Preparation of conjugated 6,6'-bibenzo[b]selenophenes

Article abstract of DOI:10.1016/j.mencom.2013.12.010

6,6'-Bibenzo[b]selenophenes were prepared from 4,4'-dibromobiphenyl by the Sonogashira coupling with terminal alkynes followed by heterocyclization with SeBr₄.

Full text of DOI:10.1016/j.mencom.2013.12.010

Mendeleev
Communications
Mendeleev Commun., 2014, 24, 32–34
Preparation of conjugated 6,6'-bibenzo[b]selenophenes
Pavel Arsenyan,* Jelena Vasiljeva and Sergey Belyakov
Latvian Institute of Organic Synthesis, LV-1006 Riga, Latvia. Fax: +371 6755 0338; e-mail: pavel@osi.lv
DOI: 10.1016/j.mencom.2013.12.010
6,6'-Bibenzo[b]selenophenes were prepared from 4,4'-dibromobiphenyl by the Sonogashira coupling with terminal alkynes followed
by heterocyclization with SeBr4.
Selenophenes represent an important class of heterocycles because
of their excellent biological effects.1 They are used as building
blocks to create selenophene-containing oligomers and polymers.
Many synthetic methods, including electrophilic and transition
metal catalyzed intramolecular cyclization, have been success-
fully employed in the synthesis of selenophenes.2 Electrophilic
selenium reagents such as selenium(ii) and (iv) halogenides
play an important role in organic synthesis.3 Amosova’s group4
reported addition of selenium(ii) chloride and bromide at alkenes
and alkynes. Recently, Braverman’s group5 published cycloaddi-
tion of phenylpropargylic alcohols with SeCl4 and SeBr4 in dry
chloroform at 0°C leading to benzo[b]selenophenes, albeit no
pure hydroxymethyl derivatives have been isolated. Here we
present a simple synthesis of conjugated 6,6'-bibenzo[b]seleno-
phenes from 4,4'-dibromobiphenyl.
Substituted bibenzo[b]selenophenes 2a–c were prepared in
two steps from 4,4'-dibromobiphenyl (Scheme 1). Bromine atoms
in the starting compound were replaced with alkynyl groups by
the Sonogashira cross-coupling with terminal alkynes, affording
products 1a,b in almost quantitative yields (up to 96%). However,
in the case of 1-ethynylcyclohexanol product 1c was obtained
in only 58% yield due to steric hindrance.† At the second step, bis-
alkynes 1a–c were treated with the in situ prepared selenium(iv)
(reaction between SeO2 and HBr was used). According to the
plausible mechanism, intermediate A forms upon SeBr4 addi-
tion to CºC triple bond with the following formation of inter-
mediate B via electrophilic heterocyclization. After the bromine
molecule elimination bibenzo[b]selenophenes 2a–c were obtained
in low yields (20–25%). Apparently, in the course of cyclization
bromine molecule can add to triple bonds of the starting com-
pound that would dramatically drop the yield. To overcome this,
we used two equivalents of cyclohexene as the bromine scavenger,
which provided the yield increase to 40–45%.‡
Molecular structures of 2a,b were unambiguously confirmed
by X-ray analysis§,6 (Figure 1). In both crystals molecules lie in
special positions (center of inversion). Therefore, bibenzoseleno-
phene systems are planar and C(6)–C(6') bonds are lengthened
[1.505(4) and 1.504(9) Å for 2a and 2b, respectively] due to
repulsion of hydrogen atoms [H(5)∙∙∙H(5') and H(7)∙∙∙H(7')]. The
intermolecular hydrogen bonds of O–H∙∙∙O type [with H-bond
lengths 2.804(6) and 2.833(6) Å] are observed in the crystal
structure of 2b. All other intermolecular contacts correspond to
sum of van der Waals radii.
Bibenzoselenophene derivative 2b was converted into synthones
which seem promising for the preparation of more complicated
p-oligomers (Scheme 2).¶ 2-Hydroxyprop-2-yl substituents are
acid-sensitive, therefore debromination of compound 2b was
performed by tert-octylamine in the presence of Cu0, CuI and
‡
Synthesis of 3,3'-dibromo-6,6'-bibenzo[b]selenophenes 2a–c (general
procedure). 4,4'-Dialkynylbiphenyl 1a–c and cyclohexene (3 equiv.) in
dioxane were added to the solution of selenium dioxide (3 equiv.) in HBr
(2.5 equiv.), and the mixture was stirred at room temperature for 48 h.
After the consumption of substrate 1a–c (TLC), water (50 ml) was added
and the mixture was extracted with ethyl acetate (100 ml). The organic
phase was washed with brine, dried over anhydrous Na2SO4, filtered, con-
centrated and the residue was purified by flash chromatography on silica
gel using light petroleum–ethyl acetate (2a) or CH2Cl2–ethyl acetate (2b,c)
as eluent. For details, see Online Supplementary Materials.
R
R
R
R
Br
Br
Br
SeBr3
Br
Br
Se
Se
Br
ii
i
– HBr
– Br2
1
For 2a: yield 45%, yellow solid, mp 115–117°C. H NMR (CDCl3,
Br
Br
400 MHz) d: 0.93 (t, 6H, Me, J 6.8 Hz), 1.35–1.48 (m, 8H, CH2), 1.72–1.79
(m, 4H, CH2), 3.01 (t, 4H, CH2, J 7.6 Hz), 7.68 (dd, 2H, 5,5'-CH, J 1.5 Hz,
J 8.4 Hz), 7.85 (d, 2H, 4,4'-CH, J 8.4 Hz), 8.05 (d, 2H, 7,7'-CH, J 1.5 Hz).
13C NMR (CDCl3, 100.3 MHz) d: 13.6, 22.1, 30.5, 30.9, 31.9, 106.8,
123.5, 124.4, 124.8, 137.3, 138.1, 139.2, 144.5.
For 2b: yield 48%, yellowish solid, mp 164–167°C. 1H NMR (CDCl3,
400 MHz) d: 1.86 (s, 12H, Me), 2.62 (s, 2H, OH), 7.71 (dd, 2H, 5,5'-CH,
J 1.5 Hz, J 8.4 Hz), 7.89 (d, 2H, 4,4'-CH, J 8.4 Hz), 8.10 (d, 2H, 7,7'-CH,
J 1.5 Hz). 13C NMR (CDCl3, 100.3 MHz) d: 29.2, 74.4, 101.4, 123.6,
124.7, 125.2, 137.7, 141.2, 154.0.
Se
R
Se
R
SeBr3
Br
Br
Br
Br
R
R
2a (45%)
2b (48%)
2c (40%)
A
B
1a–c
a R = C5H11
b R = C(OH)Me2
c R= 1-hydroxycyclohexyl
For 2c: yield 40%, white solid, mp 168–170°C. 1H NMR (DMSO-d6,
400 MHz) d: 1.27–1.33 (m, 2H, 2,5-CHcyclohexanol), 1.58–1.71 (m, 14H,
CH2), 2.37–2.45 (m, 4H, CH2), 6.26 (s, 2H, OH), 7.79 (d, 2H, 4,4'-CH,
J 8.4 Hz), 7.83 (dd, 2H, 5,5'-CH, J 1.5 Hz, J 8.4 Hz), 8.44 (d, 2H, 7,7'-CH,
J 1.5 Hz). 13C NMR (DMSO-d6, 100.3 MHz) d: 21.1, 24.6, 34.2, 73.6,
98.8, 123.6, 124.0, 124.3, 136.1, 137.5, 141.1, 159.3.
Scheme 1 Reagents and conditions: i, RCºCH (2.5 equiv.), PdCl2 (5%),
Ph3P (10%), CuI (10%), DMF/Pr2iNH, 100°C, 12 h; ii, SeO2 (3.0 equiv.),
HBr, cyclohexene, dioxane.
†
For synthesis and characteristics of compounds 1a–c, see Online Sup-
plementary Materials.
© 2014 Mendeleev Communications. All rights reserved.
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Mendeleev Commun., 2014, 24, 32–34
R
R
Se
Se
Br(15)
(a)
C(4)
SnMe3
C(9)
C(2)
C(3)
C(5)
C(6)
2a or 4
C(12)
C(11)
C(10)
S
C(14)
C(8)
C(7)
S
S
C(13)
Se(1)
SiMe2R
RMe2Si
SiMe2R
6a R = (CH2)3Cl
6b R = CH2CH=CH2
7a R = (CH2)3Cl, R' = C5H11 (70%)
7b R = CH2CH=CH2, R' = C5H11 (68%)
7c R = CH2CH=CH2, R' = H (40%)
O(13)
Se(1)
C(11)
C(12)
C(10)
(b)
C(2)
C(8)
Scheme 3 Reagents and conditions: Pd(PPh3)4, Ph3As, xylene, 120°C.
C(3)
C(7)
C(6)
C(9)
Br(14)
tions. We found that microwave irradiation of 2b in the presence
of 2 equiv. of zinc cyanide and 10% Pd(PPh3)4 in DMF for only
3 min at 140°C afforded dinitrile 5 in 72% yield.
C(5)
C(4)
In past years the interest in selenophene containing oligomers
rapidly increased compared to oligothiophenes since selenium
exhibits better metallic properties than sulfur.7 In order to prolong
p-conjugation we decided to bind thiophene rings to bibenzo[b]-
selenophene moiety. For this purpose we synthesized 5-silyl-
2-trimethylstannylthiophenes 6a,b with chloropropyl and allyl-
dimethylsilyl substituents.¶ We expected that long chains would
increase final oligomer solubility due to high lipophilicity and
3-chloropropyl and allyl groups may be involved in the formation
of benzo[b]selenophene-containing p-polymers. Compounds
6a,b were prepared in two stages from thiophene in good overall
yields (60–65%). 2-[(3-Chloropropyl)dimethylsilyl]- and 2-(allyl-
dimethylsilyl)thiophenes were obtained from 2-thienyllithium and
the corresponding chlorosilane. Then these products were treated
with BuLi (1.2 equiv.) in THF followed by quenching with chloro-
trimethylstannane. Stannanes 6a,b were coupled with dibromo-
bibenzo[b]selenophenes 2a and 4 according to the Stille protocol
(Scheme 3). Typical heating (130°C) of stannanes 6a,b with 2a
or 4 in xylene in the presence of Pd(PPh3)4 led to the target com-
pounds 7a–c in low yields. To reduce the reaction time and
activate the catalyst, a catalytic amount (7%) of triphenylarsine8 was
used. This afforded the products 7a,b in reasonable (68–70%)
yields.†† However, the yield of derivative 7c was 40% only,
probably, due to the lower solubility of reactant 4 in xylene. Our
attempts to accomplish cross-coupling between 2b and 6b failed,
Figure 1 ORTEP molecular structures of (a) 2a and (b) 2b.
Me
Me
OH
Se
Se
OH
Me
Me
3 (87%)
Se
Se
i
ii
Br
Br
2b
4 (22%)
iii
Me
Me
OH
Se
Se
OH
Me
Me
C
C
N
N
5 (72%)
Scheme 2 Reagents and conditions: i, CuI, Cu0, K3PO4, Me2NCH2CH2OH,
tert-octylamine, 100°C, 72 h; ii, NaH/DMF, 120°C; iii, Zn(CN)2, Pd(PPh3)4,
DMF, microwave irradiation, 140°C, 3 min.
K3PO4 in N,N-dimethylaminoethanol medium (the yield of product
3 reached 87%). Note that the nature of amine has no effect on a
yield. For deacetonation, compound 2b was treated with NaH in dry
DMF and 3,3'-dibromo-6,6'-bibenzo[b]selenophene 4 was isolated
in 22% yield. Other deacetonation methods using NaH/THF,
K2CO3/DMSO or PriONa/PriOH were even less successful. With
the aim to raise the fugacity of 2-hydroxyprop-2-yl substituent we
introduced electron-accepting cyano groups into 3 and 3' posi-
†† Synthesis of compounds 7a–c (general procedure). A vial charged with 2a,
2b or 4 (0.30 mmol), 6a or 6b (1.20 mmol), Pd(PPh3)4 (75 mg, 0.06 mmol)
and AsPh3 (20 mg, 0.06 mmol) in xylene (5 ml) was flushed with Ar for
10 min. Then the mixture was heated at 120°C for 24–48 h. After cooling,
the mixture was poured into aqueous Na2CO3 (50 ml) and ethyl acetate
(100 ml) and stirred for 15 min. The organic phase was washed with brine
(2×50 ml), dried over anhydrous Na2SO4, filtered, concentrated and the
residue was purified by flash chromatography on silica gel using light
petroleum–ethyl acetate as eluent.
§
Crystal data. 2a: monoclinic, space group P21/a, a = 12.7455(4), b =
1
For 7a: yield 70%, yellow oil. H NMR (CDCl3, 400 MHz) d: 0.39
= 6.7102(2) and c = 14.5471(6) Å, b = 100.748(2)°, V = 1222.31(7) Å3, Z = 2,
dcalc = 1.789 g cm–3, m = 6.306 mm–1. A total of 3638 independent reflection
intensities were collected at –120°C up to 2qmax = 61°; for structure refine-
ment 2404 reflections with I > 3s(I) were used. The final R factor is 0.044.
2b: monoclinic, space group C2/c, a = 30.8260(9), b = 8.1667(3) and
(s, 12H, MeSi), 0.85–0.96 (m, 10H, MeCH2), 1.24–1.40 (m, 8H, CH2),
1.68–1.92 (m, 8H, CH2), 2.94 (t, 4H, CH2Ar, J 7.2 Hz), 3.49–3.55 (m,
4H, CH2), 7.13 (d, 2H, 3-CH-thiophene, J 3.3 Hz), 7.31 (d, 2H, 4-CH-
thiophene, J 3.3 Hz), 7.57–7.62 (m, 4H, 4,4'-CH, 5,5'-CH), 8.10 (s, 2H,
7,7'-CH). 13C NMR (CDCl3, 100.3 MHz) d: –2.2, 13.6, 14.0, 22.0, 27.2,
30.9, 32.0, 47.4, 123.3, 123.8, 124.6, 124.8, 128.3, 128.7, 134.2, 134.9,
136.9, 138.7, 139.2, 141.7, 142.1, 150.2. LC-MS, m/z: 934.0 [M+], 978.0
[M+HCOO–].
c
= 8.8183(3) Å, b = 91.496(2)°, V = 2219.2(1) Å3, Z = 4, dcalc = 1.898 g cm–3
,
m = 6.948 mm–1. A total of 2551 independent reflection intensities were
collected at –100°C up to 2qmax = 55°; for structure refinement 1843
reflections with I > 2s(I) were used. The final R factor is 0.046.
For 7b: yield 68%, yellow oil. 1H NMR (CDCl3, 400 MHz) d: 0.38–0.42
(m, 12H, MeSi), 0.88 (t, 6H, CH2Me, J 7.2 Hz), 1.19–1.39 (m, 8H,
CH2Me), 1.67–1.75 (m, 4H, CH2), 1.83–1.89 (m, 4H, CH2), 2.94 (t,
4H, CH2, J 7.2 Hz), 4.90–4.96 (m, 4H, CH2=CH), 5.80–6.26 (m, 2H,
CH2=CH), 7.12–7.13 (d, 2H, 3-CH-thiophene, J 3.3 Hz), 7.30–7.32 (m,
2H, 4-CH-thiophene, J 3.3 Hz), 7.57–7.61 (m, 4H, 4,4'-CH, 5,5'-CH),
8.10 (s, 2H, 7,7'-CH). 13C NMR (CDCl3, 100.3 MHz) d: –2.2, –1.2, 13.9,
22.3, 24.5, 31.2, 32.3, 113.8, 123.6, 124.1, 124.9, 128.7, 128.9, 134.0,
134.5, 137.2, 139.0, 139.5, 142.0, 142.4, 144.5, 150.5. LC-MS, m/z: 862.0
[M+1], 901.0 [M+HCOO–].
Diffraction data for 2a,b were collected on a Bruker-Nonius Kappa
CCD diffractometer using graphite monochromated MoKa radiation
(l = 0.71073 Å). The crystal structures were solved by direct methods
and refined by full-matrix least squares using programs.6(a)–(c)
CCDC 891124 and 891125 contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk.
For details, see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2014.
¶
For synthesis and characteristics of compounds 3–6, see Online Sup-
plementary Materials.
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Mendeleev Commun., 2014, 24, 32–34
apparently, owing to deactivation of bromine atoms in 2b by
2-hydroxyprop-2-yl groups.
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(b) E. T. Pelkey, in Comprehensive Heterocyclic Chemistry III, eds. A. R.
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2008, vol. 3, pp. 975–1006.
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1411; (b) T. G. Back, in Organoselenium Chemistry, ed. D. Liotta, John
Wiley, New York, 1987, p.1.
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In summary, a new simple strategy for the preparation of a
new type of conjugated bibenzo[b]selenophenes starting from
4,4'-dibromobiphenyl has been developed. Further studies will
be connected with the synthesis and properties of conjugated
bibenzo[b]selenophenes with more branched structures.
This work was supported by the Latvian Council of Science
(447/2012).
Online Supplementary Materials
5 S. Braverman, H. E. Pechenick-Azizi, T. Gottlieb, E. Hugo and M. Sprecher,
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2013.12.010.
Synthesis, 2011, 4, 577.
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For 7c: yield 40%, yellow oil. 1H NMR (CDCl3, 400 MHz) d: 0.41–0.45
(m, 12H, MeSi), 1.86–1.92 (m, 4H, CH2), 4.94–5.00 (m, 4H, CH2=CH),
5.83–5.94 (m, 2H, CH2=CH), 7.33 (d, 2H, 3-CH-thiophene, J 3.3 Hz),
7.40 (d, 2H, 4-CH-thiophene, J 3.3 Hz), 7.75 (dd, 2H, 5,5'-CH, J 1.5 Hz,
J 8.4 Hz), 8.06 (s, 2H, 7,7'-CH), 8.18 (d, 2H, 4,4'-CH, J 8.4 Hz), 8.24 (d,
2H, 2,2'-CH, J 1.5 Hz). 13C NMR (CDCl3, 100.3 MHz) d: –2.2, –1.3,
22.6, 24.4, 114.0, 124.4, 124.5, 126.7, 127.3, 133.6, 133.9, 134.9, 137.5,
138.1, 138.8, 142.6, 144.0. LC-MS, m/z: 722.0 [M+1].
Received: 12th August 2013; Com. 13/4178
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