CN104262164A - Preparation method of dinitolmide intermediate 3,5-dinitro-ortho-methyl benzoic acid - Google Patents
Preparation method of dinitolmide intermediate 3,5-dinitro-ortho-methyl benzoic acid Download PDFInfo
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- CN104262164A CN104262164A CN201410481432.9A CN201410481432A CN104262164A CN 104262164 A CN104262164 A CN 104262164A CN 201410481432 A CN201410481432 A CN 201410481432A CN 104262164 A CN104262164 A CN 104262164A
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Abstract
The invention relates to a preparation method of a dinitolmide intermediate 3,5-dinitro-ortho-methyl benzoic acid. The method comprises the following steps: dissolving ortho-methyl benzoic acid in an organic solvent, slowly and dropwisely adding 95-98 wt% nitric acid, and stirring at 50-84 DEG C to react for 0.5-3 hour; after the reaction finishes, distilling to recover the organic solvent, thereby obtaining a concentrated reaction solution; and stirring the concentrated reaction solution and water in a mass ratio of 1:(0.5-1) for 0.5-1 hour to precipitate a crystal, filtering, washing, and drying the filter cake to obtain the dinitolmide intermediate 3,5-dinitro-ortho-methyl benzoic acid, wherein the mass ratio of the ortho-methyl benzoic acid to the organic solvent is 1:(3-5), the mole ratio of the ortho-methyl benzoic acid to the nitric acid is 1:2.05, and the temperature is controlled at 50-80 DEG C in the nitric acid dropwise addition process. By using the organic solvent as a digestion nitration solvent, the solvent can be conveniently recovered and reutilized, thereby saving the cost and avoiding the problem of abundant wastewater generated in the preparation process; and thus, the invention provides an environment-friendly, green and efficient dinitolmide synthesis method.
Description
Technical field
The present invention relates to a kind of preparation method of dinitolmide intermediate 3,5-dinitrobenzene-o-tolyl acid.
Background technology
dinitolmide (3,5-dinitrobenzene-2-tolyl acid amine) is the anticoccidial drug of wide spectrum, efficient, safety, noresidue, for promoting the growth of chicken in feed.To the multiple eimeria tenella of chicken, as tender, murder by poisoning, Bu Shi, heap shape, the eimeria tenella such as huge and turkey coccidia etc. effectively.Particularly effective with murder by poisoning eimeria tenella to Eimeria Tenella, mainly suppress to embrace without the fragmentation bud in sexual cycle.This product not only for prevention, and may be used for treatment, application for the treatment of amount to the growth of chicken, grow, the hatching rate of laying eggs all has no adverse effects, and also has good preventive and therapeutic effect to the coccidiosis of rabbit.
Dinitolmide intermediate 3, traditional synthesis technique of 5-dinitrobenzene-o-tolyl acid is for be dissolved in the vitriol oil by o-tolyl acid, nitrosonitric acid is dripped in 1h, then 90-100 DEG C is continued reaction 1h, after placing 3-4h again, reactant is poured into crystallize out in 7 times amount cold water, filtration drying obtains target product 3,5-dinitrobenzene-o-tolyl acid.The shortcoming of this technique is that employing sulfonitric nitration mixture carries out nitration reaction to o-tolyl acid, and sulfonitric belongs to strong acid, very large to instrument and supplies corrosive pipeline, is unfavorable for operation; Reaction times is long, and production efficiency is not high; After reaction, acid solution can not recovery, and cost is higher; After having reacted, crystallization in large water gaging need be joined, produce a large amount of waste water, need a large amount of alkali neutralizing treatment, also significantly increase production cost, be unfavorable for environment protection.
Summary of the invention
The object of the invention is to solve the deficiencies in the prior art, provide a kind of preparation method of dinitolmide intermediate 3,5-dinitrobenzene-o-tolyl acid, the inventive method preparation technology is simple, and cost is low, pollution-free, and output is high.
The technical solution adopted for the present invention to solve the technical problems is:
Dinitolmide intermediate 3, the preparation method of 5-dinitrobenzene-o-tolyl acid, o-tolyl acid is dissolved in organic solvent, slowly drip the nitric acid of massfraction 95-98%, in 50-84 DEG C of stirring reaction 0. 5-3h, by organic solvent Distillation recovery after reaction terminates, obtain concentration of reaction solution, the ratio of concentration of reaction solution and water 1:0.5-1 is in mass ratio stirred 0.5-1h crystallize out, then filter, washing, filtration cakes torrefaction, obtain dinitolmide intermediate 3, 5-dinitrobenzene-o-tolyl acid, the mass ratio that feeds intake of described o-tolyl acid and organic solvent is 1:3-5, be preferably 1:4.5, the mol ratio of o-tolyl acid and nitric acid is 1:2.05, in described nitric acid dropping process, temperature controls at 50-80 DEG C.
As preferably, described organic solvent is one of following: chloroform, tetracol phenixin or ethylene dichloride, be preferably chloroform or ethylene dichloride one.
As preferably, described nitric acid content is preferably 98%.
As preferably, described temperature of reaction is preferably 60-84 DEG C, more preferably 83-84 DEG C.
As preferably, described nitric acid dropping temperature is 50-60 DEG C.
As preferably, the described reaction times is 0. 5-3h, is preferably 1-2h, more preferably 1.5h.
As preferably, after described reaction completes, add the water stirring of mass ratio 1:1.
As preferably, described dinitolmide intermediate 3, the preparation method of 5-dinitrobenzene-o-tolyl acid preferably carries out as follows: in reactor, add chloroform or ethylene dichloride, o-tolyl acid is added under stirring, after dissolving, 50 ~ 60 DEG C slowly drip the nitric acid of massfraction 98%, the mol ratio of described o-tolyl acid and nitric acid is 1:2.05, in 83 ~ 84 DEG C of reaction 1.5h, by organic solvent Distillation recovery after reaction terminates, obtain concentration of reaction solution, in concentration of reaction solution, 1:1 ratio adds water and stirs 0.5h to crystallize out in mass ratio, then filter, filtration cakes torrefaction, obtain two denitration amine intermediates 3, 5-dinitrobenzene-o-tolyl acid, the mass ratio that feeds intake of described o-tolyl acid and chloroform or ethylene dichloride is 1:4.5.
Reaction equation of the present invention is:
Compared with prior art, beneficial effect of the present invention is mainly reflected in: the present invention uses a kind of organic solvent as digestion reaction solvent, be conducive to solvent recuperation to apply mechanically, save cost, and avoid a large amount of useless water problem of generation in preparation process, a kind of environmental friendliness, the synthetic method of dinitolmide intermediate 3, the 5-dinitrobenzene-o-tolyl acid of green high-efficient.
Embodiment
Below in conjunction with specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in this:
Embodiment 1:
Dinitolmide intermediate 3, the preparation method of 5-dinitrobenzene-o-tolyl acid: in the 250mL four-hole boiling flask that reflux condensing tube and thermometer are housed, add ethylene dichloride 60g, o-tolyl acid 20g(0.148mol), opening stirring makes it dissolve completely, 98% nitric acid 19.50g is dripped in 50-60 DEG C, in 83-84 DEG C of reaction 1.5h, reaction terminates rear Distillation recovery ethylene dichloride 58.5g, the water adding mass ratio 1:0.5 stirs rear filtration, by reaction solution suction filtration, filter cake clear water washs, filter, filter cake 100 DEG C oven dry, obtain described intermediate 3, 5-dinitrobenzene-o-tolyl acid 32.13 g, its content of liquid chromatogram measuring is 98.05% (calculating with external standard method), yield 94.83%.
Embodiment 2:
Dinitolmide intermediate 3, the preparation method of 5-dinitrobenzene-o-tolyl acid: in the 250mL four-hole boiling flask that reflux condensing tube and thermometer are housed, add ethylene dichloride 90g, o-tolyl acid 20g(0.148mol), opening stirring makes it dissolve completely, 98% nitric acid 19.50g is dripped in 50-60 DEG C, 83-84 DEG C of reaction 1.5h, reaction terminates rear Distillation recovery ethylene dichloride 89.1g, the water adding mass ratio 1:0.5 stirs rear filtration, filter cake clear water washs, filter, filter cake 100 DEG C oven dry, obtain described intermediate 3, 5-dinitrobenzene-o-tolyl acid 33.28g, its content of liquid chromatogram measuring is 99.56% (calculating with external standard method), yield 98.99%.
Embodiment 3:
Dinitolmide intermediate 3, the preparation method of 5-dinitrobenzene-o-tolyl acid: in the 250mL four-hole boiling flask that reflux condensing tube and thermometer are housed, add ethylene dichloride 100g, o-tolyl acid 20g(0.148mol), opening stirring makes it dissolve completely, 98% nitric acid 19.50g is dripped in 50-60 DEG C, 83-84 DEG C of reaction 1.5h, reaction terminates rear Distillation recovery ethylene dichloride 98.7g, the water adding mass ratio 1:0.5 stirs rear overanxious, filter cake clear water washs, filter, filter cake 100 DEG C oven dry, obtain described intermediate 3, 5-dinitrobenzene-o-tolyl acid 33.16g, its content of liquid chromatogram measuring is 98.46% (calculating with external standard method), yield 97.55%.
Embodiment 4:
Dinitolmide intermediate 3, the preparation method of 5-dinitrobenzene-o-tolyl acid: in the 500mL four-hole boiling flask that thermometer and addition funnel are housed, add chloroform 90g, o-tolyl acid 20g(0.148mol), opening stirring makes it dissolve completely, 95% nitric acid 20.1g is dripped in 50-60 DEG C, 83-84 DEG C of reaction 1.5h, reaction terminates rear Distillation recovery chloroform 88.7g, the water adding mass ratio 1:1 stirs rear filtration, filter cake clear water washs, filter, filter cake 100 DEG C oven dry, obtain described intermediate 3, 5-dinitrobenzene-o-tolyl acid 33.23g, its content of liquid chromatogram measuring is 98.82% (calculating with external standard method), yield 98.11%.
Embodiment 5:
Dinitolmide intermediate 3, the preparation method of 5-dinitrobenzene-o-tolyl acid: in the 250mL four-hole boiling flask that reflux condensing tube and thermometer are housed, add ethylene dichloride 90g, o-tolyl acid 20g(0.148mol), opening stirring makes it dissolve completely, 95% nitric acid 20.1g is dripped in 50-60 DEG C, 83-84 DEG C of reaction 1.5h, reaction terminates rear Distillation recovery ethylene dichloride 89.1g, the water adding mass ratio 1:0.5 stirs rear overanxious, filter cake clear water washs, filter, filter cake 100 DEG C oven dry, obtain described intermediate 3, 5-dinitrobenzene-o-tolyl acid 32.51g, its content of liquid chromatogram measuring is 96.23% (calculating with external standard method), yield 93.47%.
Embodiment 6:
The real reaction time is 1h, and other operation is with embodiment 2.Obtain described intermediate 3,5-dinitrobenzene-o-tolyl acid 31.85g, its content of liquid chromatogram measuring is 96.53% (calculating with external standard method), yield 91.86%.
Embodiment 7:
The real reaction time is 2h, and other operation is with embodiment 2.Obtain described intermediate 3,5-dinitrobenzene-o-tolyl acid 31.41g, its content of liquid chromatogram measuring is 97.09% (calculating with external standard method), yield 91.11%.
Embodiment 8:
After real reaction completes, the water adding mass ratio 1:1 stirs, and other operation is with embodiment 2.Obtain described intermediate 3,5-dinitrobenzene-o-tolyl acid 33.31g, its content of liquid chromatogram measuring is 99.49% (calculating with external standard method), yield 99.01%.
Comparative example:
Implement traditionally:
In the 250mL there-necked flask that thermometer is housed, add 7.5 times amount of the o-tolyl acid of vitriol oil 150g(), o-tolyl acid 20g(0.148mol), open stirring and be warming up to 40 DEG C of insulation 10min, make it dissolve completely, drip 98% nitric acid 19.5g in 50-65 DEG C, add in 1h.90-100 DEG C of reaction 1h, place 3h, above-mentioned reactant is added drop-wise in 1337g cold water, crystallize out, filters, filter cake clear water washs, 100 DEG C of oven dry, obtain described intermediate 3,5-dinitrobenzene-o-tolyl acid 30.83g, its content of liquid chromatogram measuring is 92.55% (calculating with external standard method), yield 85.25%.
As can be seen from the result of embodiment 1-8 and comparative example, of the present invention 3, the product yield of the preparation method of 5-dinitrobenzene-o-tolyl acid is high, product content is high, organic solvent, as digestion reaction solvent, is conducive to solvent recuperation and applies mechanically, and has saved cost, and avoid a large amount of useless water problem of generation in preparation process, be a kind of eco-friendly preparation method.
Above-described embodiment is one of the present invention preferably scheme, not does any pro forma restriction to the present invention, also has other variant and remodeling under the prerequisite not exceeding the technical scheme described in claim.
Claims (8)
1. dinitolmide intermediate 3, the preparation method of 5-dinitrobenzene-o-tolyl acid, it is characterized in that, described method is: be dissolved in organic solvent by o-tolyl acid, slowly drip the nitric acid of massfraction 95 ~ 98%, in 50 ~ 84 DEG C of stirring reaction 0. 5 ~ 3h, by organic solvent Distillation recovery after reaction terminates, obtain concentration of reaction solution, the ratio of concentration of reaction solution and water 1:0.5-1 is in mass ratio stirred 0.5-1h crystallize out, then filter, washing, filtration cakes torrefaction, obtain dinitolmide intermediate 3, 5-dinitrobenzene-o-tolyl acid, the mass ratio that feeds intake of described o-tolyl acid and organic solvent is 1:3-5, the mol ratio of o-tolyl acid and nitric acid is 1:2.05, in described nitric acid dropping process, temperature controls at 50 ~ 80 DEG C.
2. the preparation method of dinitolmide intermediate 3,5-dinitrobenzene-o-tolyl acid according to claim 1, is characterized in that, described organic solvent is one of following: chloroform, tetracol phenixin, ethylene dichloride.
3. the preparation method of dinitolmide intermediate 3,5-dinitrobenzene-o-tolyl acid according to claim 2, is characterized in that, the preferred chloroform of described organic solvent or ethylene dichloride.
4. the preparation method of dinitolmide intermediate 3,5-dinitrobenzene-o-tolyl acid according to claim 1, is characterized in that, described temperature of reaction is 83 ~ 84 DEG C.
5. the preparation method of dinitolmide intermediate 3,5-dinitrobenzene-o-tolyl acid according to claim 1, is characterized in that, described nitric acid massfraction preferably 98%.
6. the preparation method of dinitolmide intermediate 3,5-dinitrobenzene-o-tolyl acid according to claim 1, is characterized in that, described nitric acid dropping process temperature controls at 50 ~ 60 DEG C.
7. the preparation method of dinitolmide intermediate 3,5-dinitrobenzene-o-tolyl acid according to claim 1, is characterized in that, preferred 1.5h of described reaction times.
8. dinitolmide intermediate 3 according to claim 1, the preparation method of 5-dinitrobenzene-o-tolyl acid, it is characterized in that: described dinitolmide intermediate 3, the preparation method of 5-dinitrobenzene-o-tolyl acid preferably carries out as follows: in reactor, add chloroform or ethylene dichloride, o-tolyl acid is added under stirring, after dissolving, 50 ~ 60 DEG C slowly drip the nitric acid of massfraction 98%, the mol ratio of described o-tolyl acid and nitric acid is 1:2.05, in 83 ~ 84 DEG C of reaction 1.5h, by organic solvent Distillation recovery after reaction terminates, obtain concentration of reaction solution, in concentration of reaction solution, 1:1 ratio adds water and stirs 0.5h to crystallize out in mass ratio, then filter, filtration cakes torrefaction, obtain two denitration amine intermediates 3, 5-dinitrobenzene-o-tolyl acid, the mass ratio that feeds intake of described o-tolyl acid and chloroform or ethylene dichloride is 1:4.5.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106800512A (en) * | 2017-01-06 | 2017-06-06 | 浙江荣耀生物科技有限公司 | The preparation method and preparation facilities of a kind of 3,5 dinitro o methyl benzoic acid |
| CN108586276A (en) * | 2018-06-05 | 2018-09-28 | 广东新科农生物科技有限公司 | Dinitolmide produces processing and the recoverying and utilizing method of waste liquid |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106800512A (en) * | 2017-01-06 | 2017-06-06 | 浙江荣耀生物科技有限公司 | The preparation method and preparation facilities of a kind of 3,5 dinitro o methyl benzoic acid |
| CN106800512B (en) * | 2017-01-06 | 2019-05-07 | 浙江荣耀生物科技股份有限公司 | A kind of preparation method and preparation facilities of 3,5- dinitro o methyl benzoic acid |
| CN108586276A (en) * | 2018-06-05 | 2018-09-28 | 广东新科农生物科技有限公司 | Dinitolmide produces processing and the recoverying and utilizing method of waste liquid |
| CN108586276B (en) * | 2018-06-05 | 2020-10-09 | 广东新科农生物科技有限公司 | Treatment and recycling method of dinitolmide production waste liquid |
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