CN113214147A - Preparation method of 2-thioether-N, N-dimethylnicotinamide - Google Patents
Preparation method of 2-thioether-N, N-dimethylnicotinamide Download PDFInfo
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- CN113214147A CN113214147A CN202110177024.4A CN202110177024A CN113214147A CN 113214147 A CN113214147 A CN 113214147A CN 202110177024 A CN202110177024 A CN 202110177024A CN 113214147 A CN113214147 A CN 113214147A
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- dimethylnicotinamide
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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
- C07D213/82—Amides; Imides in position 3
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Abstract
The invention relates to a preparation method of 2-thioether-N, N-dimethylnicotinamide, which comprises the steps of adding 2-chlorine-N, N-dimethylnicotinamide, sodium thiosulfate pentahydrate and substituent-containing alcohol into an organic solvent at a certain temperature, and carrying out a one-pot condensation substitution reaction to obtain a product 2-thioether-N, N-dimethylnicotinamide. The method has the advantages of more raw material sources, obvious cost advantage, safer and more convenient preparation method, high total yield and less three wastes, particularly no emission of toxic gases such as ammonia gas or hydrogen sulfide and the like, and is favorable for industrialization.
Description
Technical Field
The invention relates to the field of pesticides, relates to a synthetic technology of a nicosulfuron intermediate, and particularly relates to a preparation method of 2-thioether-N, N-dimethylnicotinamide.
Background
2-thioether-group-N, N-dimethyl nicotinamide is commonly used in the synthesis of medicines and pesticides, and particularly used as an intermediate of herbicide nicosulfuron receives multiple attention and researches, in the synthesis method in the prior art, 2-chloro-N, N-dimethyl nicotinamide, sodium hydrosulfide/sulfur or sodium sulfide/sulfur or thiourea is mainly used as a raw material, high-temperature substitution and acidification are performed to obtain a mercaptan intermediate, and the mercaptan intermediate is condensed with a halide to prepare the 2-thioether-group-N, N-dimethyl nicotinamide, wherein a large amount of toxic gas hydrogen sulfide or ammonia gas is released in the process and is difficult to release to the production stage.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a preparation method of 2-thioether-group-N, N-dimethylnicotinamide, which is characterized in that 2-chlorine-N, N-dimethylnicotinamide, sodium thiosulfate pentahydrate and substituent-containing alcohol are added into an organic solvent at a certain temperature for a one-pot condensation substitution reaction to obtain a product 2-thioether-group-N, N-dimethylnicotinamide.
The technical scheme for realizing the purpose of the invention is as follows: a preparation method of 2-thioether-N, N-dimethylnicotinamide comprises the following steps: adding 2-chloro-N, N-dimethylnicotinamide, sodium thiosulfate pentahydrate and alcohol containing substituent groups into an organic solvent at a certain temperature to perform a one-pot condensation substitution reaction to obtain a product 2-thioether-N, N-dimethylnicotinamide;
the reaction formula is as follows:
in the reaction formula, R is one of alkyl and aryl.
Further, a preparation method of the 2-thioether-N, N-dimethylnicotinamide, which comprises the following steps: sequentially adding an organic solvent, 2-chloro-N, N-dimethyl nicotinamide, sodium thiosulfate pentahydrate, alcohol containing substituent groups and water into a reaction container under the protection of nitrogen, stirring uniformly, and then heating to a set temperature; keeping the temperature at the temperature until the normalized content of the 2, 4, 2-chloro-N, N-dimethyl nicotinamide liquid chromatogram in the total material is less than 1 percent; and cooling, separating liquid, heating and distilling the organic layer to obtain the 2-thioether-N, N-dimethylnicotinamide.
The molar ratio of the 2-chloro-N, N-dimethyl nicotinamide, sodium thiosulfate pentahydrate and the alcohol containing the substituent group in the technical scheme is 1: 1-10: 1-10.
The molar ratio of the amount of the organic solvent to the 2-chloro-N, N-dimethylnicotinamide in the technical scheme is 1-10: 1.
The set temperature of the technical scheme is-20-150 ℃.
The organic solvent in the technical scheme is any one of halogenated hydrocarbon solvents, aromatic solvents, ether solvents, ester solvents, alcohol solvents and strong polar solvents containing hetero atoms.
In the technical scheme, the substituent group in the substituted alcohol is any one of alkyl and aryl.
The set temperature of the technical scheme is 120-150 ℃.
In the technical scheme, the halogenated hydrocarbon solvent is one or more of dichloromethane, dichloroethane and chloroform, the aromatic solvent is one or more of chlorobenzene, toluene and xylene, the ether solvent is tetrahydrofuran, the ester solvent is one or two of methyl acetate and ethyl acetate, the alcohol solvent is one or more of methanol, ethanol and isopropanol, and the strong polar solvent containing hetero atoms is one or more of DMF, DMA, DMSO, NMP, sulfolane and DMI
After the technical scheme is adopted, the invention has the following positive effects:
the method comprises the steps of adding 2-chloro-N, N-dimethylnicotinamide, sodium thiosulfate pentahydrate and alcohol containing substituent groups into an organic solvent at a certain temperature, and carrying out a one-pot condensation substitution reaction to obtain the product 2-thioether-N, N-dimethylnicotinamide. The method has the advantages of multiple raw material sources, obvious cost advantage, safer and more convenient preparation method, high total yield and less three wastes, particularly no discharge of toxic gases such as ammonia gas or hydrogen sulfide and the like, and is favorable for industrialization.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are a part of the embodiments of the present invention, but not all of the embodiments.
(example 1) 2-benzylthio-N' N-dimethylnicotinamide
Preparing a target product in a small trial:
adding 38.6g (0.20mol) of 2-chloro-N, N-dimethylnicotinamide, 99.2g (0.4mol) of sodium thiosulfate pentahydrate, 21.6g (0.20mol) of benzyl alcohol, 2mL of water and 100g of xylene into a 500mL four-neck flask, heating and stirring, carrying out reflux reaction at 120-140 ℃ for 5 hours, cooling, adding 50mL of water, carrying out liquid separation to obtain an oil layer, recovering the xylene, and carrying out reduced pressure distillation to obtain 480g of 98% of target 2-benzylthio-N' N-dimethylnicotinamide, wherein the yield is 88%.
(example 2) 2-benzylthio-N' N-dimethylnicotinamide
Pilot plant preparation of target product:
putting 386kg of 2-chloro-N, N-dimethyl nicotinamide, 1000kg of sodium thiosulfate pentahydrate, 216kg of benzyl alcohol, 20kg of water and 1000kg of dimethylbenzene into a 3000L enamel reaction kettle, slowly heating to reflux, keeping the temperature for 5 hours after the reaction is finished, cooling to 60 ℃, dropwise adding 500kg of water, separating to obtain an oil layer, distilling under reduced pressure after normal pressure to recover dimethylbenzene, and recovering 92% of recovery; after the recovery, the reduced pressure distillation is carried out to obtain 460kg of the target product 2-benzylthio-N' N-dimethylnicotinamide with the yield of 85 percent, wherein the target product is 98 percent.
(example 3) 2-thioether-N' N-dimethylnicotinamide
Preparing a target product in a small trial:
the optimized partial results of the parallel reaction for different alcohols with different substituents are as follows:
| serial number | Alcohol(s) | Solvent(s) | Yield of |
| 1 | 1-Butanol | Xylene | 54％ |
| 2 | 1-pentanol | Water (W) | 76％ |
| 3 | 1-octanol | DMSO | 80％ |
| 4 | Phenol and its preparation | DMF | 57％ |
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are only exemplary embodiments of the present invention, and are not intended to limit the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (9)
1. A preparation method of 2-thioether-N, N-dimethylnicotinamide is characterized by comprising the following steps: adding 2-chloro-N, N-dimethylnicotinamide, sodium thiosulfate pentahydrate and alcohol containing substituent groups into an organic solvent at a certain temperature to perform a one-pot condensation substitution reaction to obtain a product 2-thioether-N, N-dimethylnicotinamide;
the reaction formula is as follows:
in the reaction formula, R is one of alkyl and aryl.
2. The method of claim 1, comprising the steps of: sequentially adding an organic solvent, 2-chloro-N, N-dimethylnicotinamide, sodium thiosulfate pentahydrate, alcohol containing a substituent group and water into a reaction container under the protection of nitrogen, uniformly stirring, and then heating to a set temperature; keeping the temperature at the temperature until the normalized content of the 2, 4, 2-chloro-N, N-dimethyl nicotinamide liquid chromatogram in the total material is less than 1 percent; and cooling, separating liquid, heating and distilling the organic layer to obtain the 2-thioether-N, N-dimethylnicotinamide.
3. The method of claim 2, wherein the step of preparing the 2-thioether-N, N-dimethylnicotinamide is as follows: the mol ratio of the 2-chloro-N, N-dimethylnicotinamide, sodium thiosulfate pentahydrate and alcohol containing substituent groups is 1: 1-10: 1-10.
4. The method of claim 2, wherein the step of preparing the 2-thioether-N, N-dimethylnicotinamide is as follows: the molar ratio of the dosage of the organic solvent to the 2-chloro-N, N-dimethylnicotinamide is 1-10: 1.
5. The method of claim 2, wherein the step of preparing the 2-thioether-N, N-dimethylnicotinamide is as follows: the set temperature is-20 to 150 ℃.
6. The method of claim 2, wherein the step of preparing the 2-thioether-N, N-dimethylnicotinamide is as follows: the organic solvent is any one of halogenated hydrocarbon solvents, aromatic solvents, ether solvents, ester solvents, alcohol solvents and strong polar solvents containing hetero atoms.
7. The method of claim 2, wherein the step of preparing the 2-thioether-N, N-dimethylnicotinamide is as follows: the substituent in the substituted alcohol is any one of alkyl and aryl.
8. The method of claim 5, wherein the step of preparing the 2-thioether-N, N-dimethylnicotinamide is as follows: the set temperature is 120-150 ℃.
9. The method of claim 6, wherein the step of preparing the 2-thioether-N, N-dimethylnicotinamide is as follows: the halogenated hydrocarbon solvent is one or more of dichloromethane, dichloroethane and chloroform, the aromatic solvent is one or more of chlorobenzene, toluene and xylene, the ether solvent is tetrahydrofuran, the ester solvent is one or two of methyl acetate and ethyl acetate, the alcohol solvent is one or more of methanol, ethanol and isopropanol, and the strong polar solvent containing heteroatoms is one or more of DMF, DMA, DMSO, NMP, sulfolane and DMI.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN87101735A (en) * | 1986-03-07 | 1987-09-16 | 纳幕尔杜邦公司 | Herbicidal pyridine sulfonamides |
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- 2021-02-09 CN CN202110177024.4A patent/CN113214147B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN87101735A (en) * | 1986-03-07 | 1987-09-16 | 纳幕尔杜邦公司 | Herbicidal pyridine sulfonamides |
Non-Patent Citations (1)
| Title |
|---|
| XIANTAO MA 等: "Promoting Effect of Crystal Water Leading to Catalyst-Free Synthesis of Heteroaryl Thioether from Heteroaryl Chloride, Sodium Thiosulfate Pentahydrate, and Alcohol", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
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