Cathodic Reduction of Caffeine: Synthesis of an Amino-Functionalized Imidazole from a Biobased Reagent

Published as part of the Cluster Electrochemical Synthesis and Catalysis

Abstract

The electrochemical reduction of caffeine, never carried out previously, yielded in DMF–Et₄NBF₄ N-formyl-N,1-dimethyl-4-(methylamino)-1H-imidazole-5-carboxamide, a highly functionalized imidazole product derived from the opening of the uracil ring. This reactivity is different from that of the methylated salt of caffeine, the cathodic reduction of which leads to the opening of the imidazole ring. Moreover, the product obtained by cathodic reduction, formylated at the exocyclic amide nitrogen, is different from that formed by treatment in an aqueous solution of sodium hydroxide followed by formylation. The latter is formylated at the exocyclic amine nitrogen.

Key words

cathodic reduction - caffeine - ring opening - electrolysis - cyclic voltammetry

• References and Notes

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• 14 Experimental Procedure Constant potential electrolysis was performed under a nitrogen atmosphere, at 25 °C, in a divided glass cell separated through a porous glass plug filled up with a layer of gel [i.e., methyl cellulose 0.5% vol dissolved in DMF–Bu₄NBF₄ (1.0 mol dm^–3)]; Pt spirals (apparent area 0.8 cm²) were used as both cathode and anode. Catholyte: DMF (5 mL, 0.1 M DMF–Bu₄NBF₄). Anolyte: the same solvent as the catholyte (2 mL). Starting caffeine (0.5 mmol) [and water (1.0 mmol) when reported in Table 1] were present in the catholyte during electrolysis. The electrolysis was stopped after 3 F. At the end of the electrolysis, the solvent was eliminated under reduced pressure (15 Pa) and the crude reaction mixture was analyzed by ¹H NMR spectroscopy. Product C was purified by flash column chromatography (eluent: CH₂Cl₂–MeOH 70:30) and two subsequent PLCs with the same eluent.
• 15 N-Formyl-N,1-dimethyl-4-(methylamino)-1H-imidazole-5-carboxamide C: ¹H NMR (200 MHz, CD₃OD): δ = 8.52 (s, 1 H, C H O), 7.56 (s, 1 H, C2 H ), 3.90 (s, 3 H, 1-N Me ), 3.15 (s, 3 H, 4-N Me ), 2.66 (s, 3 H, CON Me ) ppm. ¹³C NMR (50.3 MHz, CDCl₃): δ = 162.5, 159.3, 143.5, 138.1, 120.1, 35.2, 34.1, 26.2 ppm. MS (ESI): m/z [M – 28 + H⁺] = 169.2. MS (EI): m/z (%) = [M]^+. absent, 168 (12) [M^+. – 28], 138 (4) [M^+. – NMeCHO], 110 (85) (4) [M^+. –CONMeCHO], 42 (100).