Introduction
Safrole laboratory synthesis from eugenol is described in this topic by reason of growing interest to alternative sources to safrole as MDMA precursor. Due to ban of PMK glycidates in China, safrole got more interest around clandestine chemists. This synthesis is not adjusted for large reaction yield but give an idea about procedures.
Difficulty rating: 4/10
Difficulty rating: 4/10
Equipment and glassware:
- Two necked round bottom flask 500 ml;
- Reflux condenser;
- Magnetic stirrer with heating plate;
- Funnel;
- Spatula;
- Laboratory scale (0.1 g-200 g is suitable);
- Measuring cylinders 100 ml and 20 ml;
- Rotory evaporator (optional);
- Beakers 500 ml x2; 100 ml x4; 50 ml x3;
- Pipette;
- Drip funnel 200 ml;
- Laboratory grade thermometer (0 °C to 200 °C) with flask adapter;
- Separating funnel 500 ml;
- Claisen adapter;
Reagents:
- Toluene 250 ml;
- Eugenol 8.01 g;
- Aluminum chloride (AlCl3) 8.8 g;
- Pyridine 18.2 g;
- Hydrochloric acid (HCl aq 23.3%) 6.4M 300 ml;
- Diethyl ether 450 ml;
- Distilled water 360 ml;
- Sodium sulphate (NaSO4) anhydrous;
- Dimethyl sulfoxide (DMSO) 60 ml;
- Dichloromethane (DCM) 20 ml;
- Potassium carbonate (K2CO3) 4.39 g;
Safrole Synthesis From Eugenol Scheme
4-Allylcatechol Synthesis From Eugenol
1. To the 500 ml two necked round bottom flask with a stirring bar, toluene 250 ml is added.
2. Eugenol 8.01 g is also added into the flask by a pipette followed by aluminum chloride (AlCl3) 8.8 g. After AlCl3 addition, the solid precipitate turns orange-reddish.
3. In the addition (or separatory, if you don’t have addition one) funnel, pyridine 18.2 g is poured.
4. Then, pyridine has to be added dropwise.
5. After that, the mixture is stirred well and refluxed for 5 hours with the reflux condenser. The solution started cloudy. Then got kind of orange, then went clear and then started to reflux. After 5 hours, it turned into dill looking beige with some blue sports around it.
6. The mixture is decanted into a 250 ml beaker.
7. The remainder solids are rinsed by HCl acid 6.4M 300 ml with an additional external heating.
8. The reaction mixture is transferred into the separatory funnel 500 ml and extracted by diethyl ether 3 x 100 ml.
9. Ether extract is washed by distilled water 3 x 100 ml and then dried over anhydrous NaSO4 for 10-15 min. Molecular sieves also can be used for drying.
10. Next, ether is distilled off. Color of the reaction mixture is changed during solvent evaporation. The product is deep purple liquid.
11. The mixture additionally undergone vacuum distillation to completely remove the solvents.
12. The yield of 4-allylcatechol is 3.88 g (52.9%).
2. Eugenol 8.01 g is also added into the flask by a pipette followed by aluminum chloride (AlCl3) 8.8 g. After AlCl3 addition, the solid precipitate turns orange-reddish.
3. In the addition (or separatory, if you don’t have addition one) funnel, pyridine 18.2 g is poured.
4. Then, pyridine has to be added dropwise.
5. After that, the mixture is stirred well and refluxed for 5 hours with the reflux condenser. The solution started cloudy. Then got kind of orange, then went clear and then started to reflux. After 5 hours, it turned into dill looking beige with some blue sports around it.
6. The mixture is decanted into a 250 ml beaker.
7. The remainder solids are rinsed by HCl acid 6.4M 300 ml with an additional external heating.
8. The reaction mixture is transferred into the separatory funnel 500 ml and extracted by diethyl ether 3 x 100 ml.
9. Ether extract is washed by distilled water 3 x 100 ml and then dried over anhydrous NaSO4 for 10-15 min. Molecular sieves also can be used for drying.
10. Next, ether is distilled off. Color of the reaction mixture is changed during solvent evaporation. The product is deep purple liquid.
11. The mixture additionally undergone vacuum distillation to completely remove the solvents.
12. The yield of 4-allylcatechol is 3.88 g (52.9%).
4-Allylcatechol Synthesis From Eugenol
Safrole Synthesis From 4-Allylcatechol
13. In the 100 ml round bottom flask, DMSO 50 ml and DCM 5 ml are added. Reflux condenser, pressure equalized drip funnel with Claisen adapter are installed.
14. 4-Allylcatechol is heated in order to make it more viscous and transferred into a beaker with help of DMSO 10 ml. The solution has beautiful violet blue color.
15. NaOH 2.5g or 4.39 g of K2CO3 (in case of NaOH absence) in water 10 ml. The solution is poured into the drip funnel.
16. The reaction mixture is heated up to 120℃, alkali solution adding is started. After complete alkali adding, 4-allylcatechol is added dropwise.
17. The reaction is refluxed for 2 hours. DCM 5-10 ml is added during reflux procedure.
18. Next, the reaction mixture is cooled down to room temperature and distilled water 50 ml is added.
19. The resulting mixture is decanted into the separatory funnel.
20. The mixture is extracted with 3 x 25 ml diethyl ether. Leftovers of the reaction mixture are moved from the reaction flask into the separatory funnel with the first extractant portion of ether.
21. Combined ether extract is dried over anhydrous NaSO4 and some molecular sieves.
22. Dried extract is decanted into the distillation flask.
23. The solvent is distilled off (rotovap can be used). The light brown oil is a resulting product on the distillation flask bottom.
14. 4-Allylcatechol is heated in order to make it more viscous and transferred into a beaker with help of DMSO 10 ml. The solution has beautiful violet blue color.
15. NaOH 2.5g or 4.39 g of K2CO3 (in case of NaOH absence) in water 10 ml. The solution is poured into the drip funnel.
16. The reaction mixture is heated up to 120℃, alkali solution adding is started. After complete alkali adding, 4-allylcatechol is added dropwise.
17. The reaction is refluxed for 2 hours. DCM 5-10 ml is added during reflux procedure.
18. Next, the reaction mixture is cooled down to room temperature and distilled water 50 ml is added.
19. The resulting mixture is decanted into the separatory funnel.
20. The mixture is extracted with 3 x 25 ml diethyl ether. Leftovers of the reaction mixture are moved from the reaction flask into the separatory funnel with the first extractant portion of ether.
21. Combined ether extract is dried over anhydrous NaSO4 and some molecular sieves.
22. Dried extract is decanted into the distillation flask.
23. The solvent is distilled off (rotovap can be used). The light brown oil is a resulting product on the distillation flask bottom.
Safrole Synthesis From 4-Allylcatechol
Steam Distillation of Safrole
24. Water 150 ml is added to the distillation flask. The mixture of safrole and water is heated up and steam distilled.
25. Safrole is extracted from the distilled solution by 3 x 25 ml diethyl ether.
26. The ether extract is dried over Na2SO4 and then decanted in fresh distillation flask.
27. Ether is evaporated. The yield of pure safrole is 1.04 g (24.8%).
25. Safrole is extracted from the distilled solution by 3 x 25 ml diethyl ether.
26. The ether extract is dried over Na2SO4 and then decanted in fresh distillation flask.
27. Ether is evaporated. The yield of pure safrole is 1.04 g (24.8%).
Sources
- Rao, Sethi, and Subba Rao. "Synthesis of 4-Allylcatechol & Mechanism of Claisen Rearrangement in Catechols." Ind. J. Chem 2 (1964): 323. https://www.erowid.org/archive/rhodium/chemistry/allylcatechol.html
-
Chemdelic
Unraveling the mysteries of chemistry. I am a chemistry student currently and want to learn and showcase the beautiful world of reactions. Take a seat and enjoy the ride through this digital journey into our world. For business inquiries: [email protected]
www.youtube.com
