Phenylacetone (P2P) Synthesis via BMK Ethyl Glycidate

Advantages of P2P via BMK Ethyl Glycidate Conversion Way

This phenylacetone (P2P; BMK oil ) synthesis approach is a simple way how to get phenylacetone from BMK ethyl glycidate and its synthesis from benzaldehyde. PMK ethyl glycidate can be hydrolyzed into P2P. This reaction isn't sensitive to water like BMK methyl glycidate synthesis. There is such advantage like a quite high yield conversion (82% from benzaldehyde to P2P). Moreover, the reaction doesn't take any elaborated equipment and can be easily scailed.

Equipment and glassware:

• Four necked round bottom reaction flask 3 L , equipped with reflux condenser , top stirrer and pressure equalized drip funnel 250 mL ;
• Funnel;
• Retort stand and clamp for securing apparatus ;
• pH indicator paper;
• Water/ oil bath;
• Retort stand and clamp for securing apparatus ;
• Laboratory grade thermometer (up to 10 - 100 °С);
• Glass rod;
• Silicone hoses;
• Measuring cylinder s for 100 mL and 1 L;
• Laboratory scale (1-200 g is suitable);
• Glass rod;
• Beakers 3 L; 1 L x2; 500 ml x2;
• Separatory funnel 2 L;

Reagents:

• Dimethylformamide 900 ml;
• Benzaldehyde 300 ml;
• Ethyl 2-chloropropionate 540 g;
• Benzyltriethylammonium chloride (TEBAC) 32 g;
• Potassium carbonate 780 g;
• Sodium hydroxide (NaOH) 135 g;
• Distilled water ~1.9 L ;
• Concentrated (37%) aqueous hydrochloric acid (HCl) ~250 mL ;

BMK Ethyl Glycidate Synthesis From Benzaldehyde

• 1. Dimethylformamide 900 ml is poured into a 3 L four necked round bottom reaction flask, equipped with reflux condenser, top stirrer and drip funnel.
• 2. Then, benzaldehyde 300 ml is added. A top stirrer is turned on.
• 3. Ethyl 2-chloropropionate 540 g is poured into the reactor. Benzyltriethylammonium chloride (TEBAC) catalyst 32 g is added. Next, potassium carbonate 780 g is added into the reaction mixture.
• 4. A heating of the water or oil bath is set at 40°C.
• 5. Reaction mixture is stirred for 48 h on the warm bath.
• 6. Sodium hydroxide (NaOH) 30% water solution 450 ml is prepared in advance.
• 7. After 48h, the stirrer is turned off. Reaction mixture (liquid layer without sediment) is decanted into a large beaker.
• 8. Pure distilled water 1 L is poured into the beaker and mix thoroughly.
• 9. A glycidate ester layer (BMK ethyl glycidate) is separated down. Layers are separated with help of separatory funnel.
  

Note: Glycidate ester (BMK Ethyl Glycidate) is used in following reactions without purification. If a chemist wants to use it as a product, he has to distill it from side reaction products due to an excess of ethyl 2-chloropropionate.

BMK Glycidic Acid Sodium Salt (BMK Powder CAS 5449-12-7) Synthesis BMK Ethyl Glycidate 

• 10. Glycidic ester (BMK ethyl glycidate; CAS: 41232-97-7) is loaded back into the clean reaction flask.
• 11. The previously prepared and cooled NaOH sln. is poured into the drip funnel.
• 12. The stirrer is turned on. NaOH 30% aq. Solution 450 mL is slowly added to the reaction mixture. A reaction mixture temperature ha s to be maintained below <30°C.
• 13. Next, the reaction mixture is stirred for 12 h at room temperature.
• 14. After a while, distilled water 500 ml is added and the mixture is heated a little (no more than 60°C).
• 15. Benzene, toluene or other similar solvent 500 ml is poured into the heated reaction mixture.
• 16. The stirrer is turned off. The layers are formed.
• 17. With help of the separating funnel, the reaction by-products are extracted (not previously distilled ester by-product s ). The water layer with dissolved BMK g lycidic a cid sodium salt ( BMK Powder ) is separated back into the flask. BMK sodium salt is BMK powder (same subastance CAS 5449-12-7).

Phenylacetone (P2P) Synthesis From BMK Glycidic Acid (Sodium Salt)

BMK powder to BMK oil ( Phenylacetone; P2P; CAS 103-79-7)

• 18. Using the drip funnel, concentrated (37%) aqueous hydrochloric acid (HCl) is carefully poured into the flask with BMK powder ( CAS 5449-12-7 ) to reach pH1.
• 19. The mixture is heated to 60°C and decarboxylated with constant stirring for 5 h.
• 20. Then, the stirrer is turned off and the mixture is separated into two layers. BMK oil layer is a top layer.
• Note: If the mixture is cooled down, BMK oil layer will be at the bottom.
• 21. BMK layer is separated into a beaker using separatory funnel for further syntheses.

Note: After a while, remaining water in the beaker is completely separated from BMK oil (Phenylacetone; P2P; CAS 103-79-7) .

BMK oil yield is ~300 ml (82%) .

Conclusion

The synthesis of phenylacetone (P2P) through BMK Ethyl Glycidate presents a practical and efficient approach for chemical conversion. This method offers several advantages, including high yield, straightforward procedures, and minimal equipment requirements, making it suitable for scaled-up applications. The multi-step process, beginning from benzaldehyde and proceeding through BMK Ethyl Glycidate and its sodium salt derivative, provides a reliable pathway to obtain BMK oil. Due to its relatively mild reaction conditions and the stability of intermediates, this route has become a preferred option in laboratory settings where efficiency and reproducibility are critical.

Sources

1. United Nations Office on Drugs and Crime (UNODC). Recommended Methods for the Identification and Analysis of Amphetamine, Methamphetamine and Their Ring-Substituted Analogues in Seized Materials. United Nations, New York, 2006.
2. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Precursors and Pre-precursors Used in the Illicit Manufacture of Drugs. Technical Report, EMCDDA, 2020.
3. Merck Index, 15th Edition. An Encyclopedia of Chemicals, Drugs, and Biologicals. Royal Society of Chemistry, 2013.
4. Sigma-Aldrich. Product Information and Safety Data Sheets for BMK Ethyl Glycidate and Related Chemicals.
   
5. Chemical Abstracts Service (CAS). Registry Numbers and Substance Information for BMK Ethyl Glycidate (CAS 41232-97-7), BMK Powder (CAS 5449-12-7), and Phenylacetone (CAS 103-79-7).
   
6. Vogel, A. I. Vogel’s Textbook of Practical Organic Chemistry, 5th Edition. Longman Scientific & Technical, 1989.