(Hive Bee)
09-14-02 15:17
No 356265
(Rated as: excellent)
On Rhodiumīs site there is a writeup for making MDP-2P oxime from MDP-2P, using the ketone, hydroxylamine HCl and sodium acetate. When the method is tried with other phenylacetones it gives nothing. Believe me, Iīve tried!! This fact has really pissed me off since there has been a few oximes Iīve wanted to play with. So while whining the way only I can do, I decided I WOULD make those oximes at any cost.
I found this patent Patent US6235935 in which they made oximes from aqueous free hydroxylamine and the ketone. They stated that in some cases it may be necessary to acidify the solution slightly to initiate oxime formation.
I tried this:
2,4-dimethoxyphenylacetone (10g, 51 mmol) was added to hydroxylamine ( 2g, 60 mmol) as a 40% aqueous solution, and enough MeOH was added to form a homogenous solution. This mixture was allowed to stir for 2 hours at room temperature and then acidified to pH 5.5 with acetic acid. Stirring was continued overnight. In the morning there was a thick, slightly orange oil at the bottom. 100ml cold water was added to the reaction mixture which caused more oil to fall out from solution: This was allowed to settle at the bottom and the remaining liquid was decanted off. The oil was dissolved in 50 ml MeOH, 1g activated carbon added, the solution filtered and the MeOH was removed by distillation in a rotovap. This gave 9.8g of a slightly orange oil which solidified over a couple of hours.
The solid cake was dissolved in about 30ml boiling i-PrOH and slowly chilled to 0 deg C while scratching of the walls with a glass rod now and then. This produced 2,4-dimethoxyphenylacetone oxime as white needles. Yield 8.4 g (40 mmol 78%)
(Synaptic Self-Mutilator)
09-14-02 16:16
No 356268
I've used Sonson's method to make 2,4,5-TMp2p oxime, 4-Mp2p oxime and 3,4-MDp2p oxime using sodium acetate, bicarbonate or carbonate; hydroxylamine sulfate; water or distilled water; methanol or ethanol. Some oximes oiled out (eg tmp2p oxime) but I blame that on using undistilled ketone... I know AB2 has used it to form 3,4-MD-2,5-DMp2p oxime as well.
Maybe you're following a different procedure? I found Sonson's explanation to be a bit lacking, but the procedure works quite well.
(Hive Bee)
09-14-02 17:16
No 356273
No it was sonsons method I followed. This really puzzled me.
By the way, which method did you use to make the 2,4,5-TMP-2-P?
(Hive Bee)
09-14-02 17:58
No 356284
Barium, why did you not try Post 319296 (Rhodium: "P2P oxime in quantitative yield", Novel Discourse)?
(Synaptic Self-Mutilator)
09-14-02 18:26
No 356287
(Rated as: excellent)
If you follow his method, you'll find a white slime immediately precipitates. This isn't the oxime and that's obvious as it's a water-soluble slime. If you add the small amount of water as directed and put it in the freezer (1hr if your ketone is quite pure, longer) it should crystallize. If the oxime doesn't crystallize overnight, it ain't gunna... all you're going to get is a viscous oil of an oxime. I've tried hitting it with dilute HCl, etc, but it just doesn't seem to form crystals. (I never did try a recrystallization, the idea of recrystallizing an oil trying to get a crystal seems odd to me... could this work?) Anyways, so if it doesn't crystallize right there, add the rest of the water (ie the amount directed that you can use for washing). Then extract the oxime with DCM and rotovap off the DCM for the uncrystallized oxime oil.
To clarify in non-ambiguous terms, reflux for 45min - 90min:
1.25 eq hydroxylamine salt
1.35 eq base
1 eq ketone
750ml alcohol
150ml water
... if you're using bicarbonate as the base, go slow as the rxn produces a lot of CO2. Then add 400ml water, move to freezer. If it doesn't crystallize, add 2L of water, separate off most of the oxime and extract with DCM (wash with dilute acid and rotovap). If it does crystallize, filter at the pump and wash the oxime with up to 2L water.
The tmp2p was made by the buffered peracetic in dcm followed by 15% H2SO4 in MeOH rearrangement. The yields were crummy (but the product yummy!) as the tmp2p wasn't distilled. I posted the info (and then tripped out, posting on the board) the info of my first success with this route.
Although I do really like the clean up in your procedure, in the end you deal with harder to obtain/make/handle reagents and there's no clear advantage.
(West Coast Cowboy)
09-23-02 10:30
No 359429
I was some time since I made this writeup and I don't remember all the details anymore, but I'm sure that the first precipitate is nothing but NaCl...the water is added to dissolve the NaCl and to make the soulubility of the oxime lower thus allowing it to crystallize.