Alkylating bis(2-chloroethyl)amine

[josef_k]

Is it possible to alkylate bis(2-chloroethyl)amine hydrochloride with an alkylchloride without freebasing it, or at least freebasing it in situo? (Is it possible to alkylate ANY amine in the salt form? Can't seem to find the right keywords to search for.)

If it is not possible I guess it's better just to alkylate diethanolamine and then chlorinate. Everything to avoid gassing yourself with that nitrogen mustard analogue.

[Rhodium]

You can probably not alkylate that compound with an alkyl halide without polymerizing it, unless you work in insanely dilute solutions.

[Nicodem]

True, you can't aklylate it with an alkylhalide, but a reductive alkylation could well work. I would recomend you give it a try with a Leuckart rxn. Since you probably want to attach a methyl (I guess) the Leuckart should be preferable as it gives good yields with formaldehyde for the prep of tertiary amines. However, I don't know if you should transform the hydrochloride into a formiate before.

[Ritter]

When working with the protonated form (-HCl) of this insidious poison, the best thing to do is freebase the amine and alkylate the deprotonated phenylacetonitrile in one step before worrying about adding a tertiary alkyl group.

I assume you are trying to make a pethidine congener-- I can't imagine what else you'd want this stuff for besides mustard gas.  If one uses a large excess of POWDERED NaOH in DMF to deprotonate the phenylacetonitrile, the red dianion will be visible in no time at room temp. At that point add the amine salt, it will be freebased simultaneously as the nitrile is alkylated.  If the solvent wasn't overloaded with NaOH, the NaCl metathesis product can easily be detected as it precipitates.

One final word:  Straight demerol can do some really nasty things to your heart.  If you must make this krappy drug, alkylate the amine with phenethyl bromide- the potency is doubled to trippled and it is not nearly as bad on your cardiac function.

[josef_k]

Actually I was planning to alkylate it with phenylpropylchloride or possibly cinnamylchloride. That is if I ever get around to it.

I didn't know it was possibly to alkylate the phenylacetonitrile with NaOH as the base without a PTC? Where did you learn that? But I admit I have some faint memories of DMF making NaOH stronger or something.

Edit: I hope it doesn't sound as I don't believe you. I just want to know more about it   .

[Rhodium]

You can alkylate phenylacetonitrile in any of the common polar aprotic solvents (DMF, DMSO etc.) as long as you use anhydrous conditions. Check the Methadone doc on my page for similar reactions with diphenylacetonitrile.