1978 653 N-lodo-amides : Cyclisation of Substituted Biphenyl-2-carboxamides By Stephen A. Glover and Andre Goosen,rdquo; Organic Chemistry Research Laboratories, University of Port Elizabeth, P.O. Box 1600, Port Elizabeth, South Africa Homolysis of N-iodo-amides leads to 2lsquo;-, 3lsquo;-, and 4lsquo;-substituted biphenyl-2-carboxamidyl radicals which cyclise intramolecularly to give y-and 8-lactams in parallel processes. The proportion of Ar,-5 and Ar,-6 cyclised products is in accord with the steric and electronic effects of the substituents. 4lsquo;-lodo-4lsquo;-methoxy-N-methyl-3-oxoiso-indoline-1 -spiro-1 lsquo;-cyclohexa-2rsquo;,5rsquo;-dienes have been identified as spiro-intermediates in the cyclisation of N-rnethyl-4lsquo;-methoxybiphenyl-2-carboxamide. THE intramolecular cyclisation of biphenyl-z-carbox-amides has been effected by persulphate oxidation lp2 and irradiation or thermolysis of the corresponding N-iodo- amide~.~-~The thermal persulphate oxidations of substituted biphenyl-2-carboxamides gave amongst other products phenanthridones, dibenzopyranones (through oxygen cyclisation) , nitrogen dealkylation products, and products arising from displacement of 2rsquo;-substituents by both nitrogen and oxygen.Hey et aZ.1 also illustrated the pH dependence of the product distribution, basic media favouring spiro- or Ar,-5 cyclisation. Recently, it was reported that treatment of biphenyl- 2-carboxamides with t-butyl hypolodite, and irradiation or heating in t-butyl alcohol, afforded a method of trapping intermediate spirodienyl radicals as spiro-dienyl t-butyl ethers and dienones and it has been proposed that the Ar,-5 and Ar2-6 cyclisations occur by reaction of the amido-radical in the C and It electronic states respectively.The effect of substituents on the course of cyclisation has now been investigated. RESULTS AND DISCUSSION The results of irradiation of 4rsquo;-substituted biphenyl-2- carboxamides with t-butyl hypoiodite in t-butyl alcohol at room temperature are given in Table 1. The cyclis- ations were not effected in the dark at this temperature. TABLE1 Time Phenanthridone Spirodienone (h) Amide I I2.5 (14 (2a) ~71 (34 ~51 2.5 (lb) (2b) n.e. (3b) 681 4 (Ic) (2~)171 (34 ~701 8 (1d) w)~71 (3a) 40 3 (le) (2e) ~51 3 (If) a n.e. = Not estimated; fraction with vmax, 1 670 cm-l isolated.Yields based on 1i.m.r. N-methyl signals. 4rsquo;-Methyl-N-rnethylbiphenyl-Z-carboxamide(le) also afforded an intractable mixture of spiro-components while the 4rsquo;-nitrile substrate (If) failed to react under the reaction conditions. A detailed study of the cyclisation of 4rsquo;-methoxy-N- methylbiphenyl-2-carboxamide (1a) at room temperature showed (n.m.r.) that after one hour of irradiation the D. H. Hey, G. H. Jones, and M. J. Perkins, J.C.S. Perkin I, 1972, 118. A.R. Forrester, A. S.Ingram, and R. H. Thomson, J.C.S. Perkin I, 1972, 2847. S. A. Glover, A. Goosen, and H. A. H. Laue, J.C.S. Perkin I, 1973, 1647. mixture contained, in addition to 3-methoxy-N-methyl- phenanthridone (2a), 14y0 and the spirodienone (3a), 17y0, another Ar,-5 cyclised product (56) which re- arranged slowly to the dienone.This rearrangement 0 I1 a; R1= Me, R2 = OMe, R3 = R4 = H a; R1 = Me, b; R1 = R3 = R4 = H, R3 = OMe R4 = H c; R1 = Me, R2 = I, R3 = R4= H b; Rrsquo;= H, d; R1 = Me, R2 = C1, R3 = R4 = H R4 = H e; R1 = Me, R2 = Me, R3 = R4 = H c; R1 = Me, f; R1 = Me, R2 = CN, R3 = R4 = H R4= OMe g; R1 = Me, R2 = R4 = H,R3 = OMe d; Rrsquo;= H, h; R1= Me, R2 = R3 = H,R4 = OMe R4= OMe i; R1 = R2 = R3 = H, R4 = Ohle j; R1 = Me, R2 = R3 = R4 = 1 was accelerated by irradiation. N.m.r. data of this labile product were consistent with 4rsquo;-iodo-4rsquo;-methoxy- N-methyl-3-oxoisoindoline-l-spiro-lrsquo;-cyclohexa-2rsquo;,5lsquo;-dienes (4a). The two isomeric spirodienyl iodides (4a) C; X = OMe, Y = H were rapidly converted into the dienone (3a) with methanolic silver nitrate in contrast to the methanolysis products obtained by similar treatment of other spiro- dienyl iodides6 In an attempt to dimerise (4a) the mixture, in dry benzene, was irradiated with a medium-pressure mercury lamp 6a through quartz.However, only the dienone (3a) was formed. The transformation was likewise effected by addition of molecular iodine to (4a) in CDC1,. The isomeric spirodienyl iodides (4a) were synthesised from the spirodienone (3a) by sodium S. A. Glover and A. Goosen, J.C.S. Perkin I, 1974, 2353. S. A. Glover and A. Goosen, J.C.S. Perkin I, 1977, 1348. ti D. H. Hey, G. H. Jones, and M. J. Perkins, J.C.S.Perkin 1, 1972, (a)1155; (b) 1162. borohydride reduction to the dienols (4b) which in methanol-sulphuric acid afforded the methoxy-dienes (4c) whose n.m.r. spectra were consistent with reported data.6b Irradiation of the methoxy-dienes (4c) in the presence of t-butyl hypoiodite gave a mixture (n.m.r.) of dienone (3a), unchanged methoxydienes (4c), and spirodienyl iodides (4a). The detection of methoxy-spirodienyl iodides as intermediates in the cyclisation of (la) and the failure to isolate 4'-t-butoxy-spirodienyl iodides from our earlier cyclisations of N-methyl-biphenyl-2-~arboxamide,~~~are in accord with the more favourable dealkylation of the corresponding t-butoxy- spirodienyl iodides to give (3a). The formation of the spirodienone (3a) from the 4'-iodo-and 4'-chloro-N-methylcarboxamides( 1 c) and (Id) is proposed to arise from the corresponding t-butoxy-spirodienyl halides (5)which rapidly decompose to the dienone (3a).Comparative rate studies showed that, like the parent amide, N-methylbiphenyl-2-~arboxamide,~the cyclis-ation of 4'-substituted amides (la, c, and d) gave pro- ducts by pseudounimolecular parallel reactions. The relative rate constants at 26 "C (Table 2) indicate that TABLE2 Rate constants for cyclisation at 26 "C 104k (overall) 104k(Ar,-5) 104k(Ar,-6) k(Ar,-5) Substrate S-1 S-1 S-1 h(Ar,-6) (la) 6.7 5.80 1.00 6.0 (11) 1.5 1.oo 0.50 2.0 (14 0.53 0.45 0.10 4.7 (Id) 0.25 0.21 0.04 4.9 the 4'-substituents facilitate cyclisation at the 1'-position in the expected order for substitution involving an electrophilic radical.Further, radical stability in the transition state is not a dominant effect. 7 R. S. Neale, Synthesis, 1971, 1, 1; S. A. Glover, A. Goosen, D. Graham, and J. Lovelock, J. S. African Chew. Inst., 1976, 29, 46. J.C.S. Perkin I The mode of cyclisation was altered dramatically when a 3'-methoxy group was present (lg). The mixture contained only Ar2-6 cyclisation products, 2-methoxy-N- methylphenant hridone (2g) and 4-methoxy-N-methyl- phenanthridone (6), formed in similar yields, thus providing evidence for a considerable electronic effect in the radical cyclisation process. The lack of selectivity in this experiment contrasts with that found by Hey et al.in the persulphate oxidation of (lg) .l 2'-Methoxy-~ubstituted amides (lh) and (li) gave nearly quantitative yields of 2'-methoxy-spirodienones L(3c) and (3d)l in accord with the electronic effect of the 2'-substituent. However, with this substrate the steric (5) X = I or CI effect of the 2'-substituent also favours orthogonality of the aryl rings. A similar steric effect was found in the cyclisation of ~is-o-methoxy-~Y-methylcinnamamide.~ The formation of the methoxy-spirodienones (3c) and (3d)l is consistent with the ready formation of the resonance-stabilised carbocation (8; K = H or Me) which is solvolysed to give the diether (9; R = H or Me). Conversion to the methoxy-dienone (3c) and (3d)l upon irradiation with t-butyl hypoiodite 4,5is due to the easier elimination of the t-butyl group as opposed to the methyl group from the intermediate diether carbocations.In an attempt to synthesise the linear dienone (13; R = H) (13; K = Me) was obtained by Hey et al. from persulpliate oxidation of (111) l, (li) was irradiated with t-butyl hypoiodite (from potassium t-butoxide and iodine monochloride 4.5)-iodine in carbon tetrachloride, which unlike t-butyl alcohol could not solvolyse the intermediate (8; R = H). Only starting material was recovered whereas in a control experiment,with t-butyl alcohol as solvent, the same reagents effected complete conversion into dienone (3d). In addition, although biphenyl-2-carboxamide and N-methylbiphenyl-2-car-boxamide showed a preference for Ar2-6 cyclisation in non-trapping media (benzene or CC1,) the absence of394 l-methoxy-phenanthridone (11; R = H) in the reaction of the 2'-methoxy-amide (li) supports our proposal that Ar,-6 cyclisation requires a planar conformation of the aromatic rings. The Ar,-5 cyclisation in this case is prob- ably reversible in non-trapping media and a hetero-lytic ring opening of (7; K = H) is suggested.The 2'-methoxy-N-methyl-3-oxoisoindoline-1-spire-1'-cyclo-hexa-2',5'-dienyl radical (12; R = Me) does not re-arrange even at high temperatures (130 "C).8 The D. H. Hey, G. H. Jones, and M. J. Pcrkins, J.C.S. Perkin I, 1972, 113. difference in reactivity in t-butyl alcohol and carbon tetrachloride'was not due to different solubilities of the oxidant, iodine, in the two solvents since the formation of the dienone (3d) from (li) in t-butyl alcohol with t-butyl 0 hypoiodite was relatively unaffected when the reaction was carried out with or without additional iodine.In contrast to the results obtained from the analogous persulphate oxidations lp2 no demethoxylation of the 2'-methoxy substrates was observed and cyclisation was in all cases through nitrogen. The mode of cyclisation of all the substrates was predictable on the basis of elec- tronic and steric effects. EXPERIMENTAL M.p.s were determined with a Kofler hot-stage apparatus. 1.r. spectra were run on Unicam SP 200G and SP 1000 spectrometers. Hydrogen-1 n.m.r. spectra (60 MHz) were recorded with a Perkin-Elmer R12A spectrometer, with tetramethylsilane as internal standard and mass spectra (A.E.I.MS 9 instrument) were recorded at the N.C.R.L./ @ R. L. Dannley and M. Sternfield, J. Amer. Chem. Sac., 1954,76, 4543. lo T. Muroi, Nippon Kagaku Zasshi, 1956, 77, 1084 (Chem. Abs., 1959, 53, 5250a). C.S.I.R. laboratories in Pretoria. Irradiations were per-formed with a 1000 W tungsten lamp unless otherwise specified. Silica gel for preparative t.1.c. was Merck HF 254 + 366 type 60 (nach Stahl). f (3) c; R = Me d; R'= H Preparation of Carboxylic Acids and Carboxavnides.-The following were prepared from 4'-arninobiphenyl-Z-carb-oxylic acid, synthesised by reduction (H,-PtO) of 4'-nitro- biphenyl-2-carboxylic acid, by standard procedures.(a) 4'-Methoxybiphenyl-2-carboxyEic acid, G(CDC1,) 3.78 (3 H, s), 6.83 2 HI d, J(AB) 10 Hz, 7.1-7.6 (5 H, m), and 7.77-7.97 (1 H, m); wmx, (CHC1,) 840, 1 625, 1 712, and 3 OOObr cm-1. The amide (lb) (plates from benzene-light petroleum, b.p. 40-60 "C) had m.p. 112-114 "C (1it.,lo 114-115 "C). The N-methylamide (la) (prisms from ethanol) had m.p. 13G132 "C (lit.,l 131-133 "C). (b) 4'-IodobiphenyZ-2-curboxyZic acid l1,l2 (plates from benzene), m.p. 189-193 "C, M+ 324, G(CDC1,) 7.0-8.15 (8 H, m), and 10.1 (1HI broad s); wmaX. (CHC1,) 830, 1 710, and 3 600br cm-l. The N-methylamide (lc) (prisms from benzene) had m.p. 168-172 "C, Mf 337; G(CDC1,) 2.71 (3 H, d), 5.55 (1 H, broads), 7.17 2 H, d, J(AB) 9 Hz, 7.3-7.7 l1 A.H. Blatt, Org. Synth., 1963, COIL Vol. 11,p. 355. l2 W. J. Hickenbottom, ' Reactions of Organic Compounds,' Longmans, 3rd edn., 1959. (4 H, m), and 7.78 2 H, d, J(BA) 9 Hz; vmax. (CHCl,)1 660 and 3 465 cm-1. (c) 4'-Chlo~obiphenyl-2-carboxylicacid 12913 (needles after sublimation), m.p. 162-164 "C (1it.,lo 162-164 "C). The N-methylamide (Id) (needles from benzene) had m.p. 147-150 "C, Mf 226; S(CDC1,) 2.69 (3 H, d), 5.6 (1 H, broad s),and 7.29-7.69 (8 H, m) ; vmax. (CHCl,) 842, 1 663, and 3 465 cm-l. (d) 4'-Cyanobi~henyZ-2-carboxylicacid l2 (prisms from ethanol), m.p. 215-218 "C, M' 223; vmax. (CHC1,) 846, 1 712, 2 245, and 3 600br cm-l. The N-methylamide (If) needles from chlorof orm-benzene-li gh t petroleum (b.p . 40-60 "C) had m.p. 167-168 "C, MS 236; 8(CI)Cl,) 2.76 (3 H, d), 5.55 (1 H, broad s),and 7.32-7.86 (8 H, m) ; vmax. (CHC1,) 850, 1 668, 2 245, and 3 465 cm-l (Found: C, 75.7; H, 5.1; N, 11.9. C1,H1,N,O requires C, 76.25; H, 5.1; N, 11.85). (e) 4',N-DimethyZbiphenyl-2-carboxamide( le). 4'-Cyano-N-methylbiphenyl-2-carboxamide (2g) was reduced to the 4'-formyl analogue (1.2 g) (sodium dihydrogen phosphite over Raney nickel 14)which crystallised from benzene-light petroleum (b.p. 40-60 "C), m.p. 166-167 "C, amp;If 239; G(CDC1,) 2.75 (3 H, s), 5.5 (1 H, broad s), 7.4-8.07 (8 H, m), and 10.13 (1H, s); vmax. (CHC1,) 848, 1665, 1 710, and 3 465 cm-l. Clemmensen reduction of 4'-formyl-N-methyl- biphenyl-2-carboxamide ( 1.2 g) gave 4',N-dimethylbi-phenyl-2-carboxamide ( le) prisms from benzene-light petroleum (b.p.60-80 "C), m.p. 107-109 "C, M+ 225; S(CDC1,) 2.37 (3 H, s), 2.65 (3 H, d), 5.5 (1 H, broad s), and 7.15-7.80 (8 H, m); vnIax. 830, 1 660, and 3 465 cm-l. (f) 3'-Methoxy-N-met/~ylbi~/~enyZ-2-carboxanzide( 18). A mixture of methyl 3'-nitrobiphenyl-2- and 4-carboxylates (12 g; 47 and 38, respectively), isolated by column chromatography from the Goniberg reaction of m-nitro-aniline (50 g) with methyl benzoate (1 1),l5 was saponified (aqueous 10 sodium hydroxide) to give, after acidification, a component soluble in CH,Cl,, 3'-nitrobiphenyl-2-carboxylic acid (5 g), m.p. 154-155 "C plates from CHC1,- ether-light petroleum (b.p. 40-60 "C) (lit.,I5 m.p.155- 157 "C). The N-methylamide crystallised from benzene-light petroleum (b.p. 80-100 "C) as needles, m.p. 118- 120 "C, M' 256; G(CDC1,) 2.29 (3 H, s),6.1 (1 H, broad In), 7.26-7.8 (6 H, m), and 8.03-8.2 (2 H, m); vnIax. (CHC1,) 1552, 1680, and 3 500 cm-l (Found: C, 66.0; H, 4.9; N, 10.8. Cl4HlZN2O3 requires C, 65.6; H, 4.9; N, 10.8). The amide (2 g) was reduced (H,-PtO) to 3'-alninobiphenyl- 2-carboxylic acid (plates from benzene), m.p. 162-164 "C, M+ 226 (Found: C, 73.8; H, 6.2; N, 12.4. Cl,H14N,0 requires C, 74.3; H, 6.25; N, 12.4). The corresponding diazonium sulphate was converted into 3'-methoxy-N-methylbiphenyl-2-carboxyamide (prisms from benzene), m.p. 91-93 "C (lit.,l 92-94 "C). (g) 2'-MethoxybiphenyZ-2-carboxamides (lh and i).Bi-phenyl-2-carboxylic acid (10 g) was oxidised to benzo-coumarin (5 g) l5which, after refluxing in alkaline dimethyl sulphate, afforded 2'-methoxybiphenyl-2-carboxylic acid (2.71g),S(CDC1,) 3.64 (3 H, s),6.7-8.0 (8 H, m), and 11.61 (1 H, s); vmax. (CHC1,) 1 702 and 3 060br cm-l. The N-methylamide plates from benzene-light petroleum (b.p. 40-60 "C) had m.p. 113-115 "C (lit.,l 113-115 "C). The * Doublet carbonyls are diagnostic of N-alkyl-3-substituted phenanthridones (cf. ref. 16). l3 H. Gilman and A. H. Blatt, Org. Synth., Coll. Vol. I, 1964, p. 162. J.C.S. Perkin I alnide had m.p. 107-108.5 "C, M+ 227, S(CDC1,) 3.65 (3 H, s); v,,,. (CHCl,) 1 685, 3 425, and 3 550 cm-l (Found: C, 73.3; H, 3.7; IT, 6.2. C14Hl,NOz requires C, 73.9; H, 5.75; h-,6.24,).Reactions. General procedure. Cyclisation of Substituted Amides.-t-Butyl hypochlorite (! .28 g, 11.9 mniol), potas- sium t-butoxide (1.33 g, 11.9 mmol), and the amide (2.37 mniol) were added in the dark at 15 min intervals to a stirred mixture of iodine (3 g, 11.9 nimol) and t-butyl alcohol (25 nil). The mixture was irradiated at room temperature, then shaken with excess of aqueous sodium thiosulpliate, which was extracted with chloroform (2 x 50 rnl). Concentration of the combined extracts gave solids or gums which were analysed by n.m.r., and purified by crystallisation or separation on preparative thin-layer plates (silica gel). (a) 4'-~netho~r~~b~~/zenyl-2-carboxa~ide(lh). This gave 3- oxoisoindoline- l-spiro- l'-cyclohexa-2',5'-dien-4'-one (68y0), identical (n.m.r, i.r., t I.c., 1ii.p.) with an authentic speci- men,4 and a minor amount of impure solid which contained a 8-lactam v,~~~,.(CHC1,) 1 670 cm-l.(b) rbsol;T-i~zethyZ-4'-inet/zoxyb~p/~enyl-2-ca~boxalnide(la).This gave after chromatography N-methyl-3-oxoisoindo- line-l-spiro-l'-cycloliexa-2',5'-dien-4'-one (65Y0),m.p. 218- 219 "C (lit.,4 m.p. 218-219 "C), and the less polar 3-metlioxy-N-metliylplienanthridone (1 7",) (similar spectro- scopically to that reported by Hey et aZ.16),M+239 ; S(CDC1,) 3.78 (3 H, s), 3.95 (3 H, s), 6.82-7.1 (I H, d, and 1 H, dd), 7.27-8.0 (2 H, m,) 8.24 (2 H, d), and 8.58 (1 H, d); vlllaX. (CHC1,) 1 615 and 1 650 cm-l (doublet, carbonyl).* (c) 4'-lodo-N-i~zetliylbzpheny1-2-carboxal?ze ( lc).This afforded N-me thyl- 3-oxoisoindoline- 1 -spire-1 '-cyclohexa- 2', 5'-dien-4'-one (TO:,) and 3-iodo-N-nzet/zyl~lienanthridone ( 170,/,) which crystallised from benzene-ether as needles, m.p. 149-152 "C, illt 335; G(CDC1,) (3 H, s), 7.2-8.58 (7 H, m); vInax. (CHCI,) 1 600, 1 612, and 1 650 cm-l (Found: C, 50.4; H, 3.0; X, 3.9. C14Hl,IN0 requires C, 50.15; H, 3.0; N, 4.2). (d) 4'-C/iloro-n'-nzetl~ylbi~lienyl-2-carboxanzide(Id). This gave A'-methyl- 3-oxoisoindoline- 1 -spire-1'-cyclohexa-2', 5'-dien-4'-one (409'0, n.m .r.) , 3-chloro-N-methylphenanthri-done (170/;, ; n.m.r.),m p. 129-130 "C ether-light petrol- eum (b.p. 40-60 "C), Mt 243; S(CDC1,) 3.76 (3 H, s), 7.18-7.97 (4H, m), 8.18 (2 H, d), and 8.57 (1 H, dd); vmaX.(CHCI,) 1 608 and 1 650 cn1-l (doublet, carbonyl) ; and a minor quantity of spiro-components vnlaX. (CHC1,) 1700 cm-l. (e) 4',T?iT-Di~zetlzylbi~/zenyl-2-carboxanzide (le). This afforded a complex mixture which was separated into 3,N- dimethylphenanthridone ( 15) (needles from benzene), m.p. 110-112.5 "C, Mi223; G(CDC1,) 2.39 (3 H, s), 3.64 (3 H, s), 7.05 (2 H, overlapping s and d), 7.25-8.2 (4 H, m), and 8.51 (1 H, dd); v,,, (CHC1,) 1 614 and 1 650 cm-l (doublet, carbonyl) (Found: C, 79.8; H, 5.6; N, 6.2. C15-H,,NO requires C, 80.7; H, 5.8; N, 6.2576). (f) 4'-Cyano-N-nzetla~ylbi~/ienyl-2-carboxamide(If). This was recovered unchanged from the reaction mixture. (g) Identification of 4'-iodo-4'-metlzoxy-N-methyZ-3-oxoiso-indoline- 1-spiro- l'-cyclohexa-2', 5'-dienes (4a).4'-Methoxy- N-methylbiphenyl-2-carboxamidewas treated as in the l4 0,G. Backeberg and B. Staskun, J. Chem. SOC.,1962, 3961. l5 G. W. Kenner, M. A. Murray, and C. M. B. Taylor, Tetra-hedron, 1957, 1, 269. l6 D. H. Hey, G. H. Jones, and M. J. Perkins, J.C.S. Perkin I, 1972, 105, 1150. general procedure. A sample worked up after 1 h was analysed by i.r. vmax. (CHCl,) 1 695vs (y-lactam) and 1685 cni-l (shoulder, dienone) and n.m.r. which, from integration of N-methyl resonances, showed it to contain starting amide 6 2.7 (d), 13O/O, spirodienone (6 3.01, 17), 3-methoxy-N- methylphenanthridone (6 3.76 and 3.95, 14.3y0), and iso- chloride (0.284 g)J and excess of iodine in t-butyl alcohol (50 ml).Irradiation for 2.5 h at room temperature gave 2lsquo;- methoxy-dienone (3d) (26) and starting material (74). (v) The experiment as in (iv) was repeated, except that iodine was omitted, and gave 2rsquo;-metlioxy-dienone (3d), (22) and starting material (78). meric 4rsquo;-iodo-4rsquo;-methoxy-N-methyl-3-oxoisoindoline-l-spiro-lrsquo;-cvclohexa-2rsquo;,5rsquo;-diene(4a) 6 2.95 (3 H, s), 3.47 and 3.42 (3 H, 2 x s), 5.56 (2 H, m), and 6.32 (2 H, m) 56:/,. The mixture, in methanol (5 ml) was treated with methanolic silver nitrate, diluted (30 ml) and extracted with dichloro- methane (2 10 nil). Concentration afforded a mixture (n.m.r.) of spirodienone (3a) (6 3.01, 73) and 3-methoxy- N-methylphenanthridone (6 3.75, 1476).The reaction mixture upon work-up gave a straw-coloured gum (0.63 g) which was divided into three portions. (i) Addition of iodine to an n.m.r. sample in CDCl, effected rapid conversion of spirodienyl iodides (55) into dienone (3a) (730,;). (zi) lsquo;The mixture (0.5 g) in dry benzene (70 ml) in a quartz flask was irradiated for 2 h with a medium-pres-sure mercury lamp. -4nalysis (n.m.r.) of the product showed formation of dienone (3a) (73). (iii) A portion of the mixture left (12 h) in benzene contained (n.ni.r. after work-up) one of the isomeric spirodienyl iodides (4a) 6 2.95 (3 H, s), 3.47 (3 H, s), 5.56 (2 H, d, J 10 Hz), and 6.32 (2 H, d, J 10 Hz), 42y0, dienone (6 3.01, 31y0), and 3-niethoxy-N-methylphenantliridone(6 3.76, 14).(11) Rate studies. 4rsquo;-Methoxy-4rsquo;-iodo-and 4rsquo;-chloro-N-methylbiphenyl-2-carboxamides (la, c, and d) and N-niethylbipl1cnyl-2-carboxamide(lj) were treated at 26 ldquo;C. The reaction was monitored as bef~re.~The overall first- order rate constants Jz(overall) were obtained from plots of lnaniidej 7rsquo;s. time while k(Ar1-5) and K(Ar,-6) were found from the plots of total spiro-products concentration and phenanthridone concentration vs. l -exp(-kt) (Table 2).(i) 3-Methoxy-N-nzethylphenanthridone (lg). This afforded, after irradiation (2.5 h) and chromatographic separation, 2-methoxy-N-niethylphenanthridone, m.p. 157-159 ldquo;C (1it.,17 161 ldquo;C), vmax. (CHC1,) 1 642 cm-l, and 4-rnethoxy-A-methylphenanthridone, m ,p. 12 1-1 23 ldquo;C (lit.,17 125 ldquo;C), v,,,,~~,(CHC1,) 1 643 cm-l, in 23 and 17 yield, respectively.(j) (2) 2rsquo;-,Methoxybiphenyl-2-carboxanzi~e( li). This was converted quantitatively (2.5 h) into 2rsquo;-methoxy-3-oxo-isoindoline-l-spiro-lrsquo;-cyclohexa-2rsquo;,5rsquo;-dien-4rsquo;-one(3d), m.p. 246-248 ldquo;C, 241; G(CDC1,) 3.58 (3 H, s), 5.73 (1 H, d, J 0.5 Hz), 6.36 (2 H, overlapping s and cl, J 0.5 Hz), and 7.09-7.95 (4 H, In);vmax, (CHCl,), 1 600, 1 669, 1 719, and 3 462 cm-1 (Found: C, 69.4; H, 4.6; N, 5.8. C14Hl,Tcrsquo;O, requires C, 69.7; H, 4.6; N, 5.8). (ii) The amide (li) (0.4 g), t-butyl hypoiodite from potassium t-butoxide (0.68 g), iodine chloride (0.85 g), and iodine (2.55 g)in carbon tetrachloride (40 nil) was irradiated. Work-up after 2.5 h afforded unchanged amide. (iii) The experi- ment as in (ii) repeated with t-butyl alcohol as solvent gave the dienone (3d) quantitatively. (iv) The amide (li) (0.4 g) was added to an equimolar amount of t-butyl hypoiodite from potassium t-butoxide (0.202 g) and iodine (k) 2rsquo;-MetJzoxy-N-methylbiphenyl-2-carboxanzzde ( 1h).This gave 2rsquo;-methoxy-N-methyl-3-oxoisoindoline-l-spiro-1rsquo;-cyclohexa-2rsquo;, 5rsquo;-dien-4rsquo;-one (96y0), m.p. 230--23 1 ldquo;C (lit.,6a232-236 ldquo;C),Af+ 255; G(CDC1,) 2.9 (3H, s),3.6 (3 H, s), 5.82 l H, d, J(XA) 1.5Hz1, 6.21 l H, d, J(I3A) 9.5Hz1, and 6.47 l H, dd, J(AI3) 9.5, (AX) 1.5 Hz; v,~,~,~,(CHC1,) 1602, 1669, and 1700 cm-l (Found: C, 70.5; H, 5.0; N, 5.7. C,,H,,NO, requires C, 70.6; H, 5.15; N, 5.5). Synthesis of 4rsquo;-Iodo-4rsquo;-methoxy-N-methyl-3-oxozsoindoline-l-spiro-lrsquo;-cyclohexa-2rsquo;,5rsquo;-dienes(4a).-A mixture of 4lsquo;-methoxy-N-methylbiphenyl-2-carboxamide(la) ( 13y0), 3- methoxy-N-methylphenanthriclone (2a) ( I40/)),and N-methyl-3-oxoisoindoline-1-spiro- 1 rsquo;-cyclohexa-2rsquo;, 5rsquo;-dien- 4rsquo;-one (3a) (73oj,) (0.60 g) in absolute ethanol (25 ml) was treated with NaBH, (0.2 g) in ethanol (10 ml). After 20 min the mixture was diluted (5 acetic acid solution, 20 ml), and extracted with CHCl, (2 x 20 ml).The extract was dried (Na,S04) and concentrated to a gum (0.56 g) which was a mixture (n,m.r.) of amide (13?;), phenan- thridone ( lay0), and isomeric 4rsquo;-hydroxy-S-methy1-3-oxoisoindoline- 1-spiro- lrsquo;-cyclohexa-2rsquo;,5lsquo;-dienes(4b) (73) identical (n.m.r., t.1.c.) with an authentic mixture., The mixture in methanolic sulphuric acid (2 nil acid in 25 ml alcohol) was refluxed for 6 min, diluted, and extracted with CH,Cl, (2 x 20 ml) which gave a gum (0.42 h).Analysis (n.m.r.) of the mixture showed amide (127$), Ir~amp;hoXy-phenanthridone (22y0), and isomeric 4rsquo;-methoxy-N-niethyl- 3-oxoisoindoline- 1 -spire-1rsquo;-cyclohexa-2rsquo;, 5rsquo;-dienes (4c)(66) sb G(CDCl,) 2.84 and 2.93 (3 H, 2 x NMe s), 3.42 and 3.46 (3 H, 2 x metlioxy s), 4.53 (1 H, m), and 5.47 and 6.33 (4 H, 2 x overlapping dd). The mixture (0.2 g) in t-butyl alcohol (5 ml) was added to a solution of t-butyl hypoiodite from iodine (2.05 g, 0.0081 mol), t-butyl hypo- chlorite (0.291 g; 0.002 7 moll, and potassium t-butoxide (0.302 g, 0.002 7 mol) in t-butyl alcohol (10 ml) and the product was irradiated for 0.75 h at 26 ldquo;C. Analysis (n.ni.r.) of the mixture after work-up showed amide (la) 6 2.7 (d); 7, 3-methoxy-N-methylphenanthridone (2a) G 3.76 (s); 21y0, methoxy-dienes (4c) G 2.84 (s); lo0/,, spiro-dienone (3a) (6 3.01; 28y0), and 4rsquo;-iodo-4rsquo;-niethoxy-dienes (4a) a 2.95 (s), 5.58 and 6.33 (2 x d, J 10 Hz); 32y0. Treatment with niethanolic silver nitrate as above gave (n.m.r.) amide (la) (7Y0), phenanthridone (2a) (22:4), niethoxydienes (4c) (1 1 yo),and spirodienone (3a) (607;). We thank the South African Council for Scientific and Industrial Research for financial support and the recording of mass spectra (Dr. R. H. Hall). 7/1543 Received, 26th August, 19771 l7 D. H. Hey, J. A. Leonard, C. W. Rees, and A. I. Todd, J. Chem. SOC.(C). 1967, 1513.
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