Phenylpropanolamines from Propenylbenzenes


Cheap and easy method of aminoalcohols production - for example phenylpropanolamine, pseudo-ephedrine and so on, (and ring methoxylated too!)

Place in 1 l RB flask 37 ml (35 g) propenylbenzene (bp 69°C at 13 mmHg), then 250 ml of DMSO, add 15 ml H2O, and with stirring, add 106 g of N-bromosuccinimide in small portions during 15 min. A yellow color appears when NBS is added, and by the time the addition is complete, the color is bright-orange. During the addition temp rose up to 50 C. Stir another 15 min, then pour into 1 l of cold water and 3-5 times extract with 100-ml portions of ether. The combined etheral extracts washed water, then NaCl soln, extract dried over MgSO4 and ether was distilled off. Obtained 70 g of yellow oil PhCH(OH)CH(Br)CH3. Yield almost quantitative.

Dissolve this oil in 100 ml of methanol. Saturate 400 ml of methanol with ammonia at -10°C (bubble ammonia until volume grows with 50%, up to 550-600 ml). Mix methanolic soln of bromohydrine with ammonia soln, place it in sealed bomb and heat at 110-120°C 4-5 hrs. After cooling open it carefully (ammonia evolution!) poll in 1 l glass (carefull, please - mixture foamy as freshly-opened champagne) and allow main quantities of ammonia fly out at slowly heated water bath. Distill of methanol and obtained semi-cryst oil dissolve in 300 ml of 20% HCl. Wash milky soln twice with hexane, basify and extract PPA with methylene chloride (3x100 portions). Dry with NaSO4, and remove solvent. Result - about 42 g of oil, cryst on chilling with mp 53-55°C. Conversion of isopropenylbenzene - PPA is 92%. Not bad, I think.

Reference: Organic Syntheses, vol 59, p.16.