MDMA/Synthesis: Difference between revisions

Line 74:

=== Synthesis ===

3,4-Methylenedioxyphenyl-2-propanone (MDP-2-P) was synthesized by two different routes, i.e. by oxidation of isosafrole in an acid medium and by reduction of 1-(3,4- methylenedioxyphenyl)-2-nitropropene which was previously prepared by condensation of piperonal and nitroethane. The syntheses were performed according to the procedures described by Shulgin and Shulgin [11]. ~~Subse- quently~~, MDP-2-P, prepared by the oxidation of isosafrole, was used in Leuckart reaction, cyanoborohydride reduction, dissolving metal reduction and borohydride reduction in low temperature. MDP-2-P prepared by the reduction of 1-(3,4- methylenedioxyphenyl)-2-nitropropene was only subjected to borohydride reduction in low temperature.

3,4-Methylenedioxyphenyl-2-propanone (MDP-2-P) was synthesized by two different routes, i.e. by oxidation of isosafrole in an acid medium and by reduction of 1-(3,4-methylenedioxyphenyl)-2-nitropropene which was previously prepared by condensation of piperonal and nitroethane. The syntheses were performed according to the procedures described by Shulgin and Shulgin [11]. Subsequently, MDP-2-P, prepared by the oxidation of isosafrole, was used in Leuckart reaction, cyanoborohydride reduction, dissolving metal reduction and borohydride reduction in low temperature. MDP-2-P prepared by the reduction of 1-(3,4-methylenedioxyphenyl)-2-nitropropene was only subjected to borohydride reduction in low temperature.

Leuckart method was performed according to the ~~mod- ified~~ MDA synthesis procedure described by Elks and Hey [12]. Safrole bromination was carried out according to the procedure described by Biniecki and Krajewski [13]. Cyanoborohydride reduction (NaBH4CN) was performed according to the modified MDA synthesis procedure described by Shulgin and Shulgin [11]. Dissolving metal reduction (aluminium–mercury amalgam) was performed according to the procedure described by Shulgin and Shulgin [11]. Borohydride reduction (NaBH4) was performed as follows: aqueous solution (40%) of methylamine (2 ml) was added to a cold mixture of MDP-2-P (1.51 g) in MeOH (5 ml). The mixture was cooled to 20 8C and then NaBH4 (30 mg) was slowly added. After dissolving of reductive agent, reaction mixture was left at 20 8C for 2 h. The addition of NaBH4 was repeated three times, in portions of 30, 30 and 40 mg, and reaction mixture was left at 20 8C for 24 h. Methanol was evaporated, 10% HCl (10 ml) was added to a residue and the solution was washed with CH2Cl2 (3 ml x 8 ml). The organic solution was extracted with 10% HCl, combined aqueous layers were alkalized with 25% NaOH (~10 ml) and extracted with CH2Cl2 (3 ml x 10 ml). Combined extracts were dried over MgSO4, evaporated, a residue was dissolved in Et2O (18 ml) and dry HCl was passed through the solution. Precipitate of MDMA HCl was filtered off, dried and homogenised prior to analysis.

Leuckart method was performed according to the modified MDA synthesis procedure described by Elks and Hey [12]. Safrole bromination was carried out according to the procedure described by Biniecki and Krajewski [13]. Cyanoborohydride reduction (NaBH4CN) was performed according to the modified MDA synthesis procedure described by Shulgin and Shulgin [11]. Dissolving metal reduction (aluminium–mercury amalgam) was performed according to the procedure described by Shulgin and Shulgin [11]. Borohydride reduction (NaBH4) was performed as follows: aqueous solution (40%) of methylamine (2 ml) was added to a cold mixture of MDP-2-P (1.51 g) in MeOH (5 ml). The mixture was cooled to 20 8C and then NaBH4 (30 mg) was slowly added. After dissolving of reductive agent, reaction mixture was left at 20 8C for 2 h. The addition of NaBH4 was repeated three times, in portions of 30, 30 and 40 mg, and reaction mixture was left at 20 8C for 24 h. Methanol was evaporated, 10% HCl (10 ml) was added to a residue and the solution was washed with CH2Cl2 (3 ml x 8 ml). The organic solution was extracted with 10% HCl, combined aqueous layers were alkalized with 25% NaOH (~10 ml) and extracted with CH2Cl2 (3 ml x 10 ml). Combined extracts were dried over MgSO4, evaporated, a residue was dissolved in Et2O (18 ml) and dry HCl was passed through the solution. Precipitate of MDMA HCl was filtered off, dried and homogenised prior to analysis.

=== Extraction of impurities ===

Two hundred milligrams of MDMA HCl was dissolved in 2 ml of buffer. Two different buffers, phosphate buffer, pH 7, and carbonate buffer, pH 10, were tested. The suspension was vigorously shaken (25 min) following by the addition of 200 ml of ''n''-heptane, containing diphenylamine as an internal standard, and then again shaken (25 min). The extracts were subjected to GC/MS analysis and impurity profiles were obtained.

@@ Line 74: / Line 74: @@
 === Synthesis ===
-,4-Methylenedioxyphenyl-2-propanone (MDP-2-P) was synthesized by two different routes, i.e. by oxidation of isosafrole in an acid medium and by reduction of 1-(3,4- methylenedioxyphenyl)-2-nitropropene which was previously prepared by condensation of piperonal and nitroethane. The syntheses were performed according to the procedures described by Shulgin and Shulgin [11]. Subse- quently, MDP-2-P, prepared by the oxidation of isosafrole, was used in Leuckart reaction, cyanoborohydride reduction, dissolving metal reduction and borohydride reduction in low temperature. MDP-2-P prepared by the reduction of 1-(3,4- methylenedioxyphenyl)-2-nitropropene was only subjected to borohydride reduction in low temperature.
+,4-Methylenedioxyphenyl-2-propanone (MDP-2-P) was synthesized by two different routes, i.e. by oxidation of isosafrole in an acid medium and by reduction of 1-(3,4-methylenedioxyphenyl)-2-nitropropene which was previously prepared by condensation of piperonal and nitroethane. The syntheses were performed according to the procedures described by Shulgin and Shulgin [11]. Subsequently, MDP-2-P, prepared by the oxidation of isosafrole, was used in Leuckart reaction, cyanoborohydride reduction, dissolving metal reduction and borohydride reduction in low temperature. MDP-2-P prepared by the reduction of 1-(3,4-methylenedioxyphenyl)-2-nitropropene was only subjected to borohydride reduction in low temperature.
-Leuckart method was performed according to the mod- ified MDA synthesis procedure described by Elks and Hey [12]. Safrole bromination was carried out according to the procedure described by Biniecki and Krajewski [13]. Cyanoborohydride reduction (NaBH<sub>4</sub>CN) was performed according to the modified MDA synthesis procedure described by Shulgin and Shulgin [11]. Dissolving metal reduction (aluminium–mercury amalgam) was performed according to the procedure described by Shulgin and Shulgin [11]. Borohydride reduction (NaBH<sub>4</sub>) was performed as follows: aqueous solution (40%) of methylamine (2 ml) was added to a cold mixture of MDP-2-P (1.51 g) in MeOH (5 ml). The mixture was cooled to  20 8C and then NaBH<sub>4</sub> (30 mg) was slowly added. After dissolving of reductive agent, reaction mixture was left at  20 8C for 2 h. The addition of NaBH<sub>4</sub> was repeated three times, in portions of 30, 30 and 40 mg, and reaction mixture was left at  20 8C for 24 h. Methanol was evaporated, 10% HCl (10 ml) was added to a residue and the solution was washed with CH2Cl2 (3 ml x 8 ml). The organic solution was extracted with 10% HCl, combined aqueous layers were alkalized with 25% NaOH (~10 ml) and extracted with CH2Cl2 (3 ml x 10 ml). Combined extracts were dried over MgSO4, evaporated, a residue was dissolved in Et<sub>2</sub>O (18 ml) and dry HCl was passed through the solution. Precipitate of MDMA HCl was filtered off, dried and homogenised prior to analysis.
+Leuckart method was performed according to the modified MDA synthesis procedure described by Elks and Hey [12]. Safrole bromination was carried out according to the procedure described by Biniecki and Krajewski [13]. Cyanoborohydride reduction (NaBH<sub>4</sub>CN) was performed according to the modified MDA synthesis procedure described by Shulgin and Shulgin [11]. Dissolving metal reduction (aluminium–mercury amalgam) was performed according to the procedure described by Shulgin and Shulgin [11]. Borohydride reduction (NaBH<sub>4</sub>) was performed as follows: aqueous solution (40%) of methylamine (2 ml) was added to a cold mixture of MDP-2-P (1.51 g) in MeOH (5 ml). The mixture was cooled to  20 8C and then NaBH<sub>4</sub> (30 mg) was slowly added. After dissolving of reductive agent, reaction mixture was left at  20 8C for 2 h. The addition of NaBH<sub>4</sub> was repeated three times, in portions of 30, 30 and 40 mg, and reaction mixture was left at  20 8C for 24 h. Methanol was evaporated, 10% HCl (10 ml) was added to a residue and the solution was washed with CH2Cl2 (3 ml x 8 ml). The organic solution was extracted with 10% HCl, combined aqueous layers were alkalized with 25% NaOH (~10 ml) and extracted with CH2Cl2 (3 ml x 10 ml). Combined extracts were dried over MgSO4, evaporated, a residue was dissolved in Et<sub>2</sub>O (18 ml) and dry HCl was passed through the solution. Precipitate of MDMA HCl was filtered off, dried and homogenised prior to analysis.
 === Extraction of impurities ===
 Two hundred milligrams of MDMA HCl was dissolved in 2 ml of buffer. Two different buffers, phosphate buffer, pH 7, and carbonate buffer, pH 10, were tested. The suspension was vigorously shaken (25 min) following by the addition of 200 ml of ''n''-heptane, containing diphenylamine as an internal standard, and then again shaken (25 min). The extracts were subjected to GC/MS analysis and impurity profiles were obtained.