Introduction
Helional [CAS 1205-17-0] is rather interesting substance, which can serve as MDA precursor in the represented simple synthesis. In addition, it has opportunity to become a new MDMA precursor in case MDA conversion to MDMA. BB Forum team are working on this issue after recent China's government ban of PMK glycidate esters.Difficulty rating: 5/10
Reagents:
- Helional (6.00g, 31.22 mmol) [CAS 1205-17-0];
- Ethanol 10 ml;
- Sodium carbonate (Na2CO3) 7.6 ml, 32% w/v, 22.64 mmol water sln;
- Hydroxylamine hydrochloride (NH2OH*Hcl) 6.6 ml, 49% w/v, 46.91 mmol;
- Distilled water 240 ml;
- Brine (NaCl aq solution) 125 ml;
- Anhydrous sodium sulphate (Na2SO4);
- Xylene 20 ml;
- Nickel (2) acetate tetrahydrate 144 mg, 0.58 mmol;
- Dichloromethane (DCM) 460 ml;
- Sodium hydroxide (NaOH) 1.45 ml, 10.61 mmol;
- Trichloroisocyanuric acid (149.9 mg, 0.65 μmol);
- Anhydrous ether 10 ml;
- Hydrogen chloride solution (1 ml, 2 M in diethyl ether);
Equipment and glassware:
- Round bottom flask 100 ml;
- Separating funnel 250 ml;
- Beakers (200 ml x2, 100 ml x 4, 50 ml x2);
- Dropping funnnel 100 ml;
- Heating plate with magnetic stirrer;
- Rotary evaporator;
- Retort stand and clamp for securing apparatus;
- Petri dishes;
- Reflux condenser;
- Conical flask 250 ml;
- Measuring cilinder 100 ml;
- Vacuum source;
- Laboratory scale (0.1-200 g is suitable);
- Cold water bath;
- Glass rod and spatula;
- Laboratory grade thermometer;
- Suction (vacuum) filtration setup;
- Hirsh funnel (optional);
MDA Synthesis From Helional
Synthesis
1. a-Methyl-1,3-benzodioxole-5-propanal oxime
Helional (1) (6.00g, 31.22 mmol) [CAS 1205-17-0] was dissolved in ethanol 10 ml in 100 ml round bottom flask and an aqueous solution prepared from sodium carbonate (7.6 ml, 32% w/v, 22.64 mmol) and hydroxylamine hydrochloride (6.6 ml, 49% w/v, 46.91 mmol) was added dropwise using a dropping funnnel. The mixture was stirred at room temperature for 19 h. The reaction mixture was poured into a separating funnel, water 25 ml was added, and then extracted using dichloromethane 3 x 30 ml. The organic layers was washed with distilled water 25 ml and brine 25 ml, dried over anhydrous sodium sulphate and filtered under vacuum. Solvent was removed using a rotary evaporator. The crude product obtained was a dark orange transparent oil. Upon standing, the oil crystallised to give a yellow-orange solid (2) 5.97-6.30 g.
2. a-Methyl-1,3-benzodioxole-5-propanamide
a-Methyl-1,3-benzodioxole-5-propanal oxime (2) (5.00 g, 24.13 mmol) was dissolved in xylene 20 ml and nickel (2) acetate tetrahydrate (144 mg, 0.58 mmol) was added. The mixture was heated under reflux at 140°C for 5h with stirring. After cooling, the solution was transferred to a conical flask and dichloromethane 200 ml was added. The reaction mixture was divided into four portions, and each was added to distilled water 25 ml and extracted with dichloromethane 2 x 20 ml. The organic layer was washed with distilled water 25 ml and brine 25 ml, dried over anhydrous sodium sulfate and filtered under vacuum. The organic layers were combined, and the solvent was removed using a rotary evaporator. The crude product was a light-brown solid. The crude product was purified by triturating with dichloromethane to produce a white fluffy solid (3) (3.82-4.88g).
3.1 3,4-Methylenedioxyamphetamine (MDA) (4)
Synthesis using trichloroisocyanuric acid. a-Methyl-1,3-benzodioxole-5-propanamide (3) (0.4 g, 1.92 mmol) was dissolved in watter 14 ml, NaOH (1.45 ml, 10.61 mmol) was added dropwise and stirred for 15 min on ice at 0°C. Trichloroisocyanuric acid (149.9 mg, 0.65 μmol) was added, and the reaction mixture was left on ice at 0°C for an additional 1 h. The reaction mixture was then brought to room temperature, then 75°C and held for 30 min. The reaction mixture was poured into a separating funnel and extracted with dichloromethane 3 x 30 ml. The organic layer was washed with de-ionised water 25 ml and brine 25 ml, dried over anhydrous sodium sulfate and filtered under vacuum. The organic layers were combined, and solvent was removed using the rotary evaporator. The synthesised crude MDA was a brown transparent oil (4) (286.4 — 351.5 mg).
Optional ways 3.2 and 3.3:
3.2 3,4-Methylenedioxyamphetamine (MDA) synthesis using sodiun hypochlorite.
Purified a-methyl-1,3-benzodioxole-5-propanamide (3) (0.4 g, 1.92 mmol) dissolved in water 14 ml, NaOH (1.45 ml, 10.61 mmol) was added dropwise and stirred for 15 min on ice at 0°C. Sodium hypochlorite solution (6.4 ml, 94.3 mmol) was added, and the reaction muxture was left on ice at 0°C for an additional 1 h. The reaction mixture was then brought to room temperature then 75°C and held for 30 min. The reaction mixture was poured into a separating funnel and extracted with dichloromethane 3 x 30 ml. The organic layer was then washed with de-ionised water 25 ml and brine 25 ml, dried over anhydrous sodium sulfate and filtered under vacuum. The organic layers were combined, and solvent was removed using the rotary evaporator. The final product was a black-brown soil (4) (248.1-293.3 mg).
3.3 3,4-Methylenedioxyamphetamine (MDA) synthesised in alcoholic solution
Pure a-methyl-1,3-benzodioxole-5-propanamide (3) (0.4 g, 1.92 mmol) was dissolved in water 12.6 ml and alcohol methanol or ethanol 1.4 ml, NaOH (1.45 ml, 10.61 mmol) was added dropwise and left to stir for 15 min on ice at 0°C. Trichloroisocyanuric acid (149.9 mg, 0.65 μmol) was added, and the reaction mixture was left on ice at 0°C for additional 1 h. The reaction mixture was then brought to room temperature then 75°C and held for 30 min. The reaction mixture was poured into a separating funnel and extracted with dichloromethane 3 x 30 ml. The organic layer was then wahshed with de-ionised water 25 ml and brine 25 ml, dried over anhydrous sodium sulfate and filtered under vacuum. The organic layers were combined, and solvent was removed using the rotary evaporator. The final product (4) was a brown transparent oil. From methanol: 307.1 mg. From ethanol: 265.7 mg.
4. 3,4-Methylenedioxyamphetamine (MDA) hydrochloride (5)
3,4-Methylenedioxyamphetamine (270.3-382.2 mg) (4) was dissolved in anhydrous ether 10 ml with stirring and hydrogen chloride solution (1 ml, 2 M in diethyl ether) was added dropwise. The resultant precipitate was filtered using a Hirsh funnel and washed with diethyl ether. Vacuum suction was applied for a further 5 min to draw air through the solid to assist in drying. When prepared from relatively pure MDA, the final product was an off-white powder (241-278.4 mg) and when prepared from the impure brown black MDA, a brown wax formed, When a wax was formed, the material was triturated with dichloromethane and filtered using a Hirsch funnel to give an off-white powder (5) (13.5-90.6 mg).
Source
- Mercieca, Alexandra L., et al. "Organic impurity profiling of 3, 4-methylenedioxyamphetamine (MDA) synthesised from helional." Forensic Science International 350 (2023): 111788. https://www.sciencedirect.com/science/article/abs/pii/S0379073823002384
