阅读说明：本技术 一种n,n-二取代氰基甲酰胺的合成方法 (Synthesis method of N, N-disubstituted cyano formamide ) 是由 王少华 金大平 雷林生 于 2019-02-28 设计创作，主要内容包括：本发明涉及一种N,N-二取代氰基甲酰胺的合成方法,其反应通式如下：<Image he="126" wi="700" file="DDA0001981785260000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>本发明在无机碱或者有机碱促进下,使N,N-二取代胺基丙二腈氧化脱氰基后转化为N,N-二取代氰基甲酰胺；该方法具有条件温和、广泛的底物范围和便捷的操作的优点,为氰基甲酰胺化合物的合成提供了新的高效方法。(The invention relates to a synthetic method of N, N-disubstituted cyano formamide, which has the following reaction general formula: the invention converts N, N-disubstituted amino malononitrile into N, N-disubstituted amino malononitrile after oxidation and decyanation under the promotion of inorganic base or organic baseSubstituted cyanocarboxamides; the method has the advantages of mild conditions, wide substrate range and convenient operation, and provides a new high-efficiency method for synthesizing the cyano formamide compound.)

1. a synthetic method of N, N-disubstituted cyano formamide is characterized in that N, N-disubstituted amino malononitrile and alkali are sequentially added into a solvent, and N, N-disubstituted cyano formamide is obtained under the condition of heating, wherein the reaction formula is as follows:

wherein:

(1)R¹、R²when not in the same ring system, R¹、R²Are the same groups selected from methyl, ethyl, propyl, butyl;

(2)R¹、R²when not in the same ring system, R¹、R²Are not identical radicals R¹Selected from methyl,Ethyl, propyl, butyl groups; r²Selected from phenyl, substituted phenyl, benzyl, substituted benzyl groups;

(3)R¹、R²when on the same ring system, R¹、R²Together with the N atom is selected from indolinyl, 1,2,3, 4-tetrahydroisoquinolinyl, piperidinyl, 2-methylpiperidinyl, 3-methylpiperidinyl, 4-methylpiperidinyl, morpholinyl, 2, 6-dimethylmorpholinyl;

(4) the alkali is selected from one or more of cesium fluoride, cesium carbonate, cesium acetate, sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, calcium carbonate, ammonia water, pyridine, triethylamine and 1, 8-diazabicycloundecene-7-ene;

(5) the reaction solvent is selected from: one or more of acetonitrile, 1, 4-dioxane, dimethyl sulfoxide, N-dimethylformamide, tetrahydrofuran, 1, 2-dichloroethane, dichloromethane, N-heptane, N-hexane, toluene and cyclohexane;

(6) the reaction temperature is 20-120 ℃, and the reaction duration is 0.5-36 hours.

2. The method of claim 1, wherein the ratio of the amounts of the reactants is selected from the group consisting of: n, N-disubstituted amino malononitrile: alkali: the solvent is 1:0.5-10: 0.5-100.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of N, N-disubstituted cyano formamide.

Background

Cyanoformamides are of great interest for their excellent biological activity and as key structures in chemical synthesis as numerous drugs and materials. The natural products of the cyanoformamide extracted and separated from the nature are many, in 1996, the Ceratinamine separated from the sponge Pseudoceratitin apurea by Fusetani and colleagues is the first reported related natural product, the Ceratinamine has cytotoxicity and effective antifouling activity, and then the sponge Aplysinellas also separates a cyanoformamide compound-7-hydroxyformamine, and a pesticide degradation metabolite-N, N-dimethyl cyanoformamide is also separated from vegetables and fruits such as tomatoes, oranges, apples and the like; in organic synthesis, cyanoformamides are widely used in the synthesis of nitrogen heterocycles such as tetrazoles, indolines, acrylonitriles, symmetrically/asymmetrically substituted ureas and lactams, and also as stable sources of isocyanates and hydrogen cyanide.

In the previous reports, the preparation of the cyanoformamide is rarely reported, and the cyanoformamide is prepared by reacting amine with carbonyl cyanide, isonitroso Meldrum's Acid, bis (trichloromethyl) carbonate and other reagents (Tetrahedron,2007,63, 2978.; Heterocycles,1997,46, 503.; Tetrahedron Lett.,2001,42, 8197.; org. Lett.,2015,17,809.), the reactions have many defects, such as toxicity of the used reagents, complexity in preparation of key substrates, complex reaction conditions, complex operation, and active and easy-variable values of the used raw materials and high price; disadvantages limit the usefulness of these methods. The invention innovatively provides the method for preparing the polysubstituted cyano formamide by mild reaction of the N, N-disubstituted amino malononitrile which has low toxicity and is easy to prepare and alkali in an organic solvent.

Disclosure of Invention

The invention aims to provide a method for synthesizing N, N-disubstituted cyano formamide, which has the advantages of quick reaction process, simple and easily obtained starting materials, good yield and safe and convenient operation, and replaces the conventional complex and dangerous preparation method.

The technical scheme of the invention is as follows: a synthetic method of N, N-disubstituted cyano formamide is characterized in that N, N-disubstituted amino malononitrile and alkali are sequentially added into a solvent, and N, N-disubstituted cyano formamide is obtained under the condition of heating, wherein the reaction formula is as follows:

wherein:

(1)R¹、R²when not in the same ring system, R¹、R²Are the same groups selected from methyl, ethyl, propyl, butyl;

(2)R¹、R²when not in the same ring system, R¹、R²Are not identical radicals, R¹Selected from methyl, ethyl, propyl, butyl groups; r²Selected from phenyl, substituted phenyl, benzyl, substituted benzyl groups;

(3)R¹、R²when on the same ring system, R¹、R²Together with the N atom is selected from indolinyl, 1,2,3, 4-tetrahydroisoquinolinyl, piperidinyl, 2-methylpiperidinyl, 3-methylpiperidinyl, 4-methylpiperidinyl, morpholinyl, 2, 6-dimethylmorpholinyl;

(4) the alkali is selected from one or more of cesium fluoride, cesium carbonate, cesium acetate, sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, calcium carbonate, ammonia water, pyridine, triethylamine and 1, 8-diazabicycloundecene-7-ene;

(5) the reaction solvent is selected from: one or more of acetonitrile, 1, 4-dioxane, dimethyl sulfoxide, N-dimethylformamide, tetrahydrofuran, 1, 2-dichloroethane, dichloromethane, N-heptane, N-hexane, toluene and cyclohexane;

(6) the reaction temperature is 20-120 ℃, and the reaction duration is 0.5-36 hours;

(7) the mass ratios of the various reactants are: n, N-disubstituted amino malononitrile: alkali: the solvent is 1:0.5-10: 0.5-100.

Detailed Description

The present invention will be further described with reference to specific examples, but it should not be construed that the scope of the above-described subject matter of the present invention is limited to the following examples, and that all the technologies implemented based on the above-described contents of the present invention belong to the scope of the present invention.