From azides to nitro compounds in a few seconds using HOF·CH3CN

Article abstract of DOI:10.1021/ja035616d

HOF·CH₃CN, a very efficient oxygen-transfer agent, was reacted with various azides to form the corresponding nitro compounds in excellent yields and in very short reaction times. The respective nitroso derivatives were found to be intermediates in this reaction. When the azides were reacted with MCPBA or DMDO, no reaction took place, and the starting materials were fully recovered. Copyright

Full text of DOI:10.1021/ja035616d

Published on Web 06/14/2003
3
From Azides to Nitro Compounds in a Few Seconds Using HOF‚CH CN
Shlomo Rozen* and Mira Carmeli
School of Chemistry, Raymond and BeVerly Sackler Faculty of Exact Sciences, Tel-AViV UniVersity,
Tel-AViV 69978, Israel
Received April 14, 2003; E-mail: rozens@post.tau.ac.il
Professor Sharpless, the 2001 Nobel Laureate, stated in a recent
The speed of the reaction made us wonder if other oxygen-
transfer agents would be as effective as HOF‚CH CN. We refluxed
methylene chloride solutions of 1 with 8 mol equiv of MCPBA
for 6 h and recovered more than 98% of the starting material.
1-Azidodecane (1) was quantitatively recovered also after treatment
with 14 mol equiv of dimethyldioxirane (DMDO) for several hours.
paper that azides “usually make fleeting appearance in organic
3
1
synthesis” mainly because of “irrational fear”. Their chemistry is
indeed conspicuously underdeveloped and mainly associated with
reduction to amines. The “opposite” reaction, namely oxidation to
nitro compounds, is practically unknown with the exception of
Corey’s multistep method of converting the azides first to phosphine
3
It seems that HOF‚CH CN is a stand-alone oxygen-transfer agent
imines (RN
3
f RNdPR
3
) followed by ozone oxidation. The nitro
when the transformation of azides to nitro compounds is in question.
derivatives thus obtained (40-70% yield) were accompanied by
the corresponding phosphine oxides as well as by aldehydes, which
in certain cases were the sole products.2
The only limitation of this reaction is the ability of making the
azides, but once they are at hand the rest is easy. Although HOF‚
16
CH
3
CN is known to react with aromatic rings, this reaction is
1
3
3
Some years ago we developed the HOF‚CH CN complex, simply
relatively slow, and therefore the ring in benzyl azide (3) will
not interfere with the immediate reaction of the azido moiety to
give almost quantitatively R-nitrotoluene (4). Neither will an ester
group, which remains intact for the duration of the reaction.
5-Azidopentyl acetate (5), obtained in 94% yield from 5-bromopen-
by bubbling diluted fluorine (commercially available) through
3
aqueous acetonitrile. This oxygen-transfer agent was used for
4
5
epoxidations of various types of olefins, oxidation of alcohols
6
and methyl ethers to ketones as well as the conversion of ketones
to esters via the Bayer-Villiger reaction, oxidation of sulfides,
including electron-depleted ones, to sulfones, and much more.
This reagent has also been used to convert primary amines and
even amino acids10 to the corresponding nitro compounds. HOF‚
5
17
tyl acetate, was quickly converted to 5-nitropentyl acetate (6) in
7
8
3
90% yield. HOF‚CH CN is able to substitute tertiary hydrogens
9
18
with a hydroxyl group in a slow reaction. It is not surprising then
to find that 1-azidoadamantane (7) was converted to 1-nitroada-
11
19
CH
3
CN was also reacted with tertiary amines to produce N-oxides,
mantane (8) in 95% yield without affecting the three tertiary
12
and reacts with 1,10-phenanthroline to furnish the N,N′-dioxide,
a compound which has eluded synthesis for more than 50 years.
These processes strongly supported the notion that the oxygen atom
of this reagent is a very strong electrophile indeed. This and the
fact that many transformations could be accomplished only by HOF‚
hydrogens found in the starting azide. Secondary azides are excellent
substrates as well. Preparing cyclohexyl (9) and cyclopentyl (10)
1
3
azides from the corresponding bromides is straightforward, and
again a 5-s, 0 °C reaction with 3 mol equiv of the reagent is all it
takes to obtain nitrocyclohexane (11) and nitrocyclopentane (12)
in good yields.
3
CH CN and not by any other oxygen-transfer agent encouraged us
to examine if the carbon-bonded nitrogen of azides would be
3
One of the advantages of HOF‚CH CN is that its electrophilic
nucleophilic enough to interact with the oxygen atom of HOF‚
oxygen comes from water, which is the best source for all oxygen
3
CH CN. One quick experiment was enough to provide an encour-
isotopes. We have passed fluorine through a solution of acetonitrile
1
8
18
aging answer.
and H
2
3
O and obtained H OF‚CH CN, which was reacted with
1
8
1
-Azidodecane (1) was easily prepared from bromodecane and
1. HRMS (CI) data [m/z ) 190.157446, calcd for C10H20N O (M
2
13
sodium azide in excellent yields following a literature procedure.
- 1) 190.15789] confirmed that the two oxygen atoms of the
nitrodecane (11, 98% yield) are the expected [18]O isotope.
A solution of 3 mol equiv of HOF‚CH
methylene chloride solution of 1 at 0 °C. A release of N
3
CN was then added to a
was
2
immediately observed, and in a few seconds the reaction was over,
forming 1-nitrodecane (2)14 in 92% yield.
15
The reaction works also with aromatic azides, although it is not
as practical as the reaction with the aliphatic ones, mainly because
these azides are usually made from the corresponding aromatic
amines, which are themselves excellent substrates for oxidation by
CN to the nitro derivatives.9 Still, the reactions of
a
HOF‚CH
3
aromatic azides could shed light on the mechanism of this reaction.
In contrast to the short reaction times required for oxidation of
aliphatic azides, conversion of azidobenzene (12) to nitrobenzene
(
(
13) required almost an hour. On the other hand, nitrosobenzene
14) was oxidized by HOF‚CH CN immediately. The more electron-
3
rich carbon-bonded nitrogen of 4-methoxyazidobenzene (15) reacted
considerably faster than 12 (10 min versus 1 h), to give 4-nitroani-
8118
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J. AM. CHEM. SOC. 2003, 125, 8118-8119
10.1021/ja035616d CCC: $25.00 © 2003 American Chemical Society

C O MMU N I C A T I O N S
sole in 65% yield. What is more, one could clearly observe the
development of an intensive blue color of the nitroso derivative
element. Today there are more than a hundred. We hope this work
will contribute to increase this number.
(
17) which was formed and then disappeared after a few seconds.
Acknowledgment. This work was supported by the Israel
Science Foundation, founded by the Israel Academy of Sciences
and Humanities.
It should be noted that 4-azidonitrobenzene (18) was found to be
unreactive toward the electrophilic oxygen of the reagent because
of the low electron density of the carbon-bonded azido nitrogen.
These observations support a two-step reaction mechanism. The
first and rate-limiting step involves attack of the electrophilic oxygen
on the relatively electron-rich azido nitrogen, resulting in formation
of a nitroso compound, N , and HF. Consequently, the respective
2
nitroso reacts fast with an additional molecule of HOF‚CH
form the desired nitro compound.
References
(
1) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew.
Chem., Int. Ed. 2002, 41, 2596.
(2) Corey E. J.; Samuelsson, B.; Luzzio, F. A. J. Am. Chem. Soc. 1984, 106,
3682.
(3) Rozen, S.; Brand, M. Angew. Chem., Int. Ed. Engl. 1986, 25, 5, 554.
3
CN to
(4) (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, 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.
(
(
(
5) Rozen, S.; Bareket, Y.; Kol, M. Tetrahedron 1993, 49, 8169.
6) Rozen, S.; Dayan, S.; Bareket, Y. J. Org. Chem. 1995, 60, 8267.
7) (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.
(
8) (a) Rozen, S. Acc. Chem. Res. 1996, 29, 243. (b) Rozen, S. Pure Appl.
Chem. 1999, 71, 481.
(
9) (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.
(
10) Rozen, S.; Bar-Haim, A.; Mishani, E. J. Org. Chem. 1994, 59, 1208.
11) (a) Dayan, S.; Kol, M.; Rozen, S. Synthesis 1999, 1427. (b) Chavez, D.
E.; Hiskey, M. A. J. Energ. Mater. 1999, 17, 357.
(
(
(
(
(
12) Rozen, S.; Dayan, S. Angew. Chem., Int. Ed. 1999, 38, 3471.
13) Alvarez, G. S.; Alvarez, M. T. Synthesis 1997, 413.
14) Crandalland, J. K.; Reix, T. J. Org. Chem. 1992, 57, 6759.
15) General procedure for working with fluorine: 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 11a. For the occasional
2
user, however, various premixed mixtures of F in inert gases are
commercially available, simplifying the process. If elementary precautions
are taken, work with fluorine is relatively simple, and we have had no
bad experiences working with it. General procedure for producing the
HOF‚CH
in this work. They were passed at a rate of about 400 mL/min through a
cold (-10 °C) mixture of 60 mL of CH CN and 6 mL of H O. The
3 2
CN complex: Mixtures of 10-15% F with nitrogen were used
3
In conclusion, we have demonstrated that the HOF‚CH CN is
probably the best oxygen-transfer agent chemistry has to offer. It
is capable of transformations which cannot be completed by any
3
2
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 mol/L. With the exception of the [18]O-labeled 11, the
final nitro products are known. Their spectral properties are in full
agreement with those described in the literature.
other reagent, and the reaction RN
example. The only “problem” with this agent is the reluctance of
some chemists to work with F . This should not be so. Today,
3 2
f RNO is an important
2
(
16) Kol, M.; Rozen, S. J. Org. Chem. 1993, 58, 1593.
prediluted fluorine is commercially available, and the work with it
is as easy as turning a valve on and off. All reaction vessels are
standard glassware, and a simple basic trap takes care of small
(17) Compound 6 was made previously in 42% yield in a 3-day reaction: Zee-
Cheng, K. Y.; Cheng, C. C. J. Med. Chem. 1969, 12, 157.
(
18) Rozen, S.; Brand, M.; Kol, M. J. Am. Chem. Soc. 1989, 111, 8325.
(19) Krishnamurthy, V. V.; Iyer, P. S.; Olah, G. A. J. Org. Chem. 1983, 48,
373.
3
amounts of F
2
which had not reacted with water. Twenty years
ago, only a handful of organic laboratories were working with this
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J. AM. CHEM. SOC.
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