J. Jacoway et al. / Tetrahedron Letters 53 (2012) 6782–6785
6785
in 1,2-DCE. Isomer distribution in both systems is strongly ortho/
para (with little or no meta isomer being observed), but there are
some variations in regioselectivity, with higher ortho/para ratios
in IL relative to 1,2-DCE (except in anisole).
substrates that can be nitrated. Although many mechanistic ques-
tions remain, relative reactivity trends suggest a SET mechanism
for these heterogeneous nitration reactions.
A similar reactivity trend was observed in the nitration of
p-xylene, mesitylene, tetramethylbenzene, and 1,3-dimethoxy-
benzene (Table 3), with reactions in IL proceeding faster relative
to 1,2-DCE under the same set of conditions and with some var-
iation in product distribution. For instance, formation of the 2-
nitro isomer in nitration of 1,3-dimethoxybenzene was only ob-
served in the IL and dinitro-mesitylene was only detected in 1,2-
DCE.
Acknowledgment
Support of this work via research support provided to K.L. by
UNF is gratefully acknowledged.
References and notes
1. Review: Leonard, N. M.; Wieland, L. C.; Mohan, R. S. Tetrahedron 2002, 58,
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To determine the scope and limitation of arene nitration with
BN a variety of other substrates were subsequently examined in
both media and the results are summarized in Table 4. Whereas
chlorobenzene, bromobenzene, and p-bromoanisole were quanti-
tatively nitrated in both systems, longer reaction times were
needed with 1,2-DCE to reach the same conversions. As in previous
examples, variations in isomer distributions were also observed.
Lowering arene reactivity further by introducing more deactivating
substituents (runs 4–7) led to no reaction with BN/IL but reactions
proceeded in 1,2-DCE to eventually give the nitro derivatives in
respectable yields.
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13. General procedure for the nitration of aromatic compounds in ionic liquid: The
ionic liquid (3.5–4.0 mL) was charged into an oven-dried Schlenk tube under a
nitrogen atmosphere and Bi(NO3)3Á5H2O (1.5 mmol) was added. The respective
aromatic compound (1 mmol) was then introduced into the Schlenk tube
under a nitrogen atmosphere. The reaction mixture was magnetically stirred,
initially at rt for about 10 min followed by stirring in a pre-heated oil bath at
80–85 °C, until completion (as monitored by GC–MS). Once the reaction was
over, the contents were cooled to rt and extracted with EtOAc–Hexane (2:3 vol/
vol), until the final extraction did not show a spot corresponding to the starting
material or to the product. The combined organic extracts were washed with
10% NaHCO3 solution, dried with MgSO4, and concentrated to give the crude
product. Isomer distributions were determined by GC–MS, and/or by 1H NMR.
14. General procedure for the nitration of aromatic compounds in 1,2-dichloroethane:
A mixture of aromatic compound (1 mmol) and Bi(NO3)3Á5H2O (1.5 mmol) in
1,2-DCE (4 mL) was stirred at 80–85 °C. On completion (as monitored by GC–
MS), the contents were cooled to rt and dissolved in DCM (5 mL). The
combined organic layers were washed with 10% NaHCO3 solution, dried over
MgSO4, and concentrated under reduced pressure to give the crude product.
Isomer distributions were determined by GC–MS, and/or by 1H NMR.
15. (a) Laali, K. K.; Borodkin, G. I. J. Chem. Soc., Perkin Trans. 2 2002, 953–957; (b)
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16. Observations made in mesitylene/durene competitive nitration (absence of
nitromesitylene) appear unusual considering their independent reactions with
BN (see Table 2 entries 2–3) and imply that the formation of durene radical
cation is somehow suppressing a SET process for mesitylene!
Additional insights were obtained via the reactions of p-
methoxybenzaldehyde and p-methoxyacetophenone (runs 6 and
7) where products of nitro-deformylation and nitro-deacetylation
were observed indicative of ipso substitution.
Relative reactivity of mesitylene and durene (KMes/KDur) is com-
monly used as a good indicator to distinguish between a classical
polar mechanism (SEAr) and the single electron transfer (SET)
mechanism.15 A KMes/KDur <1 is typically indicative of SET mecha-
nism.15b,c Competitive nitration of mesitylene/durene (1:1) was
examined in the present study via GC monitoring. Analysis of an
aliquot withdrawn after 30 min showed only unreacted mesitylene
and nitrodurene. In an effort to slow down the nitration sufficiently
to determine KMes/KDur, the competitive reaction was performed in
1,2-DCE. But again due to a large difference in relative reactivity
substrate selectivity could not be measured. These observations
appear consistent with a SET process. The large difference in rela-
tive reactivity in IL versus 1,2-DCE, and observation of minor prod-
ucts arising from ipso substitution are also compatible with a SET
mechanism for arene nitration with BN.16
Although BN is a readily available low cost reagent, the ability
to recover and reuse the IL provides an added cost saving incentive.
Table 5 summarizes the results of recovery and reuse of the IL for
three runs showing a gradual decrease in the conversions from
quantitative to 86%.
In summary the ready availability and the low cost of BN, sim-
ple operation under mild conditions, and the absence of promoters,
coupled to recycling and reuse of the IL provide an attractive, envi-
ronmentally more acceptable, alternative to classical nitration
methods for activated arenes. Switching from Bi(NO3)3Á5H2O/
[bmim][PF6] to Bi(NO3)3Á5H2O/1,2-DCE increases the scope of the