Method for preparing aryl thioamide compound

Abstract

The invention discloses a method for preparing an aryl thioamide compound. The method comprises the following steps: under the protection of inert gas, performing stirring to react for 6-12 hours at the reaction temperature of room temperature to 60 DEG C by taking aryl methanol as a substrate, sublimed sulfur as a sulfur source, an alkali metal complex formed by combining alkali metal salt and ligand as a catalyst, alkali as an accelerant, formamide as a solvent and an amine source; and carrying out post-treatment on the reaction product to obtain the aryl thioamide compound. According to theinvention, cheap and easily available aryl methanol is used as a substrate for three-component reaction to prepare the corresponding thioamide compound; the method for preparing the aryl thioamide compound has the technical advantages of simple technological process, high yield, less pollution, safety, environmental protection, greenness, mildness and the like.

Description

technical field [0001] The invention relates to a method for synthesizing organic compounds, in particular to a method for synthesizing arylthioamide compounds, an important class of pharmaceutical intermediates, and belongs to the field of organic synthesis. Background technique [0002] Arylthioamide compounds widely exist in drugs and natural product molecules, and have strong biological and pharmaceutical activities; they are often used as DNA gyrase inhibitors, P-glycoprotein inhibitors, non-nucleoside reverse transcriptases Inhibitors, etc. (Med. Chem. 2007, 3, 513-519; J. Med. Chem. 2011, 54, 2207-2224). At the same time, it is also one of the most important precursors for the construction of various sulfur-containing heterocycles (such as thiazole, thiazoline, thiazolone, etc.) (Adv.Synth.Cata1.2017, 359, 4300-4304; Org.Lett. 2016, 18, 356-359). [0003] Traditionally, there are two main methods for synthesizing thioamides: [0004] The first is to carry out the s...

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Problems solved by technology

[0004] The first is to carry out the sulfidation (Chem.Commun.2009,46,7122-7124) of carbonamide by amide and Lawson's reagent or phosphorus pentasulfide; in this type of synthetic method, the Lawson's reagent used is unstable and expensive, Low atom economy, strong odor, and varying degrees of damage to the environment and human body. The required amide must be prepared in advance by condensation of carboxylic acid (or acid chloride) and amine, and the step economy is low.

[0005] The second method is to use the classic Willgerodt-Kindler reaction to prepare thioamide compounds. This method uses sulfur as a sulfur source, aryl aldehydes, aryl / alkyl ketones, aryl acetylenes, benzylamines, aryl acetic acids, etc. As a raw material to synthesize thioamide compounds (Chem.Soc.Rev.2013, 42, 7870-7880), compared with the first method, this method improves the atom utilization and step economy, but the substrate universality Not wide, some substrates have harsh reaction conditions, the highest reaction temperature is 320°C, many raw materials are not easy to obtain, and the use of organic solvents also limits its practicability

[0006] In recent years, the thioamidation reaction of aryl alkynes with amides and sulfur has appeared, and thiobenzamides are prepared by cracking C≡C of alkynes (Org. Lett. 2018, 20, 2228); but this The atom economy of the method is poor, the substrate is not easy to obtain, and industrial production is difficult

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