Author Topic: Alkyl nitrates as nitrating agents  (Read 1754 times)

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Aengus

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Alkyl nitrates as nitrating agents
« on: August 17, 2004, 11:04:00 AM »
A nitro group can be introduced on an active carbon atom by a Claisen-type reaction with an alkyl nitrate. "Organic Syntheses" describes the preparation of methyl nitrate. I have not tried it, but suggest anyone who does ought to take the precaution of adding urea to the nitric acid mixture; and not make any more than is required for the next job. Gattermann ."Laboratory Methods of Organic Chemistry" describes the preparation of ethyl nitrate. This is a commercially available material, used as an additive to raise the cetane number of diesel fuels.

Both "Organic Syntheses" and Gattermann describe the use of these reagents to nitrate phenylacetonitrile to form sodium phenylacinitroacetonitrile, with a view to hydrolysis and decarboxylation to give phenylnitromethane. The reaction conditions are typical: sodium ethoxide in ethanol solution. A literature search would no doubt turn up other examples.

The implication is that a phenylethylamine could be produced by substitution of malonic ester with the appropriate benzyl chloride analogue, nitration, hydrolysis, and reduction of the resulting nitro compound.

The nitrate esters are of course potentially explosive materials. Admittedly, only someone properly qualified, who knows the hazards of the materials involved, should actually do synthetic organic chemistry. However, this particular risk can be avoided by resorting to a standard method for synthesizing amino acids. Diethyl malonate with sodium nitrite in an acid medium gives oximinomalonic ester, which is reduced with zinc dust in acetic acid to acetylaminomalonic ester. This can be substituted in the usual way with the benzyl chloride analogue. Hydrolysis will give the phenylalanine analogue of the phenylethylamine. Amionacids are decarboxylated in a high-boiling solvent, with a suitable catalyst. Rhodium gives the procedure for tryptophan, but it is general. A reference that is to hand is: Takano, S., Nishimura, T. & Ogasawara, K. (1977). Efficient synthesis of tryptamine. Heterocycles, 6(8), 1167-1171.

Other method for synthesizing amino acids could be adaptable. Is there any information on psychoactive effects of amino acid analogues of phenylethylamines? One, methyl-DOPA (Aldomet) is used as an anti-hypertensive agent.

One other question: Are there not ways of substituting an aminoacid on the alpha-carbon atom?


Nicodem

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The implication is that a phenylethylamine...
« Reply #1 on: August 17, 2004, 04:38:00 PM »
The implication is that a phenylethylamine could be produced by substitution of malonic ester with the appropriate benzyl chloride analogue, nitration, hydrolysis, and reduction of the resulting nitro compound.

You don't need ethylnitrate for that. In

Post 499541

(Rhodium: "Archive of "Wanted References" Volume 2", Novel Discourse)
you can find a paper entitled "Synthesis of alpha-functional nitrocompounds by the nitration of activated carbonyl derivatives in two-phase system" which was kindly retrieved by Azole and where 1,3-dicarbonyl compounds are nitrated with nitric/sulphuric acid. However, I'm not so sure that such a biphasic system would prevent the nitration also at the phenyl. (The paper is in Russian.)

Is there any information on psychoactive effects of amino acid analogues of phenylethylamines?

The amino acid analogue of DOM is inactive and experiments did not show signs of in vivo decarboxylation. The active transport system for amino acids probably does not even recognize ring substited phenylalanines and beside this there is nothing else that could make such aminoacids pass the blood-brain barrier and be decarboxylated to an active species.