阅读说明：本技术 一种可见光诱导无金属参与制备酰胺的方法 (Method for preparing amide under induction of visible light without participation of metal ) 是由 宋汪泽 董锟 李明 于 2019-10-30 设计创作，主要内容包括：本发明属于有机合成技术领域,提供了一种可见光诱导无金属参与制备酰胺的方法,步骤如下：在有机溶剂中,以9-均三甲苯基-10-甲基吖啶四氟硼酸盐为光敏剂,催化硫代酸类化合物与胺类化合物的反应制备酰胺类化合物。本发明中新型酰胺的可见光诱导氧化还原合成的制备方法反应条件温和,产物收率不低于71％。这种绿色方法在形成酰胺键时表现出出色的官能团选择性,而不会影响其他官能团,例如醇,酚,醚,酯,卤素和杂环。(The invention belongs to the technical field of organic synthesis, and provides a method for preparing amide without participation of metal under the induction of visible light, which comprises the following steps: in an organic solvent, 9-mesityl-10-methylacridine tetrafluoroborate is used as a photosensitizer to catalyze the reaction of thioacid compounds and amine compounds to prepare amide compounds. The preparation method of the novel amide by visible light-induced redox synthesis has mild reaction conditions and the product yield is not lower than 71%. This green approach exhibits excellent functional group selectivity in the formation of amide bonds without affecting other functional groups such as alcohols, phenols, ethers, esters, halogens and heterocycles.)

1. A method for preparing amide without participation of metal under the induction of visible light is characterized by comprising the following steps:

in an organic solvent, 9-mesityl-10-methylacridine tetrafluoroborate is taken as a photosensitizer to catalyze the reaction of thioacid compounds and amine compounds to prepare amide compounds, wherein the reaction formula is as follows:

wherein R is¹And R²Is alkyl or aryl, R¹And R²The same or different;

i is a thioacid compound;

the reaction temperature is room temperature, the used light source is a blue light lamp, the reaction time is 5 hours, and the amide compound with the yield not lower than 71 percent is prepared;

the molar ratio of the thioacid compounds to the amine is 2:1, and the concentration of the amine compounds is 0.01-0.1 mmol/ml.

2. The method for preparing amide without metal participation under visible light induction according to claim 1, wherein the amount of the 9-mesityl-10-methylacridine tetrafluoroborate used is 0.5 to 50 mol% of the amine compound.

3. The method for preparing amide without metal participation under visible light induction as claimed in claim 1 or 2, wherein the organic solvent is one or more of benzene, toluene, diethyl ether, methyl tert-butyl ether, dichloromethane, tetrahydrofuran, trifluorotoluene, cyclohexane and petroleum ether.

Technical Field

The invention belongs to the technical field of organic synthesis, and relates to a method for synthesizing amide by redox under the condition of visible light.

Background

Amide bonds are not only ubiquitous in various natural products, peptides, pharmaceuticals and fine chemicals, but are also one of the important functional groups in organic synthesis. In 2006, two thirds of candidate drug structures contain amide bonds, such as paracetamol, melatonin, moclobemide and acetazolamide (org. biomol. chem.2006, 4, 2337-. Statistics in 2016 showed that about 60% of reactions in the modern literature were attributed to amide bond formation (J.Med.chem.2016,59, 4443-4458). Therefore, the development of a novel method for forming an amide bond is of great significance in organic synthesis and medicinal chemistry.

Amide bonds are formed primarily by the condensation of carboxylic acids (or derivatives thereof) and amines. Such processes typically require strict anhydrous and high temperature conditions. In addition, amide formation may also use metal catalysts or stoichiometric coupling agents and bases to increase the activity of the reaction substrate, but may produce excessive and undesirable chemical waste. The traditional amide synthesis method requires harsh and environmentally unfriendly conditions, and does not meet the requirements of green chemistry. Therefore, it is very urgent and meaningful to develop new methods for forming green synthetic amides.

At present, photochemical reactions that make full use of light energy are considered as a promising reaction in green chemistry. Many photoredox systems have recently been developed to mimic the photosynthetic process, and photoinduced chemical transformations driven by electron, atom or energy transfer have been achieved. Amides may also be prepared by means of photo-redox catalysis. For example, the Tan project group uses Ru (bpy)₃Cl₂Preparation of amides as photosensitizers by formation of disulfide intermediates (ACS. Catal.2016,6,1732-1736), a panel of Biswas publishedCdS nanoparticles can be used as heterogeneous photosensitizers to prepare amides from sulfuric acid (appl. However, the above methods mostly use expensive or toxic metal catalysts for converting light energy. In addition to this, the use of large amounts of organic or inorganic bases is required, limiting the further use of these processes. Therefore, it is very important to develop a new strategy for photo-redox catalysis of amide bond formation without metals, bases and additives, especially in the pharmaceutical industry where the index of metal residues is high.

The invention adopts various thioacid and amine compounds as raw materials, and uses 2mol percent of Mes-Acr-MeBF₄As a photosensitizer, the amide compound is obtained with the yield of 71-96 percent after 5 hours of reaction under the irradiation of a 36W blue light lamp. The method has the advantages of no metal, no alkali and no additive, mild reaction condition and the like.

Disclosure of Invention

The technical problem to be solved by the invention is to provide a method for using Mes-Acr-MeBF₄As photosensitizer, amide bond formation can be induced by visible light under the conditions of no metal, no alkali and no additive.

The technical scheme of the invention is as follows:

a method for preparing amide without participation of metal under the induction of visible light comprises the following steps:

in an organic solvent, 9-mesityl-10-methylacridine tetrafluoroborate (Mes-Acr-MeBF) is used₄) The photosensitizer catalyzes a thioacid compound to react with an amine compound to prepare an amide compound, and the reaction formula is as follows:

wherein R is¹And R²Is alkyl or aryl, R¹And R²The same or different;

i is a thioacid compound;

the reaction temperature is room temperature, the used light source is a blue light lamp, the reaction time is 5 hours, and the amide compound with the yield not lower than 71 percent is prepared;

the molar ratio of the thioacid compounds to the amine is 2:1, and the concentration of the amine compounds is 0.01-0.1 mmol/ml.

The dosage of the 9-mesityl-10-methylacridine tetrafluoroborate is 0.5-50 mol% of the amine compound.

The organic solvent is one or more of benzene, toluene, diethyl ether, methyl tert-butyl ether, dichloromethane, tetrahydrofuran, trifluorotoluene, cyclohexane and petroleum ether, and the preferable solvent is acetonitrile, dimethyl sulfoxide or dimethylformamide.

The invention has the beneficial effects that: the preparation method of the novel amide by visible light-induced redox synthesis has mild reaction conditions and the product yield is not lower than 71%. This green approach exhibits excellent functional group selectivity in the formation of amide bonds without affecting other functional groups such as alcohols, phenols, ethers, esters, halogens and heterocycles.

Detailed Description

The following further describes the specific embodiments of the present invention in combination with the technical solutions.