N-bromosuccinimide-dibenzoyl peroxide/azabisisobutyronitrile: A reagent for Z- to E-alkene isomerization

Article abstract of DOI:10.1016/S0040-4020(03)01054-8

N-Bromosuccinimide-dibenzoyl peroxide/azobisisobutyronitrile is used to carry out several types of Z- to E-alkene isomerizations. The NBS-bromination conditions are sufficient for both allylic bromination and alkene isomerization. When the allylic hydrogens are not available in substrates, only the isomerization of the alkene takes place. The present conditions for isomerization of carbon-carbon double bonds are mild and efficient.

Full text of DOI:10.1016/S0040-4020(03)01054-8

Tetrahedron 59 (2003) 6489–6492
N-Bromosuccinimide-dibenzoyl peroxide/azabisisobutyronitrile:
a reagent for Z- to E-alkene isomerizationq
*
Md. Merajuddin Baag, Anirban Kar and Narshinha P. Argade
Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pashan, Pune 411 008, India
Received 25 April 2003; revised 13 June 2003; accepted 3 July 2003
Dedicated to Dr B. G. Hazra, OCS, NCL, Pune
Abstract—N-Bromosuccinimide-dibenzoyl peroxide/azobisisobutyronitrile is used to carry out several types of Z- to E-alkene
isomerizations. The NBS-bromination conditions are sufficient for both allylic bromination and alkene isomerization. When the allylic
hydrogens are not available in substrates, only the isomerization of the alkene takes place. The present conditions for isomerization of
carbon–carbon double bonds are mild and efficient.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
dimethyl bromomethylfumarate in 85% yield. Both allylic
bromination and isomerization of the carbon–carbon
double bond took place in one-pot via an in situ addition–
elimination of the bromine radical, which was further
confirmed by obtaining the same product from dimethyl
methylfumarate (Table 1, Entry 3). On the basis of this
observation,9 we prepared a systematic plan to study the
NBS-DBP/AIBN induced Z- to E- carbon–carbon double
bond isomerization with several types of olefins having a
variety of substituents. The results are presented in Scheme 1
and Table 1. Maleic acid, on treatment with NBS-DBP in
refluxing acetic acid, gave fumaric acid in 90% yield, while
dimethyl maleate, on treatment with NBS-AIBN in reflux-
ing CCl4 gave dimethyl fumarate in 98% yield (Entries 1
and 2). The process of carbon–carbon double bond
isomerization was found to be slow in tetrasubstituted
dimethyl dimethylmaleate using 1.1 equiv. of NBS while
the use of 2.5 equiv. of NBS gave a 1:1 mixture of dimethyl
dibromomethylmaleate and dimethyl dibromomethylfuma-
rate in 96% yield (Entry 4). Interestingly, dimethyl
methoxymaleate, on treatment with NBS-DBP in refluxing
CCl4, did not show any reaction. On the contrary, the
corresponding dimethyl methoxyfumarate underwent very
smooth carbon–carbon double bond isomerization to yield
dimethyl methoxymaleate in 92% yield, revealing that the
E-isomer is thermodynamically more stable than the
Z-isomer (Entries 5 and 6). Methyl maleanilate and methyl
Z-cinnamate, under similar reaction conditions, gave the
corresponding E-products in 90% and 96% yields
respectively (Entries 7 and 8). As expected, methyl Z-oleate
on treatment with NBS-DBP in refluxing CCl4 gave the
methyl E-dibromooleate in 95% yield, while under the
same set of reaction conditions Z-stilbene was transformed
into E-stilbene in ,100% yield (Entries 9 and 10).
The generation of carbon–carbon double bonds in geo-
metrically pure form is one of the most important reactions
in synthetic organic chemistry1 and many elegant methods
are known in the literature.2 However, in some of the
reactions mixtures of Z- and E-alkenes are also formed2,3
and radical4 or photochemical5 reactions have been used to
transform the Z-isomers to the corresponding E-isomers.
Isomerization of (Z)-stilbene to the E-isomer and dimethyl
maleate to dimethyl fumarate are usually catalyzed by
bromine via the reversible addition of a bromine radical to
the double bond.6 Very recently Spencer et al. have
demonstrated7 a facile palladium(II)-catalyzed isomeriza-
tion of Z-arylalkenes to E-arylalkenes. The provision of a
new method for isomerization of Z-olefins to E-olefins is a
challenging task of current interest and in this context, we
herein report an easy access to several types of geo-
metrically pure E-olefins using N-bromosuccinimide-
dibenzoyl peroxide/azobisisobutyronitrile (NBS-DBP/
AIBN) reagent.
2. Results and discussion
In our on going studies8 on the synthesis of recently isolated
bioactive natural products, we carried out the reaction of
dimethyl methylmaleate with NBS-AIBN and obtained
q NCL Communication No. 6645.
Keywords: isomerization; NBS-bromination; carbon–carbon double bonds.
*
Corresponding author. Tel./fax: þ91-20-5893153;
e-mail: argade@dalton.ncl.res.in
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)01054-8

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Md. M. Baag et al. / Tetrahedron 59 (2003) 6489–6492
Table 1. NBS-DBP/AIBN induced carbon–carbon double bond isomerizations
Entry
1
Starting materiala
Reaction conditions
Product
Yield (%)
90
NBS (2.0 equiv.), DBP, AcOH, reflux, 6 h
2
3
4
NBS (1.1 equiv.), AIBN, CCl4, reflux, 1 h
NBS (1.5 equiv.), AIBN, CCl4, reflux, 12 h
NBS (2.5 equiv.), DBP, CCl4, reflux, 2 h
98
85
46b
5
6
NBS (2.0 equiv.), DBP, CCl4, reflux, 8 h
NBS (2.0 equiv.), DBP, AcOH, reflux, 8 h
No Reaction
0
92
7
8
9
NBS (4.0 equiv.), DBP, CCl4, reflux, 10 h
NBS (1.1 equiv.), AIBN, CCl4, reflux, 2 h
NBS (2.5 equiv.), DBP, CCl4, reflux, 4 h
90
96
95
10
NBS (2.0 equiv.), DBP, CCl4, reflux, 3 h
NBS (1.1 equiv.), DBP, CCl4, reflux, 2 h
,100
11
60c
The Z-alkenes and geometric mixtures of alkenes were prepared by using known literature procedures.7,12
50% Dimethyl dibromomethylmaleate was also formed.
10–15% Mixture of ring brominated products was also obtained. Ar¼3,5-dimethoxyphenyl; Ar0¼p-methoxyphenyl.
a
b
c
Z-Trimethoxystilbene, on treatment with NBS (1.1 equiv.)
and DBP (catalytic) in refluxing CCl4 gave the trimethoxy
derivative of bioactive resveratral11 in 60% yield and due to
the mesomeric effect of the –OMe groups, we also observed
10–15% formation of mixtures of ring brominated
E-trimethoxystilbene derivatives (Entry 11). As indicated
in Table 1, we could isomerize different types of olefins with
a variety of substituent patterns from Z- to E- forms using
NBS-DBP/AIBN and the present method is simple and
efficient.
3. Conclusion
In summary, we have demonstrated that the reagent NBS-
DBP does both allylic bromination and several types of Z- to
E- carbon–carbon double bond isomerization. The
Z-alkenes without allylic hydrogens in pure form or
mixtures of geometric isomers can be easily transformed
into the corresponding E-alkenes using NBS-DBP/AIBN in
quantitative yields. The present studies also provide a useful
caution mark to the chemists attempting allylic bromination
of Z-alkenes.
4. Experimental
4.1. General
Melting points are uncorrected. Column chromatographic
separations were carried out on silica gel (60–120 mesh).
Commercially available N-bromosuccinimide, dibenzoyl
peroxide, azobisisobutronitrile, maleic acid, dimethyl
maleate and ethyl Z-oleate were used. The Z-alkenes and
Scheme 1.

Md. M. Baag et al. / Tetrahedron 59 (2003) 6489–6492
6491
geometric mixtures of alkenes were prepared by using
known literature procedures.7,12
4.2.10. E-Stilbene. ,100% Yield; crystalline solid; mp
122–1238C (lit.13 mp 122–1248C). Spectroscopic data are
identical to that reported in the literature.14
4.2. General procedure for the isomerization of
Z-alkenes to E-alkenes
4.2.11. E-4-Methoxy-30,50-dimethoxystilbene. 60% Yield;
crystalline solid; mp 788C. Spectroscopic data are identical
to that reported in the literature.7
A mixture of Z-alkene, N-bromosuccinimide and catalytic
amount of DBP/AIBN (10 mol%) in carbon tetrachloride
(5–10 mL per mmol of substrate) was gently refluxed (see
Table 1). The mixture was allowed to cool to room
temperature and then filtered. The residue was washed
with CCl4 and the combined organic layer was washed with
water, brine, dried over Na2SO4 and concentrated in vacuo.
The obtained residue was purified by silica gel column
chromatography using petroleum ether/ethyl acetate as an
eluent to obtain the desired E-alkene.
Acknowledgements
M. M. B. and A. K. thank CSIR, New Delhi, for the award of
a research fellowship. N. P. A. thanks the Department of
Science and Technology, New Delhi, for financial support.
We thank Dr K. N. Ganesh, Head, Division of Organic
Chemistry (Synthesis) for constant encouragement.
4.2.1. Fumaric acid. 90% Yield; crystalline solid; mp 298–
3008C (sublimes) [lit.13 mp 299–3008C (sublimes)].
Spectroscopic data are identical to that reported in the
literature.14
References
4.2.2. Dimethyl fumarate. 98% Yield; crystalline solid; mp
100–1018C (lit.13 mp 103–1048C). Spectroscopic data are
identical to that reported in the literature.14
1. Evans, D. A.; Trotter, B. W.; Cote, B.; Coleman, P. J.; Dias,
L. C.; Tyler, A. N. Angew. Chem., Int. Ed. Engl. 1997, 36,
2744.
2. (a) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863.
(b) Evans, D. A.; Fitch, D. M.; Smith, T. E.; Cee, V. J. Am.
Chem. Soc. 2000, 122, 10033. (c) Ley, S. V.; Brown, D. S.;
Clase, J. A.; Fairbanks, A. J.; Lennon, I. C.; Osborn, H. M. I.;
Stokes, E. S. E.; Wadsworth, D. J. J. Chem. Soc., Perkin Trans.
1 1998, 2259. (d) Evans, D. A.; Carter, P. H.; Carreira, E. M.;
Charette, A. B.; Prunet, J. A.; Lautens, M. J. Am. Chem. Soc.
1999, 121, 7540. (e) Fleming, I.; Barbero, A.; Walter, D.
Chem. Rev. 1997, 97, 2063. (f) Hamon, D. P. G.; Spurr, P. R.
Synthesis 1981, 873 and refs cited therein 2a–f.
4.2.3. Dimethyl bromomethylfumarate. 85% Yield; thick
oil. Spectroscopic data are identical to that reported in the
literature.8a
4.2.4. Dimethyl dibromomethylmaleate. 50% Yield; thick
oil. Spectroscopic data are identical to that reported in the
literature.2f
4.2.5. Dimethyl dibromomethylfumarate. 46% Yield;
thick oil. Spectroscopic data are identical to that reported
in the literature.2f
3. Nicolaou, K. C.; He, Y.; Vourloumis, D.; Vallberg, H.;
Roschangar, F.; Sarabia, F.; Ninkovic, S.; Yang, Z.; Trujillo,
J. I. J. Am. Chem. Soc. 1997, 119, 7960.
4.2.6. Dimethyl methoxymaleate. 92% Yield; thick oil.
Spectroscopic data are identical to that reported in the
literature.12b
4. (a) Bosanac, T.; Yang, J.; Wilcox, C. S. Angew. Chem., Int. Ed.
Engl. 2001, 40, 1875. (b) Ali, M. A.; Tsuada, Y. Chem. Pharm.
Bull. 1992, 40, 2842. (c) Taniguchi, M.; Nozaki, K.; Miura, K.;
Oshima, K.; Utimoto, K. Bull. Chem. Soc. Jpn 1992, 65, 349
and refs cited therein 4a–c.
4.2.7. Methyl fumaranilate. 90% Yield; mp 164–1658C;
1H NMR (CDCl3, 200 MHz) d 3.83 (s, 3H), 6.85–7.65 (m,
7H), 7.90–8.20 (m, 1H); 13C NMR (CDCl3, 125 MHz) d
52.3, 120.1, 121.6, 125.2, 129.2, 132.2, 137.3, 161.5, 165.9;
IR (CHCl3) nmax 3325, 1717, 1684, 1659 cm21. Anal. calcd
for C11H11NO3: C, 64.38; H, 5.40. Found: C, 64.42; H,
5.37.
5. (a) Deter, D. F.; Chu, Y. W. J. Am. Chem. Soc. 1955, 77, 4410.
(b) Camps, F.; Chamorro, E.; Gasol, V.; Guerrero, A. Synth.
Commun. 1989, 19, 3211. (c) Jacobsen, E. N.; Deng, L.;
Furukawa, Y.; Martinez, L. E. Tetrahedron 1994, 50, 4332 and
refs cited therein 5a–c.
6. Kodomari, M.; Sakamoto, T.; Yoshitomi, S. Bull. Chem. Soc.
Jpn 1989, 62, 4053.
4.2.8. Methyl E-cinnamate. 96% Yield; mp 36–388C (lit.13
mp 36–388C). Spectroscopic data are identical to that
reported in the literature.14
7. Yu, J.; Gaunt, M. J.; Spencer, J. B. J. Org. Chem. 2002, 67,
4627.
8. (a) Kar, A.; Argade, N. P. J. Org. Chem. 2002, 67, 7131.
(b) Deshpande, A. M.; Natu, A. A.; Argade, N. P. J. Org.
Chem. 1998, 63, 9557.
4.2.9. Ethyl 9(E)-8,11-dibromooctadecenoate. 95% Yield;
1
thick oil; H NMR (CDCl3, 200 MHz) d 0.88 (t, J¼6 Hz,
9. (a) Walling, C.; Rieger, A. L.; Tanner, D. D. J. Am. Chem. Soc.
1963, 85, 3129. (b) McGrath, B. P.; Tedder, J. M. Proc. Chem.
Soc. 1961, 80. (c) Godye, R. N.; Nechvatal, A. J. Chem. Soc.
1964, 5925. (d) Ucciani, E.; Chouteau, J.; Naudet, M. Bull.
Soc. Chim. Fr. 1960, 1511 and refs cited therein 8a–c.(e) In
1970, Dreiding et al. obtained methyl g-bromotiglate from the
NBS-bromination of both methyl tiglate and methyl angelate,
but by the separation of a formed structural isomer.10
3H), 1.26 (m, 21H), 1.50–2.00 (m, 4H), 2.29 (t, J¼8 Hz,
2H), 4.13 (q, J¼8 Hz, 2H), 4.40–4.90 (m, 2H), 5.70–6.00
(m, 2H); 13C NMR (CDCl3, 125 MHz) d 14.0, 14.2, 21.0 (2-
CH2), 22.6, 24.8, 29.1–29.6 (8-CH2), 31.9, 34.3, 60.0, 128.3
(2-CH2), 173.8; IR (neat) nmax 1730, 1462, 1373, 1180,
1034, 962 cm21. Anal. calcd for C20H36Br2O2: C, 51.30; H,
7.75. Found: C, 51.25; H, 7.83.

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Md. M. Baag et al. / Tetrahedron 59 (2003) 6489–6492
10. Loffler, A.; Norris, F.; Taub, W.; Svanholt, K. L.; Dreiding,
A. S. Helv. Chim. Acta 1970, 53, 403 and refs cited therein.
11. Jang, M.; Cai, L.; Udeani, G. O.; Slowing, K. V.; Thomas,
C. F.; Beecher, C. W. W.; Fong, H. H. S.; Fransworth, N. R.;
Kinghorn, A. D.; Mehta, R. G.; Moon, R. C.; Pezzuto, J. M.
Science 1997, 275, 218.
50, 8969. (b) Sahoo, M. K.; Mhaske, S. B.; Argade, N. P.
Synthesis 2003, 346. (c) Easwar, S.; Argade, N. P. Indian
J. Chem. 2002, 41B, 1899.
13. Aldrich Catalog Handbook of Fine Chemicals; Aldrich:
Milwaukee, 2003–2004.
14. IR and 1H NMR spectra obtained were compared with the
spectra reported in respective Aldrich catalogs.
12. (a) Naganawa, A.; Ichikawa, Y.; Isobe, M. Tetrahedron 1994,