Studies on heterocyclic chemistry. Part XVIII. Thermally induced isomerisation of 3-p-alkoxyphenyl-5-methoxyisoxazoles in aryl aldehydes and dehydration of 5-amino-3,4-diarylisoxazoles in hexamethylphosphoric triamide

摘要

1974 1867Studies on Heterocyclic Chemistry. Part XVIII.l Thermally Inducedlsomerisation of 3-p-Alkoxyphenyl-5-methoxyisoxazoles in Aryl Alde-hydes and Dehydration of 5-Amino-3,4-diarylisoxazoles in Hexamethyl-phosphoric TriamideBy Tarozaemon Nishiwaki," Kenji Azechi, and Fusako Fujiyama, Department of Chemistry, YamagochiUniversity, Yamaguchi City 753, Japan3-p-Alkoxyphenyl-5-methoxyisoxazoles (1 ), when heated in an aryl aldehyde under reflux, yield 4'-alkoxybenz-anilides (5) through isomerisation of the initially produced methyl 3-p-alkoxyphenyl-2H-azirine-2-carboxylate ( 2 )to a ketenimine (3). In addition, isomerisation to 2-p-ethoxyphenyl-5-methoxyoxarole (4; Arl = p-EtOC6Hp)was observed for the isoxazole (1 ; Arl = p-EtOC6ti,). 5-Amino-3.4-diarylisoxazoles (7).when heated in hexa-methylphosphoric triamide under reflux. undergo dehydration via 2.3-diaryI-2H-azirine-2-carboxamides ( 8 ) .producing 2-arylindole-3-carbonitriles (1 1 ) as the major product.5-AEKOXY-3-ARYLISOXAZOLES undergo thermally-inducedvalence-bond isomerisation to alkyl 3-aryl-ZH-azirine-Z-carboxylates.2 Among the isoxazoles studied, 5-meth-oxy-3-fi-methoxyphenylisoxazole (1 ; Arl = p-MeOC,H,)often reacts so vigorously at ZOO" that methyl 3-9-meth-oxyphenyl-ZH-azirine-2-carboxylate (2 ; Arl = 9-MeOC,H,) cannot be isolated. In order to determinethe fate of this isoxazole and the corresponding azirineat high temperature, the thermal reactions of this andrelated isoxazoles (1 ; Arl = fi-EtOC,H, and o-MeOC,H,)in arylaldehydes were studied; if ring-opening of theazirine (2) to the corresponding ketenimine (3) occurs athigh temperature, the latter might form an adduct witha carbonyl compound by means of the thermal rW2, +n ZGcy~loaddition.~ The present study is also concernedwith the chemistry of the short-lived 2,3-diaryl-2-1 Part XVII, T.Nishiwaki and T. Takahashi, Synthesis, 1973,2 T. Nishiwaki, T. Kitamura, and A. Nakano, Tetrahedron,363.1970, 26, 453.cyan0-2H-azirines.~ These azirines, if produced at hightemperature, are expected to change to a more thermallystable valence bond isomer and some insight regardingtheir thermal behaviour could be gained.Heating 5-methoxy-3-~-methoxyphenylisoxazole ( 1 ;Arl = fi-MeOC,H,) in benzaldehyde under reflux yielded4'-methoxybenzanilide (5; Arl = p-MeoC,H,, Ar2 =Ph) .Similar reactions of this isoxazole with p-tolualde-hyde, fi-anisaldehyde, and o-chlorobenzaldehyde, eitherneat or in decalin solution, produced 4-methyl-4'-meth-oxy-, 4,4'-dimethoxy-, and Z-chloro-4'-rnethoxy-benz-anilides, respectively. The reaction mixtures were care-fully chromatographed, but no products other thanthese were identified.However, heating 3-~-ethoxyphenyl-5-methoxyisoxa-zole (1 ; Arl = $-EtOC,H,) in benzaldehyde-decalingave two products, 4'-ethoxybenzanilide (5; Arl =3 G. R. Krow, Angew. Chem. Internat. Edn., 1971, 10, 436.4 T. Nishiwaki and F. Fujiyama, J.C.S. Perkin I, 1973, 8171868 J.C.S. Perkin Ip-EtOC,H,, Ar2 = Ph) and 2-9-ethoxyphenyl-5-meth-oxyoxazole (4 ; Arl = p-EtOC,H,), the latter identified(m.p., i.r.J and t.1.c.) by comparison with an authenticspecimen prepared from 9-ethoxyhippuric acid.This isthe first instance in which an isoxazole derivative under-goes thermally induced isomerisation to an oxazolederivative, but this is not unexpected; the azirine havingan a-carbonyl function at C-2 undergoes ring expansionto an oxazole and the isoxazole (1; Arl = p-EtOC,H,)must have first isomerised to methyl 3-P-ethoxyphenyl-2H-azirine-2-carboxylate (2 ; Arl = p-EtOC,H,) underthe conditions employed.Further, this reaction could not be induced photoche mic-ally. Irradiation of the isoxazole (1 ; Arl = $-MeOC,H,)in benzaldehyde-ether (1 : 5) with 2537 A light did notproduce the benzanilide (5; Arl = $-MeOC,H,, Ar2 =Ph) , although 3,4,5-triphenylisoxazole is known to isomer-ise to benzoylphenylketen N-phenylimine under irradi-ation.,Heating the 5-amino-3,4-diphenylisoxazoles (7 ; Ar =Ph, R = H or Cl) in hexamethylphosphoric triamide(HMPT) under reflux afforded two products formed withconcomitant evolution of dimethylamine ; the firstwere the 2-phenylindole-3-carbonitriles (11 ; Ar = Ph,p Ar1N=C=CHC02Me Ar2CH0 ___)I Ar'CO-NHAr'The oxazole (4) is not an intermediate for the anilide( 5 ) ; the compound (4; Arl = $-EtOC,H,) was largelyunchanged after heating in the presence or absence ofbenzaldehyde. Formation of the anilide (5) from theisoxazole (1) requires migration of a P-alkoxyphenylgroup from carbon to nitrogen and strongly suggeststhe intermediacy of the ketenimine (3); formation of9-alkoxyaniline and oxidation of the aldehyde under thereaction conditions are unlikely.Thermal instabilityof the azirine (2; Arl = P-MeOC,H4)2 may be due to itsrapid isomerisation to the corresponding ketenimine (3 ;Arl = fi-MeOC,H,) and further reactions of the latter.However, the formation of the anilide (5) from theketenimine (3) cannot be accounted for on the basis ofthe ,2, + ,,2J cycloaddition of the ketenimine (3) andthe arylaldehyde to give a 2-imino-oxetan and thenfurther reactions of this. One of the likely intermediatesis the 1,3-oxazetidine derivative (6). Its ring-openingas shown could produce the benzanilide (5). However,formation of methyl propiolate was not confirmed;possibly it may have eluded detection.R = H or C1) which were identified by spectrometryand by reference to the reported physical data.Theindoles (11) must have arisen via dehydration of theinitially produced 2,3-diaryl-2H-azirine-2-carboxamide(8) to 2,3-diaryl-2-cyano-2H-azirine (9) and ring-openingof (9) to the corresponding vinylnitrene (10). It isknown that azirines bearing a 2-aryl group undergo ringexpansion to indoles when heated at high temperatureand HMPT dehydrates primary amides to nit rile^.^The other products obtained in a smaller quantity werealso nitriles C,,H1,R,N, (R = H or Cl) as inferred byi.r. spectrometry, but unfortunately they could not beidentified ; the molecular formulae indicate that theyare fragmentation products of the azirine (9).CO*NH, CN/CNAr-C=C, - CO.NH2I C~HLR-p R ' ArH R ' a T A r H :N:(12) (10) (11)The indole (11) and the nitrile C,,H,,R,N, were alsoproduced in comparable yields when the corresponding2,3-diaryl-2H-azirine-2-carboxamides ( 8 ; Ar = Ph, R =Ar 2co' NHAr' 4- HC=C'C02Me( 5 )The thermal isomerisation of the isoxazole derivativesto ketenimine (3) appears feasible only when the 3-arylgroup bears a 9-alkoxy-substituent ; the isoxazoles (1 ;Arl = O-MeOC,H, or Ph), when heated in benzaldehyde-decalin, did not yield the corresponding benzanilides.5 G.L'abbd and A. Hassner, Angew. Chem. Internat. Edn.,1971, 10, 98.6 D. W. Kurtz and H. Schechter, Chem. Comm., 1966, 689.7 J. D. Loudon and G.Tennant, J. Chem. SOC., 1960, 3466.H or C1) were heated in HMPT under reflux. To supportthe precedence of the dehydration of the azirine-2-carboxamide (8) over the ring-opening of the azirine (9)K. Isomura, S. Kobayashi, and H. Taniguchi, TetrahedronLetters, 1968, 3499; H. Hementsberger, D. Knittel, and H.Weidmann, Monatsh., 1970, 101, 161; T. L. Gilchrist, G. E.Gymer, and C. W. Rees, J.C.S. Perkin I , 1973, 655; J. H. Bowieand B. Nussey, ibid., p. 1693.R. S. Monson and D. N. Priest, Canad. J. Chem., 1971, 49,28971974to the corresponding vinylnitrene and cyclisation ofthis to the 2-arylindole-3-carboxamide (12), the azirine(8; Ar = Ph, R = H) and the isoxazole (7; Ar = Ph,R = Cl) were each heated in diphenyl ether under reflux.The only products isolated were the 2-arylindole-3-carboxamides (12; Ar = Ph, R = H or Cl).The amide(12), when heated in HMPT under reflux, gave the indole-3-carbonitriles (11) in moderate yield but not the nitrileC22H,,R,N, -EXPERIMENTALPetroleum refers to the fraction of b.p. 70-110" unlessotherwise stated. Commercial arylaldehydes were washedwith aqueous sodium hydrogen carbonate solution anddistilled under reduced pressure immediately before use.N.m.r. spectra were recorded at 60 MHz.Reaction of 3-p-A lkoxyphenyl-5-methoxyisoxazole with A ryl-aZdeJzydes.-The isoxazole (1 ; Arl = p-MeOC,H,) (0.99 g)was heated in benzaldehyde (20 ml) under reflux for 4 h innitrogen (method A). The reaction of the isoxazole withp-tolualdehyde was carried out similarly, whereas the re-action with p-anisaldehyde or o-chlorobenzaldehyde wasperforinecl by heating the isoxazole (1 ; Arl = p-MeOC,H,)Physical data and analyses ofCryst.Arl _4r2 M.p.("C) solvent *p-iVeOC,H, Ph 153-155 C9-MeOC,H, p-MeC,H, 161-163 * Cp-MeOC,H, p-MeOC,H, 200-201 b Ep-MeOC,H, o-ClC,H, 133-133-5' EP-EtOCeH, Ph 169-170 E8 yield), n1.p. 74-76' (Found: C, 65.8; H, 5.95; N,6.3. C,,H,,NO, requires C, 65.7; H, 6.0; N, 6.4y0), Amar(EtOH) 289 nm (log E 4.55). This compound was identifiedas 2-p-ethoxyphenyl-5-methoxyoxazole (4 ; Arl = p-EtOC,H,)by mixed m.p. (74-75"), i.r., and t.1.c. comparison with anauthentic specimen (see below-). Elution with ether-ethylacetate (3 : 1) gave 4'-ethoxybenzanilide (5; Arl = p-EtOC,H,, Ar2 = Ph) (see the Table).2-p-Ethoxyphenyl-5-methoxyoxazole (4 ; Arl = 9-EtOC,H,) .-Dry hydrogen chloride was passed into amixture of p-ethoxyhippuvic acid prepared by a standardprocedure,12 m.p.143-145" (from water) (Found: C, 59.3;H, 5.8. C1,Hl,NO, requires C, 59.2; H, 5.9); 10.0 gand dry methanol (200 ml) and the solvent was removedunder reduced pressure. Methyl p-etlzoxyhippurate (7.0 g,66) crystallised from ethyl acetate-petroleum as rods,1n.p. 82-84" (Found: C, 60.5; H, 6-1. Cl,H15N04 re-quires C, 60.75; H, 6.4). A mixture of this ester (7-0 g)and phosphorus pentaoxide (35.0 g) was heated on a boilingwater-bath for 4 h and worked up as described.13 Evapora-tion of the ethereal solution and alumina chromatographyof the residue with petroleum (b.p.30-70deg;)-ether (3 : 1)gave 2-p-etlzoxyphenyZ-5-methoxyoxazoZe (0-80 g, 13), whichcrystallised from petroleuiii as needles, m.p. 73-75".benzanilides (5) (Ar2CO-NHL4r1)Yield c-*-y * (I c H NFound () Required (x)Formula C H N2210 74.2 6.0 5.8 CI5Hl5NO2 74-7 6.3 5.86 70.3 5-9 5.4 C,,HlSN03 70.0 5.9 5.46 64.15 4-5 5.3 C14H12C1N02 64-25 4.6 6.354 74.4 6.2 C16H15N02 74.7 6.3* C = Carbon tetrachloride, E == ethyl acetate-petroleum.Lit.,lo 166". b M.p. not depressed on admisture with an authentic specimen.(1.00 g) and the aldehyde ( 4 - 5 ml) in decalin (5 nil) for 1.5h under nitrogen (method B). The excess of solvent andaldehyde was removed under reduced pressure and theresidue dissolved in ether.The ethereal solution ~7aswashed with 5 aqueous sodium hydrogen carbonatesolution, the solvent evaporated, and the residue chroniato-graphed on alumina with ether and then ether-ethyl acetate(10 : 1). The 4'-methoxybenzanilides (5; Arl = p-MeOC,H,) were isolated from the first eluates and theirphysical data and analyses are shown in the Table. Thelast eluate gave the starting material in the case of thereaction with o-chlorobenzaldehyde. The benzanilides ( 5 )had vInax. (NH) and v,. (GO) in the expected region of theiri.r. spectra.The isoxazde (1; Arl = o-MeOC,H,) was treated withbenzaldehycle by method B. The starting material (23recovery) and a small amount of a compound, m.p. 108-11 7", were isolated from the reaction mixture.Althoughthe product could not be purified, the presence of 2'-meth-oxybenzanilide (5; Arl = O-MeOC,H,, Ar2 = Ph) was ruledout by the m.p. (1it.,l1 66-69") and t.1.c.The isoxazole (1 ; -4r1 = P-EtOC,H,) (1.00 g) was treatedwith benzaldehyde by method B. The solvent and thealdehyde were removed under reduced pressure andalumina chromatography of the residue with ether gave asolid, which crystallised from petroleum as needles (0-07 g,lo R. Grammaticakis, Bull. SOC. chim. Frnnce, 1948, 979.l1 I. A. S. Smith, J . Amer. Chenz. SOC., 1954, 76, 431.l2 W. Jngersoll and S. H. Babcock, O Y ~ . S y ~ t h . , Coll. 1-01. 11,1943, p. 328.3-p-Ethoxy~henyl-5-inethoxyisoxazole ( 1 ; Arl = p-EtOC,H,) .-p-Ethoxybenzoylacetonitrile prepared by themethod described l4 m.p. 120" (from petroleum) (Found:C, 69.7; H, 6-0.CllHl1iSO2 requires C, 69.8; H, 5.9y0)was condensed with hydroxylamine hydrochloride asreported l5 to give 5-auniizo-3-p-et~~oxyphenylisoxazole, m.p.125-126" (from benzene) (Found: C, 64.8; H, 5.9.CllH,2N20, requires C, 64.7; H, 5-9), v,,,. (CHC1,) 3470and 3380 cm-1 (NH,), A,,,. (EtOH) 255 nni (log E 4.33).This was hydrolysed with 6x-sulphuric acid in niethanol togive 3-p-ethoxy~henylisoxnzol-5 (4H) -one, m.p. 133-1 34.5"(from benzene-petroleum) (Found: C, 64.6; H, 5-6; N,6-8. C11H11N03 requires C, 64.4; H, 5.4; N, 6-8), v,(CHCl,) 1800 cm-1 (GO), A,l,,, (EtOH) 279 nin (log E 4-33).Treatment of this compound with ethereal diazomethanegave 3-p-ethoxyphenyl-5-inethoxyisoxazole (87 yo), whichcrystallised from methanol as plates, m.p.8 A 8 6 O (Found:C, 65.7; H, 6.2; N, 6.6. C12H13N03 requires C, 65.7; H,6-0; N, 6.4), A,, (EtOH) 255 nm (log E 4-30).5-il.iTethoxy-3-o-metJ~oxyphenylisoxazole ( 1 ; Arl = o-MeOC,H,) .---o-Methoxyben,~oyZacetoizitrile prepared by themethod described l4 m.p. 86-88" (from benzene-petroleum)(Found: C, 68.5; H, 5.2. C,,H,N02 requires C, (38.6; H,5.2 yo) J was condensed with hydroxylamine hydrochlorideby the method of Obrkgia l6 and the crude materiall3 P. Iiarrcr, E. illiyamichi, H. C. Storm, and R. Widmer,Hch. CJiitn. Acta, 1925, 8, 205.l4 T. Nishiwaki and T. Saito, J . CJienz. SOC. ( C ) , 1971, 3021.l5 T. Nishiwaki and T. Saito, J . CJzem. SOG. ( C ) , 1971, 2648.l6 A.Obre'gia, Anitaleii, 1891, 266, 3241870 J.C.S. Perkin Iwas extracted with chloroform. 5-Amino-3-o-methoxy-phenylisoxazole was isolated from the extracts, m.p. 95-97"(from carbon tetrachloride) (Found: C, 62-9; H, 5.1; N,14.5. CloHloN,O, requires C, 63.15; H, 5.3; N, 14.7),v,, (CHC1,) 3470 and 3380 cm-l (NH,), A,, (EtOH) 237and 286 nm (log E 4.22 and 3-91), and was hydrolysed asdescribed above to give 3-o-methoxyphenyZisoxazol-5( 4H)-one, as needles (from ethanol), m.p. 103-105" (Found: C,62.9; H, 4.6; N, 7.3. CloH,NO, requires C, 62.8; H, 4.75;N, 7-3), u,, (CHCl,) 1800 and 1725 cm-l (GO), A,,(EtOH) 249 and 300 nm (log E 4.12 and 3.99). The i.r.spectrum indicates that this compound contains an appreci-able quantity of the -5(2H)-one tautomer.This isoxazoline(6.50 g ) was treated with ethereal diazomethane, and theproduct was distilled at 150-160" at 2 mmHg. The distil-late solidified on cooling, and two recrystallisations frompetroleum (b.p. 30-70") gave 5-methoxy-3-o-methoxyphenyZ-isoxazole as prisms, (1.47 g, 21), m.p. 55-56" (Found: C,64.4; H, 5.3; N, 6.7. Cl1H,,NOs requires C, 64.4; H, 5-4;N, 6*8), ATaz (EtOH) 240 and 293 nm (log E 4.19 and3.72). The 1.r. spectrum showed no absorption at 1725cm-l. The filtrates were combined and concentrated,giving crystals (0.46 g), m.p. 43-48", which had a strongi.r. absorption at 1725 cm-1 and were discarded.Reaction of 5-Amino-3,4-diphenylisoxazole (7 ; Ar = Ph,R = H) with HMPT.-A solution of the isoxazole (2.00 g)in HMPT (30 ml) was heated under reflux for 1 h and thesolvent was removed under reduced pressure.Aluminachromatography of the residue with petroleum (b.p. 30-70")-ch1oroform ( 5 : 1) gave a solid (0.07 g) which crystal-lised from petroleum as light green needles, m.p. 205-206"(Found: C, 86.35; H, 4.6; N, 901; Mf, 306. Calc. forC,,H,,N,: C, 86.25; H, 4-6; N, 9.15; M , 306), vmsx.(Nujol) 2210 cm-l ( E N ) , AmX (EtOH) 252, 265, and 342 nm(log E 4.38, 4.38, and 3-84), z (CD,),SO 1.7-2.5 (m).Elution with ether gave 2-phenylindole-3-carbonitrile (1 1 ;Ar = Ph, R = H) (0.185 g, 8), which crystallised frombenzene as light yellow rods, m.p. 237-239" lit.,' 243"(decomp.) (Found: C, 82.55; H, 4-8; N, 12.2 ; Mf, 218.Calc. for C,,HloN,: C, 82.5; H, 4.6; N, 12.8; M , 218),v,, (Nujol) 3220 (NH) and 2230 cm-l (CEN), amp;, (EtOH)239 and 306 nm (log E 4-50 and 4-43), 7 (CD,),SO 1.8-2.75Reaction of 2,3-Diphenyl-2H-azirine-2-carboxamide (8 ;Ar = Ph, R = H) with HMPT.-A solution of the azirine(1.60 g) and HMPT (25 ml) was heated under reflux for 1 hand treated as described above, giving the nitrile C,,H,,N,(0.06 g) and 2-phenylindole-3-carbonitrile (0.18 g, 8 ) .2-Phenylindole-3-carboxamide (12; Ar = Ph, R = H).-Asolution of 2,3-diphenyl-2H-azirine-2-carboxamide (8 ; Ar =Ph, R = H) (1.00 g) in diphenyl ether (50 ml) was heatedunder reflux for 1 h and the solvent was removed underreduced pressure. Trituration of the residue with ethergave 2-phenylindole-3-carboxamide (0.47 g, 47 ) , whichcrystallised from chloroform as rods, m.p.180-181"(Found: C, 66.4; H, 4.5; h', 10.0; C1, 13.1. C,,H,2N20,-(m) *0.33CHC1, requires C, 66-7; H, 4.5; N, 10.15; Cl, 12-8y0),v,, (Nujol) 3480 and 3280 (NH,), 3150 (NH), and 1640 cm-1(C=O), amp;, (EtOH) 241 and 300 nm (log E 4.42 and 4.22),T (CD,),SO 1.8-3.0 (m). This compound (0.37 g) andHMPT (10 ml) were heated under reflux for 1 h and thesolvent was removed under reduced pressure. Aluminachromatography of the residue with ether gave 2-phenyl-indole-3-carbonitrile (0.18 g, 53), m.p. 236-238" (frombenzene).Reaction of 5-Amino-4-p-chlorophenyZ-3-phenylisoxazole (7 ;Ar = Ph, R = C1) with HMPT.-A solution of the isoxazole(3.00 g) and HMPT (40 ml) was heated under reflux for 1 hand the solvent was removed under reduced pressure.Alumina chromatography of the residue with petroleum(b.p.30-70") and then with petroleum-chloroform (5 : 1)gave a solid (0.023 g) which crystallised from cyclohexaneas light yellow needles, m.p. 232-234" (Found: C, 70.7; H,3.2; N, 7.7; C1, 18.4; Mf, 376/375/374. Calc. for376/375/374), vmaxa (Nujol) 2200 cm-1 (EN), A,, (EtOH)262 and 353 nm (log E 4-62 and 4-00). Elution with ethergave 6-chlo~o-2-~henyEindole-3-carbonitri~e (1 1 ; Ar = Ph,R = C1) (0.043 g, 14), which crystallised from benzene-petroleum as tan-coloured plates, m.p. 283-285O (Found :C, 71.3; H, 3.6; N, 11.0; Mf, 254/252. Cl,H,C1N2 re-quires C, 71.3; H, 3.6; N, 11.1; M , 254/252), vma,(Nujol) 3240 (NH), 2220 ( E N ) , 850 (isolated benzene lH),and 800 cm-l (adjacent benzene 2H), A,, (EtOH) 240 and315 nm (log E 4-50 and 4-41), z (CD,),SOJ 2-2-2-9 (m).Mixed m.p.with the dehydration product of 6-chloro-2-phenylindole-3-carboxamide (12; Ar = Ph, R = C1) wasnot depressed.Reaction of 2-p-Chlorophenyl-3-Phenyl-2H-azirine-kcarb-oxamide ( 8 ; Ar = Ph, R = C1) with HMPT.-A solutionof the azirine (0.90 g) in HMPT (20 ml) was heated underreflux for 1 h and treated as before. The nitrile C,,H,,Cl,N,(0.01 g) and 6-chloro-2-phenylindole-3-carbonit~ile (0- 11 g,13) were obtained.6-Chloro-2-phenylindole-3-carboxamide (12 ; Ar = Ph,R = C1) .-A solution of 5-amino-4-~-chlorophenyl-3-phenyl-isoxazole (7 ; Ar = Ph, R = C1) (1.00 g) and diphenyl ether(50 ml) was heated under reflux for 2 h. The solvent wasremoved under reduced pressure and trituration of theresidue with ether gave 6-chloro-2-phenylindole-3-carbox-amide (0.12 g, 12). Crystallisation from chloroform-petroleum gave cream needles, m.p. 237-239" (decomp.)(Found: C, 66.15; H, 4.1; N, 10.35. C,5H11C1N,0 re-quires C, 66-55; H, 4.1; N, 10.35), v,= (Nujol) 3450 and3300 (NH,), 3150 (NH), and 1620 cm-l ( G O ) , lux. (EtOH)242 and 307 nm (log E 4.46 and 4-18), 7 (CD,),SO 2.2-3.0(m), This compound (0.20 g) and HMPT (10 ml) wereheated under reflux for 1 h, the solvent was removed underreduced pressure, and the residue was chromatographed onalumina with ether-ethyl acetate (3 : 1). 6-Chloro-2-phenylindole-3-carbonitrile (0.06 g , 30) was obtained.4/108 Received, 21st January, 19741C22HlzC12N2: C, 70.4; H, 3.2; N, 7.4; C1, 18.9; M