J. CHEM. SOC. PERKIN TRANS. 1 1992 Acyliminium Ion Cyclisations to Pyrrolo- and Pyrido-I ,2-fphenanthridine and Benzode pyrrolo2,1 -a isoquinoline Ring Systems Gregory J. Hitchings, Michael D. Thomas and John M. Vernon Department of Chemistry, University of York, Heslington, York YO I 5DD, UK Pyrrolo- and pyrido- 1,2-f phenanthridines and benzodepyrrolo2,1 -aisoquinolines are obtained by acid-catalysed cyclodehydration of appropriate hydroxy lactams and keto amides derived from N-substituted succinimide and glutarimide derivatives. In previous syntheses of pyrido 172-f)phenanthridine deriv- atives, the additional pyridine ring was elaborated onto a preformed phenanthridine.' Also, pyrrolo- and pyrido- 1,2- flphenanthridine derivatives are among the products obtained from phenanthridine, 6-methylphenanthridine7 and its 5-oxide with acetylenic esters2 We wished to test an alternative approach involving the versatile method of acyliminium ion cyclisation (see structure 1)3 for the construction of fused heterocyclic systems containing a bridgehead nitrogen.More specifically, this approach follows that of our earlier synthesis of isoindolo2,1 -fphenanthridines 2," and other examples in which the C--C bond undergoing cyclisation in structure 1 is part of an aromatic ring.' Although reactions of this kind have been reported with intermediates derived from succinimides and gl~tarimides,~*~-* they have not previously been applied to the synthesis of those fused heterocyclic systems which are described herein.Results and Discussion The requisite precursors for cyclisation via acyliminium ion intermediates were keto amides 5 or hydroxy lactam deriv- atives 8,in which the hydroxy group is a to the nitrogen. These were variously obtained starting from keto acids 3,enol lactones 4, or appropriate N-substituted imides 7,as described in the Experimental section. The result of heating of the keto amide 5b in polyphosphoric acid (PPA) was a double cyclisation in 62 yield to give the pyrrolo 1,2$ Jphenanthridine 9b,analogous to the formation of compound 2 (R = Ph).4 In the same way, the homologous keto amide 5a was cyclised to the pyrido1,2-fl- phenanthridine 9a, which was also obtained in a single step (27 yield) from keto acid 3a and o-aminobiphenyl in hot PPA.The hydroxy lactam 8a was obtained either by Grignard addition to the succinimide 7b or by heating a-angelicalactone 4a with o-aminobiphenyl. Heating of lactam 8a in PPA afforded the pyrrolo 1,2-fphenanthridine 9c (75). Reduction of the same imide 7b with sodium borohydride in the presence of acid, the method developed by Speckamp and co-w~rkers,~ gave a mixture of the desired hydroxy lactam 8b (48) and by- 1 2 RGO 3a; n = 3 4a; R=Me b; n =2 b; R=Ph O -PhC6H4NHCOCHamp;OH 6a; n = 4 b; n=3 0QRT R' 8a; R1= 0-PhCd4, $= Me, R3 = H b; R1 = 0 -PhCamp;, $= R3 = H c; R' = PhCH2, R2= H, R3 = Et d; R' = a-CloH7Camp;, R2 = R3 = H e; R' = a-CIOH$H2CH2, R2 = R3 = H succinimides 7c and 7d was uncomplicated by ring-opening.The hydroxy lactam 8d was obtained from imide 7d by using alkaline conditions for work-up, and the ethoxy lactam 8c from imide 7c using acidic conditions for work-up. No cyclisation to pyrrolo2,1-aisoindole derivatives 12 was ob-served on acid treatment of lactam 8c or of the related keto amide 5c under conditions of varying severity, despite the presence of a phenyl group to stabilise the iminium ion intermediate (11; R = Ph) derived from keto amide 5c. These'product amido alcohol 6b (40).The latter is the result of ring- '3'and other examples reflect the general difficulty of 5-endo- opening and over-reduction of imide 7b,which is a common side-reaction occurring with N-aryl irnides.'-' ' Reduction of N(o-biphenyly1)glutarimide 7a under similar conditions affor- ded only the corresponding open-chain product 6a, a result which is consistent with the greater ease of ring-opening of the 6-membered in comparison with the 5-membered cyclic imide.Cyclodehydration of the hydroxy lactam 8b in PPA gave the tetracyclic lactam 9d. Lithium aluminium hydride reduced lactams 9a and 9b to the tertiary amines 10a and lob, respectively; as compound 10s was a somewhat air-sensitive oil, it was characterised as the picrate. Sodium borohydride reduction of the N-benzylic substituted trigonaf cyclisation of an N-benzyliminium ion (11). The only products detected, but incompletely characterised, were com- pound 13 and a dimeric product from lactam 8c on heating in trifluoroacetic acid (TFA).The structure of the dimer is probably 14 on analogy with others already known.g,' On the other hand, an alternative 6-endo-trigonaf cyclisation (to the naphthalene 8-position) is available in an intermediate iminium ion containing an N-a-naphthylmethyl group. Thus, the keto amide 5d and the related hydroxy lactam 8d underwent cyclodehydration in refluxing TFA to give the benzodepyrrolo2,1-aisoquinoline derivatives 15a and 15b, respectively. These structures are analogous to those of J. CHEM. SOC. PERKIN TRANS. 1 1992 9a; n=3,R=Ph 1Oa; R=H b; n =2,R=Ph b; R=Pn c; n =2,R=Me d; n =2,R=H p0 0 11 12 A0 GO CH2Ph (NXOCHIPhCHzPh 13 14amp;0 0 15a; R = Ph 16a; R= Ph b; R=H b; R=H 17a; X=H b; X=OMe products (16a, b) obtained in the same way from precursors derived from N-(~-naphthylmethyl)phthalimide.~In contrast, the hydroxy lactam 8e, the homologue of amp;I,is reported to undergo cyclisation to the naphthalene 2-position to give compound 17a.6 Three groups of resonances for the aryl hydrogen atoms were clearly resolved in the 300 MHz 'H NMR spectrum of compound 15b.By comparison with the spectrum of 1,8-dimeth~lnaphthalene,'~these could be assigned to 1-H and 6-H (6 7.25-7.33, two doublets), 2-H and 5-H (6 7.42-7.51, two pseudo-triplets), and 3-H and 4-H (6 7.72-7.77, two overlapping doublets), respectively. Appropriate selective NMR decoupling experiments confirmed the correctness of these assignments and hence of the 1,8-naphthalene substitution pattern in structure 15b.Irradiation at the frequency of the resonance assigned to 1-H caused collapse of the 2-H resonance to a doublet; similarly irradiation of the 6-H resonance caused collapse of the 5-H resonance to a doublet, but no other changes in the NMR spectrum. Characteristically, the most abundant ion-peaks in the mass spectra of compounds 15a and 15b and of the other fused heterocyclic compounds 9a-d were always due to loss of the atom or group at the ring junction adjacent to nitrogen. For this reason, the elemental composition of tetracycles 9d and 15b was confirmed by high-resolution measurement of m/z for the ionM -HI+. Experimental IR spectra were recorded for Nujol mulls and calibrated with polystyrene (Pye-Unicam 1025 and SP3-200 and Perkin-Elmer 257 and 1420 spectrophotometers).'H NMR spectra were recorded at 60 (Varian EM360-A), 90 (JEOL-JNM-FX90Q), or 300 (Bruker MSL300) and 13C NMR spectra at 22.5 MHz (JEOL-JNM-FX90Q) for solutions in 2Hchloroform (unless otherwise stated) with tetramethylsilane as internal standard. J- Values are given in Hz. Mass spectra were obtained by electron impact at 70 eV (Kratos MS30). Preparative TLC (PLC) was performed on silica-coated plates by using centrifugal assistance to achieve radial separation (Chromatron), whereby all new compounds were obtained chromatographically pure. Light petroleum refers to the fraction boiling in the range 40-60 "C.Diethyl ether and tetrahydrofuran (THF) for Grignard re-actions were dried before use. Keto Amides 5a-d.-0-Aminobiphenyl (1.4 g) and 5-0x0-5- phenylpentanoic acid 3a (1.6 g) were heated together at 150 "C for 2.5 h. The mixture was cooled, dissolved in chloroform, and washed successively with dil. hydrochloric acid and aq. sodium hydrogen carbonate. After evaporation of the chloroform, the crude product was redissolved in ethanol and boiled with addition of charcoal; the solution was filtered and the filtrate was evaporated to dryness; the residue afforded the keto amide 5a (0.2 g), m.p. 74-78 "C (from toluene-light petroleum) (Found: M +,343.1570. C23H21N02 requires M, 343.1572); vmax/cm-l 3220br (NH) and 1680 and 1640 (GO);'H and 13C NMR spectra were complicated by the effects of restricted rotation of the N-o-biphenylyl group; m/z 343 (M+, l), 192 (7), 169 (4), 120 (12), 105 (100) and 77 (31).o-Aminobiphenyl(l.8 g) and 5-phenylfuran-2( 3H)-one 4b (1.7 g) were heated togethet at 100 "C for 1 h. The melt was cooled and the resulting solid was crushed, and washed successively with dil. hydrochloric acid and water, then recrystallised to give the keto amide 5b (2.5 g, 71), m.p. 132-133 "C (from MeOH) (Found: C, 79.9; H, 5.8; N, 4.6. C22H19N02 requires C, 80.2; H, 5.8; N, 4.3); v,,,/cm-' 3260 (NH) and 1690 and 1665 (M); 6H(2H3C)2so 2.58 and 3.26 (each 2 H, t, CH,), 7.2-8.1 (14 H, m, ArH) and 9.30 (1 H, s, NH); m/z 329 (M', 879,170 (14), 169 (loo), 161 (53), 105 (28) and 77 (21).A solution of N-benzylsuccinimide 7c (0.20 g) in dry THF (5 cm3) was added to the Grignard reagent prepared from bromobenzene (0.33 g) and magnesium (0.05 g) in dry diethyl ether (4 cm3). The mixture was stirred at room temperature for 24 h. Aq. ammonium chloride was added; the organic layer was separated and evaporated to dryness; the residue was chromatographed and eluted with ethyl acetate-chloroform (1 :4 v/v) to give the keto amide 5c (0.23 g, 81), m.p. 108.5-110 "C (from EtOH) (Found: M+, 267.1256. Cl,H,,N02 requires M, 267.1259); v,,,/cm-' 3300 (NH) and 1690 and 1635 (GO); dH2.67 and 3.38 (each 2 H, t, J 7, CH,CO), 4.42 (2 H, d, J5.5, CH,N), 6.33 (1 H, br, NH), 7.2-7.7 (6 H, m, ArH) and 7.9- 8.1 (2 H, m, ArH); m/z 267 (M +,5), 189 (19), 161 (1 5), 132 (lo), 106 (loo), 105 (39), 91 (35) and 77 (60).A solution of N-(a-naphthylmethy1)succinimide 7d (0.20 g) in dry THF (4 cm3) was added to the Grignard reagent prepared from bromobenzene (0.26 g) and magnesium (0.04 g) in dry diethyl ether (5 cm3). The mixture was stirred at room temperature for 23 h, then acidified with dil. hydrochloric acid. The organic layer was separated and evaporated to dryness. The residue was chromatographed and eluted with ethyl acetate- chloroform (1 : 3 v/v) to give the keto amide 5d (0.23 g, 91), m.p. 129-131 "C (from EtOH) (Found: M+, 317.1452. CZ1H19N02 requires M, 317.1452); v,,,/cm-' 3295 (NH) and 1680 and 1640 (C=O); dH2.60 and 3.33 (each 2 H, t, J6.5, CH,CO), 4.88 (2 H, d, J5.5, CH,N), 6.19 (1 H, br t, NH) and 7.25-8.06 (12 H, m, ArH); J.CHEM. SOC. PERKIN TRANS. 1 1992 m/=317 (M+, 12), 239 (6), 156 (loo), 149 (16), 141 (28), 105 (19)and 77 (22). lmidrs 7a--d.-The general method was to treat equimolar quantities of glutaric or succinic anhydride with the appropriate amine in reffuxing THF or toluene, then to dehydrate the re- sulting amido acid by heating it in refluxing acetic anhydride or by heating it alone until a condensate of water was seen on a cold surface above the heated sample. Imides 7a-c obtained by this procedure had m.p., after recrystallisation, in agreement with lit. value^.'^,'^ Sodium hydride (0.58 g) was added to a solution of succinimide (2.0 g) in anhydrous N,N-dimethylformamide (DMF) (20 cm3) at 0"C and the mixture was stirred for 2.5 h while it was allowed to warm to room temperature.A solution of 1-(chloromethy1)naphthalene(3.3 g) in DMF (10cm3) was added and the mixture was stirred for 14 h, diluted with chloroform, and extracted with water; the chloroform extract was then dried (MgS04) and evaporated to dryness; the residue afforded the imide 7d (3.36 g, 70), m.p. 103-104deg;C (from EtOH); vmax/cm-l 1770 and 1695 (C=O); SH 2.48 (4H, s, ring CH,), 4.95 (2 H, s, CH2N) and 7.15-8.37 (7 H, m, ArH); m/z 239 (M+, loo), 210 (29), 183 (19),182 (15), 167 (15), 154 (22)and 141 (18). Hydroxy and Ethoxy Lactams 8a-d.-o-Aminobiphenyl (1.2g) and angelicalactone 4a (0.7g) were heated together at 100"C for 1.5 h.The mixture was cooled, and triturated with diethyl ether; the resulting solid was filtered off and re-crystallised from toluene to give 1 -(o-biphenylyl)-5-hydroxy-5-methyfpyrrolidin-2-one 8a (0.5 g, 28), m.p. 11 3-1 15 "C (Found: C, 76.3;H, 6.4;N, 5.2.Cl7HI7NO2requires C, 76.4;H, 6.4;N, 5.3); v,,,/cm-' 3400br (OH) and 1680br (C=O); ~3~0.77and 1.27(together 3 H, 2 s, Me of two rotamers), 1.5-2.8(4H, m, 2 x CH,), 3.9(1 H, br, OH, exchangeable), and 7.30and 7.38 (9 H, 2 s, ArH); dC26.0(9, Me), 29.4and 34.8 (2 t, CH,), 91.5(s, C-5), 127.3-131.1 (7 lines, ArCH), 132.9'139.7and 142.5(3 s, Arc), 177.1(s, CO) and several less intense lines attributable to the minor rotamer; m/z 267 (M+,25), 249 (22), 234 (14),169 (100) and 99 (1 3).The other compounds (8b-d) were prepared by the following general procedure. The appropriate imide was dissolved or suspended in ethanol, cooled, and stirred with addition of an excess of sodium borohydride and of 10 drops of either hydrochloric or toluene-p-sulfonic acid (PTSA) (2mol dm-3 in ethanol). Further acid was added at the rate of 1 drop every 5 min during the reaction time and at the temperature stated. 'Basic work-up' involved pouring the reaction mixture into an excess of aq. sodium hydrogen carbonate and extraction with dichloromethane; the extract was washed successively with dil. hydrochloric acid and aq. sodium hydrogen carbonate, dried (MgS04), and filtered, and the filtrate was evaporated under reduced pressure.Alternatively, 'acidic work-up' involved the addition of more ethanolic acid until the pH of the solution was 2, then allowing the mixture to warm to room temperature and to stand for 48 h, after which it was poured into an excess of saturated aq. sodium hydrogen carbonate and the organic product(s) was(were) extracted into dichloromethane or chloro- form, as above for 'basic work-up'. The residue left after evaporation of solvent was purified by PLC, and the following products were obtained. From the imide 7a (0.20g) and sodium borohydride (0.15g) in ethanol (75 cm3) with addition of PTSA (2 mol dm-3 in ethanol) and acidic work-up after reaction for 5.5 h at -20 "C; elution with chloroform-ethyl acetate (1 : 1 v/v) gave only N-(0-biphenylyI)-5-hydroxypentanamide6a (0.19g, 96) as a viscous oil (Found: M', 269.1412.C1,Hl9NO2 requires M, 269.1416); vmaX/cm-'3260-3420br (OH) and 1665 (GO); a,., 1.30-1.70 897 (4H, m, 2 x CH2), 2.19 (2 H, t, J 6.3, CH,CO), 3.02(1 H, s, OH), 3.49(2 H, t, J6.3,CH,OH), 7.01-7.56 (9 H, m, ArH) and 8.09(1 H, s, NH); m/z 269 (M', 1 I), 169 (100)and 168 (64).From the imide 7b (0.50 g) and sodium borohydride (0.52g) in ethanol (75 cm3) with addition of hydrochloric acid (2 mol dm-3 in ethanol) and basic work-up after reaction for 7 h at -30 "C; chloroform-thy1 acetate (1 : 1 v/v) eluted first 1-(0-biphenyIyl)-5-hydroxypyrrolidin-2-one8b (0.24 g, 48), m.p. 148-149 "C (from toluene-light petroleum) (Found: C, 75.9;H, 5.9;N, 5.55; M+, 253.1089.C1,Hl5NO2 requires C, 75.9;H, 6.0 N, 5.5; M, 253.1103); v,,,/cm-' 3220 (OH) and 1675 (M);dH 1.55-2.75(4H, m, 2 x CH,), 3.89(1 H, d, J6,OH), 4.70(1 H, br s, 5-H) and 7.35 (9H, br s, ArH); m/z 253 (M+,loo), 252 (43), 236 (29), 206 (18), 180 (58), 170 (25), 169 (61), 168 (32), 167 (27), 154(35) and 152 (22).Further elution afforded N-(o-biphenylyl)-4-hydroxybutan-amide 6b (0.20g, 40), m.p. 82584deg;C (from toluene-light petroleum) (Found: C, 75.3;H, 6.7;N, 5.5. C16H17N02requires C, 75.3;H, 6.7;N, 5.5); v,,,/cm-' 3350br (OH), 3230br (NH) and 1680(M);6,1.85 (2 H, quintet, J 6,CH2CH20H),2.30 (2 H, t, J6,CH2CO),3.60 (2 H, t, J6,CH,OH), 7.10-7.60( 9H, m, ArH) and 8.17(1 H, br s, OH); m/z 255 (M', 16), 169 (loo),168 (32) and 167 (25).From the imide 7c (0.20g) and sodium borohydride (0.20g) in ethanol (70 cm3) with addition of PTSA (2 mol dm-j in ethanol) and acidic work-up after reaction for 5 h at 0 "C; chloroform-ethyl acetate (1 : 1 v/v) eluted 1-benzyl-5-ethoxy- pyrrolidin-2-one 8c (0.20 g, 85) as an oil (Found: M', 219.1255.C13H17N02 requires M, 219.1259); v,,,/cm-l 1700 (C=O);SH 1.17(3 H, t, J 7,Me), 1.85-2.80(4H, m, 2 x CH,), 3.39 (2 H, q, J 7, CH,Me), 4.03 and 4.91(each 1 H, d, J 15, CH,N), 4.70(1 H, m, 5-H) and 7.24(5 H, s, ArH); m/z 219 (M', 9), 174 (20), 146 (22), 104(18)and 91 (100). From the imide 7d (0.30g) and sodium borohydride (0.34g) in ethanol (75cm3) with addition PTSA (2 mol dm-3 in ethanol) and basic work-up after reaction for 4.5 h at 0"C; diethyl ether eluted 5-hydroxy- l-(a-naphthylmethyl)pyrrolidin-2-one8d (0.26 g, 86), m.p.14C143"C (from toluene-light petroleum) (Found: M', 241.1105. CI5Hl5NO2 requires M, 241.1103); v,,,/cm-' 3275br (OH) and 1675 (C=O); aH 1.60-2.80(4H, m, 2 x CH,), 4.52and 5.29(each 1 H, d, J 15.5,CH2N),4.93(1 H, br t, J 7.5,5-H), 6.25(1 H, d, J 7.5, OH) and 7.40-8.45 (7 H, m, ArH); m/z 241 (M+,9) 223 (28), 154 (lo), 142 (19),141 (100) and 115 (18). Pyrido- and Pyrrolo-1,2-f-phenanthridines9 and 10.-The keto amide 5a (72 mg) was dissolved in PPA (10g) and the solution was heated at 150 "C for 1 h, then at 170 "C for 15 min. The mixture was cooled, stirred with ice-water, and extracted with chloroform. The extract was washed with aq.sodium hydrogen carbonate, dried (MgS04), then filtered, and the filtrate was evaporated to dryness. PLC of the residue with chloroform as developer afforded 1 1,12,13,13a-tetrahydro-13a-phenylpyridoC1,2-fphenanthridin-lO-one9a (24mg, 3579,m.p. 192-194 "C (from toluene-light petroleum) (Found: M ', 325.1451.C23HlgN0 requires M, 325.1466); v,,/cm-' 1660 (GO); 6, 1.85-3.02(6H, m, 3 x CH2) and 6.95-7.89(13 H, m, ArH); m/z 325 (M+, 8)' 256 (15), 248 (M -Ph, 22), 93 (40) and 91 (100).The same product (9a) (0.15 g, 27) was also obtained by heating o-aminobiphenyl (0.30g) and 5-0x0-5- phenylpentanoic acid 3a (0.37g) in PPA (10g) at 150 "C for 2.5h, followed by work-up as above. The keto amide 5b (3.0g) was dissolved in PPA (45 g) and heated to 200deg;C for 45 min.The mixture was cooled and poured onto stirred, crushed ice; then, after storage for 1 h, the orange precipitate was collected, washed with water, and recrystallised several times from aq. acetic acid with addition of charcoal to afford 12,12a-dihydro-12a-phenylpyrrof01,2-f- phenanthridin-l0(4 lH)-one 9b (1.75 g, 62), m.p. 22W222 "C (Found: C, 84.8; H, 5.4; N, 4.5. C22H17NO requires C, 84.9; H, 5.5; N, 4.5); vmax/cm-' 1695 (GO),1600 and 1490; 6, 2.2-2.8 (4 H, m, 2 x CH2) and 6.7-8.3 (13 H, m, ArH); 6,24.4 and 29.4 (2 t, CH,) 61.8 (s, C-l2b), 115.6-136.9 (12 lines, aromatic carbons) and 168.1 (s, CO); m/z 311 (M', 13), 235 (17), 234 (M -Ph, 100), 233 (10) and 206 (10). This lactam 9b (0.5 g) was heated with lithium aluminium hydride (0.2 g) in dry THF (10 cm3) under reflux for 17 h.The mixture was cooled, aq. ammonium chloride (10) was added, the mixture was filtered, the filtrate was evaporated to dryness, and the residue was recrystallised to give 10,11,12,12a-tetra- hydro- 12a-phenylpyrroloC 1,2-fphenanthridine 10b (0.16 g, 3479, needles, m.p. 170-172 "C (from CHCI,-MeOH) (Found: C, 88.9; H, 6.4; N, 4.7. C2,H19N requires C, 89.0; H, 6.4; N, 4.7); 6, 2.02, 2.72 and 3.70 (each 2 H, m, CH,) and 6.8-7.8 (1 3 H, m, ArH); m/z 297 (M', lo), 221 (18), 220 (M -Ph, 100) and 217 (14). Solutions of 10b developed a blue colour on storage. The hydroxy lactam 8a (0.90 g) was heated with PPA (15 g) at 150 "C for 45 min, then at 170 "C for 15 min. The mixture was cooled, poured onto crushed ice, and extracted with diethyl ether.The extract was separated, washed, dried, and evaporated under reduced pressure. The residue afforded 12,12a-dihydro- 12a-methylpyrroloC 1,2-f)phenanthridin- 10( 1 1 H)-one 9c (0.63 g, 7573, m.p. 164165 "C (from toluene-light petroleum, then from CC14) (Found: C, 82.0; H, 6.1; N, 5.5. CI7Hl5NO requires C, 81.9; H, 6.1; N, 5.6); v,,,/cm-' 1690 (C=O); 6, 1.32 (3 H, S, Me), 2.3-2.8 (4 H, m, 2 x CH,), 7.0-7.4 and 7.6-7.9 (7 H, m, ArH) and 8.28 (1 H, dd, J 7 and 2,8-H); m/z 249 (M+, 1 l), 235 (18), 234 (M -CH,, 100), 206 (13) and 178 (14). The hydroxy lactam 8b (0.50 g) was heated with PPA (30 g) at 150 "Cfor 1 h, then at 170 "C for 15 min. After the usual work- up procedure and PLC with chloroform-ethyl acetate (1 : 1 v/v) as developer, the pyrroloC 1,2-fphenanthridin-lO-one9d (0.39 g, 84) was obtained as a solid which darkened on exposure to air, more rapidly in solution (Found: M+ -I, 234.0921.C 6H ,NO requires m/z, 234.09 19); vmax/cm-l 1780 (C=O); 6, 2.18-2.94 (4 H, m, 2 x CH,), 5.05 (1 H, m, 12a-H) and 7.09- 7.47,7.68-7.88 and 8.28-8.41 (5 H, 2 H and 1 H, respectively, m, ArH); m/z 235 (M', 7379,234 (loo), 180 (38) and 179 (28). Reduction of compound 9d with lithium aluminium hydride (0.24 g) in dry THF (45 cm3) heated under reflux for 46 h, followed by work-up with aq. sodium hydroxide and extraction of organic material into chloroform, gave 10,l 1,12,12a-tetra- hydropyrrolo 1,2-flphenanthridine 10a as a greenish oil, which with saturated ethanolic picric acid gave a red precipitate of the picrate, m.p.184-189 "C (decomp.) (from water) (Found: C, 58.3; H, 3.9; N, 12.3. C,,H,,N,O, requires C, 58.7; H, 4.0 N, 12.4); 'H and I3CNMR spectra in (,H,C),CO confirmed the presence of three CH2 groups, but the 12a-H and C-12a resonances were obscured by absorptions due to the solvent. Benzode pyrroloC2,l -aisoquinolines 15.-The keto amide 5d (57 mg) was dissolved in TFA (4 cm3) and the solution was heated under reflux for .5.8 h; the mixture was then cooled and worked up as described above. PLC with chloroform-ethyl acetate (3: 1 v/v) afforded 11,l la-dihydro-1 la-phenyfbenzoCde1- pyrrolo2,l-aisoquinolin-9(7H,lOH)-one 15a (35 mg, 62"/,), J.CHEM. SOC. PERKIN TRANS. 1 1992 m.p. 177-179 "C (from EtOH) (Found: M+, 299.1312. C21H17N0 requires M, 299.1310); vma,/cm-' 1675 (GO);6, 2.40-3.10 (4 H, m, 2 x CH,), 4.16 and 5.37 (each 1 H, d, J 16.5, CH2N) and 6.72-7.92 (1 1 H, m, ArH); m/z 299 (M+, 25), 223 (15) and 222 (M -Ph, 100). The hydroxy lactam 8d (112 mg) was dissolved in TFA (4 ml) and the solution was heated under reflux for 5 h. The mixture was cooled, poured into an excess of saturated aq. sodium hydrogen carbonate, and extracted with chloroform. The extract was washed, dried, filtered, and evaporated to dryness, and the residue was purified by PLC (ethyl acetate). The product 15b (67 mg, 65) darkened on exposure to air (Found: M -1, 222.0917.C15H12N0 requires m/z, 222.0919); 6, 2.00-3.02 (4 H, m, 2 x CH,), 4.38 and 5.38 (each 1 H, d, J 17.2, CH,N), 5.04 (1 H, t, J 7.0, 1 la-H) and 7.16-7.85 (6 H, m, ArH); m/z 223 (M +,6673,222 (loo), 167 (29) and 166 (20). References 1 B. P. Das, A. C. D. Gupta, S. S. Chakravorti and U. P. Basu, Indian J. Chem., 1969,7,674; T. L. Wimmer, F. H. Day and C. K. Bradsher, J. Org. Chem., 1975,40, 1198. 2 R. M. Acheson and A. 0.Plunkett, J. Chem. SOC.,1962,3758; R. M. Acheson, A. S. Bailey and I. A. Selby, J. Chem. SOC.C, 1967, 2066; R. M. Acheson and M. S. Verlander, J. Chem. SOC. C, 1969, 2311; R. M. Acheson and I. A. Selby, J. Chem. SOC.,Perkin Trans. I, 1974, 423. 3 W. N. Speckamp and H. Hiemstra, Tetrahedron, 1985,41,4367, and references therein; D.J. Hart, in Alkaloids: Chemical and Biological Perspectives, ed. S. W. Pelletier, Wiley-Interscience, New York, 1988, vol. 6, p. 227, and references therein. 4 M. Ahmed and J. M. Vernon, J. Chem. SOC.,Perkin Trans. I, 1977,601. 5 M. Winn and H. E. Zaugg, J. Org. Chem., 1968, 33, 3779; G. J. Hitchings, M. Helliwell and J. M. Vernon, J. Chem. SOC.,Perkin Trans. I, 1990,83, and references therein. 6 W. N. Speckamp, J. C. Hubert and H. 0. Huisman, Tetrahedron Lett., 1972,4493. No details are given of the yield or characterisation of compound 17a, but the known methoxy derivative 17b was obtained in the same way. 7 B. E. Maryanoff and D. F. McComsey, Tetrahedron Lett., 1979,3797; B. E. Maryanoff, D. F. McComsey and B. A. Duhl-Emswiler, J. Org. Chem., 1983, 48, 5062; B. E. Maryanoff, D. F. McComsey, H. R. Almond, M. S. Mutter, G. W. Bennis, R. R. Whittle and R. A. Olofson, J. Org. Chem., 1986, 51, 1341; 0. Meth-Cohn, R. R. Vif, R. K. Smalley and R. Bass, J. Chem. Rex, 1989, (S) 124 (M) 1001. 8 c$ T. Kametani, K. Kigasawa, M. Hiiragi, H. Ishimaru and S. Haga, J. Heterocycl. Chem., 1974, 11, 1023. 9 J. C. Hubert, J. B. P. A. Wijnbergand W. N. Speckamp, Tetrahedron, 1975,31,1437. 10 A.-I. Horii, C. Iwata and Y. Tamura, J. Org. Chem., 1961,26,2273. 11 G. J. Hitchings and J. M. Vernon, J. Chem. SOC.,Perkin Trans. I, 1990,1757. 12 J. B. P. A. Wijnberg, J. J. J. de Boer and W. N. Speckamp, Red. Trav. Chim. Pays-Bas, 1978,97,277. 13 N. K. Wilson and J. B. Stothers, J. Magn. Reson., 1974,15,31. 14 E. Ritchie, J. Proc. R. SOC.,N. S. Wales, 1945,78, 147 (Chem. Abstr., 1946,40, 8779). 15 H. W. Arnold and N. E. Searle, U.S. Pat. 2 462 835, 1949 (Chem. Abstr., 1949,43, P4422b). Paper 1 /05478C Received 28th October 1991 Accepted 2nd December 1991
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