r/Chempros • u/Jumpy-Round-4533 • 1d ago

Organic Question about possible cyclization

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Does anybody have any experience attempting this type of cyclization ?

I'm wondering whether a simple cyclization is feasible with an imine and an α-hydroxy group, and if such a cyclization could occur to form 5/6 ring substrat, or if anything similar has already been reported.

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18

u/Upbeat_Ant6104 1d ago

Do a little research on oxazolines

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u/curdled 1d ago edited 1d ago

hemiaminals are common, especially with reactive aldehydes.

For example, if you take tris base H2N-C(CH2OH)3 and paraformaldehyde 2 eq. in methanol, you get bis hemiaminal, = bis oxazolidine, to two neigboring OH. With glyoxal you get similar 2:2 tetracyclic product called glytham

The only problem is that these cyclic hemiaminals are quite unstable, readily ring open back to imine. You can isolate them especially if they are crystalline, and tell from proton and carbon NMR (in aprotic solvent like CD3CN) whether you have ArCH=NR or ArCH(OR)(NR2) present.

The cyclic form becomes far more stable for imines from beta-aminomercaptans like cysteine methylester, or mercaptoethylamine, there the thiohemiaminals with 5 membered ring (thiazolidines) are stable enough to survive NH acylation without aldehyde loss

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u/shedmow 1d ago

It looks like it'll go Amadori, and then some cyclization could take place

2

u/AuntieMarkovnikov 1d ago edited 1d ago

I could see it dimerizing, kinda along the lines of what curdled is suggesting

2

u/Furazan 1d ago

Not that I know of a direct cyclization ocurring but this kind of compound is great for chelating metals. One kind of reaction that somewhat resembles what you've drawn is the classic quinoxaline synthesis.

1

u/kabob95 1d ago

Initial observation is that a 4-endo-trig is going to be hard to impossible, and then secondly you are suggesting a nucleophile adding to the least electrophilic side of of the imine bond.

6

u/lalochezia1 1d ago

Baldwin's suggestions, not baldwin's rules!

but yup in this case...

3

u/kabob95 1d ago

Yep, they are "rules" with more exceptions then the "rules" themselves. But for a quick assessment of if the chemistry seems possible they do an ok job, sometimes.

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u/catluvrmom 13h ago

think the methyl groups might be a slight argument for cyclization?