Does anyone have any information of benzophenone having been used in Henry/Knoevenagel or other active methylene condensations with nitroalkanes, esters, etc.?
If one could form the nitroalkenes in the conventional way, I was thinking it might be usable as a stepping-stone for elaboration to methadone, dipipanone or similar analgesics.
When benzophenone is boiled hard with nitromethane and aq. dimethylamine, the solution slowly yellows and finally reddens. When filtered, a red oil is retained in the filter, but it does not crystallize.
In any case, benzophenone seems much less reactive than benzaldehydes, and does not form a soluble addition complex with sodium bisulfite after stirring overnight.
If benzophenone can be used in base-catalyzed condensations with nitroalkenes, another difficulty seems to be the enamines. Enamines are traditionally made from aldehydes, and most ketones are not very reactive. And in the case of acetone, I have seen no report of enamines having been made from it. However, I was thinking that one could maybe make an enamine from ethyl acetoacetate (there is a ref on Orgsyn:
http://www.orgsyn.org/orgsyn/prep.asp?prep=cv6p0592
, and then decarboxylate the resulting carboxylic acid condensation product.
General idea:
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Molecule:
benzophenone (" O=C(c1ccccc1)c2ccccc2 ")
Benzophenone + 1-nitropropane (Henry rxn) ->
Molecule:
(2-nitro-1-phenylbut-1-enyl)benzene (" CCC(=C(\c1ccccc1)c2ccccc2)\[N+]([O-])=O ")
Molecule:
acetone enamine (" O1CCN(C(=C)C)CC1 ")
2-nitro-1-phenylbut-1-enyl)benzene + acetone morpholine enamine (Michael addition, acidification) ->
Molecule:
5-nitro-4,4-diphenylheptan-2-one (" C(C(c1ccccc1)(c2ccccc2)C([N+]([O-])=O)CC)C(C)=O ")
5-nitro-4,4-diphenylheptan-2-one + dimethylamine (Michael addition) ->
Molecule:
2-Dimethylamino-4,4-diphenyl-5-nitrohept-2,3-ene (" C(/C(c1ccccc1)(c2ccccc2)C([N+]([O-])=O)CC)=C(/C)N(C)C ")
2-Dimethylamino-4,4-diphenyl-5-nitrohept-2,3-ene + sodium borohydride (reduction) ->
Molecule:
2-Dimethylamino-4,4-diphenyl-5-nitroheptane (" C(C(c1ccccc1)(c2ccccc2)C([N+]([O-])=O)CC)C(C)N(C)C ")
2-Dimethylamino-4,4-diphenyl-5-nitroheptane + (1.) NaOH, (2.) HCl (Nef reaction) ->
Molecule:
methadone (" C(C(c1ccccc1)(c2ccccc2)C(=O)CC)C(C)N(C)C ")