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              Nitration of Substituted Styrenes With Nitryl Iodide
                         Tet Lett 26, 1193-1196 (1985)
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In connection with the search for a more efficient synthesis of 2,3,5-trimethoxy-
amphetamine [1], for use as a drug standard, we have found that nitryl iodide is 
a particularly effective general reagent for the nitration of substituted styrenes. 
Beta-Nitrostyrenes are generally prepared by direct nitration of styrenes or by 
condensation of the corresponding aldehyde with nitroethane [2]; reduction of the 
beta-nitrostyrene gives the amphetamine. Nitration of styrene by tetranitromethane 
is difficult and yields vary greatly. Nitration reagents such as HgCl2-NaNO2 [3] 
lead to varying degrees of ring nitration as well as the intended reaction at the 
double bond.

Nitryl iodide is generated in situ by the reaction of silver nitrite with iodine. 
First reported by Birchenbath in 1932 [4], this reaction was virtually disregarded 
until 1964. Its synthetic utility and the mild conditions of its application were 
initially described by Hassner et al [5] Two reports [6] on the use of this reagent 
with unsaturated carbohydrate derivatives appeared later. However, the application 
of nitryl iodide in general synthesis has not yet been widely explored.

The mechanism of the reaction was examined in detail by Hassner. Nitryl iodide 
underwent regioselective addition to styrene to form the 1-iodo-2-nitrostyrene 
which upon treatment with base generated the beta-nitrostyrene. However, contrary 
to Hassner's claim, we have found that the use of excess iodine does not improve 
the yield. We deduce that poor yield is attributable to degradation of the unstable 
iodonitro intermediate which is sensitive to moisture and oxygen. In some instances,
hydroxynitro compounds and nitroketones could be detected. However, good yields of 
beta-nitrostyrene could be consistently assured by treatment of the crude addition 
product with triethylamine, immediately following the disappearance of the styrene
substrate, as judged by tlc monitoring of the course of the reaction.

The solubility of the beta-nitrostyrene product in the reaction medium is a major 
factor affecting the yield realized: Beta-nitrostyrenes which are relatively 
insoluble in the reaction medium co-precipitate with the reagent, forming a solid 
cake which inhibits further reaction. In such a circumstance, changing to a more 
suitable solvent such as THF is necessary to ensure a respectable yield.

A representative nitration was performed as follows:

I2 (1016 mg, 4 mMol) and AgN02 (616 mg, 4 mMol) were stirred in anhydrous ether 
(20 ml) at r.t. under nitrogen for 45 min. (beta-Methylstyrene [propenylbenzene] 
(236 mg, 2 mMol) and pyridine (632 mg, 8 mMol) in ether were added and the mixture 
was stirred at r.t. for 31 h; after this time the yellow solid was removed by 
filtration. The filtrate was treated with 0.5 ml Et3N and evaporated to dryness. 
The residue was then treated with Et3N (1 ml) in CH2CI2 (1 ml) at r.t. for 1 h. 
The resulting solution was evaporated to dryness, the residue was dissolved in 
CH2Cl2, washed with 5% aqueous NaHSO3, 5% aqueous HCl, saturated aqueous NaHCO3 
and water, dried over Na2SO4 and solvent removed under reduced pressure to give a 
dark brown liquid. This material was chromatographed on silica and eluted with 8% 
ether in hexane to give the pure product (249 mg, 76.4%).


Table 1: 

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Starting material		Solvent	  Yield	   Product
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2,3,5-MeO-propenylbenzene	Ether	  80.3%	   2,3,5-MeO-phenylnitropropene
4-MeO-propenylbenzene           THF       81.8%    4-MeO-phenylnitropropene
Isosafrole                      THF       69.8%    beta-nitro-isosafrole
Isomyristicin                   THF       53.0%    beta-nitro-isomyristicin
Propenylbenzene                 Ether     76.4%    Phenylnitropropene
Styrene                         Ether     45.3%    Nitrostyrene
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References and notes:
---------------------

1. W.-W. Sy and A.W. By, Microgram, in press.
2. A.T. Shulgin, J. Med. Chem. 9, 45 (1966).
3. E.J. Corey and H. Estreicher, J. Am. Chem. Soc. 100, 6294 (1978).
4. L. Birchenbach, J. Goubeau and E. Berniger, Ber., 65, 1339 (1932).
5. A. Hassner, J.E. Kropp and G.J. Kent, J. Org. Chem. 34, 2628 (1969).
6. (a) W.A. Szarek and R.L. Beach, J. Chem. Soc. Chem. Commun. 356 (1968).
   (b) W.A. Szarek and R.L. Beach, Carbohydrate Res. 13, 75 (1976).
7. D.B. Miller, P.W. Flanagan and H. Schechter, J. Org. Chem. 41, 2112 (1976).
8. Starting materials (S-methylstyrenes) are mixtures of cis and trans isomers. 
   All products gave satisfactory spectral data. Nitrostyrenes have been shown  
   to predominate in the ground state trans (E) configuration; see: 
   (a) K. Bailey and D. Legault, Org. Magn. Reson. 16, 47 (1981). 
   (b) L. Leseticky and M. Flieger, Coll. Czech. Chem. Commun. 41, 2744 (1975).
9. A.T. Shulgin, Can. J. Chem. 46, 75 (1968).


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From CHEMISTRY LETTERS, pp. 1747, yr 1986

"A Practical Preparations of conjugated Nitroalkenes

...

Treatment of alkenes (1a -5a) with sodium nitrite and iodine in ethyl acetate 
(or ether) and water in the presence of ethylene glycol (or propylene glycol)
provides conjugated nitroalkenes (1b -5b)_in 49 - 82% yields.

...

A typical procedure is as follows:  To a solution of sodium nitrite (1324 mg, 
19.2 mmol) and ethylene glycol (893, 14.4 mmol) in 2.0 mL of water, a solution
of styrene, 3a (500 mg, 4.8 mmol) in 15 mL of ethyl acetate was added followed 
by addition of iodine (1828 mg, 7.2 mmol) at 0 C.  The reaction mixture
was stirred at room temperature for 48 hrs under nitrogen and then was poured 
into a seperatory funnel together with ethyl acetate and partitioned. The ethyl 
acetate solution was succesively washed with water, aqueous 10% thiosulfate and 
aqueous saturated NaCl.  After drying over anhydrous magnesium sulfate, the 
ethyl acetate solution was evaporated to to obtian crude products. These were 
purified by silica gel column chromotography...  to afford pure beta-nitrostyrene, 
3b in 81% yield.  ..."

Ritter: 
      
Just so you guys know, SWIM has been using this rxn for ages to produce the 
nitropropene from asarone. It is the best rxn out there for this type of 
nitration. Yields from asarone are always at least 75% of extremely dense dark 
yellow crystals unlike the fluffy ones produced with the pseudonitrosite route.  
The only byproduct is unreacted asarone and this is easily separated from the 
crystals by EtOH recrystallization.

The N2 atmosphere is aboloutely necessary.  Yields are in the 40% range without 
it.  Simply take a balloon of N2 and stick it on the mouth of the rxn flask and 
secure with wire ties. 

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