Syntheses of novel dibenzo[d,f]heteronins incorporating group 15 and 16 heavier elements

Article abstract of DOI:10.3987/COM-12-S(N)90

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

Full text of DOI:10.3987/COM-12-S(N)90

HETEROCYCLES, Vol. 86, No. 2, 2012
941
HETEROCYCLES, Vol. 86, No. 2, 2012, pp. 941 - 945. © 2012 The Japan Institute of Heterocyclic Chemistry
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, 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
M
M
1
2
M = a: S, b: Se, c: Te, d: PPh, d': P(O)Ph, e: AsPh, f: SbPh
Scheme 1
Dedicated to Professor Dr Ei-ichi Negishi on the occasion of his 77th birthday

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HETEROCYCLES, Vol. 86, No. 2, 2012
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(-bromovinyl)biphenyl (4) via a common 1,8-dilithium intermediate (5).
The key starting compound, (Z)-2,2’-bis(-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 (J
=
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′).
3
4
5
2
6
Br
Br
Li
Li
i
ii
iii
CHO
CHO
1
13
M
7
8
12
9
10
11
3
4
5
1
Scheme 2. Reagents and conditions: i, Ph3P+CH2Br-Br (x 2), t-BuOK, THF, -80 °C C to rt, 12 h, 57 %; ii,
t-BuLi, Et2O, -80 °C, 5 min; iii, Metal reagents [(PhSO2)2S, SeCl4, TeI4, PhPCl2, PhAsCl2 or PhSbBr2],
Et2O, -80 to -10 °C, 2.5 h.
Table 1. Selected 1H-NMR Spectroscopic Data of Heteronins (1) (400 MHz, CDCl3: ).
Compd.
1a
M
S
J5,6(8,9) (Hz)
11.0
Ar
6-H and 8-H ()
5-H and 9-H ()
5.86
6.15
6.45
6.52
6.92
7.40
7.12–7.40
7.08–7.39
7.02–7.39
6.78–7.44
6.92–7.48
6.95–7.44
1b
Se
11.0
1c
Te
11.0
P(O)Ph
AsPh
SbPh
6.07
5.92
6.12
6.15
6.13
6.37
7.09
7.08
7.43
7.40
7.26
7.62
10.6a) (13.9)b)
10.1 (13.6)
11.4 (13.9)
1d′
1e
1f
a) JP,6(8) = 13.6 and JP,5(9) = 35.5 Hz, b) JP,6(8) = 17.6 and JP,5(9) = 33.0 Hz.

HETEROCYCLES, Vol. 86, No. 2, 2012
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The structures of the heteronins (1a-c, d′, e, f) obtained here were established from their spectral
1
1
properties (HR-MS and H-NMR). The H-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 (
5.86–6.45 for 6-H and 8-H,  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 (: 
5.89–6.79; :  6.72–7.62; J = 9.2–9.9 Hz),4b than those of aromatic Group 16 1-benzoheteroles (: 
7.39–8.75; : 7.30–8.00; J = 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  6.04 (JP,H = 24 Hz and JH,H = 14 Hz) and  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.

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HETEROCYCLES, Vol. 86, No. 2, 2012
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.
REFERENCE AND NOTES
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 –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.
3. (a) E. D. Middlemas and L. D. Quin, J. Am. Chem. Soc., 1980, 102, 4838; (b) L. D. Quin, E. D.
Middlemas, and N. S. Rao, J. Org. Chem., 1982, 47, 905.
4. (a) S. Yasuike, H. Ohta, S. Shiratori, J. Kurita, and T. Tsuchiya, J. Chem. Soc., Chem. Commun.,
1993, 1817; (b) S. Yasuike, T. Kiharada, J. Kurita, and T. Tsuchiya, Chem. Commun., 1996, 2183;
(c) S. Yasuike, S. Shiratori, J. Kurita, and T. Tsuchiya, Chem. Pharm. Bull., 1999, 47, 1108; (d) S.
Yasuike, T. Kiharada, J. Kurita, and T. Tsuchiya, Chem. Pharm. Bull., 2003, 51, 1283, and references
cited therein.
5. S. Yasuike, S. Tsukada, J. Kurita, T. Tsuchiya, Y. Tsuda, F. Kiuchi, and S. Hosoi, Heterocycles,
2000, 53, 525.
1
6. 4: colorless oil; H-NMR (400 MHz, CDCl3, J = Hz):  6.31 (2H, d, -H), 6.66 (2H, d, -H),
7.21-7.89 (8H, m, Ar-H), J= 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; (b) M. A. Romero and A. G.
Fallis, Tetrahedron Lett., 1994, 35, 4711.
1
9. 1,8-dideuterio compound: mp 73-74 °C; H-NMR (400 MHz, CDCl3, J = Hz):  5.08 (2H, d, -H),
6.40 (2H, dt, -H), 7.14-7.67 (8H, m, Ar-H), J= 8.1, J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

HETEROCYCLES, Vol. 86, No. 2, 2012
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oil.
11. (a) J. Kurita, M. Ishii, S. Yasuike, and T. Tsuchiya, J. Chem. Soc., Chem. Commun., 1993, 1309; (b)
J. Kurita, M. Ishii, S. Yasuike, and T. Tsuchiya, Chem. Pharm. Bull., 1994, 42, 1437; (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, 46.