,,H,,N,OS requires C, 76.8; H, 4.45; N, 6.9; M, 406.2045), vmx. (CCl,) 1 125 cm-l (SO), 6 (CS,) 6.6-8.2 (m,ArH), m/e 406 (M+,87), 358 (M+-SO, loo), and 253 (M+-PhNNSO, 79). Elution with benzene-ether (10 : 1) afforded 2',4'-diphenylfluorene-9-spiro-5'-A2'-l',3',4'-thiadiazoline 1'-oxide (2d) (1.1 g, 54y0), m.p. 173-174 "C (from ethanol) (Found: C, 76.65; H, 4.5; N, 6.9; S, 7.9. C,,Hl,N20S requires C, 76.8; H, 4.45; N. 6.9; S, 7.9y0), vrnax. (CC1,) 1070 cm-l (SO), 6 (CS,) 6.6-8.2 (m, ArH). As described for (2a),oxidation of (2d) 0.25 g, 1.36 mmol) with mPPA (3.6 mmol) for 6 days at 6 "C gave the sulphone (5d) (0.17g, 30y0), m.p.146-147 "C from CH,Cl,-hexane (1 : l) (Found: C, 73.3; H, 4.35; N, 6.6; S, 7.6. C,,H,,N,O,S requiresC, 73.9; H, 4.3; N, 6.65; S, 7.6~0),v,,,x~(CC1,)1335 and 1135 cm-l (SO,) and unchanged sulphoxide (2d). Thermolysis of (5d) afforded SO,, benzonitrile, and fluoren- one anil 24 (6d). Cycloaddition with SuZphines (le and f ) .-The reaction with the E-sulphine (le) (0.82 g, 3.6 mmol) was carried out as described for (la). After heating for 0.5 h, the mixture was stirred for 48 h at 20 "C. After filtration, evaporation of the solvent, and chromatography on silica benzene-ether (1 : l)a 9 : 1mixture of the adducts (2e and f) (1.10 g, 72) was obtained. Upon crystallization from methanol only 24 G. Reddelieu, Ber., 1910, 42, 4760. J.C.S.Perkin I adduct (2e) was obtained, m.p. 132-133 "C (Found: C, 75.85; H, 5.3; N, 6.6; S, 7.6. C,,H,,N,OS requires C, 76.75; H, 5.25; N, 6.65; S, 7.6), vmaX. (CCl,) 1070 cm-l (SO),6 (CS,) 2.38 (3 HI s, Me) and 6.7-8.0 (19 H, m, ArH). The minor component having a methyl signal at 6 2.07 (CS,) could not be isolated. The tentative assignment of the antz-structure to the more stable isomer (2e) and the syn- structure (2f) was based on the position of the methyl signals in comparison with that of the parent compound (3e), 6 2.27. The reaction with the Z-isomer (If) was performed in the same manner. After chromatography and crystallization from methanol adduct (2e) was isolated (54). As des-cribed for (3a), 2-methylthiobenzophenone (3.0g, 14.2 mmol) gave 2,4,5-triPhenyl-5-tolyl-A2-1,3,4-thiadiazoline (3e) (3.25 g, 57y0), m.p.173-174 "C (from methanol) (Found: C, 80.1; H,5.6; N, 7.8. C,,H,,N,SrequiresC, 79.8; H,5.45; N, 6.9y0), 6(CS,) 2.27 (3 H, s, Me) and 6.5-8.0 (19 H, m, ArH). Adduct (3e) (2.5g, 6.1 mmol) was oxidized with mPPA (6.1 mmol) in ether (50ml) for 3 days at 5 "C. After removal of the phthalic acid and evaporation of the solvent, the product was chromatographed on alumina. Elution with benzene gave starting material (0.55 g), elution with benzene-ether (10 : 1) gave a 10 : 1 mixture of (2e and f ). The ratio of the products was determined by the integration of the 2-Me signals at 6 (CS,) 2.07 and 2.38 and is essentially the same as in the cycloaddition of sulphines (le and f ) .Oxidation of adduct (2e) (0.22 g, 0.48 mmol) with m-chloroperbenzoic acid (0.200 g, 1.OO mmol) in ether-CHC1, (3 : 1; 20 ml) for 16 h at 20 "C gave, after removal of m-chlorobenzoic acid with aqueous NaHCO, and chroma- tography, benzonitrile (0.35 g, 71) and anil (6e) (0.105 g, SO), m.p. 100-103 "C (from methanol) (Found: C, 88.5; H, 6.3; N, 5.0. C,,,H,,N requires C, 88.55; H, 6.25; N, 5.15y0),vmx. (KBr) 1620 cm-l (C=N), 6 (CDCl,) 2.01 (3 H, s, Me) and 6.65-7.80 (14 H, m, ArH). The intermediate sulphone (5e) fragmented spontaneously during the oxid- ation. Isomerization of Sulphines (le and f) .-E-Sulphine (le) (0.40 g, 1.75 mmol), triethylamine (0.5 ml), and Et,N,HCl (0.30 g, 2.20 mmol) in benzene (15 ml) were heated at re-flux for 0.5 h.After standing for 24 h at 20 "C, the mixture was filtered and concentrated in vacuo. The relative amounts of E-and Z-sulphine were determined by the inte- gration of the methyl signals at 6 2.14 and 2.24. The E :2 ratio was 88 : 12 after 24 h. When Z-sulphine (If) was used instead the E :Z ratio was 84 : 16 after 24 h. Cycloaddition with Sulphines (lg and h) .-As described for (Za),sulphine (lg) (0.080 g, 0.30 mmol), DPNI precursor (0.100 g, 0.43 mmol), and triethylamine (0.10 g, 1.00 mmol) in benzene (15 ml) gave after chromatography adduct (2g) (0.117 g, 85y0),m.p. 15G155 "C (from dioxan) (Found: C, 77.7; H, 4.7; N, 6.0. C,,H,,N,OS requires C, 78.6; H, 4.85; N, 6.1y0), vrnsx.(KBr) 1060 cm-l (SO), 6 (CDC1,) 6.66-8.01 (18 H, m, ArH) and 8.01-8.44 (4 H, ni, ArH). Similarly sulphine (lh) (0.180 g, 0.68 mmol) gave adduct (2g) (0.200 g, 64y0), which appeared to be identical in all respects with the product obtained from the cyclization of sulphine (WCycloaddition with Sulphines (li and j).-Sulphine (li) (0.200g, 0.76 mmol) was treated with DPNI precursor (1.00 mmol) in the presence of triethylamine (0.20 g, 2.00 mmol) in benzene (20 ml) as described for (2a). After standing for 3 days at 20 "C the mixture was worked up in the usual way to give a 1: 1 mixture of adducts (2i and j) (0.312 g, 90) 1978 as an oil, v,,,. (neat) 1065 cm-l (SO),6 (CDCl,) 2.58 and 2.65 (3H, s, ratio 1 : 1, Me), 7.0-7.7 (16H, m, ArH), and 7.0- 8.2 (2 H, m, ArH).A solution of (2i and j), ratio 1 : 1, in chloroform changed upon standing or heating at reflux to a ratio of 2 : 3. Sulphine (lj) (0.24g, 0.91 mmol) in benzene (20 ml) gave, as for (li), a 2 : 3 ratio of adducts (2i and j). Efforts to separate (2i and j) were unsuccessful. The ad- ducts (2i and j) were prepared independently by oxidation of (3i). The latter was obtained by cyclization of 4-chloro-4'- methylthiobenzophenone (0.54 g, 2.20 mmol) with DPhTI precursor (0.507 g, 2.20 mmol) and triethylamine (0.30 g, 3.00 mmol) in benzene (40 ml). After standing for 24 h at 20 "C the mixture was filtered, the filtrate was concentrated in vacuo and the residue was crystallized from ethyl acetate- MeOH (10 : 1) to give thiadiazoline (3i) (0.69 g, 91yo), m.p.141-144 OC, 6 (CDCl,) 2.70 (3 H, s, Me) and 7.0-8.1 (18 H, m, ArH). Oxidation of (3i) (0.30 g, 0.68 mmol) was per- formed by treatment for 2 h at 0 "C with m-chloroperben- zoic acid (0.13 g, 0.68 mmol) in CHC1,-ether (1 : 1; 30 ml). After standing for 12 h at 20 "C m-chlorobenzoic acid was removed with aqueous NaHCO, and the mixture was chro- matographed (preparative t.l.c., development with benzene, elution with ether) to afford adducts (2i and j) (0.30 g, 97) in the ratio of 1 : 2. On standing the ratio changed to 2 :3, as determined by integration of the methyl signals at 6 2.58 and 2.65. The assignment of these signals to (2i and j) is arbitrary. Cycloaddition with Sulphines (lkand 1).-As described for (2a),a 3 : 1mixture of sulphines (lkand 1) (0.35g, 2.13 mmol) gave one adduct (2k) (0.87 g, 93).It is assumed that the anti-isomer (2k) is thermodynamically more stable because of less steric hindrance. An analytical sample of (2k) was obtained by recrystallization from methanol, m.p 163-166 "C (decomp.) (Found: C, 70.7; H, 4.5; N, 6.4; S, 14.5. C,,H,,N,OS, requires C, 70.9; H, 4.6; N, 6.35; S, 14.55y0), vmsx. (KBr) 1060 cm-l (SO), 6 (CDCl,) 7.1-8.3 (m, ArH). When the cycloaddition was carried out with either the pure E-or Z-isomer one adduct was isolated. When the reaction of the E-isomer (lk)with DPNI was worked up after an incomplete reaction, the adduct (2k) (35) as well as the starting sulphine (59)were isolated.The geometry of the recovered sulphine was completely (98) retained, as de-termined by n.m.r. and t.1.c. Similarly, in case of the Z-isomer (ll), the adduct (2k) (33) and sulphine (11) (57) were obtained. The n.ni.r. spectrum as well as t.1.c. showed that the geometry of the recovered sulphine was completely ( 98yo)unchanged. Isomerization of Sulphines (Ikand 1).-A solution of sul- phine (lk)(0.10 g, 0.44 mmol) and triethylamine (0.10 g, 1.O mmol) in benzene (5 ml) was allowed to stand at 20 "C. After removal of the volatiles the ratio of sulphines (lkand 1) was determined by n.m.r. After standing for 12 h no isomerization was detected, but after 4 days the ratio of (lkand 1) was 69 : 31. Similarly, the Z-isomer (11) equili- brated to the same ratio (69 : 31) of the E-and Z-isomers.Methyl PhenyZ Sulphine (Im and n) .-A solution of mPPA (22.0 mmol) in ether was added slowly at 0 "C to a stirred solution of thioacetophenone 25 (6.0 g, 44.1 mmol) in ether (60 nil). The precipitated phthalic acid was removed by filtration, the filtrate was concentrated, and the residue was chromatographed on a silica gel column. Elution with benzene gave the excess of thione and acetophenone ;further elution with benzene-ethyl acetate (10 : 1) afforded methyl 26 J. W. Scheeren, P. H. J. Ooms, and R. J. F. Nivard, Synthe-sis, 1973, 149. 1223 Phenyl sulphine (1.6 g, 48) as a 5 : 1mixture of the Z-and E-isomers (Found: C, 63.4; H, 5.2; s, 21.3. C,H,OS re-quires C, 63.1; H, 5.3; S, 21.05), vmx.(CS,) 1070 and 1090 cm-l (CSO), 6 (CS,) 2.16 and 2.47 (3 H, s, ratio 1:5, Me) and 7.1-7.2 (5 H, m, ArH). The geometry of these sulphines was determined by the chemical shifts in C,D, (ASIS),26 Cycloaddition with the Sulphines (lm and n).-A mixture of sulphines (lm and n) (E :Z ratio 1 : 5) (1.5g, 10.0 mmol) was treated with DPNI as described for (la). After stand- ing for 35 h the reaction mixture was filtered, the solvent was removed, and the residue was chromatographed on a silica gel column. Elution with benzene gave DNPI precursor (0.9 g). Elution with benzene-ether (10 : 1)gave acetophenone and adducts (em and n) (0.92 g, 44), Z :E ratio 2 : 5, m.p. 160--169deg;C (Found: C, 72.5; H, 5.2; N, 7.9; S, 9.2.C21H18N,0S requires C, 72.8; H, 5.25; N, 8.05; S, 9.25y0),vmax. (KBr) 1055 cm-l (SO),6 (CDCl,) 1.80and 2.01 (3 H, s, ratio 2 :5) and 6.7-8.0 (15 H, m, ArH), m/e 346 (M+),330 (M+-0) and 315 (M+-OMe). The major isomer with the methyl signal absorbing at the lowest field (6 2.01) has the anti-structure (2n) (deshielding of methyl by the adjacent sulphoxide function). The adducts (2m and n) were also obtained as follows. Thioacetophenone (3.40 g, 25.0 mmol) was treated with DPNI precursor (5.76 g, 25.0 mmol) and triethylamine (5.05 g, 50.0 mmol) in ben- zene (150 ml). After stirring for 24 h at 20 "C the mixture was worked up in the usual way. Elution with light petro- leum (b.p. 60-80 "C) gave unchanged precursor (1.2 g) and with benzene gave 5-methyl-3,4,5-triphenyl-A2-1,3,4-thiadi-azoline (3m) (2.8 g, 43y0), m.p.84 "C (from ethanol) (Found: C, 75.95; H, 5.55; N, 8.35. C21Hl,N,S requires C, 76.3; H, 5.5; N, 8.5), 6 (CS,) 2.13 (3H, s, Me) and 6.8-8.0 (15 H, m, ArH). Oxidation of adduct (3m) (0.9 g, 2.73 mmol) with m-chloroperbenzoic acid (0.55 g, 2.73 mmol) at -30 "C for 2 h in ether (30 ml) gave after filtration the adducts (2m and n) (0.62 g), in the ratio of 3.7 : 1. The mother liquor afforded, after removal of the acid and solvents, a second crop of adducts (2m and n) (0.1g, total yield 76). Silylation of Adducts (2m and n).-Adducts (2m and n) (ratio 1 :5; 0.20 g, 0.59 mmol) in benzene (20 ml) were treated with Me,SiCl (1 .O ml). After stirring for 3 h at 20 "C the mixture was filtered and the filtrate was concentrated and chromatographed (preparative t.l.c., development with benzene, elution with ether), affording acetophenone (0.030 g, 40) and 1,3,4,5-tetraphenyl- 1,2,4,5-tetrazine (7) (0.040 g, 36).The product obtained in this reaction was identi- cal in all respects with the dimer of DPNI. Trapping of the Intermediate Sulphenic Acid.-A mixture of adducts (2m and n) (0.40 g, 1.16 mmol) and acetic anhy- dride (12 ml) in benzene (40 ml) was heated at reflux. After 6 h the solvent was removed and the residue was chromato- graphed (preparative t.l.c., development with benzene, elu- tion with ether) to give 6-acetyl-2,4,5-triphenyl-1,3,4-thia-diazine (IOa) (0.30 g, 70y0), m.p. 129-132 "C (from meth- anol) (Found: C, 74.4; H, 4.8; N, 7.6. C,,H1,N,OS re-quires C, 74.55; H, 4.9; N, 7.55), v,,,. (KBr) 1 700 (CO) and I 590 cm-l (C=N), 6 (CDCl,) 2.04 (3 H, s, Me) and 6.4- 7.4 (15 H, m, ArH), m/e 370 (M+),327 (M+-MeCO), 295 M' -(MeCO + S), 194 (PhC=N-NPh), and 180 (PhN= CPh). Similarly 2,4,5-triphenyl-6-propionyl-1,3,4-thiadiazine (lob) (0.23 g, 60) was obtained from the adducts (2m and 26 A. Tangerman and B. Zwanenburg, Tetrahedron Letters, 1973, 79. n) (0.34 g, 1.0mmol) and propionic anhydride (7.5 ml), m.p. 1OP-106 "C (from methanol) (Found: C, 74.3; H, 5.2; N, 7.3. C,,H,,N,OS requires C, 75.0; H, 5.25; N, 7.3),vmxm (CHCI,) 1 700 (CO) and 1 590 cm-1 (C=N), 6 (CDCl,) 0.94 (3 H, t, J 7 Hz, Me), 2.23 (2 H, q, CH,), and 7.0-7.7 (15 H, m, ArH), m/e 384 (M+). Reaction of Adduct (2a) with Thiobenzoj5henone.-Adduct (2a) (0.20 g, 0.48 mmol) and thiobenzophenone (0.097 g, J.C.S. Perkin I 0.48 mmol) dissolved in benzene (15 ml) were heated at reflux for 10 h. After filtration, the filtrate was concen- trated in vacuo and the residue was chromatographed (preparative t.l.c., development with benzene, elution with ether) to give benzophenone (0.08g, 92) and thiadiazoline (3a) (0.174 g, 92), m.p. 163-164 "C (from ethanol). 7/2191 Received, 15th December, 19771