A Fast, High-Yield Preparation of Vicinal Dinitro Compounds Using HOF·CH3CN

Article abstract of DOI:10.1021/jo030217m

HOF·CH₃CN, a very efficient oxygen-transfer agent, was reacted with various aliphatic and aromatic vicinal diamino compounds. The products were the rare, vicinal dinitro derivatives formed in excellent yields and short reaction times. This is in contrast to other oxygen-transfer agents which tend to break the central C-C bond of the diamino precursor. This reaction was also used for making dinitro compounds with all four oxygens, being the [18]O isotope.

Full text of DOI:10.1021/jo030217m

N-oxides,12 oxidizing sulfides, including electron depleted
ones to sulfones,13 transforming primary amines to the
corresponding nitro compounds,14 and much more.15
HOF‚CH3CN is unique among all oxidants since it
possesses a very strong electrophilic oxygen atom which
can be transferred to nucleophilic centers under very mild
conditions (0 °C, few seconds). Such conditions help to
avoid many side reactions usually associated with ele-
vated temperatures and long reaction times. This was
indeed the main factor responsible for the successful
reaction of amino acids with HOF‚CH3CN that yielded
the corresponding R nitro acids with no decarboxylation
or deamination.16 We found that these properties also
enabled the oxidation of vicinal diamino compounds to
the corresponding dinitro derivatives without breaking
the central C-C bond as other reagents do.
It took 3 min for HOF‚CH3CN to convert 1,2-diamino-
propane (1) to 1,2-dinitropropane (2) in 82% yield. For
comparison, this product was previously prepared from
propene and N2O4 in 20% yield,17 so even the common
spectral properties of 2 and similar compounds could not
be found in the literature until today. The reaction also
proceeded well with tertiary amines, and it took only a
minute to transform 1,2-diamino-2-methylpropane (3) to
1,2-dinitro-2-methylpropane (4) in 90% yield. Cyclic
diamino compounds were also subjected to reaction with
HOF‚CH3CN, and trans-1,2-diaminocyclohexane (5) pro-
duced the trans-1,2-dinitrocyclohexane (6) in 95% yield.
Again, this product was obtained in the past by using
N2O4,6 but in 25% yield only. cis-1,2-Diaminocyclohexane
(7) behaved somewhat differently, and while we could
detect the corresponding dinitro derivative 8, we were
unable to purify it since upon workup it spontaneously
eliminated the elements of HNO2, producing 1-nitro-
cyclohexene (9) isolated in 71% yield.18
A F a st, High -Yield P r ep a r a tion of Vicin a l
Din itr o Com p ou n d s Usin g HOF ‚CH3CN
Elizabeth Golan and Shlomo Rozen*
School of Chemistry, Raymond and Beverly Sackler Faculty
of Exact Sciences, Tel-Aviv University,
Tel-Aviv 69978, Israel
rozens@post.tau.ac.il
Received J uly 7, 2003
Abstr a ct: HOF‚CH3CN, a very efficient oxygen-transfer
agent, was reacted with various aliphatic and aromatic
vicinal diamino compounds. The products were the rare,
vicinal dinitro derivatives formed in excellent yields and
short reaction times. This is in contrast to other oxygen-
transfer agents which tend to break the central C-C bond
of the diamino precursor. This reaction was also used for
making dinitro compounds with all four oxygens, being the
[18]O isotope.
Nitro compounds have found numerous uses in organic
chemistry. More than 25 years ago, Seebach had already
dubbed them “ideal intermediates in organic synthesis”.1
However, the difficulties associated with the preparation
of 1,2-dinitro derivatives limited their use to being only
precursors for tetrasubstituted olefins2 and electronic
switching devices.3
In aliphatic chemistry, two main methods were usually
employed. The first was fusing two molecules, each
containing an oxime4 or a nitro group,5 while the second
was based on reacting olefins with the highly toxic
dinitrogen tetroxide (N2O4). The latter resulted, in most
cases, in low yields of the 1,2-dinitro products.6 To obtain
1,2-dinitro aromatic compounds is even more challenging
since nitration of nitroaromatics tends to give mainly
m-dinitro derivatives. These limited methods have never-
theless been used, since conventional oxidation of vicinal
diamino groups could not have been employed due to the
“push-pull” effect generated during the oxidation process
which tends to break the central C-C bond.7
Although it is reasonable to assume a direct attack of
the electrophilic oxygen atom of the HOF‚CH3CN on the
nucleophilic nitrogen, we have observed in the past
attacks of this reagent on the carbon atom R to electron-
donating heteroatoms.10,11 This, however, is not the case
with the family of the vicinal diamines. The stereochem-
istry around the nitrogen-bonded carbons is fully retained
as evident from the reaction of (1S,2S)-(-)-1,2-diphenyl-
Some years ago, we developed the HOF‚CH3CN com-
plex, which is conveniently generated in situ by bubbling
diluted fluorine (commercially available) through aque-
ous acetonitrile.8 This oxygen-transfer agent was used
for epoxidations of various types of olefins,9 converting
alcohols10 and methyl ethers11 to ketones, preparing
(9) (a) Rozen, S.; Kol, M. J . Org. Chem. 1990, 55, 5155. (b) Hung,
M. H.; Smart, B. E.; Feiring, A. E.; Rozen, S. J . Org. Chem. 1991, 56,
6, 3187. (c) Rozen, S.; Bareket, Y.; Dayan, S. Tetrahedron Lett. 1996,
37, 531. (d) Dayan, S.; Ben-David, I.; Rozen, S. J . Org. Chem. 2000,
65, 8816.
(10) Rozen, S.; Bareket, Y.; Kol, M. Tetrahedron 1993, 49, 8169.
(11) Rozen, S.; Dayan, S.; Bareket, Y. J . Org. Chem. 1995, 60, 8267.
(12) Dayan, S.; Kol, M.; Rozen, S. Synthesis 1999, 1427.
(13) (a) Rozen, S.; Bareket, Y. J . Org. Chem. 1997, 62, 1457. (b)
Toyota, A.; Ono, Y.; Chiba, J .; Sugihara, T.; Kaneko, C. Chem. Pharm.
Bull. 1996, 44, 703.
* Author to whom correspondence may be addressed. Fax: 972-3-
6409293.
(1) Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. Chimia 1979,
33, 1.
(2) Korenblum, N. Aldrichimica Acta 1990, 23 (3), 71.
(3) Chen, J .; Reed, M. A.; Rawlett, A. M.; Tour, J . M. Science 1999,
286, 1550.
(14) (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.
(4) Camps, P.; Munoz-Torrero, D. Tetrahedron Lett. 1994, 35, 3187.
(5) Wade, P. A.; Kondracki, P. A.; Carrol, P. J . J . Am. Chem. Soc.
1991, 113, 8807.
(6) Baldock, H.; Levy, N.; Scaife, C. W. J . Chem. Soc. 1949, 2627.
(7) Dave, P. R.; Axenrod, T.; Qi, L.; Bracuti, A. J . Org. Chem. 1995,
60, 1895 and references therein.
(15) (a) Rozen, S. Acc. Chem. Res. 1996, 29, 243. (b) Rozen, S. Pure
Appl. Chem. 1999, 71, 481.
(16) Rozen, S.; Bar-Haim, A.; Mishani, E. J . Org. Chem. 1994, 59,
1208.
(17) Levy, N.; Scaife, C. W. J . Chem. Soc. 1946, 1093.
(18) Sreekumar, R.; Padmakumar, R.; Rugmini, P. Tetrahedron Lett.
1998, 39, 2695.
(8) Rozen, S.; Brand, M. Angew. Chem., Int. Ed. Engl. 1986, 25, 554.
10.1021/jo030217m CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/18/2003
9170
J . Org. Chem. 2003, 68, 9170-9172

ethylenediamine (10), [R]D ) -102° (EtOH), with HOF‚
CH3CN, resulting in 95% yield of (1S,2S)-(-)-1,2-dinitro-
1,2-diphenylethane (11), [R]D ) -414° (EtOH).19
compound was previously described as a low-yield byprod-
uct during the nitration of 1,2-dimethyl-4-nitrobenzene.23
The presence of an electron-withdrawing group on the
aromatic ring reduces the nucleophilicity of the amino
nitrogen atoms, and the reaction of 3,4-diaminobenzo-
phenone (15) proceeded with 55% yield only to give 3,4-
dinitrobenzophenone (16).24 An additional factor contrib-
uting to the reduced yield of this particular reaction is
the slower, but still noticeable, competitive Baeyer-
Villiger reaction with the HOF‚CH3CN.10
In conclusion, it was demonstrated that the HOF‚
CH3CN, probably the best oxygen-transfer agent chem-
istry has to offer, is capable of oxidizing vicinal diamino
compounds to their vicinal dinitro counterparts, a trans-
formation that could not be carried out before. The only
“problem” with this agent is that some chemists are
reluctant to work with F2. They should not be. Today,
prediluted fluorine is commercially available and working
with it is as easy as turning a valve on and off. All
reaction vessels are standard glassware, and a simple
basic trap removes small amounts of F2 that did not react
with the water. Twenty years ago, only a handful of
organic laboratories were working with this element.
Today, there are more than a hundred. We hope that this
work will contribute to increase this number.
One of the advantages of HOF‚CH3CN is that its
electrophilic oxygen originates in water, which is the
most convenient source for all oxygen isotopes. We have
passed fluorine through a solution of acetonitrile and
H218O and obtained H18OF‚CH3CN, which was reacted
with trans-1,2-diaminocyclohexane (5). The 18O content
of the product was difficult to quantitate using conven-
tional EI or CI techniques. Even Amirav’s supersonic GC/
MS,20 which usually solves such problems,21 was not fully
successful with this family of compounds. Fortunately,
however, Amirav developed a new ionization method
named cluster chemical ionization, which is based on
electron ionization of clusters formed from the sample
and a solvent such as MeOH, both in the supercooled
supersonic expansion stage.22 This mass spectrum (clus-
ter CI with MeOH, m/z ) 183 (M + 1)+) clearly confirms
that all four oxygen atoms of all 18O-trans-1,2-dinitro-
cyclohexane 12 (94% yield) are the expected 18O isotope.
To the best of our knowledge this is the first time that a
compound containing four 18O atoms is described.
Exp er im en ta l Section
1H NMR and 13C NMR spectra were obtained at 200 and 50.2
MHz, respectively, with Me4Si as an internal standard. The mass
spectra were recorded on a homemade GC/MS with a supersonic
molecular beam (refs 20 and 22). All clusters CI were obtained
with MeOH.
Gen er a l P r oced u r e for Wor k in g w ith F lu or in e. Fluorine
is a strong oxidant and a very corrosive material. It should be
used only with an appropriate vacuum line such as the one
described in ref 12. For the occasional user, however, various
premixed mixtures of F2 in inert gases are commercially avail-
able, simplifying the process. If elementary precautions are
taken, work with fluorine is relatively simple and we have had
no bad experiences working with it.
Gen er a l P r oced u r e for P r od u cin g HOF ‚CH3CN Com -
p lex. Mixtures of 10-15% F2 with nitrogen were used in this
work. They were passed at a rate of about 400 mL min-1 through
a cold (-10 °C) mixture of 60 mL of CH3CN and 6 mL of H2O.
The development of the oxidizing power was monitored by
reacting aliquots with acidic aqueous solution of KI. The
liberated iodine was then titrated with thiosulfate. Typical
concentrations of the oxidizing reagent were around 0.4-0.6 M.
The diamino compound (1-2 g) was dissolved in about 20 mL
of CH2Cl2, cooled to 0 °C, and added in one portion to 6 mol/
equiv of the reagent. About 2-3 g of NaF was added to all
aliphatic diamino derivatives to absorb the HF found in the
reagent and minimize the formation of amino/HF salts. The
reaction was quenched with dilute bicarbonate and extracted
with CH2Cl2, and the organic layer was dried over MgSO4.
This oxidation also proceeds well with aromatic di-
amines. We reacted 4,5-dimethyl-1,2-phenylenediamine
(13) with HOF‚CH3CN for 4 min at -15 °C and obtained
4,5-dimethyl-1,2-dinitrobenzene (14) in 87% yield. This
(19) The racemic 11 has been made by Korenblum nitro synthesis:
Crombie, L.; Roughley, B. S. Tetrahedron 1986, 42, 3147. Obviously,
such synthesis is bound to lead to racemic compounds only.
(20) (a) Dagan, S.; Amirav, A. J . Am. Soc. Mass Spectrom. 1995, 6,
120. (b) Amirav, A.; Gordin, A.; Tzanani, N. Rapid Commun. Mass
Spectrom. 2001, 15, 811.
(21) Rozen, S.; Golan, E. Eur. J . Org. Chem. 2003, 1915.
(22) (a) Dagan, S.; Amirav, A. J . Am. Soc. Mass Spectrom. 1996, 7,
550. (b) Fialkov, A. B.; Amirav, A. Rapid Commun. Mass Spectrom.
2003, 17, 1326.
(23) Fischer, A.; Henderson, G. N.; Iyer, L. M. Can. J . Chem. 1985,
63, 2390.
(24) Kametani, T.; Shio, M. J . Heterocycl. Chem. 1971, 8, 545.
J . Org. Chem, Vol. 68, No. 23, 2003 9171

Evaporation of the solvent followed by purification by either flash
chromatography or recrystallization gave the target dinitro
product. With the exception of the chiral compound 11 and the
[18]O labeled 12, the final dinitro products are known. Their
spectral properties are in full agreement with the corresponding
structures.
2.61-2.54 (2 H, m), 2.37-2.32 (2 H, m), 1.82-1.73 (2 H, m),
1.66-1.61 ppm (2 H, m); 13C NMR 134.25, 29.59, 24.70, 23.82,
21.70, 20.58 ppm. Cluster EI MS: m/z ) 127 (M)+.
(1S,2S)-(-)-1,2-Din itr o-1,2-d ip h en yleth a n e (11)19 was pre-
pared from 10 as described above in 95% yield: mp 147 °C (from
MeOH); [a]D ) -414° (EtOH); 1H NMR 7.27 (10 H, m), 6.42 ppm
(2 H, s); 13C NMR 130.63, 129.34, 127.80, 90.24 ppm.
4,5-Dim eth yl-1,2-d in itr oben zen e (14)22 was prepared from
13 as described above in 87% yield: mp 116 °C (from EtOH);
1H NMR 7.68 (2 H, s), 2.42 ppm (6 H, s); 13C NMR 143.31, 140.38,
125.49, 19.63 ppm.
3,4-Din itr oben zop h en on e (16)23 was prepared from 15 as
described above in 54% yield: mp 80 °C (from MeOH); 1H NMR
8.33-8.32 (1 H, m), 8.18-8.01 (2 H, m), 7.82-7.67 (3 H, m),
7.61-7. 53 ppm (2 H, m); 13C NMR 191.79, 141.83, 134.90,
134.05, 133.93, 129.78, 128.81, 125.94, 125.03 ppm; MS (EI): m/z
) 272 (M)+.
1,2-Din itr op r op a n e (2)17 was prepared from 1 as described
above in 82% yield: yellow oil; 1H NMR 5.25-5.22 ppm (1 H,
m), 5.11 ppm (1 H, dd, J 1 ) 16 Hz, J 2 ) 9 Hz), 4.62 ppm (1 H,
dd, J 1 ) 16 Hz, J 2 ) 2.5 Hz), 1.68 ppm (3 H, d, J ) 7 Hz); 13C
NMR 77.94, 74.66, 16.41 ppm. Cluster CI MS: m/z ) 135 (M +
1)+.
1,2-Din itr o-2-m eth ylp r op a n e (4) was prepared from 3 as
described above in 90% yield: mp 50 °C (from MeOH); 1H NMR
4.96 (2 H, s), 1.74 ppm (6 H, s); 13C NMR 84.02, 79.79, 23.68
ppm. Cluster CI MS: m/z ) 149 (M + 1)+.
tr a n s-1,2-Din itr ocycloh exa n e (6)6 was prepared from 1 as
described above in 95% yield: yellow oil; 1H NMR 5.04-4.98 (2
H, m), 2.64-2.61 (2 H, m), 1.98-1.95 (2 H, m), 1.80-1.77 (2 H,
m), 1.49-1.44 ppm (2 H, m); 13C NMR 83.84, 30.35, 23.35 ppm.
Cluster CI MS: m/z ) 175 (M + 1)+. For trans (all [18]O-1,2-
dinitrocyclohexane (12)), cluster CI MS: m/z ) 183 (M + 1)+.
1,-Nitr ocycloh exen e (9)18 was prepared from 5 as described
above in 71% yield: yellow oil; 1H NMR 7.35-7.30 (1 H, m),
Ack n ow led gm en t. This work was supported by the
Israel Science Foundation founded by the Israel Acad-
emy of Sciences and Humanities.
J O030217M
9172 J . Org. Chem., Vol. 68, No. 23, 2003