HTML by Rhodium
A mixture of 2-bromosafrole (24.1g, 0.1mol), hexadecyltributylphosphonium bromide (5.1g, 0.01mol), sodium azide (16.2g, 0.25mol), and water (50ml) is magnetically stirred at 80°C for 24 hours. Flask is cooled and phases are separated in sep funnel. The dark reddish organic layer is diluted with toluene (20ml) and poured back into flask and stirring is restarted. A solution of sodium borohydride (11.7g, 0.3mol) in water (30ml) is carefully added through an addition funnel over 30 minutes as temp is raised to 80°C and held there for 16h. Contents of flask are cooled and poured into a sep funnel. Aqueous layer is sepped off and organics are washed with 50ml dH2O. Three 40ml portions of 4M HCl (approx 10%) are used to extract MDA base from organic layer. Combine all acid extracts and neutralize with 50% NaOH soln. Golden beads of MDA base will fall out of soln. Use two portions of 50ml toluene to isolate base. At this point one of two things can be done. If you are a greedy shoddy chemist you will dry the toluene extracts with anhydrous MgSO4 then bubble with HCl gas to isolate a relatively pure white MDA hydrochloride (8-12g) OR if you have any pride in your chemistry skills and product, toluene will be evaporated down to a orange oil and vacuum distilled using standard methods to yield 6.5-11.0g of water white pristine MDA base. Distilled base is most easily crystallized by adding about 6 times volume of dry IPA and neutralizing w/ conc. HCl. Place this in the freezer over night to find glorious white crystals of the hydrochloride. At this point not all of the salt has precipitated and it won't no matter how long you leave it in the freezer, so add the same volume of dry acetone to ppt. entire yield (6-12g, or 27-56% yield from bromosafrole).
Instead of extracting the azide with toluene use xylene. Use a well dried xylene extract in the following procedure.
In a dry 50ml flask equiped with septum inlet, reflux condenser, and magnetic stirrer was flushed with nitrogen. The flask was charged with 10mL xylene and 0.98g, 1.42ml (10 mmol) of triethylborane. The solution was then heated to reflux and attached to a gas buret. Then 1.11g (10 mmol) cyclopentyl azide was added. After completion of nitrogen evolution, the flask was cooled, 30 ml diethyl ether was added and the amine extracted with 6 M HCl, two 20 ml portions. The aqueous phase was then washed with ether to remove residual borinic acid. Yield 77%.
This reference is a significant advance in alkylazide reduction techniques because it reduces the azide and methylates it in one single step. This is the only ref I am aware of which yields a N-methylamine directly from the azide precursor without using catalytic hydrogenation for the reduction.
Secondary alkylazide (0.148mmol) in CH2Cl2 (1.5ml) was added a solution of (CH3)3P in toluene (1.0M, 0.3mL) at room temp. After stirring for 1.5hr, paraformaldehyde (22.6mg, 0.753mmol) was added. The rxn. mixture was stirred for an additional 6hr at room temp then rxn was cooled to 0°C and MeOH (2.0ml) and NaBH4 (28mg, 0.74mmol) was added. After stirring for 30 min the rxn. was quenched with saturated aq. NaHCO3 and extracted with 5×10ml CH2Cl2. Extracts were pooled and evaporate to yield 83% N-methylamine.