Introduction
N-Ethyl-nor-pentedrone (also known as N-Ethylpentedrone, Ethyl-pentedrone or more commonly, NEP) is a lesser-known novel stimulant substance of the cathinone class that produces stimulating, euphoric, and mildly entactogenic effects when administered.
NEP shares a close structural relationship to its parent compound pentedrone, differing by an addition ethyl group on the terminal nitrogen on the carbon chain. This addition reportedly makes it about three times as potent as pentedrone. NEP is also closely related to N-Ethylhexedrone (commonly known as Hexen), and has been reported as producing largely-similar effects.
NEP shares a close structural relationship to its parent compound pentedrone, differing by an addition ethyl group on the terminal nitrogen on the carbon chain. This addition reportedly makes it about three times as potent as pentedrone. NEP is also closely related to N-Ethylhexedrone (commonly known as Hexen), and has been reported as producing largely-similar effects.
NEP first became known in the research chemical market during 2016. It is an example of a contemporary designer drug specifically chosen to mimic/replace the functional and structural features of its popular potent and short-lived-type stimulant predecessors, which are sometimes imprecisely referred to as "bath salts".
The synthesis of N-ethylpentedrone, a synthetic cathinone known for its stimulant properties, has garnered significant interest within both scientific and clandestine research communities due to its structural and functional similarities to other psychoactive compounds. This article outlines a comprehensive, step-by-step synthesis process for N-ethylpentedrone. The synthesis involves two main phases: the bromination of 1-phenylpentan-1-one and its subsequent amination with ethylamine to yield the final product, N-ethylpentedrone hydrochloride. Detailed descriptions of equipment and glassware required.
Difficulty rating: 4/10 The synthesis of N-ethylpentedrone, a synthetic cathinone known for its stimulant properties, has garnered significant interest within both scientific and clandestine research communities due to its structural and functional similarities to other psychoactive compounds. This article outlines a comprehensive, step-by-step synthesis process for N-ethylpentedrone. The synthesis involves two main phases: the bromination of 1-phenylpentan-1-one and its subsequent amination with ethylamine to yield the final product, N-ethylpentedrone hydrochloride. Detailed descriptions of equipment and glassware required.
N-Ethylpentedrone Synthesis From 1-Phenylpentan-1-one
Equipment and glassware:
- 2 L and 500 ml three-necked round bottom flasks;
- Funnel;
- Rotory evaporator;
- Vacuum pump;
- Buchner flask and funnel;
- Beakers 5L; 2l x2; 500 ml x3; 100 ml x3;
- Measuring cylinder 1 L and 20 ml;
- Laboratory grade thermometer (20 °C to 200 °C) with flask adapter;
- Magnetic stirrer;
- Laboratory scale (0.1 g-1 kg is suitable);
- HCl gas apparatus;
Reagents:
- 1-Phenylpentan-1-one (CAS 1009-14-9) 48.6g, 0.3 mol;
- Bromine (Br2), 16 mL, 0.3 mol;
- Dichloromethane (DCM) 2500 mL;
- Saturated Na2CO3 2000 mL solution;
- Saturated Na2S2O3 (2000 mL) solution;
- Ethylmine aqueous solution (37.32 g; 1.2 mol);
- Ethyl ether (or dioxane);
General Procedure for 1-Phenylpentan-1-one Bromination
1. Bromine (Br2, 16 mL, 0.3 mol) was added to a solution of 1-phenylpentan-1-one (48.6g, 0.3 mol) in dichloromethane (500 mL) in 2 L round bottom flask.
2. After stirring for 2 h, the reaction mixture is poured into dichloromethane 2000 mL in 5 L beaker, and the mixture washed successively with saturated Na2CO3 2000 mL solution, saturated Na2S2O3 (2000 mL) solution.
3. Layers are separated.
4. Organic layer is distilled off to dryness, affording 1-phenyl-2-bromopentan-1-one.
5. Optional: When necessary, 1-phenyl-2-bromopentan-1-one was purified by flash chromatography, using n-hexane/AcOEt mixtures as eluent.
2. After stirring for 2 h, the reaction mixture is poured into dichloromethane 2000 mL in 5 L beaker, and the mixture washed successively with saturated Na2CO3 2000 mL solution, saturated Na2S2O3 (2000 mL) solution.
3. Layers are separated.
4. Organic layer is distilled off to dryness, affording 1-phenyl-2-bromopentan-1-one.
5. Optional: When necessary, 1-phenyl-2-bromopentan-1-one was purified by flash chromatography, using n-hexane/AcOEt mixtures as eluent.
General Procedure for Amination of 1-Phenyl-2-bromopentan-1-one
6. Ethylmine aqueous solution (37.32 g; 1.2 mol) was added dropwise to 1-phenyl-2-bromopentan-1-one (72.34 g, 0.3 mol) in 500 mL round bottom flask.
7. After stirring overnight at room temperature, the mixture was distilled off to dryness, affording N-ethylpentedrone free base.
8. Optional: When necessary, products were purified by flash chromatography, using CH2Cl2 /MeOH mixtures as eluent.
9. HCl gas was bubbled for 2 min in ethanol solutions of the pure N-ethylpentedrone free base to slightly acidic pH 5.
10. Solvent was removed under reduced pressure and dry N-ethylpentedrone hydrochloride was washed with ethyl ether (or dioxane), affording pure N-ethylpentedrone hydrochloride. The yield is 70-75%.
7. After stirring overnight at room temperature, the mixture was distilled off to dryness, affording N-ethylpentedrone free base.
8. Optional: When necessary, products were purified by flash chromatography, using CH2Cl2 /MeOH mixtures as eluent.
9. HCl gas was bubbled for 2 min in ethanol solutions of the pure N-ethylpentedrone free base to slightly acidic pH 5.
10. Solvent was removed under reduced pressure and dry N-ethylpentedrone hydrochloride was washed with ethyl ether (or dioxane), affording pure N-ethylpentedrone hydrochloride. The yield is 70-75%.
Source
de Mello-Sampayo, Cristina, et al. "Designer cathinones N-ethylhexedrone and buphedrone show different in vitro neurotoxicity and mice behaviour impairment." Neurotoxicity Research 39 (2021): 392-412. https://link.springer.com/article/10.1007/s12640-020-00229-6
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