PEAs/Amphetamines from bromobenzenes in 2 simple steps

Lego · Mon Sep 05, 2005 11:14 pm

All chemicals are either OTC, unwatched and cheap or easy to prepare.

Short and Efficient Synthesis of Optically Active N-Tosyl Aziridines from 2-Amino Alcohols
Lothar W. Bieber, Maria C. F. de Araújo
Molecules, 2002, 7(12), 902-906
http://www.mdpi.org/molecules/papers/71200902.pdf

Method B: Tosyl chloride (2.5 mmol) was added portionwise at r.t. under vigorous stirring to a mixture of KOH (2.0 g), 2-aminoethanol (ethanolamine) or 2-amino-1-propanol (alaninol, enantiomeric pure alaninol can bee used to get enantiomeric pure amphetamine) (1.0 mmol), water (2.0 mL) and CH2Cl2 (2.0 mL). After 30 min, ice and water were added, the organic layer was separated, washed with water, dried over MgSO4 and evaporated. The crude products were purified by crystallization, short-path distillation or column chromatography. The optical purities of all products were proven to be identical with those of the starting materials. The pure aziridines polymerize at r.t. within a few days, but can be stored at –30º for months.

Yield: 74%/78%

A new convenient approach to chiral β-aryl(heteroaryl)alkylamines
Valentine G. Nenajdenko, Alexei S. Karpov and Elizabeth S. Balenkova
Tet. Asy., 2001, 12(18), 2517-2528
http://dx.doi.org/10.1016/S0957-4166(01)00442-6
http://rapidshare.de/files/4760094/Tet._Asy.__2001__12_18___2517-2528.pdf.html

General procedure for ring opening of N-tosyl aziridines with Grignard reagents
To Mg (0.17 g, 7 mmol) in a flame-dried flask under Ar THF (10 mL) was added. The solution of corresponding aryl(heteroaryl)bromide (7.1 mmol) in THF (5 mL) was added dropwise. The mixture was stirred for 30 min at rt, then cooled to −30°C and dry CuI (0.2 g, 1.05 mmol) was added. The suspension was stirred for 30 min at −30°C, then cooled to −78°C. A solution of the corresponding 2-alkyl-1-[(4-methylphenyl)sulfonyl]aziridine (3.5 mmol) in THF (10 mL) was added dropwise. The suspension was stirred at −78°C for 15 min, then at 0°C for 1 h, after which time it was partitioned between NH4Cl and ether, the aqueous layer extracted with ether (3×15 mL), the organic layers dried (Na2SO4), filtered and the solvent removed in vacuo to leave a brown oil which was purified by chromatography on silica gel with hexane–dichloromethane (1:1) as eluent.

With phenylbromide (for tosyl-amphetamine): White oil, yield 0.76 g (75%)
With 4-methoxyphenylbromide (for tosyl-PMA): White solid, yield 0.93 g (83%); mp 101–102°C

General procedure for desulfonylation
To a suspension of Mg (0.45 g, 20 mmol) in MeOH (5 mL) was added a solution of the corresponding N-tosylalkyl-2-aryl(heteroaryl)amine (2 mmol) in MeOH (10 mL). The resulting suspension was sonicated for 1 h until consumption of the starting material was complete. The reaction mixture was then diluted with aqueous NH4Cl and extracted with ether (3×5 mL). The organic layer was dried over MgSO4 and evaporated. To resulting oil ethanolic solution HCl (0.5 mL, c 2 M) was added. Hydrochloride was precipitated, filtered and washed with ether.

The authors did not mention the yields for the amphetamines (don't ask) but it should be around 50%.

java · Consumer

Lego .....a very nice synthesis , I will have to sit down and digeat it with time but just scanning over it it seems a very interesting method...........java