CN102863392A - Method for greatly reducing amount of solvent usage in production process of oxfendazole - Google Patents
Method for greatly reducing amount of solvent usage in production process of oxfendazole Download PDFInfo
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- CN102863392A CN102863392A CN2012103951283A CN201210395128A CN102863392A CN 102863392 A CN102863392 A CN 102863392A CN 2012103951283 A CN2012103951283 A CN 2012103951283A CN 201210395128 A CN201210395128 A CN 201210395128A CN 102863392 A CN102863392 A CN 102863392A
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- fenbendazole
- hydrogen peroxide
- oxfendazole
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Abstract
The invention discloses a method for greatly reducing amount of solvent usage in the production process of oxfendazole. The method is characterized by comprising the step of taking fenbendazole as a starting raw material and the hydrogen peroxide as the oxidant to produce oxfendazole, however, the fenbendazole has low dissolubility, and lots of solvents are adopted and cannot be recovered, which lead to high technology cost and environmental protection cannot be achieved. According to the method disclosed by the invention, the feeding sequence, the feeding way, the amount of fed materials, and the time of feeding are skillfully designed based on the characteristic of the material in crystal transfer; and the amount of the solvent usage can be greatly saved; and the method is simple and convenient in technological operation, economic and environment-friendly, and suitable for industrial production.
Description
Technical field
The present invention relates to significantly reduce in a kind of oxfendazole production process the method for solvent usage quantity, be specifically related to the improvement to charging technology, is a kind of charging technology design of ingenious innovation.
Background technology
Oxfendazole is the derivative of fenbendazole, belongs to the novel vermifuge of wide spectrum, efficient, low toxicity, and its expelling parasite spectrum is roughly identical with fenbendazole, but anthelmintic activity is stronger, mainly is take fenbendazole as raw material, and hydrogen peroxide is oxygenant, make by oxidizing reaction is synthetic, its reaction formula is as follows:
Because the solvability of fenbendazole is relatively poor, the solvent usage quantity is large and can't reclaim in the reaction process.Through research, we find why bad the solvability of fenbendazole is, mainly are because fenbendazole exists A, two kinds of crystal formations of B, and wherein the B crystal formation is difficult to dissolving more than the A crystal formation.The fenbendazole of existing explained hereafter mainly is that the A crystal formation exists, so fenbendazole is when just dropping in the solvent, it is comparatively easy to dissolve, but has very soon the nucleus of minority B crystal formation to generate under solution state, thereby induced crystallization causes a large amount of B crystal formation crystal hard to tolerate to be separated out.In order to prevent separating out in a large number solid impact reaction in the reaction, only have the increasing quantity of solvent, the common solvent usage quantity is at 3～4 times of material, uses in a large number solvent and can't receive and apply mechanically, both uneconomical also not environmental protection.
Summary of the invention
The object of the present invention is to provide the method that significantly reduces the solvent usage quantity in a kind of oxfendazole production process, and easy, the economic environmental protection of this technological operation, be fit to suitability for industrialized production.For achieving the above object, the specific design scheme is as follows:
Throw first solid-state fenbendazole, and then throw liquid solvent, specific as follows:
(1) throws first half fenbendazole of total amount, and then drip the hydrogen peroxide of its 1.0 equivalent;
(2) after hydrogen peroxide dropwises for the first time, add again the fenbendazole of second half amount, then at the hydrogen peroxide that drips its 1.4 equivalent;
(3) hydrogen peroxide dropwises for the second time, after reaction finishes, with sodium sulfite aqueous solution cancellation reaction, then carries out aftertreatment.
The invention has the advantages that: significantly reduce the method for solvent usage quantity in the described oxfendazole production process, be to have changed conventional feeding sequence, drop into first solid-state fenbendazole, and then drop into liquid solvent.And fenbendazole is divided into input twice, each time half of otal investment; The hydrogen peroxide charging capacity also is divided into twice, drips first 1.0 equivalent hydrogen peroxide of half fenbendazole, and then drips 1.4 equivalent hydrogen peroxide of half fenbendazole.
The above-mentioned process modification of present method is the feature according to the material crystal conversion, by to feeding sequence, feeding mode, charging capacity, the ingehious design on the opportunity that feeds intake, the usage quantity of significantly having saved solvent.Easy, the economic environmental protection of this technological operation is fit to suitability for industrialized production.
Description of drawings
Fig. 1 is process flow diagram of the present invention.
Embodiment
(1) a Kg fenbendazole is dropped into first in operation steps (1) and (2), and then drops into the 4aKg solvent.Design mainly is to prevent that in order to shorten dissolution time the B nucleus from forming like this; Guaranteed also that in addition quantity of solvent is 4 times of material, so that material can dissolve when beginning smoothly, so just prevented that B crystal formation crystal from separating out in a large number in the short period of time.
(2) operation steps (3), the hydrogen peroxide of 1.0 equivalents can prevent from generating a large amount of peroxidation by products before the second time, fenbendazole added.
(3) operation steps (4), because the fenbendazole of reaction system most of first batch of adding this moment reacts, after adding the aKg fenbendazole for the second time, also being equivalent to quantity of solvent is 4 times of amounts of fenbendazole, after dissolving smoothly, because the existence of a large amount of oxfendazoles, whole system is mixture state, this has just stoped fenbendazole B nucleation, thereby B crystal formation crystal can not be separated out in a large number.
(4) operation steps (5), excessive hydrogen peroxide can guarantee that the smooth oxidation of fenbendazole is complete, after reaction finishes, with fast cancellation of S-WAT reaction.
Summarize whole technological design, the fenbendazole of input is 2aKg, and the quantity of solvent of input is 4aKg, 1.2 equivalents of the hydrogen peroxide fenbendazole total amount of input.The method is mainly for feeding sequence, feeding mode, charging capacity, the ingehious design on the opportunity that feeds intake so that whole solvent usage quantity be traditional technology half.
The operation of following type reaction is used for illustrating the present invention, all belongs within the technical scheme that the present invention protects in simple replacement that those skilled in the art do the present invention or improvement etc.
Embodiment 1
In 1000 milliliters of four-hole boiling flasks that thermometer and whipping appts arranged, add the 100.0g fenbendazole, 400.0g formic acid, open and stir, begin to drip 41.3Kg hydrogen peroxide (concentration is 27.5%) after clear until material is molten, temperature remains on 20～25 ℃, approximately dropwised in 1.5 hours, after dropwising, hydrogen peroxide in reaction system, adds 100.0 fenbendazoles again, after the fenbendazole dissolving to be added, begin to drip 57.8Kg hydrogen peroxide (concentration is 27.5%), temperature remains on 20～25 ℃, approximately dropwises in 1.5 hours.After hydrogen peroxide dropwises, control in the sampling, question response finishes, and adds 70.0g sodium sulfite aqueous solution (concentration is 16.5%) cancellation reaction to system.Then underpressure distillation concentrated solvent, solvent distills complete rear adding 600g methanol eddy making beating 30 minutes, then cool to about 10 ℃, suction filtration obtains oxfendazole tide product, with 100.0g methanol wash tide product, damp product are put into 70 ℃ of baking oven oven dry 12 hours, obtain the 204.0g oxfendazole, product meets the European Pharmacopoeia standard, and yield is 97.0%.
Embodiment 2
In 1000 milliliters of four-hole boiling flasks that thermometer and whipping appts arranged, add the 100.0g fenbendazole, 400.0g mixed solvent (ethanol: the vitriol oil=20:1) stir by unlatching, begin to drip 41.3Kg hydrogen peroxide (concentration is 27.5%) after clear until material is molten, temperature remains on 20～25 ℃, approximately dropwised in 1.5 hours, after dropwising, hydrogen peroxide in reaction system, adds 100.0 fenbendazoles again, after the fenbendazole dissolving to be added, begin to drip 57.8Kg hydrogen peroxide (concentration is 27.5%), temperature remains on 20～25 ℃, approximately dropwises in 1.5 hours.Hydrogen peroxide dropwises, and controls in the sampling, and question response finishes, and adds 70.0g sodium sulfite aqueous solution (concentration is 16.5%) cancellation reaction to system.Then in reaction system, drip ammoniacal liquor 41.0g (concentration is 25.0%), the suction filtration desolventizing obtains oxfendazole tide product, damp product are transferred back in the four-hole boiling flask, add 600.0g methanol eddy making beating 30 minutes, then cool to about 10 ℃, suction filtration obtains oxfendazole tide product, with 100.0g methanol wash tide product, damp product are put into 70 ℃ of baking oven oven dry 12 hours, obtain the 200.0g oxfendazole, product meets the European Pharmacopoeia standard, and yield is 95.20%.
Embodiment 3
In 1000 milliliters the four-hole boiling flask that thermometer and whipping appts are arranged, add the 100.0g fenbendazole, 400.0g mixed solvent (ethanol: chloroform: concentrated hydrochloric acid=2:2:1) stir by unlatching, begin to drip 41.3Kg hydrogen peroxide (concentration is 27.5%) after clear until material is molten, temperature remains on 20～25 ℃, approximately dropwised in 1.5 hours, after dropwising, hydrogen peroxide in reaction system, adds 100.0 fenbendazoles again, after the fenbendazole dissolving to be added, begin to drip 57.8Kg hydrogen peroxide (concentration is 27.5%), temperature remains on 20～25 ℃, approximately dropwises in 1.5 hours.Hydrogen peroxide dropwises, and controls in the sampling, and question response finishes, and adds 70.0g sodium sulfite aqueous solution (concentration is 16.5%) cancellation reaction to system.Then in reaction system, drip ammoniacal liquor 65.0g (concentration is 25.0%), the suction filtration desolventizing obtains oxfendazole tide product, damp product are transferred back in the four-hole boiling flask, add 600.0g methanol eddy making beating 30 minutes, then cool to about 10 ℃, suction filtration obtains oxfendazole tide product, with 100.0g methanol wash tide product, damp product are put into 70 ℃ of baking oven oven dry 12 hours, obtain the 202.0g oxfendazole, product meets the European Pharmacopoeia standard, and yield is 96.1%.
Claims (1)
1. significantly reduce the method for solvent usage quantity in the oxfendazole production process, it is characterized in that: step is as follows: throw first solid-state fenbendazole, and then throw liquid solvent, specific as follows:
(1) throws first half fenbendazole of total amount, and then drip the hydrogen peroxide of its 1.0 equivalent;
(2) after hydrogen peroxide dropwises for the first time, add again the fenbendazole of second half amount, then at the hydrogen peroxide that drips its 1.4 equivalent;
(3) hydrogen peroxide dropwises for the second time, after reaction finishes, with sodium sulfite aqueous solution cancellation reaction, then carries out aftertreatment.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2012103951283A CN102863392A (en) | 2012-10-18 | 2012-10-18 | Method for greatly reducing amount of solvent usage in production process of oxfendazole |
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| CN2012103951283A CN102863392A (en) | 2012-10-18 | 2012-10-18 | Method for greatly reducing amount of solvent usage in production process of oxfendazole |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3929821A (en) * | 1972-12-29 | 1975-12-30 | Syntex Inc | 5 (6)-Benzene ring substituted benzimidazole-2-carbamate derivatives |
| GB1428933A (en) * | 1973-07-07 | 1976-03-24 | Hoechst Ag | 5-phenyl-sulphinyl-2-benzimidazolyl-carbamic acid esters and process for their manufacture |
| US4792610A (en) * | 1987-06-13 | 1988-12-20 | Hoechst Aktiengesellschaft | Process for the preparation of 5-phenylsulfinyl-1H-2-(methoxycarbonylamino)-benzimidazole |
-
2012
- 2012-10-18 CN CN2012103951283A patent/CN102863392A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3929821A (en) * | 1972-12-29 | 1975-12-30 | Syntex Inc | 5 (6)-Benzene ring substituted benzimidazole-2-carbamate derivatives |
| GB1428933A (en) * | 1973-07-07 | 1976-03-24 | Hoechst Ag | 5-phenyl-sulphinyl-2-benzimidazolyl-carbamic acid esters and process for their manufacture |
| US4792610A (en) * | 1987-06-13 | 1988-12-20 | Hoechst Aktiengesellschaft | Process for the preparation of 5-phenylsulfinyl-1H-2-(methoxycarbonylamino)-benzimidazole |
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Application publication date: 20130109 |