2,6-Divinylation of phenols with ethyne

Article abstract of DOI:10.1039/a704379a

Phenols are 2,6-divinylated by treatment with ethyne at 100°C in chlorobenzene in the presence of SnCl₄-Bu₃N, the divinylation occurring predominantly to exclusively with phenol, alkylphenols and alkoxyphenols; an appropriate amount of the tin reagent and the correct reaction temperature are essential for the divinylation.

Full text of DOI:10.1039/a704379a

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2,6-Divinylation of phenols with ethyne
Masahiko Yamaguchi,*a Mieko Arisawa,b Yoshiyuki Kidoa and Masahiro Hiramab
a Faculty of Pharmaceutical Sciences, Tohoku University, Aoba, Sendai 980-77, Japan
b Department of Chemistry, Graduate School of Science, Tohoku University, Aoba, Sendai 980-77, Japan
Phenols are 2,6-divinylated by treatment with ethyne at
100 °C in chlorobenzene in the presence of SnCl4–Bu3N, the
divinylation occurring predominantly to exclusively with
phenol, alkylphenols and alkoxyphenols; an appropriate
amount of the tin reagent and the correct reaction tem-
perature are essential for the divinylation.
effective protonation of the carbostannylated intermediate. The
amount of tin reagent (5 + 2 equiv.) is also critical to obtain the
divinylphenol predominantly. When it was changed, for
example, to 2 + 2, 2 + 5, 5 + 5 or 5 + 0 equiv., 1 :1 mixtures of
monovinylated and divinylated products were formed. Employ-
ing a large excess of reagnet (12 + 0 equiv.) resulted in the
monovinylation reaction dominating in a ratio of 6:1. The
reaction mechanism of the divinylation therefore appears to be
rather complex.
Several para- and meta-substituted phenols and phenol itself
were treated with ethyne under the above conditions, and the
results are summarized in Table 1. The reaction can be carried
out on a 1 g scale. Alkoxy and alkyl derivatives gave
divinylphenol predominantly or exclusively. p-Pivaloxyphenol
and p-phenylphenol gave comparable amounts of monovinyl
and divinyl derivatives. The divinylation is facilitated by
electron-donating substitutents on the aromatic ring. Styrenes
with oxygen functionalities at the ortho- and/or para-positions
are known to be extremely sensitive to acids.7 It is therefore
notable that the present vinylation reaction can be applied to
m-methoxyphenol and m-silyloxyphenols. Even 3,5-bis(silyl-
oxy)phenol is divinylated giving a protected 2,6-divinyl-
benzene-1,3,5-triol. In order to avoid desilylation, the reactions
of silyloxyphenols were quenched with either K2CO3 in MeOH
or K2CO3 in THF–water at room temperature. The latter
conditions were employed in the divinylation of
m-silyloxyphenols. Alcohol addition to the reactive olefin took
place when the protonation was conducted in the presence of
MeOH.
Divinylbenzenes are an important class of chemicals possessing
two reactive sites. They are popular cross-linking agents in
polymer chemistry. Alternating copolymers have been synthe-
sized by bis-addition reactions to divinylbenzenes, and use of
the Heck reaction, amine addition reaction and olefin metathesis
have been reported.1 The Diels–Alder reaction of divi-
nylbenzenes is a convenient method for the synthesis of
polycyclic aromatic compounds.2 In spite of their significance
in polymer and organic synthesis, studies have been limited to
the three isomers of divinylbenzene,3 and very few function-
alized derivatives are known. This is due to the lack of a
straightforward method for their preparation, since the direct
substitution of aromatic C–H bonds with C–CHNCH2 groups
has proved extremely problematic.4 Divinylbenzenes have been
synthesized by stepwise transformations from benzene via
diethylbenzene, dihalobenzene, diformylbenzene etc.5 Func-
tionalized divinylbenzenes can be accessed only by multi-step
syntheses if these methods are employed. Previously, we
reported the direct ortho-vinylation of phenols with ethyne.6
Described here is the direct 2,6-divinylation of phenols
(Scheme 1). Two vinyl groups are introduced to the benzene
nucleus at meta-positions in one step.
Ethyne was bubbled into a chlorobenzene solution of SnCl4–
Bu3N (5 equiv.) at 250 °C.† SnCl4–Bu3N (2 equiv.) and p-tert-
butylphenol (1 equiv.) were added, and the mixture was heated
at 100 °C for 30–60 min. The reaction was quenched with 2 m
NaOH and EtOH at reflux. After acetylation, 4-tert-butyl-
2,6-divinylphenyl acetate and 4-(tert-butyl-2-vinylphenyl ace-
tate were obtained in 71% combined yield in a ratio of 5 :1 (by
NMR spectroscopy). The divinylphenols were acetylated before
isolation for the purpose of stabilization. When the reaction was
conducted at 60 °C, monovinylphenol predominated. Serious
decomposition took place at chlorobenzene reflux temperature
(132 °C). Other aromatic solvents with high boiling points, such
as toluene, o-xylene and 1,2-dichlorobenzene, could also be
used. Treatment of isolated o-vinylphenol with ethyne under
these conditions resulted in decomposition. Analogous to the
monovinylation reaction of phenols,6 the divinylation probably
involves formation of alkynyltin and phenoxytin followed by
the carbostannylation reaction between these species. The
alkaline quench (2 m NaOH–EtOH at reflux) is essential for the
Mixtures of di- and mono-vinylphenyl acetate were treated
with K2CO3 in MeOH at room temperature to give 2,6-div-
inylphenol and 2-vinylphenol, which were readily separable by
silica gel chromatography. Thus, divinylphenols are obtained
from phenol, alkylphenols and alkoxyphenols in overall yields
ranging from 40 to 60% (Scheme 2). The treatment of 4-(tert-
butyldimethylsilyloxy)phenol with KF in MeOH gave 2,6-di-
Table 1 2,6-Divinylation of phenols with ethynea
X
Yield (%)
Divinyl:Monovinyl
H
4-Me
4-But
66
69
71
77
73
72
80
87
75
25c
48
49
41
5:1
5:1
5:1
4-MeO
!10:1
4-ButMe2SiO
4-ButPh2SiO
4-Ph
6:1
!10:1
1:1
4-ButCOO
3-Me
1:3
4:1b
!10:1
!10:1
!10:1
8:1
3-MeO
3-ButMe2SiO
3-ButPh2SiO
3,5-(ButMe2SiO)2
OH
OAc
OAc
i, SnCl4–Bu3N
ii, Ac2O, pyridine
HC CH
+
a
Yields of acetates are shown. Ratios were determined by 1H NMR
X
+
b
spectroscopy.
Monovinylated product is a 1:1 mixture of 2-vinyl-
c
5-methylphenyl acetate and 2-vinyl-3-methylphenyl acetate. The low
yield is due to decomposition of the divinylphenol under the reaction
conditions.
X
X
Scheme 1
Chem. Commun., 1997
1663

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p-methoxyphenol (1.24 g, 10 mmol) in chlorobenzene (30 ml), SnCl4 (2.3
OH
OH
ml, 20 mmol) and Bu3N (4.8 ml, 20 mmol) were added successively. After
heated at 100 °C for 1 h, 2 m NaOH (400 ml) and ethanol (150 ml) were
added, and heating was continued for another 2 h at 100 °C. The mixture
was cooled, and acidified with 2 m HCl. The organic materials were
extracted with diethyl ether, washed with brine, dried over MgSO4 and
filtered. After removal of the diethyl ether under reduced pressure, pyridine
(8.1 ml) and acetic anhydride (4.7 ml) were added to the resulted
chlorobenzene solution, and the products were acetylated by stirring at room
temperature for 12 h. An aqueous work-up followed by flash chromatog-
raphy (hexane–ethyl acetate 100:1) over silica gel gave 4-methoxy-
2,6-divinylphenyl acetate (1.49 g, 77%), containing ca. 5% of 4-methoxy-
2-vinylphenyl acetate as indicated by 1H NMR spectroscopy.
i, SnCl4–Bu3N, HC≡CH
ii, Ac2O, pyridine
iii, K2CO3, MeOH
iv, separation
X
X
X = H
44%
59%
58%
48%
X = 4-Me
X = 4-But
X = 4-MeO
X = 4-ButMe2SiO 48%
X = 4-ButPh2SiO
X = 3-Me
55%
52%
Scheme 2
1 For example, M. Suzuki, J.-C. Lim and T. Saegusa, Macromolecules,
1990, 23, 1574; A. Kumar and B. E. Eichinger, Makromol. Chem., Rapid.
Commun., 1992, 13, 311; Y. Chujo, I. Tomita, Y. Kozawa and
T. Saegusa, Macromolecules, 1993, 26, 2643; E. Thorn-Csa´nyi and
K. P. Pflug, J. Mol. Catal., 1994, 90, 69.
2 For example, L. Liu and T. J. Katz, Tetrahedron Lett., 1990, 31, 3983;
H. Hamana, K. Horiguchi, T. Hagiwara and T. Narita, Bull. Chem. Soc.
Jpn., 1990, 63, 1884; A. B. Padias, T.-P. Tien and H. K. Hall, Jr., J. Org.
Chem., 1991, 56, 5540; J. Nishimura, Y. Horikoshi, Y. Wada,
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Soc., 1994, 116, 2793.
OH
OH
OH
KF
66%
OSiMe2But
Scheme 3
vinylbenzene-1,4-diol (Scheme 3). mp 131–132 °C (toluene),
which should be an interesting building block for redox
polymers. In spite of their simple molecular structure, most of
the divinylphenols formed, including the parent 2,6-di-
vinylphenol itself, the new compounds.8 These bifunctional and
reactive substances should have various applications in polymer
chemistry and organic chemistry.
We thank Mr Katsumi Kobayashi (Tohoku University) for
his assistance in the present work. This work was supported by
grants from JSPS (Research for the Future Program), the
Ministry of Education, Science and Culture, Japan (No.
07554065 and 08404050) and a SUNBOR Grant.
3 Separation of isomeric divinylbenzenes: B. T. Storey, J. Polym. Sci., Part
A, 1965, 3, 265; R. H. Wiley, J. I. Jin and Y. Kamath, J. Polym. Sci., Part
A, 1968, 6, 1065.
4 M. Yamaguchi, Y. Kido, A. Hayashi and M. Hirama, Angew. Chem., Int.
Ed. Engl. 1997, 36, 1313 and references cited therein.
5 For example, H. W. Johnston and J. L. R. Williams, J. Am. Chem. Soc.,
1947, 69, 2065; R. H. Mitchell, B. N. Ghose and M. E. Williams, Can.
J. Chem., 1977, 55, 210; J. E. Plevyak and R. F. Heck, J. Org. Chem.,
1978, 43, 2454; D. R. McKean, G. Parrinello, A. F. Renaldo and
J. K. Stille, J. Org. Chem., 1987, 52, 422; O. Nuyken and F. Siebzehnru¨bl,
Makromol. Chem., 1988, 189, 541.
6 M. Yamaguchi, A. Hayashi and M. Hirama, J. Am. Chem. Soc., 1995,
117, 1151.
7 C. G. Overberger, L. H. Arond, D. Tanner, J. J. Taylor and T. Alfrey, Jr.,
J. Am. Chem. Soc., 1952, 74, 4848; Y. Okamoto and H. C. Brown, J. Org.
Chem., 1957, 22, 485; M. Mayen and E. Marechal, Bull. Soc. Chim. Fr.,
1972, 4662.
Footnotes and References
* E-mail: yama@mail.pharm.tohoku.ac.jp
† Typical experimental procedure: Ethyne was bubbled into chlorobenzene
(170 ml) at 250 °C for 1 h. Bubbling was stopped, and SnCl4 (5.9 ml, 50
mmol) and Bu3N (11.9 ml, 50 mmol) were added. The mixture was stirred
8 A patent for 4-methyl-2,6-divinylphenol has appeared: H. Kitano,
Jap. Pat. 74 14 319, 1974 (Chem. Abstr., 1975, 82, 114031j).
at room temperature for
1
h
under an argon atmosphere, and
Received in Cambridge, UK, 23rd June 1997; 7/04379A
1664
Chem. Commun., 1997