CN105524017B - The preparation method of the thiadiazoles of 2 methylamino, 5 tert-butyl group 1,3,4 - Google Patents
The preparation method of the thiadiazoles of 2 methylamino, 5 tert-butyl group 1,3,4 Download PDFInfo
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- CN105524017B CN105524017B CN201510996719.XA CN201510996719A CN105524017B CN 105524017 B CN105524017 B CN 105524017B CN 201510996719 A CN201510996719 A CN 201510996719A CN 105524017 B CN105524017 B CN 105524017B
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- C07—ORGANIC CHEMISTRY
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- 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 kind of tert-butyl group 1 of 2 methylamino 5; 3; the preparation method of 4 thiadiazoles; the use of pivalic acid is directly raw material; it is again cyclization reagent to be acylating reagent with solid phosgene or two surpalites or phosgene; the thiadiazoles of 2 methylamino, 5 tert-butyl group 1,3,4 is synthesized with methylthiosemicarbazone.The preparation method can obtain the thiadiazoles of 2 methylamino, 5 tert-butyl group 1,3,4 of high-purity, and the method yield is very high, safe operation, production cost are very low, it is possible to resolve the defect that existing production technology is present, environmental protection is pollution-free.
Description
Technical field
The present invention relates to the 2- methylamino -5- tert-butyl group -1, the preparation method of 3,4- thiadiazoles.
Background technology
2- methylamino -5- the tert-butyl group -1,3,4- thiadiazoles are the key intermediate of tebuthiuron, tebuthiuron
(tebuthiuron) it is also known as terbufos benzthiazuron, the phenyl ureagroup herbicides of inner sucting conduction type broad spectrum activity, can be widely used for preventing and kill off
Grass family in shrub, sugarcane field and broad leaved weed in bare place weeds, pasture etc..
Current industrial process is that, with methylthiosemicarbazone and pivaloyl chloride as raw material, POCl3 is tried as cyclisation
Agent, equation is as shown in Figure 1.
Wherein, pivaloyl chloride is obtained by the reaction of the acylating reagents such as pivalic acid and thionyl chloride, phosphorus trichloride, phosphorus trichloride method
Generation is difficult to the accessory substance phosphorous acid for removing, typically need to be through rectifying, thus the yield of product is relatively low poor with purity；Thionyl chloride
Method produces unpleasant sulfur dioxide gas, etching apparatus to pollute environment.
The documents such as US3803164A, US3887572A, US4283543A are also reported and use polyphosphoric acids, phosphorus trichloride, five
The phosphorus reagents such as phosphorus chloride are cyclization reagent.When using POCl3, polyphosphoric acids, phosphorus trichloride, phosphorus pentachloride, the cyclisation
Reaction is whard to control, and strict demand is anhydrous, and reaction condition is harsher, and accessory substance is more, and product purity and yield are all relatively low.More
Seriously to generate substantial amounts of phosphorus-containing wastewater, these phosphorus-containing wastewaters are very difficult, and environmental pollution is very serious, do not meet
The direction of green chemistry.
Document do not reported and synthesized the 2- methylamino -5- tert-butyl group -1 as cyclization reagent using solid phosgene, 3,
4- thiadiazoles, do not reported yet synthesized as cyclization reagent using two surpalites or phosgene the 2- methylamino -5- tert-butyl groups -
1,3,4- thiadiazoles.
The content of the invention
The technical problems to be solved by the invention are to provide a kind of 2- methylaminos -5- tert-butyl group -1,3,4- thiadiazoles
Preparation method.We by the detailed research to reaction mechanism, we have invented the 2- methylamino -5- tert-butyl group -1,3,4- thiophenes
The cleaning new synthetic method of diazole, is directly raw material using pivalic acid (II), with solid phosgene or two surpalites or light
Gas is acylating reagent again for cyclization reagent, and the 2- methylamino -5- tert-butyl group -1 is synthesized with methylthiosemicarbazone (I), and 3,
4- thiadiazoles (III).The preparation method can obtain the 2- methylamino -5- tert-butyl group -1 of high-purity, 3,4- thiadiazoles, and the party
Method yield is very high, safe operation, production cost are very low, it is possible to resolve the defect that existing production technology is present, environmental protection, without dirt
Dye.
Equation of the invention is as shown in Figure 2.
Specific method of the invention is as follows：
1. first pivalic acid (II) is placed in reaction bulb, adds a certain amount of solvent, such as toluene, chlorobenzene, dimethylbenzene, dichloro
Methane, chloroform, 1,2- dichloroethanes, petroleum ether, hexamethylene etc., stirring heat up, and are warmed up to uniform temperature, add a certain amount of
Solid phosgene or two surpalites or phosgene, continue to react complete at a certain temperature, the HCl gas that reaction generation is released
Body is passed through in water the hydrochloric acid that can prepare high-purity, and reaction solution is cooled to room temperature, stand-by；
2. the solvent mentioned in acylation step above, optimum solvent is toluene；
3. the reaction temperature mentioned in acylation step above is 60 DEG C -120 DEG C, and optimum temperature is 70 DEG C -90 DEG C；
4. the pivalic acid (II) mentioned in acylation step above is 1 with the molar ratio of solid phosgene: 0.33-0.67；
5. the pivalic acid (II) mentioned in acylation step above is 1 with the molar ratio of two surpalites: 0.5-1；
6. the pivalic acid (II) mentioned in acylation step above is 1 with the molar ratio of phosgene: 1-2；
7. add methylthiosemicarbazone (I) and organic base and a certain amount of solvent in another reaction bulb, such as toluene,
Chlorobenzene, dimethylbenzene, dichloromethane, chloroform, 1,2- dichloroethanes, petroleum ether, hexamethylene etc., under stirring at a certain temperature
Above-mentioned reaction solution is added dropwise, drop finishes, continues to react complete at a certain temperature, add water and reaction is quenched, extract, desolvation, i.e.,
Obtain the 2- methylamino -5- tert-butyl group -1,3,4- thiadiazoles (III)；
8. the methylthiosemicarbazone (I) mentioned in cyclisation step above, its with acylation step in the pivalic acid (II) mentioned
Molar ratio be 1: 1-1.2, best proportion is 1: 1；
9. the organic base mentioned in cyclisation step above is selected from triethylamine, pyridine, DMA etc., optimal organic
Alkali is triethylamine；
10. the methylthiosemicarbazone (I) mentioned in cyclisation step above is 1 with the molar ratio of organic base: 0.1-3；
The solvent mentioned in cyclisation step above 11., optimum solvent is toluene；
The reaction temperature mentioned in cyclisation step above 12. is 60 DEG C -120 DEG C, and optimum temperature is 90 DEG C -110 DEG C.
The invention has the advantages that：Reaction condition is not harsh, and absolute is not needed in system；Operation serialization, saves
The separating-purifying of pivaloyl chloride is removed；Yield is higher；Product content is higher；Accessory substance only has carbon dioxide, does not have any containing
Phosphorus waste water, realizes process for cleanly preparing.
Brief description of the drawings
Fig. 1 is the current industrial production 2- methylamino -5- tert-butyl group -1, the equation of the method for 3,4- thiadiazoles；
Fig. 2 is equation of the invention.
Specific embodiment
Following embodiments can be used to further illustrate the present invention, but be not intended to limit the present invention.
Embodiment 1：
30g pivalic acids, plus the dissolving of 30mL toluene are added in 250mL there-necked flasks, 80 DEG C are warming up to, solid-state light is dividedly in some parts
Gas 43g.Finish, continue to react 2 hours, the HCl gases of releasing are passed into water.Room temperature is cooled to, it is stand-by.
Methylthiosemicarbazone 28g and toluene 30mL, plus triethylamine 6g are added in 500mL four-hole bottles, 100 under mechanical agitation
DEG C above-mentioned solution is added dropwise, drop finishes, and continues to react 3 hours.Stop reaction, add water and reaction is quenched, organic layer is separated, water layer toluene
Extraction.Merge organic layer, precipitation obtains white solid 44.9g, and yield is that 98.5%, HPLC detection purity is 98.6%.
Embodiment 2：
30g pivalic acids, plus the dissolving of 30mL toluene are added in 250mL there-necked flasks, 80 DEG C are warming up to, solid-state light is dividedly in some parts
Gas 43g.Finish, continue to react 2 hours, the HCl gases of releasing are passed into water.Room temperature is cooled to, it is stand-by.
Methylthiosemicarbazone 28g and toluene 30mL, plus triethylamine 81g are added in 500mL four-hole bottles, under mechanical agitation
100 DEG C are added dropwise above-mentioned solution, and drop finishes, and continue to react 3 hours.Stop reaction, add water and reaction is quenched, organic layer is separated, water layer is used
Toluene is extracted.Merge organic layer, precipitation obtains white solid 44.3g, and yield is that 97.1%, HPLC detection purity is 97.6%.
Embodiment 3：
30g pivalic acids, plus the dissolving of 30mL toluene are added in 250mL there-necked flasks, 80 DEG C are warming up to, two optically focused are dividedly in some parts
Gas 45g.Finish, continue to react 2 hours, the HCl gases of releasing are passed into water.Room temperature is cooled to, it is stand-by.
Methylthiosemicarbazone 28g and toluene 30mL, plus triethylamine 4g are added in 500mL four-hole bottles, 100 under mechanical agitation
DEG C above-mentioned solution is added dropwise, drop finishes, and continues to react 3 hours.Stop reaction, add water and reaction is quenched, organic layer is separated, water layer toluene
Extraction.Merge organic layer, precipitation obtains white solid 45.1g, and yield is that 98.9%, HPLC detection purity is 98.8%.
Embodiment 4：
30g pivalic acids, plus the dissolving of 30mL toluene are added in 250mL there-necked flasks, 80 DEG C are warming up to, phosgene is slowly passed through
47g.Finish, continue to react 2 hours, the HCl gases of releasing are passed into water.Room temperature is cooled to, it is stand-by.
Methylthiosemicarbazone 28g and toluene 30mL, plus triethylamine 62g are added in 500mL four-hole bottles, under mechanical agitation
100 DEG C are added dropwise above-mentioned solution, and drop finishes, and continue to react 3 hours.Stop reaction, add water and reaction is quenched, organic layer is separated, water layer is used
Toluene is extracted.Merge organic layer, precipitation obtains white solid 45.0g, and yield is that 98.6%, HPLC detection purity is 98.4%.
Claims (11)
1. a kind of 2- methylaminos -5- tert-butyl group -1, the preparation method of 3,4- thiadiazoles, are directly original using pivalic acid (II)
Material, it is again cyclization reagent to be acylating reagent with solid phosgene or two surpalites or phosgene, with methylthiosemicarbazone (I)
It is synthesized the 2- methylamino -5- tert-butyl group -1,3,4- thiadiazoles (III), reaction equation is as follows：
It is characterized in that the preparation method comprises the following steps：First pivalic acid (II) is placed in reaction bulb, is added a certain amount of
Solvent, stirring heats up, and is warmed up to 60 DEG C -120 DEG C, adds solid phosgene or two surpalites or phosgene, continue 60 DEG C -
React complete at 120 DEG C, the HCl gases that reaction generation is released are passed through in water the hydrochloric acid that can prepare high-purity, reaction solution is cooled to
Room temperature, it is stand-by；Methylthiosemicarbazone (I) and organic base and a certain amount of solvent are added in another reaction bulb, under stirring
Above-mentioned reaction solution is added dropwise at 60 DEG C -120 DEG C, drop finishes, continues to react complete at 60 DEG C -120 DEG C, add water and reaction is quenched,
Extraction, desolvation obtains the 2- methylamino -5- tert-butyl group -1,3,4- thiadiazoles (III)；
Wherein described solvent is selected from toluene, chlorobenzene, dimethylbenzene, dichloromethane, chloroform, 1,2- dichloroethanes, petroleum ether, ring
Hexane.
2. a kind of 2- methylaminos -5- tert-butyl group -1 according to claim 1, the preparation method of 3,4- thiadiazoles, it is special
Levy is that described solvent is toluene.
3. the reaction temperature mentioned in acylation step according to claim 1, it is characterised in that temperature is 70 DEG C -90 DEG C.
4. a kind of 2- methylaminos -5- tert-butyl group -1 according to claim 1, the preparation method of 3,4- thiadiazoles, it is special
It is pivalic acid (II) to levy and the molar ratio of solid phosgene is 1：0.33-0.67.
5. a kind of 2- methylaminos -5- tert-butyl group -1 according to claim 1, the preparation method of 3,4- thiadiazoles, it is special
It is pivalic acid (II) to levy and the molar ratio of two surpalites is 1：0.5-1.
6. a kind of 2- methylaminos -5- tert-butyl group -1 according to claim 1, the preparation method of 3,4- thiadiazoles, it is special
It is pivalic acid (II) to levy and the molar ratio of phosgene is 1：1-2.
7. a kind of 2- methylaminos -5- tert-butyl group -1 according to claim 1, the preparation method of 3,4- thiadiazoles, it is special
It is methylthiosemicarbazone (I) to levy and the molar ratio of pivalic acid (II) is 1：1-1.2.
8. a kind of 2- methylaminos -5- tert-butyl group -1 according to claim 1, the preparation method of 3,4- thiadiazoles, it is special
Levy is that organic base is selected from triethylamine, pyridine, N, accelerine.
9. organic base according to claim 8, it is characterised in that organic base is triethylamine.
10. a kind of 2- methylaminos -5- tert-butyl group -1 according to claim 1, the preparation method of 3,4- thiadiazoles, it is special
It is methylthiosemicarbazone (I) to levy and the molar ratio of organic base is 1：0.1-3.
The reaction temperature mentioned in 11. cyclisation steps according to claim 1, it is characterised in that temperature is 90 DEG C -110
℃。
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| 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 |
| 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 |
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 |
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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》.2006,第29卷(第11期),第16-19页. * |
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