Facile synthesis of β-tribromomethyl and dibromomethylenated nitroalkanes via conjugate addition of bromoform to nitroalkenes

Article abstract of DOI:10.1021/jo802274q

Addition of bromoform to conjugated nitroalkenes in the presence of Mg provided β-tribromomefhyl nitroalkanes in good to excellent yields and diastereoselectivity. These novel Michael adducts, formed under radical conditions, underwent elimination of HBr

Full text of DOI:10.1021/jo802274q

and carboxylic acids,6 to mention a few. Similarly, the versatility
of nitroalkyl moiety to undergo transformations to a variety of
functionalities such as carbonyls, oximes, hydroxylamines,
amines, nitriles, and 1,3-dipoles such as nitrile oxides and silyl
nitronates is well-documented in the literature.7
Facile Synthesis of ꢀ-Tribromomethyl and
Dibromomethylenated Nitroalkanes via
Conjugate Addition of Bromoform to
Nitroalkenes
Haloform is a ready source of trihalomethyl and dihalom-
ethylene and the reaction of haloform with alkenes under
anionic8-12 and radical13 conditions is well-established. The base
mediated reaction, in the absence12 and more often in the
presence8-11 of phase transfer catalysts (PTC), is the method
of choice for the cyclopropanation of alkenes. While the
formation of cyclopropane derivatives from unactivated alkenes
presumably takes place via dibromocarbene addition, such
product formation from activated alkenes appears to proceed
via an initial Michael addition of the trihalomethyl carbanion
followed by intramolecular cyclization pathway.9,10 In the case
of activated alkenes, the Michael adducts and their ꢀ-elimination
products, the alkylidene dibromides, are also isolated.10
As part of our sustained interest in the chemistry of
conjugated nitroalkenes,14 we surveyed the literature reports on
the reactivity of haloform with nitroalkenes under different
conditions. Makosza and Kwast reported one example of
potassium tert-butoxide promoted addition of chloroform to
ꢀ-nitrostyrene from which they isolated 1-(1,1-dichloro-3-
nitroprop-1-en-2-yl)benzene in moderate yield.10 Cunico and
Zhang investigated the CsF catalyzed reaction of trimethylsi-
lyltrichloromethane (CCl3SiMe3) with ꢀ-nitroalkenes affording
ꢀ-(trichlomethyl)nitroalkanes in low to moderate yields.15
However, the reaction of an R,ꢀ-disubstituted nitroethylene with
bromoform mediated by aq NaOH/n-Bu4N+Cl- provided the
cyclopropanation product (in low yield) rather than the Michael
adduct.16 To our knowledge, there are no general and efficient
methods for the synthesis of ꢀ-trihalomethyl and dihalometh-
ylidene nitroalkanes.
Bichismita Sahu, Guddeangadi N. Gururaja,
Shaikh M. Mobin, and Irishi N. N. Namboothiri*
Department of Chemistry, Indian Institute of Technology,
Bombay, Mumbai 400 076, India, and National
Single-Crystal X-Ray Diffraction Facility, Indian Institute of
Technology, Bombay, Mumbai 400 076, India
irishi@iitb.ac.in
ReceiVed October 10, 2008
Addition of bromoform to conjugated nitroalkenes in the
presence of Mg provided ꢀ-tribromomethyl nitroalkanes in
good to excellent yields and diastereoselectivity. These novel
Michael adducts, formed under radical conditions, underwent
elimination of HBr in the same pot under reflux to afford
ꢀ-dibromomethylenated nitroalkanes in good yield. Alter-
natively, a one-pot high yielding synthesis of the dibromides
was possible under anionic conditions via LDA mediated
addition of bromoform to nitroalkenes.
Notably, when we reacted ꢀ-substituted nitroethylene 1a with
bromoform under the above PTC conditions,16 we isolated only
polymeric material. However, we were delighted to isolate the
tribromonitroalkane 2a when 1a was treated with bromoform
in the presence of Mg in THF (Scheme 1).17 Our optimization
studies revealed that an excess of magnesium (8 equiv) and
Polyhalonitro compounds exhibit potential biological proper-
ties.1 Such compounds are also attractive synthetic intermediates
owing to the ability of both halo and nitro groups to undergo
diverse transformations. For instance, a trihalomethyl group can
be readily converted to carboxylic acids2 and a dihalometh-
ylidene functionality is amenable for transformation to acety-
lenes,3 crossed enediynes,4 carbo- and heterocycles,5 and amides
(6) On treatment with amine and water: Huh, D. H.; Jeong, J. S.; Lee, H. B.;
Ryu, H.; Kim, Y. G. Tetrahedron 2002, 58, 9925.
(7) For recent reviews see: (a) Namboothiri, I. N. N.; Rastogi, N. Top.
Heterocycl. Chem. 2008, 12, 1. (b) Ballini, R.; Bosica, G.; Fiorini, D.; Palmieri,
A.; Petrini, M. Chem. ReV. 2005, 105, 933.
(8) (a) Weber, W. P.; Gokel, G. W. In Phase Transfer Catalysis in Organic
Synthesis; Hafner, K., Rees, C. W., Trost, B. M., Lehn, J.-M., Schleyer, P. v.
R.; Zahradnik, R., Eds.; Springer-Verlag: Berlin-Heidelberg-New York, 1977;
Vol. 4. (b) Nerdel, F.; Brodowski, W.; Buddrus, J.; Fligge, M.; Weyerstahl, P.;
Ulm, K.; Finger, C.; Klamann, D. Chem. Ber. 1968, 101, 1407.
(9) Baird, M.; Gerrard, M. E. Tetrahedron Lett. 1985, 26, 6353.
(10) Makosza, M.; Kwast, A. Tetrahedron 1991, 47, 5001.
(11) Dehmlow, E. V.; Wilkenloh, J. Chem. Ber. 1990, 123, 583.
(12) (a) Le Goaller, R.; Slaoui, S.; Pierre, J. L.; Luche, J. L. Synth. Commun.
1982, 12, 1163. (b) Karwowska, H.; Jonczyk, A. Pol. J. Chem. 2007, 81, 45.
(13) Ashton, D. S.; Shand, D. J.; Tedder, J. M.; Walton, J. C. J. Chem. Soc.,
Perkin Trans. 2 1975, 320.
(1) For the anti-microbial properties of bromo-nitro compounds see: Morita,
M.; Fukuyama, S.; Isogai, K. Japanese Patent 2003, JP 2003171209; Chem. Abstr.
2003, 139, 32087.
(2) For a recent example see: Lavecchia, G.; Berteina-Raboin, S.; Guillaumet,
G. Lett. Org. Chem. 2006, 3, 877.
(3) Via Corey-Fuchs reaction: (a) Corey, E. J.; Fuchs, P. L. Tetrahedron
Lett. 1972, 36, 3769. (b) Sahu, B.; Namboothiri, I. N. N.; Persky, R. Tetrahedron
Lett. 2005, 46, 2593. (c) Sahu, B.; Muruganantham, R.; Namboothiri, I. N. N.
Eur. J. Org. Chem. 2007, 2477. For a review see: (d) Knorr, R. Chem. ReV.
2004, 104, 3795.
(4) Via metal mediated coupling: Diederich, F.; Philp, D.; Seiler, P. J. C. S.
Chem. Commun. 1994, 205.
(14) For a recent article see: Muruganantham, R.; Mobin, S. M.; Namboothiri,
I. N. N. Org. Lett. 2007, 9, 1125.
(15) Cunico, R. F.; Zhang, C. Synth. Commun. 1991, 21, 2189.
(16) Hu¨bner, J.; Liebscher, J.; Pa¨tzel, M. Tetrahedron 2002, 58, 10485.
(17) These conditions were reported for the cyclopropanation of unactivated
alkene (e.g., cyclohexene): Huang, N.; Xu, L. Chin. Sci. Bull. 1991, 36, 831.
(5) Via metal mediated coupling: (a) Fayol, A.; Fang, Y.-Q.; Lautens, M.
Org. Lett. 2006, 8, 4203. (b) Yanagisawa, H.; Miura, K.; Kitamura, M.; Narasaka,
K.; Ando, K. Bull. Chem. Soc. Jpn. 2003, 76, 2009.
10.1021/jo802274q CCC: $40.75
Published on Web 02/24/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 2601–2604 2601

TABLE 2. Mg Mediated Diastereoselective Addition of
Bromoform to Nitroalkenes 3a
SCHEME 1
entry
3
R, R′
% yieldb of 4
drc
TABLE 1. Mg Mediated Addition of Bromoform to Nitroalkenes
1aa
1
2
3
3a
3b
3c
(CH2)4
O(CH2)3
3,4-(OCH2O)Ph, Me
60
72
56
100:0d
100:0d
75:25e
a THF:CHBr3 (10:1 v/v, 4 M). b Isolated yield after purification by
silica gel column chromatography. c Trans/cis or anti/syn. d CBr3 and
NO2 are trans e,e, see ref 19. e CBr3 and NO2 are anti in the major
isomer, see ref 20.
entry
1
R
2
% yieldb of 2
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
4-OMe-Ph
2a
2b
2c
2d
2e
2f
2g
2h
2i
93
56
74
55
58
50c
63
89
75
52
72
95
2,4-(MeO)2-Ph
2,5-(MeO)2-Ph
3,4-(MeO)2-Ph
3,4-(-OCH2O-)Ph
3-MeO-4-OH-Ph
4-NMe2-Ph
4-NO2-Ph
4-F-Ph
2-(O-allyloxy)phenyl
3-furyl
3-thienyl
TABLE 3. One-Pot Synthesis of Alkylidene Dibromides 5 from
Nitroalkenes 1 and Bromoform under Mg Mediated Conditionsa
9
entry
1
R
5
% yieldb of 5
10
11
12
1j
1k
1l
2j
2k
2l
1
2
3
4
5
6
7
1a
1d
1e
1g
1h
1k
1l
4-OMe-Ph
5a
5d
5e
5g
5h
5k
5l
58
51
65
72
62
60
58
3,4-(MeO)2-Ph
3,4-(-OCH2O-)Ph
4-NMe2-Ph
4-NO2-Ph
3-furyl
3-thienyl
a THF:CHBr3 (10:1 v/v, 4 M). b Isolated yield after purification by
silica gel column chromatography. c Excess magnesium and bromoform
were used.
a Method A. b Isolated yield after purification by silica gel column
chromatography.
bromoform (16 equiv) would be desirable to ensure complete
consumption of the starting nitroalkene 1a. Finally, the best yield
of the Michael adduct 2a (93%) was obtained by employing
further excess of bromoform (22 equiv) while maintaining a
THF:bromoform ratio of 10:1 and an overall concentration of
4 M for the reaction mixture (see Tables S1-S4, Supporting
Information).
Having fully optimized the conditions for the conjugated
addition of bromoform to p-methoxynitrostyrene 1a, we sub-
jected a variety of nitroalkenes, viz. ꢀ-aryl 1a-j (entries 1-10)
and ꢀ-heteroaryl 1k-l (entries 11 and 12) nitroethylenes to the
above reaction conditions and were pleased to isolate the
Michael adducts 2a-l in good to excellent yield (Table 1).
The structure of tribromides 2 was confirmed from their
spectral characteristics.18 Later, unequivocal structural assign-
ment was made via single crystal X-ray analysis of a representa-
tive tribromide 2c (see the Experimental Section).
Subsequently, the diastereoselectivity in the Mg mediated
addition of bromoform was investigated by using nitroalkenes
3a-c (Table 2). While the formation of adducts 4a,b from cyclic
nitroalkenes 3a,b took place in good yield (60% and 72%,
respectively) and 100% diastereoselectivity (Table 2, entries 1
and 2), similar adduct 4c from open chain nitroalkene 3c
proceeded in lower yield (56%) and selectivity (75:25, entry
3).
Since the tribromides 2 and 4 were synthesized and isolated
under mild reaction conditions, we felt that further elimination
of HBr to afford synthetically useful alkylidene dibromide 5
would take place under forcing conditions. To this end, the
reaction mixture was refluxed for 24 h, which resulted in the
formation of dibromides 5 in good to high yield (Table 3). It
may be noted that the one-pot transformation of nitroalkenes 1
to alkylidene dibromides 5 has been demonstrated for selected
aromatic nitroalkenes with electron donating groups (1a, 1d,
1e, and 1g, entries 1-4) and electron withdrawing groups (1h,
entry 5) as well as for heteroaromatic nitroalkenes 1k and 1l
(entries 6 and 7, Table 3).
As in the case of 2 and 4, spectral characteristics enabled us
to assign the structure of dibromides 5.21 Further, the structure
of dibromide 5 was unambiguously confirmed as in the case of
2 via single crystal X-ray analysis of a representative compound
5a (see the Experimental Section).
Requirement of an excess of Mg and bromoform in the above
procedure for the synthesis of tribromides 2 and 4 and
dibromides 5 prompted us to further explore the role of strong
bases in promoting the generation of the tribromomethyl
carbanion and its addition to nitroalkenes (see Tables S5 and
S6, Supporting Information).22 Thus, while the reaction of
nitroalkene 1a with bromoform mediated by bases such as
NaOMe, t-BuOK, and NaH in THF provided the desired
dibromide 5a in low to moderate yield, excess LDA (6 equiv)
provided 5a in high yield (74%). Quite remarkably, unlike in
(18) Appearance of CBr3 carbon in the range of δ 39-45 in 13C NMR and
four peaks for the molecular ion (e.g., M+, [M + 2]+, [M + 4]+, and [M + 6]+)
in ca. 1:3:3:1 ratio in the mass spectrum.
(19) The diaxial coupling between the two methine protons in 1H NMR (8.4
Hz in 4a and 7.6 Hz in 4b) was confirmed by 1H-1H COSY experiment. NOE
is also observed between the two vicinal protons. The structure was further
unambiguously established by single crystal X-ray analysis (see the Supporting
Information).
(21) Appearance of CBr2 carbon in the range of δ 99-105 in 13C NMR and
three peaks for the molecular ion (e.g. M+, [M + 2]+, and [M + 4]+) in ca.
1:2:1 ratio in the mass spectrum.
(22) The pKa reported for bromoform is 11.8: Scharlin, P. Acta Chem. Scand.
Ser. A: Phys. Inorg. Chem. 1987, A41, 480.
(20) A coupling of 9.2 Hz between the benzylic proton and the proton R to
nitro group in 1H NMR of 4c confirmed that the two are anti to each other. The
absence of any NOE between Ar and CH3 confirmed the trans relationship
between them and between CBr3 and NO2 (see the Supporting Information).
2602 J. Org. Chem. Vol. 74, No. 6, 2009

TABLE 4. One-Pot Synthesis of Alkylidene Dibromides 5 from
Nitroalkenes 1 and Bromoform under LDA Mediated Conditionsa
SCHEME 3
entry
1
R
5
% yielda of 5
bromoform and Mg and its abstraction of proton from excess
bromoform in the medium to generate tribromomethylmagne-
sium bromide 10 (Scheme 2b). Conjugate addition of 10 to
nitroalkene 1 provides tribromide 2.
1
2
3
4
5
6
7
1a
1d
1e
1g
1h
1k
1l
4-OMe-Ph
5a
5d
5e
5g
5h
5k
5l
74
66
72
77
76
88
77
3,4-(MeO)2-Ph, H
3,4-(-OCH2O-)Ph
4-NMe2-Ph
4-NO2-Ph
Although the absence of any cyclized product when nitroalk-
ene 1j26 was subjected to Mg mediated reaction (entry 10, Table
1, and in the Supporting Information, Scheme S1) prompted us
to rule out the radical mechanism,27 further confirmation of the
mechanism was sought by reacting a nitroalkene with a radical
trap such as 1,4-cyclohexadiene. Thus, the Mg mediated reaction
of nitroalkene 1a with bromoform in the presence of 3 equiv
of 1,4-cyclohexadiene provided 2a in marginally lower yield
(80%). Although GC and NMR analysis of the crude product
did not indicate the formation of benzene, the radical mechanism
could not be ruled out because a viscous liquid isolated, besides
2a, whose spectral characteristics indicated it to be an oligo-
meric/polymeric material arising from 1,4-cyclohexadiene.28
Subsequently, the EPR analysis of the reaction mixture was
carried out at 0, 5, 10, 15, 20, 25, 30, 35, and 45 min time
intervals and finally after 5 h. While no EPR signals were
observed up to 15 min, the analysis after 20 min showed the
appearance of two EPR signals with g values 2.16 and 2.09
attributable to two separate radical species, presumably the
nitroalkyl radical 829 and the CBr3 radical 7.30 The intensity of
these peaks remained high during subsequent measurements (25,
30, 35, and 45 min). After 5 h, the intensity of the signals
decreased drastically indicating the decay of the radicals.
The trans/anti stereochemistry of products 4a-c19,20 arises
from addition of hydrogen radical from the cis/syn side of the
CBr3 group, i.e., Re face of the nitronate radical, as in 11-12
(Scheme 3, Table 2).
3-furyl
3-thienyl
a Method B. b Isolated yield after purification by silica gel column
chromatography.
SCHEME 2. Mechanistic Pathways Considered for the Mg
Mediated Addition of Bromoform to Nitroalkenes 2a
Finally, a simple and convenient synthesis of ꢀ,γ,γ-triaryl
nitroalkenes, e.g., 13, via Suzuki coupling of dibromide 5a with
phenyl boronic acid is shown in Scheme 4 (see the Supporting
Information for experimental details).
In conclusion, a convenient methodology has been developed
for the one-pot synthesis of ꢀ-dibromomethylenated nitroalkanes
the case of Mg mediated reaction, this reaction required only
1.1 equiv of bromoform.
Under the above optimized conditions, i.e., bromoform (1.1
equiv) and LDA (6 equiv) in THF at -78 °C to rt, representative
ꢀ-arylated nitroethylenes with electron donating (1a, 1d, 1e,
and 1g, entries 1-4) and electron withdrawing (1h, entry 5)
groups as well as ꢀ-heteroarylated nitroethylenes (1k,l, entries
6 and 7) have been transformed to dibromides 5 in excellent
yield (Table 4). A comparison of Tables 3 and 4 shows that the
LDA mediated reaction is superior to the Mg mediated reaction
both in terms of the product yields and the requirement of
bromoform.
While the LDA mediated reaction presumably proceeds via
anionic mechanism, an alternative radical mechanism is also a
probability under Mg mediated conditions. For instance, single
electron transfer (SET) from Mg could generate dibromomethyl
radical 6,23 which could abstract H radical from bromoform to
generate tribromomethyl radical 7 (Scheme 2a). Conjugate
addition of radical 7 to nitroalkene 1 could provide tribromide
2 via resonance stabilized nitroalkyl radical 8.24,25
(24) (a) For addition of bromoform to fluoroethylene in the presence of radical
initiator: see ref 13. (b) A radical mechanism was proposed for the reaction of
cyclohexene with bromoform in the presence of Mg to form the cyclopropanation
product: see ref 17.
(25) For evaluation of the capacity of an R-nitroalkyl radical for hydrogen
abstraction see: Bolsman, T. A. B. M.; Verhoeven, J. W.; de Boer, T. J.
Tetrahedron 1975, 31, 1015.
(26) (a) Carter, M. E.; Nash, J. L., Jr.; Drueke, E. W., Jr.; Schwietert, J. W.;
Butler, G. B. J. Polym. Sci., Polym. Chem. Ed. 1978, 16, 937. See also: (b)
Deb, I.; John, S.; Namboothiri, I. N. N. Tetrahedron 2007, 63, 11991.
(27) Formation of cyclic products as an evidence for SET mechanism when
the substrate has suitably located double bonds: (a) Ashby, E. C. Acc. Chem.
Res. 1988, 21, 414. (b) Ashby, E. C.; Pham, T. N.; Amrollah-Madjdabadi, A. J.
Org. Chem. 1991, 56, 1596.
(28) The absence of benzene may be due to the inability of the highly
resonance stabilized nitroalkyl radical to abstract H radical from 1,4-cyclohexa-
diene (the product 2a could be formed during aqueous workup) or polymerization
rather than aromatization of the 1,4-cyclohexadienyl radical.
(29) For characterization of an R-nitroalkyl radical by EPR via spin trapping
experiment with 2-methyl-2-nitrosopropane: Bolsman, T. A. B. M.; de Boer,
T. J. Tetrahedron 1975, 31, 1019.
(30) EPR investigation of CBr3 radical remains obscure: (a) Stoesser, R.;
Proesch, U. Z. Chem. 1983, 23, 382. (b) Chen, S.; Ge, M.; Guo, S.; Xu, L.; Tao,
F. Youji Huaxue 1990, 10, 74; Chem. Abstr. 1990, 113, 39784. (c) Karasev,
A. L.; Petrova, A. A.; Zver’kov, V. A.; Vannikov, A. V. Khimiya Vysokikh
Energii 1991, 25, 71; Chem. Abstr. 1991, 114, 196168.
An alternative mechanism outlined in Scheme 2b envisages
initial formation of dibromomethylmagnesium bromide 9 from
(23) In bromoform a carbon-halogen bond is broken in the initiation
step: Weizmann, M.; Israelashvili, S.; Halevy, A.; Bergmann, F. J. Am. Chem.
Soc. 1947, 69, 2569.
J. Org. Chem. Vol. 74, No. 6, 2009 2603

SCHEME 4
Mediated Reaction of Bromoform with Nitroalkenes 1. To a
stirred solution of magnesium (96 mg, 4 mmol) and nitroalkene 1
(0.5 mmol) in THF (10 mL) was added bromoform (2.7 g, 1 mL,
11 mmol) dropwise over a period of 10 min at 0 °C. The reaction
mixture was gradually brought to room temperature over a period
of 0.5 h during which the solution turned dark brown. After the
nitroalkene was fully consumed (monitored by TLC), the reaction
mixture was refluxed for 24 h. The reaction mixture was then
quenched with saturated aqueous NH4Cl (5 mL). The aqueous layer
was extracted with ethyl acetate (5 × 10 mL) and the combined
organic layers were washed with H2O (3 × 10 mL) and dried (anhyd
Na2SO4). The solvent was concentrated in vacuo and the crude
residue was subjected to silica gel column chromatography (ethyl
acetate/hexane mixture, gradient elution) to obtain pure alkylidene
dibromide 5.
via conjugate addition of bromoform to nitroalkenes in the
presence of Mg or LDA. The intermediate ꢀ-tribromomethyl
nitroalkanes, including those formed in a diastereoselective
fashion, were also isolated under controlled Mg mediated
conditions. Although excess reagent is necessary to obtain high
yields of these synthetically and biologically relevant products,
the relatively inexpensive nature of the reagent, Mg or LDA,
and easily adaptable reaction conditions render this methodology
an attractive one. In the Mg mediated reaction, an anionic
mechanism has been ruled out and a radical mechanism has
been confirmed by chemical and spectroscopic methods. De-
tailed studies on the mechanism, the asymmetric version of this
conjugate addition, and various applications of the products will
be reported in due course.
Method B: LDA Mediated Reaction of Bromoform with
Nitroalkenes 1. To a stirred solution of nitroalkene 1 (0.5 mmol)
and bromoform (0.139 g, 0.55 mmol) in THF (10 mL) was added
LDA (3 mmol, generated from 3 mmol of n-BuLi and 3.3 mmol
of diisopropylamine in THF (5 mL) at 0 ꢁC) dropwise over a period
of 10 min at -78 ꢁC. Low temperature was maintained for another
3 h and then the reaction mixture was gradually brought to ambient
temperature. The resulting dark brown mixture was stirred at room
temperature overnight then quenched by saturated aqueous NH4Cl
(5 mL), and the aqueous layer was extracted with ether (5 × 10
mL). The combined organic layers were dried (anhyd Na2SO4) and
concentrated in vacuo to obtain crude alkylidene dibromide 5, which
was then subjected to silica gel column chromatography (ethylac-
etate/hexane mixture, gradient elution) to afford pure 5. Representa-
tive experimental data: 1-(1,1-Dibromo-3-nitroprop-1-en-2-yl)-
4-methoxybenzene (5a): yellow solid; yield from method A 108
Experimental Section
General Procedure for Mg Mediated Addition of Bromoform
to Nitroalkenes 1. To a stirred solution of magnesium (96 mg, 8
mmol) and nitroalkene 1 (0.5 mmol) in THF (10 mL) was added
bromoform (2.7 g, 1 mL, 11 mmol) dropwise over a period of 10
min at 0 °C. The reaction mixture was gradually brought to room
temperature over a period of 0.5 h during which the solution turned
dark brown. The reaction mixture was subsequently quenched with
saturated aqueous NH4Cl (5 mL). The aqueous layer was extracted
with ethyl acetate (5 × 10 mL) and the combined organic layers
were washed with H2O (3 × 10 mL), dried (anhyd Na2SO4), and
concentrated in vacuo to afford the crude product, which was
subjected to silica gel column chromatography (ethyl acetate/hexane
mixture, gradient elution) to afford pure 1,4-adduct 2. Representative
experimental data: 2-(1,1,1-Tribromo-3-nitropropane-2-yl)-1,4-
dimethoxy-benzene (2c): colorless solid; yield 178 mg, 74%; mp
109 ꢁC; IR (KBr, cm-1) 2998 (m), 2965 (m), 2934 (w), 2835 (w),
1552 (vs), 1504 (s), 1429 (m), 1375 (m), 1292 (s), 1222 (s), 1053
(m), 1024 (m), 815 (m), 781 (m), 687 (m), 533 (s); 1H NMR
(CDCl3, 400 MHz) δ 3.78 (s, 3H), 3.86 (s, 3H), 5.00-5.06 (br m,
1H), 5.33 (dd, J ) 13.2, 3.5 Hz, 1H), 5.50-5.60 (br m, 1H), 6.90
(ABq, J ) 15.5 Hz, the lower half is further split into d, J ) 8.8
Hz, 2H), 7.26 (br m, 1H); 13C NMR (CDCl3, 400 MHz) δ 42.3,
54.5, 55.7, 56.5, 78.0, 112.6, 113.7, 114.6, 124.0, 152.4, 153.1;
MS (ES-, Ar) m/z (rel intensity) 486 ([MNa + 4]+, 2), 484 ([MNa
+ 2]+, 10), 482 (MNa+, 10), 480 ([MNa - 2]+, 2), 363 (10), 361
(15), 253 (94), 251 (96), 212 (100); HRMS (ES-, Ar) calcd for
C11H12NO4Br3Na (MNa+) 481.8214, found 481.8191. For X-ray
data, see the Supporting Information.
ꢁ
mg, 62%, and from method B 129 mg, 74%, mp 88 C; IR (KBr,
cm-1) 3019 (s), 2966 (m), 1607 (m), 1560 (m), 1510 (m), 1367
(m), 1295 (m), 1216 (s), 1069 (w), 1031 (m), 773 (vs), 669 (s); 1H
NMR (CDCl3, 300 MHz) δ 3.82 (s, 3H), 5.39 (s, 2H), 6.92 (dt, J
) 6.7, 2.2 Hz, 2H), 7.21 (dd, J ) 6.7, 2.2 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ 55.2, 80.2, 100.8, 114.2, 129.4, 129.6, 135.9,
159.9; MS (ES-, Ar) m/e (rel intensity) 352 ([M + 3]+, 35), 350
([M + 1]+, 100), 348 ([M - 1]+, 35); HRMS (ES-, Ar) calcd for
C10H8NO3Br2 ([M - 1]+) 347.8871, found 347.8886; for X-ray data,
see the Supporting Information.
Acknowledgment. The authors thank DST, India, for finan-
cial assistance, SAIF, IIT, Bombay, for analytical support, Prof.
G. K. Lahiri for helpful discussions, Mr. Rajesh Gunjal and
Dr. Mayuri Gandhi for mass spectral data, and Ms. Nutan Agadi
for NMR spectral data. B.S. thanks CSIR, India, and G.N.G.
thanks IIT, Bombay for a research fellowship.
Supporting Information Available: Optimization tables,
X-ray data tables, ORTEP diagrams, complete experimental
procedures, characterization data, and copies of NMR and ESR
spectra. This material is available free of charge via the Internet
at http://pubs.acs.org.
General Procedure for the Preparation of Alkylidene
Dibromides 5 from Nitroalkenes 1. Method A: Magnesium
JO802274Q
2604 J. Org. Chem. Vol. 74, No. 6, 2009