Rhodium's Untested Excellent Ideas[ Back to the Chemistry Archive ]This is a new section to my page, where I propose novel and/or improved procedures for the synthesis of interesting target compounds from related proven procedures in the literature. If you try them out, please email me at rhodium@ziplip.com or send me a PM at The Hive. When more information about a certain procedure has been collected, procedures may be moved from here into other documents. Reduction of (pseudo)ephedrine to methamphetamine in nearly quantitative yieldCurrent methods for reduction of (pseudo)ephedrine suffer from low yields and impure products, often due to hasty, sloppy technique as well as the failure of most experimenters to analyze their product and determining the optimum reaction parameters. The following method was developed for simpler arylketones/benzylalcohols than (pseudo)ephedrine, but there is no reason to believe that the method would not work just as well on that substrate with just minor tweaking of the reaction parameters. The method proposed below is an optimized variation of the iodine/hypophosphorous acid reduction system. It seems like part of the reason for success in this particular method is the use of acetic acid as solvent, as without that, the reaction went much more sluggishly. Also, the reaction time is extended to 24 hours and the reaction temperature lowered to increase yields and minimize by-product formation. Experimental: 5g Iodine and 3.3g (pseudo)ephedrine freebase was dissolved in 100ml acetic acid in a flask equipped with a reflux condenser. 10ml 50% Hypophosphorous acid was added and the mixture was heated to 60°C, at which temperature the solution was stirred for 24 h, then diluted with 100ml water and washed twice with 50ml toluene. The solution was then basified to pH 11 with 25% sodium hydroxide, and possibly diluted with more water if the formed inorganic salts precipitates from the solution. The basified aqueous solution was then extracted three times with 50ml toluene, and the pooled organic extracts was dried over magnesium sulfate, filtered and gassed with anhydrous hydrogen chloride to precipitate methamphetamine hydrochloride. The yield should be 90-100%, or 3.3-3.7 grams. References: h3po2.i2.reduction-1.pdf
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