Synthesis of 3-phenylpyrazoles from 2-alkenyl-5-phenytetrazoles

摘要

J. CHEM. SOC. PERKIN TRANS. 1 1991 Synthesis of 3-Phenylpyrazoles f rorn 2-Alkenyl-5-phenytetrazoles Christopher J. Moody, Charles W. Rees and Richard G. Young Department of Chemistry, Imperial College of Science, Technology and Medicine, London SW7 2A Y, UK 2-Alkenyl-5-phenyltetrazoles 7a-e are readily converted by thermolysis or photolysis into 3-phenyl- pyrazoles lla-e in good to excellent yield (Table 2). The alkenyltetrazoles 7 are prepared by direct or indirect dehydration of the alcohols 5 formed by quenching a-lithioalkyltetrazoles with aldehydes. In previous papers we have described a new synthesis of imidazoles in which the key step is the photochemical de- composition of 1-alkenyltetrazoles; 1*2 the reaction presumably involves the electrocyclisation of an intermediate N-vinyl-imidoylnitrene followed by a rapid aromatising hydrogen shift (Scheme 1).When this hydrogen is replaced by an alkyl group, non-aromatic 4H-imidazoles can be i~olated.~ Scheme 1 In contrast, decomposition of 2,5-substituted tetrazoles is known to result in the formation of nitrilimines, which can be trapped in inter-or intra-molecular cycloadditions.'.' In particular, electrocyclisation of C,N-diphenylnitrilimine results in the formation of 3-phenylinda~ole.~ Electrocyclisation of N-vinylnitrilimines, generated from 2-alkenyltetrazoles, would therefore be expected to give pyrazoles by way of their non- aromatic 4H-isomers (Scheme 2). Such a route to pyrazoles Scheme 2 would be of interest since there are few pyrazole syntheses culminating in the formation of a ring C-C bond.' We now find that pyrazoles can indeed be obtained from 2-alken-l-yltetrazoles, and report our results in this paper.Results and Discussion Preparation of 2-ALken- 1-y1tetrazoLes.-We investigated three routes to 2-alken- 1-yltetrazoles: conjugate addition of tetrazoles to electrophilic alkynes, direct vinylation of tetrazoles, and reaction of 2-lithioalkyltetrazoles with aldehydes. We have already described the reaction of 2-(tributy1stannyl)tetrazoles 1 with electrophilic alkynes to give, after protonolysis, mixtures of 1-and 2- alkenyltetrazoles 2 and 3 (Scheme 3). The role of the R. ,R Rb? -+ =-C02Me NeN ,NSnBu3 1 2 3 Scheme 3 tributylstannyl group was to favour reaction at the tetrazole N- 1 position, and indeed 1-alkenyltetrazoles were the major products.2 Nevertheless, small quantities of the 2-alkenyl-tetrazoles (3, R = Ph, Me, C0,Me) could be obtained by this route.2 Various attempts were made to effect conjugate addition of tetrazoles to activated alkynes, avoiding the tributyltin deriv- atives, in an effort to obtain higher yields of the desired 2- isomers, although largely without success. Thus, treatment of 5-methyltetrazoles with methyl propiolate in benzene in the presence of a catalytic amount of triethylamine gave three alkenyltetrazoles: the 2-isomers 3 (R = Me) (24 E plus 15 Z) and the 1-isomer 2 (R = Me) (31 E only).Thus the reaction gives more 2-isomer than that of the corresponding tributylstannyltetrazoles,2 but it is hardly synthetically useful. Also attempted extension of the reaction to dimethyl acetylene- dicarboxylate resulted in double incorporation of the alkyne, with the formation of a 2: 1 adduct.2 The second route to 2-alkenyltetrazoles was based on the direct transition-metal catalysed N-vinylation of heterocycles with enol acetates.* Thus reaction of 5-phenyltetrazole with vinyl acetate in the presence of sodium tetrachloropalladate(I1) gave 5-phenyl-2-vinyltetrazole 4 (Scheme 4).However, the yield Na2PdC14 fa Scheme 4 was low (17), and the reaction mixture had a tendency to polymerise, and therefore this route was not investigated further. The final route to the required 2-alken- 1-yltetrazoles involved the lithiation of 2-alkyltetrazoles, which we have developed as a new synthesis of substituted tetrazoles.' Thus the 2-(2-hydroxyalkyl) tetrazoles 5a-c were prepared by lithiation of 2-methyl-5-phenyltetrazole, followed by quenching with formal- 3 30 J.CHEM. SOC. PERKIN TRANS. I 1991 Table 1 Conversion of hydroxyalkyltetrazoles into alkenyltetrazoles. 5 6 7 R' RZ Method of dehydration Yield 7 () a H H 6 (X = CI), DBU 77 b H Et 6 (X = OMS), DBU 52 C H 4-MeOC6H, 5 PTSA 99 d Me Ph 6(X = OMS), DBU, Benzene 82" d Me Ph 6 (X = OMS),DBU, THF 99 E/Z Ratio ~~~~~~~ - 95.51oo:o 86: 14' variesb Notes: At 46 conversion. 'Undergoes E/Z isomerisation in daylight. dehyde, propionaldehyde, and 4-anisaldehyde respectively, as previously described.' The tetrazole 5d was prepared similarly, as a mixture of diastereoisomers, from 2-ethyl-5-phenyltetrazole and benzaldehyde. The alkenyltetrazoles 7 were prepared by dehydration of the alcohols 5, which in the case of benzylic alcohol 5c could be effected simply by refluxing in benzene in the presence of a catalytic amount of toluene-p-sulphonic acid (PTSA).In the other cases, the elimination was effected by way of the corresponding mesylate or chloride (Table 1). The alkene 7b was also prepared as an E/Z-mixture by Peterson reaction of 5-phenyl-2-trimethylsilylmethyltetrazole8 with propionaldehyde (Scheme 5). The t-butyl derivative 7e was -i NdPh Table 2 Conversion of tetrazoles into pyrazoles 7 Tetrazole R' R2 7a(=4) H H 7a(=4) H H 7b H Et 7c H 4-MeOC6H, 7c H 4-MeOC6H, il Conditions Yield 11 () Heat, DCB" 79 hv, cyclohexaneb 60 hv, light petroleum 65 Heat, DCB 98 hv,MeOH 100 hv, MeOH 73 hv, MeOH 99 Me3SivN,N5N 7d Me Ph 7e H Bu'RYi8N5NR* " 1,2,-Dichlorobenzene, b.p.180 "C. 'Or methanol (60)yield)8 7 b; R' = H, R2= Et e; R' = H, R~ = BU' Scheme 5 Reagents: i Bu'Li or LDA,-THF, -78 "C;R'CHO prepared similarly, and these reactions are described in the previous paper.' Preparation of Pyrazo1es.-In contrast to the formation of imidazole 4(5)-esters from the tetrazole- 1-ylacrylates 2 which proceeded in good yield,2 decomposition of the 2-alkenyl isomers 3 was not a useful route to pyrazoles.Although the 5-phenyltetrazole 3 (R = Ph) gave a 39 yield of methyl 3-phenylpyrazole-4-carboxylate when heated in xylene,2 no pyrazoles could be obtained from the tetrazoles 3 (R = Me or CO,Me), either on thermal or photochemical decomposition. The only identifiable product of any sort was obtained when the tetrazole 3 (R = Me) was irradiated in methanol or ethanol. In this case the intermediate nitrilimine was trapped by the alcohol to give the ene hydrazone 9 which undergoes reaction with more starting material followed by loss of 5-methyltetrazole to give the observed product 10 formed in 50 and 73 yield for reaction in methanol and ethanol respectively (Scheme 6). The structure of compound 10 (R = Me) was fully supported by its spectroscopic properties, and confirmed by NOE enhancement measurements (see Experimental section). In contrast to the tetrazolylacrylates 3, the 2-alkenyltetrazoles 7 could be readily converted into 3-phenylpyrazoles 11 in good Me +-* MeCEN-N -CH=CHC02 Et Me02C 3 lRoH J 9 10 Scheme 6 R = Me or Et; Tet = 5-methyltetrazol-2-yl to excellent yield by thermolysis or photolysis.The results, which are summarised in Table 2, establish that this is a general route to 3-phenylpyrazoles, proceeding in high yield under either thermal or photochemical conditions. The precursor tetrazoles are now readily available by the lithiation route, and J. CHEM. SOC. PERKIN TRANS. 1 1991 hence access to a greater range of pyrazoles than presently illustrated is possible.Experimental All solvents were distilled before use. Petroleum refers to light petroleum, b.p. 4amp;60 "C, and ether refers to diethyl ether. THF and ether were distilled from potassium-benzophenone and sodium-potassium-benzophenone respectively, immediately prior to use. Other solvents were purified and dried by standard procedures. Photolyses were carried out in a Rayonet photochemical reactor using lamps emitting at 254 or 360 nm as specified, in quartz vessels. Unless otherwise stated solutions were purged with nitrogen for 0.5 h prior to irradiation, which was carried out under nitrogen purge. No cooling was employed, so that the typical temperature for photolyses was 35deg;C.The apparatus was flushed with nitrogen whilst cold and thermolyses were carried out in the solvent specified, magnetically stirred, under a nitrogen atmosphere. Flasks were heated with an oil-bath set at 10-20 "C above the relevant reflux temperature. Thin layer chromatography (TLC) on commercial plates of silca gel 60 F254on aluminium was used to monitor the progress of reactions. Column chromatography was carried out using silica gel 60H (E. Merck). IR spectra were recorded on a Perkin- Elmer 298 spectrophotometer in the range 60MOOO cm-' and calibrated against polystyrene. The spectra of solids were recorded as Nujol mulls and of oils as thin films between sodium chloride plates. UV spectra were recorded in the range 2U50 nm on a Pye Unicam SP800 spectrophotometer in quartz cells of 0.5cm path length.Unless otherwise stated the solvent was methanol. 'H NMR spectra were recorded on one of three instruments as follows: Varian Associates EM-360 (60 MHz), Perkin--Elmer R32 (90 MHz), and Bruker WM 250 (250 MHz) according to the frequency specified. Tetramethylsilane (TMS) was used as an internal reference. Carbon-1 3 spectra were recorded on the Bruker instrument operating at 62.9 MHz. Mass spectra were recorded on a VG Micromass 7070B mass spectrometer. An ionising potential of 70 or 12eV was employed using a direct insertion probe or septum inlet. Pd-Cutal??sed Ethenylation of 5-Phenyltetrazole.-Sodium tetrachloropalladate(1r) (330 mg, 1.13 mmol) was added to a suspension of 5-phenyltetrazole (1.46 g, 10 mmol) in vinyl acetate (50ml) and the whole was refluxed for 65 h.The mixture was filtered, the excess of vinyl acetate evaporated off, and the residue dissolved in ether (100 ml) and extracted with dilute aqueous sodium hydroxide to remove unchanged tetrazole. The solvent was evaporated off and the residue was chrom-atographed to give 5-phenyltetrazol-2-ylethene4 (= 7a) (287 mg, 17); 6(250 MHz, CDCI,): 5.40 (1 H, dd, J/Hz; 8.5 and lS), 6.28 (1 H, dd, J/Hz 15.5 and 1.5 Hz), 7.51 (3 H, m), 7.57 (1 H,dd, J 15.5 and 8.5 Hz), and 8.20 (2 H, m) identical (TLC, NMR) with an authentic sample.' Derrcatisation of 2-(2-euro;euro;ydroxyalkyl)tetra~oles Reaction of Tetrazole 5d with Methanesulphoiijd Chloride.- To a solution of tetrazole 5d (238.7 mg, 0.852 mmol) in dry chloroform (20 ml) were added methanesulphonyl chloride (0.1 ml, 1.28 mmol, 1.5 equiv.) and triethylamine (0.59 ml, 4.26 mmol, 5.0 equiv.).The mixture was heated at reflux for 60 h and dichloromethane (50 ml) added. The solution was washed with dilute aqueous hydrochloric acid and water, dried MgS04), and the solvent evaporated off togive (R,S)-/(S,R)-1 -methylsulphonyl- 0.~~9-1-phenj*l-2-(5-phenyltetrazol-2-yZ)propane 6d (X = OMS) 33 1 (305 mg, loo), m.p. 79-83 "C (Found: C, 57.1; H, 5.2; N, 15.3. C1,Hl8N4O3S requires C, 57.0; H, 5.1; N, 15.6); v,,,/cm-' 3030,2940, 1530, 1465, 1450, 1370vs, 1 18Ovs, 955,845,735 and 700; F(250 MHz, CDCI,) 1.50 (3 H, d, J/Hz: 7.6), 2.53 (3 H, s), 5.37-5.51 (1 H, br m), 5.98 (1 H, d, J/Hz: 9.3), 7.49 (8 H, m) and 8.20 (2 H, m); mlz(20e V): 358 (Mf),330,309,259,235,222,204, 188,179,164,150,136,117,104,91,86,78,57and 43.Reaction of Tetrazole 5a with Benzenesulphonyl Chloride.- To a solution of tetrazole 5a (212 mg, 1.1 1 mmol) and benzenesulphonyl chloride (0.156 ml, 1.23 mmol, 1.1 equiv.) in chloroform (10 ml) was added triethylamine (10 drops) and the mixture refluxed 17 h. Work-up and chromatography gave (i) 1- chloro-2-(5-phenyltetrazol-2-yl)ethane6a (X = Cl) (109 mg, 45) as an oil (Found: M', 208.05150. C9H,CIN4 requires 208.05157); v,,,/cm-' 3080, 1525, 1420, 1355, 1190, 1040 and 730; F(60 MHz, CDCI,) 4.12 (2 H, t, J/Hz: 6), 5.01 (2 H, t, J/Hz: 6), 7.45-7.75 (3 H, m), and 8.15-8.45 (2 H, m); m/z 208/210 (M+),180/182, 141, 131, 104, 89, 77 and 63; and (ii) 1-phenyl-sulphonyloxy-2-(5-phenyltetrazol-2-yl)ethane6a (X = OSO2-Ph) (92 mg, 25), m.p.79-81 "C (Found: M+ -28, 302.07250. CI5Hl4N2O3Srequires 302.07251); 6(60 MHz, CDCI,): 4.81 (4 H, br m), 7.35-7.68 (6 H, m), 7.72-7.95 (2 H, m) and 8.048.28 (2 H, m);m/z: 302 (M+ -28), 171, 141, 132, 104,77,71,57 and 51. 2-Alken- 1 -yltetrazoles by Eliminution Work-up Procedure (unless @en).-Ether (5 volumes) was added and the organic layer washed successively with dilute aqueous hydrochloric acid, aqueous sodium hydrogen carbonate and water and dried (MgS04). The solvent was removed by evaporation under reduced pressure and the residue chromato- graphed on silica gel with petroleum containing an increasing proportion of ether as eluant.Where necessary, ether containing an increasing proportion of methanol was subsequently employed. (a) Elimination in Base.-Tetrazole 6a (X = C1).-To a solution of the tetrazole 6a (X = Cl) (54 mg, 0.26 mmol) in THF (20 ml) was added DBU (10 drops) and the mixture was refluxed for 1 h. Work-up gave 5-phenyltetrazol-2-ylethene 7a (34 mg, 7773 identical (TLC, NMR) with authentic material.' Reaction of the tetrazole 5b Kith methanesulphonyl chloride. To a solution of the tetrazole 5b (393 mg, 1.80 mmol) in dioxane (15 ml) was added methanesulphonyl chloride (0.153 ml, 1.98 mmol, 1.1 equiv.) and 1,8-diazabicyclo5.4.Oundec-7-ene (DBU) (10 drops) and the mixture stirred at 100 "C for 0.25 h and 25 "C for 15 h.Work-up from dichloromethane gave an oil which was a mixture (NMR, TLC) of 2-methylsulphonyloxy- 1- (5-phenyltetrazol-2-y1)butane6b (X = OMS), 2-chloro- 1-(5- phenyltetrazol-2-y1)butane 6b (X = Cl), and 1-(5-phenyl-tetrazol-2-yl) but-1-ene 7b. The mixture was further treated with DBU (20 drops) in dry THF (20 ml) at 80 "C for 25 h. Work-up and chromatography gave (E/Z)-1-(5-phenyltetrazol-2-yl)but-1-ene E/Z-7b ( 95 :5 by NMR) (189 mg, 52"/,) as an oil identical (NMR, TLC) to material isolated from the Peterson reaction.' Tetrazole 6d (X = OMS) in benzene. To a solution of the tetrazole 6d (X = OMS) (280 mg, 0.78 mmol) in dry benzene (10 ml) was added DBU (0.129 ml, 0.86 mmol, 1.1 equiv.) and the mixture stirred at 50 "C for 16 h.Work-up and chromatography gave (i) a mixture of (E)-1-phenyl-2-(5-phenj~ltetra=ol-2-yl)prop-1-ene E-7d (66. 7 mg, 33) as an oil (Found: M' -28 = 234.1 159. C,,H14N2 requires 234.1 157); v,,,/cm-': 3060, 1660w, 1530, 1465, 1450, 1210, 1020, 765, 730 and 695; 6(90 MHz, CDCI,): 2.65 (3 H, s), 7.25-7.55 (8 H, m), 7.74 (1 H, s) and 8.15-8.30 (2 H, m); m/z 263 (M' +1), 234, 206, 193, 165, 131, 116,103,90,77,63 and 51 and (Z)-l-pheny1-2-(5-phenyltetrazol-2-y1)prop-1-ene Z-7d (10.9 mg, 576) which has 6(90 MHz, CDCl,) 2.50 (3 H, s), 6.75 (1 H, s), 6.82-6.97 (2 H, m), 7.12-7.31 (3 H, m), 7.37-7.57 (3 H, m) and 8.07-8.20 (2 H, m); and (ii) starting material (149.9 mg, 54). Tetrazole 6d (X = OMS) in THF.To a solution of the tetrazole 6d (X = OMS) 35.5 mg, 0.10 mmol) in THF (10 ml) was added DBU (0.5 ml) and the mixture stirred at 80 "C for 160 h. Work-up and removal of the solvent by evaporation gave the alkene 7d (E/Z-mixture) (25.6 mg, 99) as an oil identical with the product mixture from benzene (TLC), NMR). The alkene 7d undergoes E/Z-photoequilibration in daylight. (b) Acid-catalysed Dehydration.-Tetrazole 5c.To a solution of the tetrazole 5c (600 mg crude product) in dry benzene (20 ml) was added PTSA (ca. 100 mg) and the mixture heated at 80 "C for 36 h. Work-up and chromatography gave 1-(4-methoxy-phenyl)-2-(5-phenyltetrazol-2-yl)ethune7c(367 mg, 76 from the methyltetrazole; estimated yield for this step: 9973, m.p.105- 107 "C (Found: C,69.2; H, 5.1; N, 20.1. CI6Hl4N40 requires C, 69.05; H, 5.1; N, 20.1 ); v,,,/cm-': 3095,3005, 1605, 15 10, 1250, 1180, 1025,940, 800, 730 and 700; 6(250 MHz, CDCl,): 3.96 (3 H, s), 6.96 (2 H, d, J/Hz: 9), 7.45-7.58 (5 H, m), 7.66 (1 H, d, J/Hz: 14), 7.90 (1 H, d, J/Hz: 14 Hz) and 8.19-8.26 (2 H, m); m/z 278 (M+),250,228,222, 197, 147, 132 (base), 120, 103,91, 77, 63, 57 and 51. Photolysis of Methyl (E)-3-(5-Meth~~ltetrazol-2-ltllpvopenoute 3 (R = Me).-A solution of the tetrazole 3 (R = Me) (182 mg) in methanol (180 ml) was irradiated for 2h. The solvent was evaporated off and the residue was chromatographed to give methyl N-(2,4-dimethoxycarbonylbuta-1,3-dien- 1 -ylamino)-acetimidate 10 (R = Me) (37.2 mg, 50), m.p.133-135deg;C (Found: C, 51.6; H, 6.3; N, 10.9. C,,H,,N206 requires C, 51.6; H, 6.3; N, 10.9); v,,,/cm-': 3040vw, 3010vw,l700,1690w, 1650, 1620, 1600vs, 1400, 1205 and 1160; v,,,/nm(MeOH) 293 (log E 4.08) and 347 (4.40); 6(250 MHz, CDC1,) 2.08 (3 H, s), 3.727 (3 H, s), 3.731 (3 H, s), 3.81 (3 H, s), 6.04 (1 H, d, JjHz: 15.7), 7.46 (1 H, d, J/Hz: 15.7), 7.67 (1 H, d, J/Hz: 10.9) and 11.19 (1 H, br d, J/Hz: 10.9) (exch. D20) (in an NOED experiment irradiation of the signal at 62.08 caused 0.3 and 17 enhancements of the signals at 6 3.81 and 11.19 respectively; irradiation of the signal at 6 3.73 caused 0.9, 1.3, 0.6 and 0.4 enhancements of the signals at 6 2.08, 6.04, 7.46 and 7.67 respectively; irradiation of the signal at 6 3.8 1 caused 0.3,0.4 and 0.5 enhancements of the signals at 6 2.08, 6.04 and 7.46 respectively; irradiation of the signal at 6 6.04 caused 0.1,0.2,0.5, 1.2 and 14 enhancements of the signals at 6 2.08, 3.73, 3.81, 7.46 and 7.67 respectively; irradiation of the signal at 6 7.46 caused 0.1, 0.2, 2 and 16 enhancements of the signals at 6 3.73, 3.81, 6.04 and 7.67 respectively; irradiation of the signal at 6 7.67 caused 0.1, 10, 13 and 3 enhancements of the signals at 6 3.73, 6.04, 7.46 and 11.19 respectively; irradiation of the signal at 6 11.19 caused 5 and 2 enhancements of the signals at 6 2.08 and 7.67 respectively); mjz 256 (M'), 224, 209, 193 (base), 183, 169, 141, 127, 109,95,69,57 and 43.A solution of the same tetrazole 3 (R = Me) (237 mg) in ethanol (180 ml) was irradiated for 2.2 h.The solvent was evaporated off and the residue was chromatographed to give the ethyl acetimidate 10 (R = Et) (86.5 mg, 73); 6(60 MHz, CDC1,): 1.31 (3 H, t, J/Hz: 7), 2.08 (3 H, s), 3.72 (3 H, s), 3.80 (3 H, s), 4.13 (2 H, q, J/Hz: 7), 6.05 (1 H, d, J/Hz: 15), 7.49 (1 H, d, J/Hz: 15), 7.68 (1 H, d, J/Hz: 11) and 11.27 (1 H, br d, J/Hz: 11); amp;: 14.2, 14.6, 51.0, 51.1, 62.8, 93.4, 108.3, 142.5, 152.3, 159.2, 169.0 and 169.8 Pyrazoles by Loss of Nitrogen from 2-Alken-1 -yltetruzoles (a) Thermolysis: General Procedure.-The tetrazoles 7 in solvent (1 ml per mmol) were heated at reflux for the stated J. CHEM. SOC. PERKIN TRANS. I 1991 period. The product pyrazoles were isolated by evaporation of the solvent and chromatography or recrystallisation.Tetrazole 7a. A solution of the tetrazole 7a (22.0 mg, 0.13 mmol) in ODCB (1.5 ml) was refluxed 2 h. The solvent was evaporated off and the residue was chromatographed to give 3- phenylpyrazole lla (14.6 mg, 7973, m.p. 59-60 "C (5 ether in petroleum, 0 "C), 59-60 "C (water, 0 "C), 60-62 "C (subl. at 10 Torr, 50"C), identified as the picrate m.p. 171-172deg;C (ethanol) (lit.," 170-171 "C).The pyrazole lla has 6(60 MHz, CDCl,) 6.62 (1 H, d, J/Hz: 2), 7.24-7.92 (6 H, m) and 11.23 (1 H, br s). Tetrazole 7c. A solution of the tetrazole 7c (9.8 mg, 0.035 mmol) in ODCB (3 ml) was refluxed 1.5 h. The solvent was evaporated off and the residue was chromatographed to give 4- (4-methoxyphenyl)-3-phenylpyrazole1 lc (8.6 mg, 98), m.p.126-127 "C(Found:C,76.8;H,5.7;N, 11.1.C1,H,,N20requires C, 76.8; H, 5.6; N, 11.2); v,,,/cm-l: 3160, 1615, 1535, 1495, 1250, 1030,945, 830 and 700 cm-'; 6(250 MHz, CDCl,): 3.81 (3 H, s), 6.86 (2 H, "d, JjHz: 9), 7.22 (2 H, -d, J/Hz: 9), 7.30-7.37 (3 H, m), 7.42-7.49 (2 H, m) and 7.62 (1 H, s);m/z250 (M'), 235, 205, 190, 178,165, 152, 140, 128, 104,85,76 and 65. (b) Photolysis: General Procedure.-A solution of the tetrazole 7 in the solvent specified was irradiated in a quartz vessel under a stream of nitrogen. The irradiation was continued until no tetrazole remained (TLC) and the products were isolated by chromatography. Tetrazole 7a in cyclohexane. A solution of the tetrazole 7a (68.7 mg, 0.40 mmol) in cyclohexane (60 ml) was irradiated for 2.5 h.The solvent was evaporated off and the residue was chromatographed to give 3-phenylpyrazole 1la (34.4 mg, 60"/,), m.p. 60-61 "C after sublimation. Tetrazole 7a in methanol. A solution of the tetrazole 7a (20.0 mg, 0.12 mmol) in methanol (25 ml) was irradiated for 3 h. The solvent was evaporated off and the residue was chrom-atographed to give 3-phenylpyrazole lla and (10.0 mg, 60"/:,), identified as the picrate, m.p. 171-172 "C. Tetrazole 7b.A solution of the tetrazole EiZ-7b (69 mg, 0.345 mmol) in petroleum (60 ml) was irradiated for 1.5 h. The solvent was evaporated off and the residue was chromatographed to give 4-ethyl-3-phenylpyrazole 1 lb (38.3 mg, 65);' ' 6(250 MHz, CDCI,): 1.24 (3 H, t, J/Hz: 7.5 Hz), 2.67 (2 H, q, JiHz: 73, 7.26 (I H, s), 7.32-7.48 (3 H, m), 7.49 (1 H, s) and 7.52- 7.60 (2 H, m); m/z 172 (M+),157 (base), 140, 130, 128, 103, 77,65 and 51.Tetrazole 7c. A solution of the tetrazole 7c (13.2 mg, 0.047 mmol) in methanol (20 ml) was irradiated for 3.0 h. The solvent was evaporated off to give 4-(4-methoxphyenyl)-3-phenylpy-razole 1 lc (12.1 mg, 100)identical (TLC, NMR) with material generated by thermolysis of 7c. Tetrazole 7d.A solution of the tetrazole EiZ-7d (26.0 mg, 0.01 mmol) in methanol (30 ml) was irradiated for 3.0 h. The solvent was evaporated off and the residue was recrystallised from chloroform at 0 "C to give 5-meth)~l-3,4-~iphen~lpyra~ole1Id (17.0 mg, 7373, m.p. 176-179 "C; vmax/cm-'(CC14): 3470, 3190, 3070, 2930, 2860, 1605, 1445, 1070, 915 and 700 cm-'; 6(250 MHz, CDCl,): 2.18 (3 H, s), 7.1 5-7.43 ( 10 H, m) and 7.95-8.70 (1 H, br s); m/=234 (M') (base), 219, 202, 190, 165, 117, 109, 103, 89 and 77.Tetrazole 7e. A solution of the tetrazole E-7e (44.3 mg, 0.194 mmol) in methanol (40 ml) was irradiated for 1.5h. The solvent was evaporated off and the residue was chromatographed to give 3-phenyl-4-t-butylpyrazole 1le (38.7 mg, 9904, m.p. 162- 164 "C (Found: C, 77.8; H, 8.1; N, 14.0. C13H16N~ requires C, 78.0; H, 8.05; N, 14.0"/,); v,,,/cm-': 3180-3100, 3040, 1500, 1360, 1120,965,770and 710; 6(250 MHz, CDCl,): 1.17 (9 H, s), 7.27 (1 H, s), 7.38 (5 H, s) and 9.2-10.0 (1 H, br s); mi= 200 (M+),185, 104,93,85,82,77 and 55.J. CHEM. SOC PERKIN TRANS. 1 1991 Acknowledgements We thank Mr. J. N. Bilton (mass spectrometry), Dr. M. Casey and Mr. R. N. Sheppard (NMR) for expert assistance and valuable discussions. References 1 M. Casey, C. J. Moody and C. W. Rees, J. Chem. Soc., Perkin Trans. I, 1984, 1933. 2 M. Casey, C. J. Moody, C. W. Rees and R. G. Young, J. Chem. Soc., Perkin Trans. 1, 1985, 741. 3 M. Casey, C. J. Moody and C. W. Rees, J. Chem. Soc., Perkin Trans. 1, 1987, 1389. 4 C. Wentrup, Adu. Her. Chem., 1981, 28, 231; R. N. Butler in Comprehensive Heterocyclic Chemistry, eds. A. R. Katritzk y and C. W. Rees. Pergamon, Oxford, 1984, vol. 5, p. 791. 5 For a recent example of the intramolecular cycloaddition see L. Bruche and G. Zecchi, Tetrahedron, 1989,45, 7427. 6 C. Wentrup, A. Damerius and W. Reichen, J. Org. Chem., 1978,43, 2037. 7 J. Elguero, in Comprehensive Heterocyclic Chemistry, eds. A. R. Katritzky and C.W. Rees, Pergamon, Oxford, 1984, vol. 5, p. 167. 8 E. Bayer and K. Geckeler, Angen. Chem., Int. Ed. Engl., 1979,18,533. 9 C. J. Moody, C. W. Rees and R. G. Young, J. Chem. Soc., Perkin Trans. 1, 1991, preceding paper. 10 L. Knorr, Ber., 1895,28,688 and 696. 11 M. W. Moon and G. Kornis, Can. Patent CA 1053231,24 April 1979 (Chem. Abstr., 91: 140839). Pqer 0/03413D Received 26th July 1990 Accepted 14th August 1990