Novel synthesis method of 4-methylthiazole-5-formaldehyde

Abstract

The invention provides a novel synthesis method of 4-methylthiazole-5-formaldehyde, which comprises the following steps: by taking 4-methylthiazole-5-methanol as a raw material, carrying out catalytic oxidation reaction to obtain the 4-methylthiazole-5-formaldehyde. In the catalytic oxidation reaction, an oxidant is molecular oxygen (oxygen or air), and a catalytic system is composed of a catalyst A, a catalyst B and a catalyst C. The catalyst A is piperidine nitroxide free radicals and derivatives thereof, the catalyst B is nitrogen oxides and equivalents thereof, and the catalyst C is protonic acid, bromides or ferric iron salt. The reaction raw materials are green and cheap, the catalytic system is efficient and environmentally friendly, the whole reaction process is clean and safe, and the method has great advantages from the perspective of economy or environmental protection.

Description

technical field [0001] The invention relates to the technical field of synthesis of pharmaceutical intermediates, in particular to a novel synthesis method of 4-methylthiazole-5 formaldehyde. Background technique [0002] 4-methylthiazole-5-carbaldehyde is an important intermediate for the preparation of the third-generation cephalosporin antibacterial drug cefditoren pivoxil tablet, and its chemical structure is In actual production, when 4-methylthiazole-5-methanol is used as the starting material to synthesize 4-methylthiazole-5-carbaldehyde, expensive and toxic oxidants are often used, such as chromium reagents, manganese reagents and other transition metal oxidation agents. substances, hypervalent iodine reagents, etc., and most of the oxidants are used in excess, resulting in a large amount of waste pollutants, which has caused huge pressure on environmental protection. [0003] Currently, 2,2,6,6-tetramethylpiperidine-nitrogen-oxyl radical (TEMPO) and its derivative...

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Problems solved by technology

[0002] 4-methylthiazole-5-carbaldehyde is an important intermediate for the preparation of the third-generation cephalosporin antibacterial drug cefditoren pivoxil tablet, and its chemical structure is In actual production, when 4-methylthiazole-5-methanol is used as the starting material to synthesize 4-methylthiazole-5-carbaldehyde, expensive and toxic oxidants are often used, such as chromium reagents, manganese reagents and other transition metal oxidation agents. substances, hypervalent iodine reagents, etc., and the amount of oxidants is mostly excessive, resulting in a large amount of waste pollutants, which has caused huge pressure on environmental protection

The former method has a higher yield, but sodium hypochlorite will be used at low temperature, and the conditions are harsher; the latter method has higher product purity, but the yield is not high, and the use of heavy metal oxidants also leads to increased solid waste, environmental pollution and Unstable product quality and other shortcomings

[0005] In the patent CN103030604A, TEMPO is used as a catalyst, and calcium hypochlorite or sodium hypobromite is used as an oxidizing agent to oxidize 4-methylthiazole-5-methanol to obtain 4-methylthiazole-5-carbaldehyde, although potassium bromide is not required A kind of cocatalyst, but the reaction yield is not high

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