I came across a method of synthesizing enantiomerically pure S-cathinone using S-alanine which is chlorinated to the corresponding acid chloride which is used in a Friedel-Crafts acylation of benzene. In the first step, the S-alanine is N-acetylated to "protect" the amino group. I was wondering if the amino group will be replaced by chlorine by reaction with the PCl5 hence requiring protection with an acetyl group. This of course will bring about the problem of causing dehydration of the amide to a nitrile when chlorinating the carboxylic acid to an acid chloride. So why acetylate the amino group in S-alanine?
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1$\begingroup$ Is that last step supposed to be heat? The fact that it's equilateral makes it look more like cyclopropane. Anyway, I'd expect that the amine lone pair messes with the Lewis acid used in the FC acylation. $\endgroup$– orthocresolCommented Feb 13, 2022 at 14:29
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$\begingroup$ @Waylander The acetylated amine is an amide that is dehydrated to an imidoyl chloride which I think you refer to as "chlorimine". The imidoyl chloride upon heating decomposes to give a nitrile and HCl. $\endgroup$– Samuel WangoCommented Feb 13, 2022 at 16:08
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$\begingroup$ @SamuelWango To get a nitrile from an imidoyl chloride you have to heat under forcing conditions. In the absence of such treatment the imidoyl chloride readily hydolyses back to the N-acetyl compound and can be recovered unchanged. $\endgroup$– WaylanderCommented Feb 13, 2022 at 16:40
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1 Answer
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The treatment of N-acetyl-S-alanine with PCl5 gives the acid chloride of the carboxylic acid and converts the N-acetyl group to the imidoyl chloride. This species undergoes classical F-C acylation with benzene and then on aqueous work-up the N-acetyl group is regenerated by hydrolysis.
Contrast this with the reaction of S-alanine with PCl5. This paper here shows that L-alanine forms the acyl chloride hydrochloride which will be unable to give the acylium cation on treatment with AlCl3 as it is already a charged species.
