H3PO2/Iodine causing N-Demethylation?

[Rhodium]

The article gives no examples of N-demethylation of secondary amines, and usually the Hypophosphorous Acid/Iodine reduction of (pseudo)ephedrine is conducted under less harsh conditions, but this may be something to bear in mind...

Hypophosphorous Acid-Iodine: An Efficient and Mild Reagent for Cleavage of N–C Bond
Ge Meng, Yan-Ping He, and Fen-Er Chen

Synth. Commun. 33(15), 2593–2598 (2003)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/h3po2-i2.n-dealkylation.pdf)
DOI:

10.1081/SCC-120021978

Abstract
A mixture of hypophosphorous acid (H₃PO₂) and iodine in acetic acid can selectively cleave the N-alkyl bond in a variety of substituted heterocylic compounds in good to excellent yields without any damage to amide bond present in the substrates.

[halfkast]

Rhodium can you give one or two examples of secondary amines, and also what N-demethylation would do to those theoretically? (theoretically if it happened to work using this route)

Well, I'd know what the demethylation did from looking at the starting material, but I want you to choose one yo like!

[Rhodium]

I inferred that amphetamine could perhaps be formed from methamphetamine (which is an N-methylated secondary amine) if either the precursor (pseudo)ephedrine or the product was demethylated.

[halfkast]

fuck! a revelation, I didn't think that was possible, thanks!

[WizardX]

Rhodium stated:

I inferred that amphetamine could perhaps be formed from methamphetamine (which is an N-methylated secondary amine) if either the precursor (pseudo)ephedrine or the product was demethylated.

The -OH reduction of the ephedrine WILL predominate completely, before demethylation occurs.

[halfkast]

Wiz, are you saying that an ephedrine reduction using H3PO2, I2 and acetic will first reduce to methamphetamine, and then on to amphetamine?

[WizardX]

Yes! BUT ONLY under VERY EXTREME reaction condition. ie. very long reflux time.

Methamphetamine has a secondary amine, and this demethylation reagent will not be very effective.

A mixture of hypophosphorous acid (H3PO2) and iodine in acetic acid can selectively cleave the N-alkyl bond in a variety of substituted heterocylic compounds in good to excellent yields without any damage to amide bond present in the substrates.

Note that the demethylation of substrates are tertiary amines.