I'm just curious. The Oxime route kinda sucks. Swinl followed this recently:
54g sodium carbonate and 40ml water was combined in a 500ml round-bottomed flask. The mixture was heated gently with stirring until the acetate was in solution. 200 ml MeOH was added followed with 45g MDP2P. To this there was added 23g hydroxylamine hydrochloride and the mixture was refluxed with stirring for 1.5h. After this period 10ml water was added and the heating source was removed and the mixture was allowed to cool in a waterbath with the stirring continued. After returning to room temp the flask was put in the freezer for an hour or so. The white crystalline material was filtered and washed with 500ml water (the filtrate may turn cloudy as small amounts of product crystallizes). The product was dried over magnesium perchlorate. Final weight was 41.4g (92%). Mp: 84-85°C. Litt: 84-87°C (H2O-EtOH)
Then ....
In a 4l beaker with mag stirring, 0.75 moles of activated Al (19.5g) [2] is added to 1l 95% EtOH and 100mls dH2O, followed by 0.33 moles oxime of MDP-2-P (65g), and 3 moles HOAc (180g). The Rxn is heated to 60C and heat removed. There follow three additions of 0.75 moles of activated Al at 30 minutes, 1 hour, and two hours. Temperature was maintained at 60C by placing beaker in a cold water bath as necessary. There is a vigourous evolution of hydrogen as the rxn progresses, care must be taken the rxn vessel does not overflow. An additional 150mls 95% EtOH and 15mls dH2O is added at 2hours. At 3 hours the rxn is a viscous gel which has stopped the stir bar. An additional 300mls 95% EtOH and 30mls dH2O is added . The rxn was allowed to stir until it has returned to room temperature, during which time 1 l of 15M NaOH was prepared and cooled. The rxn vessel was placed in a cold water bath and the basic solution was added slowly over 20 minutes, with care being taken the tempertaure did not rise above 60C. 500g of NaCl was added, much of which precipitated after stirring. 500mls toluene is added with stirring. The toluene/EtOH/amine layer is separated and decanted into 750mls of dH2O, causing the EtOH to migrate to the aqueous layer. The toluene layer is separated and the aqueous/alcoholic layer is extracted 2 times with 250mls toluene. The pooled toluene extracts are washed
once with 400mls dH20 and once with 400mls brine, then driied through MgSO4 and gassed w/ dry HCl gas.
yeild 0.267 moles MDA.HCl (54g) 81% molar yeild
1) see Post No189985 2) activated by refluxing in 19.5g Al in 800mls of 50/50
dH2O/MeOH, with 1g HgCl2 for 15 minutes, the mercuric solution was decanted, and
Al was washed once with 400mls 95% EtOH, which was also decanted. Same mercuric
solution was used for all four activations.
The whole thing is sort of clumsy and haphazard IMHO. How could this be shaped up? I'm thinking something like MM's Nitro/Al/Hg thing. Same concept. Could the oxime be formed and then subsequently reduced all in the same pot, like as soon as it precipitates with the Hyrdoxolymine somehow?
Let's say you run MM's amination, but throw out the NitroMethane and have ~12g Hydroxylamine in the pot already mixing. Would Ethanol be advantageous to use instead of Methanol as discussed before? I never saw why, but what do I know? The Nitro sort of boosts up the reaction, but with some initial external heating, the same effect could be achieved no? I don't know much about chem., never pretended to, just curious from a functional viewpoint, dig?
We need new drugs.