LSH / LSI doubts

[Transform]

Short-chain aldehydes are fairly reactive, so I for one would be willing to accept the plausibility of adducts even with something as relatively unreactive as an amide nitrogen. The supporting evidence of the example with acetaldehyde and acetamide seems sound enough and, while the product there resulted from a 2:1 amide to aldehyde ratio, lysergamide itself is bulky enough to limit the stoichiometry to 1:1.

Whether I'll get to test these hypotheses experientially myself remains to be seen.

 

[shilo]

I'm not a chemist. This is about lysergic acid isovaleraldehyde vs lysergic acid hydroxyethylamide I assume. I asked an AI since I'm dumb. Please correct me if this information is inaccurate:

"The dramatic difference in stability between the two adducts comes down to physical crowding, known in chemistry as steric hindrance. When the adduct forms, LSH attaches a small, compact methyl group to the central connecting carbon, which fits comfortably next to the massive lysergic acid backbone and allows the molecule to remain relaxed. In contrast, LSI forces a bulky, branching isobutyl group into that exact same space. The sprawling structure of the isobutyl group physically collides with the rest of the molecule, creating severe internal pressure. This crowding acts like a spring-loaded trap, making LSI so highly strained that the mild warmth and moisture of the mouth cause it to rapidly snap apart, whereas the uncrowded LSH holds together long enough to be absorbed sublingually."

 

[secpropyl]

This is about lysergic acid isovaleraldehyde vs lysergic acid hydroxyethylamide I assume.

Fwiw the proper naming is lysergic acid isopentylamide (not isovaleraldehyde), but the form produced from this theorised LSA/aldehyde adduct has an additional α-hydroxy.

 

[doubledog]

It's really fascinating that these decades long speculations about lysergamide aldehyde adducts are still alive, but still without any real progress.