Reactions with arenesulphonyl azides of some indoles with oxygen- and nitrogen-containing substituents

摘要

1975 1471 Reactions with Arenesulphonyl Azides of Some Indoles with Oxygen- and Nitrogen-containing Su bstituents By A. Sydney Bailey,rsquo; Christopher M. Birch, David Illingworth, and Janet C. Willmott, Dyson Perrins Laboratory, South Parks Road, Oxford OX1 3QY Treatment of 2,3,4,5-tetrahydro-5-methyl-2-tosyl-lH-pyrido4,3-bindolewith p-nitrobenzenesulphonyl azide affords 1-methyl-2-p-nitrophenylsulphonylimino-l lsquo;-tosylindoline-3-spiro-3rsquo;-pyrrolidine in moderate yield : 1.3.4.5-tetrahydro-5-methylpyrano3,4-bindolereacts with p-chlorobenzenesulphonyl azide to form 3-p-chlorophenyl- sulphonylimino-1 -methylindoline-2-spiro-3lsquo;-tetrahydrofuran. The reaction of methyl 1.3-dimethylindole-2-carboxylate with p-nitrobenzenesulphonyl azide involves migration of the methoxycarbonyl group.From the reaction of methyl 1.3-dimethylindol-2-ylacetate with azides derivatives containing the 2-methylene- indoline nucleus have been isolated. WE have reported that the y-carboline (1; X = NMe) pound (1 ; X = NTs) with azides, since formation of an reacts smoothly with tosyl azide to form the ring- intermediate such as (2; X = NTs) appeared unlikely. enlarged compound (3), and we suggested that the form- ation of (3) occurs via the intermediate (2; X = NMe, r Me L Me Ts Me 13) I41 TsCbsNH QITPNNbsNCbs Me Me (51 (61 QJ;-pJTs NHNbsMe (71 2 = Ts). In contrast the sulphur analogue (1; X = S) formed mainly tars when treated with arenesulphonyl azides; the only crystalline materials isolated, in small quantities, were the orange-coloured spiran (4; X = S) and the 1 : 2 adduct (5).This work has now been extended by an examination of the reactions of com-A. S. Bailey, A. G. Holton, and J. F. Seager, J.C.S. Perkin I, 1972, 1003. A. S. Bailey, P. A. Hill, and J. F. Seager, J.C.S. Perkin I, 1974, 967. A. S. Bailey, R. Scattergood, and W. A. Warr, J. Chem. SOC. (C),1971, 2479. The y-carboline (1; X = NTs) was far less reactive than (1; X = NMe) and it did not react with 9-chloro- benzenesulphonyl (Cbs) azide. However, boiling the compound in ethanol with $-nit robenzenesulphon yl (Nbs) azide afforded a small quantity of crystalline material to which we assign structure (6); the 1i.m.r. and U.V. spectral data eliminated structures of types (3), (4), (7)J and (s)*3 rsquo; This series has now been completed by an examination of the oxygen analogue (1; X = 0).Although com-plex pyrano4,3-bindoles are known,4 there appears to be no reference in the literature to the parent compound. Tetrahydropyran-4-one formed a crystalline phenyl- hydrazone but all (fifteen) attempts to cyclise it to the corresponding indole with acid or thermally gave black amorphous material. However, the N-methylated com- pound (1; X = 0)was obtained, in poor yield, by treat- ment of tetrahydropyran-4-one with N-methyl-N-phenylhydrazine followed by acid-catalysed cyclisation H2deg;H Me (9) s Me (101 under very mild conditions. This indole is unstable and so it was treated with Cbs azide in chloroform at room temperature, to give the yellow fluorescent spiran H.Behringer and H. Weissauer, Chem. Ber., 1952, 85, 743. R. Artenzen, Y. T. Yan Kui, and C. B. Reese, Synthesis, 1975, 8, 509. R. J. Sundberg, lsquo;The Chemistry of Indoles,rsquo; Academic Press, New York, 1970, pp. 142-164. 1472 J.C.S. Perkin I (4; X = 0)in 89 yield. This is by far the largest mixed with dilute sulphuric acid and a stream of nitrogen yield of this type of spiran obtained with any indole. bubbled through the mixture; the mixture was then All attempts to rearrange the spiran either thermally slowly distilled and the vapours were passed through 1 NHCbs NHCbs Me Me Me - (19) 1 (171 Me (18) C0,Me m N N b s Me Me CH3 (21) (22 1 or with trifluoroacetic acid gave dark-coloured decom- position products. These results indicate that structures of type (2) are not formed when X = 0, S, or NTs, and that the most favoured reactions involve ring contraction to spirans.As reported above we were unable to obtain the simple indole (1; X = 0, NH replacing NMe) and the N-methyl derivative (1 ; X = O) is far less stable to acid than the X = S or NMe analogues. When compound (1 ; X = 0)is warmed to 80 ldquo;C with M-sulphuric acid a purple polymeric solid rapidly separates. Protonation of (1 ; X = NMe) would occur on the aliphatic nitrogen atom, but an indole such as (1; X = 0) might be expected to undergo protonation at the p-position of the indole nucleus to form the ion (9), which would then decompose to form N-methylisotryptophol (10) and formaldehyde.* A sample of the indole (1 ; X = 0)was Ref.6, pp. 3-6.* Ref. 6, pp. 39-56; E. Leete, J. Amer. Chem. SOC.,1959, 81, 023. aqueous 2,4-dinitrophenylhydrazinehydrochloride. No formaldehyde was detected, and the mechanism of the breakdown of (1; X = 0)with acid remains obscure. Barnes had observed that the oxime (11; R = Me) reacted with Cbs azide to form the isoxazolo-derivative (13) by attack of the OH group of the oxime in the intermediate (12) on C(3) of the indole nucleus. In order to examine the generality of this cyclisation the oxime (11; R = CH,Ph) has been prepared. This oxime reacted smoothly with Cbs azide; however the product was not the isoxazole (13; R = CH,Ph) but the fluores- cent imine (14) ; this is the first time this type of struc-ture has been obtained which does not contain a spiran ring of type (4).It appears that in the intermediate (12) the large benzyl group (R = CH,Ph) prevents attack at C(3) of the indole nucleus, hence the intermediate (15) is formed and in (15) there is no hydrogen atom in the group attached to C(2) which may be lost to form a A. S. Bailey, C,. J. Barnes, and I?. A. Wilkinson, J.C.S. Perkin I, 1974, 1321. methyleneindoline ~tructure.~In order to determine whether formation of the imine (14) was a particular feature of the benzyl group at C(3) in (ll),compound (16) was prepared; on treatment with Cbs azide it formed the 2 : 1 adduct (17) via the intermediate (18), behaviour similar to that of 1,2,3-trimeth~dindole.~ We have reported that 2-acylindoles do not react with Me HNTs Me (23) (2d) (27) (28) Me Me (25) (26) f azides; the methyl ester (20) has now been prepared in order to study its reactions.1,3-Dimethylindole did not react with trichloroacetyl chloride under conditions which are successful with pyrroles lo but the indole reacted smoothly with trifluoroacetic anhydride to form the ketone (19). hlethanolysis of (19) gave (20) but the yields were erratic and it was more convenient to hydro- lyse (19) to the corresponding acid and to esterify the latter a photochemical synthesis of compounds of type (20) has subsequently been reported ll.This ester slowly reacted with $-nitrobenzenesulphonyl azide to form a compound to which we ascribe structure (21),by a process involving migration of the methoxycarbonyl group; the alternative structure (22) was rejected since it contains the same chromophore as compounds (4) and (14) and would be expected to have a characteristic U.V.spectrum and to fluoresce in ~olution.~ In order to explain the formation of many of the pro- ducts obtained by the reactions of various indoles with azides 293J2 the formation of methyleneindoline inter-mediates cf. (IS) has been suggested. Although the reaction of the Fischer base (23) with azides has been lo J. W. Harbuck and H. Rapoport, .J. Org. Chem., 1972, 37, 3618.. A. G. Schultz and W. K. Hagmann, J.C.S. Chem. Comm., 1976, 726. l2 A. S. Bailey and P. A. Wilkinson, J.C.S. Pevkin I, 1976, 481; G. A. Bahadur, A. S. Bailey, and P. A. Baldry, ibid., 1977, 1619. l3 A. S. Bailey, A. J. Buckley, and J. I;.Seager, J.C.S. Perkin I, 1973, 1809. l4 A. McKillop and E. C. Taylor, Endeavour, 1976, 35, 88; E. C. Taylor, R. L. Robey, K.-T. Liu, B. Favre, H. T. Bozimo,K. A. Conley, C.3. Chiang, A. McKillop, and M. E. Ford, J. Amer. Chem. SOC.,1976, 98, 3037. examined, and compound (24) has been prepared and its reactions with azides have been studied,13 no methylene-indoline has been isolated directly from the reaction of an indole with an azide. We, therefore, prepared methyl 1,3-dimethylindo1-2-ylacetate (26) to study its reactions with azides.The first attempt involved treatment of the ketone (25) with thallium nitrate,l* a reaction used successfully on acetylpyrr01es.l~ Under a variety of conditions black amorphous materials were obtained and none of the desired product. However the Will- gerodt reaction afforded the thiomorpholide (27; R = Me) in satisfactory yield, but methanolysis with meth- anol-HC1 failed to produce the ester (26) although the reaction was successful with the related compound (27; R = H).16 Compound (27; R == Me) was methylated l7 and the methiodide boiled with methanol. This, how- ever, afforded the amide (28) and not the desired ester. The thiomorpholide was, therefore, hydrolysed and the free acid immediately esterified with diazomethane affording (26).The ester (26) was boiled in chloroform solution with Cbs azide affording a 1: 1 adduct to which we ascribe structure (29 ; 2 = Cbs); the n.m.r spectrum contains a singlet at T 5.29 (=CH*CO,Me) arid the U.V. spectrum is very similar to that of the alkaloid pseudo- vincadifformine.18 A similar compound (29; 2 = Nbs) was obtained using $-nitrobenzenesulphonyl azide in chloroform. Huisgen l9 has shown that ap-unsaturated esters react more slowly with azides than do simple olefins; hence (29), formed via (31), is sufficiently unreactive to allow isolation. When compound (26) was heated with Nbs azide in propan-1-01 the 2 : 1 adduct NHZ NHNbs (29) (30) 1 t r NHZ 1 L (31 1 (30) was isolated, the side-chain being lost from (29) (cf.the reactions of enamino-ketones with azides 20). l5 G. W. Kenner, J. Rimmer, K. M. Smith, and J. brsquo;. Unsworth, J.C.S. Perkin I, 1977, 332. l6 C. F. Jones, D. A. Taylor, and D. P. Bowyer, Tetrahedvon, 1974, 30, 957. R. Gompper and W. Elser, Annalen, 1969, 725, 64. J. P. Kutney, R. T. Brown, E. Piers, and J. R. Hadfield, J. Amer. Chem. SOC.,1970, 92, 1708. R. Huisgen, G. Szeimies, and L. Mobius, Chem. Ber., 1966, 99, 475; 1967, 100, 2494. 20 R. Fusco, G. Bianchetti, D. Pocar, and R. Ugo, Chem. Ber., 1963, 96, 802; P. D. Croce and R. Stradi, Tetrahedron, 1977, 33, 865. 1474 Compound (30)was identical with the product obtained from 1,3-dimethylindole with Nbs azide in the presence of pyridine.al The isolation of compounds of stmcture (29) provides valuable evidence for the mechanism we have suggested for the reactions of indoles with azides.EXPERIMENTAL General details and instruments used have been re-ported.,, U.V. spectra were determined for solutions in ethanol and n.m.r. spectra for solutions in CDCl,; i.r. spectra were recorded for Nujol mulls. l-Methyl-2-p-nitro~henylsul~honylimino-1 '-tosylindoline- 3-s~irocycZo-3'-~yrrolidine (6) .-N-Tosylpiperidone (m,p. 129-131"; lit.,,, 128-131') (2.8 g) and phenylhydrazine (1.2 g) were mixed in ethanol (15 ml) and warmed for 2 min. Sulphuric acid (w; 15 ml) was added and the solution boiled (30 min; prolonged boiling yields tar). Next day 2,3,4,5-tetra?~~~dro-~-tosyl-1H-~yrido~4,3-b~indolecol-was lected (80) and recrystallised (MeOH) ; m.p.196.5-198.5' (Found: C, 66.3; H, 5.5; N, 8.6; S, 10.0. Cla-H,,N,O,S requires C, 66.3; H, 5.5; N, 8.6; S, 9.804,); A,, 225, 273, and 289 nni (E 44 300, 6 730, and 5 330); vWx, 3400 cm-l; T 2.10 (1 H, NH), 2.25 (2 H, d, J 8 Hz), 2.5-3.0 (6 H, m), 5.62 2 H, s, C(l)H2, 6.59 2 H, t, J 6 Hz, C(3)H2, 7.16 2 H, t, J 6 Hz, C(4)H2, and 7.59 (3 H, s, ArMe). This indole did not react with p-chlorobenzene- sulphonyl azide (90 h , boiling EtOH) . N-Tosylpiperidone (2.84 g) and N-methyl-N-pkenylhydrazine(1.38 g) were dis-solved in EtOH (15 ml); the solution was boiled (1 min) and 15 min later sulphuric acid (M; 17 ml) was added. The solution was boiled for 20 min; next day the solid was collected and recrystallised (EtOH) .2,3,4,5-Tetrahydro-5-methyZ-2-tosyZ-lH-~y~id04,3-bindoZe(1; X = NTs) formed needles, m.p. 172.5-174.5" (56) (Found: C, 66.9; H, 5.9; N, 8.2. C,,H,,N,O,S requires C, 67.1; H, 5.9; N, 8.2); Lx,228, 273sh, 283, and 292 nm (E 60 400, 8 200, 8 700, and 7 600); T2.2-3.0 (8 H, m), 5.62 2 H, s, C( 1)H2, 6.38-6.55 5 H, m, C(3)H,, NMe, 7.20 2 H, t, J 8 Hz, C(4)H2, and 7.61 (3 H, ArMe). This indole was recovered after boiling for 16 h with TsN, in MeOH. The indole (62 mg) was boiled (70 h) with p-nitrobenzenesulphonyl azide (42 mg) in EtOH (3 ml). On cooling the sfiiro-comfiound (6) separated (34) ; it formed small prisms from EtOH containing solvent of crystallisation, m.p. 165-168" J.C.S.Perkin I darkened and no analysis was attempted; vmx. 3 370 crn-l; T 2.7-3.3 (6 H, m, Ar and NH), 6.10-6.35 (2 H, m), and 7.4-7.7 (2 H, m). All attempts to cyclise this hydrazone failed. N-Methyl-N-phenylhydrazine(4.05 g) and tetra- hydropyran-4one (3.3 g) were mixed and acetic acid (1drop) was added. The mixture was heated (90'C) for 20 min and MeOH (3 ml) was added. Next day sulphuric acid (M; 15 ml) was added and the mixture shaken; after 30 min the solid was collected, washed with water, and recrystallised from ethanol (yield 17). The indole (1; X = 0)formed plates, m.p. 83.5-85" (Found: C, 77.0; H, 7.0; N, 7.6. C12HJJO requires C, 76.8; H, 7.1; N, 7.5); hmaK 227, 283, and 290sh nm (E 43 600, 9 000, and 8 200); 't 2.55-3.0 (4 H, m), 5.09 C2 H, S, C(l)H,, 5.92 r2 H, t, J 7 Hz, C(3)H2, 6.37 (3 H, s, NMe), and 7.19 2 H, t, br, J 7 Hz, C(4)H2; m/e 187 (ME,1000/;), 186 (42), 159 (13; m* 135), 157 (77), 143 (lo),and 142 (12; m* 107).3-p- CI~lorophenylsuEphonylimino-1-methyZindoline-2-spiro-3'-tetra/iydrofuran (4; X = O).-The indole (1; X = 0) (2.6 g) and Cbs azide (3.0 g) were dissolved in chloroform (20 mlj and kept at room temperature for 190 h. The chloroform was removed and the residue recrystallised from MeOH. The spiro-com~ound formed orange-yellow needles (4.66 g), m.p. 196-197" (Found: C, 57.4; H, 4.6; Cl, 9.3; N, 7.3; S, 8.7. ClaH,,C1N20,S requires C, 57.4; H, 4.5; C1, 9.4; N, 7.4; S, 8.5); LL208, 228, 281, and 468 nm (E 32 000, 23 600, 5 050, and 3 500); vmX.1620 cm-l; T 1.52 111 H, d, J 8 Hz, C(4)H, 2.02 (2 H, d, J 9 Hz), 2.65 (3H, m), 3.1-3.4 (2 H, m), 5.68-6.35 4 33,m, C(2')H2 and C(5')H2, 6.9 (3 H, s, NMe), and 7.62-7.83 2 H, m, C(4')-H,; m/e 376 (M+, lo), 201 (ILI -Cbs, loo), 173 (201 --C,H,, 33; m* 149), 171 (201 -CH,O, 53y0),and 111 (17). All attempts to rearrange this compound either thermally or by treatment with CF,CO,H failed. 2-A cetyZ-2-benzyl-3-p-chZorophenyZsulp/~onylimino- l-methyl- indoline Oxime (14) .-3-Benzylindole t4 was methylated (Me,SO-NaH-MeI) forming 3-benzyl- 1 -methylindole .l~26 3-Benzyl-l-methylindole (5.3 g) was dissolved in Ac20 (5 ml) and HOAc (25 ml). To the ice-cold mixture was added (drop-wise with stirring) BF,-Et,O (5.5 ml) followed by dry Et,O (50 ml), After 15 h at room temp.Et,O (50 ml) was added, followed by Na,CO, (50 ml; 2~). The ethereal layer was washed and dried (MgSO,) , the solvent removed, and the product recrystallised from petroleum (b.p. 60- 80 "C) . 2-Acetyl-3-benzyE- l-methylindole formed tiny prisms, (Found: C, 55.1; H, 5.0; N, 9.2; S, 10.5. C2H,0 requires C, 55.3; H, 5.0; N, 9.6; S, 10.9); A,,,, 224 and 270 nm (E 54 500 and 18 500); vmax. 1 530(C=N) and 3 400 cm-1 (OH) (after crystallisation from PhH the band at 3 400 was absent); T 1.82 (2 H, d, J 9 Hz), 2.05-2.45 (4 H, m), 2.66-2.95 (4 H, m), 3.0-3.4 (2 H, m), 3.28 (1H, s, OH, exchanged with D,O), 5.25 2 H, s, C(2')H2, 6.30 (3 H, s, NMe), 6.40-6.66 4 H, m, C(5')H2, and HOCH,- CH,, 6.85-6.71 2 H, m, C(4')H2, 7.62 (3 H, s, ArMe), and 9.87 (3 H, t, J 8 Hz, HOCH,CH,); m/e 540 (Mf, 0.30:/,), 198 (88), 182 (85), 181 (as), 171 (33), 123 (57), and 91 (100).1,3,4,5-Tetrahydro-5-methylpyrano4,3-bindole(1; X = 0).-Phenylhydrazine (5.4 g) was mixed with tetrahydro- pyran-Cone 5 (5.04 g) and MeOH (3 ml) was added. Next day the solid was collected and recrystallised from MeOH (yield 6.33 g); m.p. 60-63". The compound slowly 21 A. S. Bailey, A, J. Buckley, and W. A. Warr, J.C.S. Perkin I, 1972, 1626. 22 A. S. Bailey, T. Morris, and 2.Rashid, J.C.S.Perkira I, 1975,420. C25H24N408Sa*m.p. 64-65.5' (57) (Found: C, 82.1; H, 6.5; N, 5.3. ClaH1,NO requires C, 81.7; H, 6.5; N, 5.5); Lx209, 240, and 309 nm (E 25 000, 15 500, and 16 100); vmx. 1 610 and 1660 cm-1; T 2.35-2.95 (9 H, m, Ar), 5.52 (2 H, s), 6.02 (3 H, s, NMe), and 7.48 (3 H, s, CMe); m/e 263 (M+,loo), 248 (45), 220 (58), 186 (18), and 172 (32).The oxime (11; R = CH2Ph) (prepared ir. pyridine) formed needles, m.p. 113--116O (from MeOH) (Found: C, 77.6; H, 6.6; N, 10.0. Cl,HlaN,O requires C, 77.7; H, 6.5; N, 10.1); m/e 278 (M+, 320/,), and 261 (100). This oxime (0.49 g) and Cbs azide (0.42 g) were dissolved in ethyl propionate (5 ml) and the mixture heated (100 'C, 48 h). The solvent was removed, the residue chromatographed (silica; PhH-EtOAc, 9 : l), and the product recrystallised from propan-1-01 (yield 0.71 g). The oxime (0.67 g) was 23 W.N. Speckamp, J. Dijkink, A. W. J. D. Dekkers, andH. 0. Huisman, Tetrahedron, 1971,27, 3151. 24 E.F.Pratt and L. W. Botimer, J. Amer. Chem. Soc., 1957,79, 6248. 2s S. Pietra and G. Tacconi, Gazzetta, 1959, 89, 2304. heated (100 "C; 48 h) in PrrlOH (5 ml) with CbsN, (0.69 g). On cooling the product separated (0.67 g). The imine (14) formed orange-coloured prisms, m.p. 215-217" (Found: C, 61.8; H, 5.2; N, 8.8. C,,H,,C1N,02S requires C, 61.7; H, 4.8; N, 9.0); A,,, 230, 290, and 473 nm (amp; 32 000, 10 700, and 11 000); vmx. 1 615 (C=N) and 2 950 cm-l (OH) ; 7 1.74 l H, d, J 8 Hz, C(4)H, 2.0 (2 H, d, J 8 Hz), 2.5-3.6 (10 H, m), 2.26 (1 H, s, OH, exchanged with D,O), 6.56 (2 H, s, CH,Ph), 6.97 (3 H, s, NMe), and 8.42 (3 H, s, CMe); in (CD,),SO solution the CH,Ph signal formed a pair of doublets T 6.45 and 6.72 (J 15 Hz); m/e 467 (M+,60/,), 376 (68), 292 (18), 235 (65), 201 (loo), and 91 (36).3-Benzyl-3-p-chloro~henyZsulphonylamino-2-p-chloro-phenylsulphonylimino- l-methylindoline (17).-3-Benzyl-2-methylindole 26 was methylated to form 3-benzyl-1,2-dimethylindole.26 This indole (1.1 g) was heated (50 "C; 36 h) with Cbs azide (1.1 g). The resulting solid was chromatographed affording the indoline (17), recrystallis-ation from propan-1-01 gave prisms, m.p. 200-202" (0.5 g) (Found: C, 55.8; H, 4.0; C1, 12.0; N, 6.8; S, 10.6. C,,H,,Cl,N,O,S, requires C, 55.7; H, 3.9; C1, 11.7; N, 7.0; S, 10.7); A,,,,. 226, 289, and 305 nni (E 34 900, 12 400, and 9 100); v,,,. 1585, 1 630, and 3 280 cm-l; T 1.95 (2 H, d, J 8 Hz), 2.32 (1 H, s, NH, exchanged with D,O), 2.50 (2 H, d, J 8 Hz), 2.9-3.6 (13 H, m, Ar), 6.10 (1 H, d, J 13 Hz), 6.65 (1 H, d, J 13 Hz), and 7.12 (3 H, s, NMe); m/e 599 (amp;I+,4), 508 (loo), 268 (48), 175 (29), and 111 (48)-Methyl 1,3-DimethyZindoZe-2-carboxylate(20).-Trifluoro-acetic anhydride (4 ml) in ether (8 ml) was added dropwise to a stirred ice-cold solution of 1,3-dimethylindole (2 g) in ether (5 ml).After 24 h (room temp.) the solution was poured into water; the ethereal layer was washed (aqueous sodium carbonate), dried, and evaporated. The residue was triturated with light petroleum and the resulting solid recrystallised from MeOH. 1,3-Dimethy1-2-tri$uoroacetyZ-indole (19) formed yellow plates, m.p.69-70" (2.2 g) (Found: C, 59.9; H, 4.2; N, 5.8. C,,H,,F,NO requires C, 59.8; H, 4.2; N, 5.8); A,,,,, 208, 245, and 330 nm (E 23 000, 12 400, and 24 000); vmAx. (CCl,) 1 620 and 1 678 cm-l; 7 2.3-3.0 (4 H, m, Ar), 6.08 (3 H, s, NMe), and 7.38 (3 H, s, CMe); m/e 241 (A!!+,83) and 172 (100). This ketone (1 g) was dissolved in MeOH (11 ml) containing sodium methoxide from sodium (0.2 g) and the solution boiled for 48 h. Water was then added and the solid which separated was collected and recrystallised (MeOH) . The ester (0.66 g) formed rods, m.p. 78-77' (Found: C, 70.9; H, 6.3; N, 7.0. C1,H,,N02 requires C, 70.9; H, 6.4; N, 6.9); v,,, 1 615 and 1 705 cm-l; T 2.3-3.0 (4 H, m), 6.0 (3H, s, OMe), 6.05 (3H, s, NMe), and 7.4 (3 H, s, CMe); m/e 230 (Mt, loo), 188 (70), and 144 (39).The yields by this method were variable. The ketone (1 g) was boiled for 1 h with NaOH (1 g) in EtOH-H,O (10 ml; 1 : 1). The solution was diluted with water and extracted with ether, and the aqueous phase was acidified. The solid which separated was extracted into ether; the solvent was removed and the residue recrystallised (EtOH) yielding needles (0.73 g), m.p. 216-218" (lit.,27213"); m/e 189 (M+, loo), 156 (58), and 144 (45). This acid was then esterified (CH,N,) affording (20). Methyl 1,3-Dimethyl-2-p-nz'trofiheny ZsuZfihony Ziminoindo-line-3-carboxylate (21) .-The indole (20) (0.2 g) and NbsN, 26 D. W. Ockenden and K. Schofield, J.Chem. SOC.,1953,3440;T. C.Bruice and R.W. Huffman, J. Amer. Chem. SOC.,1967, 89, 6243. (0.24 g) were heated in pyridine (80 "C; 4 weeks). Ben-zene was then added and the solution washed with dilute hydrochloric acid. The solvent was removed and the solid was recrystallised (MeOH) giving needles (0.1 g), m.p. 182-185" (Found: S, 7.9. Cl8Hl7N3O,S requires S, 7.9) ; vnlax (CHCl,) 1570, 1610, 1 625, 1 705, and 1 745 cm-l; T 1.75 (2 H, d, J 8 Hz), 1.85 (2 H, d, J 8 Hz), 2.5-3.0 (4 H, m), 6.30 (3 H, s, OMe), 6.60 (3H, s, NMe), and 8.0 (3 H, s, CMe); m/e 403 (M+,43), 217 (35), 158 (loo), and 145 (54).MethyZ 1,3-Dimethylindol-2-yZacetate(26).--2-Acetyl-l ,3-dimethylindole @ (6 g),sulphur (2 g),and morpholine ( 10 ml) were heated under reflux (oil-bath; 160 "C; 18 h).The excess of morpholine was removed in vacuo, the residue triturated with EtOAc, and the product recrystallised from propan-l-ol. The thiomorpholide (27) formed pale yellow needles, m.p. 224-227' (6 g) (Found: C, 66.8; H, 6.9; N, 9.6; S, 10.8. C,,H,,N,OS requires C, 66.8; H, 6.9; N, 9.7; S, 11.1) ; v,,,~, 1 560, 1 610, and 1 650 cm-l; T 2.4-3.1 (4 H, m, Ar), 5.6-5.8 (4 H, m, OCH,), 5.72 (2 H, s, -CH,*C=S), 6.4-6.8 (4 H, m, NCH,), 6.31 (3 H, s, NMe), and 7.76 (3 H, s, CMe); m/e 288 (M+, 37), 158 (loo), and 144 (30). The thioamide (1 g) was boiled (4 h) in CH,Cl, (20 ml) with Me1 (4 ml). The solvent was re-moved and the methiodide recrystallised (MeCN) forming yellow needles (1.3 g), m.p. 227-228" (Found: C, 47.5; H, 5.4; I, 29.4; N, 6.6.C,,HzBIN2OS requires C, 47.4; H, 5.4; I, 29.5; N, 6.5). The methiodide (1 g) was boiled (3 h) in MeOH (30 ml). The solution was concen- trated yielding 1,3-dimethyZindol-2-yZacetomor~holide(28) (0.48 g), needles (MeOH), m.p. 235-238" (Found: C, 70.4; H, 7.4; N, 10.2. C,,H,,N,O, requires C, 70.6; H, 7.4; N, 10.3); v,,~~.1650 cm-1; T 2.P-3.0 (4 H, in, Ar), 6.20 (2 H, s, CH,-CO), 6.32 (3 H, s, NMe), 6.3-6.6 (8 H, m), and 7.70 (3 H, s, CMe); m/e 272 (M+, 33) and 158 (looyo).The thiomorpholide (27) (10.8 g) was boiled under reflux with KOH (43 g) in water (60 ml) and EtOH (380 ml). After 3 h the solid had dissolved and the bulk of the EtOH was removed in vacuo. The aqueous solution was cooled in ice and acidified with ice-cold aqueous HCl.The solid which separated was collected and immediately esterified (CH,N,). The ester (26) formed needles, m.p. 66-68" from petroleum (b.p. 60-80 "C) (yield 5.4 g) (Found: C, 71.8; H, 6.9; N, 6.6. C,,H15N0, requires C, 71.9; H, 6.9; N, 6.5); vmax. 1730 cm-1; z 2.4-3.1 (4 H, m), 6.23 (2 H, s), 6.33 (6 H, s, OMeand NMe), and 7.71 (3 H, s, CMe); m/e 217 (M+, 85), 158 (loo), and 143 (13). Since the OMe and NMe signals coincided, a sample of the ester was reduced with LiAlH, in ether yielding 2-(1,3-dimethylindol-2-yZ)ethanol,cubes, m.p. 92-93" (from PhH) (82) (Found: C, 76.0; H, 8.0; N, 7.4. CI2Hl5NO requires C,-76.3; H, 7.9; N, 7.4); v,,, 3 350br cm-l; 7 2.4-3.0 (4 H, m), 6.25 (2 H, t, J 8 Hz, OCH,), 6.33 (3H, s, NMe), 7.00 (2 H, t, J 8 Hz, CH,), 7.73 (3 H, s, CMe), and 8.4 (1 H, s, OH); m/e 189 (M+, 34), 158 (loo), and 144 (4).Reactions of MethyZ 1,3-DimethyZindol-2-yZacetatewith Azides.-The ester (26) (0.4 g) was boiled (2 days) in chloro- form (5 ml) with Cbs azide (0.4 g) ; the solvent was removed and MeOH added. The solid which separated was collected and recrystallised from propan- l-ol. Methyl 3-p-chloro-fihenylsulphonyZamino-1,3-dimethylindoZin-2-ylidene acetate 27 W. 0. Kermack, W. H. Perkin, and R. Robinson, J. Chem. SOC.,1921, 1636; H. R. Snyder and E. L. Eliel, J. Amev. Chem. SOC.,1948, 70, 1857. (29; Z = Cbs) formed pale yellow prisms (0.23 g), m.p. 165-168" (Found: C, 55.9; HI4.6; C1, 8.8; N, 7.0; S. 7.7, Ci,H1,ClN,O,S requires C, 56.1; H, 4.7; C1, 8.7; N, 6.9; S, 7.9); A,,,.233, 301, and 336 nm (E 18 000, I1 200, and 11 200); vrnax. 1580, 1660, and 3 160 cm-l; T 1.63 (1 H, s, NH, exchanged with D,O), 2.6-3.5 (8 H, m, Ar), 5.29 (1 H, s, =CH*CO), 6.29 (3 H, s, OMe), 7.07 (3 H, s, NMe), and 8.28 (3 H, s, CMe); m/e 406 (M+,63), 216 (85), 184 (loo), and 111 (13). The ester (0.5 g) was boiled (24 h) with p-nitrobenzenesulphonyl azide (1.O g) in chloroform solution. The usual work-up gave methyl 1,3-dimethyl-3-p-nZtro-$henylsulphonylaminoindoline-2-ylideneacetate z= Nbs), orange-coloured prisms, m.p. 198-iE;i (from PrnOH) (0.83 g) (Found: C, 54.4; H, 4.7; N, 10.0; S, 7.4. C1,H,,N30,S requires C, 54.7; H, 4.6; N, 10.1; S, 7.8); A,,,. 234, 298, and 336 nm (E 22 000, 16 100, and 14 800); v,,,.1 590, 1 670, and 3 lOObr cm-l; T 1.45 (1 H, NH, exchanged with D,O), 1.5-3.2 (8 H, m, Ar), 5.18 (1 H, s), 6.23 (3 H, s), 6.96 (3 H, s), and 8.23 (3 H, s); m/e 417 (M', 40), 216 (46), 186 (loo), 184 (75), and 122 (66). J.C.S. Perkin I The ester (26) (0.4 g) and Nbs azide (1.0 g) were dissolved in PrnOH (5 ml) and heated (100 "C; 3 days). On cooling a solid separated ; this crystallised from 2-methoxyethanol as minute prisms, m.p. 294--297" (0.57 g), identical (m.p., i.r., n.m.r.) with material obtained as follows. 1,3-Di-methylindole (2 g) and p-nitrobenzenesulphonyl azide (8 g) were dissolved in pyridine (10 ml). After 3 days the pyri- dine was removed and MeOH added. The product was recrystallised from 2-methoxyethanol (yield 4.7 g). 1.3-Dimethyl- 3-p-nitro$laenylsul~ honylamino-2-p-nitrophenyl-sulphonylzminoindoline (30) had m.p. 295-297" (Found : C, 48.5; H, 3.5; h-, 12.8; S, 11.9. C,zHl,N,S,08 requires C, 48.4; H, 3.5; N, 12.8; S, 11.7); A,,,,. 210, 270, and 295sh (c 23 100, 19 600, and 9 000); v,,,. 1 610, 1 630, and 3 300 cm-l; T(CD,),SO 0.63 (1 H NH, exchanged with D,O), 1.5-3.5 (12 H, m, Ar), 6.62 (3 H, s, NMe), and 8.22 (3 H, s, CMe); m/e 545 (M', 55), 359 (44), 173 (loo), 159 (40), 158 (42), and 132 (48). 7/ 1994 Received, 1 Ith November, 19771