Synthesis of pethidine can be relatively long and difficult. A synthesis procedure found on Rhodium Archive Index describes the formation of five intermediates before producing pethidine as a final product. I chose to reference this particular synthesis because it describes the entire procedure from start to finish in thorough detail. Additionally, the procedure gives the reader the option to omit difficult steps, if desired, by recommending the purchase of a pethidine derivative. Synthesis of pethidine begins by creating a slurry of an isonicotinic acid. This slurry is refluxed for 60 hours, vacuum filtered, and reduced with sodium thiosulfate. A second slurry is created to be placed in a column. This column chromatography is meant to elute the previous slurry for the purpose of removing iodine. This eluted solution is recrystallized and then reduced in a high-pressure reaction vessel. From this stage forward, the procedure suggests purchasing hydrochloride to surpass the two previous steps. The purchased intermediate is placed in a mixture of acid and refluxed for 6 hours. Unwanted material is removed, and additional solvents are brought in to create another slurry. Several more steps are taken to add reagents and allow for proper mixing, leaving a brown oil left to be fractionally distilled. The fourth intermediate can be prepared by passing chlorine gas into a mixture containing some of the previously product formed. The final intermediate is produced by forming several mixtures, putting it through a reflux, and extracting the organic layer with water. Extracts are combined, and pH of the solution is adjusted. Finally, a hydrochloride salt is refluxed to produce the final product pethidine whose Raman spectra can be viewed in Figure 2. Figure 2. Raman shift of Pethidine Hydrochloride after injection in water in various levels of concentration. Each graph will represent the values from the different levels of concentration
Synthesis of pethidine can be relatively long and difficult. A synthesis procedure found on Rhodium Archive Index describes the formation of five intermediates before producing pethidine as a final product. I chose to reference this particular synthesis because it describes the entire procedure from start to finish in thorough detail. Additionally, the procedure gives the reader the option to omit difficult steps, if desired, by recommending the purchase of a pethidine derivative. Synthesis of pethidine begins by creating a slurry of an isonicotinic acid. This slurry is refluxed for 60 hours, vacuum filtered, and reduced with sodium thiosulfate. A second slurry is created to be placed in a column. This column chromatography is meant to elute the previous slurry for the purpose of removing iodine. This eluted solution is recrystallized and then reduced in a high-pressure reaction vessel. From this stage forward, the procedure suggests purchasing hydrochloride to surpass the two previous steps. The purchased intermediate is placed in a mixture of acid and refluxed for 6 hours. Unwanted material is removed, and additional solvents are brought in to create another slurry. Several more steps are taken to add reagents and allow for proper mixing, leaving a brown oil left to be fractionally distilled. The fourth intermediate can be prepared by passing chlorine gas into a mixture containing some of the previously product formed. The final intermediate is produced by forming several mixtures, putting it through a reflux, and extracting the organic layer with water. Extracts are combined, and pH of the solution is adjusted. Finally, a hydrochloride salt is refluxed to produce the final product pethidine whose Raman spectra can be viewed in Figure 2. Figure 2. Raman shift of Pethidine Hydrochloride after injection in water in various levels of concentration. Each graph will represent the values from the different levels of concentration
SP18A05_Sample.docx