Direct One-Pot Synthesis of Propofol from Paracetamol Tablets

Author(s)

Messina, Leonardo Costa ; de Espindola, Carollyny Silva ; Omori, Alvaro Takeo

• Document type: Journal article
• Source: ACS SUSTAINABLE CHEMISTRY & ENGINEERING; v. N/A, p. 5-pg., 2023-01-26.

Abstract

The COVID-19 pandemic has affected millions of people in the entire world and caused a shortage of several drugs, including propofol. Therefore, several protocols for propofol synthesis have been published in recent years. Herein, we present a process starting from paracetamol, a very common and abundant active pharmaceutical ingredient. Since the first three steps (Friedel-Crafts double alkylation, acetyl deprotection, and diazotization) are done in acidic media, a one-pot approach was developed. Furthermore, we observed that the extraction of the final product can be simplified by steam-distillation, leading to propofol in 47% isolated yield with high purity. This presented process could be an example of active pharmaceutical ingredient reuse since similar results were observed with commercial paracetamol tablets (with excipients) regardless of expiration date. (AU)

• FAPESP's process: 21/13573-5 - Alternative methodologies in the synthesis of intubation drugs and Molnupiravir applying green and circular chemistry principles
• Grantee: Alvaro Takeo Omori
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/18007-2 - EXPANDING THE USE OF CARROT BITS (Daucus carota) IN ORGANIC SYNTHESIS - APPLICATIONS IN TOTAL SYNTHESIS OF BIOACTIVE MOLECULES, NOVEL SUBSTRATES AND THE DEVELOPMENT OF A SCALE-UP METHODOLOGY
• Grantee: Alvaro Takeo Omori
• Support Opportunities: Regular Research Grants