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<nomobile>{{decree|type=delete|message=MDMA, its synthesis and most of its precursors are illegal in most parts of the world. If you do not have | <nomobile>{{decree|type=delete|message=MDMA, its synthesis and most of its precursors are illegal in most parts of the world. If you do not have exceptional chemistry experience and lack an appropriate approval from the respective drug enforcement agency in your country, do not follow and apply the methods as outlined here. This material is educational, and we are in no way responsible for your actions.}}</nomobile> | ||
{{Decree/SynthesisProtection}} | {{Decree/SynthesisProtection}} | ||
=== Registry numbers === | === Registry numbers === | ||
Note that some of these CAS numbers have been removed, but still hold value when obtaining compounds (i.e. at | Note that some of these CAS numbers have been removed, but still hold value when obtaining compounds (i.e. at Sigma-Aldrich). | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
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=== Synthesis === | === Synthesis === | ||
* From piperonal (with nitromethane) to the | * From piperonal (with nitromethane) to the nitroethylene; (with electrolytic reduction) to MDPEA (Tanaka and Midzuno, 1929). | ||
* From 3,4-methylenedioxybenzaldehyde (with malonic acid) to 3,4-methylenedioxycin namic acid; (with Na, Hg) to 3,4-methylenedioxypropionic acid; (with NH3) to 3,4-methyl enedioxypropionamide; (with NaOCl) to MDPEA (Slotta and Heller, 1930). | * From 3,4-methylenedioxybenzaldehyde (with malonic acid) to 3,4-methylenedioxycin namic acid; (with Na, Hg) to 3,4-methylenedioxypropionic acid; (with NH3) to 3,4-methyl enedioxypropionamide; (with NaOCl) to MDPEA (Slotta and Heller, 1930). | ||
* From 3,4-methylenedioxyhydrocinnamamide (Kindler, 1931). | * From 3,4-methylenedioxyhydrocinnamamide (Kindler, 1931). | ||
* From piperonal (with nitromethane) to the | * From piperonal (with nitromethane) to the nitroethylene; (with Pd, H2) to MDPEA (Schales, 1935a; Maurer and Schiedt, 1935). | ||
* Synthesis by catalytic hydrogenation of homopiperonyloximine (Schales 1935b). | * Synthesis by catalytic hydrogenation of homopiperonyloximine (Schales 1935b). | ||
* From piperonal (with nitromethane) to the | * From piperonal (with nitromethane) to the nitroethylene; (with LAH) to MDPEA (Erne and Ramirez, 1950; Dallacker et al., 1971). | ||
* From piperonal (with nitromethane) to the | * From piperonal (with nitromethane) to the nitroethylene; (with Raney Ni, or Raney Co, H2) to MDPEA (Reeve and Eareckson, 1950). | ||
* From piperonal (with malonic acid) to 3,4-methylenedioxycinnamic acid; (with Pd, H2) to 3,4-methylenedioxyphenylpropionic acid; (with SOCL2, NH3) to 3,4- | * From piperonal (with malonic acid) to 3,4-methylenedioxycinnamic acid; (with Pd, H2) to 3,4-methylenedioxyphenylpropionic acid; (with SOCL2, NH3) to 3,4-methylenedioxyphenylpropionamide; (with aq. KOCI ) to MDPEA (Habermehl and Khalique, 1967). | ||
* Synthesis by reduction of the 2-nitrophenylethane with Fe powder in ethanol in the presence of ammonium chloride (Ran et al., 2000). | * Synthesis by reduction of the 2-nitrophenylethane with Fe powder in ethanol in the presence of ammonium chloride (Ran et al., 2000). | ||
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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.<ref name="pihkal">Al. Shulgin, A. Shulgin, PIHKAL—A Chemical Love Story, Transform Press, Berkeley, 1991.</ref> 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. | 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.<ref name="pihkal">Al. Shulgin, A. Shulgin, PIHKAL—A Chemical Love Story, Transform Press, Berkeley, 1991.</ref> 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 modified MDA synthesis procedure described by Elks and Hey.<ref>J. Elks, D.H. Hey, b-3,4-Methylenedioxyphenylisopropylamine, J. Chem. Soc. 55 (1943) 15–16.</ref> Safrole bromination was carried out according to the procedure described by Biniecki and Krajewski.<ref>S. Biniecki, E. Krajewski, Production of D,L-N-methyl-b-(3,4-methylenedioxyphenyl)-isopropylamine and D,L-N-methyl-β-(3,4-dimethoxyphenyl)-isopropylamine, Acta Pol. Pharm. XVII (1960) 421–425.</ref> Cyanoborohydride reduction (NaBH<sub>4</sub>CN) was performed according to the modified MDA synthesis procedure described by Shulgin and Shulgin.<ref name="pihkal"/> Dissolving metal reduction (aluminium–mercury amalgam) was performed according to the procedure described by Shulgin and Shulgin.<ref name="pihkal"/> 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 | Leuckart method was performed according to the modified MDA synthesis procedure described by Elks and Hey.<ref>J. Elks, D.H. Hey, b-3,4-Methylenedioxyphenylisopropylamine, J. Chem. Soc. 55 (1943) 15–16.</ref> Safrole bromination was carried out according to the procedure described by Biniecki and Krajewski.<ref>S. Biniecki, E. Krajewski, Production of D,L-N-methyl-b-(3,4-methylenedioxyphenyl)-isopropylamine and D,L-N-methyl-β-(3,4-dimethoxyphenyl)-isopropylamine, Acta Pol. Pharm. XVII (1960) 421–425.</ref> Cyanoborohydride reduction (NaBH<sub>4</sub>CN) was performed according to the modified MDA synthesis procedure described by Shulgin and Shulgin.<ref name="pihkal"/> Dissolving metal reduction (aluminium–mercury amalgam) was performed according to the procedure described by Shulgin and Shulgin.<ref name="pihkal"/> 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°C and then NaBH<sub>4</sub> (30 mg) was slowly added. After dissolving of the reductive agent, the reaction mixture was left at -20°C for two hours. The addition of NaBH<sub>4</sub> was repeated three times, in portions of 30, 30 and 40 mg, and the reaction mixture was left at -20°C 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 CH<sub>2</sub>Cl<sub>2</sub> (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. The precipitate of MDMA HCl was filtered off, dried and homogenized before analysis. | ||
=== Extraction of impurities === | === 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. | 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. | ||
<references/> | <references/> | ||
Revision as of 22:01, 26 April 2017
 |
MDMA, its synthesis and most of its precursors are illegal in most parts of the world. If you do not have exceptional chemistry experience and lack an appropriate approval from the respective drug enforcement agency in your country, do not follow and apply the methods as outlined here. This material is educational, and we are in no way responsible for your actions. |
 |
This manual is protected. It was independently verified and is fully based on publicly available publications. |
Registry numbers
Note that some of these CAS numbers have been removed, but still hold value when obtaining compounds (i.e. at Sigma-Aldrich).
| Name | CAS# | DEA# |
|---|---|---|
| HCI salt | [64057-70-1] | 7405 |
| Freebase | [42542-10-9] | |
| R-(-)-Isomer HCI salt | [69558-31-2] | |
| S-(+)-Isomer HCI salt | [69558-32-3] | |
| R-(-)-Isomer freebase | [81262-70-6] | |
| S-(+)-Isomer freebase | [66142-89-0] | |
| [d5]-MDMA | [136765-43-0] | |
| N-CH2-[3H]-labeled | [128671-19-2] | |
| N-[11C]-Me | [153506-20-8] | |
| R-Isomer N-[11C]-Me | [165172-59-8] |
Synthesis
Shulgin
Synthesis
- From piperonal (with nitromethane) to the nitroethylene; (with electrolytic reduction) to MDPEA (Tanaka and Midzuno, 1929).
- From 3,4-methylenedioxybenzaldehyde (with malonic acid) to 3,4-methylenedioxycin namic acid; (with Na, Hg) to 3,4-methylenedioxypropionic acid; (with NH3) to 3,4-methyl enedioxypropionamide; (with NaOCl) to MDPEA (Slotta and Heller, 1930).
- From 3,4-methylenedioxyhydrocinnamamide (Kindler, 1931).
- From piperonal (with nitromethane) to the nitroethylene; (with Pd, H2) to MDPEA (Schales, 1935a; Maurer and Schiedt, 1935).
- Synthesis by catalytic hydrogenation of homopiperonyloximine (Schales 1935b).
- From piperonal (with nitromethane) to the nitroethylene; (with LAH) to MDPEA (Erne and Ramirez, 1950; Dallacker et al., 1971).
- From piperonal (with nitromethane) to the nitroethylene; (with Raney Ni, or Raney Co, H2) to MDPEA (Reeve and Eareckson, 1950).
- From piperonal (with malonic acid) to 3,4-methylenedioxycinnamic acid; (with Pd, H2) to 3,4-methylenedioxyphenylpropionic acid; (with SOCL2, NH3) to 3,4-methylenedioxyphenylpropionamide; (with aq. KOCI ) to MDPEA (Habermehl and Khalique, 1967).
- Synthesis by reduction of the 2-nitrophenylethane with Fe powder in ethanol in the presence of ammonium chloride (Ran et al., 2000).
M. Swist, J. Wilamowski, A. Parczewski
The following procedures are extracted from (Swist, Wilamowski, Parczewski; 2004).[1]
Chemicals and reagents
In the synthesis of MDMA, the following reagents were used:
- formic acid (98%)
- hydrochloric acid (36–38%)
- methylene chloride
- sodium hydroxide
- acetic acid (99.5%)
- acetone
- diethyl ether
- toluene
- isopropanol
- hydrogen peroxide (~33%)
- sulfuric acid (95%) (all POCh, Poland, analytical grade)
- piperonal (99%, Aldrich, for synthesis)
- isosafrole (97%, Aldrich, for synthesis)
- safrole (97%, Aldrich, for synthesis)
- nitroethane (96%, Aldrich, for synthesis)
- cyclohexylamine (99%, Aldrich, for synthesis)
- ethyl formate (97%, Aldrich, for synthesis)
- hydrobromic acid (62%, Aldrich, analytical grade)
- methylamine solution (33% in abs. ethyl alcohol, Aldrich, analytical grade)
- methylamine aqueous solution (40%, Aldrich, analytical grade)
- diethyl ether (anhydrous, >99%, Aldrich, A.C.S. Reagent)
- methanol (Merck, HPLC grade)
- NaBH4 (Aldrich, for synthesis)
- NaBH3(CN) (Aldrich, for synthesis).
In impurity profiling experiments, the following reagents were used:
- carbonate buffer, pH 10 (10.7 ml, 0.1 M NaOH; 50 ml, 0.05 M NaHCO3; 39.3 ml H2O)
- n-heptane (Aldrich, HPLC grade)
- phosphate buffer, pH 7 (Merck)
- diphenylamine (Supelco, used as internal standard).
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.[2] 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 modified MDA synthesis procedure described by Elks and Hey.[3] Safrole bromination was carried out according to the procedure described by Biniecki and Krajewski.[4] Cyanoborohydride reduction (NaBH4CN) was performed according to the modified MDA synthesis procedure described by Shulgin and Shulgin.[2] Dissolving metal reduction (aluminium–mercury amalgam) was performed according to the procedure described by Shulgin and Shulgin.[2] 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°C and then NaBH4 (30 mg) was slowly added. After dissolving of the reductive agent, the reaction mixture was left at -20°C for two hours. The addition of NaBH4 was repeated three times, in portions of 30, 30 and 40 mg, and the reaction mixture was left at -20°C 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. The precipitate of MDMA HCl was filtered off, dried and homogenized before 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.
- ↑ Świst, M., Wilamowski, J., & Parczewski, A. (2005). Basic and neutral route specific impurities in MDMA prepared by different synthesis methods: Comparison of impurity profiles. Forensic Science International, 155(2–3), 100–111. https://doi.org/10.1016/j.forsciint.2004.11.003
- ↑ 2.0 2.1 2.2 Al. Shulgin, A. Shulgin, PIHKAL—A Chemical Love Story, Transform Press, Berkeley, 1991.
- ↑ J. Elks, D.H. Hey, b-3,4-Methylenedioxyphenylisopropylamine, J. Chem. Soc. 55 (1943) 15–16.
- ↑ S. Biniecki, E. Krajewski, Production of D,L-N-methyl-b-(3,4-methylenedioxyphenyl)-isopropylamine and D,L-N-methyl-β-(3,4-dimethoxyphenyl)-isopropylamine, Acta Pol. Pharm. XVII (1960) 421–425.