phenethylamines via phenylacetaldehydes

[psycosmo]

In

Post 244973

(Rhodium: "Re: Friedel-Crafts formylation?", Novel Discourse) the reduction of phenylaceteldehyde to phenethylamine is discuessed. Of course one could always decarboxylate but that might not always be the most desirable option, for example if one wanted a phenethylamine with methoxy groups on it. Ive always wondered what o-methyl tyrosine would do, or o,o-dimethyl dopa)

So could a general method of producing PEAs be

1) Strecker degradation of an amino acid to an aldehyde
2) Amination of the aldehyde to a primary amine

[Rhodium]

Yes, but don't expect stellar yields.

[psycosmo]

from any particular step or both? Thanks...

[Rhodium]

I'd say you could expect ~50% in each step, making the overall yield somewhere between 20-25%...

[neuromodulator]

I once read in a perfumery book that alpha-phenylacetaldehyde (2-phenylethan-1-one) was used as a scent in the cologne industry, but decomposed rapidly.

However, assuming one were to work quickly, I have also wondered about ozonolysis of purified elemi oil followed by reductive amination as a more easily accomplished route to mescaline than the rather laborious vanillin route.

[psycosmo]

well if were on the subject of allylbenzenes, then Ill mention an idea thats been floating around in my head
1) KMnO4 oxidative cleavage of the allylbenzene to a carboxylic acid
2) Replacement of OH with NH3 with urea a la the methylamine faq's acetamide synth
3) Reduction with NaBH4/Iodine have some refs that discuss this, will look them up tomorrow and make a post about this method of reducing amides..

[neuromodulator]

KMnO4 would give 3,4,5-trimethoxybenzoic acid (in the case of elemicin) under harsh enough reaction conditions to cleave the double bond of an essential oil to a carboxylic acid.

Making an amide directly from a carboxylic acid is energetically unfavorable.  It is better to convert the acid to an acyl halide and then react with an amine to get from a carboxylic acid to an amide.

Amides are notoriously difficult to reduce because of their high stability which stems from the fact that the amide's nitrogenous lone pair of electrons is able to feed some of its electron density to the electron deficient carbon of the adjacent carbonyl moiety.  LiAlH4 (LAH) can do the trick, but it won't be easy due also to LAH's highly sensitive reaction to moisture.

[psycosmo]

here are some refs for LAH-less reductions of amides
1)Tetrahedron Letters no. 10, pp. 763-66, 1976-Sodium Acyloxyborohydrides as New Reducing agents, Reduction of Carboxamides to the corresponding amines; Umnio, Takeo & Itoh

2) Unusual Reactivity of Zinc Borohydride; Synthetic Communications, 27(3), 391-394, 1997; Narasimhan, Madhavan, Balakumar & Swarnalakshmi

3) Convenient Methods for the Reduction of Amides, Nitriles, Carboxylic esters, Acids and hydroboration of Alkenes using NaBH4/I2 system; Tetrahedron vol 48 No22 pp 4623-8, 1992, Prasad, Bhaskar, & Periasamy.

As for making amides from carboxylic acids, is there something different in this case that would make it more difficult than making acetamide from acetic acid as per the methylamine faq?

[Barium]

In Vogel´s 5:th edition p 774 there is an example of sodium triacetoxyborohydride reduction of an amide to an amine.

To a stirred suspension af sodium borohydride (1.89g, 50mmol) and benzamide (1.21g, 10mmol) in 20ml 1,4-dioxane is added glacial acetic acid (3.0g, 50mmol) mixed with 10ml dioxane over a period of 10 min at 10 deg C; the reaction mixture is stirred at reflux for 2 hours. The reaction mixture is concentrated to dryness in vacuo, excess reagent is decomposed with water and the solution extracted with chloroform. The extract is washed with water and dried over anhydrous sodium sulphate. The chloroform layer is treated with dry hydrogen chloride, evaporated in vacuo and the residue recrystallised from methanol-ether to give benzylamine hydrochloride (1.09g, 76.2%)

[psycosmo]

If the Oxidative Cleavage step is a bottleneck in allylbenzenes ---> phenethylamines, maybe this reference will help:

Sand Catalyzed Oxidative Cleavage of Double Bonds; Synthetic Communications 26(1), 165-78, 1996
Bingnan Huang, Hohn T Gupton, Kieth C Hansen, John P Idoux, Lamar University

Abstract: The discovery of a catalytic effect of sand on the activity of KMnO4/NaI04 or KMnO4/NaClO oxidant systen provides a convenient method for double bond cleavage under mild conditions. An oxidative rearrangement if a-bromostyrene to 2-bromoacetophenone was also observed

Article sez that permangante/hypochlorite/sand on PhCH=CH2 ---> PhCOOH 80% yields.

[neuromodulator]

KMnO4 will turn the C attached to any benzene ring to a
Ar-CO2H *as long as* that carbon has at least 1 H attached to it as well. 

In the case of elemicin, you will still get the following:

3,4,5-trimethoxyallylbenzene +KmN04 + sand + Chlorox -->
3,4,5-trimethoxybenzoic acid