Formation of heterocyclic compounds from 1,3-diazabuta-1,3-diene derivatives

摘要

1528 J.C.S. Perkin IFormation of Heterocyclic Compounds f rom 1,3-Diazabuta-l,3-dieneDe r iva t ivesBy lsamu Matsuda," Sakae Yamamoto, and Yoshio Ishii, Department of Synthetic Chemistry, Faculty ofEngineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464, JapanN-Trimethylsilyl(diphenylmethylene)amine gives quantitatively various open-chain 1.3-diazabutadienes (V) bycoupling with benzimidoyl chlorides. The 1.3-diazabutadienes react with isocyanates, diphenylketen, diketen (4-methyleneoxetan-2-one), and dimethyl acetylenedicarboxylate to give the 3.4-dihydro-I ,3,5-triazin-2 (1 H ) -ones(VI), the azetidinone (VIII), the dihydro-1.3-oxazinones (XII), and the pyrimidinone (XIV), respectively.1 ,~-CYCLOADDITION reactions of heteradienes would beexpected to be applicable to the synthesis of heterocycliccompounds containing two or more heteroatoms.Al-though many examples of dienes containing two nitrogenatoms are reported l y 2 there are few reports of the 1,3-di-azabuta-l,3-diene (N=C-N=C) ~ y s t e m . ~ One clear caseof cycloaddition of the N=C-N=C linkage, in the form-amidine derivatives (I), is reported, in which one C=Nbond is part of a heterocyclic ring.4We have reported that the 1 : 1 insertion product (11),M. Lora-Tamayo and J. L. Soto, ' 1,4-Cycloaddition Reac-W. Bartman, Chem. Bey., 1967, 100, 2938.C . Grundmann, G. Weisse, and S. Seide, Annalen, 1952,R. Richter and H. Ulrich, Chem. Bey., 1970, 103, 3525.tions,' ed. J. Hamer, Academic Press, New York, 1967, p. 179. 577, 771976 1529obtained in the reaction of N-trimethylsilyl(dipheny1- butadienes (V) with 1 equiv.of isocyanate in benzene,methy1ene)amine with phenyl isocyanate, behaves as a the dihydrotriazinones (VI) were obtained in good yieldsynthetic equivalent of the N=C-N=C system in that its as a result of 4 -+ 21 cycloaddition. The presence of anreaction with the dienophile A=B gave the formal 1,4- excess of isocyanate did not give any 2 : 1 cycloadduct,cycloaddition product (III).g*6 In this paper a simplified such as has been reported.2 The 1,3,5-triazinone struc-method for preparing 1,3-diazabutadienes and their ture (VI) was confirmed by the i.r. spectrum ( G O andHNMez (11 X = N or S (,/,C-N=C x bsol;PhPhcycloadditions to give four- or six-membered hetero-cycles, depending on the dienophiles, are described.RESULTS AND DISCUSSIONPye9aYation of 1,3-Diaxabutadiertes.-The reaction ofN-trimethylsilyl(diphenylmethylene)amine with 1 equiv.of benzimidoyl chloride in benzene gave quantitativelyC=N stretching bands at 1 672-1 700 and 1 630-1 642cm-l, respectively). A 1 : 1 cycloadduct of the 1,3-di-azetidinone type from Z + 21 addition of isocyanatewith either C=N bond would show a G O stretching bandabove 1 750 cm-l.On the other hand, triazinone deriv-atives obtained from the reactions of isocyanates with2 equiv. of imine have C=O stretching bands at ca. 1 670TABLE 1Results of 4 fYieldsProduct R R' Conditions (I(VIa) Me Ph C6H6, reflux, 34 h 90(VIb) Et P h C,H,, reflux, 30 h 100(VIc) P h Ph C6H6, reflux.25 h 85(VId) Me Me CeH,, 95 "c," 180 h 68(VIe) Ph Me CH2C12, 45 OC," 173 h 78a In a21 cycloadditionsRecr ys t .jolvents M.p. ("C)MeOH 188-190MeOH 199-201MeOH 182.5-1 83.5MeOH 213.5-215sealed tube,EtOH 193.5-195-r (CDCl,) vmax./cm-' (KBr)6.98 (3 H, s)9.37 (3 H, t)6.36 (2 H, q)7.25 (3 H, s)7.06 (3 H, s)7.21 (3 H, s)1 686 (CZO), 1 640 (C:N)1 672 (C:O), 1 630 (C:N)1692 (CO), 1641 (CN)1688 (C:O), 1640 (CN)1700 (CIO), 1642 (C:N)the benzamidine derivatives (V), with elimination oftrimethylsilyl chloride. The same products (Va and c)were obtained from the reaction of diphenylmethylene-amine with benzimidoyl chloride in the presence oftriethylamine or 1,8-diazabicyclo5.4.OJundec-7-ene asacceptor of the hydrogen chloride generated.Howeverfollowing advantages: (a) no need for a hydrogencm-l.7 Although compounds (V) behaved as a hetera-1,3-diene toward isocyanates, they were less reactive thanbsol; ,Ph R' Ph, ,PhPhN//C N I I "Cbsol;/'0 II Ph /cbsol;N/c-o( i i i ) I + c - II 1use of N-trimet hylsilyl( diphenylmet h ylene) amine has thechloride acceptor; (b) isolation of (V) from the reaction (Y)ph I C * N RR(YI) R = Me,Et, or PhR'= Me o r Phthe analogues (I) because of the absence of the electron-(Y1 donating dimethylamino-group. This suggests that thefirst step in the cyclization is nucleophilic attack of theterminal imino-nitrogen atom at the central isocyanate2 + 21 CycZoadditiosz.-The reaction of compoundJ.P. Chupp and E. R. Weiss, J . Org. Chem., 1967, 33,Th Ph,C=N-SiMe, + I?:C=NR .+. RN=C-N=CPh, ( i i la;R=Me b;R = E tc ; R = P hmixture before carryingout cycloadditions is unnecessary; carbon The are summarized inand (c) the yield is higher. r4 $- '1 Cyczoaddition.-ln the reactions Of the 6 1. Matsuda, S. bsol; T a ~ ~ ~ a ~ ~ o t o , and Y . Ishii, preceding paper.6 I. Matsuda, K. Itoh, and Y. Ishii, J.C.S. Perkin I, 1972,678. 23571530 J.C.S. Perkin I(Va) with 1 equiv. of diphenylketen proceeded smoothlyat room temperature to give the azetidinone (VIII)quantitatively. The i.r. spectrum showed the presenceof a p-lactam (v- 1 746 cm-l) and a C=N double bond(1 648 cm-l). The unusual high-field proton resonanceof the N-methyl protons (T 8.39) could be caused by thediamagnetic anisotropy of the phenyl rings in the di-phenylmethyleneamino-group.The formation of thedihydropyrimidinone (IX) would be expected by analogyP h C=C= 0excludes the possibility of the 1,3-oxazinone structure(XIII) which might be expected to be formed throughthe zwitterionic intermediate (X). The appearance ofthe ions M+ - (MeN=CPh + H) (m/e 263) and 263 -NCO (mle 221) indicates the presence of a pendantN-methylbenzimidoyl group.The reaction path may be deduced from the structureof the product. Initial nucleophilic attack of the ter-minal nitrogen atom of (V) on the carbonyl carbon atomPhDc)SCHEME 1P t l ,C=N,Ph/C=NR ( a)lbsol;I 4- - + I C=O I_ MefMea ; R = M eb ; R PhSCHEME 2with the reactions with isocyanates.The differencebetween the reactions may be explained by steric factors:nucleophilic attack of C-6 a t C-1 to form (IX) would beinhibited by the four phenyl substituents.Reactions of Diketen (4-MethyZeneoxetan-2-orte) .-A dif-ferent type of heterocyclic compound, a 1 ,amp;oxazinone(XII), was obtained in the reaction of the heteradienes(V) with 1 equiv. of diketen. The n.m.r. spectra of(XIIa and b) showed C-methyl (7 8.51 and 8.46) andvinyl proton ( T 5.32 and 5.17) signals consistent with theassigned structure.8~~ The mass spectrum of (XIIa)of diketen to give the zwitterionic intermediate (X) ispresumably followed by cyclization involving attack atthe carbonyl carbon atom of (X) (Scheme 2). The reactionresembles that of the urea (11) with diketen, which isinitiated by nucleophilic attack of the amino-nitrogenatom of the urea on the carbonyl carbon atom of diketen.6Reaction of the Heteradiene (Vc) with Dimethyl Acetylene-dicarboxpamp;.-The reaction of (Vc) with 1 equiv.ofdimethyl acetylenedicarboxylate was carried out inethanol with the aim of effecting a pyrimidine synthesisby a 4 + 21 cycloaddition. Two products, the pyrimi-8 T. Kato and H. Sakamoto, Yakugaku Zasshi, 1967, 87, H. Suzuki, I. Matsuda, K. Itoh, and Y. Ishii, Bull. Chern.1322. SOC. Japan, 1974, 47, 27361976 1531dinone (XIV) and bemophenone diethyl acetal (XV),were obtained, but not the expected pyrimidine (XVI).The structure of (XIV) was determined by elementalanalysis and Lr., n.m.r., and mass spectral data.TheEXPERIhlENTALI.r., n.m.r., u.v., and mass spectra were recorded withJASCA IR-403G and IR-S, JEOL C-GOHL, Hitachi 124, andJEOL JMS-O1SG instruments, respectively. N-Trimethyl-Ph, ,OEt (ivlNrsquo;~lsquo;CH C EtOH - I1 I1 i- c c Ph/ lsquo;OEtPhrsquo; lsquo;Nrsquo; lsquo; COzMe PhC0,MeICI + iii __cX = S or NRlsquo;presence of an O-methyl group (T 6.40), a vinyl proton( T 3.37), and two phenyl groups (7 ca. 2.83) was confirmedby the n.m.r. spectrum. Elemental analysis suggestedthe formula C,,H,,N,O,, consistent with the mole-cular ion peak at m/e 306. Other diagnostic frag-ment ions were Mf - PhCN (m/e 203) 203 - CO(m/e 175), and 175 -0Me (m/e 144). The acetal(XV) was identified by comparison (i.r. and n.m.r.spectra) with an authentic sample.The formationof both products involves, formally, a novel 3 + 31cyclization with elimination of a diphenylmethylene and0II0silyl(diphenylmethy1ene) amine and diphenylketen l2 wereprepared according to the literature. All reactions werecarried out under nitrogen. Analyses are summarized inTable 2.Preparation of 1,3-Diazabutadienes.-(i) N-Diphenyl-methydene-W-metlaylbenzumidine (Va) . A solution of N-methylbenzimidoyl chloride (0.38 g, 2.47 mmol) and N-tri-methylsilyl(diphenylmethylene)amine (0.63 g, 2.47 mmol)in benzene (4 ml) was heated for 24 h under reflux. Themixture was evaporated under reduced pressure and theresidue was washed with diethyl ether. The amidine (Va)was filtered off (0.74 g, quantitative) and gave pale yellowTABLE 2AnalysesFound () Re@ ()Formula CC,IHlSN2 84.4C22H2oN, 84.7C26HZON2 86.9C28H23NS0 80.45C2QH25N30 80.95C,SH,,N3O 82.55CZ8HZ,N,O 80.7CS5HZ8N20 85.45C25H!22N202 78.4C3oHz4NzO2 80.7ClSHIP2O3 70.8C23H21NS0 77.75a methoxy-group.Similar elimination of a methoxy-group from dimethyl acetylenedicarboxylate to givecyclic compounds has been reported in the condensationof thiourea and guanidine derivatives with dimethylacetylenedicarboxylate reactions (v) .loJ1 The reaction(iv) thus has good precedent.lo J. MT. Lown and J . C. N. Ma, Calzad. J. Ckem., 1967, 45,l1 J. W. Lown and J . C. N. Ma, Canad. J . Chem., 1967, 45,939.953.H6.156.655.85.76.055.45.75.456.05.66.754.8ldquo;9.48.857.8510.059.658.7511.8510.055.557.56.259.05lsquo; c84.5584.686.6580.5580.782.6577.780.5585.3578.581.0570.6H6.16.455.65.555.855.255.955.555.755.85.454.6N9.48.957.7510.059.768.7511.810.055.757.36.39.15needles on recrystallization from ethanol-n-hexane (3 : 1 ),m.p.135-136 OC, v,,,. (KBr) 1 627s and 1 614s cm-1 (CN),?r (CDCl,) 7.20 (3 H, s, NMe) and 2.3-2.8 (15 H, m, 3 Ph).When a solution of diphenylmethyleneamine (1.36 g,7.48 mmol), N-methylbenzimidoyl chloride (1.13 g, 7.35mmol), and triethylamine (1.41 g, 15.4 mmol) was refluxedfor 5 h, crude (Va) (1.64 g, 73) was also obtained after theremoval of triethylamine hydrochloride and. evaporation.l2 E.C. Taylor,1972, 52, 36.A. McKillop, and G. H. Hawks, Org. Synth.1532(ii) N-Diphenylmethylene-N'-etJ~ylbewainidiite (Vb) . Simi-larly compound (Vb) was obtained quantitatively fromN-ethylbenzimidoyl chloride (1.03 g , 6.12 mmol) and N-tri-methylsilyl(diphenylmethylene)amiiie (1.65 g , 6.50 mmol)in benzene (5 ml) , as pale yellow needles, n1.p 126.5-127.5 "C(from 90 aqueous ethanol), vmx (KBr) 1 623s and 1 606scm-' (C:N), T (CDCl,) 8.85 (3 H, t, iMe, J 7.0 Hz), 6.81 ( 2 H, q,CH,, J 7.0 Hz), and 2.3-2.9 (15 H, m, 3 Ph).(iii) N-Diphenylmethylene-N'~JieizyIbe~~~amidine (Vc) .Compound (Vc) was obtained quantitatively by the sametreatment from N-phenylbenzimidoyl chloride (0.37 g,1.7 1 mmol) and N-trimethylsilyl(diphenylmet1iylene) amine(0.46 g , 1.79 mmol) in benzene ( 5 ml) , as yellow needles, m.p.142-143 "C (from ethanol), v,, (KBr) 1 626s and 1 609scm-f (CN) .When a solution of diphenylniethyleneniine (2.66 g,14.7 mmol), N-phenylbenzimidoyl chloride (2.75 g, 12.8mmol) , and 1,8-diazabicyclo5.4.0undec-7-ene (DBU) (2.11g, 15.3 mmol) in benzene was refluxed for 3 h, crude (Vc)(2.78 g, 60) was also obtained (after removal of DBUhydrochloride and evaporation).4 + 23 Cycloadditions.-A typical procedurc is describedfor the lieteradiene (Va).Results and reaction conditionsare summarized in Table 1. h solution of (Va) (1.36 g,4.56 mmol) and phenyl isocyanate (0.59 g, 5.01 mmol) inbenzene (5 ml) was heated under reflux. After 36 h thebenzene was evaporated off under reduced prcssure and theresidue was washed with cliethyl ether.Crude 3,4-di-hydvo- 1 -metlzyE-3 , 4,4,6-tetrapheiyZ- 1,3,5-fviazin-2 ( 1H) -one(VIa) was filtered off (1.71 g, 90;;); it crystallized frommethanol as a white powder.Reaction of Diphenylketen with the IIetes.adieize (Va) .-A solution of N-methylbenzimidoyl chloride (0.42 g, 2.32nimol) and N-trimethylsilyl( diphenylmethylene) amine(0.62 g, 2.45 mmol) in benzene ( 3 ml) was heated for 20 hunder reflux. Methylene chloride (4 ml) and diphenylketen(0.38 Q, 2.00 mmol) were added, and the mixture was keptfor 24 11 a t room temperature. The solvent was evaporatedoff under reduced pressure a i d the residue was washed withether. Recrystallization from chloroform-n-hesane (1 : 2)gave prisms of 4-diphenylmetJ~ylenet1mi.pzo-l-methyl-3,3,4-tvi-~~ienylazetidi9z-Z-one (VIII) (82), n1.p. 156-157 "C, amp;(EtOH) 250 nm (log E 4.93), vmx.(KBr) 1746s (C:O) andJ.C.S. Perkin I1648m cm-l (CZN), T (CDC1,) 8.39 ( 3 H, s, NMe) and 2.3-3.2 (25 H , m, 5 Ph).Reactions of Diketerc with the Heteradienes (V) .-(i) 2,3-Dihydro-6-methyl-3-(N-methylbenzinzidoyl) -2 , 2-diphenyl- 1,3-oxazin-4-one (XIIa) . A solution of N-methylbenzimidoylchloride (0.41 g, 2.66 mmol) and N-trimethylsilyl(dipheny1-methy1ene)amine (0.69 g, 2.72 mmol) in benzene was re-fluxed for 20 h. After evaporation, the residue was dis-solved in methylene chloride ( 2 ml) and diketen (0.19 g,2.32 mmol) was added. The mixture was heated for 19 ha t 90-100 "C in a sealed tube.Evaporation, washing withdiethyl ether, and recrystallization from methylene chloride-hexane gave the oxazinone (0.58 g, 65) as white needlesm.p. 261-262 "C, v,, (KBr) 1710s and 1686s (C:O) and1 640s cm-l (GIN), T (CDCl,) 8.51 ( 3 H, s, CMe), 7.15 ( 3 H, s,C=CH), and 2.3-2.8 (15 HI m, 3 Ph).(ii) 2,3-Dihydro-6-methytyl-2,2-dipJ~en~l-3-(N~henylbenz-e'midoyZ)-1, 3-oxazin-4-one (XIIb) . An analogous procedurewith diketen (0.13 g, 1.54 mmol) and (Vc) obtained in situfrom N-phenylbenzimidoyl chloride (0.74 g, 2.18 mmol) andN-trimethylsilyl(diphenylmethylene)amine (0.56 g, 2.22mmol) in benzene, gave the oxazinone (XIIb) (0.39 g, 57)as white needles, m.p. 170-172 "C (from ethanol), vmaK(KBr) 1706s and 1700s (C:O) and 1648s cm-l (CZN),T (CDC1,) 8.46 ( 3 H, s, CMe), 5.17 ( 1 H, s, CH), and 2.3-3.2 (20 H , m, 4 Ph).Reaction of Dimethyl Acetylenedicarboxylate with t hHeteradiene (Vb).-An ethanolic solution (20 ml) of (Vb)(0.25 g, 0.69 mmol) and dimethyl acetylenedicarboxylate(0.10 g, 0.70 mmol) was heated for 48 h under reflux. Theethanol was evaporated off under reduced pressure. Theresidue was washed with diethyl ether and the product wasfiltered off and recrystallized from benzene-n-hexane (1 : 2 )t o give pale yellow needles (as), m.p. 162-163 "C, vmX.(KBr) 1 752s and 1 656s cm-l (C:O), T (CDCl,) 6.40 ( 3 H, s,OMe), 3.37 ( 1 H, s, C=CH), and 2.7-3.1 (20 H, m, 4 Ph).Benzophenone diethyl acetal (0.09 g, 53) was obtainedfrom the filtrate by evaporation and washing the residuewith 50 aqueous ethanol, as white needles, m.p. 51-52 "C(from 2 : 1 ethanol-water), T (CDC1,) 8.86 (6 H, t, CMe),6.75 ( 4 H, q, OCH,), and 2.4-2.9 (10 H, m, 2 Ph).5/2496 Received, 22nd December, 1975