A Convenient Route to 2-Bromo-3-chloronorbornadiene and 2,3-Dibromonorbornadiene

Article abstract of DOI:10.1055/s-0034-1380417

Substituted norbornadienes are useful in a wide range of applications, including molecular solar-thermal (MOST) energy storage systems. An important precursor for 2,3-substituted norbornadienes is 2-bromo-3-chloronorbornadiene, where the two halogen atoms

Full text of DOI:10.1055/s-0034-1380417

SYNLETT
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©
Georg Thieme Verlag Stuttgart · New York
2015, 26, 1501–1504
1501
letter
Synlett
A. Lennartson et al.
Letter
A Convenient Route to 2-Bromo-3-chloronorbornadiene and
,3-Dibromonorbornadiene
2
Anders Lennartson
Maria Quant
Cl
Kasper Moth-Poulsen*
Br
Department of Chemistry and Chemical Engineering, Chalmers University of
Technology, 41296 Gothenburg, Sweden
Kasper.moth-poulsen@chalmers.se
This paper is dedicated to Prof. K. P. C. Vollhardt on the occasion of his 69th birthday.
Thank you for inspirational leadership and enlightening supervision.
Br
Br
Received: 05.03.2015
Accepted after revision: 15.04.2015
Published online:
This approach to store solar energy has recently been
referred to as molecular solar-thermal (MOST) energy stor-
3
DOI: 10.1055/s-0034-1380417; Art ID: st-2015-b0150-l
age, and studies of norbornadienes as potential MOST sys-
4
tems have been reviewed. Not only are norbornadienes in-
teresting for energy storage, but norbornadienes have
5
Abstract Substituted norbornadienes are useful in a wide range of ap-
plications, including molecular solar-thermal (MOST) energy storage
systems. An important precursor for 2,3-substituted norbornadienes is
found a wide range of other applications in science. We
6
have a special interest in 2-bromo-3-chloronorbornadiene
3), since the 2- and 3-positions can be selectively substi-
tuted through two consecutive Suzuki cross-coupling reac-
tions, one at ambient temperature and one at elevated tem-
perature. The previously published routes to 2- and 2,3-di-
(
2-bromo-3-chloronorbornadiene, where the two halogen atoms can be
substituted selectively through two consecutive Suzuki cross-coupling
reactions. Previous routes to 2-bromo-3-chloronorbornadiene have
used 1,2-dibromoethane as a brominating agent, a substance known to
be carcinogenic and the use of which is restricted in certain countries.
Herein is reported a one-pot route to 2-bromo-3-chloronorbornadiene
in 50% yield using p-toluenesulfonyl bromide as a bromine source. In
addition, the procedure has been adapted to allow synthesis of 2,3-di-
bromonorbornadiene in 37% yield.
7
halogenated norbornadienes are summarized in Scheme
1,8–14
2.
Early attempts to deprotonate 1 with alkyllithium or al-
kylsodium failed due to rapid decomposition into sodium
cyclopentadienide and sodium acetylenide.15 Later, it was
found that 1 is readily deprotonated by Schlosser’s base in
THF at low temperature,16 and treatment of the metalated
norbornadiene with 1,2-dibromoethane or p-toluenesulfo-
nyl chloride affords 2-bromonorbornadiene (4), or 2-chlo-
Key words bromine, chlorine, organometallic reagents, regioselectiv-
ity, alkenes
Norbornadiene (1) was first obtained through a Diels–
13
Alder reaction between cyclopentadiene and acetylene and
ronorbornadiene (5), in 34% or 40% yield, respectively.
1
reported in a patent from 1951. It was soon found that nor-
Synthesis of 2,3-dihalogenated norbornadienes is less
straightforward, since 2,3-dimetalated norbornadiene is
unstable due to decomposition into metal cyclopentadi-
enide and metal acetylide. Also, 2-bromonorbornadiene
undergo fast lithium–bromine exchange when treated with
alkyllithium, thus forming 2-lithionorbornadiene rather
than 2-bromo-3-lithionorbornadiene,13 so the two sites
cannot be deprotonated successively. It was found, howev-
er, that 2-potassionorbornadiene (6) was a strong enough
base to deprotonate 4 to yield 2-bromo-3-potassionorborn-
adiene (7). Consecutive reaction with 1,2-dibromoethane
gives 2,3-dibromonorbornadiene (8).13 This strategy was
further investigated by Tam and co-workers who developed
a practically useful route to 8.14 By treating 8 with tert-bu-
bornadiene and its derivatives undergo a photoinduced in-
tramolecular [2+2] cycloaddition to yield its valence isomer
2
quadricyclane (2, Scheme 1). This reaction is reversible,
and since 2 is a strained molecule this reaction can be used
to store solar energy.
hν
heat or
catalyst
2
1
Scheme 1 Reversible isomerization of 1
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1501–1504

1
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Synlett
A. Lennartson et al.
Letter
Cl
Cl
I-Ph
2
OTf–
Cl
Cl
Cl
I-Ph
Cl
KOH
ref. 8
PPh3
ref. 12
ref. 8
I-Ph 2 OTf-
ref. 11
Ph-I
Cl
Cl
I
Br
Br
Br
KOH
ref. 9
I
H
H
ref. 1
ref. 10
1
2
) t-BuOK, n-BuLi
) TsCl
ref. 13
Br
Br
Cl
Br
1
2
) t-BuOK, n-BuLi
) BrCH2CH2Br
ref. 13
1
2
) t-BuOK, n-BuLi
) BrCH2CH2Br
ref. 13
KOH
ref. 10
1
2
) t-BuLi
) H2O
Br
Br
ref. 14
1) t-BuLi
2
) BrCH2CH2Br
Br
1) t-BuLi
1
2
) t-BuLi
) TsCl
ref. 13
2) I2
ref. 14
ref. 14
I
Cl
Br
Br
Scheme 2 Synthesis of 2- and 2,3-halogenated norbornadienes1,8–14
tyllithium followed by water, p-toluenesulfonyl chloride, or
iodine, they obtained 4, 3, or 2-bromo-3-iodonorborna-
diene in 61%, 75%, and 82% yield, respectively.
sulfonyl bromide, which is easily prepared19 from commer-
cially available p-toluenesulfonyl hydrazide.20 When stored
in the dark at –20 °C, p-toluenesulfonyl bromide was stable
for at least one month.
The use of 1,2-dibromoethane as a brominating agent is
problematic since it has been known for a long time to be
To deprotonate norbornadiene (Scheme 3), n-butyllith-
ium is slowly added to a solution of norbornadiene and po-
tassium tert-butoxide in THF to give a yellow solution of the
metalated norbornadiene 6 where, for the sake of simplici-
ty, it is assumed that potassium rather than lithium coordi-
nate the deprotonated norbornadiene. Addition of butyl-
lithium should be slow, and an excess of norbornadiene ap-
pears to be necessary, since treating norbornadiene with a
stoichiometric amount of Schlosser’s base did not give a
clean metalation. We found that adding 0.5 equivalents of
p-toluenesulfonyl bromide to such a solution followed by
stirring at –41 °C gave a thick brown gel. These conditions
are circumvented by using an excess of norbornadiene. Tam
and co-workers14 used two equivalents (meaning that the
maximum conversion of norbornadiene is 25% in the syn-
thesis of 8; we reduced this excess to 1.2 equivalents).
17
carcinogenic, and its use is restricted in some countries
including Sweden). Although unrestricted in other coun-
(
tries, its use should be strongly discouraged. In this context,
it should also be noted that some products obtained by bro-
mination of norbornadiene with bromine have also been
18
reported to be toxic. Alternative routes to 3 via 5,5,6-halo-
norbornenes (Scheme 2) requires high temperatures and
pressures, and we were not able to obtain 3 by these proce-
dures. Thus, we set out to modify the procedure introduced
by Tam and co-workers to produce 3, using an alternative
brominating agent and to reduce the long reaction times al-
lowing halonorbornadienes to be conveniently produced
during a normal working day.
Since metalated norbornadiene can be conveniently
chlorinated by p-toluenesulfonyl chloride, a logical choice
for a replacement of 1,2-dibromethane would be p-toluene-
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Synlett
A. Lennartson et al.
Letter
t-BuOK, n-BuLi
K
Br
K
TsBr (0.5 equiv)
+
6
1
4
6
TsCl
Br
Cl
+
7
K
5
1
n-BuLi
TsBr (0.5 equiv)
Br
Cl
+
Li
Br
9
8
1
TsBr
Cl
Br
3
Scheme 3 Synthesis of 3 and 8 from 1
To prepare 3, the solution of 6 is treated with p-toluene-
sulfonyl chloride to give 5, which is not isolated. Compound
35% in our lab, very similar to the 37% we obtained in this
study. The yield based on 1 was 15% compared to 16% in the
previously published procedure. In conclusion, we have re-
ported modified routes to 3 and 8 avoiding the use of toxic
1,2-dibromoethane and significantly reducing the reaction
times.
5
can be deprotonated in situ with n-butyllithium to give 9.
On treating the resulting brown suspension with p-toluene-
sulfonyl bromide, the brown color is lost within a few min-
utes, and 3 can be extracted from the reaction mixture.21
This allows 3 to be produced in a one-pot reaction, rather
than first preparing and isolating 8.
Acknowledgment
Having found a route to 3, we also adapted this proce-
dure to the synthesis of 8: 0.5 equivalents p-toluenesulfonyl
bromide are added to the solution of 6, which gives a brown
solution of 6 and 4. At –41 °C, this mixture gives 7 and 1
and the color remains dark brown. This deprotonation is
apparently incomplete and we, as did Tam and co-workers,
obtained 4 as a byproduct. When another 0.5 equivalents of
p-toluenesulfonyl bromide are added, the dark color disap-
pears within a few minutes, and 8 is obtained by extraction
The authors would like to thank the following funding agencies for fi-
nancial support: Swedish Research Council (young research grant),
Swedish Strategic Research Council (Future Research Leader 5), K. & A.
Wallenberg Foundation (Wallenberg Academy Fellow 2014),
Chalmers Materials and Energy Areas of Advance.
References and Notes
22
(1) Hyman, I. BE 498176, 1951.
and distillation.
(2) (a) Cristol, S. J.; Snell, R. L. J. Am. Chem. Soc. 1958, 80, 1950.
The yield of 3 was 50%, close to the previously reported
yield of 49% over two steps. However, our yield based on 1,
the most expensive starting material, was 42%, while the
previous protocol had a 12% yield based on 1. The yield of 2
reported in the literature is 65%, but obtaining these high
yields requires great care, and we typically obtained around
(
(
b) Dauben, W. G.; Cargill, R. L. Tetrahedron 1961, 15, 197.
c) Hammond, G. S.; Turro, N. J.; Fischer, A. J. Am. Chem. Soc.
1961, 83, 4674. (d) Smith, C. D. Org. Synth. 1971, 51, 133.
(
3) (a) Moth-Poulsen, K.; Coso, D.; Börjesson, K.; Vinokurov, N.;
Meier, S. K.; Majumdar, A.; Vollhardt, K. P. C.; Segalman, R. A.
Energy Environ. Sci. 2012, 5, 8534. (b) Börjesson, K.; Lennartson,
A.; Moth-Poulsen, K. ACS Sustainable Chem. Eng. 2013, 1, 585.
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Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1501–1504

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Synlett
A. Lennartson et al.
Letter
(
4) (a) Bren, V. A.; Dubonosov, A. D.; Minkin, V. I.; Chernoivanov, V.
(20) (a) Litvinenko, L. M.; Dadali, V. A.; Savelova, V. A.; Krichevtsova,
T. I. Zh. Obshch. Khim. 1964, 34, 3730. (b) Shcherbakova, I.
Science of Synthesis; Vol. 31a; Ramsden, C. A., Ed.; Georg Thieme
Verlag: Stuttgart, 2007, 775.
A. Russ. Chem. Rev. 1991, 60, 451. (b) Dubonosov, A. D.; Bren, V.
A.; Chernoivanov, V. A. Russ. Chem. Rev. 2002, 71, 917.
(c) Lennartson, A.; Roffey, A.; Moth-Poulsen, K. Tetrahedron Lett.
2015, 56, 1457.
(21) 2-Bromo-3-chloronorbornadiene (3)
(
5) (a) Dalkilic, E.; Guney, M.; Dastan, A.; Saracoglu, N.; De Lucchi,
O.; Fabris, F. Tetrahedron Lett. 2009, 50, 1989. (b) Borsato, G.;
Linden, A.; De Lucchi, O.; Lucchini, V.; Wolstenholme, D.;
Zambon, A. J. Org. Chem. 2007, 72, 4272. (c) Tranmer, G. K.; Tam,
W. J. Org. Chem. 2001, 66, 5113. (d) Fan, C.-A.; Ferber, B.; Kagan,
H. B.; Lafon, O.; Lesot, P. Tetrahedron Asymmetry 2008, 19, 2666.
Potassium tert-butoxide (11.2 g, 0.10 mol) was dissolved in THF
(200 mL), and the solution was cooled to –84 °C. Norbornadiene
(12.2 mL, 0.12 mol) was added, followed by n-BuLi (2.5 M in
hexanes, 40 mL, 0.10 mol) over 60 min. The yellow solution was
stirred for 5 min at –84 °C and 60 min at –41 °C. The solution
was cooled again to –84 °C, and p-toluenesulfonyl chloride (19.0
g, 0.10 mol) was added. The mixture was stirred for 30 min and
n-BuLi (2.5 M in hexanes, 40 mL, 0.10 mol) was added over 60
min. The mixture was stirred for 5 min at –84 °C and 60 min at
–41 °C. The solution was cooled to –84 °C, and p-toluenesulfo-
nyl bromide (23.4 g, 0.10 mol) was added. The mixture was
stirred for 15 min and was then heated to ambient temperature
on a room-tempered water bath. The reaction mixture was
(
(
5
e) Wigglesworth, T. J.; Branda, N. R. Adv. Mater. 2004, 16, 123.
f) Monti, H.; Corriol, C.; Bertrand, M. Tetrahedron Lett. 1982, 23,
539. (g) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J.
Am. Chem. Soc. 2003, 125, 11508. (h) Mayo, P.; Tam, W. Tetrahe-
dron 2002, 58, 9513.
(6) Gray, V.; Lennartson, A.; Ratanalert, P.; Börjesson, K.; Moth-
Poulsen, K. Chem. Commun. 2014, 50, 5330.
(
(
(
7) Yoo, W.-J.; Tsui, G. C.; Tam, W. Eur. J. Org. Chem. 2005, 1044.
8) Schmerling, L. US 1956-580469 2914571, 1959.
9) Adam, W.; De Lucchi, O.; Pasquato, L.; Will, B. Chem. Ber. 1987,
quenched with H O (50 mL), the phases were separated, and the
2
aqueous phase was extracted with Et O (3 × 20 mL). The sol-
2
vents from the combined organic phases were slowly removed
on a rotary evaporator (40 °C, 300 mbar). The residue was dis-
120, 531.
(
(
(
10) Schmerling, L. US 1956-580467 2905725, 1959.
11) Stang, P. J.; Zhdankin, V. V. J. Am. Chem. Soc. 1991, 113, 4571.
12) Stang, P. J.; Schwarz, A.; Blume, T.; Zhdankin, V. V. Tetrahedron
Lett. 1992, 33, 6759.
solved in pentane (50 ml), washed with H O (10 × 10 mL), brine
2
(20 mL), and dried over Na SO . The solvent was removed in
2
4
vacuo (40 °C, 300 mbar) and the product distilled (2 × 10–2
mbar) using a short Vigreux column, collecting the main frac-
tion at 25–27 °C. This afforded 3 as a colorless liquid; yield 10.24
g (50%). Analytical data were consistent with previous reports.14
The product was stored at –20 °C and should be used within a
few weeks to avoid decomposition.
(
(
(
13) Kenndoff, J.; Polborn, K.; Szeimies, G. J. Am. Chem. Soc. 1990,
112, 6117.
14) Tranmer, G. K.; Yip, C.; Handerson, S.; Jordan, R. W.; Tam, W.
Can. J. Chem. 2000, 78, 527.
15) (a) Finnegan, R. A.; McNees, R. S. Tetrahedron Lett. 1962, 755.
(22) 2,3-Dibromonorbornadiene (8)
(
(
b) Wittig, G.; Hahn, E. Angew. Chem. 1960, 72, 781.
c) Streitwieser, A. Jr.; Caldwell, R. A. J. Org. Chem. 1962, 27,
Potassium tert-butoxide (11.2 g, 0.10 mol) was dissolved in THF
(200 mL), and the solution was cooled to –84 °C. Norbornadiene
(12.2 mL, 0.12 mol) was added followed by n-BuLi (2.5 M in
hexanes, 40 mL, 0.10 mol) under 60 min. The yellow solution
was stirred for 5 min at –84 °C and 60 min at –41 °C. The solu-
tion was cooled again to –84 °C, and p-toluenesulfonyl bromide
(11.7 g, 0.050 mol) was added. The mixture was stirred for 15
min at –84 °C and 60 min at –41 °C. The solution was cooled to
–84 °C, and p-toluenesulfonyl bromide (11.7 g, 0.05 mol) was
added. The mixture was stirred for 15 min and was then heated
to ambient temperature on a room-tempered water bath. The
3
360. (d) Wittig, G.; Otten, J. Tetrahedron Lett. 1963, 4, 601.
16) (a) Staehle, M.; Lehmann, R.; Kramar, J.; Schlosser, M. Chimia
985, 39, 229. (b) Verkruijsse, H. D.; Brandsma, L. Recl. Trav.
(
1
Chim. Pays-Bas 1986, 105, 66.
(
17) (a) Ramsey, J. C.; Park, C. N.; Ott, M. G.; Gehring, P. J. Toxicol.
Appl. Pharmacol. 1979, 47, 411. (b) Ott, M. G.; Scharnweber, H.
C.; Langner, R. R. Br. J. Ind. Med. 1980, 37, 163.
18) Winstein, S. J. Am. Chem. Soc. 1961, 83, 1516.
19) p-Toluenesulfonyl Bromide
(
(
p-Toluenesulfonyl hydrazide (50 g, 0.27 mol) was mixed with
reaction mixture was quenched with H O (50 mL), the phases
2
CHCl (500 mL) at 0 °C. Small amounts of ice were also added to
were separated, and the aqueous phase was extracted with Et O
3
2
the reaction mixture throughout the reaction. Bromine (27 mL,
(3 × 20 mL). The solvents from the combined organic phases
were slowly removed on a rotary evaporator (40 °C, 300 mbar).
0.54 mol) was added in small portions allowing the orange
color to disappear between each addition. If, when the last
portion of bromine was added, the color was still white, a small
amount of extra bromine was added until a light orange colour
persisted. The phases were separated and the organic phase
was washed with sat. aq NaHCO3 solution (200 mL) and 1% aq
Na S O solution (100 mL). The organic phase was dried over
The residue was dissolved in pentane (50 mL), washed with H O
2
(10 × 10 mL), brine (20 mL), and dried over Na SO . The solvent
2
4
was removed in vacuo (40 °C, 300 mbar) and the product dis-
–2
tilled (5 × 10 mbar) using a short Vigreux column, collecting
the main fraction at 29–31 °C. This afforded 8 as a colorless
liquid; yield 4.63 g (37%). Analytical data were consistent with
2
2
3
14
Na SO , filtered, and the solvent was removed on a rotary evap-
previous reports. The product was stored at –20 °C and should
be used within a few weeks to avoid decomposition.
2
4
–2
orator. The product was ground to powder and dried at 5·10
mbar until NMR showed no traces of solvents or H O; yield:
2
59.6 g (94%).
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1501–1504