Alkylation of nitroalkanes

[Aengus]

Does anyone have anything on alpha-alkylation of nitroalkanes? Looking for information on melatonin, I came across:
     Snyder, H.R. & Katz, L. (1947). "The alkylation of aliphatic nitro compounds with gramine. A new synthesis of tryptamines." J. Am. Chem. Soc. 69, pp. 3140-3142
     Lyttle, D.A. & Weisblat, D.I. (1947). "The chemistry of nitroacetic acid and its esters. I. The alkylation of alkylnitroacetates with gramine." J. Am. Chem. Soc. 69, pp. 2118-2119
     Snyder and Katz refluxed 3-indolylmethyl dimethylamine or its methiodide with excess nitromethane, nitroethane or ethyl nitroacetate, in the presence of solid NaOH as a catalyst, and obtained mostly the di-(indolylmethyl) derivatives. Lyttle and Weisblat refluxed the 3-indolylmethyl dimethylamine with ethyl nitroacetate in xylene without any catalyst, and got the monoalkyl product, which was hydrogenated to tryptophan ethyl ester. With NaOH as a catalyst, the product was again the dialkyl derivative.
     Those papers are a long time back. There must have been some more recent work. How would a benzyl trimethylammonium iodide derivative react with nitroethane or nitroethane for instance?

[otto]

hi aengus,

otto thinks he saw something about it on rhodiums site concerning the synthesis of alpha-methyltryptamine, but yields seemed to be discouragingly low for the short chain nitros. however your second idea intrigued me since an intermediate of such kind was used for the synthesis of 2-CB by assholium. check rhodiums site for 2-CB via the mannich reaction.

there, 4-methoxyphenol (which is now easy and otc thanks to antoncho) is reacted w/ formaldehyde and dimethylamine followed by methyl iodide to give 2-Hydroxy-5-Methoxy-benzyltrimethylammonium iodide. this was then reacted w/ poisonous cyanide (which isnt otc either).

can the use of nitroethane/nitromethane instead give us some succesful dreams?

yours (full of questions)

otto

[Aengus]

Many thanks.

Snyder & Katz quote an earlier reference on alkylation of nitromethane with Mannich bases from acetophenones, which I have not had a chance to see, so I don't know what the yield was. Anyway, the reference is: Reichert & Posemann (1937) Arch. Pharm. 275, p. 67. This looks like a possible variation on the Assholium synthesis.

I checked Rhodium's site. The AMT procedure is from the Snyder and Katz paper. The low yield is due to dialkylation.

If you like working with that kind of reagent, a nitro group can be introduced, for instance on malonic ester, by a Claisen-type reaction with ethyl nitrate. Apparently this is reasonably safe to use. Gattermann's "Practical Organic Chemistry" gives preparation of ethyl nitrate, including distillation, as a student exercise - though advising us it comes in the same category as nitroglycerine. He goes on to use it to make alpha-nitrophenylacetonitrile. I guess that, if diethyl nitromalonate can be made safely, it would give good yields with a Mannich base methiodide.

Will let you know anything else that turns up.

Aengus