I would go for converting the NH into N2 then reaction with some source of SH...has anybody better ideas? (do not have the chance to use H2S)
You have not mentioned whether you wish to retain the configuration on the C bearing the amino group or if inversion will be fine, as this is going to have a bearing on either the number of steps required or the requirement for a chiaral catalyst. Mild oxidation of the cysteine into a disulphide followed by treatment with tosyl chloride may be an alternative means of converting the NH2 into a better leaving group which will then mean that other S nucleophiles can be used.
Dear Paul I do not have any concern about racemization, as then this will be used as linker....which S nucleophile would you suggest to use? thank you for your suggestion....
My personal preference is to use thiourea followed by aqueous sodium hydroxide to liberate the thiol.
Thank you :) and....would then the product condense with salicylaldehyde by simply refluxing them in the appropriate solvent, as it would apply in the case of oxazolidines?
Ah, now I see what you are attempting to do, yes once you have your thiol and cleaved the disulphide to make your dithiol, this should react directly and cleanly with salicylaldehyde in the way that you wish.
in this regard, i would go for the conversion of the N into O by treating with HCl/HNO3 followed by treatment with some kind of alkaline solution for OH introduction...then I hope it works for the subsequent condensation with sal. aldh. .....usually such condensations are done employing the most fancy sort of catalyst....so i wondered if it works by simply heating the two component....in the end is a simple condensation where the only issue should be the insidious water released
If you use a diol, to form an acetal with an aldehyde, the best way of dealing with the water is to use a sulphonic acid catalyst and carry out the reaction under azeotropic conditions using toluene and a Dean-Stark trap (the acid group on the cystein needs to be a methyl ester to make it soluble in the toluene, because amino acids being zwitter ionic are usually not soluble in hydrocarbon solvents. However, the thiol groups form thioacetals with aldehydes much more readily and are a lot more resilient to many other organic functional group conversions - which is probably why you initially want to convert the amino group to SH. Now that I have a beeter idea of what you are trying to achieve (and it happens to be similar to something I attempted with hydroxynaphthaldehyde some 20 years ago), I will try to locate my old lab book and send you what results I got.
thank you very much Paul Carolan. I am having fun with heterocycles recently, though their synthesis is not the final aim....right now another experiment being carried on is the synthesis of an oxazolidine still between sal aldh. and a diethanolamine based linker, attached onto a acid stable resin.....a while ago, I was performing the same reaction between a thr (still on the same resin) and sal. aldh, in AcOH/Py 1:1 mol mol, and it looked it worked pretty well though within prolonged reaction time....now the reaction in toluene....let´s hope for the best......anyway it looks you have quite lot experiences in all this enjoyable chemistry.....in case you have ever done a synthesis of sal. aldh. based oxazolidine in solution, would you be able to provide any explanation why, when attempting the condensation between H-thr-OH and sal aldh, in AcOH/Py 1:1 mol mol there is no way to detect the product in TLC? in this regard the only proof I have tht the product formed, is its insolubility in most organic solvents and tht it does show pretty strong under UV light....when I try to make an hplc i see sal. aldh.....lol.....I have also tried the same condensation in solution with dietanolamine....this time i obtain not a solid like before but an unsoluble oil which in tlc drags to the top giving sal aldh....again.....whatever the solvent the result is the same....looking forward to having your advises :)
- Badges
- Science topic