Natural Science Forum / Chemistry / Organic Synthesis / September 2003

Monoalkylation as you have it is not a good route to anything but
quats.  It is exceptionally hard to control the degree of alkylation,
even using binary addition into a solvent in which the teriary amine
salt is insoluble.  On the average you'd be much better off using the
appropriate aldehdye or ketone, the amine, and sodium cyanoborohydride
in mild aqueous acid buffer.

Given your question about hydrohalogenation (even assuming it is a
reasonable synthetic route), you don't know anything about organic
chemistry.  If this is industry you'd better ante up and retain an
organic chemist.  If this is recreational pharmaceuticals, get a
better cookbook.

Monoalkylation as you have it is not a good route to anything but
quats.  It is exceptionally hard to control the degree of alkylation,
even using binary addition into a solvent in which the teriary amine
salt is insoluble.  On the average you'd be much better off using the
appropriate aldehdye or ketone, the amine, and sodium cyanoborohydride
in mild aqueous acid buffer.

Given your question about hydrohalogenation (even assuming it is a
reasonable synthetic route), you don't know anything about organic
chemistry.  If this is industry you'd better ante up and retain an
organic chemist.  If this is recreational pharmaceuticals, get a
better cookbook.

I guess the cis / trans nature would still be apparent - as far as I'm
aware hydrohalogenation is a stereospecific process. You'd probably
get enantiomers (or diastereomers) depending on the exact nature of
the alkene)

Hofman alkylation? The only procedure I know that takes RX to RNH2
(wihout over alkylation) is the Gabriel synthesis, which, again, afaik
effectively just swaps the halogen for the NH2.

dextro and levo are emperical terms, based on the roation of polarised
light at the Sodium D-line. There's no real correlation to the fine
structure of the chemical - some dextro compounds are R, some S...

HTH,

Stepphan

Uncle Al <UncleAl0@hate.spam.net> wrote in message news:<biiph5$arq@panther.Gsu.EDU>...

The alkylation will be limited by the fact that I am alkylating a
cyclic secondary amine and the steric hindrance of the
1,2-diphenylethyl group.
There are vast refs on analogous alkylations using the same amine, I
am not at all worried about that
part. Perhaps you can synthesize a di-(1,2-diphenylethyl-)sec amine
and write it up in a journal. You'd be famous! But where would all the
"room" come from for that other 1,2-diPhEt moiety?

Although I am not an organic chemist by trade, I know a great deal
about the subject. If 1,2-diphenylethyl chloride was commercially
available, I would buy it. It seems one of the major purposes of
message boards is for people to ask questions of those who know more
than they do. So, what's the problem?
"Recreational pharmaceuticals". You are very rude.
James

In article <bjam5o$j3q@panther.Gsu.EDU>, permuter@yahoo.com says...

OK, I screwed up a little bit. I was initially thinking of
halogenation of a double bond, which can be shown to be stereospecific
in ring systems (as you allude to later) and so presumably in
alicyclic systems too, and at a first thing thought
that was similar. I've since seen that it's not the case as there's
only room for two electrons with the hydrogen, and no "bromonium" ion
style intermediate.

I then moved on to thinking about the reverse reaction (elimination),
and noted that in several cases (like E1), the hydrogen and the halide
have to be antiperiplanar. So, by microscopic reversibility and all
that, I thought the addition would also have to be stereospecific.

Granted, but for instance in the case of (R)-3-fluoro-2-methylbut-1-
ene, the difference between the fluorine and the hydrogen on C3 is not
that great, and so any steric directing effect that you speak of is
not going to be that great. Hence you may get addition from either
side of the double bond with a fixed chiral centre at C3 and so
possibly a mixture of diastereomers?

I'm thinking more along the lines of matched and mismatched substrate
pairs. The key word in your reply being "preferred", (i.e. not
exclusive).

Stephan

Hi Stephan,

Stephan Bird <stephan.j.bird@mad.scientist.comREMOVE> wrote in message news:<bjl1o9$qhu@panther.Gsu.EDU>...

I think it would be the requirements on the two groups being in the
right place at the right time that stops this from being the case and
favours forming the carbocation.

Well, the ring argument above is irrelevant to this case of course.
There can be no preferred cis-trans isomer, since there will be no
cis-trans isomers possible in the product. There is no 'preferred'
product in that sense.

Not to say there isn't a selection among various theoretical or
possible products with this reaction, just that there's not selection
among cis-trans isomers - in this particular case.

So the example doesn't relate to the rings, but it does relate to the
statement I made about only being able to produce a racemate when a
chiral centre is being introduced into an achiral molecule with
achiral reagents and conditions. The difference being, of course, that
the molecule in question is not achiral or the racemate but is an
enantiomer. In this case, as you state, both configurations will occur
at C3 and a mixture of diastereomers will be created, around 50%, I
expect.

I interpreted the original question as being about a specific
enantiomer being produced at a stereogenic centre introduced during
the course of the hydrohalogenation due to the cis-trans isomerism
present in the starting material (after I ignored the idea of some
spirit of the cis-trans isomerism living on). I think we probably both
agree that this can't occur.

regards,
Simu