ipso-nitration of arylboronic acids with chlorotrimethylsilane-nitrate salts

Article abstract of DOI:10.1021/ol0493249

A mixture of nitrate salt and chlorotrimethylsilane is found to be an efficient regioselective nitrating agent for the ipso-nitration of arylboronic acids to produce the corresponding nitroarenes in moderate to excellent yields. High selectivity, simplicity, and convenience are the key features of the reaction.

Full text of DOI:10.1021/ol0493249

ORGANIC
LETTERS
2
004
Vol. 6, No. 13
205-2207
ipso-Nitration of Arylboronic Acids with
Chlorotrimethylsilane−Nitrate Salts
2
G. K. Surya Prakash,* Chiradeep Panja, Thomas Mathew,
Vijayalakshmi Surampudi, Nicos A. Petasis, and George A. Olah*
Loker Hydrocarbon Research Institute and Department of Chemistry,
UniVersity of Southern California, Los Angeles, California 90089-1661
gprakash@usc.edu
Received April 13, 2004
ABSTRACT
A mixture of nitrate salt and chlorotrimethylsilane is found to be an efficient regioselective nitrating agent for the ipso-nitration of arylboronic
acids to produce the corresponding nitroarenes in moderate to excellent yields. High selectivity, simplicity, and convenience are the key
features of the reaction.
9
10
Nitration of aromatic compounds is one of the most
extensively studied reactions, and nitroaryl moieties play
tion and nitration of arylboronic acids with N-halosuccin-
1
11
imides and Crivello’s reagent (ammonium nitrate/trifluro-
key roles in the physical and chemical properties of many
target molecules in organic synthesis. For electrophilic
nitration of aromatic compounds, a wide variety of reagents
acetic anhydride), respectively. However, during nitration
with the relatively powerful Crivello’s reagent, dinitration
was also observed and the temperature had to be carefully
regulated to avoid undesirable side reactions.
2,3
are available to date. Most of them are very strong nitrating
agents and often lead to further nitration and mixture of
isomers. Since most nitrating agents are oxidants, oxidation
of other functional groups can also occur, giving a mixture
of products. Thus, a search for milder and selective nitrating
agents is a good research goal. In the last few decades,
Herein we report a simple, convenient and mild method
for the ipso-nitration of arylboronic acids using inorganic
nitrate salt and chlorotrimethylsilane. This method provides
the ipso-nitrated product in moderate to high yield (∼95-
9
8% purity for the crude product itself) and is found to be
4
arylboronic acids have been extensively used as versatile
more selective than our previously reported method using
synthons in organic synthetic transformations involving
1
1
5
Crivello’s reagent. The reaction is easy to perform, and
workup avoids further purification in many cases. Another
various reactions such as Suzuki coupling and multicom-
ponent reactions for the synthesis of various amino acids
and trifluoromethylated amines.6 Fluorination of various
,7
8
(6) (a) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M.
Chem. ReV. 2002, 102 (5), 1359 and references therein. (b) Petasis, N. A.;
Boral, S. Tetrahedron Lett. 2001, 42 (4), 539. (c) Petasis, N. A.; Goodman,
A.; Zavialov, L. A. Tetrahedron 1997, 53 (48), 16463.
(7) Prakash, G. K. S.; Mandal, M.; Schweizer, S.; Petasis, N. A.; Olah,
G. A.J. Org. Chem. 2002, 67 (11), 3718 and references therein.
(8) (a) Diorazio, L. J.; Widdowson, D. A.; Clough, J. M. Tetrahedron
1992, 8 (37), 8073. (b) Petasis, N. A.; Yudin, A. K.; Zavialov, L. A.;
Prakash, G. K. S.; Olah, G. A. Synlett 1997, 5, 606.
derivatives of aryl/alkenylboronic acids has been reported.
In earlier studies, we have shown regeoselective halogena-
(1) (a) Olah, G. A.; Malhotra, R.; Narang, S. C. Nitration: Methods
and Mechanisms; VCH: New York, 1989. (b) Kuhn, S. J.; Olah, G. A. J.
Am. Chem. Soc. 1961, 83, 4564. (c) Schofield, K. Aromatic Nitration;
University Press: Cambridge, 1980.
(2) Olah, G. A.; Kuhn, S. J. J. Am. Chem. Soc. 1962, 84, 3684.
(
3) Olah, G. A.; Prakash, G. K. S.; Wang, Q.; Li, X. In Encyclopedia of
(9) Thiebes, C.; Prakash, G. K. S.; Petasis, N. A.; Olah, G. A. Synlett
1998, 141.
Reagents for Organic Synthesis; Paquette, L. A.; Wiley: Chichester, 1995;
Vol. 6.
(10) Stefan, S.; Jurgen, S.; Prakash, G. K. S.; Petasis, N. A.; Olah, G.
A. Synlett 2000, 1485.
(4) Negishi, E. Comp. Organomet. Chem. 1983, 7, 323.
(5) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11, 513.
(11) Crivello, J. V. J. Org. Chem. 1981, 46, 3056.
1
0.1021/ol0493249 CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/02/2004

significant feature of this method is the complete absence
of dinitro product!
It has been reported12 that 2-nitroketones can be synthe-
Table 1. Effect of Different Nitrate Salts in the ipso-Nitration
of Phenylboronic Acidsa
3 3
sized from olefins using TMS-Cl/AgNO /CrO as a reagent
nitrate salt
time (h)
yield (%)
system. We have previously reported13 that a mixture of
ammonium nitrate and chlorotrimethylsilane with a catalytic
AgNO3
30
36
48
98b
95c
95c
NH4NO3
NaNO3
KNO3
Ba(NO3)2
Fe(NO3)3
3
amount of AlCl can function as a good nitrating system for
the electrophilic nitration of aromatics. During our search
for a milder and convenient nitrating agent for ipso-nitration
100
>100
8
95c
0d
of arylboronic acids, we decided to use NH
system without strongly Lewis acidic AlCl present. Without
AlCl in the system, the direct nitration of aromatics is rather
4
NO
3
/TMS-Cl
40e
3
a
Conditions: nitrate salt (2.2 equiv), TMS-Cl (2.2 equiv), DCM (10
b
3
mL), stirred at rt for the time specified. Only 2% nitrochlorobenzene was
observed (GCMS). c Nitrochlorobenzene (5-10%) was observed. No
d
sluggish. However, with arylboronic acids, ipso-substitution
was observed. We explored this reaction using different
arylboronic acids and obtained ipso-nitro substitution in all
cases with moderate to excellent yields. The behavior and
activity of different nitrates and solvents have also been
explored.
e
desired product was observed. Some unidentified impurities, which could
not be separated from the product.
such as 1,2-dichloroethane, the amount of chlorination
increases. Oxygenated solvents such as ether and THF are
not suitable, as TMSCl can interact with them. Alcohols are
also unsuitable, as they can undergo O-silylation under the
reaction conditions. No nitration was observed in acetonitrile
solution. Since a relatively polar solvent is needed without
any chemical interaction for the dissolution of the arylboronic
acid, the solvent choice was narrowed down to haloalkanes,
with DCM as the most suitable solvent.
Use of chlorotrimethylsilane in conjunction with inorganic
salts as reagents for various organic oxidations and other
reactions is well-known.14 Lee et al. reported that the
reaction of chlorotrimethylsilane with sodium nitrate and
nitrite gives nitryl and nitrosyl chloride, respectively. Syn-
thetic use of the nitryl chloride generated in situ from TMS-
Cl and nitrate salts has not been mentioned. A mixture of
chlorotrimethylsilane and sodium nitrate was used for
deoximation of aldoximes/ketoximes and for nonaqueous
diazotization.15
15
Table 2. Effect of Solvents in the ipso-Nitration of
Nitration of arylboronic acids with a mixture of TMS-Cl
and nitrate salts takes place at the ipso-position of the aryl
ring without ring nitration or sequential nitration. However,
along with the ipso-nitration, 2-10% nitrochlorination was
also observed in certain cases. This is not surprising since a
mixture of TMS-Cl and nitrate salt can also act as a
4 3
Phenylboronic Acid with NH NO /TMSCl
solvent
time (h)
yield (%)a
CH2Cl2
CHCl3
30
48
95
90
70b
80c
0
CCl4
48
ClCH2CH2Cl
CH3CN
20
>72
chlorinating agent. We have found that when AgNO
3
was
used instead of NH NO as the nitrate salt, the extent of
4
3
a
Crude yield (without further purification) of the product. b Dichlorinated
chlorination significantly decreased. This may be due to the
fact that the silver ion can remove chloride efficiently from
the system by the precipitation of AgCl. The amount of
chlorinated product increases, as the phenyl ring becomes
more electron rich. Thus, with p-tolylboronic acid, a mixture
of nitrated and chlorinated products was obtained. We have
studied the effect of different nitrate salts on ipso-nitration
c
products (∼25%) were observed. Unidentified byproducts (∼20%) were
observed.
The reaction system is also good for arylboronic acids with
different functionalities, though the yields vary. m-Chloro/
bromo nitrobenzenes can be easily obtained from m-chloro/
bromophenylboronic acids under mild conditions. Thus, the
boronic acid group orients the nitro group very easily toward
the ipso position to give the desired nitro aromatics in
excellent yields. The method is very useful in cases where
the preparation of the nitro derivatives is rather difficult or
needs drastic conditions. Though a small amount of chlori-
nated byproduct is formed, its amount, compared to the
desired nitro product, is insignificant. Nitroarylboronic acid
also undergoes nitration by the same reagent system, but
needs heating and purification of the final product by column
chromatography. Reaction of the trifluoromethyl-substituted
phenyl boronic acid has been found to be very sluggish.
There can be several possible explanations for the regio-
selective nitration of arylboronic acid. It is well-known that
TMS-Cl reacts with nitrate salts to generate the TMS-O-
3
and found AgNO to give the best results. Table 1 shows a
comparative study of the reactions using various nitrate salts.
With ferric nitrate, a mixture of products was obtained, and
further decomposition resulted in a low yield of the desired
product.
The effect of different solvents on the reaction system has
also been investigated (Table 2). Dichloromethane (DCM)
was found to be the most suitable solvent. In other solvents
(
12) Ram Reddy, M. V.; Kumareswaran, R.; Vankar, Y. D. Tetrahedron
Lett. 1995, 39, 7149.
13) Olah, G. A.; Ramaiah, P.; Sandford, G.; Orlinkov, A.; Prakash, G.
K. Synthesis 1994, 468.
14) Vankar, P. S.; Ram Reddy, M. V.; Vankar, Y. D. Org. Prep. Proc.
Int. 1998, 30 (4), 373 and references therein.
15) (a) Lee, J. G.; Kwak, K. H.; Hwang, J. P. Tetrahedron Lett. 1990,
1, 6677. (b) Lee, J. G.; Cha, H. T. Tetrahedron Lett. 1992, 33, 3167.
(
(
(
3
2206
Org. Lett., Vol. 6, No. 13, 2004

Scheme 1. ipso-Nitration of Arylboronic Acids
Table 3. Ipso-nitration of arylboronic acids using TMSCl/
nitrate salts
NO
2
species. Since we have not observed the dinitro product
in any case, it is likely that there exists a prominent electronic
interaction between the boronic acid group and the interme-
diate active nitrating agent TMS-O-NO species through
2
boron and the siloxy group due to the high oxophilicity of
boron (Scheme 2). This helps the nitration to occur at the
Scheme 2. Suggested Mechanism for ipso-Nitration of
Arylboronic Acid
a
Heated in a sealed tube at 50 °C. b Isolated chemical yield (by column
chromatography).
2
ipso position. TMS-O-NO can undergo further reaction with
excess TMS-Cl to give hexamethyldisiloxane and nitryl
chloride, which can also act as the nitrating species. For the
generation of the nitryl chloride, an excess of TMSCl is
required, but we have found that phenylboronic acid can
undergo nitration completely with 1 equiv of TMS-Cl. The
reaction takes 72 h for completion. This indicates that the
In conclusion, we have developed a simple and convenient
method for the ipso-nitration of arylboronic acids. The
method works well with a variety of functionalized aryl-
boronic acids. Mild conditions and ease of workup are the
salient features of this method.
2
TMS-O-NO species is the likely active nitrating intermedi-
ate. However, the reaction rate was found to increase with
the increase in concentration of TMS-Cl. With more than 2
equiv of the reagents, it is possible that some nitryl chloride
could be formed, which could act as a nitrating as well as a
chlorinating agent. This explains the minor amount of
chlorinated product formed in some cases. With aliphatic
boronic acids, we were unable to obtain any nitrated product.
This shows that the aromatic ring plays an important
electronic role in the ipso-nitration.
Acknowledgment. Support of our work by Loker Hy-
drocarbon Research Institute is gratefully acknowledged.
Supporting Information Available: General experimen-
tal paragraph and experimental procedure for ipso-nitration
of arylboronic acid. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL0493249
Org. Lett., Vol. 6, No. 13, 2004
2207