Help about benzoin condensation

chem_tr

Hello friends,

I am planning to do one new instance of benzoin condensation, with pyridine-4-carboxaldehyde as the carbonyl compound to receive, 2-hydroxy-1,2-dipyridin-4-ylethanone, the resultant benzoin compound. However I have some doubts as suggested in this website, since pyridine nitrogen is a good mesomeric effect provider; this is told to make the reactions harder. Would this pretreating works? First quaternizing the pyridine nitrogens by, say, methyl iodide, and after performing the benzoin reaction, remove them?

I am waiting for your comments, thank you.

chem_tr

GCT

It's a possibility that the ring will become unstable, since the quaternary structure requires more of a sp3 hybridized state. I'm not quite sure about the other aspects of this problem so I won't bother to criticize, until I become more familiar with them (don't have time right now).

chem_tr

Thank you for your interest, GeneralChemTutor.

I've been thinking about it, and found that phenyl group pulls electrons from carbon, making it more positive than any positively induced mesomeric phenyl groups, therefore makes it possible for any nucleophilic attack onto carbon.

I'm not sure how hard it would be if I want to remove the methyl groups on the quaternary pyridinium nitrogens. This would allow the compound to be soluble in water, though, but I'm planning something different with the nitrogens, so I need them.

movies

The methyl pyridinium won't be very sp3 like, actually. The electron pair that you methylate is in the same plane as the pyridine ring. I'm not sure that this will give the desired reactivity, however. Just by glancing at the mechanism, I would assume that the reaction would be okay with pyridine just as it is, since pyridine is an electron deficient aromatic system (relative to benzene). That should activate the aldehyde moiety to attack by CN.

You might also look into pyridine N-oxides. I don't recall a lot about them, but I know that they have some pretty unique reactivity that allows you to functionalize pyridine rings in ways that are usually very difficult.

GCT

Chem tr mentioned a quaternary structure, thus I was a bit suspicious. I'll have to research on this topic a bit further.

movies

I think that by "quartenary" he means a nitrogen with 4 alkyl substituents (counting the C-N double bond as two alkyl substituents). Similarly pyridine is sometimes referred to as a tertiary amine base.

chem_tr

Dear Movies,

I understand that you recommend me try the unsubstituted pyridine derivative first, and if unsuccessful, switch to the N-oxide one. Am I correct? Secondly, I'm planning to quaternize pyridine nitrogens to decrease the reactivity; if I have to do this, how can I cleave the Me-N bond of pyridine?

movies

Chem_tr, I'm not certain that the pyridine N-oxide will do what you want, but you might try looking it up in the literature. It was mentioned in one class that I took, and I recall that it had very different reactivity from regular pyridine. I don't recall the specifics, however.

I don't know the typical method for cleaving a quaternary ammonium species, but I know it can be done. I just did a quick search and it looks like you can do it by heating with some other amine, for example, piperidine. Another way seems to be heating in pyridine*HCl.

I hope this helps.

chem_tr

We've quaternizing pyridine nitrogens frequently, by using methyl iodide in a dark place at the ambient temperature for one day; the resulting compounds has a solubility in water, it is sometimes not very good, but the original compound seems to be never dissolved in water.

I've searched Chemical Abstracts in the period 2004-1998, and found that all kinds of pyridoins, i.e., pyridine aldehyde-derived benzoin derivatives, are present, so you are right, Movies, about the decreased reactivity of benzene ring. I think it won't be very hard to synthesize these compounds. At least it is worth a try.

Thanks.

GCT

What was I thinking, a six membered ring, whether sp3 or sp2 hybridized would be stable anyhow (despite a slight deviance in bond angles from a non-ring structure). Also note that the lone pairs of the nitrogen in pyridine do not contribute to delocalization. Yes, I'm talking to myself.