J. CHEM. SOC. PERKIN TRANS. I 1989 Heterocyclic Mesomeric Betaines. Part 3.' Synthesis and Base-catalysed Exchange Reactions of N-Methyl-5H-pyrrolo[l,2-c]imidazolium Iodide W. David Ollis" and Stephen P. Stanforth Department of Chemistry, The University, Sheffield, S3 7HF, England Christopher A. Ramsden The Research Laboratories, May and Baker Ltd., Dagenham, Essex, England Methylation of 5H-pyrrolo[I ,2-c]imidazole (10) with methyl iodide gave N-methyl-5H-pyrrolo[I ,2-c]imidazolium iodide (11). This salt underwent an unusual base-catalysed exchange of deuterium for hydrogen via a transient dipolar intermediate (9a; Scheme 2). This dipolar intermediate (9a) was trapped with dimethyl acetylenedicarboxylate giving a 2: 1 adduct (21). -Conjugated heterocyclic mesomeric betaines which are isoconjugate with the pentalenyl dianion have been described as heteropentalenes.2-6 Four types of heteropentalene mesomeric betaines have been recognised and designated as types A, B, C, and D2'3 (Scheme 1).The allocation of heteropentalene + (41 (8a) Scheme 1. mesomeric betaines to one of these types is dependent upon the relative location of the two heteroatoms which each formally contribute two electrons to the 7c-molecular orbitals. Types A, B, C, and D have the general formulae (1)-(4), where a-h represent suitably substituted carbon or heteroatoms. The superscripts indicate the number of p-electrons contributed to the n-orbitals by each atom. The structures (5)-(8) depict generalised examples of these heteropentalene mesomeric betaines where X and Y represent heteroatorn~.~.~The investigation now reported is associated with the examination of a new type C system.The first example of a type C heteropentalene was described in 1976 by Potts and Mar~hall.~ Subsequently other systems have been We now describe our work directed towards the synthesis of the novel type C heteropentalene (9). 5H-PyrroloC 1,2-c]imidazole (10) was prepared from imida- zole-4-carbaldehyde by the method described by Antonini, Franchetti, Grifantini, and Martelli.,, The 'H n.m.r. spectrum of this molecule (10)exhibits two singlets (6 6.78 and 7.65) for 1-H and 3-H and an ABX, system for protons 5-H2,6-H, and 7-H. Protons 6-H and 7-H were observed as the AB component of the ABX, system (13~6.52 and 6,6.18, JAB 6 Hz, JAx2 Hz, and JBX 2 Hz): the two protons, 5-H, (6,4.39) were observed as the X, component. When compound (10) was treated with methyl iodide, N-methyl-5H-pyrrolo[ 1,2-c]irnidazolium iodide (11) (91% yield) was formed.The empirical formula (C,H,IN,) of compound (11) was established. The 'H n.m.r. spectrum (CD,OD) of compound (11) showed two singlets, 1-H (6 7.47) and 3-H (6 9.1 l), one singlet for the N-methyl group (64.01) and one singlet for the two protons, 5-H, (6 5.06). Surprisingly, the protons 6-H and 7-H were observed as a 2 H singlet (6 6.82). The coincidental chemical shifts of the protons 6-H and 7-H, and the zero coupling constants between these protons and the two protons, 5-H,, was unexpected.When the 'H n.m.r. spectrum was redetermined in CD,0D-[2H,]nitrobenzene (ca. 1 :1) solution, a narrow multiplet (6 6.75-6.90) was observed for the protons 6-H and 7-H and a multiplet for the two protons, 5-H, (6 5.13). The '3C n.m.r. spectrum (CD,OD) of compound (11) was also unusual in that only six of the seven expected signals were observed. This was attributed to the coincidental chemical shift of atoms C-6 and C-7 (6 137.2). A low intensity signal (6 134.3) was assigned to carbon atom C-7a and signals at 6 55.7 and 37.3 were attributed to the atom C-5 and the methyl carbon, respectively. The two remaining signals were assigned to atoms C-1 (6 113.0) and C-3 (6 119.7). These assignments were confirmed by off-centre double resonance techniques.When a solution ofthe quaternary iodide (11) in CD30D was treated with sodium [2H,]methoxide (ca. 0.18 equiv.) in a 'H n.m.r. tube, no signals that could be associated with the conjugated heterocyclic mesomeric betaine (9) were observed. However, partial exchange of deuterium for hydrogen at posi- tions 3, 5, and 7 in compound (11) was noted (Table 1).Exchange at positions 3, 5, and 7 was incomplete after 24 h. When an additional amount of sodium [2H,]methoxide solution (ca. 0.72 equiv.) was then added and the spectrum redetermined, the following degrees of exchange were apparent: 1-H, 0%; 3-H, 90%; 5-H,, 90%; 6-H, 0%; and 7-H, 90%. Only one of the protons 6-H or 7-H is exchanged for deuterium because the intensity of the singlet signal associated with these two protons decreased by 50%.When a similar experiment was monitored by 3C n.m.r. spectroscopy using off-centre double resonance, the results were complementary to those described above. It was firmly established that deuterium for hydrogen exchange did not occur at positions 1 and 6 (Table 2). If the conjugated heterocyclic mesomeric betaine (9), with its implied delocalisation, was an intermediate in the base-catalysed deuterium for hydrogen exchange, then exchange of the four hydrogen atoms at positions 1, 3, 5, and 7 would have been expected. This is not observed. Exchange occurs only at positions 3, 5, and 7. The absence of exchange at position 1 could, in principle, be associated with low electron density in position 1 in the conjugated heterocyclic mesomeric betaine (9).This rationalisation (pathway A; Scheme 2) cannot be firmly excluded. However, we much prefer an alternative rationalis- ation involving pathway B (Scheme 2). Our preference (pathway B; Scheme 2) is best represented as involving the dipolar structure (9a), in which the 6n-imidazolium grouping is positively charged and aromatic. The corresponding negative charge is associated with a delocalised 4n-allylic carbanionoid system. The structure (9a) is, therefore, associated with a high degree of mesomeric stabilisation. We now consider the mechanism of deuteriation. We propose that the base-catalysed exchange of deuterium for hydrogen at positions 5 and 7 in the compound (11) involves the dipolar intermediate (9a) (pathway B; Scheme 2).A close analogy is provided by the base-catalysed exchange of deuterium for hydrogen of indene (13) in which the base- catalysed exchange is limited to positions 1 and 3.23-26This is clearly a consequence of the retention of 6n-aromatic character by the benzene ring and a separate 4n-allylic carbanionoid system (14). This explains why base-catalysed exchange does not involve the benzene ring of indene (13). It is well known that imidazolium (15), thiazolium (16), and oxazolium (17) cations undergo base-catalysed exchange of deuterium for hydrogen at position 2.27-31The corresponding 0-ylides (18)-(20) have been postulated as intermediates in these exchange proce~ses.~ 2p34 A different exchange process involving an addition-elimination mechanism has been pro- posed for the thiazolium cation (16),35 but a subsequent communication argues persuasively against this me~hanism.~~ We believe that the exchange process at position 3 in compound (I 1) involves the o-ylide (12).With this pathway (pathway B; Scheme 2) for the exchange of deuterium for hydrogen at positions 3, 5, and 7 in compound (ll), it is possible from the 13C n.m.r. spectrum of compound J. CHEM. SOC. PERKIN TRANS. I 1989 2H2D:q l? IDD DID H+,I -D', I -4 D I Table 1. The exchange of hydrogen for deuterium in N-methyl-5H- pyrrolo[ 1,2-c]imidazolium iodide (1 1). Monitored by 'H n.m.r.Scheme 2. spectroscopy Percentage incorporation of deuterium at position a (1 1) to assign the chemical shifts of the carbon atoms C-1 and C-Time 1 -H 3-H 5-H 6-H + 7-H 3 unambiguously. I-H IS not expected to undergo exchange cu. 2 min 0 25 34 20 min 0 89 50 24 h 0 90 85 24 hb 0 90 90 'Determined by integration with an accuracy of & 15%; of further 0.72 equivalents of sodium [2H,]methoxide. 12 with deuterium so, after the exchange process has taken place, 19 the carbon atom C-1 is expected to be observed as a doublet in 30 the off-centre double resonance spectrum. This was observed 50 experimentally. After addition Further evidence that the dipolar structure (9a) is generated as a transient intermediate by treatment of compound (11) with Table 2.The exchange of hydrogen for deuterium in N-methyl-5H-pyrrolo[ 1,2,-c]imidazolium iodide (11). Monitored by I3C n.m.r. spectroscopy Conditions Before addition of base After (22 days) addition of base s = singlet, d = doublet, t = triplet, q Multiplicity of signals associated with chemical shift (8)' 113.0 119.7 55.7 137.2 134.3 37.3 (C-1) (C-3) (C-5) (C-6 and C-7) (C-7a) (CH,)d d t d S 9 d h h d b q = quartet; 'This signal had broadened and could not be observed above the noise level. J. CHEM. SOC. PERKIN TRANS. I 1989 (13) (14) (15) X =NR (18) X = NR (16) X = S 119) x =s (17) X = 0 (20) x =o base has been provided by a trapping experiment. Compound (1 I) and dimethyl acetylenedicarboxylate with an excess of methanolic sodium methoxide at 0°C yielded the 2:l cycloadduct (21) (10% yield).A similar 2: 1 cycloadduct is produced by the reaction of dimethyl acetylenedicarboxylate with the type C hetero-pentalene (22).7 RR Ph -(21) R = COzMe (22) Experimental General experimental directions are given in Part 1 .37 N--Meth~tl-5H-pitrrolo[ 1,2-c]imidazolium Iodide (1l).-To a solution of SH-pyrrolo[ 1,2-c]imidazole (10) (1.17 g) 22 [S 7.65 (1 H, S, 3-H), 6.78 (1 H, S, 1-H), 6.34 (2 H, ABX, system, GA6.52 and 6, 6.18, JAB 6 Hz, J,, 2 Hz, and JBx2 Hz) and 4.39 (2 H, m, ABX, system, JAX 2 Hz and JBx2 Hz)] in methyl acetate (12 ml) was added methyl iodide (1.0 ml). A yellow precipitate immediately formed. The mixture was kept overnight (nitrogen atmosphere) and the yellow solid was then collected giving the title compound (11) (2.52 g, 91%).Recrystallisation from acetonitrileeether gave tan prisms, m.p. 132-1 36 "C (Found: C, 34.0; H, 3.6; I, 51.1; N, 11.0. C,H,IN2 requires C, 33.9; H, 3.7; I, 51.2; N, 11.3x); v,,,.(KBr) 1 565, 1 530, 1 320, 1 140, and 770 cm-'; G(CD,OD) 9.1 1 (1 H, s, 3-H), 7.47 (1 H, s, 1-H), 6.82 (2 H, s, 7-H and 6-H), 5.06 (2 H, s, 5-H), and 4.01 (3 H, s, CH,); G(CD,0D-[2H,]nitrobenzene, cu. 1:1) 9.22 (1 H, s, 3-H), 7.47 (1 H, s, 1-H), 6.75-6.90 (2 H, m, 7-H and 6-H), 5.13 (2 H, m, 5- H), and 4.16 (3 H, s, CH,); G,(CD,OD) 137.2 (C-6 and C-7), 134.3 (C-7a), 119.7 (C-3), 113.0 (C-l), 55.7 (C-5), and 37.3 (CH3).Tetramethyl 4a,8a-Dih~)dro-1 -methyl- 1H- 1,8 b-diazacyclo- pent[cd]azulene-5,6,7,8-tetracarbo.~ylate(21).-To a cooled (0 "C), stirred solution of N-methyl-5H-pyrrolo[ 1,2-c]imi- dazolium iodide (1 1) (0.44 g) and dimethyl acetylenedi-carboxylate (0.80mi) in dry methanol (7 ml) was added (5 min) sodium methoxide solution (1.1 ml) [prepared from sodium (0.20 g) and dry methanol (5 ml)]. The deep red mixture was then stirred (45 min). After evaporation, the residue was purified by preparative thick layer chromatography (silica gel; ether). The yellow band (RFO.U.5) was collected giving a yellow oil which on trituration with di-isopropyl ether gave a solid. Recrystallisation from ethanol-ether gave the title compound (21) (68 mg, 10%) as pale yellow plates, m.p.136-139 "C (Found: C, 56.5; H, 5.2; N, 6.8%; M+*,404. C,,H,,N,O, requires C, 56.4; H, 5.0; N, 6.9%; M, 404); v,,,. 1 720br; G(C6D6) 9.66 (1 H, br s, 5-H), 6.61 (1 H, dd, J4 and 3 Hz, 3-H or 4-H), 6.57 (1 H, s, l-H or 2-H), 6.35 (1 H, s, l-H or 2-H), 5.94 (1 H, dd, J 4 and 3 Hz, 3-H or 4-H), 3.82 (3 H, s, OCH,), 3.52 (3 H, s, OCH,),3.46(3 H, s,0CH3),3.32(3 H,s,OCH,),and 2.58(3 H, s, NCH,). Base-cutalysed E-xchange of Hydrogen for Deuterium in N- Metlzj+ 5 H-pyr rolo[1,2-c] im idazolium Iodide (11).--Monitored by 'H y1.m.r. spectroscopy. To a solution of N-methyl-5H- pyrrolo[ 1,2-c]imidazolium iodide (11) in [2H,]methanol (0.5 ml) was added sodium [2H,]methoxide solution (0.18 equiv.) [prepared from sodium (30 mg) and [2H,]methanol (0.25 ml)].The 'H n.m.r. spectrum was determined at various time intervals and the results are summarised in Table 1. After 24 h a further portion (0.72 equiv.) of sodium C2H,]methoxide was added and the spectrum redetermined. With time, the mixture slowly turned brown and after 4 days the spectrum was dominated by decomposition products. Monitored by 13C n.m.r. spectroscopy. To a solution of N-methyl-5H-pyrrolo[ 1,2-c]imidazolium iodide (1 1) in ['H4]-methanol was added sodium [2H3]methoxide solution (0.1 equiv.). The I3C n.m.r. spectrum of the mixture was monitored until the exchange process was complete (cu. 22 days). The off- centre double resonance spectrum was then determined. The results are summarised in Table 2.Acknowledgements We warmly thank the S.E.R.C. and May and Baker Ltd. for the award of a CASE Research Studentship (to S. P. S.). References 1 Part 2, W. D. Ollis, S. P. Stanforth, and C. A. Ramsden, J. Chem.Soc., Perkin Trans. I, 1989, preceding paper. 2 C. A. Ramsden, Terruhedron, 1977, 33, 3203; 'Comprehensive Heterocyclic Chemistry,' ed. A. R. Katritzky and C. W. Rees, Pergamon Press, Oxford, 1984, 6, 1027. 3 W. D. Ollis, S. P. Stanforth, and C. A. Ramsden, Tetrahedron, 1985, 41, 2239. 4 J. Elguero, R. M. Claramunt, and A. J. H. Summers, Adv. Hererocycl. Chem., 1978, 22, 183. 5 H. Volz and H. Kowarsch, Heterocqeles, 1977, 7, 1319. 6 K. T. Potts in 'The Chemistry of Heterocyclic Compounds,' ed. A. Weissberger and E.C. Taylor, Wiley, New York, 1977, 30, 317. 7 K. T. Potts and J. L. Marshall, J. Org. Chem., 1976, 41, 129. 8 H. Shimoharada, S. Ikeda, S. Kajigaeshi, and S. Kanemasa, Chem. Lett., 1977, 1237. 9 0.Tsuge, H. Shiraishi, and T. Takata, Chew. Lett., 1980, 1369. 10 J. M. Kane, J. Org. Chem., 1980, 45, 5396. 11 V. A. Chuiguk and A. G. Maidannik, Khirn. Geterotsikl. Soedin., 1980, 12, 1695 (Chem. Ahstr., 1981, 94, 175032e). 12 0.Tsuge, H. Shiraishi, and M. Noguchi, Chem. Lett., 1981, 213. 13 V. A. Chuiguk and Yu. A. Federov, Klzin?.Geterotsikl. Soedin., 198I, 991 (Chem. Ahslr., 1981, 95, 169090b). 14 V. A. Chuiguk and I. A. Rudnik, Khim.Geterotsikl. Soedin., 1982,993 (Chem. Ahstr., 1982, 97, 162933m). 15 V. A. Chuiguk, A. G. Maidennik, and R.V. Onis'ki, Ukr. Khim.Zh. (Russ. Ed.), 1982, 48, 647 (Chem. Abstr., 1982, 97, 127572~). 16 S. Kanemasa, S. Ikeda, H. Shimoharada, and S. Kajigaeshi, Chem. Lett., 1982, 1533. 17 0.Tsuge, S. Kanemasa, and T. Hamamoto, Chem. Lett., 1982, 1491. 18 E. K. Mikitenko and N. N. Romanov, Khim. Geterosikl. Soedin., 1983, 933 (Chem. Ahstr., 1983, 99, 158334r). 19 G. Ege, R. Heck, K. Gilbert, H. Irngartinger, U. Huber-Patz, and H. Rodewald, J. Heteroc.ycl. Chmm., 1983, 20, 1629. 20 0.Tsuge, S. Kanemasa, and T. Hamamoto, Chem. Lett., 1983, 85 and 763. 21 0.Tsuge, S. Kanemasa, and T. Hamamoto, Heteroqdes, 1983, 20, 647. 22 I. Anlonini, P. Franchetti, M. Grifantini, and S. Martelli, J. Hetero-cjd. Cliem, 1976, 13, 1 1 1. 23 A.F. Thomas, ‘Deuterium Labelling in Organic Chemistry,’ Apple- ton-Century-Crofts, New York, 1971. 24 W. G. Brown, M. S. Kharasch, and W. R. Sprowls, J. Org. Cham., 1939, 4, 442. 25 1. Willner, M. Halpern, and M. Rabinovitz, J. Clzen;. Soc.., Chem. Cornniun., 1978, 155. 26 T. Yoshida, T. Matsuda, T. Okano, T. Kitani, and S. Otsuka, J. Aim Chen?. Sot.., 1979, 101, 2027. 27 R. A. Olofson, W. R. Thompson, and J. S. Michelmann, J. Am. Chenz. Soc., 1964, 86, 1865. 28 H. A. Staab, M.-Th. Wu, A. Mannschreck, and G. Schwalbach, Telrulzedron Lett., 1964, 845. J. CHEM. SOC. PERKIN TRANS. I 1989 29 R. A. Olofson and J. M. Landesberg, J. Am. Chem. Soc., 1966, 88, 4263. 30 R. A. Olofson, J. M. Landesberg, K. N. Houk, and J. S. Michelmann, J. Am. Chem. Snc., 1966, 88, 4265. 31 P. Haake, L. P. Bowsher, and W. B. Miller, J. Am. CIieni. Soc., 1969, 91, 11 13. 32 R. Breslow, J. Am. Clieni. Soc., 1957, 79, 1762. 33 R. Breslow, J. Am. Clicni. Soc., 1958, 80, 3719. 34 H. Stetter, Angew. Clzem., hi. Ed. Engl., 1976, 15, 639. 35 K. Karimian, I. Ganjian, and M. Hokari, Tctralzedror~Lett., 1981, 581. 36 P. Haake, Tetrukedrnn Lett., 1981, 2939. 37 Part 1, W. I).Ollis, S. P. Stanforth, and C. A. Ramsden, J. Chem. Soc., Perkin Truns. 1, 1989, 945. Received 24th February 1988; Paper 8/00732B
展开▼
