Synthesis of 4-(2,2-dibromovinyl)phenol and its one-pot esterification

Article abstract of DOI:10.1007/s11164-011-0432-6

In situ treatment of 4-(2,2-dibromovinyl)phenol, which was prepared from 4-hydroxybenzaldehyde and carbon tetrabromide in CH₂Cl₂ under Corey-Fuchs conditions, with a diverse range of acids in the presence of dicyclohexyl-carbodiimide

Full text of DOI:10.1007/s11164-011-0432-6

Res Chem Intermed (2012) 38:957–964
DOI 10.1007/s11164-011-0432-6
Synthesis of 4-(2,2-dibromovinyl)phenol and its one-pot
esterification
•
Wensheng Zhang Wenjing Xu Fei Zhang
•
•
•
Jitao Li Mei Liu Wei Li
•
Received: 21 August 2011 / Accepted: 27 October 2011 / Published online: 16 November 2011
Ó Springer Science+Business Media B.V. 2011
Abstract In situ treatment of 4-(2,2-dibromovinyl)phenol, which was prepared
from 4-hydroxybenzaldehyde and carbon tetrabromide in CH2Cl2 under Corey–
Fuchs conditions, with a diverse range of acids in the presence of dicyclohexyl-
carbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) gave the corresponding
esters in high yields.
Keywords gem-Dibromoalkene Á Corey–Fuchs condition Á One-pot Á Synthesis Á
Esterification
Introduction
gem-Dibromoalkenes are versatile organic intermediates in organic synthesis. They
have found wide applications in the synthesis of trisubstituted alkenes of defined
stereochemistry by transition-metal-catalyzed site-selective monoarylation and
monoalkylation reactions. The cross-coupling reaction of gem-dibromoalkenes
with alkynes and organometallic reagents such as Grignard reagents, organozinc
reagents, organostannanes, boronic acids, and derivatives can be stopped at the
monosubstituted stage, giving the trans-configured main products [1, 2]. gem-
Dibromoalkenes have also been widely used for the synthesis of alkynes [3, 4].
Besides, allylsilanes, one of the most useful functional groups for carbon–carbon
bond forming reactions, can also be achieved by tandem cross-coupling of gem-
dibromoalkenes with trimethysilylmethyl Grignard reagent and selective
W. Zhang (&) Á W. Xu Á J. Li Á M. Liu Á W. Li
School of Biological and Chemical Engineering, Jiaozuo Teachers’ College, Shanyang Road 998,
Jiaozuo 450001, China
e-mail: tongjizws@163.com
F. Zhang
Jiaozuo Vocational Education Center, Huayuan Road 57, Jiaozuo 454001, China
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protodesilylation of the corresponding intermediates [5]. Direct coupling of 1,1-
dibromoethenes with 2-aminophenols was proven to be useful method under mild
reaction conditions for the synthesis of benzoxazoles, an important class of
heterocyclic compounds due to their wide spectrum of biological and photochro-
matic activities [6]. Recently, a novel method for the iron-catalyzed ketonization of
2-aryl-1,1-dibromoalkenes with KOAc was reported achieving a series of a-acetoxy
aryl ketones [7]. In addition, reduction of gem-dibromoalkenes provides an
important method for the stereoselective synthesis of (E)-vinyl bromides [8],
another kind of important cross-coupling reagent.
Condensation of aromatic aldehydes with CBr4, known as Corey–Fuchs reaction,
is an important method for the synthesis of gem-dibromoalkenes [9, 10]. However,
the preparation of 4-(2,2-dibromovinyl)phenol, a kind of gem-dibromoalkene
containing phenol fragment that shows some important properties in organic
chemistry, was seldom reported. Our research on the synthesis of 4-(2,2-
dibromovinyl)phenol showed that the reaction of 4-hydroxybenzaldehyde with
carbon tetrabromide under an improved Corey–Fuchs condition could proceed
smoothly although the expected product 4-(2,2-dibromovinyl)phenol is instable.
According to Corey–Fuchs’ procedure, dibromoolefins were formed by the addition
of the aldehyde (1 equiv.) to a mixture of triphenylphoephine (4 equiv.) and carbon
tetrabromide (2 equiv.) in methylene chloride at 0 °C with a reaction time of 5 min.
In our procedure, a triphenylphoephine (4 equiv.) solution of methylene chloride
was added dropwise to a stirred methylene chloride solution of 4-hydroxybenzal-
dehyde and carbon tetrabromide (2 equiv.) at 0 °C. The reaction system was stirred
for 30 min at 0 °C and 5 h at room temperature. The product turns from a light-
yellow solid to a vicious and brownish black solid when separated from the reaction
system and exposed to the air for 5 days or stored in refrigerator at 4 °C for 20 days.
In this paper, we wish to report the synthesis and tandem esterification of 4-(2,2-
dibromovinyl)phenol, which may provide more stable derivatives of the synthetic
intermediate (Scheme 1).
Results and discussion
4-(2,2-Dibromovinyl)phenol 2 was obtained in a yield of 90% by the reaction of
4-hydroxybenzaldehyde 1 and CBr4 according to an improved procedure of Corey–
Fuchs reaction [9, 10]. One-pot esterification of the intermediate 2 with various
R-CO2H (3)
Br
O
O
Br
PPh3
DCC-DMAP
rt, 5-12 h
Br
R
Br
CBr4
+
CHO
HO
HO
CH2Cl2
oc, 30 min.
rt, 5 h
0
1
2
4
R = alkyl, aryl
Scheme 1 Synthesis and one-pot esterification of 4-(2,2-dibromovinyl)phenol
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Synthesis of 4-(2,2-dibromovinyl)phenol
959
acids, without isolation from the condensation system, was achieved in high yields
at room temperature. The results are summarized in Table 1.
This tandem esterification proved to be applicable not only for aliphatic acids
such as formic acid, acetic acid, butyric acid, and ferrocenylformic acid, affording
the corresponding esters 4a–d in 84–91% yields (Table 1, entries 1–4), but also for
aromatic acids such as benzoic acid, 4-methylbenzoic acid and 4-chlorolbenzoic
acid, giving 4e–g in 84–86% yields (Table 1, entries 5–7). In the case of a,b-
unsaturated acids including cinnamic acid, (E)-3-(4-bromophenyl)acrylic acid and
3-ferrocenyl acrylic acid, the corresponding 3-acrylates 4 h–j were also isolated in
yields of 80–83% (Table 1, entries 8–10). The structures of 4a–j were characterized
1
by IR, H NMR, 13C NMR and elementary analysis.
Experimental
Melting points were recorded using WRS-1B digital melting point apparatus and
were uncorrected. IR spectra were obtained on a Perkin-Elmer FT-IR spectropho-
1
tometer. H NMR and 13C NMR spectra were recorded using a Bruker DPX-400
spectrometer with SiMe4 as an internal standard. Elemental analyses were
performed with a Perkin-Elmer 2,400 CHNS elemental analyzer. All reactions
were monitored by TLC with HuanghaiGF254 silica gel-coated plates. Column
chromatography was carried out using 300–400 mesh silica gel at medium pressure.
Synthesis of 4-(2,2-dibromovinyl)phenol
To a stirred CH2Cl2 solution (10 mL) of 4-hydroxybenzaldehyde 1 (122 mg,
1 mmol) and CBr4 (663 mg, 2 mmol) was added dropwise PPh3 (1,049 mg,
4 mmol) in CH2Cl2 (10 mL) at 0 °C. The reaction system was stirred for 30 min at
0 °C and 5 h at room temperature. After the completion of the reaction monitored
by TLC, the reaction mixture was filtered through silicon gel. The filtrate was
extracted with 10% NaOH (30 9 3 mL). To the combined aqueous layer was added
10% HCl under stirring to a pH of 5. The precipitate was filtered, washed with
water, and dried over vacuum desiccator. Purification by column chromatography
(silica gel, EtOAc-petroleum ether) afforded 2 as a light-yellow solid. Mp:
105.3–107.3 °C. IR (KBr): 3410, 1605, 1507, 1438, 1232, 873, 819 cm-1. 1H NMR
(400 MHz, CDCl3): d 6.83 (2H, d, J = 8.8 Hz), 7.39 (1H, s), 7.43 (2H, d,
J = 8.8 Hz), 7.55–7.67 (1H, br). 13C NMR (100 MHz, CDCl3): d 87.19, 115.41,
127.80, 130.08, 136.33, 156.06. Anal. Calcd for C8H6Br2O: C, 34.57; H, 2.18; Br,
57.50. Found: C, 34.51; H, 2.21; Br, 57.54.
One-pot esterification of 4-(2,2-dibromovinyl)phenol
To the reaction system for the synthesis of 4-(2,2-dibromovinyl)phenol was added
acids 3 (1 mmol), DCC (231 mg, 1.1 mmol), and DMAP (12 mg, 0.1 mmol). The
reaction system was stirred for 5–12 h at room temperature. After the completion of
the esterification screened by TLC, the reaction mixture was filtered through silicon
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gel. The filtrate was washed with saturated brine (20 9 2 mL) and water (20 mL).
The organic layer was dried over Na2SO4, concentrated under reduced pressure, and
dried in high vacuum. Purification of the residue by column chromatography (silica
gel, EtOAc-petroleum ether) afforded 4.
4-(2,2-Dibromovinyl)phenyl formate 4a
1
Mp: 99.3–99.8 °C. IR (KBr): 3006, 1604, 1506, 1231, 1180, 873, 819 cm-1. H
NMR (400 MHz, CDCl3): d 5.11 (1H, s), 6.82 (2H, d, J = 8.8 Hz), 7.39 (1H, s),
7.46 (2H, d, J = 8.8 Hz). 13C NMR (100 MHz, CDCl3): d 87.50, 115.31, 128.11,
130.09, 130.12, 136.20, 155.66. Anal. Calcd for C9H6Br2O2: C, 35.33; H, 1.98; Br,
52.23. Found: C, 35.35; H, 1.97; Br, 52.27.
4-(2,2-Dibromovinyl)phenyl acetate 4b
Vicious light-yellow liquid. IR (KBr): 2926, 1763, 1603, 1504, 1206, 1169,
1
913 cm-1. H NMR (400 MHz, CDCl3): d 2.31 (3H, s), 7.10 (2H, d, J = 8.8 Hz),
7.46 (1H, s), 7.55 (2H, d, J = 8.8 Hz). 13C NMR (100 MHz, CDCl3): d 21.09,
89.82, 121.58, 129.54, 132.87, 135.88, 150.49, 169.09. Anal. Calcd for
C10H8Br2O2: C, 37.54; H, 2.52; Br, 49.94. Found: C, 37.59; H, 2.50; Br, 49.91.
4-(2,2-Dibromovinyl)phenyl butyrate 4c
Mp: 44.8–45.8 °C. IR (KBr): 3015, 2963, 1750, 1598, 1505, 1209, 1174, 1147,
836 cm-1. 1H NMR (400 MHz, CDCl3): d 1.04 (3H, t, J = 7.2 Hz), 1.74–1.83 (2H,
m), 2.54 (2H, t, J = 7.2 Hz), 7.09 (2H, d, J = 8.8 Hz), 7.45 (1H, s), 7.55 (2H, d,
J = 8.8 Hz). 13C NMR (100 MHz, CDCl3): d 13.64, 18.44, 36.24, 89.80, 121.65,
129.57, 132.81, 135.98, 150.64, 171.85. Anal. Calcd for C12H12Br2O2: C, 41.41; H,
3.48; Br, 45.92. Found: C, 41.46; H, 3.49; Br, 45.85.
4-(2,2-Dibromovinyl)phenyl benzoate 4d
Mp: 104.9–106.7 °C. IR (KBr): 1738, 1595, 1504, 1450, 1263, 1204, 1171, 1059,
1
707 cm-1. H NMR (400 MHz, CDCl3): d 7.24 (2H, d, J = 8.8 Hz), 7.49 (1H, s),
7.52–7.67 (5H, m), 8.20 (2H, d, J = 8.8 Hz). 13C NMR (100 MHz, CDCl3):
d 98.93, 121.79, 128.64, 129.33, 129.66, 130.22, 133.00, 133.76, 135.97, 150.83,
164.91. Anal. Calcd for C15H10Br2O2: C, 47.16; H, 2.64; Br, 41.83. Found: C,
47.25; H, 2.69; Br, 41.75.
4-(2,2-Dibromovinyl)phenyl 4-methylbenzoate 4e
1
Mp: 110.9–111.5 °C. IR (KBr): 1736, 1609, 1508, 1278, 1218, 1077 cm-1. H
NMR (400 MHz, DMSO-d6): d 2.43 (3H, s), 7.34 (2H, d, J = 8.4 Hz), 7.42 (2H, d,
J = 8.0 Hz), 7.70 (2H, d, J = 8.0 Hz), 7.82 (1H, s), 8.03 (2H, d, J = 8.4 Hz). 13C
NMR (100 MHz, DMSO-d6): d 21.42, 89.53, 122.25, 126.14, 129.70, 129.73,
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Synthesis of 4-(2,2-dibromovinyl)phenol
963
130.03, 132.89, 136.38, 144.81, 150.70, 164.51. Anal. Calcd for C16H12Br2O2: C,
48.52; H, 3.05; Br, 40.35. Found: C, 48.58; H, 3.03; Br, 40.32.
4-(2,2-Dibromovinyl)phenyl 4-chlorobenzoate 4f
Mp: 127.4–127.9 °C. IR (KBr): 1733, 1590, 1504, 1278, 1210, 1167, 1081 cm-1
.
1H NMR (400 MHz, DMSO-d6): d 7.37 (2H, d, J = 8.4 Hz), 7.69 (2H, d,
J = 5.2 Hz), 7.71 (2H, d, J = 5.2 Hz), 7.83 (1H, s), 8.13 (2H, d, J = 8.4 Hz). 13C
NMR (100 MHz, DMSO-d6): d 89.66, 122.18, 127.81, 129.33, 129.76, 131.84,
133.09, 136.35, 139.25, 150.51, 163.74. Anal. Calcd for C15H9Br2ClO2: C, 43.26;
H, 2.18; Br, 38.37. Found: C, 43.21; H, 2.15; Br, 38.45.
4-(2,2-Dibromovinyl)phenyl ferrocenylcarboxylate 4 g
Mp: 77.0–78.7 °C. IR (KBr): 1731, 1598, 1506, 1451, 1266, 1204, 1099, 817 cm-1
.
1H NMR (400 MHz, DMSO-d6): d 4.36 (5H, s), 4.62 (2H, s), 4.93 (2H, s), 7.29 (2H,
d, J = 8.4 Hz), 7.69 (2H, d, J = 8.4 Hz), 7.82 (1H, s). 13C NMR (100 MHz,
DMSO-d6): d 69.35, 70.03, 70.45, 72.37, 89.40, 122.28, 129.73, 132.65, 136.43,
150.61, 169.62. Anal. Calcd for C19H14Br2FeO2: C, 46.58; H, 2.88; Br, 32.62.
Found: C, 46.65; H, 2.85; Br, 32.53.
4-(2,2-Dibromovinyl)phenyl cinnamate 4 h
Mp: 117.3–118.3 °C. IR (KBr): 1743, 1634, 1600, 1576, 1505, 1310, 1220, 1138,
767 cm-1. 1H NMR (400 MHz, DMSO-d6): d 6.89 (1H, d, J = 15.6 Hz), 7.28 (2H,
d, J = 8.8 Hz), 7.44–7.48 (3H, m), 7.68 (2H, d, J = 8.8 Hz), 7.80–7.83 (3H, m),
7.88 (1H, d, J = 15.6 Hz). 13C NMR (100 MHz, DMSO-d6): d 89.47, 117.16,
122.15, 128.85, 129.17, 129.72, 131.11, 132.79, 133.97, 136.38, 146.87, 150.54,
164.88. Anal. Calcd for C17H12Br2O2: C, 50.03; H, 2.96; Br, 39.16. Found: C,
50.10; H, 2.99; Br, 39.07.
(E)-4-(2,2-Dibromovinyl)phenyl 3-(4-bromophenyl)acrylate 4i
Mp: 147.1–148.4 °C. IR (KBr): 3089, 2947, 1741, 1635, 1505, 1220, 1145, 1071,
820 cm-1. 1H NMR (400 MHz, DMSO-d6): d 6.94 (1H, d, J = 16.0 Hz), 7.28 (2H,
d, J = 8.8 Hz), 7.66 (2H, d, J = 6.0 Hz), 7.68 (2H, d, J = 6.0 Hz), 7.78 (1H, d,
J = 8.8 Hz), 7.81 (1H, s), 7.86 (1H, d, J = 16.0 Hz). 13C NMR (100 MHz, DMSO-
d6): d 89.50, 118.07, 122.12, 124.55, 129.73, 130.76, 132.15, 132.83, 133.28,
136.37, 145.52, 150.49, 164.74. Anal. Calcd for C17H11Br3O2: C, 41.93; H, 2.28;
Br, 49.22. Found: C, 41.96; H, 2.24; Br, 49.27.
4-(2,2-Dibromovinyl)phenyl 3-ferrocenyl acrylate 4j
Mp: 138.7–139.9 °C. IR (KBr): 1716, 1624, 1598, 1505, 1208, 1170, 1143,
876 cm-1. 1H NMR (400 MHz, DMSO-d6): d 4.23 (5H, s), 4.54 (2H, s), 4.80 (2H,
s), 6.37 (1H, d, J = 15.6 Hz), 7.26 (2H, d, J = 8.4 Hz), 7.67 (2H, d, J = 8.4 Hz),
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7.75 (1H, d, J = 15.6 Hz), 7.81 (1H, s). 13C NMR (100 MHz, DMSO-d6): d 69.27,
69.75, 71.48, 78.14, 89.31, 113.18, 122.18, 129.64, 132.54, 136.41, 148.98, 150.73,
164.81. Anal. Calcd for C21H16Br2FeO2: C, 48.88; H, 3.13; Br, 30.97. Found: C,
48.94; H, 3.10; Br, 30.91.
Conclusions
In conclusion, we developed a facile method for the synthesis of 4-(2,2-
dibromovinyl)phenol and its tandem esterification catalyzed by DCC-DMAP under
mild conditions in high yields. The synthetic applications of these gem-
dibromoalkene compounds in metal-catalyzed cross-coupling reaction were in
progress in our laboratory.
Acknowledgments This work was supported by Program for Science & Technology Innovation Talents
in Universities of He’nan Province (No. 2011HASTIT032), Foundation of He’nan Educational
Committee (No. 2011C150001) and Foundation of He’nan Scientific and Technological Committee
(No. 112300410236, 102300410181).
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