Efficient Flow Electrochemical Alkoxylation of Pyrrolidine-1-carbaldehyde

Published as part of the Cluster Electrochemical Synthesis and Catalysis

Abstract

We report on the optimization of the alkoxylation of pyrrolidine-1-carbaldehyde by using a new electrochemical microreactor. Precise control of the reaction conditions permits the synthesis of either mono- or dialkoxylated reaction products in high yields.

Key words

C–H activation - electrochemistry - flow chemistry - heterocycles - alkoxylation - pyrrolidinecarbaldehyde

• References and Notes

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• 15 2-Methoxypyrrolidine-1-carbaldehyde (2); Typical ProcedureA 0.1 M solution of aldehyde 1 in MeOH (60 mL) containing Et₄NBF₄ (0.05 M) was sonicated to ensure complete dissolution of the reactant, then pumped through one microreactor at 0.5 mL/min by using a syringe pump or the Vapourtec E series, while a constant current of 640 mA was applied. The first 5 mL were discarded, and the remaining reaction mixture was collected for 110 min (55 mL). MeOH was removed under reduced pressure, and the crude product was washed with H₂O (50 mL), to remove the supporting electrolyte, then extracted with CH₂Cl₂ (3 × 30 mL). The organic layers were combined, dried (MgSO₄), filtered, evaporated, and dried under high vacuum. The residue was purified by chromatography [silica gel, hexane–EtOAc (1:1)] to give a colorless oil; yield: 629 mg (89%). The NMR spectra showed the presence of a ~5:1 mixture of rotamers.¹H NMR (400 MHz, CDCl₃): δ (major) = 8.40 (s, 1 H), 4.92 (d, J = 4.8 Hz, 1 H), 3.58−3.40 (m, 2 H), 3.26 (s, 3 H), 2.13−1.79 (m, 4 H); δ (minor) = 8.29 (s, 1 H), 5.37 (d, J = 4.8 Hz, 1 H), 3.58−3.40 (m, 2 H), 3.38 (s, 3 H), 2.13−1.79 (m, 4 H). ¹³C NMR (101 MHz, CDCl₃): δ (major) = 161.4, 89.7, 54.4, 42.7, 31.8, 21.4; δ (minor) = 162.6, 85.5, 56.6, 45.2, 31.9, 22.1.