HETEROCYCLES

Communication | Special issue | Vol. 86, No. 2, 2012, pp. 941-945
Received, 6th July, 2012, Accepted, 10th August, 2012, Published online, 20th August, 2012.
DOI: 10.3987/COM-12-S(N)90

■ Syntheses of Novel Dibenzo[d,f]heteronins Incorporating Group 15 and 16 Heavier Elements

Shuji Yasuike,* Satoshi Tsukada, Naoki Kakusawa, Takashi Tsuchiya, and Jyoji Kurita*

Faculty of Pharmaceutical Sciences, Hokuriku University, 3-Ho, Kanagawa machi, Kanazawa 920-1181, Japan

Abstract

Fully unsaturated dibenzo[d,f]heteronins incorporating Group 15 (P, As, Sb) and Group 16 (S, Se, Te) heavier elements have been prepared via a common 1,8-dilithium intermediate. These heteronins, except for dibenzothionin, are the first examples of fused nine-membered heterocyclic ring.　Proton NMR spectra of the heteronins revealed that two olefinic bonds in the heteronin ring have the cis configurations and the nine-membered rings exist in a buckled, non-planar conformation.

A variety of fully unsaturated nine-membered heterocyclic rings (heteronins) such as azonines and oxonins have been prepared, and their molecular structures and aromatic character have been studied.1 However, heteronins containing Group 15 (P, As, Sb) and Group 16 (S, Se, Te) elements have not been reported, except for dibenzothionins (1a)2 and phosphonins (2d).3 We recently reported the syntheses and physical properties of seven-membered (heteroepins)4 and ten-membered (heteroecins)5 heterocyclic compounds incorporating such heavier elements from the corresponding 1,6- and 1,9-dilithium intermediates, along with their physical properties and thermal stabilities. As part of our studies on the synthesis of new heterocyclic compounds incorporating Group 14, 15, and 16

heavier elements, we report here the synthesis and structures of the title dibenzoheteronins (1a-f) from (Z)-2,2’-bis(2-bromovinyl)biphenyl (4) via a common 1,8-dilithium intermediate (5).
The key starting compound, (Z)-2,2’-bis(2-bromovinyl)biphenyl (4),6 was prepared stereoselectively in 57% yield by a double Wittig reaction of 2,2’-diformylbiphenyl (3)7 with bromomethyltriphenyl- phosphonium bromide.8 In the NMR spectrum of 4, the coupling constant of the vinylic protons (Jα, β = 8.1 Hz) of the bromovinyl moiety supports the all-cis configuration. Treatment of 4 with tert-butyllithium in dry ether under an argon atmosphere, and then with deuterium oxide resulted 1,8-dideuterio compound in 85% yield.9 This result clearly shows the generation of the 1,8-dilithium species (5) in high efficiency. However, the reaction of 5 with electrophilic reagents such as (PhSO2)2S, SeCl4, TeI4, PhPCl2, PhAsCl2, and PhSbBr2 gave the desired dibenzo[d,f]heteronins (1a-f) in low yields (10–17%) as the sole characterizable product.10　The heteronins (1) except for phosphonin (1d) were stable enough to be eluted using silica gel column chromatography and isolated in pure form. The phosphorus-containing heteronin (1d) is susceptible to air oxidation and was isolated as its P-oxide (1d').

The structures of the heteronins (1a-c, d', e, f) obtained here were established from their spectral properties (HR-MS and 1H-NMR). The 1H-NMR spectroscopic data of the nine-membered ring protons for 1 are given in Table 1. The spectroscopic data [1H-NMR and UV (253 nm, ε 5000, EtOH)] and mp (121–123 °C) of the thionin (1a) obtained here are in good accordance with those of dibenzo[d, f]thionin, reported by Bindra et al.2 The vinyl proton signals of 6-H and 8-H as well as 5-H and 9-H for the Group 16 heteronins (1a-c) exhibit one AB doublet with coupling constant J5,6(8,9) = 11.0 Hz. This magnetic equivalence of the olefinic protons implies that 1a-c have a symmetrical structure in solution with rapid conformational exchange on the NMR time scale, and both olefinic bonds have the cis configuration. It is also suggested that, because the vinyl protons of 1a-c were observed at the relatively high field (δ 5.86–6.45 for 6-H and 8-H, δ 6.52–7.40 for 5-H and 9-H), without the deshielding associated with aromatic character, 1a-c should be classified as non-aromatic compounds. We have already reported that the vinyl protons of non-aromatic Group 16 3-benzoheteroepins were observed at a higher field (α: δ 5.89–6.79; β: δ 6.72–7.62; Jα,β = 9.2–9.9 Hz),4b than those of aromatic Group 16 1-benzoheteroles (α: δ 7.39–8.75; β: δ 7.30–8.00; Jα,β = 5.5–7.0 Hz).11 In the 1H-NMR spectra of Group 15 heteronins (1d′, e, f), the vinyl proton signals corresponding to 5-H and 9-H as well as 6-H and 8-H were observed in different positions with the coupling constant J5,6 = 10.1-10.6 Hz and J8,9 = 13.6-13.9 Hz. The magnetic nonequivalence of the olefinic protons implies that these Group 15 heteronins (1d′, e, f) exist in buckled, non-planar conformations. It should be emphasized that both the olefinic bonds of 1d′, C(5)–C(6) and C(8)–C(9), should have the cis configuration.5 Quin has recently reported the synthesis and structure of dibenzo[d, f]phosphonin P-oxide (2d′), which have cis and trans olefinic bonds, for which two vinyl proton signals were observed at δ 6.04 (JP,H = 24 Hz and JH,H = 14 Hz) and δ 6.08 (JP,H = 14 Hz and JH,H = 4 Hz).3a
All the dibenzoheteronins (1a-c, d′, e, f) isolated here displayed relatively high thermal stability and remained unchanged even when heated at 110 °C for 24 h in toluene-d8. The thermal stabilities of these dibenzoheteronins is in contrast to these of benzoheteroepins4 and monocyclic heteronins.1
We have developed a general route for the synthesis of Group 15 (P, As, Sb) and Group 16 (S, Se, Te) fully unsaturated dibenzo[d,f]heteronins (1) from a common starting material, 2,2’-bis(2-bromo- vinyl)biphenyl (4) via 1,8-dilithium intermediate (5). All the heteronins obtained here exist in buckled, non-planar conformations and are classified as non-aromatic compounds.
Further studies on the molecular structures and chemical properties of these novel dibenzo[d,f]heteronins containing heavier elements are in progress.

ACKNOWLEDGMENTS
Partial financial support for this work was provided by a Grant-in Aid for Scientific Research (J. K.) from the Ministry of Education, Sciences, Sports and Culture of Japan, and a Special Research Fund from Hokuriku University.

References

1. For reviews; (a) A. G. Anastassiou, ‘‘Comprehensive Heterocyclic Chemistry: Large rings except crown ethers and heterophanes,’’ Vol. 7, ed. by A. R. Katritzky and C. W. Rees, Pergamon, Oxford, 1984, pp. 709–730; (b) A. G. Anastassiou and H. S. Kasmai, ‘‘Advances in Heterocyclic Chemistry: Medium-large and large π–excessive heteroannulenes,’’ Vol. 23, ed. by A. R. Katritzky, Academic Press, London, 1978, pp. 55–102; (c) R. M. Borzilleri, ‘‘Science of Synthesis: eight- and nine-membered hetarenes and heteroannulenes with one or more heteroatoms,’’ Vol. 17, ed. by S. M. Weinreb, Georg Thieme Verlag, Stuttgart-New York, 2004, pp. 979–1024.
2. A. P. Bindra, J. A. Elix, P. J. Garratt, and R. H. Mitchell, J. Am. Chem. Soc., 1968, 90, 7372. CrossRef
3. (a) E. D. Middlemas and L. D. Quin, J. Am. Chem. Soc., 1980, 102, 4838; CrossRef (b) L. D. Quin, E. D. Middlemas, and N. S. Rao, J. Org. Chem., 1982, 47, 905. CrossRef
4. (a) S. Yasuike, H. Ohta, S. Shiratori, J. Kurita, and T. Tsuchiya, J. Chem. Soc., Chem. Commun., 1993, 1817; CrossRef (b) S. Yasuike, T. Kiharada, J. Kurita, and T. Tsuchiya, Chem. Commun., 1996, 2183; CrossRef (c) S. Yasuike, S. Shiratori, J. Kurita, and T. Tsuchiya, Chem. Pharm. Bull., 1999, 47, 1108; CrossRef (d) S. Yasuike, T. Kiharada, J. Kurita, and T. Tsuchiya, Chem. Pharm. Bull., 2003, 51, 1283, and references cited therein. CrossRef
5. S. Yasuike, S. Tsukada, J. Kurita, T. Tsuchiya, Y. Tsuda, F. Kiuchi, and S. Hosoi, Heterocycles, 2000, 53, 525. CrossRef
6. 4: colorless oil; 1H-NMR (400 MHz, CDCl3, J = Hz): δ 6.31 (2H, d, β-H), 6.66 (2H, d, α-H), 7.21-7.89 (8H, m, Ar-H), Jα,β = 8.1; HR-MS m/z 361.9327 (M+, calc. for C16H12Br2: 361.9307).
7. P. S. Bailey and R. E. Erickson, Org. Synth., Coll. Vol. V, 1973, 489.
8. (a) M. Matsumoto and K. Kuroda, Tetrahedron Lett., 1980, 21, 4021; CrossRef (b) M. A. Romero and A. G. Fallis, Tetrahedron Lett., 1994, 35, 4711. CrossRef
9. 1,8-dideuterio compound: mp 73-74 °C; 1H-NMR (400 MHz, CDCl3, J = Hz): δ 5.08 (2H, d, β-H), 6.40 (2H, dt, α-H), 7.14-7.67 (8H, m, Ar-H), Jα,β = 8.1, JΗ,D = 1.0; HR-MS m/z 208.1221 (M+, calc. for C16H12D2: 208.0939).
10. 1a: 10% yield, mp 121–123 °C (Lit.,2 121–122 °C); 1b: 16% yield, mp 113–115 °C; 1c: 14% yield, mp 155–156 °C; 1d´: 10% yield, colorless oil; 1e: 10% yield, colorless oil; 1f: 17% yield, colorless oil.
11. (a) J. Kurita, M. Ishii, S. Yasuike, and T. Tsuchiya, J. Chem. Soc., Chem. Commun., 1993, 1309; CrossRef (b) J. Kurita, M. Ishii, S. Yasuike, and T. Tsuchiya, Chem. Pharm. Bull., 1994, 42, 1437; CrossRef (c) A. Muranaka, S. Yasuike, C.-Y. Liu, J. Kurita, N. Kakusawa, T. Tsuchiya, M. Okuda, N. Kobayashi, Y. Matsumoto, K. Yoshida, D. Hashizume, and M. Uchiyama, J. Phys. Chem. A, 2009, 113, 464. CrossRef