Tricky
(Stunning)
07-30-02 00:10
No 338869
      Robinson's tropinone: improving method!
(Rated as: excellent)
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Quoting from: Yahontov, Sintez khimiko-farmatsevticheskih preparatov, p174.

To solution of 58,5g succindialdehyde in 1000ml water was added 2N solution of NaOH till pH=5-6. Then to solution of succindialdehyde were mixtured: 237g of sodium acetate, 117g of 97% acetondicarboxylic acid and 53,5g of 98,5% methylamine hydrochloride. After mixturing of all components, solution's pH is usually = 4-4,5. Mixture was stirring 30min at 42-43 (NB! the CO2 isolation and foaming) and cooled to 30, then 251g of technical potassium carbonat was added and mixture cooled to 18-20.
Product was extracted with dichloromethane (900/600/200ml). Combined extractions were dried over Na2SO4(till content of moisture = 0,3%) and dichloromethane was distill off at atmospheric pressure (residuums of vehicle were distilled off in vacuum of water-pump at 80-100; for more better of volatile admixture moving off, the product dissolved in 30ml of dry benzene with following distilling off in vacuum).
Tropinone was redistilled at 83-85 at 5mm/Hg. Yield is 75,5g or 72%(for recalculation by the succindialdehyde).

There's a hole in our soul that we fill with dope
And we're feeling fine.
 
 
 
 
    Rhodium
(Chief Bee)
07-30-02 01:34
No 338902
      Faster, Better, Cheaper  Bookmark   

Wow! That is considerably faster than Robinson's original method. I wonder if this method can be extended to work with monomethyl beta-ketoglutarate instead of the acetonedicarboxylic (beta-ketoglutaric) acid to directly form 2-carboxymethyltropinone, thereby saving one step on the way to the famous alkaloid.
 
 
 
 
    terbium
(Old P2P Cook)
07-30-02 07:00
No 338973
      No problem.  Bookmark   

I wonder if this method can be extended to work with monomethyl beta-ketoglutarate instead of the acetonedicarboxylic (beta-ketoglutaric) acid to directly form 2-carboxymethyltropinone, thereby saving one step on the way to the famous alkaloid.
Yes, simple, high yield preparation of tropinone, carbomethoxytropinone or dicarbomethoxytropinone starting with the acetonedicarboxylic acid diester has been in the literature for many decades. Control of the pH of the reaction determines which product is formed.
 
 
 
 
    Rhodium
(Chief Bee)
07-30-02 11:20
No 339032
      Concerning 2-Carboxymethyltropinone  Bookmark   

Terbium: I'm aware of the method of using the mono-ester to make 2-carboxymethyltropinone from JOC 22, 1385 (1957), but that one takes 24h to give 86% yield. If this faster method could be adapted, perhaps high yield and a short reaction time can be combined?
 
 
 
 
    Tricky
(Stunning)
07-30-02 13:09
No 339058
      Wow.  Bookmark   

Rhod, can you quotin' JOC 22, 1385 (1957), here, pliz. I've no access to this source. It's really very interesting.

There's a hole in our soul that we fill with dope
And we're feeling fine.
 
 
 
 
    Rhodium
(Chief Bee)
07-30-02 13:54
No 339079
      JOC 22, 1385 (1957)  Bookmark   

Post 488336 (Rhodium: "Synthesis of Tropinone & 2-CMT", Methods Discourse)
 
 
 
 
    terbium
(Old P2P Cook)
08-04-02 21:56
No 341476
      Dicarbomethoxytropinone is prochiral.  Bookmark   

Terbium: I'm aware of the method of using the mono-ester to make 2-carboxymethyltropinone from JOC 22, 1385 (1957)
Yes, my memory fails me, I thought I had something better but this paper is the best that is in my library and seems to be what I had been working from.

Actually though, I had been more interested in synthesizing the dicarbomethoxytropinone since it is achiral (prochiral). It is only when one carbomethoxy group is removed that symmetry is broken and the chiral carbomethoxytropinone is formed. My thought had been that it might be possible to effect the decarboxylation using an asymmetric reagent in order to obtain carbomethoxytropinone of high enatiomeric purity. My wishfull speculation had been that there might even be a common enzyme that would do this.

Of course, given the current low cost of the natural product, all of this speculation is purely of academic value.