[Johte]

Hey all,

This applies to a couple of reactions I'm trying to perform. Unfortunately, bringing to neutral pH and extraction with DCM doesn't seem to be giving me good yields at all. I want to put an acetic acid moiety on both ends of variable lengths diamines.

My starting amines are just diamines or N,N' dimethyl ethylenediamide. I've attempted H+/Zn reduction because glyoxylic acid is a mono hydrate salt and NaBH4 was still reacting well over the calculated equivelent ( pink, schiff base, was still observed. )  I've tried bromo and iodo acetic acid with the N,N' dimethyl ethylenediamide but there is an immediate precipitate which redissolves when brought to reflux in ACN. Removal of solvent left a yellow liquid/oil which gave me a M+H of 245 that I can't seem to figured out even with MS/MS/MS.

I'm assuming there's some reaction occurring at the carboxylic acid first based off this papers ( dx.doi.org/10.1021/jm401603e | J. Med. Chem. 2014, 57, 2213−2236 ) routes suggestion Me or Et protection of the acid first. I want to try this ( I don't have thionyl chloride so I would do fischer esterification with H2SO4 and MeOH ) but like with the original reductive amination I'm worried about losing my product in the aqueous.

Suggestions Appreciated!

[phth]

You can make SOCl₂ easily or sulphuryl chloride(liquid phase Cl₂ that decomposes upon reflux); http://www.google.com/patents/US5879652.  Main requirement is a high pressure high temperature reactor.  SO₂ and Cl₂ can be generated from salts; just do some thermal gravimetic analysis to figure out what salts to use to get sulphur dioxide, iron is bad but Fe₂(SO₄)₃ is an example.  Purify with PPh₃ to remove the metal content and byproducts like SCl₂, S₂Cl₂, metals.  POCl₃ also complexes very well with metals.

 e.g. malonic esters can be deprotected using Cl^- in DMSO; ethyl ester withstands this SN2 deprotection better.

[Babcock_Hall]

If you did not esterify your carboxylic acid, would your molecule be a zwitterion in solution?