CN108484458A - A kind of 3- methyl -4-（4- trifluoromethylthio benzene）The Industrialized synthesis method of oxygroup nitrobenzene - Google Patents
A kind of 3- methyl -4-（4- trifluoromethylthio benzene）The Industrialized synthesis method of oxygroup nitrobenzene Download PDFInfo
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- CN108484458A CN108484458A CN201810299164.7A CN201810299164A CN108484458A CN 108484458 A CN108484458 A CN 108484458A CN 201810299164 A CN201810299164 A CN 201810299164A CN 108484458 A CN108484458 A CN 108484458A
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- oxygroup
- benzene
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- trifluoromethylthios
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
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Abstract
The present invention relates to technical field of medicine synthesis, relate in particular to a kind of 3 methyl 4（4 trifluoromethylthio benzene）The Industrialized synthesis method of oxygroup nitrobenzene, using potassium carbonate as acid binding agent, using dimethyl sulfoxide as solvent, flows back using toluene as deicer, at 120 ~ 140 DEG C and 3 methyl 4 is obtained by the reaction using 4 trifluoromethylthio phenol and 2 chlorine, 5 nitrotoleune as raw material（4 trifluoromethylthio benzene）Oxygroup nitrobenzene.The present invention uses back flow reaction under the reaction temperature higher than toluene water azeotropic temperature, utilizes toluene and water azeotropic principles so that moisture is free in except reaction system, to which driving a reaction carries out；Reaction yield is increased to 97 ~ 98% from 85% or so of existing method, and product can put into without purifying and react in next step.
Description
Technical field
The present invention relates to technical field of medicine synthesis, relate in particular to a kind of 3- methyl -4- (4- trifluoromethylthios benzene)
The Industrialized synthesis method of oxygroup nitrobenzene.
Background technology
Toltrazuril category triazineon compounds have wide spectrum coccidiostat activity, are widely used in chicken coccidiasis.Toltrazuril pair
The site of action of coccidia is very extensive, has effect to two asexual cycles of coccidia, such as inhibits schizont, the core of microgametophyte
The wall of division and microgametophyte forms body.Since this product interferes coccidia nuclear division and mitochondria, influence polypide breathing and
Metabolic function can be such that endocytoplasmic reticulum expands again in addition, and serious ghost occurs, thus with worm effect of killing.
On domestic market, toltrazuril has been realized in production domesticization, but is limited to process conditions and cost of material, production
Product price costly, therefore improves technique, and New Research Method becomes the research hotspot of such veterinary drug worker.
3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene is the important intermediate of synthesis toltrazuril, but to it
Study of synthesis method, the technique study for being especially suitable for industrialization large-scale production are still insufficient.
Invention content
The purpose of the present invention is to provide a kind of 3- methyl -4- of high yield (4- trifluoromethylthios benzene) oxygroup nitrobenzene works
Industry is combined to method.
To solve the above problems, the technical solution adopted by the present invention is as follows：A kind of 3- methyl -4- (4- trifluoromethylthios benzene)
The Industrialized synthesis method of oxygroup nitrobenzene：
Using 4- trifluoromethylthios phenol and the chloro- 5- nitrotoleunes of 2- as raw material, using potassium carbonate as acid binding agent, with dimethyl sulfoxide
For solvent, flows back using toluene as deicer, at 120~140 DEG C and 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitre is obtained by the reaction
Base benzene；The dosage of the solvent dimethyl sulfoxide can dissolve raw material just at the reaction temperatures and be preferred；Specifically, the solvent two
The dosage of first sulfoxide is 0.5~2 kilogram/every mole 4- trifluoromethylthio phenol；Further, the use of the solvent dimethyl sulfoxide
Amount is 0.6~1 kilogram/every mole 4- trifluoromethylthio phenol.
Preferably, the 4- trifluoromethylthios phenol and the chloro- 5- nitrotoleunes molar ratios of 2- are 1：1.
Preferably, the reaction temperature is 130 DEG C.
Preferably, the volume ratio of the dimethyl sulfoxide and toluene is 2~6：1.Further, the dimethyl sulfoxide and toluene
Volume ratio be 2~5：1.
Preferably, the mole dosage of the potassium carbonate is the 0.6~0.8 of 4- trifluoromethylthio phenol moles.
Preferably, the reaction time is 3~5 hours, and solvent is evaporated under reduced pressure out in 90~110 DEG C after the completion of reaction, and
Add water and toluene to be washed, extracted, toluene phase is collected after extraction, can direct plunge into and react in next step.
Preferably, the toluene dosage for washing, extracting is product 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitro
2~5 times of benzene quality；The further toluene dosage for washing, extracting is product 3- methyl -4- (4- trifluoromethylthios benzene)
2~2.5 times of oxygroup nitrobenzene quality.
Preferably, the water consumption for washing, extracting is 0.9~2 times of toluene quality.
It is generally acknowledged that being reacted as follows by the generation of acid binding agent of potassium carbonate：
a.K2CO3+HCl→KHCO3+KCl
If it is, then the input amount of potassium carbonate should reach at least hydrogen chloride mole can just play it is good
" tiing up acid " acts on, and the mole of potassium carbonate only has 0.6~0.8 in the present invention；Actually when reaction temperature reach 100 DEG C with
On, saleratus can occur to react as follows：
b.2KHCO3→K2CO3+CO2+H2O
The equation of two-step reaction merge just at：
c.K2CO3+2HCl→2KCl+CO2+H2O
Usual etherification reaction avoids water, is that not will produce water method by reaction equation a, but at a temperature of this reaction, carbon
The decomposition of potassium hydrogen phthalate is also inevitable.Therefore, a reaction that will not conventionally generate water is given birth to due to reaction temperature
At water, but due to the low boiling point of raw material, and the conventional mode that vacuumizes can not be used to remove water, cause reaction yield that can not obtain
It breaks through.
In the application as chemical name conflicts with structural formula, it is subject to structural formula.
The advantageous effect of technical solution using the present invention is：Using under the reaction temperature higher than toluene-water azeotropic temperature
Back flow reaction utilizes toluene and water azeotropic principles so that moisture is free in except reaction system, to which driving a reaction carries out；Both
Avoid traditional loss for vacuumizing 4- trifluoromethylthios phenol under mode, the product for high yield of getting back, by reaction yield
97~98% are increased to from 85% or so of existing method, and product can put into without purifying and react in next step, it is significantly simple
Change reaction condition, reduces production cost.
Specific implementation mode
The present invention is further described specifically with reference to embodiments, but not limited to this.
Embodiment 1
Take 4- trifluoromethylthio phenol 194kg, 2- chloro- 5- nitrotoleunes 172kg, potassium carbonate 82.8kg, dimethyl sulfoxide
600kg, toluene 118kg are added in reaction kettle；Controlled at carrying out back flow reaction within the scope of 120~130 DEG C；React 5h after in
90~110 DEG C are evaporated under reduced pressure out solvent, and 1600kg water and 800kg toluene are added to be washed, extracted, and toluene is collected after extraction
Phase removes solvent and obtains 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene 323kg, purity 99%, yield 97.2%.
Embodiment 2
Take 4- trifluoromethylthio phenol 194kg, 2- chloro- 5- nitrotoleunes 172kg, potassium carbonate 110kg, dimethyl sulfoxide
700kg, toluene 250kg are added in reaction kettle；Controlled at carrying out back flow reaction within the scope of 130~140 DEG C；React 3h after in
100~110 DEG C are evaporated under reduced pressure out solvent, and 600kg water and 650kg toluene are added to be washed, extracted, and toluene is collected after extraction
Phase removes solvent and obtains 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene 325kg, purity 99%, yield 97.7%.
Embodiment 3
Take 4- trifluoromethylthio phenol 194kg, 2- chloro- 5- nitrotoleunes 172kg, potassium carbonate 96.6kg, dimethyl sulfoxide
1000kg, toluene 160kg are added in reaction kettle；Controlled at carrying out back flow reaction within the scope of 125~135 DEG C；After reacting 4h
It is evaporated under reduced pressure out solvent in 100~110 DEG C, and 600kg water and 650kg toluene is added to be washed, extracted, toluene is collected after extraction
Phase removes solvent and obtains 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene 326kg, purity 99%, yield 98.1%.
All documents that the present invention refers to are incorporated herein by reference, and are individually drawn just as each document
It is used as with reference to such.
Claims (10)
1. a kind of Industrialized synthesis method of 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene, it is characterised in that including
Following steps：
It is molten with dimethyl sulfoxide using potassium carbonate as acid binding agent using 4- trifluoromethylthios phenol and the chloro- 5- nitrotoleunes of 2- as raw material
Agent flows back using toluene as deicer, at 120~140 DEG C and 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitro is obtained by the reaction
Benzene.
2. the Industrialized synthesis method of 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene according to claim 1,
It is characterized in that, the 4- trifluoromethylthios phenol and the chloro- 5- nitrotoleunes molar ratios of 2- are 1：1.
3. the Industrialized synthesis method of 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene according to claim 1,
It is characterized in that, the reaction temperature is 130 DEG C.
4. the Industrialized synthesis method of 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene according to claim 1,
It is characterized in that the volume ratio of the dimethyl sulfoxide and toluene is 2~6：1.
5. the Industrialized synthesis method of 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene according to claim 4,
It is characterized in that the volume ratio of the dimethyl sulfoxide and toluene is 2~5：1.
6. the Industrialized synthesis method of 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene according to claim 1,
It is characterized in that the mole dosage of the potassium carbonate is the 0.6~0.8 of 4- trifluoromethylthio phenol moles.
7. according to the industrialization of claim 1~6 any one of them 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene
Synthetic method, it is characterised in that the reaction time is 3~5 hours, is evaporated under reduced pressure out in 90~110 DEG C after the completion of reaction molten
Agent, and water and toluene is added to be washed, extracted, toluene phase is collected after extraction, can be direct plungeed into and be reacted in next step.
8. the Industrialized synthesis method of 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene according to claim 7,
It is characterized in that the toluene dosage for washing, extracting is product 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene matter
2.5~5 times of amount.
9. the Industrialized synthesis method of 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene according to claim 7,
It is characterized in that the dosage of the water for washing, extracting is 0.9~2 times of toluene quality.
10. the industry side of being combined to of 3- methyl -4- (4- trifluoromethylthios benzene) oxygroup nitrobenzene according to claim 1
Method, it is characterised in that the dosage of the solvent dimethyl sulfoxide is 0.5~2 kilogram/every mole 4- trifluoromethylthio phenol.
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| CN201810299164.7A CN108484458A (en) | 2018-04-04 | 2018-04-04 | A kind of 3- methyl -4-（4- trifluoromethylthio benzene）The Industrialized synthesis method of oxygroup nitrobenzene |
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| CN201810299164.7A CN108484458A (en) | 2018-04-04 | 2018-04-04 | A kind of 3- methyl -4-（4- trifluoromethylthio benzene）The Industrialized synthesis method of oxygroup nitrobenzene |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101108831A (en) * | 2006-07-18 | 2008-01-23 | 洛阳普莱柯生物工程有限公司 | Method of producing toltrazuril |
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- 2018-04-04 CN CN201810299164.7A patent/CN108484458A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101108831A (en) * | 2006-07-18 | 2008-01-23 | 洛阳普莱柯生物工程有限公司 | Method of producing toltrazuril |
Non-Patent Citations (1)
| Title |
|---|
| 周春隆编: "《精细化工实验法》", 31 July 1998, 中国石化出版社 * |
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Application publication date: 20180904 |