Facile synthesis of novel photochromic 1,2-diheteroaryl-substituted cycloalkenes by titanium-induced intramolecular coupling reaction

Article abstract of DOI:10.1055/s-1998-2129

Intramolecular reductive coupling reaction of a series of diketones 1 and dioxo sulfides 3 induced by a low-valent titanium reagent at reflux in tetrahydrofuran affords 1,2-diheteroarylcycloalkenes 2 and 3,4-diheteroaryl-substituted 2,5-dihydrothiophenes

Full text of DOI:10.1055/s-1998-2129

SHORT PAPERS
1092
Facile Synthesis of Novel Photochromic 1,2-Diheteroaryl-Substituted Cycloalkenes by
Titanium-Induced Intramolecular Coupling Reaction
Zhen-Nian Huang,a, c Bao-An Xu,b Sheng Jin,b Mei-Gong Fan*a
a Institute of Photographic Chemistry, Academia Sinica, Beijing 100101, P. R. China
b Department of Chemistry, Peking University, Beijing 100871, P. R. China
c State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. China
Received 13 June 1997; revised 18 December 1997
Abstract: Intramolecular reductive coupling reaction of a series
of diketones 1 and dioxo sulfides 3 induced by a low-valent tita-
nium reagent at reflux in tetrahydrofuran affords 1,2-diheteroaryl-
cycloalkenes 2 and 3,4-diheteroaryl-substituted 2,5-dihydro-
thiophenes 4, which show photochromic properties on irradiation
with UV and visible light.
Key words: intramolecular reductive coupling, low-valent titan-
ium, photochromic compounds, 1,2-diheteroarylcycloalkenes,
3,4-diheteroaryl-2,5-dihydrothiophenes
In recent years, the reductive coupling of carbonyl com-
pounds by using low-valent titanium reagents has been
widely investigated and employed in the synthesis of var-
ious olefins.1–3 One of the most important applications for
the titanium-induced coupling reaction lies in the fact that
the intramolecular coupling of dicarbonyl compounds can
lead to the formation of cycloalkenes.4, 5 However, in spite
of numerous examples concerning the synthesis of cy-
cloalkenes using low-valent titanium reagents, there are
few examples of the preparation of 1,2-diheteroarylcy-
cloalkenes.6 Recently much effort has been devoted to the
development of new photochromic compounds, due to
their potential use in optical data storage media and other
applications. Among these compounds, 1,2-diarylethenes
possess promising properties for practical use.7–12 With a
view to developing novel photochromic 1,2-diaryl-
ethenes, we are particularly interested in the preparation
of 1,2-diheteroarylcycloalkenes. Thus, in the course of
our synthetic studies, we observed that the intramolecular
coupling of 1,5- and 1,6-diketones using low-valent tita-
nium reagent could conveniently produce the desired
products. Herein we reported the preliminary results.
Starting materials, 1,6-bis(1-alkyl-2-methylindol-3-yl)-
hexane-1,6-diones 1a–c and 1,5-bis(1-alkyl-2-methylin-
dol-3-yl)pentane-1,5-diones 1g–i were respectively pre-
pared by treatment of adipoyl and glutaryl dichloride with
2-methylindol-3-ylmagnesium bromide, followed by
alkylation under basic conditions. Diketones 1d–f and 1j
were readily available by Friedel–Crafts acylation with
SnCl4 as catalyst. Dioxo sulfides 3k,l were accessible by
reaction of an α-halo ketone with sodium sulfide in re-
fluxing ethanol.
The cycloalkenes 2a–j were obtained in moderate yields
by the general procedure described in the experimental
section. But using this procedure, only traces of 4k,l were
isolated. Improvement of the yield of 4k,l by varying the
reaction conditions was attempted; finally adding pyri-
dine into the reaction system proved to be effective in rais-
ing yields of 4k,l. All the compounds we obtained are new

SYNTHESIS
August 1998
1093
Table. The Preparation of Cycloalkenes 2 and 2,5-Dihydrothiophenes 4
Com-
pound
Yielda
(%)
m.p.b
(°C)
Molecular
Formulae
UV
UV
1H NMR (CDCl3/TMS)e
δ
MSf
m/z
λmax (nm)d
λmax (nm)d
(ε: mol–1)
(M+)
Colorless Form Colored Form
2a
2b
2c
26
23
44
196–198
272–274
<30
C28H32N2
396.59
236 (40800)
230 (19080)
238 (32100)
484
478
486
1.02 (t, 6H, 2NCH2CH3), 1.62 (s, 6H, 2CH3), 396
1.97–2.97 (m, 8H, (CH2)4), 3.86 (q, 4H,
2NCH2CH3), 6.72–7.65 (m, 8Harom
)
C38H36N2
520.72
1.84 (s, 6H, 2CH3), 2.00–2.91 (m, 8H, 520
(CH2)4), 5.10 (s, 4H, 2NCH2), 6.30–7.62 (m,
18Harom
)
C56H88N2
789.33
0.92 (t, 6H, 2CH3), 1.10–1.43 (m, 28H, 788
(CH2)14CH3), 1.60 (s, 6H, 2CH3), 1.71–2.97
(m, 8H, (CH2)4), 3.75 (q, 4H, 2CH2), 6.98–
7.55 (m, 8Harom
)
2d
2e
2f
40
25
33
42
141–142
42–44
C24H22S2
374.56
233 (27700)
232 (27500)
216 (34100)
236 (56600)
444
450
396
488
1.94 (s, 6H, 2CH3), 1.98 (m, 4H, 2CH2), 2.28 374
(m, 2H, CHa), 2.69 (m, 2H, 2CHb), 7.26–7.62
(m, 8Harom
)
C8H22S2
302.49
1.77 (m, 4H, 2CH2), 1.94 (s, 6H, 2CH3), 2.30 302
(t, 4H, 2CH2), 2.33 (s, 6H, 2CH3), 6.33 (s,
2Harom
)
52–54
C8H22O2
270.37
1.72 (m, 4H, 2CH2), 1.82 (s, 6H, 2CH3), 2.18 270
(s, 6H, 2CH3), 2.24 (t, 4H, 2CH2), 5.69 (s,
2Harom
)
2g
182–184
C27H30N2
382.55
1.15 (t, 6H, 2NCH2CH3), 1.67 (s, 6H, 2CH3), 382
2.21 (m, 2H, CH2CH2CH2), 3.04 (t, 4H,
CH2CH2CH2), 3.96 (q, 4H, 2NCH2CH3),
7.04–7.06 (m, 8Harom
)
2h
2i
35
65
174–176
32–34
C37H34N2
506.69
230 (48200)
238 (60010)
482
490
1.82 (s, 6H, 2CH3), 2.22 (m, 2H, 506
CH2CH2CH2), 3.04 (t, 4H, CH2CH2CH2),
5.14 (s, 4H, 2NCH2), 6.67–7.51 (m, 18Harom
)
C55H86N2
775.31
0.90 (t, 6H, 2CH3), 1.18–1.58 (m, 28H, 774
2(CH2)14), 1.64 (s, 6H, 2CH3), 2.18 (m, 2H,
CH2CH2CH2), 3.00 (t, 4H, CH2CH2CH2),
3.86 (t, 4H, 2CH2), 6.98–7.55 (m, 8Harom
)
2j
54
187–188
C23H20S2
360.53
234 (60039)
445
453
1.93 (s, 6H, 2CH3), 2.26 (m, 2H, CH2), 2.72 360
(m, 2H, CHa), 3.22 (m, 2H, 2CHb), 7.19–7.65
(m, 8Harom
)
4k
4l
18
11
106–108
89–91
C24H24N2S
372.53
290 (27110)
233 (11000)
2.70 (s, 6H, 2CH3), 2.76 (s, CH2SCH2) 3.70 (s, 372
6H, 2NCH3), 7.20–8.00 (m, 8Harom
)
C16H18S3
306.50
2.41 (s, 6H, CH3), 2.65 (s, 6H, CH3), 2.82 (s, 306
4H, CH2), 6.99 (s, 2Harom
)
a Yield of pure isolated product.
b Uncorrected, measured with Yanaco MP-500 apparatus.
c Satisfactory microanalyses obtained: C ± 0.18, H ± 0.20, N ± 0.27, S ± 0.35.
d Measured in cyclohexane on Hitachi 557 UV-vis spectrophotometer.
e Recorded on Varian UNITY-300 NMR spectrometer.
f Recorded on AEI MS-50 spectrometer.
compounds and characterized by elemental analyses, IR, forms in polar and nonpolar solvents according to the
1H NMR, and mass spectra (Table). In our preliminary ex- Woodward–Hoffmann rule; the colored forms can also
periment these compounds exhibited a typical photochro- bleach and return to the initial colorless forms by exposure
mic behavior except for 4k. On irradiation with UV light, to visible light. The Figure shows the absorption spectra
the colorless 2a–j and 4l undergo hexa-1,3,5-triene/cyclo- change of a cyclohexane solution of 2e before and after
hexa-1,3-diene interconversion to afford the colored photoirradiation at 254 nm. The absorption maxima of 2a–

SYNTHESIS
Short Papers
1094
was extracted with Et2O (3 × 100 mL). The combined organic extracts
were dried and evaporated to give an oil. The pure product 2 was thus
purified by flash chromatography (silica gel, EtOAc/petroleum
ether).
Symmetrical 2,5-Dihydrothiophenes 4k,l; General Procedure:
TiCl4 (1.5 mL, 10 mmol) was added dropwise using a syringe to a
stirred suspension of zinc powder (1.30 g, 20 mmol) in freshly dis-
tilled anhyd THF (100 mL) at –10°C under argon. After completion
of the addition, the mixture was heated to reflux for 1 h. The suspen-
sion was cooled to 20°C, then the pyridine (0.5 mL) and the dioxo
sulfide (5 mmol) were added carefully. Reflux was continued for 6 h
under argon and then most of the solvent was removed under vacuum.
The residue was poured into 10% aq K2CO3 (100 mL) and the aque-
ous layer was extracted with Et2O (3 × 50 mL). The combined organic
extracts were dried and evaporated to give an oil. The pure product 4
was isolated by flash chromatography (silica gel, EtOAc/petroleum
ether).
___
Figure. Absorption spectra of 2e (1.3 × 10–5 mol/L)(
) and in the
….
)
photostationary state under irradiation with 254 nm light (
j and 4l and their colored forms in cyclohexane are col-
lected in the Table.
This work was supported by National Nature Science Foundation of
China (No: 29702009).
The results show that the low-valent titanium induced in-
tramolecular coupling reaction is a general and conve-
nient method for the synthesis of photochromic 1,2-dihet-
eroarylcycloalkenes which are otherwise difficult to pre-
pare. Additionally, the flexibility of the cycloalkene
moiety of the compounds gives the possibility for us to
investigate the effect of cyclic strain and heteroatoms in
the cycloalkene moiety on the photochromic properties,
such as thermal stability, fatigue resistance, etc., which is
of significant academic and practical value. The detailed
studies on the photochromic properties of these com-
pounds will be published elsewhere.
(1) McMurry, J. E. Acc. Chem. Res. 1983, 16, 405.
(2) McMurry, J. E. Chem. Rev. 1989, 89, 1513.
(3) Lenoir, D. Synthesis 1989, 883.
(4) Baumstark, A. L.; McCloskey, C. J.; Witt, K. E. J. Org. Chem.
1978, 43, 3609.
(5) McMurry, J. E.; Kees, K. L. J. Org. Chem. 1977, 42, 2655.
(6) Nakayama, J.; Machida, H.; Saito, R.; Akimoto, K.; Hoshino,
M. Chem. Lett. 1985, 1173.
Nakayama, J.; Machida, H.; Hoshino, M. Tetrahedron Lett.
1985, 26, 1981.
(7) Irie, M.; Mohri, M. J. Org. Chem. 1988, 53, 803.
(8) Uchida, K.; Nakayama, Y.; Irie, M. Bull. Chem. Soc. Jpn. 1990,
63, 1311.
Symmetrical 1,2-Diheteroarylalkenes 2; General Procedure:
TiCl4 (2.26 mL, 15 mmol) was added dropwise using a syringe to a
stirred suspension of zinc powder (1.96 g, 30 mmol) in freshly dis-
tilled anhyd THF or dioxane (100 mL) at –10°C under argon. The
resulting dark mixture was heated under reflux for 1 h. The suspen-
sion was cooled to 20°C and the diketone (10 mmol) was added care-
fully. Reflux was continued for 20 h under argon. The resulting mix-
ture was poured into 10% aq K2CO3 (200 mL) and the aqueous layer
(9) Nakayama, Y.; Hayashi, K.; Irie, M. J. Org. Chem. 1990, 55,
2592.
(10) Nakayama, Y.; Hayashi, K.; Irie, M. Bull. Chem. Soc. Jpn.
1991, 64, 789.
(11) Frederick, J. H.; Fujiwara, Y.; Penn, J. H.; Yoshihara, K.; Petek,
H. J. Phys. Chem. 1991, 95, 2845.
(12) Hanazawa, M.; Sumiya, R.; Horikawa, Y.; Irie, M. J. Chem.
Soc., Chem. Commun. 1992, 206.