Barium (Hive Bee)
06-27-02 06:42
No 326043
      Proposed novel route to phenylethylamines  Bookmark   

This is just theory so far but according to patent EP 0 389 876 N-methyl-3,4-dimethoxyphenylethylamine can be made by the following route:

”3,4-dimethoxybenzaldehyde which, by means of a Darzens condensation, gives an epoxyester that, by alkaline hydrolysis and subsequent decarboxylation, gives the 3,4-dimethoxyphenylacetaldehyde. This aldehyde gives the title amine by reaction with monomethylamine followed by reduction with sodium borohydride.”

There are several interesting aspects in this patent…

Easy reaction from the benzaldehyde to the phenylacetaldehyde

Aqueous imine formation and borohydride reduction

No heating involved at all, just quite mild cooling

76.5% yield of final amine calculated from starting benzaldehyde

I propose, from the theory of this patent, that benzylamine is used instead of monomethylamine and the generated N-benzyl phenylethylamine is converted to the phenylethylamine by hydrogenolysis by either CTH (ammonium formate/Pd-C) or regular low pressure hydrogenation.   

Couldnīt also a great number of N-mono or dialkyl tryptamines be made by this route as well, starting from the corresponding indole-3-carboxaldehyde???

Proposed route to 2C-H from 2,5-dimethoxybenzaldehyde:

2,5-dimethoxybenzaldehyde is allowed to react with an alkylester of an alpha-haloacetic acid (eg. 2-butyl chloroacetate) in an alcoholic media at 15-20 deg C, in the presence of a strong base (eg. sodium methoxide) to give an alpha,beta-epoxyester.
This epoxyester gives by alkaline hydrolysis (aq. NaOH or KOH) the alkaline salt of the epoxyacid. Decarboxylation of this epoxyacid salt by acid hydrolysis gives  2,5-dimethoxyphenylacetaldehyde.

2,5-Dimethoxyphenylacetaldehyde is allowed to react with benzylamine and the formed imine is reduced to the amine by aq. Sodium borohydride without isolation. The N-benzyl-2,5-dimethoxyphenylethylamine is isolated and debenzylated by conventional hydrogenolysis.

Iīm currently ordering the chemicals needed for some trials. Reports will follow shortly.
(Hive Bee)
06-29-02 02:02
No 326766
      Sorry!!!  Bookmark   

I thought it would interest you to have another synthetic pathway to phenylethylamines, avoiding the nitrostyrene or acetonitrile routes. But I guess I was wrong......frown
(Hive Prodigy)
06-29-02 06:11
No 326792
      No, you were correct.  Bookmark   

Some of us here really do appreciate your posts. Don't get upset please. Apparantly a lot of the chemically inclined bees are away on vacation, and the chemistry forums are running close to dry these days.
(Hive Bee)
06-29-02 07:07
No 326799
      Itīs just amazing what a poor bee has to do to be ...  Bookmark   

Itīs just amazing what a poor bee has to do to be noticed here...wink

I just want to have some INPUTS.
Has someone checked the patent?
Has this pathway been mentioned before, or even tried before?

It will take me some three weeks to get the chemicals I need to try this.
Meanwhile, Iīm soooo fucking curious I can hardly sleep at night.

/a very impatient non-noble metal
(Hive Bee)
06-29-02 12:12
No 326879
      It has been mentioned: http://www.rhodium.  Bookmark   

It has been mentioned: ../rhodium/chemistry /2ch.darzen.html
(Hive Bee)
06-30-02 02:39
No 327121
      Oh shit!!  Bookmark   

Blushing all over and feeling utterly silly...

Itīs the same patent I found, except I found the european version.
One problem I can see with the method at Rhodiumīs site is that the aldoxime is a BITCH to reduce with good yields.
(Hive Bee)
07-02-02 08:46
No 328005
      Wonder  Bookmark   

How weak base could be used for a Darzen condensation?
(Chief Bee)
07-02-02 09:06
No 328011
      The Darzen reaction mechanism requires the ...  Bookmark   

The Darzen reaction mechanism requires the carbanion of the ester to form, but I don't know what it takes for that to happen.