gammma-chlorobutyrate from Sandmeyer w/ GABA

[leungkachong]

After SWIM searched TFSE, he found no reference either here (or in the rhodium.ws document) about side-reactions for the newly added Sandmeyer reaction with GABA to produce a desired final product.  To my understanding, the reaction as originally written involved the replacement of a halide in the position of the primary amine by using a acidified NaNO2 with a copper salt (can't remember whether cupric or cuprous) halide.  However, if the hydrohalic acid has a different halide than the salt, some product will take the copper's halide in place of the amine, and some will take it from the acid.  Would this not mean that the reaction may produce gamma-chlorobutyrate (if using HCl as the acidfying agent as described on rhodium), along with our desired hydroxy counterpart?

[Chromic]

The major product of the reaction is GBL/GHB. Read the Bull.Soc.Chim.Fr. reference. There is no doubt some side-products, but the percentages are likely small (see my post on the GC results of the GBL obtained). 4-chlorobutyric acid may also be a GHB receptor agonist so eliminating it may not even be something necessary? (perhaps check Neuropharmacology, 1976, 15, 29-38? I'm not sure on where to find details of GHB analogues other than 4-hydroxy-TCA, 1,4-BDO etc). Substitution to chloro derivatives requires the absence of water because water acts as a good nucleophile on alphatic diazonium salts.

For those not in the know

https://www.thevespiary.org/rhodium/Rhodium/chemistry/gaba2gbl.html

has been recently posted to rhodium.ws.