阅读说明：本技术 一种使用金属配合物催化伯胺生成酰胺的方法 (Method for generating amide by catalyzing primary amine with metal complex ) 是由 李瑞祥 聂旭凤 付海燕 陈华 于 2020-09-04 设计创作，主要内容包括：本发明公开了一种使用金属配合物催化伯胺生成酰胺的方法,在氮气保护下向反应管中加入金属前体、配体、碱、有机溶剂和伯胺mol比为1:1:200:200:100,在60-120℃,优选80℃条件下搅拌反应,气相色谱监测原料完全消失后,停止反应收集反应液,对所述反应液进行离心、取上清液,用二氯甲烷萃取,合并有机相,用无水硫酸镁干燥,过滤后在减压下蒸去有机溶剂得到滤液,对所述滤液进行柱层析纯化,得目标产物酰胺。本发明催化剂活性好,反应结束后,催化体系单一,产物选择性好,后续处理简单,体系普适性好,对多种芳基、烷基和杂芳基取代的伯胺都有较好的催化效果。(The invention discloses a method for catalyzing primary amine to generate amide by using a metal complex, which comprises the steps of adding a metal precursor, a ligand, alkali, an organic solvent and primary amine into a reaction tube under the protection of nitrogen, stirring and reacting at 60-120 ℃, preferably 80 ℃, stopping the reaction and collecting reaction liquid after the raw materials are monitored by gas chromatography to completely disappear, centrifuging the reaction liquid, taking supernate, extracting with dichloromethane, combining organic phases, drying with anhydrous magnesium sulfate, filtering, evaporating the organic solvent under reduced pressure to obtain filtrate, and purifying the filtrate by column chromatography to obtain the target product amide. The catalyst has the advantages of good activity, single catalytic system after the reaction is finished, good product selectivity, simple subsequent treatment and good system universality, and has better catalytic effect on various aryl, alkyl and heteroaryl substituted primary amines.)

1. A method of catalyzing the formation of an amide from a primary amine using a metal complex, comprising the steps of:

A. adding a metal precursor, a ligand, a base, an organic solvent and primary amine into a reaction tube under the protection of nitrogen according to a mol ratio of 1:1:200:200:100, and stirring for reaction at a temperature of between 60 and 120 ℃, preferably at a temperature of 80 ℃. After the gas chromatography monitors that the raw materials completely disappear, stopping the reaction and collecting reaction liquid;

B. centrifuging the reaction solution, taking supernatant, extracting with dichloromethane, combining organic phases, drying with anhydrous magnesium sulfate, filtering, and evaporating the organic solvent under reduced pressure to obtain filtrate;

C. and carrying out column chromatography purification on the filtrate to obtain the target product amide.

2. The method of using a metal complex to catalyze the formation of an amide from a primary amine as in claim 1, which isCharacterized in that the ligand is a ligand containing double CNP structures, and two CNP structures pass through R₁And (4) key connection.

Wherein R is₁One of alkyl, aryl, heterocycle, condensed ring and bridged ring; r₂、R₃、R₄Hydrogen, alkyl, aryl, heterocycle, condensed ring, bridged ring or a plurality of them; r₅One of an electron donating group such as methoxy group and an alkyl group having various structures, and an electron withdrawing group such as trifluoromethyl group, carboxyl group, sulfonic group, or nitro group; x is one of fluorine, chlorine, bromine, iodine, tetrafluoroborate ion, tetraphenylborate ion, or hexafluorophosphate ion; n is 1-8.

3. The method of claim 1, wherein the metal precursor is RuCl₃、RuH₂(CO)(PPh₃)₃、RuHCl(CO)(PPh₃)₃、RuCl₂(PPh₃)₃、RuHCl(PPh₃)₃、[Ru(C₆H₆)Cl₂]₂、[Ru(p-cymene)Cl₂]₂、RuCl₂(DMSO)₄、Ru₃(CO)₁₂、Pd(CH₃CN)₂Cl₂、Pd₂(dba)₃One or more of.

4. The method of claim 1, wherein the base is one or more of DBU, potassium acetate, potassium carbonate, potassium bicarbonate, potassium hydroxide, sodium tert-butoxide, potassium phosphate, cesium carbonate, cesium hydroxide, sodium hydride.

5. The method of claim 1, wherein the solvent is one or more of DMSO, DMF, DCE, THF, toluene, o-xylene, mesitylene, 1, 4-dioxane.

6. The method of catalyzing the formation of an amide from a primary amine using a metal complex of claim 1, wherein the substrate is unsubstituted or substituted with a substituent comprising: aryl, alkyl, heterocyclic aryl. The aryl substrate comprises ortho, meta and para positions on a benzene ring, and is substituted by methyl, methoxy, tert-butyl, amino, phenyl, fluorine, chlorine, bromine and trifluoromethyl; alkyl substrates include substitution of long or short chain alkyl groups; heterocyclic substrates include furyl, thienyl, pyridyl, indolyl substitutions.

Technical Field

The invention relates to the field of chemical reaction synthesis, in particular to a method for catalyzing primary amine to generate amide by using a metal complex.

Background

Cyano groups are present in many natural products, drugs, and functional materials that have biological activity. As an important intermediate for organic synthesis, amides can be easily converted into various fine and useful complex molecules by simple treatment. Methods for producing amide compounds have been reported, such as sandmeyer reaction, rosemond-von braun reaction, conversion of compounds such as alcohols, oxidative dehydration of primary amines, and the like. However, the above-mentioned method is generally carried out under relatively severe high-temperature conditions, requires addition of highly toxic metal cyanide, metal catalyst, strong oxidizer, etc., and always produces stoichiometric by-products, which have a large environmental impact and poor atomic economy. In contrast, metal-catalyzed, acceptor-free dehydrogenation of primary amines is the cleanest process because the primary amine strips two molecules of hydrogen in the reaction, and the only by-product hydrogen is a clean, efficient fuel. Therefore, the method for preparing the amide by the primary amine acceptor-free dehydrogenation is an atom-economical and environment-friendly method, and meets the requirements of green chemistry and sustainable chemistry.

On the other hand, the receptor-free dehydrogenation of amines to amides is a very challenging problem, since amines have a strong nucleophilicity and β -H elimination of amino group-containing compounds is more difficult to occur. To date, only a few successful examples have been reported. However, these reported systems still suffer from low reaction efficiency, limited substrate range, moderate selectivity and low TON. Therefore, there remains an urgent need to develop a more efficient and stable system for catalyzing the dehydrogenation of primary amines to amides. Therefore, there is an urgent need to devise a method for catalyzing the formation of amides from primary amines using metal complexes to solve such problems.

Disclosure of Invention

The invention aims to provide a method for preparing amide by catalyzing primary amine acceptor-free dehydrogenation, which is simple to operate, good in atom economy and environment-friendly.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows:

the invention comprises the following steps:

A. adding a metal precursor, a ligand, a base, an organic solvent and primary amine into a reaction tube under the protection of nitrogen according to a mol ratio of 1:1:200:200:100, and stirring for reaction at a temperature of between 60 and 120 ℃, preferably at a temperature of 80 ℃. After the gas chromatography monitors that the raw materials completely disappear, stopping the reaction and collecting reaction liquid;

b, centrifuging the reaction solution, taking supernatant, extracting with dichloromethane, combining organic phases, drying with anhydrous magnesium sulfate, filtering, and evaporating the organic solvent under reduced pressure to obtain filtrate;

C. and carrying out column chromatography purification on the filtrate to obtain the target product amide.

Further, the ligand is a ligand containing double CNP structures, and two CNP structures pass through R₁And (4) key connection.

Or

Wherein R is₁One of alkyl, aryl, heterocycle, condensed ring and bridged ring; r₂、R₃、R₄Hydrogen, alkyl, aryl, heterocycle, condensed ring, bridged ring or a plurality of them; r₅One of an electron donating group such as methoxy group and an alkyl group having various structures, and an electron withdrawing group such as trifluoromethyl group, carboxyl group, sulfonic group, or nitro group; x is one of fluorine, chlorine, bromine, iodine, tetrafluoroborate ion, tetraphenylborate ion, or hexafluorophosphate ion; n is 1-8.

Further, the metal precursor may be RuCl₃、RuH₂(CO)(PPh₃)₃、RuCl₂(PPh₃)₃、RuHCl(PPh₃)₃、RuHCl(CO)(PPh₃)₃、[Ru(C₆H₆)Cl₂]₂、[Ru(p-cymene)Cl₂]₂、RuCl₂(DMSO)₄、Ru₃(CO)₁₂、Pd(CH₃CN)₂Cl₂、Pd₂(dba)₃One kind of (1).

Further, the base may be one of DBU, potassium acetate, potassium carbonate, potassium bicarbonate, potassium hydroxide, sodium tert-butoxide, potassium phosphate, cesium carbonate, cesium hydroxide, sodium hydride, and the like.

Further, the solvent may be one of DMSO, DMF, DCE, THF, toluene, o-xylene, mesitylene, 1, 4-dioxane, and the like.

Further, the substrate is the following group which is unsubstituted or substituted by a substituent: aryl, alkyl, heterocyclic aryl. The aryl substrate comprises ortho, meta and para positions on a benzene ring, and is substituted by methyl, methoxy, tert-butyl, amino, phenyl, fluorine, chlorine, bromine and trifluoromethyl; alkyl substrates include substitution of long or short chain alkyl groups; heterocyclic substrates include furyl, thienyl, pyridyl, indolyl substitutions.

Compared with the prior art, the invention has the following beneficial effects:

(1) the catalyst of the invention has good activity. These complexes still have 100% conversion at levels as low as 0.5 mol%.

(2) After the reaction is finished, the catalytic system is single, the product selectivity is good, and the post-treatment is simple.

(3) The system has good universality and has good catalytic effect on various aryl, alkyl and heteroaryl substituted primary amines. The secondary amine also has better dehydroamidation performance.

(4) If the substrate contains a group capable of being reduced by hydrogen, one-step completion of dehydrogenation and reduction can be achieved.

(5) For containing two-CHs₂NH₂Substituted substrate, if two-CH₂NH₂On an aromatic ring, one of which, after the reaction has ended, is-CH₂NH₂Dehydrogenation to give a cyano group (-CN), the other-CH₂NH₂Conversion to an amide (-CONH)₂). If two are providedIs one of₂NH₂On the alkyl group, a product containing both cyano groups (-CN) is obtained.

Detailed Description

The present invention is further illustrated by the following examples, which include, but are not limited to, the following examples.

A. Adding a metal precursor, a ligand, a base, an organic solvent and primary amine into a reaction tube under the protection of nitrogen according to a mol ratio of 1:1:200:200:100, and stirring for reaction at a temperature of between 60 and 120 ℃, preferably at a temperature of 80 ℃. After the gas chromatography monitors that the raw materials completely disappear, stopping the reaction and collecting reaction liquid;

b, centrifuging the reaction solution, taking supernatant, extracting with dichloromethane, combining organic phases, drying with anhydrous magnesium sulfate, filtering, and evaporating the organic solvent under reduced pressure to obtain filtrate;

C. and carrying out column chromatography purification on the filtrate to obtain the target product amide.

The present invention is specifically described by the following embodiments. It should be noted that the present embodiment is only for further illustration of the present invention, but not for limitation of the protection scope of the present invention, and that those skilled in the art can make some insubstantial modifications and adjustments according to the present disclosure.