dormouse (Member)
04-19-00 11:30
No 122746
      dehydrating reagents for amide synthesis -drone342  Bookmark   

Author Topic:   dehydrating reagents for amide synthesis
drone 342
Member posted 09-03-98 11:38 AM          
I've always been a bee who's felt that the practical LSD synthesis has remained far too underinvestigated. Just as we've taken a good idea like MDMA and run amok with simplifying its practical chemistry, I feel LyserSauereDiaethylamid needs some improvement. I want to make it simple enough for almost anyone with a year of college lab chemistry to make.

There seem to be countless problems with its synthesis: aquisition of raw materials, isolation of starting material, appropriate lab hygiene and material handling, purification, and of course the synthesis itself.

All of these details are worthy of at least some discussion, though I feel the synthesis is perhaps the finest starting point for discussion. In the past, using dehydrating reagents like thionyl chloride and SO3, the yield of LSD from lysergic acid was around 30%. With the advent of the use of POCl3, yields between 60 and 70% became a reality. This obviously essentially doubled the world's potential acid output.

However, it is my belief that this is still merely the beginning. Using gentler conditions and more modern reagents, like DCC and other reagents currently in common use amongst peptide chemists, the yield and purity of product could be significantly improved further. I mentioned my thoughts on DCC (dicyclohexylcarbimide) before, but got little response to this idea. What other reagnets might be suitable for such a task?

Also, I wanted to discuss the issue of purification. While column chromatography is common, I must admit my suspicions about this method when it applies to the 3 to 4-ounce batches fairly commonly synthesized by clandestine chemists. I've column chromatographed my small share of organics, and I know that trying to flash chromatograph such a quantity is a herculean effort -- worthy of a well-trained, well-disciplined professional. So do these guys all have PhD's, HPLC machines, or what?

Another purification step commonly employed is the use of a chiral organic salt (like tartaric acid), which will react with the amino group of one isomer, but not the other -- thus salting out the desired product, while leaving the remaining crap behind. I have ref's on this, but I assume everybody else does as well. Still, this may be worthy of discussion.

drone 342
Member posted 09-05-98 05:53 PM          
My appologies; DCC is of course "dicyclohexylcarbodiimide", not "dicyclohexylcarbimide". Its important to pay attention to these details, and I appologise if this may have caused any inconvenience or cunfusion.

-drone #342

Member posted 09-26-98 06:10 PM          
benzotriazol-1-yl diethylphosphate
molecular sieves
N,N,N',N'-tetramethylsuccinimido uronium tetrafluoroborate
chlorosulfonyl isocyanate
pyridinium salts-Bu3N
heating with other amides of carboxylic acids (exchange)
sulfonic acids
phosphoric acids,eg. RCOOH + Ph2PONH2 ---> RCONH2 + Ph2POOH
trisalkylaminoboranes B(NHR)3
R'COOH + B(NR2)3 ---> R'CONR2
bis(diorganoamino)magnesium reagents, R2N)2Mg

Maybe some of these above can be made to work in LSD synthesis?

Member posted 09-28-98 04:45 PM          
What's up drone, lost interest in peptide chemistry?

drone 342
Member posted 09-29-98 01:47 PM          
Heaven's no! Amides and peptides are lovely creatures, and deserve the interest of any curious bee. I'd say the carbodiimine species sound the most fascinating as dehydrating reagents, due to their success in gentle conditions with large, delicate molecules. I just can't think of much to say on this topic right now. I've played with DCC, and I've learned to cherish it and the reaction conditions it works under. POCl3 has its place, but I'm nowhere near as sentimental about it. Has anybody had any experience with the use of any of these reagents? Do any of these pop out to anybody as being particularily attactive to ergot chemistry?

-drone #342