Synthesis of Mexiletine.
A simple three-step synthesis is used to arrive at Mexiletine.
Chloroacetone is the most difficult. It is somewhat more expensive; Sigma-Aldrich offer 500 g of it for US$205, which is about 10x their price for 2,6‑xylenol. However, it can be prepared by the chlorination of acetone. One method uses CuCl2 and acetone, both of which are cheap enough, but multi-chlorinated side products are common meaning that much effort in distillations and disposals are necessary in order to purify the chloroacetone prepared this way.
The hydroxylamine is not expensive, but it should be noted that it comes as a solution in water as the freebase quickly degrades.
The final step, a hydrogenation, requires hydrogen gas and a catalyst. The catalyst can be re-used for each batch, but the Parr hydrogenator can be a great expense, especially one that can hold 2–5 L.
Synthesis of Thiola.
A simple three-step synthesis has been used to arrive at Thiola (tiopronin) and was published in the Chinese Journal of Modern Applied Pharmacy. α-Bromopropionyl chloride and glycine were used as start materials．The mercapto group was introduced by exposure to thioacetic acid, followed by removal of the acetyl group.
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The α-bromopropionyl chloride is obtained by treating 2-bromopropionic acid with thionyl chloride. I have seen Sigma-Aldrich quote a price of US$282 for 1 Kg of 2-bromopropionic acid. That is 28c per gram but I imagine that larger quantities could be found for purchase for even less per gram.
Thioacetic acid can be prepared by the reaction of acetic anhydride with hydrogen sulphide in the presence of a catalytic amount of acetyl chloride or acetyl bromide. I have seen Sigma-Aldrich quote a price of US$848 for 5 Kg of thioacetic acid. That is 17c per gram but I imagine that larger quantities could be found for purchase for even less per gram.
The deprotection step is done here using ammonia. I imagine that its ammonia dissolved in water. There are other options to deacylate a thiol that can be tried if this one proves to be inconvenient.