An expedient synthesis of allylic/secondary bromides from dehydration of tertiary-β-bromo alcohols

Article abstract of DOI:10.1081/SCC-120024749

Tertiary-β-bromo alcohols, derived from simple monoterpenes and olefins, react with BF₃·OEt₂ in refluxing benzene in 1-2h to afford the corresponding allylic/secondary bromides in 45-90% yield. In case of substrates containing olefin

Full text of DOI:10.1081/SCC-120024749

Synthetic Communications
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ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
An Expedient Synthesis of Allylic/Secondary
Bromides from Dehydration of Tertiary-β-bromo
Alcohols
B. K. Bettadaiah & Dr. P. Srinivas
To cite this article: B. K. Bettadaiah & Dr. P. Srinivas (2003) An Expedient Synthesis of
Allylic/Secondary Bromides from Dehydration of Tertiary-β-bromo Alcohols, Synthetic
Communications, 33:20, 3615-3620, DOI: 10.1081/SCC-120024749
To link to this article: http://dx.doi.org/10.1081/SCC-120024749
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 20, pp. 3615–3620, 2003
An Expedient Synthesis of Allylic/Secondary
Bromides from Dehydration of
Tertiary-b-bromo Alcohols
B. K. Bettadaiah and P. Srinivas*
Plantation Products, Spices and Flavour Technology
Department, Central Food Technological Research
Institute, Mysore, India
ABSTRACT
Tertiary-b-bromo alcohols, derived from simple monoterpenes and
olefins, react with BF .OEt in refluxing benzene in 1–2 h to afford
3 2
the corresponding allylic/secondary bromides in 45–90% yield. In
case of substrates containing olefinic or hydroxyl groups, formation
of cyclic ethers was observed.
Key Words: Tertiary-b-bromo alcohols; Dehydration; BF
Allylic bromides; Secondary bromides.
3
ÁOEt
2
;
*
Correspondence: Dr. P. Srinivas, Central Food Technological Research
Institute, Plantation Products, Spices and Flavour Technology Depart-
ment, Cheluvamba Mansion, Mysore 570013, Karnataka, India; Fax: 0821-
5
17233; E-mail: ppft@cscftri.ren.nic.in.
3
615
DOI: 10.1081/SCC-120024749
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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3
616
Bettadaiah and Srinivas
Selective synthesis of allylic bromides and functionalized allylic
[
1]
halides plays an important role in organic synthesis. They serve as
[
useful precursors for allylic organometallic reagents and oxygenated
2]
[3]
monoterpenes, which are important flavor compounds. The allylic
halides are generally obtained by direct halogenation with reagents viz.,
[4]
[5]
NBS, NCS, NIS, and t-BuOCl. Alternatively, electrophilic addition of
halonium ion to olefins in polar solvents, referred to as co-halogenation
[
reaction, leads to the formation of halohydrin derivatives.
6]
Bromohydrins serve as useful intermediates for the functionalization of
olefins to oxygenated compounds. The trans stereochemistry of halo-
hydrins renders them useful intermediates for several applications
in organic synthesis; mention may be made of, radical cyclization to
[
7]
[8]
lactones, selective reduction with HSn(Bu) to stereo-specific alcohols
3
and a tandem approach to generate reactive radical intermediate
[
9]
by cohalogenation and homolytic carbocyclization. As a part of our
continuing work on the funtionalization of monoterpenic hydrocarbons,
we synthesized bromohydrins of monoterpenes and olefins (Table 1,
1a–f ). These compounds have specific trans stereochemistry, described
earlier in the stereo-specific synthesis of trans-b-terpineol from
[10]
limonene.
To our knowledge, synthesis of reactive allylic halides
from tertiary-b-bromo alcohols is not reported in literature. On the
other hand, dehydration of tertiary and benzylic alcohols has been
[
11,12]
reported by a number of catalysts.
[
Recently, we studied direct
In the present study, we investigated
13]
oxidation of bromohydrins.
their dehydration with a view to obtaining allylic bromides.
In our studies, we found that of the several Lewis acid catalysts
tried, BF ꢀOEt effected dehydration of tertiary-b-bromo alcohols.
3
2
While these bromohydrins, 1a–1d, under basic conditions gave internal
cyclized epoxides, with catalytic quantity of BF ꢀOEt (10 mol%) in
3
2
refluxing benzene readily afforded allylic halides (Sch. 1) in good yields.
Results of this reaction are summarized in Table 1. Interestingly, 1e upon
reaction with acidic catalysts gave exclusively trans-2-bromo-1,8-cineole
(
2e), a key intermediate for the synthesis of trans-2-acetoxy-1,8-cineole,
[
14]
a major aroma constituent of Alpinia galanga Willd. This, apparently,
results from the internal addition of hydroxyl moiety to the isopropenyl
double bond between C-8 and C-9 carbons. Also, in case of bromohydrin
1f the product was trans-2-bromo-1,8-cineole, which again could be
due to cyclic ether formation between hydroxyl groups on C-1 and C-8
carbons.
In summary, dehydration of tertiary-b-bromo alcohols by simple and
inexpensive BF ꢀOEt reagent in catalytic quantity is reported. These
3
2
reactions take place rapidly and can be conveniently carried out on

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Tertiary-b-bromo Alcohols
3617
Table 1. Reaction of tertiary-b–bromo alcohols with BF ꢀOEt in refluxing
3
2
benzene.
a
Product 2
b
Yield (%)
Entry
A
Substrate 1
Reaction time (h)
1
OH
Br
60
75
Br
Br
OH
Br
B
2
c
82
C
OH
Br
2
Br
OH
Br
D
Br
O
45
1.5
O
OH
Br
E
F
Br
90
50
1
2
O
OH
Br
Br
O
OH
a
1 13
Characterized by H, C NMR, and mass spectra.
b
Yield after purification by distillation under reduced pressure.
Formation of 15% of vinylic halide was observed.
c
OH
Br
(10 mol %)
BF .OEt2
R
R
3
Reflux, Benzene
R1
R1
Br
2
1
45-90 %
R = Alkyl or aryl ,
1
R = Alkyl
Scheme 1.
large scale to afford corresponding allylic bromides. The method adopted
here to get the reactive halides from the corresponding olefins through
bromohydrin intermediates provides a new synthetic methodology useful
for the preparation of oxygenated terpene derivatives, which are impor-
tant flavor constituents of several essential oils.

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618
Bettadaiah and Srinivas
General Procedure: Reaction of Tertiary-b-bromo
Alcohols with BF ÁOEt
3
2
In a round-bottomed flask, a solution of tertiary-b-bromo alcohol
Entry 1a–f, 5 mmol) in dry benzene (10 mL) was taken. To this BF ꢀOEt
(
(
3
2
10 mol%) was added, and the mixture was set for reflux. The reaction
ꢁ
ꢁ
ꢁ
was monitored on GC (HP-1 Column, 60 /8 /220 C-5 min) by periodic
injection of aliquot of worked-up sample for the disappearance of the
bromohydrin. At the end of the reaction, the product was put into 5%
NaHCO (20 mL) and organic layer separated. It was washed with water
3
(
10 mL ꢂ 2) and dried over anhydrous Na SO . Evaporation of solvent
2
4
afforded crude product, which was distilled under reduced pressure to
afford pure halide. The physical, spectral, and analytical data of products
are given below. The optical rotations were recorded at Perkin-Elmer 243
digital polarimeter. NMR spectra were recorded at Bruker AMX-400
instrument. Mass spectra and elemental analysis were carried
out at Shimadzu QP 5000 GC-MS and Elementar EL-III instruments
respectively.
ꢁ
20
D
6
-Bromo-1-methyl-cyclohex-1-ene (2a). B.p. 62–64 C/4.5 Torr. ½ꢀꢃ
ꢁ
1
þ1.5 (c ¼ 2, CHCl ). H NMR ꢁ ppm ¼ 1.79 (s, 3H), 1.33–1.65 and
3
1
3
1
5
1
.94–2.23 (m, 6H), 4.63 (s, 1H), 5.55 (br, 1H). C NMR: 134.3, 127.1,
4.7, 33.1, 25.2, 22, 17.4. MS (m/z): 176 (2.5), 174 (2.5), 161 (2), 159 (0.5),
49 (0.5), 147 (1.5), 135 (2), 133 (0.5), 121 (3), 119 (3), 96 (10), 95 (100), 79
(
45), 77 (35), 67 (80), 55 (50), 41 (45). Anal. calcd. for C and H: 48.02 and
6
.33. Found: 48.31 and 5.77 respectively.
-Bromo-1-methyl-4-(1-methylethyl)-cyclohex-1-ene(2b).B.p.78–80 C/
ꢁ
6
20
ꢁ
1
1
.5 Torr. ½ꢀꢃ þ16 (c ¼ 2, CHCl ). H NMR ꢁ ppm ¼ 0.86 (d, 6H,
D
3
J ¼ 3 Hz), 1.80 (s, 3H), 1.13–1.56 and 1.86–2.26 (m, 6H), 4.60 (s, 1H),
1
.53 (br, 1H). C NMR: 134.1, 127.3, 55.8, 36.5, 34.4, 31.7, 29, 21.4, 19.7,
9.4. MS (m/z): 218 (2), 216 (2), 203 (0.5), 201 (0.5), 175 (1), 173 (1), 138
3
5
1
(
6), 137 (48), 95 (48), 93 (30), 81 (100), 79 (33), 67 (33), 41 (50). Anal.
calcd. for C and H: 55.60 and 7.89. Found: 55.61 and 7.20 respectively.
ꢁ
1
-Bromo-2-phenyl-prop-1-ene (2c). B.p. 80–82 C/1.5 Torr. H NMR ꢁ
3
ppm ¼ 4.41 (s, 2H), 5.58 (s, 1H), 5.51 (s, 1H), 7.36–7.42 (m, 3H),
1
.52–7.54 (m, 2H). C NMR: 144.4, 128.5, 128.3, 127.8, 127.6, 126.2,
3
7
126, 117.2, 34.2. MS (m/z): 198 (22), 196 (22), 117 (100), 115 (75), 103
(
8), 102 (6), 91 (30), 77 (10), 58 (35), 51 (22), 39 (18). Anal. calcd. for C
and H: 54.85 and 4.60. Found: 54.85 and 4.62 respectively.
-Bromo-1-methyl-4-(1-methylethyl)-cyclohex-1-en-5-one (2d). B.p.
6
ꢁ
1
9
1
1
6–98 C/1.5 Torr. H NMR ꢁ ppm ¼ 1.28 (d, J ¼ 6.9 Hz, 6H), 2.17 (s,
H), 2.29 (s, 3H), 1.86–2.05 (m, 2H), 3.18–3.27 (m 1H), 4.93 (br, 1H).
C NMR: 152.8, 126.2, 121.5, 52.7, 33.2, 26.8, 22.7, 22.4, 20.8, 20.6. MS
3

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Tertiary-b-bromo Alcohols
3619
(
(
(
m/z): 232 (0.5), 230 (0.5), 217 (0.5), 215 (0.5), 204 (1), 202 (1), 190 (6), 188
6), 152 (3), 151 (12), 135 (9), 121 (1), 109 (12), 107 (3), 82 (100), 69 (6), 54
15), 41 (28). Anal. calcd. for C and H: 51.96 and 6.54. Found: 51.86 and
6
.63 respectively.
-Bromo-1,3,3-trimethyl-2-oxabicyclo[2.2.2]-octane(2e).B.p.78–80 C/
ꢁ
6
20
ꢁ
1
0
.7 Torr. ½ꢀꢃ þ8.6 (c ¼ 3, CHCl ). H NMR ꢁ ppm ¼ 0.92 (s, 3H), 0.94
D
3
(
s, 3H), 1.44 (s, 3H), 1.53–1.57 (m, 1H), 1.62–1.67 (m, 2H), 1.72–1.75 (m,
1
1
H), 1.99–2.02 (m, 1H), 2.3–2.35 (m, 1H), 2.51–2.57 (m, 1H), 3.86 (br,
1
3
H). C NMR: 55.9, 56.8, 53.1, 22.8, 22, 21.7, 21.3, 21, 20.4, 19.8. MS
(
(
m/z): 234 (3), 232 (3), 219 (2), 217 (2), 191 (20), 189 (24), 153 (55), 135
10), 109 (20), 95 (45), 82 (25), 71 (60), 55 (40), 43 (100), 41 (95). Anal.
calcd. for C and H: 51.52 and 7.35. Found: 51.79 and 7.35 respectively.
ACKNOWLEDGMENT
BKB is thankful to Council of Scientific and Industrial Research,
New Delhi, India, for the fellowship. Assistance of Sophisticated
Instrument Facility, Indian Institute of Science, Bangalore, India in
1
13
recording of H and C NMR spectra is gratefully acknowledged.
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