CN102399216A - Method for producing thiacloprid technical - Google Patents
Method for producing thiacloprid technical Download PDFInfo
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- CN102399216A CN102399216A CN201110389533XA CN201110389533A CN102399216A CN 102399216 A CN102399216 A CN 102399216A CN 201110389533X A CN201110389533X A CN 201110389533XA CN 201110389533 A CN201110389533 A CN 201110389533A CN 102399216 A CN102399216 A CN 102399216A
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Abstract
The invention discloses a method for producing thiacloprid technical, which comprises the following steps of: synthesizing cyanamide, caustic soda liquid and carbon disulfide which are used as raw materials under the action of a catalyst; then performing a reaction on the obtained product and dimethyl sulfate to obtain N-cyanoimido-S,S-dimethyl-dithiocarbonate; performing a reaction on the obtained N-cyanoimido-S,S-dimethyl-dithiocarbonate and cysteamine hydrochloride to synthesize 2-cyanoimino-1,3-thiazolidine; and finally, performing a reaction on the 2-cyanoimino-1,3-thiazolidine and 2-chloro-5-chloromethylpyridine in a solvent, completing dropwise adding carbon disulfide in a temperature range of 5 DEG C to 20 DEG C and then performing a temperature rising reaction, wherein the catalyst is tetrabutyl ammonium bromide and after being extracted by using chloroform as an extracting solvent, the N-cyanoimido-S,S-dimethyl-dithiocarbonate directly reacts with the cysteamine hydrochloride.
Description
Technical field
The present invention relates to a kind of chloro nicotinic insecticide, the working method of the former medicine of particularly a kind of thiophene worm quinoline.
Background technology
Thiophene worm quinoline is the chloro nicotinoids new pesticides of Bayer farmingization company and the joint study exploitation of Japanese Bayer farmingization company, and is effective to piercing mouth parts and some biting mouth parts insects, is the sterilant of interior suction wide spectrum.The chemical name of thiophene worm quinoline is: 3-[(6-chloro-3-pyridyl) methyl]-1,3-thiazoles quinoline-2-base fork cyanogen (acyl) amine or (3-(6-chloro-3-pyridyl) first
Base-1,3-thiazoline-2-subunit) cyanamide, molecular formula is C
10H
9ClN
4S; English common name is: thiacloprid, and structural formula is:
Thiophene worm quinoline toxicity test: acute oral LD50 rat (hero): 836mg/kg body weight, (female): 444mg/kg body weight; Acute deadly LD50 (24h) rat (male, female):>The 2000mg/kg body weight; Acute suction LC50 (4h, aerosol) rat (hero):>2535mg/m
3Air, (female): ~ 122mg/m
3Air.The same with Provado, thiophene worm quinoline also acts on the nicotinic acid acetylcholine receptor, and it and common insecticides do not have cross resistance as intending deinsectization polyester, organic phosphates and amino formate, thereby can be used for resistance management.In soil, the transformation period of thiophene worm quinoline is short, and 7-21 days, movability was low to moderate medium.To birds, fish and multiple beneficial arthropods safety.To rabbit skin have no stimulation (4h); To lagophthalmos eyeball have no stimulation (24h); Guinea pig skin there is not sensitization; Rat there is not carcinogenesis; Rat and rabbit there is not former development toxicity; No heredity and mutagenesis.
Zhang Pin, Wu Daoxin etc. are published in " fine-chemical intermediate " the 40th volume 23-26 page or leaf in December, 2010 the 6th phase synthesising process research of low toxic pesticide thiophene worm quinoline " efficient, " and have highlighted in the laboratory; With cyanamide, dithiocarbonic anhydride, methyl-sulfate, Mercaptamine etc. is raw material; Mineral alkali is made acid binding agent Synthetic 2-itrile group imines-1,3-thiazoles quinoline; Then, under the propyl carbinol solvent again with 2-chloro-5-PMC react thiophene worm quinoline.Wherein, when synthesizing disodium salt, be that the triethyl benzyl ammonia chloride that adopts is a catalyzer.Concrete synthetic route is following:
The price of the used catalyzer and the solvent, n-butanol in later stage is all than higher in
this method; And propyl carbinol is difficult for reclaiming or cost recovery is too high, is inappropriate for very much suitability for industrialized production.
So; At present the general technology that adopts mainly is to be raw material with cyanamide, liquid caustic soda, dithiocarbonic anhydride in the suitability for industrialized production, and benzyl trimethyl ammonium chloride is a catalyzer, synthetic at a lower temperature disodium salt; Generate N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester with the methyl-sulfate effect again.Under alkaline condition, with the Mercaptamine cyclization, generating thiazolidine, is that solvent and CCMP effect generate product at last with ethanol.But, also there is following shortcoming:
1) catalyzer can not reclaim, and brings the postorder reaction into, causes waste and postorder is reacted influence.
2) the disodium salt synthesis reaction temperature is low, and the reaction times is longer, generally more than 20 hours.
3) after diester is synthetic, carry out processing such as crystallisation by cooling, filtration, washing, drying to product, technical process is comparatively loaded down with trivial details, and the product loss is more.
4) the synthetic ethanol that adopts of thiophene worm quinoline is made solvent, and it is too high to be difficult for recovery or cost recovery.
Summary of the invention
Can not recovery in order to solve catalyzer that prior art exists, deficiency such as long reaction time, product loss be many; The invention provides the working method of the former medicine of a kind of thiophene worm quinoline, have that the synthetic catalyst system therefor of disodium salt can reclaim and advantage cheap, that the reaction times short, the product loss is few.
Technical scheme of the present invention is: the working method of the former medicine of a kind of thiophene worm quinoline; With cyanamide, liquid caustic soda, dithiocarbonic anhydride is raw material synthetic (hereinafter to be referred as disodium salt) in the presence of catalyzer; Obtain N-cyanogen imido grpup-S with the methyl-sulfate reaction then; S-dithiocarbonic acid dimethyl ester (abbreviation diester) is again with Mercaptamine reaction Synthetic 2-cyanic acid imines-1,3-thiazoles alkane; At last; In solvent again with 2-chloro-5-PMC react thiophene worm quinoline; In 5 ℃～20 ℃ TR, dithiocarbonic anhydride is dropwised, and then temperature reaction, described catalyzer is a Tetrabutyl amonium bromide; With the N-cyanogen imido grpup-S that obtains, S-dithiocarbonic acid dimethyl ester is the direct and Mercaptamine reaction in extraction solvent extraction back with the chloroform.
Described solvent is a methyl alcohol.
When synthetic
; Temperature of reaction is 30 ℃～60 ℃ reactions; When synthesizing thiophene worm quinoline, temperature of reaction is the reflux temperature of methyl alcohol.
Described Tetrabutyl amonium bromide finishes the after-filtration separation in reaction and re-uses.
Described solvent methanol is reacting after come into operation after the rectification process again.
Described extraction solvent haloform reaction finishes the back negative pressure and distillates recovery set usefulness.
Beneficial effect:
1, in disodium salt is synthetic, selected a kind of new catalyzer Tetrabutyl amonium bromide, not only price is much lower than benzyl trimethyl ammonium chloride, and reaction effect is more obvious, and catalyzer adds the back CL and participates in reaction, has accelerated speed of response.Reaction is all separated out after finishing, and directing terminal arrives, and can reuse through filter cloth with the catalyzer elimination.Both reduced production costs, and can not bring down catalyzer into the step reaction again, reduced the possibility that negative reaction takes place.
2, in disodium salt is synthetic, we are employed under 5 ℃～20 ℃ the temperature and drip off dithiocarbonic anhydride, then solution temperature slowly are promoted to 30 ℃-60 ℃, are allowed to condition at high temperature under and react.Improve speed of response greatly, shortened the reaction times, reduced production cost, improved efficiency.
3, behind the diester end of synthesis, we adopt chloroform as extraction solvent, with the N-cyanogen imido grpup-S that generates; S-dithiocarbonic acid dimethyl ester is dissolved in chloroform, forms chloroform two ester solutions, makes diester and aqueous phase separation; The purity of diester is higher, directly is used for synthesizing of step thiazolidine down.Avoided that diester is carried out crystallisation by cooling, filtration, washing and dry supervisor and reached parcel and the product loss that in this process, produces impurity.Only need after the thiazolidine reaction finishes, the chloroform negative pressure to be distillated, can realize recovery set usefulness.Simplified operation steps, reduced product and too much lost.And, adopt liquid to drip and replace solid to feed intake, shortened the reaction times, make reaction more abundant.
4, when thiophene worm quinoline is synthetic,, adopt methyl alcohol as solvent through selecting; Not only price is low but also reduced the temperature of building-up reactions than propyl carbinol; Make temperature by 70 ℃-85 ℃ original methanol eddy temperature of reducing to 40 ℃-65 ℃, reduced the waste of the energy, reduced production cost.Also reduce the generation of by product simultaneously, reduced the solubleness of product in solvent, improved product content and yield.Reaction back solvent is easier to recovery set usefulness than propyl carbinol, after propyl carbinol uses, because moisture in the system,
Propyl carbinol content is reduced to60-80%wt, if will be recycled to the 99.9%wt propyl carbinol, cost is too high.Use methyl alcohol to make solvent, mother liquor only needs solvent after thick the steaming, is carried out rectifying again in still, is easy to reach more than the 99%wt, can realize applying mechanically.
Description of drawings
Fig. 1 is a process flow sheet of the present invention.
Embodiment
The agents useful for same source:
30%wt cyanamide: Rugao Zhongru Chemical Co., Ltd.
30%wt sodium hydroxide: the sky, Xuzhou becomes chlor-alkali ltd
Dithiocarbonic anhydride: Shanghai White aurification worker Group Co.,Ltd
Tetrabutyl amonium bromide: Shuyang County Feng Tai chemical ltd
30%wt hydrochloric acid: permanent Tonghua of sun coal, Shandong worker limited-liability company
Methyl-sulfate: the far rich chemical industry ltd in Linyi
Chloroform: Jiangsu Meilan Chemical Co
Half Guang ammonia hydrochloric acid salt: pacify little emerging eastern chemical industry ltd
Methyl alcohol: Xinyi branch office of Xuzhou auspicious trade of goods and materials far away ltd
Formaldehyde: the elder brother of Xinyi City army resin ltd
2-chloro-5-chloro-picoline: the industrial chemical industry in Langfang, Hebei ltd
Synthesis route of the present invention is following:
(1) the building-up reactions formula of disodium salt:
(3) the building-up reactions formula of 2-cyanic acid imines-1,3-thiazoles alkane:
(4) the building-up reactions formula of thiophene worm quinoline:
Concrete operations are as follows:
Embodiment 1:
1, the synthesis procedure of disodium salt
The cyanamide aqueous solution of a certain amount of 30%wt is dropped in the reaction kettle, be cooled to 0-5 ℃, according to the mol ratio cyanamide: sodium hydroxide is the sodium hydroxide solution that the ratio of 1:1.5～3.5 drips 30%wt; After dripping off, the amount according to 1mol cyanamide adding 0.1-2g four butyl bromation amine adds the catalyzer four butyl bromation amine; Ratio according to mol ratio cyanamide: dithiocarbonic anhydride=1:1～3 drips dithiocarbonic anhydride; Dropping temperature must not be higher than 20 ℃, after dripping off, material slowly is warming up to 30 ℃-60 ℃.Under this temperature stirring reaction 3-10 hour.After reaction is accomplished, with-0.01～-little vacuum distillation of 0.03MPa goes out unreacted dithiocarbonic anhydride.Distillation finishes, with material through suction filtration groove suction surge tank, with the catalyzer elimination.
2, N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester synthesis procedure
Filter pump is squeezed into N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester synthesis reactor.Be cooled to 10-20 ℃; In still, add hydrochloric acid and regulate pH=7-10 in the still; Regulate the still temperature at 10-30 ℃. the ratio according to mol ratio disodium salt: methyl-sulfate=1:1～3 is added dropwise to methyl-sulfate in still, under above-mentioned temperature and pH value condition, methyl-sulfate has been thrown.Control temperature in the kettle at 10-30 ℃, in still the pH value in half a hour constant basically till (needing 2-5 hour approximately).With chloroform extraction 2 times, extraction for the first time is according to 50-90mL chloroform/mole N-cyanogen imido grpup-S, the adding of the amount of S-dithiocarbonic acid dimethyl ester; Extraction is according to 10-30mL/ mole N-cyanogen imido grpup-S for the second time; The amount of S-dithiocarbonic acid dimethyl ester adds, and with twice extraction liquid merging, weighs up chloroform layer weight after the extraction; Sampling analysis N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester content.
3,2-cyanic acid imines-1,3-thiazoles alkane synthesis procedure
According to mass ratio half Guang ammonia hydrochloric acid salt: the ratio of water=1:2～5 is injected water and is fed nitrogen in reaction kettle, according to mol ratio N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester: the ratio of half Guang ammonia hydrochloric acid salt=1:1～2 adds Mercaptamine in still.When being cooled to 0-5 ℃, according to mol ratio: N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester: the ratio of sodium hydroxide=1:1～2 drips the sodium hydroxide solution of 30%wt in still, drips off back insulation 30-60 minute.In still, drip N-cyanogen imido grpup-S, the chloroformic solution of S-dithiocarbonic acid dimethyl ester. after adding, clock reaction 2-8 hour.After reaction finishes, drive vacuum pump, close nitrogen, to pH=2-6, open hot water with the regulation system acidity of 20-30%wt hydrochloric acid, temperature raising steams chloroform to 40-60 ℃.Emptying hot water, water flowing are cooled to 0-10 ℃, put into whizzer and dry, in discharging to the drying plant dry 2-4 hour.The qualified back discharging of moisture content, sampling analysis, calculated yield.
4, thiophene worm quinoline synthesis procedure
Ratio according to the 500-1000ml/mol thiazolidine is squeezed into a certain amount of anhydrous methanol in thiophene worm quinoline synthesis reactor; Step synthetic 2-cyanic acid imines-1 on the input; The 3-thiazolidine; Starting vacuum pump, is the formaldehyde solution (consumption: 5-10 ‰) (making catalyzer) of 30-40% according to the ratio of mol ratio thiazolidine: picoline=1:1～2 suction 2-chloro-5-PMC and mass percent concentration in still.When feeding the steam temperature raising to 40-65 ℃, the liquid caustic soda that drips 30%wt is regulated the pH value between 7-11, after dripping off, and clock reaction 2-4 hour, sampling analysis.After qualified, material is gone to crystallization kettle.Water flowing is cooled to 0-10 ℃, and feed liquid is put into whizzer, changes material over to the washing still after the drying.With 50-80 ℃ of hot water wash twice, finish the back centrifuge dripping.Discharging is to drying plant, to dry materials 2-5 hour, until moisture qualified (water content≤1%).Cooling discharge.
Embodiment 2:
1, the synthesis procedure of disodium salt
The cyanamide aqueous solution of 30%wt is dropped in the reaction kettle, be cooled to 10 ℃, according to the mol ratio cyanamide: sodium hydroxide is the sodium hydroxide solution that the ratio of 1:1.5 drips 30%wt; After dripping off, the amount according to 1mol cyanamide adding 0.1g four butyl bromation amine adds the catalyzer four butyl bromation amine; Ratio according to mol ratio cyanamide: dithiocarbonic anhydride=1:1 drips dithiocarbonic anhydride; Dropping temperature must not be higher than 20 ℃, after dripping off, material slowly is warming up to 50 ℃.Under this temperature stirring reaction 3-10 hour.After reaction is accomplished, with-0.01～-little vacuum distillation of 0.03MPa goes out unreacted dithiocarbonic anhydride.Distillation finishes, with material through suction filtration groove suction surge tank, with the catalyzer elimination.
2, N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester synthesis procedure
Filtrating is squeezed into N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester synthesis reactor.Be cooled to 20 ℃; In still, add hydrochloric acid and regulate pH=7-10 in the still; The still temperature is at 30 ℃. and the ratio according to mol ratio disodium salt: methyl-sulfate=1:1 is added dropwise to methyl-sulfate in still, after having thrown solution is reacted under 30 ℃ of temperature to pH value constant basically in half a hour (needing 2-5 hour approximately).With chloroform extraction 2 times, extraction for the first time is according to 50-90mL chloroform/mole N-cyanogen imido grpup-S, the adding of the amount of S-dithiocarbonic acid dimethyl ester; Extraction is according to 10-30mL/ mole N-cyanogen imido grpup-S for the second time; The amount of S-dithiocarbonic acid dimethyl ester adds, and with twice extraction liquid merging, weighs up chloroform layer weight after the extraction; Sampling analysis N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester content.
3,2-cyanic acid imines-1,3-thiazoles alkane synthesis procedure
According to mass ratio half Guang ammonia hydrochloric acid salt: the ratio of water=1:2 is injected water and is fed nitrogen in reaction kettle, according to mol ratio N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester: the ratio of half Guang ammonia hydrochloric acid salt=1:1 adds Mercaptamine in still.When being cooled to 5 ℃, according to mol ratio: N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester: the ratio of sodium hydroxide=1:1 drips the sodium hydroxide solution of 30%wt in still, drips off back insulation 30-60 minute.In still, drip N-cyanogen imido grpup-S, the chloroformic solution of S-dithiocarbonic acid dimethyl ester. after adding, clock reaction 2-8 hour.After reaction finishes, drive vacuum pump, close nitrogen, to pH=2-6, open hot water with the regulation system acidity of 20-30%wt hydrochloric acid, temperature raising to 60 ℃ steams chloroform.Emptying hot water, water flowing are cooled to 0-10 ℃, put into whizzer and dry, and drive and expect to the drying plant dry 2-4 hour.The qualified back discharging of moisture content, sampling analysis, calculated yield.
4, thiophene worm quinoline synthesis procedure
Ratio according to the 500-1000ml/mol thiazolidine is squeezed into a certain amount of anhydrous methanol in thiophene worm quinoline synthesis reactor; Step synthetic 2-cyanic acid imines-1 on the input; The 3-thiazolidine; Starting vacuum pump, is the formaldehyde solution (consumption: 5-10 ‰) (making catalyzer) of 30-40% according to the ratio of mol ratio thiazolidine: picoline=1:1～2 suction 2-chloro-5-PMC and mass percent concentration in still.When feeding steam temperature raising to 65 ℃, the liquid caustic soda that drips 30%wt is regulated the pH value between 7-11, after dripping off, and clock reaction 2-4 hour, sampling analysis.After qualified, material is gone to crystallization kettle.Water flowing is cooled to 10 ℃, and feed liquid is put into whizzer, changes material over to the washing still after the drying.With 50-80 ℃ of hot water wash twice, finish the back centrifuge dripping.Discharging is to drying plant, to dry materials 2-5 hour, until moisture qualified (water content≤1%).Cooling discharge.
Embodiment 3:
1, the synthesis procedure of disodium salt
The cyanamide aqueous solution of 30%wt is dropped in the reaction kettle, be cooled to 15 ℃, according to the mol ratio cyanamide: sodium hydroxide is the sodium hydroxide solution that the ratio of 1:1.5～3.5 drips 30%wt; After dripping off, the amount according to 1mol cyanamide adding 0.1-2g four butyl bromation amine adds the catalyzer four butyl bromation amine; Ratio according to mol ratio cyanamide: dithiocarbonic anhydride=1:3 drips dithiocarbonic anhydride; Dropping temperature must not be higher than 20 ℃, after dripping off, material slowly is warming up to 50 ℃.Under this temperature stirring reaction 3-10 hour.After reaction is accomplished, with-0.01～-little vacuum distillation of 0.03MPa goes out unreacted dithiocarbonic anhydride.Distillation finishes, with material through suction filtration groove suction surge tank, with the catalyzer elimination.
2, N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester synthesis procedure
Filtrating is squeezed into N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester synthesis reactor.Be cooled to 10-20 ℃; In still, add hydrochloric acid and regulate pH=7-10 in the still; The still temperature is at 15-30 ℃. and the ratio according to mol ratio disodium salt: methyl-sulfate=1:1～3 is added dropwise to methyl-sulfate in still, after having thrown solution is reacted under 15-30 ℃ of temperature to pH value constant basically in half a hour (needing 2-5 hour approximately).With the chloroform extraction that reclaims among the embodiment 12 times, extraction for the first time is according to 50-90mL chloroform/mole N-cyanogen imido grpup-S, the adding of the amount of S-dithiocarbonic acid dimethyl ester; Extraction is according to 10-30mL/ mole N-cyanogen imido grpup-S for the second time; The amount of S-dithiocarbonic acid dimethyl ester adds, and with twice extraction liquid merging, weighs up chloroform layer weight after the extraction; Sampling analysis N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester content.
3,2-cyanic acid imines-1,3-thiazoles alkane synthesis procedure
According to mass ratio half Guang ammonia hydrochloric acid salt: the ratio of water=1:2～5 is injected water and is fed nitrogen in reaction kettle, according to mol ratio N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester: the ratio of half Guang ammonia hydrochloric acid salt=1:1～2 adds Mercaptamine in still.When being cooled to 0-5 ℃, according to mol ratio: N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester: the ratio of sodium hydroxide=1:1～2 drips the sodium hydroxide solution of 30%wt in still, drips off back insulation 30-60 minute.In still, drip N-cyanogen imido grpup-S, the chloroformic solution of S-dithiocarbonic acid dimethyl ester. after adding, clock reaction 2-8 hour.After reaction finishes, drive vacuum pump, close nitrogen, to pH=2-6, open hot water with the regulation system acidity of 20-30%wt hydrochloric acid, temperature raising steams chloroform to 40-60 ℃.Emptying hot water, water flowing are cooled to 0-10 ℃, put into whizzer and dry, and drive and expect to the drying plant dry 2-4 hour.The qualified back discharging of moisture content, sampling analysis, calculated yield.
4, thiophene worm quinoline synthesis procedure
In thiophene worm quinoline synthesis reactor, squeeze into the anhydrous methanol that reclaims among a certain amount of embodiment 1 according to the ratio of 500-1000ml/mol thiazolidine; Step synthetic 2-cyanic acid imines-1 on the input; The 3-thiazolidine; Starting vacuum pump, is the formaldehyde solution (consumption: 5-10 ‰) (making catalyzer) of 30-40% according to the ratio of mol ratio thiazolidine: picoline=1:1～2 suction 2-chloro-5-PMC and mass percent concentration in still.When feeding the steam temperature raising to 40-65 ℃, the liquid caustic soda that drips 30%wt is regulated the pH value between 7-11, after dripping off, and clock reaction 2-4 hour, sampling analysis.After qualified, material is gone to crystallization kettle.Water flowing is cooled to 0-10 ℃, and feed liquid is put into whizzer, changes material over to the washing still after the drying.With 50-80 ℃ of hot water wash twice, finish the back centrifuge dripping.Discharging is to drying plant, to dry materials 2-5 hour, until moisture qualified (water content≤1%).Cooling discharge.
Comparative Examples 1 (using the benzyl trimethyl ammonium chloride catalyzer)
1, the synthesis procedure of disodium salt
The cyanamide aqueous solution of a certain amount of 30%wt is dropped in the reaction kettle, be cooled to 0-10 ℃, according to the mol ratio cyanamide: sodium hydroxide is the sodium hydroxide solution of the 30%wt that drips of the ratio of 1:1.5～3.5; After dripping off, the amount according to 1mol cyanamide adding 0.1-2g adds a certain amount of benzyl trimethyl ammonium chloride; Ratio according to mol ratio cyanamide: dithiocarbonic anhydride=1:1～2 drips dithiocarbonic anhydride; Dropping temperature must not be higher than 20 ℃, after dripping off, material slowly is warming up to 20-30 ℃.Under this temperature stirring reaction 10-20 hour.After reaction is accomplished, stop stirring, left standstill 2-4 hour, tell unreacted dithiocarbonic anhydride.
After telling dithiocarbonic anhydride; Open stirring and temperature of reaction is reduced to 10-20 ℃; In still, add hydrochloric acid and regulate pH=7-10 in the still, the still temperature is at 10-30 ℃. and the ratio according to mol ratio disodium salt: methyl-sulfate=1:1～3 is added dropwise to methyl-sulfate in still, the pH value of inspection reaction solution that will be constant after dropping into 2/3 methyl-sulfate; The pH value is held between the 7-10, methyl-sulfate has been thrown.
After having thrown solution is reacted constant basically in half a hour to the pH value under 10-30 ℃ of temperature.With chloroform extraction 2 times, extraction for the first time is according to 50-90mL chloroform/mole N-cyanogen imido grpup-S, the adding of the amount of S-dithiocarbonic acid dimethyl ester; Extraction is according to 10-30mL/ mole N-cyanogen imido grpup-S for the second time; The amount of S-dithiocarbonic acid dimethyl ester adds, and with twice extraction liquid merging, weighs up chloroform layer weight after the extraction; Sampling analysis N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester content.
Diester yield data with benzyl trimethyl ammonium chloride and two kinds of schemes of its brometo de amonio of four fourths is following:
Table one: benzyl trimethyl ammonium chloride
| Charging capacity | The diester quality | Two ester contents | Yield |
| 2kmol | 578 | 42% | 83.13% |
| 2kmol | 684 | 37.3% | 87.37% |
| 2kmol | 621 | 40.2% | 85.49% |
| 2kmol | 543 | 44.4% | 82.57% |
| 2kmol | 566 | 45% | 87.22% |
Table two: Tetrabutyl amonium bromide
| Charging capacity | The diester quality | Two ester contents | Yield |
| 2kmol | 676 | 39.2% | 90.75% |
| 2kmol | 631 | 41.5% | 89.68% |
| 2kmol | 572 | 46.3% | 90.7% |
| 2kmol | 546 | 49.2% | 92.0% |
| 2kmol | 541 | 51% | 94.49% |
Can find out that from above table though benzyl trimethyl ammonium chloride also can be used this reaction, it is good on effect, to be not so good as Tetrabutyl amonium bromide.
Comparative Examples 2 (with toluene, ethylene dichloride, methylene dichloride, cyclohexane give extraction solvent)
1, the synthesis procedure of disodium salt
The cyanamide aqueous solution of a certain amount of 1mo 30%wt is dropped in the reaction flask; Be cooled to 0-10 ℃, according to the mol ratio cyanamide: sodium hydroxide is the sodium hydroxide solution of the 30%wt that drips of the ratio of 1:1.5～3.5, after dripping off; The amount that adds the 0.1-2g four butyl bromation amine according to the 1mol cyanamide; Add a certain amount of catalyzer, according to the ratio dropping dithiocarbonic anhydride of mol ratio cyanamide: dithiocarbonic anhydride=1:1～2, dropping temperature must not be higher than 20 ℃; After dripping off, material slowly is warming up to 30-50 ℃.Under this temperature stirring reaction 3-10 hour.After reaction was accomplished, little vacuum distillation went out unreacted dithiocarbonic anhydride.Distillation finishes, with material through suction filtration groove suction surge tank, with the catalyzer elimination.
2, N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester synthesis procedure
Pour filtrating into flask; Be cooled to 10-20 ℃; In bottle, add hydrochloric acid and regulate pH=7-10 in the still; The still temperature is at 10-30 ℃. and the ratio according to mol ratio disodium salt: methyl-sulfate=1:1～3 is added dropwise to methyl-sulfate in bottle, after having thrown solution is reacted under 10-30 ℃ of temperature to pH value constant basically in half a hour (needing 2-3 hour approximately).
3, the extraction of diester
After the diester reaction is accomplished, use toluene, ethylene dichloride, methylene dichloride and cyclohexane give to extract respectively as solvent.Extraction results is following: table three
| The cyanamide charging capacity | The diester yield | Solvent for use | Consume volume |
| 1mol | In 90% | Chloroform | 80ml |
| 1mol | In 90% | Toluene | 210ml |
| 1mol | In 90% | Methylene dichloride | 110ml |
| 1mol | In 90% | Ethylene dichloride | 135ml |
| 1mol | In 90% | Hexanaphthene | Basically insoluble |
From above table, can find out: toluene, ethylene dichloride, methylene dichloride all can be used as extraction solvent and use; If but use toluene, these two kinds of SXs of ethylene dichloride; Can bring down toluene and ethylene dichloride into the step reaction; Treat that the thiazolidine reaction finishes, and needs these two kinds of solvents are steamed.But the boiling point of these two kinds of solvents all is higher than 80 ℃ (83.3 ℃ of ethylene dichloride, 110 ℃ of toluene) all than higher.And experiment proof thiazolidine is resolvent when being higher than 80 ℃.Therefore if will it be steamed, not only to consume lot of energy, and can be influential at the yield to next step thiazolidine, so can not use this two kinds of SXs.Though the boiling point of methylene dichloride is lower, the solubleness of methylene dichloride in water is 2.5 times of chloroform.Methylene dichloride is not so good as chloroform as extraction agent on the effect that is separated.So chloroform is best extraction solvent.
Comparative Examples 3 (making solvent) with ethanol
4, thiophene worm quinoline synthesis procedure
Ratio according to the 500-1000ml/mol thiazolidine is squeezed into a certain amount of absolute ethyl alcohol in thiophene worm quinoline synthesis reactor; Step synthetic 2-cyanic acid imines-1 on the input; The 3-thiazolidine; Starting vacuum pump, is the formaldehyde solution (consumption: 5-10 ‰) (making catalyzer) of 30-40% according to the ratio of mol ratio thiazolidine: picoline=1:1～2 suction 2-chloro-5-PMC and mass percent concentration in still.When feeding the steam temperature raising to 40-65 ℃, the liquid caustic soda that drips 30%wt is regulated the pH value between 7-11, after dripping off, and clock reaction 2-4 hour, sampling analysis.After qualified, material is gone to crystallization kettle.Water flowing is cooled to 0-10 ℃, and feed liquid is put into whizzer, changes material over to the washing still after the drying.With 50-80 ℃ of hot water wash twice, finish the back centrifuge dripping.Discharging is to drying plant, to dry materials 2-5 hour, until moisture qualified (water content≤1%).Cooling discharge.Make solvent with methyl alcohol and ethanol, the data of gained thiophene worm quinoline are following:
Table four: use ethanol to make solvent
| Thiazolidine throwing amount | Product content | Product yield | Quality product |
| 2kmol | 95.7% | 73.65% | 372.3kg |
| 2kmol | 96.4% | 74.75% | 377.9kg |
| 2kmol | 96.9% | 74.55% | 376.9kg |
| 2kmol | 96.2% | 75.15% | 380kg |
| 2kmol | 96.7% | 75.75% | 382.9kg |
Table five: use methyl alcohol to make solvent
| Thiazolidine throwing amount | Product content | Product yield | Quality product |
| 2kmol | 97.5% | 79.45% | 401.7kg |
| 2kmol | 97.9% | 80.75% | 408.2kg |
| 2kmol | 98.2% | 80% | 404.6kg |
| 2kmol | 98% | 81.4% | 411.6kg |
| 2kmol | 98.3% | 79.9% | 404kg |
Can find out from top experimental data: use methyl alcohol to make solvent, can make product content improve 1-2%, make product yield improve 3-5%.On commercially available price, the anhydrous methanol price is about 2500 yuan/ton simultaneously, and the absolute ethyl alcohol price is about 6500 yuan/ton.No matter from cost, still from product content with see qualitatively, use methyl alcohol all effective than use ethanol.
In sum, four embodiment have only example one no matter can both reach best effect from each step yield, content and cost, can draft being the former medicine working method of a kind of reliable thiophene worm quinoline.
Claims (7)
1. the working method of the former medicine of thiophene worm quinoline; With cyanamide, liquid caustic soda, dithiocarbonic anhydride is that raw material is synthetic in the presence of catalyzer, obtains N-cyanogen imido grpup-S, S-dithiocarbonic acid dimethyl ester with the methyl-sulfate reaction then; Again with Mercaptamine reaction Synthetic 2-cyanic acid imines-1,3-thiazoles alkane; At last; In solvent again with 2-chloro-5-PMC react thiophene worm quinoline, it is characterized in that, in 5 ℃～20 ℃ TR, dithiocarbonic anhydride is dropwised; And then temperature reaction; Wherein said catalyzer is a Tetrabutyl amonium bromide, and with the N-cyanogen imido grpup-S that obtains, S-dithiocarbonic acid dimethyl ester is the direct and Mercaptamine reaction in extraction solvent extraction back with the chloroform.
2. the working method of the former medicine of thiophene worm quinoline as claimed in claim 1 is characterized in that described solvent is a methyl alcohol.
3. the working method of the former medicine of thiophene worm quinoline as claimed in claim 1 is characterized in that, when synthetic, 30～60 ℃ of reactions, when synthesizing thiophene worm quinoline, temperature of reaction is the reflux temperature of methyl alcohol.
4. the working method of the former medicine of thiophene worm quinoline as claimed in claim 1 is characterized in that, 2-cyanic acid imines-1,3-thiazoles alkane and 2-chloro-5-PMC react to such an extent that the temperature of reaction of thiophene worm quinoline is the reflux temperature of methyl alcohol.
5. the working method of the former medicine of thiophene worm quinoline as claimed in claim 1 is characterized in that, described Tetrabutyl amonium bromide finishes the after-filtration separation in reaction and re-uses.
6. the working method of the former medicine of thiophene worm quinoline as claimed in claim 1 is characterized in that, described solvent is reacting after come into operation after the rectification process again.
7. the working method of the former medicine of thiophene worm quinoline as claimed in claim 1 is characterized in that, described extraction solvent reaction finishes the back negative pressure and distillates recovery set usefulness.
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| CN103145701A (en) * | 2013-03-27 | 2013-06-12 | 杨文茂 | Method for synthesizing thiacloprid active compound and co-producing carbon powder |
| CN107629045A (en) * | 2017-11-10 | 2018-01-26 | 上海生农生化制品股份有限公司 | A kind of aqueous synthesis method of thiacloprid |
| CN109354590A (en) * | 2018-12-18 | 2019-02-19 | 山东省联合农药工业有限公司 | A kind of new synthetic method of thiacloprid |
| CN113354632A (en) * | 2021-07-07 | 2021-09-07 | 利民化学有限责任公司 | Preparation method and system of thiacloprid |
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