The use of methanol as a C1 building block

Abstract

Methanol is a key building block in the chemical industry. In recent years, it has been used as a C1 source in various organic transformations in the presence of a transition-metal catalyst. This protocol describes the ruthenium- and cobalt-catalyzed utilization of methanol in different types of methylation reactions and heterocycle synthesis. Initially, we describe the synthesis of tridentate ligands (L1–L3) and their corresponding Ru(II) complexes (Ru-1, -2 and -3) and then detail how to apply these Ru(II) complexes and Co/PP3 (PP3 = P(CH2CH2PPh2)3) in various methanol dehydrogenative coupling reactions. We discuss six types of transformations by using methanol or a methanol/water mixture. The experimental setup for all the catalytic reactions is similar and involves adding all the respective reagents and solvents to an argon-filled pressure tube, which is sealed (by screw cap) and refluxed at the indicated temperature before the desired products are isolated and characterized. The catalytic systems described in this protocol work well for both small-scale and preparative-scale synthesis of various N-methylated amines/amides, C-methylated products and quinazolinones. These catalytic reactions are greener and more sustainable than conventional synthesis methods, with only H2 and/or H2O as by-products, and we evaluate the ‘green chemistry metrics’ for a typical substrate. The total time required for the catalytic experiments described in this protocol is 16–28 h, and the operation time is 4 h. An average level of expertise in organic synthesis is required to carry out these protocols. This protocol details methods for using methanol in methylation reactions, including the synthesis of suitable transition metal-containing catalysts, and in the synthesis of heterocycles. The methods described produce only H2 and H2O as by-products.