chloe ( )
06-12-99 18:38
No 102365
      making Clomethiazole: Need answers!  Bookmark   

   I read  Post 108494 (dormouse: "RHODIUM  -John Doe", Novel Discourse)  all the way through. It seems like it should work, but I have no access to reference. Please, can some kind bee (like Douglas R or Jaan the Man) help me out, here. Chemspaz, you have read them, yes?

The initial production of sulfurol seems to have been quite well tested by several bees yet the final chlorination doesn't seem to have been dreamed by a hive person. I propose a test & beg for someone to type up the reference for chlorination.

dream proposal:

26.88g of sulfurol in 53.76cc of 1,2-dichloroethane is chilled to -5C then placed in an addition funnel connected to a 2-way adaptor sitting on top of a 500ml RB flask containing a solution of 44.62g of SOCl2 in 174.72cc of 1,2-dichloroethane and a 24mm egg-shaped magnetic stirbar, all chilled to -5C. The flask is sat in a 2l beaker itself sat on a magnetic stirrer. an ice/saltwater solution fills the beaker. (periodically the ice/water is drained slightly & more ice & water added to maintain -5c within the flask). The 2 way adaptor has a CaCl2 moisture-guard & is connected by vaccum-tubing to a wash bottle filled with glass-wool & a concentrated NaOH solution (via an empty bottle for safety). The exit of the wash-bottle is blown up a chimmney to ensure no odour escapes. All parts are quickfit with joint-clips & grease.

The SOCl solution is slowly dripped into the rapidly stirred Sulfurol solution keeping down the temperature at all times.
 Once all the SOCl2 is added, the mixture is stirred at -5C for a total of 15 hours.

Here is a question. The HCl is supposed to have been formed, will this precipitate (I guess it will)

The still-chilled mixture is cold filtered & the filtrate washed with a little more 1,2DCE (if the .HCl does precipitate) and the excess SOCl2 destroyed by carefully dripping in dH2O whilst cooling (the resulting gasses being washed and vented).

The 1,2 DCE is extracted with hydrochloric acid (to extract the last of the product if precipitation occured, or to extract ALL the product if the .HCl is soluable.
 The extractions are added to the filtrate & the acid vaccum distilled off. The product is recrystalized from alcohol.

As you can see, I just scaled down Chemspaz's comments whilst expanding detail. My questions:

1. Will the HCl precipitate?
2. Does the cold conditions/dilution mean that the chemist is trying to maintain the intermediate chlorosulphite (is it soluable itself?). They use benzene, but I wonder if hexane will work (low DC makes chlorosulfite stable)? I'm guessing that the 1,2 DCE will work. I have toluene, but I don't know.
Here is example of intermediate

3. 71% yield? What side-products should I look for. 1-chloro? HCl attacking the 2 position? Fragmentation? Should I vaccum distill freebase (I hear freebase is unstable so If I can avoid it).

4. Why do both examples us a 1.77:1 excess of SOCl2?

Thanks for imput to you all.

PS 66g of B1 in 1l 2.6N busulphite should produce just the right ammount of alcohol needed.


(Chief Bee)
11-18-01 02:48
No 237875
      Re: making Clomethiazole: Need answers!  Bookmark   

What happened to the old holy grail for making chlomethiazole from vitamin B1? This should be investigated. Search for chlomethiazole and the vitamin in TFSE, and prepare to read lots of an almost finished synthesis.