SYNTHESIS: To a well stirred solution of 14.8 g hydroxylamine hydrochloride in 120 mL MeOH there was added 3.6 g of 3,4-methylenedioxyphenylacetone (see under for its preparation) followed by 1.0 g sodium cyanoborohydride. The oxime, prepared from the ketone and hydroxylamine in MeOH with pyridine, may be substituted for these two components. Concentrated HCl was added over the course of a couple of days, to keep the pH near neutrality. When the reaction was complete, it was added to H₂O, made strongly acidic with HCl, and washed with 3×100 mL CH₂Cl₂. The aqueous phase was made basic with 25% NaOH, and reextracted with 3×100 mL of CH₂Cl₂. The extracts were pooled, and the solvent removed under vacuum to give 1.7 g of an oily residue which, with pumping under a hard vacuum for a few minutes, changed to a white solid. This can be Kugelrohred if the vacuum is sufficiently good to keep the temperature during the distillation below 100 °C. The extremely viscous distillate formed crystals immediately upon wetting with IPA. It was dissolved in 20 mL of warm IPA and neutralized with concentrated HCl, with the titration end-point being red rather than orange on universal pH paper. Modest addition of Et₂O allowed the formation of 3,4-methylenedioxy-N-hydroxyamphetamine hydrochloride (MDOH) as white crystals, which weighed 1.4 g when air dried. If the temperature of distillation exceeded 100 °C, there was extensive decomposition during distillation, with the formation of 3,4-methylenedioxyamphetamine () and the oxime of the ketone. Under these circumstances, the only base isolated was MDA. The surest isolation procedure was to obtain MDOH as the free base, as a crystalline solid which could be recrystallized from 5 volumes of boiling IPA. The free base had a mp of 94–95 °C (and should not be confused with the oxime of 3,4-methylenedioxyphenylacetone which has a mp of 86–88 °C since the mixed mp is depressed, mp 56–62 °C, or with the free base of MDA which is an oil). Anal. (C₁₀H₁₃NO₃) N. The hydrochloride salt had a mp of 149–150 °C (and should not be confused with the hydrochloride of MDA which has a mp of 185–186 °C since the mixed mp is depressed, mp 128–138 °C). Anal. (C₁₀H₁₄ClNO₃) N. Acetic anhydride can serve as a useful tool for distinguishing these materials. MDA gives an N-acetyl derivative with an mp of 92–93 °C. MDOH gives an N,O-diacetyl derivative with a mp of 72–74 °C. Methylenedioxyphenylacetone oxime gives an O-acetyl derivative that is an oil.

DOSAGE: 100–160 mg.

DURATION: 3–6 h.

QUALITATIVE COMMENTS: (with 100 mg) “I felt hampered the first hour by some internal barrier, which prevented total enjoyment. However, this began to break through in a wonderful way just before the supplement was offered. Since I felt I was beginning to move through the barrier, I declined the supplement, particularly since I was anxious to compare the after-effects with my first experience. I had found the first time very remarkable, but felt unusually tired for several days following. I feel it is important to know whether this is a specific drug-induced effect, or the result of psychological phenomena. The experience continued in a rich, meaningful way. There was a marvelous inner glow, the warmth from all the other participants was wonderful to feel, nature was most beautiful. There were no dramatic breakthroughs, or rushes of insight or energy, but just a wonderful contemplative space where things gently unfolded as you put your attention on them.”

EXTENSIONS AND COMMENTARY: The first time that MDOH was synthesized, it had inadvertently and unknowingly been converted to . And the search for proper dosage and characterization of effects of this product was, of course, the rediscovery of the dosage and the effects of MDA. It is one of the world’s most remarkable coincidences that after the second synthesis of MDOH, when MDOH had really and truly been actually prepared, the brand new search for proper dosage and characterization of effects revealed that they were almost identical to the earlier observations for (the inadvertently produced) MDA.