Mechanochemical Grignard Reactions with Gaseous CO2 and Sodium Methyl Carbonate

Abstract

A one-pot, three-step protocol for the preparation of Grignard reagents from organobromides in a ball mill and their subsequent reactions with gaseous carbon dioxide (CO₂ ) or sodium methyl carbonate providing aryl and alkyl carboxylic acids in up to 82 % yield is reported. Noteworthy are the short reaction times and the significantly reduced solvent amounts [2.0 equiv. for liquid assisted grinding (LAG) conditions]. Unexpectedly, aryl bromides with methoxy substituents lead to symmetric ketones as major products.

Keywords: Ball milling; Carbon dioxide; Carboxylation; Grignard reaction; Mechanochemistry.

Scheme 1

Previously reported mechanochemical reactions with CO₂ (a and b),[ ⁷ , ⁸ ] mechanochemical Grignard reactions (c and d),[ ¹¹ , ¹² ] and mechanochemically conducted Grignard reactions with CO₂ in this work.

Scheme 2

Scope of organobromides in mechanochemical Grignard reactions with CO₂ (4.0 mmol scale). Reaction conditions (for steps I–III, see Table 1): Step I=Mg (2.5 equiv.) and LiOH (1.1 equiv.) in a ZrO₂‐M milling vessel (20 mL) with gas inlet/outlet valves and 5 ZrO₂‐M balls (Ø 10 mm) under Ar; step II=addition of 2‐MeTHF (2.0 equiv.) and 1 (4.0 mmol) under Ar; step III=CO₂ (4 bar). The yields refer to product amounts obtained after column chromatography.

Scheme 3

Scope of aryl and alkyl bromides in a mechanochemical Grignard reaction with SMC (1.0 mmol scale). Reaction conditions: Step I=Mg (2.5 equiv.) and LiOH (1.1 equiv.) in a ZrO₂‐M milling vessel (12 mL) with 3 ZrO₂‐M balls (Ø 9 mm); step II=addition of 2‐MeTHF (2.0 equiv.), SMC (1.5 equiv.), and 1 (1.0 mmol). The yields refer to product amounts obtained after column chromatography.