Author Topic: Phenethylamine synthesis idea.  (Read 698 times)

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amine

  • Guest
Phenethylamine synthesis idea.
« on: June 17, 2004, 12:13:00 AM »
I've been looking at an alternate route to synthezing phenethylamines, not the classic aldahyde-->nitroethene-->amine route.

Assuming one were to start with 1,4-dimethoxybenzene here are two of the routes.

I.

A. 1,4-dimethoxybenzene is brominated via NBS to give a 1-bromo-2,5-dimethoxy benzene.

B. An allybenzene grignard reagent is added to the 1-bromo,2-5-dimethoxybenzene to give a 2,5-dimethoxyallybenzene compound.

from:(

https://www.thevespiary.org/rhodium/Rhodium/chemistry/safrole.html

)

C. the 2,5-dimethoxyallybenzene is then oxidized using KMnO4/ Ozone/ H2O2 to give the corresponding phenylacetylaldahyde.

D. the aldahyde is reacted with hydroxylamine, to give the oxime and the oxime reduced to the amine.

from: (

https://www.thevespiary.org/rhodium/Rhodium/chemistry/allylbenzene2phenylacetaldehyde.html

)

the other idea was to use a Friedel-Craft type rxn to get the allybezene formed by using allyl bromide and AlBr3.

The only concern I have is the allyl bromide reacting with its self? (will this occur?).

Any criticism would be appreciated.

Thanks.

ning

  • Guest
Aren't phenylacetaldehydes really touchy?
« Reply #1 on: June 17, 2004, 06:31:00 AM »
I hear they're pretty unstable. How again were you preventing the KMnO4 from oxidizing the aldehyde to an acid?


GC_MS

  • Guest
bzzzzzz
« Reply #2 on: June 17, 2004, 09:07:00 AM »
Some hints you might consider useful:

What I have in mind starts from p-methoxyphenol and can be read at Rh's www:

Synthesis of 2.5-dimethoxyallylbenzene

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/25.meo.allylbenzene.html). In short, p-methoxyphenol is reacted with allylbromide to yield the corresponding ether, which is subsequently subjected to a Claisen rearrangement. The 2-hydroxy-5-methoxyallylbenzene obtained this way can be methylated (the article uses DMS but there probably are alternatives, such as phosphate esters - UTFSE) and voila, you have 2.5-dimethoxyallylbenzene.

Next, you proceed by making the ?-bromo analogue. A good starting point is also featured on Rh's site (anything that isn't to be found there?  ;) ):

Chloro/Bromo/Iodosafrole Synthesis Notes

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/halosafrole.txt). Substitution of the halogen compound is documented on Rh's site as well as on the forum - UTFSE.

Have fun  ;)

Edit: Forgot something... In case you are interested in Grignard reactions involving 2.5-dimethoxybromobenzene, you should read

Post 354784

(Rhodium: "Tips & Tricks regarding dimethoxybenzene Grignards", Novel Discourse)
.



amine

  • Guest
ozonolysis maybe?
« Reply #3 on: June 17, 2004, 06:50:00 PM »
ning, i'm wondering for the cleavage could ozonolysis be used instead of oxidation.

GC. thx, I'm sure the method you mentioned is much higher yielding than the grignard, TMP should be able to methylate the hydroxyl (or so I hope). Swims hasn't had the greatest luck with grignard reactions as yields are often low.