CN104016913B - A kind of method preparing amide compound - Google Patents

A kind of method preparing amide compound Download PDF

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Publication number
CN104016913B
CN104016913B CN201410227369.6A CN201410227369A CN104016913B CN 104016913 B CN104016913 B CN 104016913B CN 201410227369 A CN201410227369 A CN 201410227369A CN 104016913 B CN104016913 B CN 104016913B
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Prior art keywords
amide compound
prepare
solvent
compound
reaction
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CN104016913A (en
Inventor
周宇扬
王筱梅
叶常青
朱赛江
徐鹏杰
梁作芹
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Suzhou University of Science and Technology
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Suzhou University of Science and Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/06—Preparation of carboxylic acid amides from nitriles by transformation of cyano groups into carboxamide groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Abstract

The invention belongs to field of organic compound preparation, be specifically related to a kind of method preparing amide compound.Be specially in a heated condition, using the mixed solvent of protic solvent and non-protonic solvent as reaction medium, under air atmosphere and base catalysis condition, by cyano compound selective hydrolysis, the corresponding amide compound of efficient preparation; Simultaneously can also utilizing carbon carbon linked reaction further, reacting containing with the compound of cyano group and halogen group and boronic acid compounds by selecting simultaneously, single stage method can prepare the amide compound after coupling.This method avoid the use of the poisonous and harmful oxygenants such as traditional hydrogen peroxide, is prepare a kind of simple and effective of amide compound, the synthetic method of environmental protection.

Description

A kind of method preparing amide compound
Technical field
The invention belongs to field of organic compound preparation, be specifically related to a kind of method preparing amide compound.
Background technology
Amide compound is the important chemical raw material of a class, has a wide range of applications in fields such as biology, medical science, pharmacy.The mode preparing amide compound in prior art has two kinds: a kind of is prepare acid amides by carboxyl and amino condensation reaction, but this reaction needs to carry out activation treatment to raw material usually, and reaction conditions is usually harsher.
Be then prepare amide compound by cyan-hydrolysis mode in addition, be mainly divided at acidic conditions or hydrolyzed under basic conditions cyano group.In the basic conditions, the method for hydrogen peroxide oxidation is utilized hydrolysis nitrile to be acid amides in the at room temperature short period of time; But the method is not easy the progress controlling reaction usually, and makes cyano group complete hydrolysis become carboxylic acid.
Therefore find new synthetic method tool that is efficient, controlled synthesis amide compound to be of great significance.
Summary of the invention
The object of this invention is to provide a kind of preparation method of amide compound.
To achieve the above object of the invention, the technical solution used in the present invention is: a kind of method preparing amide compound, comprise the steps: in air atmosphere, take cyano compound as raw material, with the mixed solvent of protic solvent and non-protonic solvent for reaction medium, in the presence of a base, at 40-150 DEG C, amide compound is prepared by cyan-hydrolysis reaction;
The structural formula of described cyano compound is the one in following structural formula:
In formula, R 1, R 2, R 3, R 4independently be selected from H, F, Cl, Br, I, CH 3, OMe, CH 2cH 3in one; N is 0-4;
The structural formula of described amide compound is the one in following structural formula:
In formula, R 1, R 2, R 3, R 4independently be selected from H, F, Cl, Br, I, CH 3, OMe, CH 2cH 3in one; N is 0-4.
In technique scheme, described non-protonic solvent is one or more mixtures in toluene, dimethylbenzene, tetrahydrofuran (THF), acetone, DMF, N, N-dimethyl sulfoxide (DMSO); Described protic solvent is one or more mixtures in water, ethanol, ethylene glycol ethyl ether, ethylene glycol monomethyl ether.
In technique scheme, described alkali is sodium carbonate, salt of wormwood, sodium tert-butoxide, potassium tert.-butoxide, sodium methylate, potassium methylate, sodium hydroxide, potassium hydroxide, strong aqua, pyridine or 1,8-diazabicylo 11 carbon-7-alkene.
In technique scheme, the time of described cyan-hydrolysis reaction is 0.5-48h.
In preferred technical scheme, the temperature of described cyan-hydrolysis reaction is reflux temperature.
In technique scheme, the mol ratio of described cyano compound and alkali is 1: 10-100.
Technique scheme also comprises purification step, is specially after reaction terminates, is spin-dried for solvent, obtains product amide compound after then utilizing silica gel column chromatography to carry out purifies and separates.
In technique scheme, the mass concentration of strong aqua is 22-25%; 1,8-diazabicylo 11 carbon-7-alkene is also known as DBU, and its structural formula is:
。
In the present invention, the mixing of protonic solvent and aprotic solvent can improve the efficiency of reaction; Heating overcomes the activation energy of reaction, is conducive to carrying out smoothly of reaction.
Prepare 2-acid amides pyridine for 2-cyanopyridine, the present invention can represent with following reaction formula:
Because technique scheme is used, the present invention compared with prior art has following advantages:
1. the method preparing amide compound newly disclosed by the invention avoids the use of oxygenant in prior art, thus effectively inhibit the excessive hydrolysis of cyano group, avoid the phenomenon that acid amides is hydrolyzed to carboxylic acid further, greatly improve the reaction yield of amide compound, even more than 90%;
2. the method that cyan-hydrolysis disclosed by the invention prepares amide compound can be reacted with other, and such as carbon carbon linked reaction is carried out simultaneously, prepares more multiamide compound, and the industrialization for amide compound generates has important marketable value and economic benefit;
3. the synthetic route preparing amide compound disclosed by the invention is short, only needs a step; Preparation process is simply controlled, and efficiency is high, and environmental protection is easy to industrialization.
Embodiment
Below in conjunction with embodiment, the invention will be further described:
embodiment 1
By 2-cyanopyridine (10mmol, 1.04g), NaOH (0.1mmol, 4mg) be dissolved in the mixed solvent of toluene/water (V:V=3:1), back flow reaction is after 6 hours, and stopped reaction, after leaving standstill room temperature, after being spin-dried for by solvent, after utilizing silica gel column chromatography to carry out purifies and separates, obtain white solid 2-acid amides pyridine 0.95g (productive rate: 78%); Ms (M/Z): 122.0 (M +).
embodiment 2
By 2-cyanopyridine (10mmol, 1.04g), K 2cO 3(0.5mmol, 69mg) be dissolved in the mixed solvent of toluene/water/ethanol (V:V:V=6:2:1), back flow reaction is after 12 hours, stopped reaction, after leaving standstill room temperature, after being spin-dried for by solvent, after utilizing silica gel column chromatography to carry out purifies and separates, obtain white solid 2-acid amides pyridine 1.04g (productive rate: 85%); Ms (M/Z): 122.0 (M +).
embodiment 3
By bromo-for 2-5-cyanopyridine (10mmol, 1.83g), sodium tert-butoxide (0.1mmol, 9.6mg) be dissolved in the mixed solvent of dimethylbenzene/ethanol (V:V=3:1), back flow reaction is after 4 hours, and stopped reaction, after leaving standstill room temperature, after being spin-dried for by solvent, after utilizing silica gel column chromatography to carry out purifies and separates, obtain white solid 2-bromo-5-acid amides pyridine 1.84g (productive rate: 92%); Ms (M/Z): 201.0 (M +).
The structural formula of above-mentioned 2-bromo-5-acid amides pyridine is:
。
embodiment 4
By benzyl cyanide (10mmol, 1.17g), strong aqua (2mL, mass concentration is 23%) be dissolved in the mixed solvent of acetone/water (V:V=3:1), back flow reaction is after 12 hours, and stopped reaction, after leaving standstill room temperature, after being spin-dried for by solvent, after utilizing silica gel column chromatography to carry out purifies and separates, obtain white solid phenylacetamide 1.2g (productive rate: 89%); Ms (M/Z): 135.1 (M +).
embodiment 5
Will to iodobenzene cyanogen (10mmol, 2.28g), Na 2cO 3(0.5mmol, 57mg) be dissolved in the mixed solvent of tetrahydrofuran (THF)/water (V:V=3:1), back flow reaction is after 6 hours, stopped reaction, after leaving standstill room temperature, after being spin-dried for by solvent, obtain white solid after utilizing silica gel column chromatography to carry out purifies and separates to iodobenzene acid amides 2.2g (productive rate: 89%); Ms (M/Z): 247.0 (M +).
The above-mentioned structural formula to iodobenzene acid amides is:
。
embodiment 6
By bromo-for 2-5-cyanopyridine (10mmol, 1.83g), 2,4 difluorobenzene boric acid (10mmol, 1.58g), Na 2cO 3(0.5mmol, 57mg), four triphenyl phosphorus palladiums (0.1mmol, 115mg) are dissolved in the mixed solvent of toluene/ethanol/water (V:V:V=5:2:1), and back flow reaction is after 24 hours, stopped reaction, after leaving standstill room temperature, after utilizing methylene dichloride to wash, collect organic phase, then white solid 2-(2 ', 4 '-difluorophenyl)-5 '-acid amides pyridine 2.1g (productive rate: 89%) is obtained after utilizing silica gel column chromatography to carry out purifies and separates; Ms (M/Z): 234.1 (M +); 1hNMR (DMSO- d 6 , 400MHz), δ ppm:9.15 (s, 1H), 8.33 (dd, J=8Hz, 2Hz, 1H), 8.22 (s, 1H), 8.06 (m, 1H), 7.88 (m, 1H), 7.66 (s, 1H), 7.44 (m, 1H), 7.27 (m, 1H).
The structural formula of above-mentioned 2-(2 ', 4 '-difluorophenyl)-5 '-acid amides pyridine is:
。

Claims (5)

1. prepare the method for amide compound for one kind, it is characterized in that, comprise the steps: in air atmosphere, take cyano compound as raw material, with the mixed solvent of protic solvent and non-protonic solvent for reaction medium, in the presence of a base, at 40-150 DEG C, amide compound is prepared by cyan-hydrolysis reaction; The mol ratio of described cyano compound and alkali is 1: 0.01 or 1: 0.05;
The structural formula of described cyano compound is the one in following structural formula:
In formula, R 1, R 2, R 3, R 4independently be selected from H, F, Cl, Br, I, CH 3, OMe, CH 2cH 3in one; N is 0-4;
Described non-protonic solvent is one or more mixtures in toluene, dimethylbenzene, tetrahydrofuran (THF), acetone; Described protic solvent is one or more mixtures in water, ethanol, ethylene glycol ethyl ether, ethylene glycol monomethyl ether;
The structural formula of described amide compound is the one in following structural formula:
In formula, R 1, R 2, R 3, R 4independently be selected from H, F, Cl, Br, I, CH 3, OMe, CH 2cH 3in one; N is 0-4.
2. prepare the method for amide compound according to claim 1, it is characterized in that: the temperature of described cyan-hydrolysis reaction is reflux temperature.
3. prepare the method for amide compound according to claim 1, it is characterized in that: described alkali is sodium carbonate, salt of wormwood, sodium tert-butoxide, potassium tert.-butoxide, sodium methylate, potassium methylate, sodium hydroxide, potassium hydroxide, strong aqua, pyridine or 1,8-diazabicylo 11 carbon-7-alkene.
4. prepare the method for amide compound according to claim 1, it is characterized in that: the time of described cyan-hydrolysis reaction is 0.5-48h.
5. prepare the method for amide compound according to claim 1, it is characterized in that: also comprise purification step, be specially after reaction terminates, be spin-dried for solvent, after then utilizing silica gel column chromatography to carry out purifies and separates, obtain product amide compound.
CN201410227369.6A 2014-05-27 2014-05-27 A kind of method preparing amide compound Expired - Fee Related CN104016913B (en)

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CN110773144A (en) * 2019-10-28 2020-02-11 湖南科技学院 Catalytic system for preparing amide by hydrolyzing cyano and application thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102603563A (en) * 2012-01-16 2012-07-25 山东康乔生物科技有限公司 Preparation method of metominostrobin
CN103342654A (en) * 2013-07-02 2013-10-09 扬州大学 Novel method for hydrolyzing nitrile group to acylamino

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JPS56128761A (en) * 1980-03-12 1981-10-08 Dai Ichi Seiyaku Co Ltd Preparation of pyridoxine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102603563A (en) * 2012-01-16 2012-07-25 山东康乔生物科技有限公司 Preparation method of metominostrobin
CN103342654A (en) * 2013-07-02 2013-10-09 扬州大学 Novel method for hydrolyzing nitrile group to acylamino

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
2，6-二甲基苯甲酸的合成工艺研究;赵迎春，等;《科学技术与工程》;20130630;第13卷(第6期);第4724-4726页 *

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