Re: ORGLIST: Re: piperazine et al.

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From: Jacob Zabicky (jzabicky$##$
Date: Mon Oct 05 1998 - 13:20:07 EDT

>On Fri, 2 Oct 1998, Jacob Zabicky wrote (in part):
>> However, I may propose you try the following
>> long shot schemes, because they can work, and after having had the first
>> N-alkylation, the second one would be slowed down by deactivation.
>> 1. The first suggestion would be to carry out your reaction without a base.
>> You could get with some luck N-propylpiperazonium bromide, and the ammonium
>> center will deactivate the second near-by amine, leading preferentially to
>> monoalkylation. After you finish you can neutralize and isolate your
>> products.
>This sounds good, but won't work. The quaternary nitrogen formed by the
>first step will not stay protonated, but will quickly redistribute the
>proton to some of the unreacted starting material as well as to the
>other nitrogen in the same molecule. The alkylation of amines via
>alkyl halides is notoriously bad about giving mixtures.
>In the same line as was suggested in the quoted paragraph, what if the
>piperazine were first reacted with at least one equivalent of HBr or
>some other acid. I would think that this should favor tying up one
>amine per molecule rather than having a mixture of both amines reacted
>in some molecules along with none reacted in others. IF this were true,
>then one of the amines indeed would be deactivated, and maybe only the
>other one would react when the alkyl bromide was added.
OOPS! I missed the fact there were two amino groups in the molecule. your
suggestions to partially neutralize one of them with acid and working with
excess of piperazine in the reflux scheme seem worth trying.

>I don't know the cost of piperazine, but the most typical way to favor
>monoalkylation is to use a very large excess of the piperazine and a
>very limited amount of halide. Then one has the problem of recycling
>the unreacted piperazine, and still having to separate some dialkylation
>product, albeit less.

however there seems to be a practical limit to the excess one should use
>I like the idea of someway tying up one amine, maybe with some polymer.

i like that too. this could be using a strong cation exchanger in its acid
form, followed by treatment with a solution of PrBr. This should leave the
HBr anchored mostly on the strongest base around, namely the newly formed
terciary amine, offering some protection from quaternization. the
suspension can be heated to accelerate the slow alkylation. WORTH A TRIAL.
all thge best,


Prof. Jacob Zabicky Fax. xx-34-977-559694
c/o Prof. Alberto Coronas Tel. xx-34-977-559696
Department of Mechanical Engineering Private No.
Universitat Rovira i Virgili xx-34-930-119552
Cra. de Salou s/n
43006 Tarragona


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