Sciencemadness Discussion Board

Protecting Ethanolamine

Meltonium - 21-9-2017 at 06:39

So I'm working on a synthesis of diphenhydramine (the active chemical in sleep medications) starting from benzyl alcohol. My plan so far is to oxidize benzyl alcohol to benzaldehyde using the 10% nitric acid method, convert some benzyl alcohol to benzyl chloride, and then use both of those to form a grignard reaction to get diphenyl methanol.

The next step would be to add ethanolamine and then methylate the amine with methyl iodide. That's a problem because it isn't going to work the way I would like.

My thinking is that I would turn the diphenyl methanol to diphenyl methyl chloride and use that to make the ether part of the molecule. However, that would also attack the amine which I don't want. In order to get around this, I thought I might use the methyl iodide first on the ethanolamine and then react that product with the diphenylmethyl chloride.

The problem with that, though, is the methyl iodide would likely form an ether with the hydroxyl group. Is there a way to protect the hydroxyl group from attack of the methyl iodide? Or should I go about a different route for this?

(Please forgive my poor terminology and attempts of explaining; I have not yet formally learned all organic chemistry)

DJF90 - 21-9-2017 at 08:58

You're not going to get diphenylmethanol from benzaldehyde and benzylmagnesium chloride...

Meltonium - 21-9-2017 at 09:12

Right, in my mind, I got it confused. Benzaldehyde + phenyl magnesium bromide. Not benzyl chloride.

Melgar - 21-9-2017 at 09:30

Benzophenone is fairly easy to acquire, at least as easy as ethanolamine. And that can be reduced to diphenylmethanol. You can't actually do what you're saying anyway, because you have an extra methyl group that has to go somewhere, if you do. Also, the problem with methyl iodide would be overalkylation of the amine nitrogen, to, of all things, choline. Choline is an important nutrient, that your body can synthesize from dimethylaminoethanol, which is very inexepensive in health food stores. Look up its structure if you're not sure what it looks like yet. Search for "DMAE" too, and see what comes up.

Cryolite. - 21-9-2017 at 10:21

You could alternatively make DMAE from ethanolamine directly by using Eschweiler-Clarke conditions (formaldehyde and formic acid at reflux) to methylate the nitrogen specifically. The diphenylmethyl bromide used in the final etherification step should not touch the nitrogen for steric reasons.