Photocyclisation of enamides. Part IX. Syntheses of benzonaphthyridines by photocyclisation ofN-pyridylcyclohex-1-enecarboxamides and pyridine-(N-cyclohex-1-enyl)carboxamides

摘要

1976 1861Photocyclisation of Enamides. Part 1X.l Syntheses of Benzonaphthyri-dines by Photocyclisation of N-Pyridylcyclohex-I -enecarboxamides andPyridine-(N-cyclohex-I -enyl)carboxamidesBy lchiya Ninomiya," Toshiko Kiguchi, Sadami Yamauchi, and Takealti Naito, Kobe Women's College ofThe N-pyridylenamides (Ia-c) were photocyclised to afford equimolar mixtures of cis- and trans-lactanis (IIa-d).Photocyclisation of the N- (pyridy1carbonyl)enamines (VII1)-(IX) gave products (X)-(XVI) with incorporationof solvent alcohol.Pharmacy, Motoyamakita, Higashinada, Kobe, JapanPREVIOUSLY we have described the stereoselectivephotocyclisation of N-acylanilides as part of a study ofenamide photochemistry. We now report an extensionof this photocyclisation to N-pyridylenamides andN-(pyridylcarbonyl)enamine, thus providing a convenientroute to a variety of benzonaphthyridine systems.Photocyclisation of N-Pyridylenarutides.-Tlie N-pyridylenamides (Ia-c) were readily prepared by acyl-ation of aminopyridines with cyclohex-l-enecarbonyl~hloride.~ Their structures were readily determinedPart VIII, I.Ninomiya, T. Naito, and H. Takasugi, J.C.S.Perkin I, 1975, 1791.from their n.m.r. spectra, particularly from the presenceof an olefinic proton signal at 6 cn. 6.7-7.0 (this peakwas used for checking whether photocyclisation hadoccurred). Ogata has reported the related photocyclis-ation of N-pyridyla~rylamides.~Irradiation of the N-pyridylenamides (Ia-c) wascarried out in solution, as described previously,2 with a120 W low-pressure mercury lamp at room temperature.The reaction was monitored by t.1.c.and g.1.c. The2 I. Ninomiya, S. Yamauchi, T. Kiguchi, A. Shinohara, andT. Naito, J.C.S. Perkin I , 1974, 1747.3 M. Ogata and H. Matsumoto, Clzern. and Phann. Bull.(Japun), 1972, 20, 22641862 J.C.S. Perkin IHeating the tertiary amines (IVb-d) with palladium-charcoal yielded the corresponding aromatic benzo-naphthyridines (Vb--d)697 as sole products.Photocyclisation of 7- (Pyridylcarbonyl) enamides.-I thas been reported that photocyclisation of pyridine-carboxanilide does not O C C U ~ . ~ ~ ~ Further, the prepar-ation of benzonaphthyridines by photocyclisation ofboth benzylideneaminopyridine and N-pyridylmethylene-aniline has been described.However, these reportshave been limited to the formation of the aromatic ringsystems. For comparison with the results of photo-cyclisation of the N-pyridylenamides, we have in-vestigated the photocyclisation of N-(pyridylcarbony1)-enamines, which were readily prepared by acylation ofN-cyclohexylidenebenzylamine with pyridinecarbonylchlorides in good yields. The products (VI1)-(IX)again showed characteristic olefinic proton signals intheir n.m.r. spectra.Methanolic O.O2M-solutions of the N- (pyridylcarbony1)-enamines (VI1)-(IX) were irradiated with a 120 Wlow-pressure mercury lamp at room temperature. Thereaction proceeded very slowly, and prolonged irradi-ation only caused decomposition of the product. There-fore, the irradiation was stopped at a point where aconsiderable amount of starting enamides still remained(t.1.c.) ; this was readily removed by chromatography.Although methanol was the solvent of choice for cyclis-ation, addition of a small amount of benzene was veryeffective in raising the yield.Thus, from irradiation ofthe enamide (VII) in methanol, the photoproduct (X)was obtained in 9 yield along with the unchangedenamide (VII) (17). However, in benzene-methanol(1 : 3) the yield of (X) was raised to 25. When ethanolwas used as solvent for photocyclisation, an ethanoladduct was obtained. Oxidative photocyclisation gavethe didehydro-lactam (XI) (16).Similarly, the enamide (VIII) afforded the photocyclis-ation products (XII) and (XIII), albeit in poor yields.The presence of an alkoxy-group at the ring junction inthe photoproducts (X) and (XII) was deduced as follows.The n.m.r.spectra contained a methoxy-singlet at 63.00. Further, compounds (X) and (XII), when heated,were readily converted into the corresponding didehydro-lactams (XI) and (XIII), respectively, identical with theproducts of oxidative photocyclisation. The n.m.r.spectra of compounds (XI) and (XIII) showed signals foreight aliphatic protons, and the aromatic proton signalsclearly determined the orientation of substitution on thepyridine ring, and thus the direction of cyclisation.The methoxy-group in structures (X) and (XII)presumably arises from the solvent. Mechanistic con-siderations s and the n.m.r. analysis indicate its locationas C-6a.Photocyclisation of the nicotinoylenamine (IX) , which7 S.V. Kessar, M. Singh, P. Jit, G. Singh, and A. I<. Lumb.,* M. T. LeGoff and P. Beugelmans, Bull. Soc. chim. France,9 I. Ninomiya, T. Naito, and T. Mori, J.C.S. Perkin I, 1973,Tetvakedron Letters. 1971, 471.1972, (a) p. 1106; (b) p. 1115.505.crude photoproduct showed one spot on t.1.c. but twopeaks on g.l.c., suggesting the formation of two stereo-isomers. This was confirmed by the analyses of theproducts and by dehydrogenation which afforded asingle product .Contrary to the photocyclisations of N-acylanilides,2in which ratios of cis- and trans-products were influencedby the solvent, the ratios of the present photocyclisationproducts were not affected by the solvent; in methanol,benzene, or ether equimolar mixtures of isomers wereformed.Further, thermal interconversion of the isomerswas not observed. The structures of the photoproductswere established from analyses and n.m.r. data, whichhowever gave no hint of the stereochemistry at the ringjunction.Oxidative photocyclisations of the enamides (Ia and b)afforded in each case a single product (IIIa or b), with adouble bond at the ring junction.Whereas photocyclisation of the enamides (Ia and b)proceeded regiospecifically, the enamide (Ic) from 3-For (1)at 2 - Nb; 4-MC; 3 - NFor 111) - Y)a; 4 - Nb; 2 - NC; 1 - Nd; 3 - N 0 =azine!IVa -d) IVb-d)aminopyridine afforded a mixture of two products(IIc and d) corresponding to the two possible directionsof cyclisation.Dehydrogenation of the product (IIa) afforded thecorresponding aromatic lactam (VI) in good yield,identical with an authentic ample.^ Reduction of theproducts (IIa-d) (as equimolar mixtures of cis- andtrans-isomers) with lithium aluminium hydride affordedstereoisomeric mixtures of the tertiary amines (IVa-d) .K.Ito and Y. Kanaoka, Chenz. and Pharm. Bull. (Japan),1974, 22, 1431.5 G. H. Alt and A. J. Speziale, J. Org. Chem., 1966, 81, 1340.H. H. Perkampus and B. Behjati, J . Heterocyclic Chem.,1974, 11, 5111976 1863could afford two geometrical isomers of each of two typesof photoproduct (corresponding to the two modes ofcyclisation), was carried out. The isolated photoproductswere the two types of didehydro-lactam, (XVI) (21)and (XV) (1 yo), and the methoxy-incorporated lactam(XIV) (2).The structures of the didehydro-lactams(XVI) and (XV) were deduced from their n.m.r. spectra,in particular the aromatic proton signals which deter-mined the direction of cyclisation. The product (XIV),n n no m(XYI)which underwent ready conversion into (XV) uponheating, exhibited a methoxy-singlet at 6 3.00. Further,oxidative photocyclisation of (IX) afforded two dide-hydro-lactams, (XVI) (4) and (XV) (24). The ratioof yields of the didehydro-lactams (XV) and (XVI) wasthe converse of that obtained from non-oxidative cyclis-ation.In conclusion, the photocyclisation of N-(pyridyl-carbony1)enamines proceeded very slowly and affordedan alkoxy-incorporated lactam susceptible t o decomposi-tion under irradiation conditions, whereas the N-pyridylenamides underwent smooth photocyclisation toafford equimolar mixtures of cis- and tram-lactams,irrespective of the solvent employed.EXPERIMENTALlH N.m.r.spectra were measured for solutions in deuterio-chloroform with tetramethylsilane as internal reference.1.r. spectra were taken for chloroform solutions unlessotherwise stated. Mass spectra were measured on a JEOL-JMS-OlSG machine. M.p.s were determined with a Kofler-type hot-stage apparatus. Photochemical reactions werecarried out as described in Part I.9Acylation of 2-Aminopyridine.-T.o a stirred solution of2-aminopyridine (8.0 g) and triethylamine (15 g) in anhydrousbenzene (300 ml) cooled in ice, a solution of cyclohex-l-enecarbonyl chloride (15 g) in anhydrous benzene (60 ml)was added dropwise. The resulting solution was heatedunder reflux for 2 h, then washed with water, dried, andevaporated.The residue was chromatographed on alumina.Elution with benzene afforded N- (2-fiyridyl) cyclohex- 1-enecarboxamide (Ia) (7.4 g, 46), crystals, m.p. 64-66 "C(from n-hexane), vmx. 3 180 (NH), 1678 (NCO), and 1639cm-1 (C=C), 6 8.37br (1 H, s , NH), 8.30 (2 H, m, 3'- and 5'-H),7.75 (1 H, td, J 7.8 and 2.0 Hz, 4'-H), and 6.90 (2 H, m,6'-H, GCH) (Found: C, 71.0; H, 7.0; N, 13.95. C,,H,,-N,O requires C, 71.25; H, 7.0; N, 13.85). Elution withbenzene-chloroform afforded N-(2-pyridyl)-2-( 2-fiyridyl-amino)cyclohexanecarboxamide (2.7 g, 16y0), m.p.199-20 lo,as crystals (from methanol), vmx. 3 360 (NH), 3 150 (NH),and 1 678 cm-l (NCO), 6 10.27br (1 H, s, CONH), 6.10 (1 H,d, J 0 Hz, NH), 4.55 (1 H, m, N-CH), and 3.00 (1 H, in,COCH) (Found: C, 68.85; H, 6.8; N, 19.0. C17H,,N,0requiresc, 68.9; H, 6.8; N, 18.90/,).N- (4-PyridyZ) cyclohex- 1 -enecarboxamide (Ib) . --A similarreaction of 4-aminopyridine (3.5 g) with cyclohex- l-ene-carbonyl chloride (6.0 g) afforded the enamide (Ib) (6.7 g,go), b.p. 190" (bath temp.) at 6 x mmHg, v,,,.3 490 (NH), 1 685 (NCO), and 1 640 cm-l (C=C), 6 8.58br(1 H, s, NH), 8.49 (2 H, dd, J 5 and 1.5 Hz, 2'- and 6'-H),7.61 (2 H, dd, J 5 and 1.5 Hz, 3'- and 5'-H), and 6.75 ( 1 H,m, HC=C) (Found: C, 71.25; H, 6.95; N, 13.45).N- (3-Pyridy1)cycZohex- 1-enecarboxavnide (Ic) .-A similarreaction of 3-aminopyridine (3.8 g) with cyclohex- l-ene-carbonyl chloride (5.0 g) afforded the enamide (Ic) (6.1 g,75y0), b.p.180" (bath temp.) at 6 x mniHg, vnmx.3 470 (NH), 1679 (NCO), and 1639 cni-1 (C=C), 6 8.18br(1 €3, s, NH) and 6.78 (1 H, m, HGC) (Found: C, 71.4;H, 7.15; N, 13.95).cis- and trans-6a, 7,8,9,10,1Oa-Hexahyclrobe~zzocl,8naph-thyridin-6(5H)-om (IIa) .-A O.O2~-solution of the enamide(Ia) (370 mg) in methanol, ether, or benzene (100 ml) wasirradiated with a low-pressure mercury lamp at roomtemperature for 49 h. The solvent was removed in vucuoand the residue was chromatographed on silica gel. Elutionwith chloroform afforded the lactarn (IIa) (38-41 "/o), m.p.194-198" (from ether), vmax, 3 440 (NH) and 1685 cm-l(NCO), 6 10.10br (1 H, s, NH), 8.31 (1 H, dd-like, 3-H), 7.55(1 H, m, 1-H), and 7.00 (1 H, m, 2-H) (Found: C, 70.95;H, 6.75; N, 13.7.C,,H,,N,O requires C, 71.25; H, 7.0;N, 13.85), shown to be a mixture of cis- and trans-isomers (ca. 1 : 1) by g.1.c. and n.m.r.cis- and trans-6a, 7,8,9,10,1Oa-Hexahydrobenzocl,6nafih-thyridin-6(5H)-one (IIb) .-By the procedure given for(Ia), irradiation of the enamide (Ib) (400 mg) in methanol,ether, or benzene for 19-20 h afforded, after chromato-graphy on silica gel with chloroform as eluant, the lactam(IIb) (72.5-87.5), m.p. 240-244", as crystals (frommethanol), vmax. 3 430 (NH) and 1 693 cm-l (NCO), 6 9.20(1 H, m, NH) and 6.80 (1 H, d, J 6 Hz, 4-H) (Found: C,71.55; H, 7.25; N, 13.75), shown to be a mixture of cis-and trans-isomers (ca.1 : 1) by g.1.c. and n.ii1.r.Photocyclisation of the Enamide (Ic) .-By the procedurJ.C.S. Perkin Igiven for (Ia), irradiation of the enamide (Ic) (3.0 g) in etherfor 20 h afforded, after chromatography on silica gel withchloroform, cis- and trans-6a, 7,8,9,10,10a-hexahydrobenzo-~1,5Jna~hthyridin-6(5H)-one (IIc) (0.32 g, l l ) , m.p.236-237" (from methanol), vmx 3 440 (NH) and 1 684cm-l (NCO), 6 9.48 (1 H, m, NH) (Found: C, 71.15; H,6.9), and cis- and trans-6a,7,SJ9,10, 1Oa-hexahydrobenzoc-1,7naphthyridin-6(5H)-one (Ild) (0.54 g, 18), m.p.236-240' (from methanol), vmx. 3 440 (NH) and 1 689 cm-1(NCO), 6 9.48br (1 H, s, NH) (Found: C, 71.35; H, 6.9;N, 13.7) (each ca.1 : 1 by g.1.c. and n.m.r.). Irradiationof the enamide (Ic) in benzene gave the same lactams, butwith methanol as solvent only decomposition took place.7,8,9,1 O-Tetrahydrobenzoc 1, 8naphthyridin-6( 5H) -one(IIIa).-The enamide (Ia) (400 mg) in methanol (100 ml)was irradiated in the presence of iodine (250 mg) for 35 h.The solvent was removed and the residue was dissolved inchloroform and washed with aqueous sodium hydrogensulphate and water, dried, and evaporated. The residuewas chromatographed on silica gel ; elution with chloroformgave the didehydro-lactarn (IIIa) (40 mg, loyo), m.p. 236-237" (from methanol), vmx. 3 450 (NH) and 1 649 cm-1(NCO), 6 12.47br (1 H, s, NH), 8.75 (1 H, dd, J 5 and 1.8Hz,3-H), 8.00(1H,dd, JSand1.8Hz, l-H),and7.15(1H,dd, J 8 and 5 Hz, 2-H) (Found: C, 72.05; H, 5.9; N, 13.7.Cl,H,,N20 requires C, 72.0; H, 6.05; N, 14.0).7,8,9,1 O-Tetralzydrobenzo c 1, Glnaphthyridin-6 (5H)-oe(IIIb).-By the procedure given for (Ia), irradiation of theenamide (Ib) (400 mg) in the presence of iodine (130 mg)afforded the didehydro-lnctarn (IIIb) (310 mg, 77.5) ascrystals (from methanol), m.p.262-264", vmx. 3 440 (NH)and 1 654 cm-l (NCO), 6 (C,D,N) 9.02br (1 H, s, 1-H), 8.70(1 H, d, J 6 Hz, 3-H), and 7.43 (1 H, d, J 6 Hz, 4-H) (Found :C, 72.2; H, 6.25; N, 13.5).cis- and trans-5,6,6a,7,8,9,1O,l0a-Octahydrobenzoc 1,8-naphthyridine (IVa).-To a solution of the lactam (IIa)(500 mg) in anhydrous ether-tetrahydrofuran (10 : 3; 130ml), lithium aluminium hydride (500 mg) was added carefulIyin small portions.Theexcess of hydride was decomposed by adding water withcooling. The organic layer was separated and the aqueouslayer was extracted with ether. The combined extractswere washed with brine, dried (Na,SO,), and evaporated t ogive the secondary amine (IVa) (206 mg, 55), as crystals(from n-hexane), m.p. 89-90", vmX. 3 440 cm-l (NH),6 7.88br (1 H, d, 3-H), 7.25 (1 H, m, 1-H), 6.49 (1 H, dd,J 7.5 and 5 Hz, 2-H), and 5.25br (1 H, s, NH) (Found:C, 76.7; H, 8.4; N, 14.85. Cl,Hl,N, requires C, 76.55;H, 8.55; N, 14.9).cis- and trans-5,6,6a, 7,8,9,10,10a-0ctahyd~obenzoc 1,6-napkthyridine ( I n ) .-A similar reaction of the lactam(IIb) (310 mg) with lithium aluminium hydride (290 mg)afforded the secondary amine (IVb) (130 mg, 45) ascrystals (from ether), m.p.174-176", v,,,. 3 500 cm-l (NH),6 6.25 (1 H, d, J 5.5 Hz, 4-H) and 3.25br (1 H, s, NH) (Found :C, 76.55; H, S.55; N, 14.75).cis- and trans-5,6,6a,7,8,9,10,10a-0ctahydrobenzocl,5-nuphthyridine (IVc) .-A similar reaction of the lactam (IIc)(320 mg) with lithium aluminium hydride (300 mg) affordedthe secondary amine (IVc) (160 mg, 29) as crystals (fromn-hexane), m.p. 92-93", v,, 3 450 cm-l (NH), 6 7.90 (1 H,dd, J 1.5 and 4.5 Hz, 2-H), 6.90 (1 H, dd, J 4.5 and 8 Hz,3-H), 6.68 (1 H, dd, J 8 and 1.5 Hz, 4-H), and 3.20br (1 H,s, NH) (Found: C, 76.4; H, 8.4; N, 14.95).cis- and trans-5,6,6a, 7,8,9,10,10a-0ctahydrobenzoc 1,7-The mixture was refluxed for 1 h.waphthyridine (IVd) .-A similar reaction of the lactam (IId)(500 mg) with lithium aluminium hydride (500 mg) affordedthe secondary avnine (IVd) (330 mg, 77) as crystals (fromn-hexane), m.p.89-90', vmx. 3 470 cm-l (NH), 6 6.95 (1 H, m,1-H), and 3.75br (1 H, s, NH) (Found: C, 76.75; H, 8.45).Benzocl,Snaphthytyridin-6(5H)-one (VI) .-A mixture ofthe lactam (IIa) (200 mg) and 10 palladium-charcoal(200 mg) was heated at 220-240 'C (metal bath) for 5 h,then extracted with hot chloroform. The chloroform layerwas filtered and evaporated and the residue was recrystal-lised from chloroform to give the lactam (VI) (140 mg, 70)as crystals, m.p. 268" (lit.,4 274-276'), identical with anauthentic sample.Benzoc 1, 6lnaphthyridine (Vb) .-A similar reaction ofthe secondary amine (IVb) (320 nig) at 250 "C for 7 hafforded the benzonaphthyridine (Vb) (116 mg, 37) ascrystals (from ether), m.p.93-95' (lit.,6 10P-106") (Found:C, 79.85; H, 4.65; N, 15.5. Calc. for C,,H,N,: C , 80.0;H, 4.5; N, 15.55).Benzoc 1,5nuphtlzyridine (Vc) .-A similar reaction ofthe secondary amine (IVc) (140 mg) and 10 palladium-charcoal (140 mg) afforded the benzonaphthyridine (Vc)(120 mg, 90) as crystals (from ether), m.p. 92-93.5"(lit.,6 95-97") (Found: C, 79.7; H, 4.55; N, 15.35).Benzocl, 7naphthyridine (Vd) .-By the procedure givenfor (IVb), the secondary amine (IVd) (160 mg) afforded thebenzonaphthyridine (Vd) (140 mg, 91) as crystals (fromether), m.p.98--1100" (lit.,' 102') (Found: C, 79.7; H, 4.5;N, 15.65).Preparation of the Enamides (VI1)-(IX) .-N-Benzy2-N-cyclohex- 1-enylnicotinamide (IX) . A solution of cyclo-hexanone (9.82 g) and benzylamine (9.63 g) in benzene(200 ml) was refluxed for 5 h with removal of water asformed, then evaporated under reduced pressure. Asolution of the resulting imine and triethylamine (23 g) inanhydrous benzene (100 ml) was added dropwise to a cooledsuspension of an excess of nicotinoyl chloride. Afterstirring at room temperature for 2 h, the mixture was washedwith water, dried (Na,SO,), and evaporated t o give an oil,which was chromatographed on alumina with benzene-chloroform as eluant. Distillation of the eluted oil affordedthe enanzide (IX) (11 g, 46) as an oil, b.p.205" (bathtemp.) at 7 x lov3 mmHg, vmax. 1631 cm-l (NCO), 6 8.81(1 H, dd, J 1.5 and 1 Hz 2-H), 8.63 (1 H, dd, J 5 and 1.5 Hz,4-H), 7.91 (1 H, dt, J 7 and 1.5 Hz, 6-H), 5.31 (1 H, t-like,C=CH), and 4.85 (2 H, s, N*CH,Ph) (Found: C, 77.9; H, 6.8;N, 9.45. C,,H,,N,O requires C, 78.05; H, 6.9; N, 9.6).Similarly, N-benzyl-N-cyclohex-l-enylisonicotinanzide (VII)was prepared in 26 yield as crystals (from ether), m.p.81-82", vmaX 1 635 cm-' (NCO), 6 8.63 (2 H, m, 2- and 6-H),5.26 (1 H, approx. t, HC=C), and 4.81 (2 H, s, NCH,Fh)(Found: C, 78.1; H, 6.95; N, 9.6).N-Benzyl-W-cyclohex-l-enylpicolinamide (VIII) was alsoprepared similarly in 68.50/, yield, as crystals (from n-hexane), m.p. 56-57.5", vmx. 1635 cm-l (NCO), 6 5.10(1 H, m, HGC) and 4.81 (2 H, s, NCH2Ph) (Found: C,78.25; H, 6.8; N, 9.6).Photocyclisation of the Enamides (VI1)-(IX) .-Reactionswere carried out as described previously with 0 .0 2 ~ -solutions of the enamides in an appropriate solvent, such asmethanol or ethanol.The enavnide (VII) in methanol. The enamide (VII)(3.9 g) was irradiated in methanol for 11 h. (Prolongedirradiation caused decomposition of the products.) Thesolvent was removed and the residue was chromatographe1976 1865on alumina. Elution with benzene afforded first N-benzyl-Ga, 7,8,9,10,1Oa-hexahydvo-6a-methoxybenzoc 2, 61naph-thyridin-5(6H)-one (X) (350 mg, 9) as crystals (frommethanol), m.p. 165-167", vmax 1657 (NCO) and 1066cm-l, 6 8.66 (2 H, m, 1- and 3-H), 7.97 (1 H , d, J 5.5 Hz,4-H), 5.63 and 4.50 (2 H , ABq, J 16 Hz, NCH,Ph), and3.01 (3 H, s, OCH,) (Found: AT+, 322.168 324.C,,H,,N20,requires M , 322.168 13), then the starting enamide (VII)(650 mg, 17).The enamide (VIII)(4.8 g) in methanol (800 ml) for 80 h afforded, upon repeatedchromatography, 6-benzyl-Ga-rnethoxy-6a, 7,8,9,10,10a-hexahydrobeiizofl1,7naphthyridin-5(6H)-one (XII) (30iiig, 0.674) as a pale brown oil, vma,. 1 660 (NCO) and 1 065cni-l, 6 8.71 (1 H, m, 3-H), 7.67 (1 H, m, 1-H), 7.45 (1 H, m,3-H), 5.71 and 4.53 (2 H, ABq, J 11 Hz, NCH,Ph), and3.03 (3 H, s, OCH,).The enamide (IX) in methanol. The enamide (IX) (4.67g) was irradiated for 7-8 h. Benzene eluted 6-benzyl-6a, 7,8,9,10,10a-hexahydro-6a-rnetlioxybenzoh 1,6naph-thyridin-B(5H)-one (XIV) (50 mg, 1) as an amorphoussolid (from ether), v,,, 1647 (NCO) and 1063 cm-1, 68.70 (1 H, dd, J 5 and 2 Hz, 2-H), 8.43 (1 H, dd, J 8 and 2Hz, 4-H), 5.61 and 4.50 (2 H, ABq, J 16 Hz, NCH,Ph), 3.21(1 H, m, 10a-H), and 3.00 (3 H, s, OCH,), followed by 5-benzyZ-7,8,9,1O-tetralzydrobenzoh l, 6nuphthyridin-6(5H)-one (XV) (100 nig, 2) as pale yellow crystals (from meth-anol), m.p.172-174", vmak 1650 (NCO), 1613, and 1590cm-l, 6 8.96 (1 H, dd, J 4.5 and 2 Hz, 2-H), 8.76 (1 H, dd,J 8 and 2 Hz, 4-H), and 5.47 (2 H, s, NCH,Ph) (Found:C, 78.7; H, 6.05; N, 9.5. Cl,H1,N,O requires C, 78.6;H, 6.25; N, 9.65), and finally the enamide (IX) (1.68 g,36). Elution with benzene-chloroform then afforded6-benzyZ-7,8,9, lO-tetrahydrobenzoc 2,7nuphtlzyridin-5( 6H)-The enamide (VIII) in methanol.one (XVI) (1 g, 21) as pale yellow crystals (from methanol),m.p.189-19lo, v,, 1657 (NCO) and 1612 cm-l, 6 9.65(1 H, s, 4-H), 8.71 (1 H, d, J 6 Hz, 2-H), and 5.43 (2 H,s, NCH,Ph) (Found: C, 78.5; H, 6.15; N, 9.65. Cl,H18N,0requiresc, 78.6; H, 6.25; N, 9.65).Oxidative Photocyclisation of the Enamide (VII) .-Theenamide (VII) (1.26 g) in methanol (200 ml) in the presenceof iodine (1 g) was irradiated for 27 h. The solution wasevaporated and the residue was dissolved in chloroform.This solution was washed with aqueous sodium hydrogensulphate and water, dried, and evaporated. The residuewas chromatograplied on alumina. Elution with benzenegave the enamide (VII) (600 mg, 48), followed by 6-benzy2-7,8,9,lO-tetrahydrobenzoc 2,6naphthyridin-5( 6H) -one (XI) (200 mg, ISYO), as needles (from ether-methanol),m.p. 139-141", vmx 1652 (NCO) and 1614 cni-l, 8 9.125 Hz, 4-H), and 5.42 (2 H, s, NCH,Ph) (Found: C, 78.3;H , 6.3; N, 9.4. Cl,Hl,N,O requires C, 78.6; H, 6.25; N,9.65).Oxidative Photocyclisution of the Enamide (VIII) .-By theprocedure given for (VII), the enamide (VIII) (2.34 g)afforded 6-benzyl-7,8,9,10-tetra~zydrobenzofl 1,7naphthyri-din-5(6H)-one (XIII) (12 mg, 0.5) as a pale brown amor-phous substance, v,,,. 1 657 (NCO) and 1 613 cm-l, 6 8.91(1 H, m, 3-H), 8.03 (1 H, m, 1-H), 7.60 (1 H, m, 2-H), and5.51 (2 H, s, NCH,Ph) (Found: M+, 290.141 45. C,,HI8N,Orequires M, 290.141 91).Oxidative Photocyclisation of the Enamide (IX) .-By theprocedure given for (VII), the enamide (IX) (1.26 g) affordedthe didehydro-lactam (XV) (300 mg, 24), the enamide(IX) (150 mg, 12y0), and the didehydro-lactam (XVI) (506/073 Received, 12tJi Januavy, 19761(1 H, S, 1-H), 8.70 (1 H, d, J 5 Hz, 3-H), 8.23 (1 H, d, J*Q, 4)