1476
J. Am. Chem. Soc. 1997, 119, 1476-1477
Table 1. Reaction of Aliphatic Organolithiums or Grignards with
N2O4
Nitration of Organolithiums and Grignards with
Dinitrogen Tetroxide: Success at Melting Interfaces
yield,b %
organometallica
M ) Li
M ) MgCl
product
Keita Tani, Kirill Lukin, and Philip E. Eaton*
n-BuM
sec-BuM
t-BuM
19
4
trace
71
29
trace
n-BuNO2
sec-BuNO2
t-BuNO2
Department of Chemistry, The UniVersity of Chicago
5735 S. Ellis AVe., Chicago, Illinois 60637
a Organolithiums in alkane and Grignards in THF or Et2O were
ReceiVed October 23, 1996
1
purchased from Aldrich Chemical. b Based on H NMR integrations
against an internal standard.
Recently we reported that the sodium salts of 1,3,5,7-
tetranitrocubane and 1,2,3,5,7-pentanitrocubane can be nitrated
successfully with dinitrogen tetroxide in THF at low tempera-
ture.1 These reactions apparently1 proceed by N2O4 oxidation
of the anion to the radical and its combination with NO2 (or
N2O4). As far as we can find, these nitrations are the first
successful examples of nitration of localized2 group IA orga-
nometallics reported in the literature. As the common assump-
tion is that nitration of a carbanion is not a useful reaction, we
looked to see if the cubane cases above were special or if we
had found conditions for anion nitration that were broadly useful.
Indeed, as we now report, the latter pertains. We have a new
method to effect nitration of common organometallics with
N2O4. Our results should provide important clues for others
who might need or want to develop this reaction further.
The literature reports only that dialkylhydroxylamines are
formed from reaction of a Grignard with a dilute ethereal
solution of nitrogen dioxide.3 We find that direct N2O4 nitration
of primary and even secondary alkyl Grignards can be done
with some success (Table 1), but this depends critically on
methodology (Vide infra).4 It is noteworthy that both n-BuNO2
(71% isolated yield) and sec-BuNO2(29%) were obtained pure
even after a workup consisting of nothing more than simple
extraction and evaporation. We suppose that much of the
“missing” mass is in the butanes formed by radical abstraction
of hydrogen atom from THF by the intermediate n-butyl or sec-
butyl radicals. Both t-BuMgCl and t-BuLi gave only trace
amounts of t-BuNO2. This might be due to further oxidation,
i.e. the radical to tert-butyl cation. Cubyllithium, another tertiary
example, could not be successfully nitrated. Only cubane (13%)
and bicubyl (20%) were identifiable products. Both can form
by way of the cubyl radical. We are not sure what blocks
reaction of this radical with N2O4.
derivatives with electron-donating (e.g., methyl) or electron-
withdrawing groups (e.g., diisopropylcarboxamido) afforded the
corresponding nitro compounds in high yield (Table 2). A
significant amount (15%) of N,N-diisopropylbenzamide was also
isolated from 4-(N,N-diisopropylbenzamido)lithium, again sug-
gesting that N2O4 oxidizes the organometallic to a radical which
can abstract hydrogen from the solvent or react with N2O4.
Our nitration procedure is also useful for preparing heteroaro-
matic nitro compounds (Table 2). Some of the necessary
organolithiums, e.g., 4-pyridyllithium and 3-thienyllithium, were
obtained by simple halogen-metal exchanges between the
commercially available bromo compounds and n-BuLi. In other
cases, direct lithiation was used; 2-thienyllithium and 2-(N,N-
diisopropylbenzamido)lithium were prepared in this manner.
Each of these organolithiums was successfully nitrated in good
to very good yield specifically at the position of lithiation. Of
course, some of these nitro compounds are available by other
straightforward methods, but there are cases for which our
method is now the one of choice. For example, 3-nitrothiophene
can now be obtained in 70% overall yield from commercial
3-bromothiophene; this is far superior to the older literature
procedure (20% from thiophene).6
Table 2. Nitration of Aryllithiums with N2O4
Ar-Li
phenyllithium
p-tolyllithiuma
product (isolated yields)
nitrobenzene (87%)
p-nitrotoluene (86%)
4-(N,N-diisopropylbenzamido)- 4-nitro-N,N-diisopropylbenzamideg
lithiumb
(81%)
4-pyridyllithiumc
3-thienyllithiumd
2-thienyllithiume
4-nitropyridineh (57%)
3-nitrothiophenei (70%)
2-nitrothiophene (76%)
Although Grignards gave better yields than organolithiums
in the aliphatic series, the reverse was true with phenyl Grignard
versus phenyllithium. N2O4 nitration of phenyllithium5 and its
2-(N,N-diisopropylbenzamido)- 2-nitro-N,N-diisopropylbenzamidej
lithiumf
(57%)
a Reference 7a. b 4-(N,N-Diisopropylbenzamido)lithium was prepared
from 4-bromo-N,N-diisopropylbenzamide and n-BuLi (1.1 equiv) in
THF at -102 °C. c Reference 7b. d Reference 7c. e Reference 7d.
f Reference 7e. g Reference 7f. h Reference 7g. i Reference 7h. j Ref-
erence 7i.
(1) Lukin, K.; Li, J.; Gilardi, R.; Eaton, P. E. Angew. Chem., Int. Ed.
Engl. 1996, 35, 864.
(2) For nitration of delocalized anions, see: (a) Thiele, J. Chem. Ber.
1900, 33, 666. (b) Feuer, H. In The Chemistry of Amino, Nitroso and Nitro
Compounds and Their DeriVatiVes, Supplement F; Patai, S., Ed.; John Wiley
and Sons: New York, 1982; pp 805-848.
(3) (a) Wieland, H. Chem. Ber. 1903, 36, 2315. (b) Troyan, J. E. J.
Am. Chem. Soc. 1942, 64, 3056.
Such results lead us to believe that low-temperature N2O4
nitration of organometallics is certainly worth considering as a
simple and potentially quite efficient and effective approach to
(4) CAUTION: N2O4 is dangerous; use of an efficient hood and protecting
shield is essential. Typical reaction conditions were as follows: In one
flask a solution of the organometallic (0.50 mmol) in THF (2 mL) was
frozen solid (THF: mp -108 °C) using an external liquid nitrogen bath
(ca. -190 °C). Separately, gaseous dinitrogen tetroxide (N2O4 h 2NO2)
from a commercial cylinder was condensed into another weighed flask;
6-12 equiv was collected. This was evaporated (warm water bath), and
the gas led through a cannula and deposited (mp -11 °C) onto the frozen
organometallic/THF glass in the first flask. Once all the N2O4 had been
added, the flask was transferred from the liquid nitrogen bath to a room
temperature methanol bath and shaken vigorously as it warmed to room
temperature. The reaction appeared to start as soon as the frozen mixture
began liquefying at the interface; it was over quickly and finished (no further
color change) well before the mixture was fully liquid. Excess N2O4 and
solvent were removed (house vacuum, water bath <40 °C). The residue
was extracted with CH2Cl2, washed with water, and dried over anhydrous
MgSO4. The crude product was examined by NMR. When appropriate,
the major product was isolated by silica gel column chromatography.
Usually THF and diethyl ether gave the same results, but in the latter case
sometimes small amounts of nitrite and nitrate esters were formed.
(5) Cf.: Bunce, N. J.; Stephenson, K. L. Can. J. Chem. 1989, 67, 220.
(6) Blatt, A. H.; Bach, S.; Kresch, L. W. J. Org. Chem. 1957, 22, 1693.
(7) (a) DesEnfants, R. E., II; Gavney, J. A.; Hayashi, R. K.; Rae, A. D.;
Dahl, L. F. J. Organomet. Chem. 1990, 383, 543. (b) Phillips, J. E.; Herber,
R. H. J. Organomet. Chem. 1984, 268, 39. (c) Strekowski, L.; Harden, D.
B.; Grubb, W. B., III; Patterson, S. E.; Czarny, A.; Mokrosz, M. J.; Cegla,
M. T.; Wydra, R. L. J. Heterocycl. Chem. 1990, 27, 1393. (d) Furber, M.;
Herbert, J. M.; Taylor, R. J. K. J. Chem. Soc., Perkin Trans. 1 1989, 683.
(e) Beak, P.; Brown, R. A. J. Org. Chem. 1982, 47, 34. (f) Fong, C. W.;
Grant, H. G. Aust. J. Chem. 1981, 34, 1205. (g) Kaneko, C.; Yamamoto,
A.; Gomi, M. Heterocycles 1979, 12, 227. (h) Maag, H.; Manukian, B. K.
HelV. Chim. Acta 1973, 56, 1787. (i) 2-Nitro-N,N-diisopropylbenzamide:
mp 112.5-113.5 °C (light yellow plates from EtOH); 1H NMR (400 MHz,
CDCl3) δ 1.11 (d, J ) 6.8 Hz, 3H), 1.18 (d, J ) 6.8 Hz, 3H), 1.56 (d, J )
6.8 Hz, 3H), 1.62 (d, J ) 6.8 Hz, 3H), 3.50-3.62 (m, 2H), 7.33 (dd, J )
1.2, 7.6 Hz, 1H), 7.50-7.54 (m, 1H), 7.66-7.70 (m, 1H), 8.18 ppm (dd, J
) 1.2, 8.0 Hz, 1H).
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