Here are few interesting citations from "Synthesis of Paredrine and Related Compounds",
. I didn't know it was possible to prepare phenylnitroalkanes this way. Paredrine is a synonym for 4-hydroxyamphetamine, for the sake of TFSE.
[...]
Paredrine, a proprietary name for p-hydroxyphenyl-2-propylamine, is a synthetically-prepared, racemic mixture of the HO-C6H4-CH2CHNH2CH3 bases, which is marketed as the hydrobromide. Solutions are used for shrinking the nasal mucosa in head-colds and hay fever, for sinus irrigation, and in ophthalmology as an adjuvant to 1% atropine or 4% homatropine. It has the advantage of producing practically no stimulation of the central nervous system and minimum of side effects.
[...]
SYNTHESIS NUMBER ONE
In the first of these, p-nitrobenzyl chloride is condensed with a salt of nitroethane and the dinitro compound which results is reduced to diamine. That amino group which is atteached to the benzene ring, is then replaced by a hydroxyl group by formation and decomposition of the diazonium salt.
[...]
DISCUSSION
Synthesis Number One
The synthesis beginning with p-nitrobenzyl chloride involves, at the outset, an aralkylation of a salt of an aci-nitro alkane. Although the aralkylation has not been studied extensively enough to permit of prediction in all cases, Weisler (5) has shown that it is correlated with the stability of the aci-form of the nitro compound, and is probably dependent on the rate at which the aci-form tautomerizes to the normal form. If the stability of the aci-form is high, the tendency is toward aralkylation on the carbon atom instead of on the oxygen. Also, the greater the reactivity of the halide selected, as evidenced by its tendency to ionize or to form free radicals, the greater is the tendency for reaction with the carbon atom.
In the reaction between the salt of aci-nitroethane and p-nitrobenzyl chloride, aralkylation occurs both on carbon and oxygen, but fortunately aralkylation on carbon greatly predominates. (Reaction with an oxygen produces minor quantities of a nitronic ester or its decomposition products; p-nitrobenzaldehyde was therefore isolated as a by-product in step one.) Another competing reaction, which takes place to a greater extent than reaction on an oxygen atom, is the formation of 1,1-bis-(p-nitrobenzyl)nitroethane. If no excess nitroethane is used, this reaction predominates over the reaction desired, but formation of the monoaralkylated product can be favored by using an excess of nitroethane so that disubstitution is largely suppressed. This effect can be explained by considering the following reactions:
(I) p-O2N-C6H4CH2Cl + O-2N:CHCH3 --> p-O2N-C6H4CH2CH(NO2)CH3 + Cl-
(II) p-O2N-C6H4CH2CH(NO2)CH3 + ON:C-2HCH3 <==> p-O2N-C6H4CH2CH(:NO-2)CH3 + CH3CH2NO2
(I believe there is a typo and it should read O-2N:CHCH3 instead)
(III) p-O2N-C6H4CH2Cl + p-O2N-C6H4CH2CH(:NO-2)CH3 --> (p-O2N-C6H4CH2)CNO2CH3 + Cl-
Since the formation of the aralkylated product probably occurs in accordance with equation (III), the rate of its formation depends on the concentration of the ion p-O2-C6H4CH2CH(:NO-2)CH3. An excess of nitroethane will lower the concentration of this ion by affecting equilibrium (II). The result is to decrease the yield of bis-compound and increase the yield of monoaralkylated product.
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EXPERIMENTAL
Synthesis Number One
Preparation of 1-p-nitrobenzylnitroethane. Sodium nitroethane (24.45g., 0.25 mole) was prepared in the reaction flask by dissolving sodium (5.75 g., 0.25 mole) in a small amount of ethanol, then adding nitroethane (131.2 g., 1.75 moles). p-Nitrobenzyl chloride (42.9 g., 0.25 mole) and 500 ml. of absolute ethanol were added and the mixture was refluxed eleven hours on a steam-bath, during which the solution turned red and a precipitate formed. After filtering, the filtrate was evaporated on a hot plate. The residue was dissolved in benzene and the solution was extracted with sodium bisulfite solution to remove p-nitrobenzaldehyde. (Free p-nitrobenzaldehyde was isolated from this extract, recrystallized and identified.) After removing the benzene, the residue was distilled (b.p. 145-160° at 0.5 to 0.6 mm.) from a Claisen flask; yield 28 g., 83%. The viscous oil was dissolved in alcohol and crystallized, m.p. 51°.
