CN105524017A - Preparation method of 2-methylamino-5-t-butyl-1,3,4-thiadiazole - Google Patents
Preparation method of 2-methylamino-5-t-butyl-1,3,4-thiadiazole Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
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Abstract
The invention provides a preparation method of 2-methylamino-5-t-butyl-1,3,4-thiadiazole. Pivalic acid directly used as a raw material reacts with methylthiosemicarbazide with solid phosgene or a phosgene dimer or phosgene as an acylation reagent and a cyclization reagent to synthesize 2-methylamino-5-t-butyl-1,3,4-thiadiazole. The preparation method allows highly pure 2-methylamino-5-t-butyl-1,3,4-thiadiazol to be prepared, has the advantages of very high yield, safe operation, very low production cost, solving of the defects of existing production technologies, environmental protection and no pollution.
Description
Technical field
The present invention relates to the preparation method of the 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles.
Background technology
2-methylamino-5-the tertiary butyl-1,3,4-thiadiazoles is the key intermediate of tebuthiuron, tebuthiuron (tebuthiuron) has another name called terbufos benzthiazuron, for the phenyl ureagroup herbicides of inner sucting conduction type broad spectrum, can be widely used in and prevent and kill off the shrub in bare place weeds, pasture, the Gramineae in sugarcane field and broadleaf weeds etc.
Current industrial process is that phosphorus oxychloride is as cyclization reagent, and equation as shown in Figure 1 with methylthiosemicarbazone and pivaloyl chloride for raw material.
Wherein, pivaloyl chloride reacts obtained by trimethylacetic acid and the acylating reagent such as sulfur oxychloride, phosphorus trichloride, and phosphorus trichloride method generates the by product phosphorous acid being difficult to remove, generally need through rectifying, and thus the yield of product is lower poor with purity; Sulfur oxychloride method produces unpleasant sulfur dioxide gas, etching apparatus, contaminate environment.
The documents such as US3803164A, US3887572A, US4283543A also report that phosphorus reagents such as using polyphosphoric acid, phosphorus trichloride, phosphorus pentachloride is cyclization reagent.When using phosphorus oxychloride, polyphosphoric acid, phosphorus trichloride, phosphorus pentachloride, this cyclization is wayward, and is strict with anhydrous, and reaction conditions is harsher, and by product is many, and product purity and yield are all lower.More seriously create a large amount of phosphorus-containing wastewaters, these phosphorus-containing wastewaters are very difficult, and environmental pollution is very serious, does not meet the direction of green chemistry.
Document did not report use solid phosgene as cyclization reagent to synthesize the 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles, did not report yet and used two surpalites or phosgene as cyclization reagent to synthesize the 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of preparation method of the 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles.We are by studying in great detail reaction mechanism; we have invented the 2-methylamino-5-tertiary butyl-1; 3; the clean new synthetic method of 4-thiadiazoles; direct use trimethylacetic acid (II) is raw material, and being acylating reagent with solid phosgene or two surpalites or phosgene is cyclization reagent again, with methylthiosemicarbazone (I) the Reactive Synthesis 2-methylamino-5-tertiary butyl-1; 3,4-thiadiazoles (III).This preparation method can obtain the highly purified 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles, and the method yield is very high, operational safety, production cost are very low, can solve the defect that existing production technique exists, environmental protection, pollution-free.
Equation of the present invention as shown in Figure 2.
Concrete grammar of the present invention is as follows:
1. first trimethylacetic acid (II) is placed in reaction flask, add a certain amount of solvent, as toluene, chlorobenzene, dimethylbenzene, methylene dichloride, trichloromethane, 1,2-ethylene dichloride, sherwood oil, hexanaphthene etc., stir and heat up, be warmed up to certain temperature, add a certain amount of solid phosgene or two surpalites or phosgene, continue to react completely at a certain temperature, reaction generates the HCl gas of releasing and passes in water and can prepare highly purified hydrochloric acid, reaction solution is cooled to room temperature, stand-by;
2. the solvent mentioned in acylation step above, optimum solvent is toluene;
3. the temperature of reaction mentioned in acylation step above is 60 DEG C-120 DEG C, and optimum temps is 70 DEG C-90 DEG C;
4. the trimethylacetic acid (II) mentioned in acylation step above is 1: 0.33-0.67 with the molar ratio of solid phosgene;
5. the trimethylacetic acid (II) mentioned in acylation step above is 1: 0.5-1 with the molar ratio of two surpalites;
6. the trimethylacetic acid (II) mentioned in acylation step above is 1: 1-2 with the molar ratio of phosgene;
7. in another reaction flask, add methylthiosemicarbazone (I) and organic bases and a certain amount of solvent, as toluene, chlorobenzene, dimethylbenzene, methylene dichloride, trichloromethane, 1,2-ethylene dichloride, sherwood oil, hexanaphthene etc., under stirring, drip above-mentioned reaction solution at a certain temperature, drip and finish, continue to react completely at a certain temperature, the cancellation that adds water is reacted, extraction, desolvation, namely the 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles (III) is obtained;
8. the methylthiosemicarbazone (I) mentioned in cyclisation step above, the molar ratio of the trimethylacetic acid (II) mentioned in itself and acylation step is 1: 1-1.2, and best proportion is 1: 1;
9. the organic bases mentioned in cyclisation step above is selected from triethylamine, pyridine, DMA etc., and best organic bases is triethylamine;
10. the methylthiosemicarbazone (I) mentioned in cyclisation step above is 1: 0.1-3 with the molar ratio of organic bases;
The solvent mentioned in cyclisation step above 11., optimum solvent is toluene;
The temperature of reaction mentioned in cyclisation step above 12. is 60 DEG C-120 DEG C, and optimum temps is 90 DEG C-110 DEG C.
Tool of the present invention has the following advantages: reaction conditions is not harsh, does not need absolute in system; Operation serialization, eliminates the separating-purifying of pivaloyl chloride; Yield is higher; Product content is higher; By product only has carbonic acid gas, without any phosphorus-containing wastewater, achieve process for cleanly preparing.
Accompanying drawing explanation
Fig. 1 is the equation of the method for the current industrial production 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles;
Fig. 2 is equation of the present invention.
Embodiment
Following embodiment can be used to further illustrate the present invention, but does not mean that restriction the present invention.
Embodiment 1:
In 250mL there-necked flask, add 30g trimethylacetic acid, add 30mL toluene and dissolve, be warming up to 80 DEG C, add solid phosgene 43g in batches.Finish, continue reaction 2 hours, the HCl gas of releasing is passed in water.Be cooled to room temperature, stand-by.
In 500mL four-hole bottle, add methylthiosemicarbazone 28g and toluene 30mL, add triethylamine 6g, lower 100 DEG C of mechanical stirring drips above-mentioned solution, drips and finishes, continue reaction 3 hours.Stopped reaction, the cancellation that adds water is reacted, and organic layer is separated, and water layer toluene extracts.Merge organic layer, precipitation obtains white solid 44.9g, and yield is 98.5%, HPLC detection purity is 98.6%.
Embodiment 2:
In 250mL there-necked flask, add 30g trimethylacetic acid, add 30mL toluene and dissolve, be warming up to 80 DEG C, add solid phosgene 43g in batches.Finish, continue reaction 2 hours, the HCl gas of releasing is passed in water.Be cooled to room temperature, stand-by.
In 500mL four-hole bottle, add methylthiosemicarbazone 28g and toluene 30mL, add triethylamine 81g, lower 100 DEG C of mechanical stirring drips above-mentioned solution, drips and finishes, continue reaction 3 hours.Stopped reaction, the cancellation that adds water is reacted, and organic layer is separated, and water layer toluene extracts.Merge organic layer, precipitation obtains white solid 44.3g, and yield is 97.1%, HPLC detection purity is 97.6%.
Embodiment 3:
In 250mL there-necked flask, add 30g trimethylacetic acid, add 30mL toluene and dissolve, be warming up to 80 DEG C, add two surpalite 45g in batches.Finish, continue reaction 2 hours, the HCl gas of releasing is passed in water.Be cooled to room temperature, stand-by.
In 500mL four-hole bottle, add methylthiosemicarbazone 28g and toluene 30mL, add triethylamine 4g, lower 100 DEG C of mechanical stirring drips above-mentioned solution, drips and finishes, continue reaction 3 hours.Stopped reaction, the cancellation that adds water is reacted, and organic layer is separated, and water layer toluene extracts.Merge organic layer, precipitation obtains white solid 45.1g, and yield is 98.9%, HPLC detection purity is 98.8%.
Embodiment 4:
In 250mL there-necked flask, add 30g trimethylacetic acid, add 30mL toluene and dissolve, be warming up to 80 DEG C, slowly pass into phosgene 47g.Finish, continue reaction 2 hours, the HCl gas of releasing is passed in water.Be cooled to room temperature, stand-by.
In 500mL four-hole bottle, add methylthiosemicarbazone 28g and toluene 30mL, add triethylamine 62g, lower 100 DEG C of mechanical stirring drips above-mentioned solution, drips and finishes, continue reaction 3 hours.Stopped reaction, the cancellation that adds water is reacted, and organic layer is separated, and water layer toluene extracts.Merge organic layer, precipitation obtains white solid 45.0g, and yield is 98.6%, HPLC detection purity is 98.4%.
Claims (14)
1. a 2-methylamino-5-tertiary butyl-1; 3; the preparation method of 4-thiadiazoles; direct use trimethylacetic acid (II) is raw material; being acylating reagent with solid phosgene or two surpalites or phosgene is cyclization reagent again, with methylthiosemicarbazone (I) the Reactive Synthesis 2-methylamino-5-tertiary butyl-1,3; 4-thiadiazoles (III), reaction formula is as follows:
It is characterized in that this preparation method comprises the steps: first to be placed in reaction flask by trimethylacetic acid (II), add a certain amount of solvent, stir and heat up, be warmed up to certain temperature, add a certain amount of solid phosgene or two surpalites or phosgene, continue to react completely at a certain temperature, reaction generates the HCl gas of releasing and passes in water and can prepare highly purified hydrochloric acid, reaction solution is cooled to room temperature, stand-by; Methylthiosemicarbazone (I) and organic bases and a certain amount of solvent is added in another reaction flask, above-mentioned reaction solution is dripped at a certain temperature under stirring, drip and finish, continue to react completely at a certain temperature, the cancellation that adds water is reacted, extraction, desolvation, namely the 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles (III) is obtained.
2. a kind of 2-methylamino-5-tertiary butyl-1 according to claim 1,3, the preparation method of 4-thiadiazoles, is characterized in that described solvent is selected from toluene, chlorobenzene, dimethylbenzene, methylene dichloride, trichloromethane, 1,2-ethylene dichloride, sherwood oil, hexanaphthene.
3. solvent according to claim 2, is characterized in that optimum solvent is toluene.
4. the preparation method of a kind of 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles according to claim 1, is characterized in that the temperature of reaction mentioned in acylation step is 60 DEG C-120 DEG C.
5. the temperature of reaction mentioned in acylation step according to claim 4, is characterized in that optimum temps is 70 DEG C-90 DEG C.
6. the preparation method of a kind of 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles according to claim 1, is characterized in that trimethylacetic acid (II) is 1: 0.33-0.67 with the molar ratio of solid phosgene.
7. the preparation method of a kind of 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles according to claim 1, is characterized in that trimethylacetic acid (II) is 1: 0.5-1 with the molar ratio of two surpalites.
8. the preparation method of a kind of 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles according to claim 1, is characterized in that trimethylacetic acid (II) is 1: 1-2 with the molar ratio of phosgene.
9. the preparation method of a kind of 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles according to claim 1, is characterized in that methylthiosemicarbazone (I) is 1: 1-1.2 with the molar ratio of trimethylacetic acid (II).
10. the preparation method of a kind of 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles according to claim 1, is characterized in that organic bases is selected from triethylamine, pyridine, DMA.
11. organic basess according to claim 10, is characterized in that best organic bases is triethylamine.
The preparation method of the 12. a kind of 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles according to claim 1, is characterized in that methylthiosemicarbazone (I) is 1: 0.1-3 with the molar ratio of organic bases.
The preparation method of the 13. a kind of 2-methylamino-5-tertiary butyl-1,3,4-thiadiazoles according to claim 1, is characterized in that the temperature of reaction mentioned in cyclisation step is 60 DEG C-120 DEG C.
The temperature of reaction mentioned in 14. cyclisation step according to claim 13, is characterized in that optimum temps is 90 DEG C-110 DEG C.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109251188A (en) * | 2018-09-26 | 2019-01-22 | 河北工业大学 | A kind of preparation method of 2- methylamino -5- tert-butyl -1,3,4- thiadiazoles |
| CN110372634A (en) * | 2019-07-29 | 2019-10-25 | 宁夏晟丰元化工有限公司 | A method of synthesis 2- methylamino -5- tert-butyl -1,3,4- thiadiazoles |
Citations (3)
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|---|---|---|---|---|
| US4338449A (en) * | 1981-06-15 | 1982-07-06 | Eli Lilly And Company | Herbicidal thiadiazolines |
| CN1163881A (en) * | 1996-02-29 | 1997-11-05 | 罗纳-普朗克农业化学公司 | Phosgenation under pressure of acids and/or anhydrides for production of acid chlorides |
| CN103288777A (en) * | 2013-05-28 | 2013-09-11 | 浙江禾田化工有限公司 | Synthesis method of key intermediate of tebuthiuron, namely 2-methylamino-5-tert-butyl-1, 3, 4-thiadiazole |
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2015
- 2015-12-24 CN CN201510996719.XA patent/CN105524017B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4338449A (en) * | 1981-06-15 | 1982-07-06 | Eli Lilly And Company | Herbicidal thiadiazolines |
| CN1163881A (en) * | 1996-02-29 | 1997-11-05 | 罗纳-普朗克农业化学公司 | Phosgenation under pressure of acids and/or anhydrides for production of acid chlorides |
| CN103288777A (en) * | 2013-05-28 | 2013-09-11 | 浙江禾田化工有限公司 | Synthesis method of key intermediate of tebuthiuron, namely 2-methylamino-5-tert-butyl-1, 3, 4-thiadiazole |
Non-Patent Citations (1)
| Title |
|---|
| 信建峰; 马吉海; 张树芬; 陈韶蕊; 李海于: "酰氯制备方法综述", 《河北化工》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109251188A (en) * | 2018-09-26 | 2019-01-22 | 河北工业大学 | A kind of preparation method of 2- methylamino -5- tert-butyl -1,3,4- thiadiazoles |
| CN110372634A (en) * | 2019-07-29 | 2019-10-25 | 宁夏晟丰元化工有限公司 | A method of synthesis 2- methylamino -5- tert-butyl -1,3,4- thiadiazoles |
| CN110372634B (en) * | 2019-07-29 | 2021-03-19 | 宁夏常晟药业有限公司 | Method for synthesizing 2-methylamino-5-tert-butyl-1, 3, 4-thiadiazole |
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