Green synthesis of caffeine based on methylating reagent dimethyl carbonate and environmental friendly separating method

Abstract

In this paper, a green process for the synthesis and separation of caffeine was reported. Theophylline sodium is used as the raw material, diazabicyclo[5.4.0] undec-7-ene as the catalyst, and Turkey red oil as the solvent, particularly, dimethyl carbonate was adopted in place of high toxic dimethyl sulfate to form a mixture of caffeine and by-product sodium bicarbonate. After converting sodium bicarbonate to sodium carbonate, the solubility difference between caffeine and sodium carbonate at 40 C was for the first time utilized to achieve the purpose of separating caffeine with an excellent yield of 98.4% and a purity of greater than 99.0%. Furthermore, both the reaction mother liquor and separation mother liquor can be recycled and reused during the reaction and separation processes, respectively, with little caffeine loss. No industrial waste was discharged in the process of the improved synthesis and separation, which is therefore environmental friendly.

Purification, characterization and study of blue fluorescent substance in caffeine

“…It is widely used in the food, 1 medical, 2,3 and cosmetic industries 4 . The current caffeine synthesis process is mainly the route of cyanoacetic acid and dimethylurea synthesis, which generates the intermediate theophylline sodium salt 5 through cyanidation, condensation, cyclization, nitrosation, reduction, formylation and ring closure, and then generates crude caffeine through methylation 6 . The synthetic route has many steps and is a long process.…”

Greening up organic reactions with caffeine: applications, recent developments, and future directions

“… 26 Recently, green synthesis of caffeine has been reported from sodium theophylline using DMC as the methylating, Turkish red oil as a solvent, and DBU as the catalyst. 30 …”

Solubility and thermodynamic properties of sodium theophylline salt in aqueous sodium hydroxide solution at different temperatures

“…7–11 Sodium theophylline is usually synthesized from 6-amino-5-formamide, 1,3-dimethyluracil, and sodium hydroxide in a closed loop in a strongly alkaline environment. 12…”

“…[7][8][9][10][11] Sodium theophylline is usually synthesized from 6-amino-5-formamide, 1,3-dimethyluracil, and sodium hydroxide in a closed loop in a strongly alkaline environment. 12 The industrial production of sodium theophylline includes two processes: reactions and solid-liquid separation and purification. 6-amino-5-formamide, 1,3-dimethyluracil, and sodium hydroxide generate sodium theophylline under alkaline conditions.…”