Reaction of trithiazyl trichloride with active methylene compounds

摘要

J. Chem. Soc. Perkin Trans. 1 1997 2831 Reaction of trithiazyl trichloride with active methylene compounds Xiao-Guang Duan Xiao-Lan Duan and Charles W. Rees Department of Chemistry Imperial College of Science Technology and Medicine London UK SW7 2AY Activated allylic compounds react with trithiazyl trichloride (NSCl)3 to give 1,2,5-thiadiazoles 1 and isothiazoles 2. An allylic 2-substituent normally prevents formation of an aromatic 1,2,5-thiadiazole and isothiazole formation becomes the major pathway. Simple allylic compounds are not very reactive towards (NSCl)3 but a terminal electron withdrawing group (CO2Et) enhances the reactivity. With unsymmetrical allylic compounds isothiazole formation is regiospecific placing the more electron withdrawing group adjacent to the ring sulfur. 1,3-Diketones give 3-acyl-1,2,5-thiadiazoles; unsymmetrical 1,3-diketones give these thiadiazoles regiospecifically explicable by cyclisation of an intermediate onto the more reactive carbonyl group.1,4-Diketones give 3,4-diacyl-1,2,5-thiadiazoles; thus 1,2-dibenzoyl-ethane -ethene and -ethyne all give 3,4-dibenzoylthiadiazole (40ndash;44). Many of these trithiazyl trichloride reactions provide attractive one-step routes to 1,2,5-thiadiazoles and isothiazoles. Activated allylic compounds with (NSCl)3 Simple allylic compounds could react with trithiazyl trichloride (the lsquo;trimerrsquo;) (NSCl)3,1 as a two-carbon unit to give 1,2,5- thiadiazoles 1 2 or as a three-carbon unit to give isothiazoles 2. When cinnamyl chloride was treated with trimer (1 mol) in boiling benzene the thiadiazole 3 was formed in relatively good yield (56)); no isothiazole was isolated.With two moles of trimer in boiling tetrachloromethane the reaction was more complex 3 was isolated in low yield (17) together with the more chlorinated thiadiazole 4 (12). 1,3-Diphenylpropene3 reacted with the trimer in the opposite mode however to give an isothiazole. With two moles of the reagent in boiling tetrachloromethane a substantial amount of 3,5-diphenylisothiazole 5 (53) but no 1,2,5-thiadiazole was obtained; with one mole the isothiazole 5 was formed in lower yield (29) together with a small amount of chlorinated thiadiazole 6 (14). The introduction of a substituent on the central carbon of the allylic system should prevent formation of an aromatic 1,2,5-thiadiazole and isothiazole formation could then become the major pathway.This proved to be very largely though not exclusively so (Table 1). Compound 7 (as an E/Z mixture) 4 and compound 85 were prepared by literature methods and the remaining compounds 9 10 11a and 11b were readily prepared by Wadsworthndash; R R N S N S N R R R R Ph Cl N S N N S N Ph CHCl2 Cl Ph Ph S N N S N Ph Ph Ph Ph Ph Cl 3 4 (NSCl)3 + 5 6 1 2 (NSCl)3 + (NSCl)3 + Emmons reaction of triethyl phosphonoacetate and the respective ketone at room temperature overnight. Compound 11 Table 1 Reaction of 2-substituted allylic compounds with (NSCl)3 in boiling tetrachloromethane Allylic compound Product () Ph Me Ph Ph Me Ph Cl O Ph Ph Ph CO2Et N S Ph S N Ph Me Ph S N Ph Ph EtO2C CO2Et N S CO2Et Ph Ph CO2Et S N Ph Ph EtO2C N S N CO2Et Ph Ph Ph CO2Et 7 8 9 10 (Z)-11a (E)-11b 17 (66)a 17 (6)a 18 (23)a 16 (25)a 15 (32)a 14 (7) 12 (19) 13 (26) + + a With 4 Aring; molecular sieves.2832 J. Chem. Soc. Perkin Trans. 1 1997 previously reported as a mixture of isomers,6 was separated into the Z (11a) and the E isomer (11b) whose structures were confirmed by their NOE 1H NMR spectra. These allylic compounds were treated with (NSCl)3 (1 equiv.) in boiling tetrachloromethane overnight. In all cases isothiazoles were formed and in one case only a 1,2,5-thiadiazole was also formed (Table 1). The simplest compounds were not very reactive towards the trimer owing to the low reactivity of the allylic hydrogens; compound 8 gave the isothiazole 14 in only 7. Compound 7 with a benzylic methylene group gave the isothiazole 12 in slightly better yield (19) together with the chlorinated and oxidised product 13.To enhance the allylic reactivity further and hopefully to suppress side reactions we introduced an electron withdrawing group by preparing the esters 9 and 10. These gave the corresponding isothiazoles 15 and 16 in better yield than 12 and 14. The Z and E isomers of compound 11 showed quite different behaviour towards (NSCl)3; the E isomer 11b gave isothiazole 17 in unusually high yield (66) whilst the Z isomer gave the same isothiazole as a minor product together with the unexpected 1,2,5-thiadiazole 18 in which C-debenzylation had occurred on aromatisation (Scheme 1). We note that in the reactions of (NSCl)3 with unsymmetrical allylic compounds such as 8 9 10 and 11 two isothiazoles could be formed but in each case we have isolated only one (14 15 16 and 17 respectively).Thus in the reaction of ester 9 isothiazoles 15 and 15a could have been formed but only 15 was isolated. In the 1H NMR spectrum of this product one sharp singlet was seen at 3.68 ppm for the benzylic protons indicating that it was not a mixture of isomers; its mass spectrum showed a peak at m/z 103 for the fragment PhCN1 indicating structure 15 rather than 15a. The structures of the other isothiazoles were assigned similarly. We cannot rule out that the undetected isomers were formed in very minor amounts but the reactions are regioselective (at least) in favour of the isothiazole with the electron withdrawing ester group in the 5-position (see Scheme 2 below). Active methylene compounds with (NSCl)3 Since these reactions of active allylic compounds with (NSCl)3 involve the methylene group some other active methylene compounds such as keto alkenes and diketones were treated similarly with the trimer.It has already been shown that 1,3- diketones are converted into 3-acyl-1,2,5-thiadiazoles (7ndash;50) by treatment with tetrasulfur tetranitride S4N4 in boiling toluene,7 and some of these diketones have now been treated with the more reactive reagent (NSCl)3 for comparison. Heating dibenzoylmethane 19 with 1 equiv. of the reagent in tetrachloromethane gave a complex reaction mixture from which only colourless 3-benzoyl-4-phenyl-1,2,5-thiadiazole 20 (20) and bright yellow bis(dibenzoylmethylideneamino) trisulfide 21 (5) could be obtained. The formula of 21 was based on elemental analysis; no molecular ion could be seen in the mass spectrum where the base peak m/z 105 was that of the benzoyl fragment and a peak for (M1 2 S)/2 at m/z 268 was observed.The 1H NMR spectrum showed only phenyl protons and the IR spectrum showed a strong carbonyl absorption at 1657 cm21. Thiadiazole 20 was made alternatively and in better yield (60) by treating benzylideneacetophenone 22 with 2 equiv. of (NSCl)3 in boiling tetrachloromethane. Conversion of dibenzoylmethane 19 into thiadiazole 20 requires the elimination of water (see Scheme 3 below) which will decrease the S N S N Ph CO2Et Ph Ph Ph EtO2C Ph EtO2C Ph 9 (NSCl)3 15a + 15 yield of 20 and contribute to the complexity of the reaction mixture. To minimise this problem the reaction was repeated in the presence of 4 Aring; molecular sieves with 1.5 equiv. of (NSCl)3.After heating under reflux for 12 h the reaction mixture was cleaner than without molecular sieves and the yields of the thiadiazole 20 (41) and the trisulfide 21 (11) were doubled. We also treated the following 1,3-dicarbonyl compounds with trimer (1.5 equiv.) and molecular sieves in boiling tetrachloromethane for 12 h 1-(4-methoxyphenyl)-3-phenylpropane- 1,3-dione 23 benzoylacetone 24 indane-1,3-dione 25 pentane-2,4-dione and the diester di-tert-butyl malonate. In spite of the presence of the molecular sieves the reactions were sometimes rather complex and the yields of 1,2,5-thiadiazoles were not high (Table 2). The ester did not react with trimer under the standard conditions and the reaction of pentane-2,4- dione was complex and 3-acetyl-4-methyl-1,2,5-thiadiazole was not isolated.The reaction of indane-1,3-dione 25 was slow though excess of (NSCl)3 (3 equiv.) was used and the reaction time extended to 24 h; much unreacted 25 (61) remained and 8H-indeno1,2-c1,2,5thiadiazol-8-one 28 (16) was isolated. This product is identical with that from the reaction of indan-2- one with S4N4 in boiling toluene (4).8 When the unsymmetrical 1,3-diketones 23 and 24 reacted with (NSCl)3 only one of the two possible 1,2,5-thiadiazoles was isolated. This is explained by cyclisation of a key intermediate at the more reactive carbonyl group (see Scheme 3 below). Somewhat surprisingly the butenone 29 with 2 equiv. of trimer in boiling tetrachloromethane gave 3,4-dibenzoyl-1,2,5- Ph Ph N S N O O (PhCO)2C=N-S2-S Ph O Ph N S N (NSCl)3 Ph O Ph Ph Ph (NSCl)3 (NSCl)3 O O 21 + 20 Ph Ph 19 20 O 22 19 60 41 N S N O 28 Table 2 Reaction of 1,3-diketones with (NSCl)3 in boiling tetrachloromethane in the presence of molecular sieves R R1 O O N S N R1 O R R Ph 4-MeOC6H4 Ph o-Phenylene R1 Ph Ph Me Diketone 19 23 24 25 Thiadiazole 20 26 27 28 Yield () 41 a 33 25 16 b a With bis(dibenzoylmethylideneamino) trisulfide 21 (11).b With recovered 25 (61). J. Chem. Soc. Perkin Trans. 1 1997 2833 thiadiazole 31 (26) identical with that formed as expected from (E)-1,2-dibenzoylethene.2 Dibenzoylethyne and even 1,2- dibenzoylethane reacted smoothly with trimer (1.5 equiv.) in boiling tetrachloromethane (see mechanisms shown below) to give the same thiadiazole 31 in very similar yields (40ndash;44). Finally when fluorene was similarly treated with trimer a moderate yield (40) of a bright yellow compound bis- (fluoren-9-ylideneamino) sulfide 32 was formed identical with that from the reaction of fluorenone oxime with S4N4 in boiling toluene (22).9 Reaction mechanisms We have proposed mechanisms for the conversion of alkenes and alkynes into 1,2,5-thiadiazoles by trithiazyl trichloride (NSCl)3 based upon its electrophilic attack on or cycloaddition to the carboncarbon double or triple bond.2 Since an NSN unit was transferred we assumed that the reacting species was the intact trimer (NSCl)3.When an SN unit is transferred e.g. to an allylic compound to form an isothiazole it seems likely that the reacting species could be the highly reactive monomer N SCl which is freely available in solution at the reaction temperatures.We now suggest extensions of the trimer mechanisms for the formation of the 1,2,5-thiadiazoles reported (Schemes 1 3 and 4) together with a mechanism for the formation of isothiazoles (Scheme 2). Conversion of the 2-substituted allylic compound 11a into thiadiazole 18 presents the added complexity of debenzylation which could occur as shown in Scheme 1. The more usual conversion of 2-substituted allylic compounds (7 8 9 10 and 11) into isothiazoles (12 14 15 16 and 17 respectively) could result from their reaction with the monomer as shown in Scheme 2 which would also explain the observed regiochemistry. The dihydroisothiazole 33 is aromatised by dehydrogenation possibly via chlorination of 33 by more of the reagent. Conversion of 1,3-diketones into 1,2,5-thiadiazoles (Scheme 3) could proceed by electrophilic attack on the enol by the trimer followed by cyclisation in 34 onto the more reactive carbonyl group and this too would explain the observed regiochemistry.Loss of water and ClSNSCl1Cl2 then gives the Ph O Ph N S N O Ph Ph Cl Cl N S N O O Ph Ph 30 29 31 CCOPh N S N PhCOCH2CH2COPh PhCOC PhCOCH=CHCOPh 32 (NSCl)3 (NSCl)3 (NSCl)3 (NSCl)3 aromatic product. Formation of 3,4-dibenzoyl-1,2,5-thiadiazole 31 from 1,2-dibenzoylethane could result from similar attack on one enolic form followed by cyclisation via the second enol (Scheme 4). Experimental For general details see earlier parts of this series.10 1,3-Diphenyl-2-methylpropene 7 This was prepared by the literature method4 and obtained as a colourless oil (30) nmax(neat)/cm21 3026 2925 1947 1880 1806 1755 1650 1600 1494 1453 1377 1075 1030 917 and Scheme 1 N S N S N S Ph CO2Et Ph Cl Cl Cl N S N Cl ClS N S Cl Ph Ph CO2Et N S N Cl Ph Ph CO2Et N S N CO2Et Ph Cl _ H 11a 18 + PhCH2Cl ndash; S N S+ Clndash; Scheme 2 H S NH S R2 R1 R3 R2 R1 R3 R2 R1 R3 N S N N S R2 R1 R3 Cl H R2 R1 R3 S N Cl S R2 R1 R3 NH 33 OR H Cl .... Scheme 3 H O O R Rcent; N S N S N S Cl Cl Cl O O R Rcent; N S N S N S Cl Cl O R N S N S N S Cl Cl H O Rcent; H N S N O Rcent; R H+ ndash; HCl H+ + Cl ndash; + H2O + ClSNSCl+Clndash; 34 2834 J. Chem. Soc. Perkin Trans. 1 1997 857; dH(270 MHz CDCl3) 1.79 (3H s CH3) 3.47 3.62 (2H two singlets ratio 2 :1 PhCH2) 6.38 6.52 (1H two singlets ratio 2 1 alkene-H) and 7.14ndash;7.37 (10H m ArH). Phenylmethylidenecyclohexane 8 A solution of cyclohexyl bromide (0.01 mol 1.87 ml) and triphenylphosphine (0.01 mol 2.63 g) in sodium-dried benzene (50 ml) was stirred and heated under reflux.The initially clear solution rapidly became cloudy and the phosphonium salt precipitated as a pale yellow solid. The solid was collected and washed with ether to give the phosphonium salt. Sodium hydroxide (80 mmol 3 g) in benzene (15 ml) was added dropwise to a stirred suspension of the phosphonium salt (10 mmol 4.26 g) and benzaldehyde (10 mmol 1.0 ml) in water (15 ml) at room temperature over 20 min. Upon addition the initially clear mixture became cloudy as triphenylphosphine oxide was formed. The stirring was continued for 3 h before the mixture was evaporated and the phenylmethylidenecyclohexane 8 (1.03 g 60) was isolated as a colourless oil bp 104 8C/3 mmHg (lit.,5 bp 83 8C/5 mmHg); nmax(neat)/cm21 3027 2927 2854 1654 1598 1494 1447 918 736 and 699; dH(270 MHz CDCl3) 0.85ndash;0.88 (2H m CH2) 1.60ndash;1.62 (4H m 2CH2) 2.25 (2H t CH2) 2.36 (2H t CH2) 6.22 (1H s alkene-H) and 7.15ndash; 7.29 (5H m ArH).The following allylic compounds were synthesised by the Wadsworthndash;Emmons method with triethyl phosphonoacetate. To a dispersion of sodium hydride in mineral oil triethyl phosphonoacetate was added dropwise. The mixture was stirred until it was colourless before the respective ketone was added. The solution was stirred at ambient temperature until the reaction was complete (TLC). The products were isolated by flash chromatography on silica gel. Ethyl 3-benzyl-4-phenylbut-2-enoate 9. Colourless oil (Found M1 280.1463. C19H20O2 requires M 280.1463); nmax(neat)/cm21 3061 3027 1734 1647 1601 1584 1494 1454 1391 1369 1323 1237 1076 1032 800 and 752; dH(270 MHz CDCl3) 1.14 (3H t CH3) 3.14 (2H s PhCH2) 3.59 (2H s PhCH2) 4.03 (2H q CH2) 6.61 (1H s alkene-H) and 7.04ndash;7.39 (10H m Scheme 4 Ph O Ph O Ph O Ph O H N S N S N S Cl Cl Cl O O Ph Ph N S N S N S Cl Cl H N S N S N S Cl N S N O Ph ndash; HCl 31 O Ph ndash; HSNS Ph Ph O O H H ndash; HCl ndash; HCl ArH); m/z 280 (M1 50) 234 (M1 2 CO2 30) 206 (M1 2 CO2Et 30) 192 (35) 129 (10) 115 (25) and 91 (PhCH2 1 100).Ethyl indan-2-ylideneacetate 10. Pale yellow oil (Found M1 202.0992. C13H14O2 requires M 202.0994); nmax(neat)/cm21 3057 3020 2982 2937 1735 1614 1462 1393 1369 1332 1301 1251 1176 1097 1032 914 796 and 755; dH(270 MHz CDCl3) 1.19ndash;1.24 (3H t CH3) 3.37 (2H s CH2) 3.43 (2H s CH2) 4.07ndash;4.15 (2H q CH2) 6.62 (1H s alkene-H) and 7.08ndash;7.34 (4H m ArH); m/z 202 (M1 45) 156 (M1 2 CO2 18) 126 (M1 2 CO2Et 14) and 76 (13).(Z)-Ethyl 3,4-diphenylbut-2-enoate 11a.6 Colourless oil; nmax(neat)/cm21 3059 2980 2925 1727 (C O) 1642 1604 1548 1453 1376 1265 1223 1162 1075 1034 and 877; dH(270 MHz CDCl3) 1.10 (3H t CH3) 3.67 (2H s PhCH2) 4.04 (2H q CH2) 6.99 (1H s alkene-H) and 7.23ndash;7.48 (10H m ArH); m/z 266 (M1 100) 221 (10) 193 (M1 2 CO2Et 80) 178 (55) 165 (15) 152 (5) 115 (82) 91 (PhCH2 1 33) and 77 (Ph1 6). (E)-Ethyl 3,4-diphenylbut-2-enoate 11b.6 Colourless oil; nmax(neat)/cm21 3059 3027 2980 2930 1727 (C O) 1642 1601 1549 1453 1377 1265 1223 1162 1075 1034 877 759 and 729; dH(270 MHz CDCl3) 1.16 (3H t CH3) 4.10 (2H q CH2) 4.41 (2H s PhCH2) 6.14 (1H s alkene-H) 7.12ndash;7.29 (10H m ArH); m/z 266 (M1 100) 220 (M1 2 EtOH 97) 192 (85) 178 (25) 165 (15) 152 (5) 131 (7) 115 (55) 91 (PhCH2 1 33) and 77 (Ph1 6).Reactions of trithiazyl trichloride With cinnamyl chloride. (a) Cinnamyl chloride (freshly distilled 76 mg 0.5 mmol) in benzene (1 ml) was added at room temperature to a stirred solution of trithiazyl trichloride (122 mg 0.5 mmol) in benzene (4 ml) under nitrogen. The mixture was stirred and heated at reflux for 17 h under nitrogen. The solvent was evaporated and the residue was separated by chromatography on silica gel. Elution with dichloromethane (30) in light petroleum gave 3-chloromethyl-4-phenyl-1,2,5-thiadiazole 3 as colourless needles (59 mg 56) mp 69ndash;70 8C; nmax(neat)/cm21 3066 3027 2925 2854 1578 1497 1468 1455 1442 1402 1304 1274 1222 1178 1158 1076 1015 934 919 844 and 832; dH(270 MHz CDCl3) 4.80 (2H s CH2Cl) 7.45ndash;7.50 (3H m ArH) and 7.70ndash;7.77 (2H m ArH); m/z 212 (M1 isotope 37) 210 (M1 100) 175 (M1 2 Cl 70) 135 (PhCNS1 62) 116 (18) 103 (PhCN1 17) and 77 (Ph 18).(b) To a stirred solution of trithiazyl trichloride (244 mg 1 mmol) in tetrachloromethane (5 ml) cinnamyl chloride (76 mg 0.5 mmol) in tetrachloromethane (1 ml) was added dropwise. The mixture was heated at reflux for 17 h under nitrogen. The solvent was evaporated and the residue was separated by chromatography on silica gel. Elution with dichloromethane (30) in light petroleum gave 3-dichloromethyl-4-phenyl-1,2,5-thiadiazole 4 as a red oil (15 mg 12) dH(270 MHz CDCl3) 6.95 (1H s CHCl2) 7.52ndash;7.58 (3H m ArH) and 7.67ndash;7.73 (2H m ArH); m/z 248 (M1 isotope 10.4) 246 (M1 isotope 54) 244 (M1 75) 211 (M1 2 Cl isotope 28) 209 (M1 2 Cl 76) 187 (26) 173 (M1 2 HCl 2 Cl 100) 135 (PhCNS1 30) and 77 (Ph1 28).Elution with dichloromethane (40) in light petroleum gave 3-chloromethyl-4-phenyl-1,2,5-thiadiazole 3 (21 mg 17) mp 69ndash;70 8C identical with that described in (a). With 1,3-diphenylpropene. (a) To a stirred solution of trithiazyl trichloride (244 mg 1 mmol) in tetrachloromethane (3 ml) 1,3-diphenylpropene (97 mg 0.5 mmol) in tetrachloromethane (1 ml) was added by a syringe slowly. No significant temperature or colour change was observed. The mixture was heated at reflux for 20 h under nitrogen; it turned green and then red. The solvent was evaporated and the residue was separated on silica gel. Elution with dichloromethane (50) in light petroleum gave 3,5-diphenylisothiazole 5 (63 mg 53) as colourless needles mp 85.5ndash;86.5 8C (lit.,11 81 8C) (Found C 76.0; H 4.3; N 5.8.Calc. for C15H11NS C 76.0; H 4.6; N 5.9); nmax(Nujol)/cm21 3055 1529 1485 1455 1391 1370, J. Chem. Soc. Perkin Trans. 1 1997 2835 1337 1306 1205 1188 1153 1100 1087 1076 1028 1000 984 970 920 and 910; dH(270 MHz CDCl3) 7.40ndash;7.50 (6H m ArH) 7.61ndash;7.68 (2H m ArH) 7.75 (1H s 4-H) and 7.97ndash; 8.01 (2H m ArH); m/z 237 (M1 100) 204 (5) 135 (PhCNS1 17) 134 (24) 121 (5) 103 (PhCN1 7) 89 (6) and 77 (Ph1 16). (b) 1,3-Diphenylpropene (194 mg 1 mmol) in chloroform (0.5 ml) was added to a solution of trithiazyl trichloride (80 mg 0.33 mmol) in chloroform (2.5 ml) at room temperature and then heated at reflux for 17 h. The solvent was evaporated and the residue was separated on silica gel. Elution with dichloromethane (50) in light petroleum firstly gave a thin oil (230 mg) which appeared to be chlorinated starting material (based on the mass spectrum) and secondly gave 3-(a-chlorobenzyl )-4- phenyl-1,2,5-thiadiazole 6 as colourless needles (30 mg 14) mp 115ndash;118 8C (Found C 62.8; H 3.9; N 9.9.C15H11ClN2S requires C 62.8; H 3.8; N 9.8); nmax(Nujol)/cm21 1398 1247 1223 1198 1170 1079 1015 931 886 858 841 804 783 769 741 701 663 and 655; dH(270 MHz CDCl3) 6.35 (1H s CHClPh) 7.35ndash;7.42 (3H m ArH) 7.52ndash;7.58 (5H m ArH) and 7.60ndash;7.65 (2H m ArH); m/z 286 (M1 12) 251 (M1 2 Cl 100) 173 (39) 148 (37) 135 (PhCNS1 5) 125 (11) 116 (14) 103 (PhCN1 9) and 91 (4). Reactions of allylic compounds with trithiazyl trichloride Either procedure A or B was used. In procedure A a mixture of the organic substrate (1 mmol) and the reagent (1 mmol) in tetrachloromethane (20 ml) was heated at reflux overnight.The solvent was then evaporated and the residue was separated by flash chromatography on silica eluting with dichloromethane in light petroleum. In procedure B the same mixture in tetrachloromethane (25 ml) was heated at reflux overnight in the presence of 4 Aring; molecular sieves (2 g). The molecular sieves were then filtered off and washed with dichloromethane and the combined organic solution was evaporated and the residue was separated as in A. With 1,3-diphenyl-2-methylpropene 7. Procedure A with compound 7 (208 mg) and trithiazyl trichloride (244 mg) gave 3,5-diphenyl-4-methylisothiazole 12 (48 mg 19) mp 145ndash; 147 8C (Found C 76.3; H 5.3; N 5.8. C16H13NS requires C 76.5; H 5.2; N 5.6); nmax(CHCl3)/cm21 3084 3001 2380 1881 1490 1456 1238 1220 and 804; dH(270 MHz CDCl3) 2.32 (3H s CH3) and 7.39ndash;7.67 (10H m ArH); m/z 251 (M1 75) 250 (100) 217 (M1 2 S 2) 147 (M1 2 PhCN 10) 135 (PhCNS1 2) 121 (PhCS1 6) 115 (3) 104 (6) 103 (PhCN1 6) and 77 (Ph1 7) and 3-chloro-1,3-diphenyl-2-methylpropan-1-one 13 (62 mg 26) mp 97ndash;99 8C; nmax(CHCl3)/cm21 3020 3010 2440 1881 1710 1480 1456 1240 1220 and 899; dH(270 MHz CDCl3) 1.83 (3H br CH3) 2.05 (1H m CHMe) 5.45 (1H d CHCl) and 7.27ndash;7.40 (10H m ArH); m/z 260 (M1 1 2 0.6) 258 (M1 1.9) 243 (M1 2 Me 2.4) 223 (M1 2 Cl 18) 222 (25) 205 (24) 179 (7) 145 (7) 118 (36) 115 (49) 105 (PhCO1 100) and 77 (Ph1 48).With phenylmethylidenecyclohexane 8. Procedure A with compound 8 (172 mg) and trithiazyl trichloride (244 mg) gave 3-phenyl-4,5,6,7-tetrahydro-2,1-benzisothiazole 14 (15 mg 7) as a yellow oil (Found M1 215.0768 C13H13NS requires M 215.0769); nmax(CHCl3)/cm21 3027 2936 1667 1599 1492 1446 1409 and 913; dH(270 MHz CDCl3) 1.80ndash;1.91 (4H m 2CH2) 2.79ndash;2.89 (2H t CH2) 2.91ndash;2.94 (2H t CH2) and 7.38ndash;7.49 (5H m ArH); m/z 215 (M1 100) 187 (15) 121 (PhCS1 10) 115 (15) 91 (25) and 77 (Ph1 14).With ethyl 3-benzyl-4-phenylbut-2-enoate 9. Procedure B with compound 9 (283 mg) gave ethyl 4-benzyl-3-phenylisothiazole-5- carboxylate 15 (104 mg 32) as pale yellow oil (Found M1 323.0981. C19H17NO2S requires M 323.0980); nmax(CHCl3)/ cm21 3031 3001 1730 (C O) 1491 1447 1408 1372 1335 1265 1219 1190 1030 782 777 736 and 667; dH(270 MHz CDCl3) 1.09ndash;1.28 (3H t CH3) 3.71 (2H s PhCH2) 4.00ndash;4.08 (2H q CH2) and 7.43ndash;7.62 (10H m ArH); m/z 323 (M1 65) 250 (M1 2 CO2Et 100) 217 (10) 147 (M1 2 CO2Et 2 PhCN 25) 115 (12) 103 (PhCN1 22) and 77 (Ph1 30).With ethyl indan-2-ylideneacetate 10. Procedure B with compound 10 (203 mg) gave ethyl 4H-indeno1,2-cisothiazole-3- carboxylate 16 (45 mg 25) as orangendash;brown crystals mp 131ndash; 132 8C (Found M1 245.0511. C13H11NO2S requires M 245.0511); nmax(CHCl3)/cm21 3057 3020 2982 2937 1735 (C O) 1614 1462 1393 1369 1332 1301 1251 1176 1097 1032 914 and 796; dH(270 MHz CDCl3) 1.44ndash;1.49 (3H t CH3) 3.97 (2H s CH2) 4.43ndash;4.51 (2H q CH2) 7.36ndash;7.39 (2H m ArH) and 7.55ndash;7.64 (2H m ArH); m/z 245 (M1 60) 200 (M1 2 CO2 13) 173 (M1 2 CO2Et 100) 146 (30) 140 (M1 2 CO2Et 2 S 50) 128 (M1 2 CO2Et 2 CS 7) 101 (5) and 86 (6). With (E)-ethyl 3,4-diphenylbut-2-enoate 11b. Procedure B with compound 11b (233 mg 0.95 mmol) gave ethyl 3,4- diphenylisothiazole-5-carboxylate 17 (180 mg 66) mp 80ndash; 81 8C (Found M1 309.0823.C18H15NO2S requires M 309.0824); nmax(CHCl3)/cm21 3031 3001 1740 (C O) 1491 1447 1408 1372 1335 1219 1190 1030 782 777 736 and 667; dH(270 MHz CDCl3) 1.21ndash;1.26 (3H t CH3) 4.22ndash;4.30 (2H q CH2) and 7.19ndash;7.38 (10H m ArH); m/z 309 (M1 100) 280 (M1 2 Et 30) 262 (M1 2 SN 40) 236 (M1 2 CO2Et 22) 204 (M1 2 CO2Et 2 S 5) 190 (7) 133 (PhC2S1 10) and 86 (6). With (Z)-ethyl 4-phenyl-3-benzylbut-2-enoate 11a. Procedure B with compound 11a (213 mg 0.85 mmol) gave ethyl 3,4- diphenylisothiazole-5-carboxylate 17 (15 mg 6) mp 80ndash; 81 8C identical with that described above and ethyl 4-phenyl- 1,2,5-thiadiazole-3-carboxylate 18 (45 mg 23) identical with an authentic sample. Reactions of 1,3-diketones with trithiazyl trichloride Either procedure C or D was used.In procedure C a mixture of the organic substrate (2 mmol) and trithiazyl trichloride (2 mmol) in tetrachloromethane (30 ml) was heated at reflux under nitrogen for 12 h. The solvent was evaporated in vacuo and the residue was separated by column chromatography on silica eluting with dichloromethane in light petroleum. In procedure D a mixture of the organic substrate (2 mmol) trithiazyl trichloride (3 mmol) and dry 4 Aring; molecular sieves (4 g) in tetrachloromethane (30 ml) was heated at reflux under nitrogen for 12 h. The mixture was then filtered and the molecular sieves were washed with dichloromethane and the combined organic solution was evaporated and worked up as above. With dibenzoylmethane 19. (a) Procedure C and elution with dichloromethane (60) in light petroleum gave 3-benzoyl-4- phenyl-1,2,5-thiadiazole 20 (110 mg 20) as colourless needles mp 82ndash;83 8C (lit.,7 81ndash;83 8C); m/z 266 (M1 56) 237 (12) 219 (3) 135 (PhCNS1 9) 105 (PhCO1 100) 77 (Ph1 63) 51 (25).Elution with dichloromethane gave bis(dibenzoylmethylideneamino) trisulfide 21 (56 mg 5) as yellow needles mp 87ndash;88 8C (Found C 63.3; H 3.4; N 4.9. C30H20N2O4S3 requires C 63.4; H 3.5; N 4.9); nmax(CHCl3)/cm21 3037 3021 1657 (C O) 1598 1450 1319 1288 1245 1182 1003 979 and 876; dH(270 MHz CDCl3) 7.4ndash;7.5 (12H m PhH) and 7.52ndash;7.63 (8H m PhH); m/z 268 (M1 2 S/2 60) and 105 (PhCO1 100). (b) Procedure D gave 3-benzoyl-4-phenyl-1,2,5-thiadiazole 20 (220 mg 41) as colourless needles mp 82ndash;83 8C identical with that described above and bis(dibenzoylmethylideneamino) trisulfide 21 (122 mg 11) as yellow needles mp 87ndash;88 8C identical with that described above.With 1,3-diphenylprop-2-en-1-one 22. Procedure C but with trithiazyl trichloride (976 mg 4 mmol) gave 3-benzoyl-4- phenyl-1,2,5-thiadiazole 20 (322 mg 60) mp 82ndash;83 8C identical with that described above. With 1-(4-methoxyphenyl)-3-phenylpropane-1,3-dione 23. Procedure D but with trithiazyl trichloride (366 mg 3 mmol) gave 3-(4-methoxybenzoyl )-4-phenyl-1,2,5-thiadiazole 26 (198 mg 33) as colourless needles mp 129ndash;131 8C (Found M1 296.0620. C16H12N2O2S requires M 296.0619); nmax(CHCl3)/ 2836 J. Chem. Soc. Perkin Trans. 1 1997 cm21 3038 3007 1670 (C O) 1601 1518 1461 1423 1395 1268 1195 1163 1044 1030 900 and 835; dH(270 MHz CDCl3) 3.90 (3H s OMe) 6.97ndash;6.99 (2H d 4-MeOC6H4) 7.34ndash;7.42 (3H m PhH) 7.66ndash;7.72 (2H m PhH) and 7.93ndash;7.95 (2H d 4-MeOC6H4); m/z 296 (M1 39) 265 (M1 2 S 2) 135 (4-MeOC6H4CO1 100) 103 (PhCN1 5) 92 (13) and 77 (Ph1 20).With benzoylacetone 24. Procedure D but with trithiazyl trichloride (732 mg 3 mmol) gave 3-benzoyl-4-methyl-1,2,5- thiadiazole 27 (102 mg 25) as colourless crystals mp 72ndash; 73 8C (lit.,7 72ndash;73 8C); m/z 204 (M1 69) 105 (PhCO1 100) and 77 (Ph1 88). With indane-1,3-dione 25. Procedure D but with trithiazyl trichloride (1.46 g 6 mmol) and with refluxing for 24 h gave unreacted indane-1,3-dione 25 (178 mg 61) and 8H-indeno- 1,2-c1,2,5thiadiazol-8-one 28 (60 mg 16) mp 112ndash;114 8C (lit.,2 113 8C). With 1,2-dibenzoylethane. Procedure C with trithiazyl trichloride (732 mg 3 mmol) gave 3,4-dibenzoyl-1,2,5-thiadiazole 31 (235 mg 40) as colourless needles mp 128ndash;129 8C (lit.,2,12 124 8C); m/z 294 (M1 18) 217 (M1 2 Ph 4) 105 (PhCO1 100) and 77 (Ph1 50).With 1,2-dibenzoylethyne. Procedure C with 1,2-dibenzoylethyne (234 mg 1 mmol) and trithiazyl trichloride (366 mg 1.4 mmol) gave 3,4-dibenzoyl-1,2,5-thiadiazole 31 (129 mg 44) mp 128ndash;129 8C identical with that described above. With fluorene. Procedure C but with refluxing for 24 h gave bis(fluoren-9-ylideneamino) sulfide 32 (155 mg 40) as yellow prisms mp 290 8C (lit.,9 300 8C); m/z 388 (M1 81) 342 (M1 2 NS 16) 210 (99) 179 (100) 151 (16) 76 (12) and 64 (12). With 1-phenyl-3-benzoylprop-1-ene 29. Procedure A with compound 29 (111 mg 0.5 mol) gave 3,4-dibenzoyl-1,2,5- thiadiazole 31 (38 mg 26) mp 128ndash;129 8C identical with that described above.Acknowledgements We thank Zeneca Specialties and MDL Information Systems (UK) Ltd for financial support and the Wolfson Foundation for establishing the Wolfson Centre for Organic Chemistry in Medical Science at Imperial College. References 1 Gmelin Handbook of Inorganic Chemistry 8th edn. Sulfur-Nitrogen Compounds Part 2 Springer Verlag Berlin 1985 p. 92. 2 X.-G. Duan X.-L. Duan C. W. Rees and T.-Y. Yue J. Chem. Soc. Perkin Trans. 1 1997 2597. 3 L. M. Tolbert and M. E. Ogle J.Am. Chem. Soc. 1990 112 9519. 4 C. L. Bumgardner and H. Iwerks J. Am. Chem. Soc. 1996 88 5518. 5 Dictionary of Organic Compounds Chapman and Hall London 6th edn. vol. 1 p. 705. 6 Y. Leroux and C. Jaquelin Synth. Commun. 1976 6 597. 7 S. Mataka A. Hosoki K. Takahashi and M.Tashiro Synthesis 1982 976. 8 S. Mataka A. Hosoki K. Takahashi and M. Tashiro J. Heterocycl. Chem. 1980 17 1681. 9 S. Mataka K. Takahashi S. Ishi-i and M. Tashiro J. Chem. Soc. Perkin Trans. 1 1979 2905. 10 X.-L. Duan R. Perrins and C. W. Rees J. Chem. Soc. Perkin Trans. 1 1997 1617; C. W. Rees and T.-Y. Yuen J. Chem. Soc. Perkin Trans. 1 1997 2247. 11 R. A. Olofson J. M. Landesburg R. O. Berry D. Leaver W. A. H. Robertson and D. M. McKinnon Tetrahedron 1966 22 2119. 12 S. Mataka K. Takahashi Y. Yamada and M. Tashiro J. Heterocycl. Chem. 1979 16 1009. Paper 7/03033I Received 2nd May 1997 Accepted 6th June 1997 J. Chem. Soc. Perkin Trans. 1 1997 2831 Reaction of trithiazyl trichloride with active methylene compounds Xiao-Guang Duan Xiao-Lan Duan and Charles W. Rees Department of Chemistry Imperial College of Science Technology and Medicine London UK SW7 2AY Activated allylic compounds react with trithiazyl trichloride (NSCl)3 to give 1,2,5-thiadiazoles 1 and isothiazoles 2.An allylic 2-substituent normally prevents formation of an aromatic 1,2,5-thiadiazole and isothiazole formation becomes the major pathway. Simple allylic compounds are not very reactive towards (NSCl)3 but a terminal electron withdrawing group (CO2Et) enhances the reactivity. With unsymmetrical allylic compounds isothiazole formation is regiospecific placing the more electron withdrawing group adjacent to the ring sulfur. 1,3-Diketones give 3-acyl-1,2,5-thiadiazoles; unsymmetrical 1,3-diketones give these thiadiazoles regiospecifically explicable by cyclisation of an intermediate onto the more reactive carbonyl group.1,4-Diketones give 3,4-diacyl-1,2,5-thiadiazoles; thus 1,2-dibenzoyl-ethane -ethene and -ethyne all give 3,4-dibenzoylthiadiazole (40ndash;44). Many of these trithiazyl trichloride reactions provide attractive one-step routes to 1,2,5-thiadiazoles and isothiazoles. Activated allylic compounds with (NSCl)3 Simple allylic compounds could react with trithiazyl trichloride (the lsquo;trimerrsquo;) (NSCl)3,1 as a two-carbon unit to give 1,2,5- thiadiazoles 1 2 or as a three-carbon unit to give isothiazoles 2. When cinnamyl chloride was treated with trimer (1 mol) in boiling benzene the thiadiazole 3 was formed in relatively good yield (56)); no isothiazole was isolated. With two moles of trimer in boiling tetrachloromethane the reaction was more complex 3 was isolated in low yield (17) together with the more chlorinated thiadiazole 4 (12).1,3-Diphenylpropene3 reacted with the trimer in the opposite mode however to give an isothiazole. With two moles of the reagent in boiling tetrachloromethane a substantial amount of 3,5-diphenylisothiazole 5 (53) but no 1,2,5-thiadiazole was obtained; with one mole the isothiazole 5 was formed in lower yield (29) together with a small amount of chlorinated thiadiazole 6 (14). The introduction of a substituent on the central carbon of the allylic system should prevent formation of an aromatic 1,2,5-thiadiazole and isothiazole formation could then become the major pathway. This proved to be very largely though not exclusively so (Table 1). Compound 7 (as an E/Z mixture) 4 and compound 85 were prepared by literature methods and the remaining compounds 9 10 11a and 11b were readily prepared by Wadsworthndash; R R N S N S N R R R R Ph Cl N S N N S N Ph CHCl2 Cl Ph Ph S N N S N Ph Ph Ph Ph Ph Cl 3 4 (NSCl)3 + 5 6 1 2 (NSCl)3 + (NSCl)3 + Emmons reaction of triethyl phosphonoacetate and the respective ketone at room temperature overnight.Compound 11 Table 1 Reaction of 2-substituted allylic compounds with (NSCl)3 in boiling tetrachloromethane Allylic compound Product () Ph Me Ph Ph Me Ph Cl O Ph Ph Ph CO2Et N S Ph S N Ph Me Ph S N Ph Ph EtO2C CO2Et N S CO2Et Ph Ph CO2Et S N Ph Ph EtO2C N S N CO2Et Ph Ph Ph CO2Et 7 8 9 10 (Z)-11a (E)-11b 17 (66)a 17 (6)a 18 (23)a 16 (25)a 15 (32)a 14 (7) 12 (19) 13 (26) + + a With 4 Aring; molecular sieves. 2832 J. Chem. Soc. Perkin Trans.1 1997 previously reported as a mixture of isomers,6 was separated into the Z (11a) and the E isomer (11b) whose structures were confirmed by their NOE 1H NMR spectra. These allylic compounds were treated with (NSCl)3 (1 equiv.) in boiling tetrachloromethane overnight. In all cases isothiazoles were formed and in one case only a 1,2,5-thiadiazole was also formed (Table 1). The simplest compounds were not very reactive towards the trimer owing to the low reactivity of the allylic hydrogens; compound 8 gave the isothiazole 14 in only 7. Compound 7 with a benzylic methylene group gave the isothiazole 12 in slightly better yield (19) together with the chlorinated and oxidised product 13. To enhance the allylic reactivity further and hopefully to suppress side reactions we introduced an electron withdrawing group by preparing the esters 9 and 10.These gave the corresponding isothiazoles 15 and 16 in better yield than 12 and 14. The Z and E isomers of compound 11 showed quite different behaviour towards (NSCl)3; the E isomer 11b gave isothiazole 17 in unusually high yield (66) whilst the Z isomer gave the same isothiazole as a minor product together with the unexpected 1,2,5-thiadiazole 18 in which C-debenzylation had occurred on aromatisation (Scheme 1). We note that in the reactions of (NSCl)3 with unsymmetrical allylic compounds such as 8 9 10 and 11 two isothiazoles could be formed but in each case we have isolated only one (14 15 16 and 17 respectively). Thus in the reaction of ester 9 isothiazoles 15 and 15a could have been formed but only 15 was isolated.In the 1H NMR spectrum of this product one sharp singlet was seen at 3.68 ppm for the benzylic protons indicating that it was not a mixture of isomers; its mass spectrum showed a peak at m/z 103 for the fragment PhCN1 indicating structure 15 rather than 15a. The structures of the other isothiazoles were assigned similarly. We cannot rule out that the undetected isomers were formed in very minor amounts but the reactions are regioselective (at least) in favour of the isothiazole with the electron withdrawing ester group in the 5-position (see Scheme 2 below). Active methylene compounds with (NSCl)3 Since these reactions of active allylic compounds with (NSCl)3 involve the methylene group some other active methylene compounds such as keto alkenes and diketones were treated similarly with the trimer.It has already been shown that 1,3- diketones are converted into 3-acyl-1,2,5-thiadiazoles (7ndash;50) by treatment with tetrasulfur tetranitride S4N4 in boiling toluene,7 and some of these diketones have now been treated with the more reactive reagent (NSCl)3 for comparison. Heating dibenzoylmethane 19 with 1 equiv. of the reagent in tetrachloromethane gave a complex reaction mixture from which only colourless 3-benzoyl-4-phenyl-1,2,5-thiadiazole 20 (20) and bright yellow bis(dibenzoylmethylideneamino) trisulfide 21 (5) could be obtained. The formula of 21 was based on elemental analysis; no molecular ion could be seen in the mass spectrum where the base peak m/z 105 was that of the benzoyl fragment and a peak for (M1 2 S)/2 at m/z 268 was observed. The 1H NMR spectrum showed only phenyl protons and the IR spectrum showed a strong carbonyl absorption at 1657 cm21.Thiadiazole 20 was made alternatively and in better yield (60) by treating benzylideneacetophenone 22 with 2 equiv. of (NSCl)3 in boiling tetrachloromethane. Conversion of dibenzoylmethane 19 into thiadiazole 20 requires the elimination of water (see Scheme 3 below) which will decrease the S N S N Ph CO2Et Ph Ph Ph EtO2C Ph EtO2C Ph 9 (NSCl)3 15a + 15 yield of 20 and contribute to the complexity of the reaction mixture. To minimise this problem the reaction was repeated in the presence of 4 Aring; molecular sieves with 1.5 equiv. of (NSCl)3. After heating under reflux for 12 h the reaction mixture was cleaner than without molecular sieves and the yields of the thiadiazole 20 (41) and the trisulfide 21 (11) were doubled.We also treated the following 1,3-dicarbonyl compounds with trimer (1.5 equiv.) and molecular sieves in boiling tetrachloromethane for 12 h 1-(4-methoxyphenyl)-3-phenylpropane- 1,3-dione 23 benzoylacetone 24 indane-1,3-dione 25 pentane-2,4-dione and the diester di-tert-butyl malonate. In spite of the presence of the molecular sieves the reactions were sometimes rather complex and the yields of 1,2,5-thiadiazoles were not high (Table 2). The ester did not react with trimer under the standard conditions and the reaction of pentane-2,4- dione was complex and 3-acetyl-4-methyl-1,2,5-thiadiazole was not isolated. The reaction of indane-1,3-dione 25 was slow though excess of (NSCl)3 (3 equiv.) was used and the reaction time extended to 24 h; much unreacted 25 (61) remained and 8H-indeno1,2-c1,2,5thiadiazol-8-one 28 (16) was isolated.This product is identical with that from the reaction of indan-2- one with S4N4 in boiling toluene (4).8 When the unsymmetrical 1,3-diketones 23 and 24 reacted with (NSCl)3 only one of the two possible 1,2,5-thiadiazoles was isolated. This is explained by cyclisation of a key intermediate at the more reactive carbonyl group (see Scheme 3 below). Somewhat surprisingly the butenone 29 with 2 equiv. of trimer in boiling tetrachloromethane gave 3,4-dibenzoyl-1,2,5- Ph Ph N S N O O (PhCO)2C=N-S2-S Ph O Ph N S N (NSCl)3 Ph O Ph Ph Ph (NSCl)3 (NSCl)3 O O 21 + 20 Ph Ph 19 20 O 22 19 60 41 N S N O 28 Table 2 Reaction of 1,3-diketones with (NSCl)3 in boiling tetrachloromethane in the presence of molecular sieves R R1 O O N S N R1 O R R Ph 4-MeOC6H4 Ph o-Phenylene R1 Ph Ph Me Diketone 19 23 24 25 Thiadiazole 20 26 27 28 Yield () 41 a 33 25 16 b a With bis(dibenzoylmethylideneamino) trisulfide 21 (11).b With recovered 25 (61). J. Chem. Soc. Perkin Trans. 1 1997 2833 thiadiazole 31 (26) identical with that formed as expected from (E)-1,2-dibenzoylethene.2 Dibenzoylethyne and even 1,2- dibenzoylethane reacted smoothly with trimer (1.5 equiv.) in boiling tetrachloromethane (see mechanisms shown below) to give the same thiadiazole 31 in very similar yields (40ndash;44). Finally when fluorene was similarly treated with trimer a moderate yield (40) of a bright yellow compound bis- (fluoren-9-ylideneamino) sulfide 32 was formed identical with that from the reaction of fluorenone oxime with S4N4 in boiling toluene (22).9 Reaction mechanisms We have proposed mechanisms for the conversion of alkenes and alkynes into 1,2,5-thiadiazoles by trithiazyl trichloride (NSCl)3 based upon its electrophilic attack on or cycloaddition to the carboncarbon double or triple bond.2 Since an NSN unit was transferred we assumed that the reacting species was the intact trimer (NSCl)3.When an SN unit is transferred e.g. to an allylic compound to form an isothiazole it seems likely that the reacting species could be the highly reactive monomer N SCl which is freely available in solution at the reaction temperatures. We now suggest extensions of the trimer mechanisms for the formation of the 1,2,5-thiadiazoles reported (Schemes 1 3 and 4) together with a mechanism for the formation of isothiazoles (Scheme 2).Conversion of the 2-substituted allylic compound 11a into thiadiazole 18 presents the added complexity of debenzylation which could occur as shown in Scheme 1. The more usual conversion of 2-substituted allylic compounds (7 8 9 10 and 11) into isothiazoles (12 14 15 16 and 17 respectively) could result from their reaction with the monomer as shown in Scheme 2 which would also explain the observed regiochemistry. The dihydroisothiazole 33 is aromatised by dehydrogenation possibly via chlorination of 33 by more of the reagent. Conversion of 1,3-diketones into 1,2,5-thiadiazoles (Scheme 3) could proceed by electrophilic attack on the enol by the trimer followed by cyclisation in 34 onto the more reactive carbonyl group and this too would explain the observed regiochemistry.Loss of water and ClSNSCl1Cl2 then gives the Ph O Ph N S N O Ph Ph Cl Cl N S N O O Ph Ph 30 29 31 CCOPh N S N PhCOCH2CH2COPh PhCOC PhCOCH=CHCOPh 32 (NSCl)3 (NSCl)3 (NSCl)3 (NSCl)3 aromatic product. Formation of 3,4-dibenzoyl-1,2,5-thiadiazole 31 from 1,2-dibenzoylethane could result from similar attack on one enolic form followed by cyclisation via the second enol (Scheme 4). Experimental For general details see earlier parts of this series.10 1,3-Diphenyl-2-methylpropene 7 This was prepared by the literature method4 and obtained as a colourless oil (30) nmax(neat)/cm21 3026 2925 1947 1880 1806 1755 1650 1600 1494 1453 1377 1075 1030 917 and Scheme 1 N S N S N S Ph CO2Et Ph Cl Cl Cl N S N Cl ClS N S Cl Ph Ph CO2Et N S N Cl Ph Ph CO2Et N S N CO2Et Ph Cl _ H 11a 18 + PhCH2Cl ndash; S N S+ Clndash; Scheme 2 H S NH S R2 R1 R3 R2 R1 R3 R2 R1 R3 N S N N S R2 R1 R3 Cl H R2 R1 R3 S N Cl S R2 R1 R3 NH 33 OR H Cl .... Scheme 3 H O O R Rcent; N S N S N S Cl Cl Cl O O R Rcent; N S N S N S Cl Cl O R N S N S N S Cl Cl H O Rcent; H N S N O Rcent; R H+ ndash; HCl H+ + Cl ndash; + H2O + ClSNSCl+Clndash; 34 2834 J. Chem. Soc. Perkin Trans. 1 1997 857; dH(270 MHz CDCl3) 1.79 (3H s CH3) 3.47 3.62 (2H two singlets ratio 2 :1 PhCH2) 6.38 6.52 (1H two singlets ratio 2 1 alkene-H) and 7.14ndash;7.37 (10H m ArH). Phenylmethylidenecyclohexane 8 A solution of cyclohexyl bromide (0.01 mol 1.87 ml) and triphenylphosphine (0.01 mol 2.63 g) in sodium-dried benzene (50 ml) was stirred and heated under reflux. The initially clear solution rapidly became cloudy and the phosphonium salt precipitated as a pale yellow solid.The solid was collected and washed with ether to give the phosphonium salt. Sodium hydroxide (80 mmol 3 g) in benzene (15 ml) was added dropwise to a stirred suspension of the phosphonium salt (10 mmol 4.26 g) and benzaldehyde (10 mmol 1.0 ml) in water (15 ml) at room temperature over 20 min. Upon addition the initially clear mixture became cloudy as triphenylphosphine oxide was formed. The stirring was continued for 3 h before the mixture was evaporated and the phenylmethylidenecyclohexane 8 (1.03 g 60) was isolated as a colourless oil bp 104 8C/3 mmHg (lit.,5 bp 83 8C/5 mmHg); nmax(neat)/cm21 3027 2927 2854 1654 1598 1494 1447 918 736 and 699; dH(270 MHz CDCl3) 0.85ndash;0.88 (2H m CH2) 1.60ndash;1.62 (4H m 2CH2) 2.25 (2H t CH2) 2.36 (2H t CH2) 6.22 (1H s alkene-H) and 7.15ndash; 7.29 (5H m ArH).The following allylic compounds were synthesised by the Wadsworthndash;Emmons method with triethyl phosphonoacetate. To a dispersion of sodium hydride in mineral oil triethyl phosphonoacetate was added dropwise. The mixture was stirred until it was colourless before the respective ketone was added. The solution was stirred at ambient temperature until the reaction was complete (TLC). The products were isolated by flash chromatography on silica gel. Ethyl 3-benzyl-4-phenylbut-2-enoate 9. Colourless oil (Found M1 280.1463. C19H20O2 requires M 280.1463); nmax(neat)/cm21 3061 3027 1734 1647 1601 1584 1494 1454 1391 1369 1323 1237 1076 1032 800 and 752; dH(270 MHz CDCl3) 1.14 (3H t CH3) 3.14 (2H s PhCH2) 3.59 (2H s PhCH2) 4.03 (2H q CH2) 6.61 (1H s alkene-H) and 7.04ndash;7.39 (10H m Scheme 4 Ph O Ph O Ph O Ph O H N S N S N S Cl Cl Cl O O Ph Ph N S N S N S Cl Cl H N S N S N S Cl N S N O Ph ndash; HCl 31 O Ph ndash; HSNS Ph Ph O O H H ndash; HCl ndash; HCl ArH); m/z 280 (M1 50) 234 (M1 2 CO2 30) 206 (M1 2 CO2Et 30) 192 (35) 129 (10) 115 (25) and 91 (PhCH2 1 100).Ethyl indan-2-ylideneacetate 10. Pale yellow oil (Found M1 202.0992. C13H14O2 requires M 202.0994); nmax(neat)/cm21 3057 3020 2982 2937 1735 1614 1462 1393 1369 1332 1301 1251 1176 1097 1032 914 796 and 755; dH(270 MHz CDCl3) 1.19ndash;1.24 (3H t CH3) 3.37 (2H s CH2) 3.43 (2H s CH2) 4.07ndash;4.15 (2H q CH2) 6.62 (1H s alkene-H) and 7.08ndash;7.34 (4H m ArH); m/z 202 (M1 45) 156 (M1 2 CO2 18) 126 (M1 2 CO2Et 14) and 76 (13). (Z)-Ethyl 3,4-diphenylbut-2-enoate 11a.6 Colourless oil; nmax(neat)/cm21 3059 2980 2925 1727 (C O) 1642 1604 1548 1453 1376 1265 1223 1162 1075 1034 and 877; dH(270 MHz CDCl3) 1.10 (3H t CH3) 3.67 (2H s PhCH2) 4.04 (2H q CH2) 6.99 (1H s alkene-H) and 7.23ndash;7.48 (10H m ArH); m/z 266 (M1 100) 221 (10) 193 (M1 2 CO2Et 80) 178 (55) 165 (15) 152 (5) 115 (82) 91 (PhCH2 1 33) and 77 (Ph1 6).(E)-Ethyl 3,4-diphenylbut-2-enoate 11b.6 Colourless oil; nmax(neat)/cm21 3059 3027 2980 2930 1727 (C O) 1642 1601 1549 1453 1377 1265 1223 1162 1075 1034 877 759 and 729; dH(270 MHz CDCl3) 1.16 (3H t CH3) 4.10 (2H q CH2) 4.41 (2H s PhCH2) 6.14 (1H s alkene-H) 7.12ndash;7.29 (10H m ArH); m/z 266 (M1 100) 220 (M1 2 EtOH 97) 192 (85) 178 (25) 165 (15) 152 (5) 131 (7) 115 (55) 91 (PhCH2 1 33) and 77 (Ph1 6). Reactions of trithiazyl trichloride With cinnamyl chloride. (a) Cinnamyl chloride (freshly distilled 76 mg 0.5 mmol) in benzene (1 ml) was added at room temperature to a stirred solution of trithiazyl trichloride (122 mg 0.5 mmol) in benzene (4 ml) under nitrogen.The mixture was stirred and heated at reflux for 17 h under nitrogen. The solvent was evaporated and the residue was separated by chromatography on silica gel. Elution with dichloromethane (30) in light petroleum gave 3-chloromethyl-4-phenyl-1,2,5-thiadiazole 3 as colourless needles (59 mg 56) mp 69ndash;70 8C; nmax(neat)/cm21 3066 3027 2925 2854 1578 1497 1468 1455 1442 1402 1304 1274 1222 1178 1158 1076 1015 934 919 844 and 832; dH(270 MHz CDCl3) 4.80 (2H s CH2Cl) 7.45ndash;7.50 (3H m ArH) and 7.70ndash;7.77 (2H m ArH); m/z 212 (M1 isotope 37) 210 (M1 100) 175 (M1 2 Cl 70) 135 (PhCNS1 62) 116 (18) 103 (PhCN1 17) and 77 (Ph 18).(b) To a stirred solution of trithiazyl trichloride (244 mg 1 mmol) in tetrachloromethane (5 ml) cinnamyl chloride (76 mg 0.5 mmol) in tetrachloromethane (1 ml) was added dropwise. The mixture was heated at reflux for 17 h under nitrogen. The solvent was evaporated and the residue was separated by chromatography on silica gel. Elution with dichloromethane (30) in light petroleum gave 3-dichloromethyl-4-phenyl-1,2,5-thiadiazole 4 as a red oil (15 mg 12) dH(270 MHz CDCl3) 6.95 (1H s CHCl2) 7.52ndash;7.58 (3H m ArH) and 7.67ndash;7.73 (2H m ArH); m/z 248 (M1 isotope 10.4) 246 (M1 isotope 54) 244 (M1 75) 211 (M1 2 Cl isotope 28) 209 (M1 2 Cl 76) 187 (26) 173 (M1 2 HCl 2 Cl 100) 135 (PhCNS1 30) and 77 (Ph1 28). Elution with dichloromethane (40) in light petroleum gave 3-chloromethyl-4-phenyl-1,2,5-thiadiazole 3 (21 mg 17) mp 69ndash;70 8C identical with that described in (a).With 1,3-diphenylpropene. (a) To a stirred solution of trithiazyl trichloride (244 mg 1 mmol) in tetrachloromethane (3 ml) 1,3-diphenylpropene (97 mg 0.5 mmol) in tetrachloromethane (1 ml) was added by a syringe slowly. No significant temperature or colour change was observed. The mixture was heated at reflux for 20 h under nitrogen; it turned green and then red. The solvent was evaporated and the residue was separated on silica gel. Elution with dichloromethane (50) in light petroleum gave 3,5-diphenylisothiazole 5 (63 mg 53) as colourless needles mp 85.5ndash;86.5 8C (lit.,11 81 8C) (Found C 76.0; H 4.3; N 5.8. Calc. for C15H11NS C 76.0; H 4.6; N 5.9); nmax(Nujol)/cm21 3055 1529 1485 1455 1391 1370, J.Chem. Soc. Perkin Trans. 1 1997 2835 1337 1306 1205 1188 1153 1100 1087 1076 1028 1000 984 970 920 and 910; dH(270 MHz CDCl3) 7.40ndash;7.50 (6H m ArH) 7.61ndash;7.68 (2H m ArH) 7.75 (1H s 4-H) and 7.97ndash; 8.01 (2H m ArH); m/z 237 (M1 100) 204 (5) 135 (PhCNS1 17) 134 (24) 121 (5) 103 (PhCN1 7) 89 (6) and 77 (Ph1 16). (b) 1,3-Diphenylpropene (194 mg 1 mmol) in chloroform (0.5 ml) was added to a solution of trithiazyl trichloride (80 mg 0.33 mmol) in chloroform (2.5 ml) at room temperature and then heated at reflux for 17 h. The solvent was evaporated and the residue was separated on silica gel. Elution with dichloromethane (50) in light petroleum firstly gave a thin oil (230 mg) which appeared to be chlorinated starting material (based on the mass spectrum) and secondly gave 3-(a-chlorobenzyl )-4- phenyl-1,2,5-thiadiazole 6 as colourless needles (30 mg 14) mp 115ndash;118 8C (Found C 62.8; H 3.9; N 9.9.C15H11ClN2S requires C 62.8; H 3.8; N 9.8); nmax(Nujol)/cm21 1398 1247 1223 1198 1170 1079 1015 931 886 858 841 804 783 769 741 701 663 and 655; dH(270 MHz CDCl3) 6.35 (1H s CHClPh) 7.35ndash;7.42 (3H m ArH) 7.52ndash;7.58 (5H m ArH) and 7.60ndash;7.65 (2H m ArH); m/z 286 (M1 12) 251 (M1 2 Cl 100) 173 (39) 148 (37) 135 (PhCNS1 5) 125 (11) 116 (14) 103 (PhCN1 9) and 91 (4). Reactions of allylic compounds with trithiazyl trichloride Either procedure A or B was used. In procedure A a mixture of the organic substrate (1 mmol) and the reagent (1 mmol) in tetrachloromethane (20 ml) was heated at reflux overnight. The solvent was then evaporated and the residue was separated by flash chromatography on silica eluting with dichloromethane in light petroleum.In procedure B the same mixture in tetrachloromethane (25 ml) was heated at reflux overnight in the presence of 4 Aring; molecular sieves (2 g). The molecular sieves were then filtered off and washed with dichloromethane and the combined organic solution was evaporated and the residue was separated as in A. With 1,3-diphenyl-2-methylpropene 7. Procedure A with compound 7 (208 mg) and trithiazyl trichloride (244 mg) gave 3,5-diphenyl-4-methylisothiazole 12 (48 mg 19) mp 145ndash; 147 8C (Found C 76.3; H 5.3; N 5.8. C16H13NS requires C 76.5; H 5.2; N 5.6); nmax(CHCl3)/cm21 3084 3001 2380 1881 1490 1456 1238 1220 and 804; dH(270 MHz CDCl3) 2.32 (3H s CH3) and 7.39ndash;7.67 (10H m ArH); m/z 251 (M1 75) 250 (100) 217 (M1 2 S 2) 147 (M1 2 PhCN 10) 135 (PhCNS1 2) 121 (PhCS1 6) 115 (3) 104 (6) 103 (PhCN1 6) and 77 (Ph1 7) and 3-chloro-1,3-diphenyl-2-methylpropan-1-one 13 (62 mg 26) mp 97ndash;99 8C; nmax(CHCl3)/cm21 3020 3010 2440 1881 1710 1480 1456 1240 1220 and 899; dH(270 MHz CDCl3) 1.83 (3H br CH3) 2.05 (1H m CHMe) 5.45 (1H d CHCl) and 7.27ndash;7.40 (10H m ArH); m/z 260 (M1 1 2 0.6) 258 (M1 1.9) 243 (M1 2 Me 2.4) 223 (M1 2 Cl 18) 222 (25) 205 (24) 179 (7) 145 (7) 118 (36) 115 (49) 105 (PhCO1 100) and 77 (Ph1 48).With phenylmethylidenecyclohexane 8. Procedure A with compound 8 (172 mg) and trithiazyl trichloride (244 mg) gave 3-phenyl-4,5,6,7-tetrahydro-2,1-benzisothiazole 14 (15 mg 7) as a yellow oil (Found M1 215.0768 C13H13NS requires M 215.0769); nmax(CHCl3)/cm21 3027 2936 1667 1599 1492 1446 1409 and 913; dH(270 MHz CDCl3) 1.80ndash;1.91 (4H m 2CH2) 2.79ndash;2.89 (2H t CH2) 2.91ndash;2.94 (2H t CH2) and 7.38ndash;7.49 (5H m ArH); m/z 215 (M1 100) 187 (15) 121 (PhCS1 10) 115 (15) 91 (25) and 77 (Ph1 14).With ethyl 3-benzyl-4-phenylbut-2-enoate 9. Procedure B with compound 9 (283 mg) gave ethyl 4-benzyl-3-phenylisothiazole-5- carboxylate 15 (104 mg 32) as pale yellow oil (Found M1 323.0981. C19H17NO2S requires M 323.0980); nmax(CHCl3)/ cm21 3031 3001 1730 (C O) 1491 1447 1408 1372 1335 1265 1219 1190 1030 782 777 736 and 667; dH(270 MHz CDCl3) 1.09ndash;1.28 (3H t CH3) 3.71 (2H s PhCH2) 4.00ndash;4.08 (2H q CH2) and 7.43ndash;7.62 (10H m ArH); m/z 323 (M1 65) 250 (M1 2 CO2Et 100) 217 (10) 147 (M1 2 CO2Et 2 PhCN 25) 115 (12) 103 (PhCN1 22) and 77 (Ph1 30). With ethyl indan-2-ylideneacetate 10. Procedure B with compound 10 (203 mg) gave ethyl 4H-indeno1,2-cisothiazole-3- carboxylate 16 (45 mg 25) as orangendash;brown crystals mp 131ndash; 132 8C (Found M1 245.0511.C13H11NO2S requires M 245.0511); nmax(CHCl3)/cm21 3057 3020 2982 2937 1735 (C O) 1614 1462 1393 1369 1332 1301 1251 1176 1097 1032 914 and 796; dH(270 MHz CDCl3) 1.44ndash;1.49 (3H t CH3) 3.97 (2H s CH2) 4.43ndash;4.51 (2H q CH2) 7.36ndash;7.39 (2H m ArH) and 7.55ndash;7.64 (2H m ArH); m/z 245 (M1 60) 200 (M1 2 CO2 13) 173 (M1 2 CO2Et 100) 146 (30) 140 (M1 2 CO2Et 2 S 50) 128 (M1 2 CO2Et 2 CS 7) 101 (5) and 86 (6). With (E)-ethyl 3,4-diphenylbut-2-enoate 11b. Procedure B with compound 11b (233 mg 0.95 mmol) gave ethyl 3,4- diphenylisothiazole-5-carboxylate 17 (180 mg 66) mp 80ndash; 81 8C (Found M1 309.0823. C18H15NO2S requires M 309.0824); nmax(CHCl3)/cm21 3031 3001 1740 (C O) 1491 1447 1408 1372 1335 1219 1190 1030 782 777 736 and 667; dH(270 MHz CDCl3) 1.21ndash;1.26 (3H t CH3) 4.22ndash;4.30 (2H q CH2) and 7.19ndash;7.38 (10H m ArH); m/z 309 (M1 100) 280 (M1 2 Et 30) 262 (M1 2 SN 40) 236 (M1 2 CO2Et 22) 204 (M1 2 CO2Et 2 S 5) 190 (7) 133 (PhC2S1 10) and 86 (6).With (Z)-ethyl 4-phenyl-3-benzylbut-2-enoate 11a. Procedure B with compound 11a (213 mg 0.85 mmol) gave ethyl 3,4- diphenylisothiazole-5-carboxylate 17 (15 mg 6) mp 80ndash; 81 8C identical with that described above and ethyl 4-phenyl- 1,2,5-thiadiazole-3-carboxylate 18 (45 mg 23) identical with an authentic sample. Reactions of 1,3-diketones with trithiazyl trichloride Either procedure C or D was used. In procedure C a mixture of the organic substrate (2 mmol) and trithiazyl trichloride (2 mmol) in tetrachloromethane (30 ml) was heated at reflux under nitrogen for 12 h.The solvent was evaporated in vacuo and the residue was separated by column chromatography on silica eluting with dichloromethane in light petroleum. In procedure D a mixture of the organic substrate (2 mmol) trithiazyl trichloride (3 mmol) and dry 4 Aring; molecular sieves (4 g) in tetrachloromethane (30 ml) was heated at reflux under nitrogen for 12 h. The mixture was then filtered and the molecular sieves were washed with dichloromethane and the combined organic solution was evaporated and worked up as above. With dibenzoylmethane 19. (a) Procedure C and elution with dichloromethane (60) in light petroleum gave 3-benzoyl-4- phenyl-1,2,5-thiadiazole 20 (110 mg 20) as colourless needles mp 82ndash;83 8C (lit.,7 81ndash;83 8C); m/z 266 (M1 56) 237 (12) 219 (3) 135 (PhCNS1 9) 105 (PhCO1 100) 77 (Ph1 63) 51 (25).Elution with dichloromethane gave bis(dibenzoylmethylideneamino) trisulfide 21 (56 mg 5) as yellow needles mp 87ndash;88 8C (Found C 63.3; H 3.4; N 4.9. C30H20N2O4S3 requires C 63.4; H 3.5; N 4.9); nmax(CHCl3)/cm21 3037 3021 1657 (C O) 1598 1450 1319 1288 1245 1182 1003 979 and 876; dH(270 MHz CDCl3) 7.4ndash;7.5 (12H m PhH) and 7.52ndash;7.63 (8H m PhH); m/z 268 (M1 2 S/2 60) and 105 (PhCO1 100). (b) Procedure D gave 3-benzoyl-4-phenyl-1,2,5-thiadiazole 20 (220 mg 41) as colourless needles mp 82ndash;83 8C identical with that described above and bis(dibenzoylmethylideneamino) trisulfide 21 (122 mg 11) as yellow needles mp 87ndash;88 8C identical with that described above. With 1,3-diphenylprop-2-en-1-one 22.Procedure C but with trithiazyl trichloride (976 mg 4 mmol) gave 3-benzoyl-4- phenyl-1,2,5-thiadiazole 20 (322 mg 60) mp 82ndash;83 8C identical with that described above. With 1-(4-methoxyphenyl)-3-phenylpropane-1,3-dione 23. Procedure D but with trithiazyl trichloride (366 mg 3 mmol) gave 3-(4-methoxybenzoyl )-4-phenyl-1,2,5-thiadiazole 26 (198 mg 33) as colourless needles mp 129ndash;131 8C (Found M1 296.0620. C16H12N2O2S requires M 296.0619); nmax(CHCl3)/ 2836 J. Chem. Soc. Perkin Trans. 1 1997 cm21 3038 3007 1670 (C O) 1601 1518 1461 1423 1395 1268 1195 1163 1044 1030 900 and 835; dH(270 MHz CDCl3) 3.90 (3H s OMe) 6.97ndash;6.99 (2H d 4-MeOC6H4) 7.34ndash;7.42 (3H m PhH) 7.66ndash;7.72 (2H m PhH) and 7.93ndash;7.95 (2H d 4-MeOC6H4); m/z 296 (M1 39) 265 (M1 2 S 2) 135 (4-MeOC6H4CO1 100) 103 (PhCN1 5) 92 (13) and 77 (Ph1 20).With benzoylacetone 24. Procedure D but with trithiazyl trichloride (732 mg 3 mmol) gave 3-benzoyl-4-methyl-1,2,5- thiadiazole 27 (102 mg 25) as colourless crystals mp 72ndash; 73 8C (lit.,7 72ndash;73 8C); m/z 204 (M1 69) 105 (PhCO1 100) and 77 (Ph1 88). With indane-1,3-dione 25. Procedure D but with trithiazyl trichloride (1.46 g 6 mmol) and with refluxing for 24 h gave unreacted indane-1,3-dione 25 (178 mg 61) and 8H-indeno- 1,2-c1,2,5thiadiazol-8-one 28 (60 mg 16) mp 112ndash;114 8C (lit.,2 113 8C). With 1,2-dibenzoylethane. Procedure C with trithiazyl trichloride (732 mg 3 mmol) gave 3,4-dibenzoyl-1,2,5-thiadiazole 31 (235 mg 40) as colourless needles mp 128ndash;129 8C (lit.,2,12 124 8C); m/z 294 (M1 18) 217 (M1 2 Ph 4) 105 (PhCO1 100) and 77 (Ph1 50).With 1,2-dibenzoylethyne. Procedure C with 1,2-dibenzoylethyne (234 mg 1 mmol) and trithiazyl trichloride (366 mg 1.4 mmol) gave 3,4-dibenzoyl-1,2,5-thiadiazole 31 (129 mg 44) mp 128ndash;129 8C identical with that described above. With fluorene. Procedure C but with refluxing for 24 h gave bis(fluoren-9-ylideneamino) sulfide 32 (155 mg 40) as yellow prisms mp 290 8C (lit.,9 300 8C); m/z 388 (M1 81) 342 (M1 2 NS 16) 210 (99) 179 (100) 151 (16) 76 (12) and 64 (12). With 1-phenyl-3-benzoylprop-1-ene 29. Procedure A with compound 29 (111 mg 0.5 mol) gave 3,4-dibenzoyl-1,2,5- thiadiazole 31 (38 mg 26) mp 128ndash;129 8C identical with that described above. Acknowledgements We thank Zeneca Specialties and MDL Information Systems (UK) Ltd for financial support and the Wolfson Foundation for establishing the Wolfson Centre for Organic Chemistry in Medical Science at Imperial College.References 1 Gmelin Handbook of Inorganic Chemistry 8th edn. Sulfur-Nitrogen Compounds Part 2 Springer Verlag Berlin 1985 p. 92. 2 X.-G. Duan X.-L. Duan C. W. Rees and T.-Y. Yue J. Chem. Soc. Perkin Trans. 1 1997 2597. 3 L. M. Tolbert and M. E. Ogle J.Am. Chem. Soc. 1990 112 9519. 4 C. L. Bumgardner and H. Iwerks J. Am. Chem. Soc. 1996 88 5518. 5 Dictionary of Organic Compounds Chapman and Hall London 6th edn. vol. 1 p. 705. 6 Y. Leroux and C. Jaquelin Synth. Commun. 1976 6 597. 7 S. Mataka A. Hosoki K. Takahashi and M. Tashiro Synthesis 1982 976. 8 S. Mataka A. Hosoki K. Takahashi and M. Tashiro J. Heterocycl. Chem. 1980 17 1681. 9 S. Mataka K. Takahashi S. Ishi-i and M.Tashiro J. Chem. Soc. Perkin Trans. 1 1979 2905. 10 X.-L. Duan R. Perrins and C. W. Rees J. Chem. Soc. Perkin Trans. 1 1997 1617; C. W. Rees and T.-Y. Yuen J. Chem. Soc. Perkin Trans. 1 1997 2247. 11 R. A. Olofson J. M. Landesburg R. O. Berry D. Leaver W. A. H. Robertson and D. M. McKinnon Tetrahedron 1966 22 2119. 12 S. Mataka K. Takahashi Y. Yamada and M. Tashiro J. Heterocycl. Chem. 1979 16 1009. Paper 7/03033I Received 2nd May 1997 Accepted 6th June 1997