[LookAroundYou]

I am looking to synthesize what I thought might be a simple caffeine derivative. I am looking to reduce one or both of the ketones on the caffeine to alcohols. That is it... I have tried it twice and failed. Both times I used sodium borohydride and produced different looking powders. I injected my products on the mass spec and I didn't get any of the expected m/z.

After failing a few times and being unsure as to what I had made, I was looking to have a small amount synthesized so I might have a reference material to work off of.

I contacted 3 different chemical synthesis service providers and 2 said it would be to unstable of a product so they refused. The last one was going to charge too much so I was unable to move forward with the project.

Can we have a discussion as to why this compound has not been synthesized? I am having a difficult time understanding why a seemingly simple reaction wont work.

Cheers!

[wildfyr]

Hemiaminals are indeed unstable. What you propose would be a diamino hemiaminal (not even sure of name). Its just such an electron rich carbon center, something is bound to happen. usually it will eliminate water.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332198/

Also NaBH4 isnt strong enough to reduce amides.

[LookAroundYou]

This is fantastic, thanks for the excellent information, I appreciate the *delete me*

[rolnor]

Why do you want to make this?

[LookAroundYou]

help* not "delete me"

Anyway, thanks again!

[LookAroundYou]

Why do you want to make this?

Well, this was going to be an intermediate product. Next, I was hoping that I could perform a fisher esterification on the alcohol caffeine derivative using palmitic acid. I was hoping, this would give me some kind of caffeine palmitate compound.

This whole project was just a shower thought but I was wondering if this chemical might have a better taste profile than caffeine. I was also thinking that if consumed, the caffeine derivative would be metabolized back into caffeine and might have a delayed onset. I know esterified compounds like ascorbyl palmitate exist which is like a fat soluble form of ascorbic acid.

One day, it would be so fun to make the end product. The route would probably get pretty complicated for this molecule. I wonder how it could be done...

[rolnor]

That would be a pro-drug type of compound. I have made a lot of pro-drugs. One problem is that the pro-drug, your reduced caffeine palmitate, is also a potentially biologicaly active molecule, it could have unwanted (or wanted) effects on the human body. You could alkylate the "imidazole" nitrogen with chloromethyloxypalmitoate, this would give you a "Bundgaard" type of pro-drug. this would be a quaternized compound. Here are some references chatGPT suggested regarding modifications of the caffeine molecule:

[sjb]

Not sure those references are that good - the Chem Rev, for instance doesn't seem to exist?

[Borek]

Here are some references chatGPT suggested

It is a well know thing: this is exactly one of these situation when ChatGPT notoriously makes things up. Please don't use it as a source of posted information.

[rolnor]

It is what it is? If you know AI is making mistakes you can take it with a grain of salt? It does not always make thing up. Chemical Reviews seems to be wrong, yes.
I should ad to, have you guys tested the chatbot yourselfs? If not i suggest you do that. Its impressive although it is wrong sometimes.

[rolnor]

I will not post un-checked material from the chatbot in the future.