Carmeli and Rozen
SCHEME 1. Direct Oxidation of Azides to Nitro
Compounds
nitrocyclopentane (5) and nitrocyclohexane (6) in good yields.
The same is true for tertiary azides such as 1-azidoadamantane
(7), which was transformed to 1-nitroadamantane (8)19 in 95%
yield. Ester groups do not pose any problems either, as evident
from the reaction of 5-azidopentyl acetate (9), resulting in
5-nitropentyl acetate (10)20 in 90% yield.
The family of R-nitro acids is quite useful as a starting point
for various reactions, and several synthetic methods have been
devised for the preparation of its members. Save the oxidation
of amino acids by HOF‚CH3CN,21 most methods are based on
a combination of two fragments such as nitroacetate and an alkyl
group or carboxylic acid derivatives and a nitro compound.22
These procedures are usually characterized by long reaction
times and low yields. Direct conversion of R-azido esters to
the corresponding nitro derivatives can serve as an alternative
efficient method for preparing these compounds. Thus, reacting
ethyl azidoacetate (11) with 6 equiv of HOF‚CH3CN at 0 °C
produced ethyl nitroacetate21 (12) in a few minutes reaction.
Ethyl 2-azido hexanoate (13) behaved similarly, forming ethyl
2-nitrohexanoate (14) in good yield.
Despite the fact that the HOF‚CH3CN complex is able to
oxidize primary alcohols,8 the short reaction times with the azido
group enabled its selective oxidation without affecting such an
hydroxyl group. 11-Azidoundecanol (15) could serve as an
example by its conversion to the corresponding 11-nitrounde-
canol (16)23 in a few seconds using 3 equiv of HOF‚CH3CN
complex. Although HOF‚CH3CN is known to react slowly with
aromatics,24 the ring in benzyl azide (17) does not interfere with
the fast reaction of the azido moiety, forming almost quantita-
tively R-nitrotoluene (18). Similarly, reacting R-azido acetophe-
none (19) with 3 molar equiv of HOF‚CH3CN produced R-nitro
acetophenone (20) in a clean, few seconds reaction. The same
is true for N-(3-azidopropyl)phthalimide (21), which was reacted
with 4 equiv of the HOF‚CH3CN complex to form N-(3-
nitropropyl)phthalimide25 (22) in 80% yield. Cleavage of the
phthalimide group with hydrazine hydrate produced 1-amino-
3-nitropropane (22a),26 a member of the difficult to obtain nitro
amino derivatives.
Reacting 1-azido-6-chlorohexane (23) with 3 equiv of HOF‚
CH3CN for a few seconds produced the corresponding new nitro
derivative (24) in 87% yield. An alternative method for the
preparation of similar compounds uses direct chlorination of
the nitro derivative, but this option requires harsh conditions
and results in low yields.27 Nitriles are also tolerated, and treating
1-azido-6-cyanohexane (25) with 3 equiv of HOF‚CH3CN forms
1-cyano-6-nitrohexane (26) in a few seconds without affecting
the cyano group.
reactions and many more16 are evidence of the high synthetic
potential of HOF‚CH3CN.
We report here of a new and unprecedented direct oxidation
of azides, easily obtained from alkyl halides or alcohol deriva-
tives, to the corresponding nitro compounds by the HOF‚
CH3CN complex.5
Results and Discussion
1-Azidodecane (1) was readily prepared from bromodecane
and sodium azide in excellent yields following a literature
procedure.17 A solution of 3 molar equiv of HOF‚CH3CN (each
molar equivalent is a supplier of one oxygen atom) was added
to a methylene chloride solution of 1 at 0 °C. A release of N2
was observed, and in a few seconds the reaction was over,
forming 1-nitrodecane (2)18 in 98% yield (Scheme 1).
Secondary azides also reacted well. Cyclopentyl (3) and
cyclohexyl (4) azides, prepared from the corresponding bro-
mides,17 needed only 5 s at 0 °C in order to be converted to
Unlike the very short reaction times required by the aliphatic
azides, it took almost 1 h for 10 equiv of HOF‚CH3CN to react
with azidobenzene (27) at room temperature to form nitroben-
(18) Crandall, J. K.; Reix, T. J. Org. Chem. 1992, 57, 6759.
(19) Krishnamurthy, V. V.; Iyer, P. S.; Olah, G. A. J. Org. Chem. 1983,
48, 3373.
(20) Brewster, K.; Harrison, M. J.; Inch, D. T.; Williams, N. J. Chem.
Soc., Perkin Trans. 1 1987, 21.
(13) (a) Kol, M.; Rozen, S. J. Chem. Soc., Chem. Commun. 1991, 567.
(b) Rozen, S.; Kol, M. J. Org. Chem. 1992, 57, 7342. (c) Dirk, S. M.;
Mickelson, E. T.; Henderson, J. C.; Tour, J. M. Org. Lett. 2000, 2, 3405.
(d) Golan, E.; Rozen, S. J. Org. Chem. 2003, 68, 9170.
(14) (a) Dayan, S.; Kol, M.; Rozen, S. Synthesis 1999, 1427. (b) Chavez,
D. E.; Hiskey, M. A. J. Energ. Mater. 1999, 17, 357.
(21) Rozen, S.; Bar-Haim, A.; Mishani, E. J. Org. Chem. 1994, 59, 1208.
(22) (a) Eyer, M.; Seebach, D. J. Am. Chem. Soc. 1985, 107, 3601. (b)
Ram, S.; Ehrenkaufer, R. E. Synthesis 1986, 133.
(23) Li, Z.; Crosignani, S.; Linclau, B. Tetrahedron Lett. 2003, 44, 8143.
(24) Kol, M.; Rozen, S. J. Org. Chem. 1993, 58, 1593.
(25) Ballini, R.; Barboni, L.; Giarlo, G. J. Org. Chem. 2004, 69, 6907.
(26) Martin, P. D.; Bibart, T. R.; Drueckhammer, G. D. J. Am. Chem.
Soc. 1994, 116, 4660.
(15) (a) Rozen, S.; Dayan, S. Angew. Chem., Int. Ed. 1999, 38, 3471.
(b) Rozen, S.; Carmeli, M. J. Org. Chem. 2005, 70, 2131.
(16) For reviews dealing with the use of HOF‚CH3CN in general organic
chemistry, see: (a) Rozen, S. Eur. J. Org. Chem. 2005, 2419. (b) Rozen,
S. Acc. Chem. Res. 1996, 29, 243. (c) Rozen, S. Pure Appl. Chem. 1999,
71, 481.
(17) Alvarez, S. G.; Alvarez, M. T. Synthesis 1997, 413.
(27) Sayles, C. D.; Degering, F. E. J. Am. Chem. Soc. 1949, 71, 3161.
4586 J. Org. Chem., Vol. 71, No. 12, 2006