A useful modification of the Kraus procedure1 for preparation of ω-bromo-1-alkenes by HMPA-promoted elimination of HBR from 1,ω-dibromoalkanes

Article abstract of DOI:10.1081/SCC-100104046

A reliable, reproducible, general, and detailed procedure for the mono-elimination of hydrogen bromide from 1,ω-dibromoalkanes is described.

Full text of DOI:10.1081/SCC-100104046

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A USEFUL MODIFICATION OF
THE KRAUS PROCEDURE FOR
PREPARATION OF ω-BROMO-1-
ALKENES BY HMPA-PROMOTED
ELIMINATION OF HBR FROM
1,ω-DIBROMOALKANES
Thomas R. Hoye a , Joshua J. Van Veidhuizen a
Tricia J. Vos a & Peng Zhao a
a Department of Chemistry, University of
,
Minnesota, 207 Pleasant Street, SE, Minneapolis,
MN, 55455, U.S.A.
Version of record first published: 09 Nov 2006.
To cite this article: Thomas R. Hoye , Joshua J. Van Veidhuizen , Tricia J. Vos
& Peng Zhao (2001): A USEFUL MODIFICATION OF THE KRAUS PROCEDURE FOR
PREPARATION OF ω-BROMO-1-ALKENES BY HMPA-PROMOTED ELIMINATION OF HBR
FROM 1,ω-DIBROMOALKANES, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 31:9, 1367-1371
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SYNTHETIC COMMUNICATIONS, 31(9), 1367–1371 (2001)
A USEFUL MODIFICATION OF THE
KRAUS PROCEDURE1 FOR PREPARATION
OF v-BROMO-1-ALKENES BY
HMPA-PROMOTED ELIMINATION OF
HBR FROM 1,v-DIBROMOALKANES
Thomas R. Hoye,* Joshua J. Van Veidhuizen,
Tricia J. Vos, and Peng Zhao
Department of Chemistry, 207 Pleasant Street, SE,
University of Minnesota, Minneapolis, MN 55455
ABSTRACT
A reliable, reproducible, general, and detailed procedure for
the mono-elimination of hydrogen bromide from 1,o-dibro-
moalkanes is described.
a,o-Difunctional compounds containing an intervening number of
methylene groups and in which the two functional groups are different are
extremely valuable building blocks for the synthesis of more complex
molecules. However, these compounds are often not trivially available, so
efficient procedures for making these types of molecules are equally
valuable.
o-Bromo-1-alkenes2 comprise one very useful class of bifunctional
compounds, since the alkene is a masked precursor to many other
* Corresponding author.
1367
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

1368
HOYE ET AL.
common functional groups and Br is, for example, readily converted to
organometallic reagents or displaced by nucleophiles. Kraus and
Landgrebe1 first described the use of HMPA as a base for the preparation
fo 2a and 2b by elimination of one equivalent of hydrogen bromide from the
readily available and symmetrical dibromobutane 1a and dibromohexane
1b, respectively.2 Others have reported the conversion of 1 to 2 for various
members of this series (Scheme 1) using a variety of bases [n ¼ 4 (1a)/
HMPA,1,3 n ¼ 5/HMPA,1,3 n ¼ 6 (1b)/HMPA,1,3 n ¼ 6 (1b)/KOH,4 n ¼ 7/
HMPA,5,6 n ¼ 8 (1c)/t-BuOK7].
Scheme 1.
We recently used the Kraus method for the preparation of both com-
pounds 2a and 2b. In each instance, the procedure, although eventually
successful, was not immediately efficient and required optimization. The
problem was more acute in the case of the higher boiling homolog,
hexane 2b.8a Because of the value of the products and the convenience of
the Kraus reaction, we report here the results of our studies, which have led
to a modified procedure that we consider more reliable to the first-time user.
It is also generally applicable and succeeds for the preparation of bromooc-
tene 2c and bromodecene 2d, which have not previously been prepared via
the HMPA-mediated elimination.
Our principal change of the reported procedure has been to perform
the elimination reaction of each substrate at the same pot temperature
(ꢀ200ꢁC) and to adjust the pressure of the system (as dictated by the
volatility of the product). This permits distillative removal of the desired
o-bromo-1-alkene at essentially the same rate for any of the series 2a–2d.
Although we have not performed this procedure on the odd-numbered
members of the series (e.g. n ¼ 5, 7, 9, and 11), we would expect little
difficulty with these transformations. Each of the alkenes was prepared
several times leading to the optimized conditions listed in Table 1. We
have made the hexene 2b starting from 52 and 70 g of 1b and the octane

v-BROMO-1-ALKENES
1369
2c from 50 g of 1c and obtained 67, 60, and 70% yields, respectively, after
redistillation.
In summary, we believe the procedure detailed below to be a repro-
ducible method8b applicable to a variety of 1,o-dibromoalkanes 1.
PROCEDURE
Caution should be exercised in handling HMPA at all stages of the
procedure. A large stir bar and the dibromoalkane 1 [5 mL (X mmol, see
Tab. 1 for values of X, P, T, Y, C, and D)] were placed in a 15-mL, three-
necked, round-bottom flask equipped with a 10 mL pressure-equalizing
addition funnel, short-path distillation head, and stopper. An oil bath was
preheated to 200ꢁC, and the pressure of the distillation unit was adjusted to
P mm of Hg.9 The distillation head was thoroughly insulated with cotton,
and the solution was stirred rapidly throughout the reaction/distillation.
The round-bottom flask was lowered into the preheated oil bath to within
1 cm of the bottom of the joints, and dropwise addition of HMPA (Y mmol)
was begun immediately. The rate of addition was set to be complete within
’ 30 min. The receiver flask was cooled in a dry ice/acetone bath. Within 10
min, the distillation head temperature rapidly rose and was maintained at T
ꢁC by periodically adjusting the depth of the oil bath. Heating was contin-
ued until the head temperature fell (ꢀ30 min after addition of HMPA was
complete). The pot residue, consisting of HMPAÁHBr salts, was a black-
brown viscous oil.10 The distillate, which was clear but sometimes contained
a white precipitate of frozen HMPA, was allowed to warm to room tem-
perature, at which time it was a cloudy colorless liquid.11 This mixture was
diluted with pentane (ꢀ5 volumes), washed twice with water, dried (NaSO4),
filtered, and carefully concentrated12 to give a clear liquid (C %), which
contained virtually no HMPA (1H NMR analysis) and was >90% the
Table 1. Results of Elimination of HBr from 1,o-Dibromoalkanes 1 with HMPA
to Give o-Bromo-1-alkenes 2
Chain
length
Di-
bromide 1
Yield of 2
1st distill
Yield of 2
2nd distill
HMPA
Pressure
Temp.
ꢁ
n
X mmol
Y mmol
P (torr)
T C
C %
D %
6
8
10
32.5
27.2
22.2
42.3
40.8
44.4
100
75
50
ꢀ100
ꢀ135
ꢀ145
78
74
75
60
52
52

1370
HOYE ET AL.
desired o-bromo-1-alkene (the remainder was starting dibromide 1). This
could be further purified by redistillation12 to give a clear liquid (D %).
ACKNOWLEDGMENTS
This study was supported by the National Institutes of Health
(CA76497). We thank Ms. Elizabeth A. Colby for performing the experi-
ment described in note 8b.
REFERENCES AND NOTES
1. Kraus, G.A.; Landgrebe, K. Synthesis 1984, 885.
2. Current prices (in $/g) of CH2 ¼ CH(CH2)nÀ2Br (2) and Br(CH2)nBr
(1) for the largest quantity listed in the 1998–1999 catalog of the
Aldrich Chemical Company:
Cost of
o-Bromo-1-
alkene (2)
Cost of
1,o-Dibromo-
alkane (1)
Value Added
(cost of 2)/
(cost of 1)
Chain
Length (n)
4
5
6
8
10
12
$5.40
$4.52
$20.62
$14.40
not sold
not sold
$0.11
$0.16
$0.12
$1.04
$0.32
$1.34
49
28
172
14
na
na
3. Preparation of the 1-butene (2a), 1-pentene, and 1-hexene (2b) deriva-
tives has been reported on at least 10 subsequent occasions by use of
the Kraus protocol.1
4. Shea, K.J.; Kim, J. J. Am. Chem. Soc. 1992, 114, 3044–3051.
5. Bailey, W.F.; Nurmi, T.T.; Patricia, J.J.; Wang, W. J. Am. Chem. Soc.
1987, 109, 2442–2448.
6. Schoening, A.; Friedrichsen, W. Tetrahedron Lett. 1988, 29, 1137–
1138.
7. Rich, D.H.; Gardner, J.H. Tetrahedron Lett. 1983, 24, 5305–5308.
8. a) Different researchers in our laboratory have achieved yields of 2b
ranging from 7–28% by carefully following the reported procedure.1 In

v-BROMO-1-ALKENES
1371
every case, a large amount of 1,5-hexadiene was co-produced during
the reaction/distillation.
b) An undergraduate researcher with no prior experience with this
reaction repeated the preparation of 10-bromo-1-decene (1d) following
the procedure reported here and obtained a 72 and 51% yield after the
first and second distillations, respectively.
9. For convenience, we used a manostat to maintain a constant pressure,
but this is not necessary.
10. It is convenient to pour the contents of the pot into an HMPA waste
receptacle while the contents are still warm, otherwise the residue soli-
difies, making it more difficult to transfer. The last portions of the pot
residue can be dissolved in warm water.
11. 1H NMR analysis of the distillate at this point showed the relative
amount of (HMPA)/(dieneþbromoalkeneþdibromide). The latter
three could be distinguished for the n ¼ 6 (and n ¼ 4) case, but not
for the longer chain examples. Typically, because of the reduction in
boiling point differences, we observed ꢀ10% HMPA for n ¼ 6, ꢀ 40%
for n ¼ 8, and ꢀ 50% for n ¼ 10.
12. Bp [Br(CH2)4CH ¼ CH2 (2b)] ¼ 140–147 ꢁC at ꢀ760 torr. Bp
[Br(CH2)6CH ¼ CH2 (2c)] ¼ 72–75 ꢁC at 7 torr. Bp[Br(CH2)8CH ¼
CH2 (2d) ¼ 92–95 ꢁC at 4.5 torr. We observed that addition of a
small amount of volatile solvents (like ethyl acetate or CDCl3 used
in GC/MS or NMR analysis of aliquots) led to excessive bumping
during the redistillation. This practice should be avoided.
Received in the USA July 25, 2000