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		Selective Nitration of Styrenes with Clayfen and Clayan:
			A Solvent-free Synthesis of b-Nitrostyrenes

			  Tetrahedron Letters 39, 3977-3980 (1998)

		 Rajender S. Varma, Kannan P. Naicker and Per J. Liesen


Abstract: A facile solvent-free synthesis of b-nitrostyrenes is described
from styrene and its substituted derivatives using inexpensive 'doped' clay
reagents, Clayfen and Clayan.

beta-Nitrostyrene and its derivatives are vital starting materials for the
synthesis of a variety of useful building blocks and valuable precursors
such as nitroalkanes, amines, ketoximes, hydroxylamines and aldoximes [1].
The title compounds are generally prepared by direct nitration of styrenes
or by the condensation of appropriate aldehydes with nitroethane [2].
However, it is quite challenging to achieve direct transformation of
styrenes to beta-nitrostyrenes due to the highly sensitive nature of the
vinylic side chain. The literature to date embodies only a few scattered
reports, which include the treatment of styrene with sodium or potassium
nitrate in polyphosphoric acid,[3] nitrohalogenation with nitryl halides
(NO2X) followed by dehydrohalogenation with triethylamine,[4] the reaction
of styrene with tetranitromethane (TNM) in the presence of pyridine[5] and
nitration of a deactivated styrene with nitric acid (98%) in concentrated
sulfuric acid [6]. Nitration reagents such as HgCl2-NaNO2[7] lead to varying
degrees of ring nitration as well as the desired reaction at the olefinic
bond. The photochemical charge transfer activation of the electron
donor-acceptor (EDA) complex, derived from TNM and styrenes in
acetonitrile, has been reported to give different products depending on the
nature of styrenes, e.g. b-nitrostyrene from p-methoxy-styrene,
isoxazolidines from styrene and p-methylstyrene and an a-nitroacetophenone
from p-chlorostyrene[8] Other reagents employed for nitration of styrenes
include AgNO2/PhSeBr/HgCl2,[9] AgNO2/I2/ethylene glycol[10] and an
ultrasound promoted reaction in a sealed tube with
NaNO2-Ce(NH4)2(NO3)6-AcOH.[11] A relatively clean reaction of styrene has
been reported recently using nitrogen monoxide in 1,2-dichloroethane
followed by treatment with activated acidic alumina;[12] the protocol,
however, calls for the requirement of 4 equivalents of nitrogen monoxide
for the introduction of each nitro group.

In continuation of our ongoing research program on solvent-free organic
transformations,[13] we decided to explore the direct conversion of
styrenes to b-nitrostyrenes using clay doped with nitrate salts. The
heterogeneous reaction with Clayfen (iron(III) nitrate on clay)[14] in
various solvents failed to generate b-nitrostyrenes but the solid state
neat reactions readily provided the desired side chain nitrated styrenes.
Herein, we report the details of this simple and inexpensive nitration
method using Clayfen[14] and Clayan (ammonium nitrate on clay)[15] that
proceeds under solvent-free conditions. Clayfen has been shown to be an
efficient ring nitrating agent for a wide variety of phenols and nitrogen
heterocyclic compounds[14] but no side chain nitration has been
demonstrated. Additionally, we found that the related Clayan[15] is equally
useful for nitration of styrene and its p-substituted derivatives.

In a typical example, the neat styrene and Clayfen or Clayan are mixed well
in a glass container and then heated in an oil bath (~100-110°C, 15 min) or
irradiated in a microwave oven (~100-110°C, 3 min) in solid state (Eqn. 1).
In the case of Clayfen, the reaction mixture is irradiated continuously for
3 min whereas for Clayan intermittent warming is recommended with 30 second
intervals (temperature should not exceed ~60-70°C).

	p-R-C6H4-CH=CH2 ==> p-R-C6H4-CH=CH-NO2 + p-R-C6H4-CHO	(Eqn. 1)

Where R = H, Cl, Me, OMe. 
Reaction is carried out on Clayfen or Clayan in an oil bath or with MW.

Yields:

52-68% :        p-R-C6H4-CH=CH-NO2
 9-21% :        p-X-C6H4-CHO

Table 1: Product distribution in solventless nitration of styrenes [a]
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Entry   Substrate      beta-Nitrostyrene[b]   Aldehyde[b]     Polymer/others
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Using Clayfen
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1       Styrene 			68(56)  		21(35)  		11(09)
2       p-Chlorostyrene 	52(41)  		10(22)  		38(37)
3       p-Methylstyrene 	52(41)  		11(24)  		37(35)
4       p-Methoxystyrene      14(14)  		09(15)  		77(71)
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Using Clayan
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5       Styrene 			59(47)  		20(35)  		21(18)
6       p-Chlorostyrene 	49(37)  		11(23)  		40(40)
7       p-Methylstyrene 	44(35)  		15(26)  		41(39)
8       p-Methoxystyrene      13(12) 		12(15)  		75(73)
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[a] Reaction conditions for Clayfen. either in oil bath (15 min) or in
    microwave. MW. (3 min) at 100-110°C and for Clayan, either in oil bath
    (15 min) or in MW (3 min) at 60-70°C
[b] The relative amounts of product formation are determined by GC-MS
    analysis and the results in the parentheses refer to the corresponding
    yields obtained using MW irradiation; the products are identified by
    comparison of their m.p. and NMR spectra with those reported for the
    known compounds in the literature.

Our results for styrene and its various p-substituted derivatives such as 
p-chloro-, p-methyl- and p-methoxy-styrene using both the nitrating agents,
Clayfen and Clayan, are depicted in Table 1. In the case of styrene, p-chloro- 
and p-methyl-styrene, respectable yields (52-68%) of corresponding b-nitro-
styrenes are obtainable. In contrast, the electron rich p-methoxystyrene 
resulted in the major formation of polymeric and other unidentified products 
with only 14% of p-methoxy-b-nitrostyrene (entries 4 and 8, Table). In all the 
cases, considerable amount of the corresponding aldehyde (9-21%) formation is 
observed along with some nitrite (2-3%) from GC-MS analysis. At room temp, the 
reaction is found to be very slow and also leads to the major formation of 
polymeric products. Of the two nitrating reagents, Clayfen delivered relatively
better results (Table).

A recent report details the side chain nitration of styrenes with nitrogen
dioxide and ozone in slightly lower yields[16], in halogenated solvents,
wherein the reaction proceeds via the formation of nitro-nitrate intermediates 
(cpds 1 and 2 - Scheme) which, in turn, are converted to the required p-nitro-
styrenes using alumina or a base. Our solventless method, however, does not 
reveal the formation of such nitro-nitrate intermediates, cpds 1 and 2, 
according to GC-MS analysis.

Equation Scheme for nitration with NO2-O3 [16], where R = NO2, CF3, H, Cl, Me:

p-R-C6H4-CH=CH2  ==> 
		p-R-C6H4-CH(NO2)-CH-ONO2  +  p-R-C6H4-CH(ONO2)-CH-NO2    
									==>  p-R-C6H4-CH=CH-NO2

The investigation of the same reaction under the identical conditions 
using clay that is impregnated with NaNO3, KNO3 and NaNO2 does not produce
b-nitrostyrene; instead substantial amounts of polymeric products are
observed as discerned by GC-MS analysis. In order to improve the formation
of nitrated product, we explored the use of m-chloroperbenzoic acid which
suppresses the formation of polymeric products but results in the formation
of nitro-nitrates, cpds 1 and 2 (scheme) as the major product; only minor
amounts (~10-15%) of side chain nitrated product were obtained. Changes in 
other reaction parameters such as conducting the reaction for a longer duration 
of time or the additional use of a strong base (NaNH2) does not transform the 
nitro-nitrate intermediates, cpds 1 and 2 as reported earlier [16].

The reaction with Clayfen is investigated under heterogeneous conditions in
a variety of solvents. In contrast, we observed the following results; (a)
in ether at room temperature (16 h), 1% of b-nitrostyrene, 15% aldehyde and
11% starting material; (b) in dichloromethane under refluxing condition (5 h), 
1-2% of b-nitrostyrene, 2-3% of aldehydes; (c) upon ultrasound irradiation 
in dichloromethane at room temperature (2 h), 26% of b-nitrostyrene, 31% of 
aldehyde. The remaining material in all cases is the polymeric products.

In conclusion, the solid state reaction of styrene and its p-substituted
derivatives with Clayfen and Clayan is a very facile method to produce
b-nitrostyrenes. The operational simplicity, the use of inexpensive reagents, 
and a rapid reaction that avoids the undesirable polymerization of styrene 
(typical heterogeneous reactions in solvents), makes this a useful procedure 
and attractive alternative to the currently available methods.

General. A Sears Kenmore microwave (MW) oven operating at 2450 MHz (900 W) 
was used for all the experiments. Styrenes were purchased from Acros Organics 
and were used as received. (1)H NMR spectra were recorded in CDCl3 on Jeol 
300 MHz spectrometers using TMS as an internal standard. Clayfen (0.75g 
Fe(NO3)3.9H2O/1g clay) and Clayan (1g NH4NO3/1g clay) were prepared according 
to the published procedures. [14,15]

CAUTION: Although we did not encounter any accident during these studies, we
recommend extreme caution for reactions conducted an larger scales because
of the possible higher localized temperatures attained in the microwave (MW) 
oven, especially for Clayan that should not be heated beyond 70 C in oil bath 
or MW oven.

General procedure for the conversion of styrene to b-nitrostyrene: In a typical 
experiment, styrene (180 mg, 1.74 mmol) was admixed with Clayfen or Clayan 
(300 mg) in a glass tube. The reaction mixture was placed in an oil bath for 
15 min or irradiated for 3 min in an alumina bath [17] inside an unmodified 
household microwave oven (900 watt) at its medium power. On completion of the 
reaction, followed by TLC examination (hexane:EtOAc, 4:1, v/v), the product was 
extracted into dichloromethane (45 mL), the combined organic extract dried with 
anhydrous sodium sulfate and solvent removed under reduced pressure. 
The relative amounts of product distribution (Table) were calculated from GC-MS 
analysis (Hewlett-Packard model 5890 GC/MS). Alternatively, the crude material
was chromatographed on a silica gel column and eluted with hexane:EtOAc (4:1, 
v/v) to afford the pure product (147 mg, 57%).

ACKNOWLEDGEMENT

We are grateful for financial support to the Texas Advanced Research Program 
(ARP) in chemistry (Grant # 003606-023) and Texas Research Institute for 
Environmental Studies (TRIES) and thank Dr. Dahiya for the preparation of 
'doped' clay materials, Clayfen and Clayan.

REFERENCES AND NOTES

Per J. Liesen is an undergraduate student participant in chemistry program at 
Sam Houston State University.

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