CN101941947B - Synthesis method of 2-chloro-6-chloroquinoxaline - Google Patents
Synthesis method of 2-chloro-6-chloroquinoxaline Download PDFInfo
- Publication number
- CN101941947B CN101941947B CN2010102644715A CN201010264471A CN101941947B CN 101941947 B CN101941947 B CN 101941947B CN 2010102644715 A CN2010102644715 A CN 2010102644715A CN 201010264471 A CN201010264471 A CN 201010264471A CN 101941947 B CN101941947 B CN 101941947B
- Authority
- CN
- China
- Prior art keywords
- reaction
- acetylacetanilide
- adjacent nitro
- chlorine
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000001308 synthesis method Methods 0.000 title abstract 2
- WFOKVKYNVKVWFK-UHFFFAOYSA-N 2,6-dichloroquinoxaline Chemical compound N1=C(Cl)C=NC2=CC(Cl)=CC=C21 WFOKVKYNVKVWFK-UHFFFAOYSA-N 0.000 title 1
- 239000003960 organic solvent Substances 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 20
- 238000002425 crystallisation Methods 0.000 claims abstract description 15
- 230000008025 crystallization Effects 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 230000009467 reduction Effects 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 49
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 32
- 239000000460 chlorine Substances 0.000 claims description 32
- 229910052801 chlorine Inorganic materials 0.000 claims description 32
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 32
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 27
- 230000002829 reductive effect Effects 0.000 claims description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 23
- 239000002904 solvent Substances 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 238000006722 reduction reaction Methods 0.000 claims description 12
- SJAZZQLTKBYDHN-UHFFFAOYSA-N 6-chloro-1h-quinoxalin-2-one Chemical compound C1=C(Cl)C=CC2=NC(O)=CN=C21 SJAZZQLTKBYDHN-UHFFFAOYSA-N 0.000 claims description 11
- 239000000376 reactant Substances 0.000 claims description 11
- 238000010792 warming Methods 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 230000020477 pH reduction Effects 0.000 claims description 10
- 230000035484 reaction time Effects 0.000 claims description 10
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical group [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 10
- 239000003513 alkali Substances 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000007363 ring formation reaction Methods 0.000 claims description 8
- 238000009413 insulation Methods 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000004587 chromatography analysis Methods 0.000 claims description 6
- 238000004811 liquid chromatography Methods 0.000 claims description 6
- 239000007791 liquid phase Substances 0.000 claims description 6
- 238000005259 measurement Methods 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 239000002826 coolant Substances 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 235000010265 sodium sulphite Nutrition 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 239000010953 base metal Substances 0.000 claims description 3
- 150000002170 ethers Chemical class 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 238000005070 sampling Methods 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 238000010612 desalination reaction Methods 0.000 claims description 2
- 239000012065 filter cake Substances 0.000 claims description 2
- 230000000977 initiatory effect Effects 0.000 claims description 2
- 229920001021 polysulfide Polymers 0.000 claims description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 2
- 235000015320 potassium carbonate Nutrition 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 abstract description 15
- 238000005516 engineering process Methods 0.000 abstract description 14
- 239000002351 wastewater Substances 0.000 abstract description 8
- 230000008901 benefit Effects 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 239000002184 metal Substances 0.000 abstract 1
- JVTXVSSITAXGJQ-UHFFFAOYSA-N n-(4-chloro-3-nitrophenyl)-3-oxobutanamide Chemical compound CC(=O)CC(=O)NC1=CC=C(Cl)C([N+]([O-])=O)=C1 JVTXVSSITAXGJQ-UHFFFAOYSA-N 0.000 abstract 1
- 159000000000 sodium salts Chemical class 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- 235000011121 sodium hydroxide Nutrition 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 6
- XANCOYIVTNZKOE-UHFFFAOYSA-N 2-chloroquinolin-6-ol Chemical compound N1=C(Cl)C=CC2=CC(O)=CC=C21 XANCOYIVTNZKOE-UHFFFAOYSA-N 0.000 description 4
- 239000005614 Quizalofop-P-ethyl Substances 0.000 description 4
- 239000000498 cooling water Substances 0.000 description 4
- OSUHJPCHFDQAIT-GFCCVEGCSA-N quizalofop-P-ethyl Chemical group C1=CC(O[C@H](C)C(=O)OCC)=CC=C1OC1=CN=C(C=C(Cl)C=C2)C2=N1 OSUHJPCHFDQAIT-GFCCVEGCSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005352 clarification Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- -1 alkali metal salt Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- IHGRZJIPFXRBHE-UHFFFAOYSA-N [N+](=O)([O-])C1=C(NC(C)=O)C=CC=C1.[Cl] Chemical compound [N+](=O)([O-])C1=C(NC(C)=O)C=CC=C1.[Cl] IHGRZJIPFXRBHE-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- DPLVEEXVKBWGHE-UHFFFAOYSA-N potassium sulfide Chemical compound [S-2].[K+].[K+] DPLVEEXVKBWGHE-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000010865 sewage Substances 0.000 description 1
- 238000001577 simple distillation Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000004065 wastewater treatment Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of organic synthesis, providing a synthesis method in which an organic solvent is used as a synthesis environment of 6-chlorine-2-chloroquinoxaline. The method adopts p-chloro-m-nitroacetoacetanilide as a starting raw material, and a metal salt is obtained through closed loop, reduction and crystallization in the organic solvent under the alkaline condition. The technology is adopted to improve the stability of the whole synthesis reaction. Compared with the traditional technology, the method has the advantages of simple and practicable operation, high yield and content, wherein the use and the recycle of the organic solvent can greatly reduce the generation of waste water, relieve the pollution of environment and reduce production cost.
Description
Technical field
The invention belongs to technical field of organic synthesis, relate to the compound method of agricultural chemicals quizalofopPethyl midbody 6-chloro-2-hydroxy quinoxaline.
Background technology
QuizalofopPethyl is a kind of novel dry land cauline leaf treatment agent of high selectivity; Chemical name is (R)-2-[4-(6-chloro-quinoxaline-2-base oxygen) phenoxy] ethyl propionate; And 6-chloro-2-hydroxy quinoxaline is the important intermediate of synthetic quizalofopPethyl, and its pure article are that white is with pink tabular crystal, and industrial goods are light yellow to pink powder; Under alkaline condition, generate salt, unstable under acidic condition.
The method of domestic synthetic 6-chloro-2-hydroxy quinoxaline mainly is to be starting raw material to the chlorine o-Nitroacetanilide at present, under alkaline environment, passes through closed loop; Reduction; Three steps of crystallization are synthetic, and are ripe in the production at home of this technology, but still the part that comes with some shortcomings is mainly reflected in 6-chloro-2-hydroxy quinoxaline content and yield is generally lower; Need a large amount of water as solvent in the production; And can produce a large amount of alkaline sewages in the production process, and increased the difficulty of water treatment, improved production cost simultaneously.
Owing to the existence of above-mentioned shortcoming, be unfavorable for the scale suitability for industrialized production of quizalofopPethyl, also can't obtain good society and economic benefit.
Summary of the invention
The present invention is directed to the deficiency that existing compound method exists, adopt the synthetic environment of organic solvent, adopt this scheme, under the organic solvent alkaline condition, carry out closed loop to be starting raw material to the adjacent nitro alpha.-acetylacetanilide of chlorine as 6-chloro-2-hydroxy quinoxaline; Reduction, crystallization obtains metal-salt, carries out acidification then, obtains 2-chloro-6-hydroxyl quinoline woods; Adopt this technology to improve the stability of whole building-up reactions, compare, have that operation is simple with traditional technology; Yield is higher, the advantage that content is higher, and wherein organic solvent using and reclaiming; Significantly reduce the generation of waste water, alleviated environmental pollution, reduced production cost.
Reaction mechanism of the present invention is following:
Wherein, The contriver has changed in the past that to adopt with water in the technology be the technology of reaction solvent; Then select to be added with the solvent of the organic solvent of alkaline matter as reaction, and the reaction environment that organic solvent provides can make entire reaction more stable; Can reduce the generation of side reaction, thereby improve product content.With an organic solvent simultaneously, can reduce the sewage quantum of output.
Whole preparation process of the present invention comprises that its concrete technology is following to the closed loop and the reduction reaction of the adjacent nitro alpha.-acetylacetanilide of chlorine:
The first step: ring-closure reaction
In reactor drum, add the organic solvent that contains alkaline matter, add then to the adjacent nitro alpha.-acetylacetanilide of chlorine, under 20-30 ℃; Initiation reaction 2.5-3.5 hour, be warmed up to 50 ℃-solvent boiling point temperature then and carry out ring-closure reaction, the general reaction times is about 3 hours; Sampling is followed the tracks of the adjacent nitro alpha.-acetylacetanilide of chlorine content with liquid chromatography, calculates with the chromatogram area normalization method; If tracking results is to the adjacent nitro alpha.-acetylacetanilide of chlorine content＜0.1%,, then can descend the step to handle; If tracking results is to the adjacent nitro alpha.-acetylacetanilide of chlorine content＞0.1%, then need prolong the reaction times, follow the tracks of again; Behind adjacent nitro alpha.-acetylacetanilide＜0.1%, can descend step process to chlorine up to reactant;
Second step: reduction reaction
In above-mentioned reactor drum, add reductive agent, be warming up to about 50-150 ℃, insulation reaction 5-15 hour, whether react completely with the liquid-phase chromatographic analysis oxynitride; If tracking results is amount of nitrogen oxides＜0.1%, then can handle, if tracking results is amount of nitrogen oxides＞0.1%, then need prolong the reaction times; Carry out repetition measurement again, till the reactant amount of nitrogen oxides reaches requirement, after reaction finishes; Logical water coolant is reduced to room temperature, feeds cold salt then and reduces to 5 ℃ again, is incubated 2 hours; Making the whole crystallizations of whole generation material is metal-salt, and the frame that re-packs then obtains the crystallisate metal-salt;
The 3rd step: crystallization acidifying
The metal-salt of above-mentioned reactant crystallisation by cooling gained is used the hot water dissolving, and the adding activated carbon decolorizing being got filtrating and carrying out acidifying, in filtrating, drips acid solution, and regulating the pH value is 4-6, the washing desalination, and the filter cake oven dry had both got 6-chloro-2-hydroxy quinoxaline.
Through above-mentioned preparation technology,, saved the generation that a large amount of water has also reduced alkaline waste water owing to adopt organic solvent; Improved the stability of reaction, and W-response time decrease, thereby improved the efficient of producing; While reclaims easily owing to the present invention's employing is the solvent immiscible with water, and raw material is dissolved in wherein; Obtain better environmental benefit, improved the yield of reaction simultaneously again.
Among the above-mentioned preparation method, the solvent that is adopted is generally polar solvent, can use alcohols such as methyl alcohol, ethanol, propyl alcohol etc.; Ethers such as ether, MTBE etc.; A kind of or mixed system in ketone such as the acetone etc.; Why select like this; The first above-mentioned organic solvent of selecting for use should be able to dissolve various reactants and generate material; Second organic solvent selected for use does not react with RM; Various side reactions not taking place, can avoid organic solvent and raw material reaction to generate impurity as far as possible, reduces product content; The alkaline matter that is adopted is selected from one or more in Pottasium Hydroxide, sodium hydroxide, the salt of wormwood; The reductive agent that is adopted is one or more in an alkali metal salt of reductibilities such as sodium sulphite, sodium polysulphide, S-WAT, sodium sulfite anhy 96, POTASSIUM BOROHYDRIDE 97MIN, potassium sulphide; Above-mentioned reductive agent is to select according to the characteristic of organic solvent, why select like this be since above-mentioned reductive agent except can be organic solvent dissolution, also need be in organic solvent dispersion effect good; Wherein cool off the cold salt of usefulness, be routine techniques, just with CaCl
2Or the aqueous solution of NaCl, carry out the freezing condition that reaches subzero tens degree through freezing unit, supply industrial refrigeration to use.
In order to make entire reaction can obtain best effect; General control is 1 to the mol ratio of the adjacent nitro alpha.-acetylacetanilide of chlorine, alkali and reductive agent: 3-6: 1-2; Here the mol ratio of raw material and alkali and reductive agent is meant the hydrogen-oxygen radical that the monoatomic base metal is provided; The mol ratio of reductive agent is meant can provide the reductive agent that shifts 1 mole of electronics; That is to say that wherein mole number with alkali is according to referring to that the hydrogen-oxygen radical that the monoatomic base metal is provided converts, be meant according to providing the reductive agent that shifts 1 mole of electronics to convert with the mol ratio of reductive agent.
In follow-up crystallization and acidification technique; The crystallization processes that is adopted repeats no more at this for crystallization method commonly used, and in the acidization; Adopt general acidation treatment method in the industry; In order to reach the used acid of better effect can be the concentrated hydrochloric acid or the vitriol oil, adopts dense mineral acid can reduce discharged waste water like this, obtains better environmental benefit.
After finishing above-mentioned technology, can obtain highly purified 6-chloro-2-hydroxy quinoxaline, and in the preparation process; Having a large amount of organic solvents after the crystallization produces; This part organic solution is called mother liquor, and mother liquid obtained whole covers are used in the production of next batch and gone, and concrete working method is with noted earlier identical; Saved production cost so greatly, can make the solvent cycle utilization.In the waste water of follow-up acidification, dissolve method that partial solvent can be through simple distillation with solvent recuperation, reduced the loss amount of solvent like this, farthest rationally utilized solvent.
In sum, its purity of 6-chloro-2-hydroxy quinoxaline through above-mentioned prepared is up to more than 96%, and the yield of entire reaction has also reached more than 90%; Compare with traditional technology, have that operation is simple, yield is higher; The advantage that content is higher, wherein the using and reclaiming of organic solvent significantly reduces the generation of prior art neutral and alkali waste water; Alleviate environmental pollution, reduced production cost; Special alkaline waste water treatment unit also no longer need be set after the reaction, thereby save investment and production cost, and this technology is also more stable in production application.
Embodiment
Below, foregoing of the present invention is done further detailed description, but should this be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following instance through the embodiment of embodiment form.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1
The ring-closure reaction stage:
In the 5000L reaction kettle, drop into the 300kg sodium hydrate solid, the 1000kg methanol solution is opened stirring, is mixed with basic solvent; Logical cooling water temperature to 25 ± 5 ℃ drops into 400kg then to the adjacent nitro alpha.-acetylacetanilide of chlorine, reacts 3 hours down at 25 ± 5 ℃; Slowly be warming up to 60-65 ℃ then, reacted 2 hours, get and follow the tracks of appearance; With liquid-phase chromatographic analysis whether the adjacent nitro alpha.-acetylacetanilide of chlorine is reacted completely,, then can handle if tracking results is to the adjacent nitro alpha.-acetylacetanilide of chlorine content＜0.1%; If tracking results is to the adjacent nitro alpha.-acetylacetanilide of chlorine content＞0.1%; Then need prolong reaction times 2h, follow the tracks of again, can descend the step to handle chlorine behind adjacent nitro alpha.-acetylacetanilide＜0.1% up to reactant;
The reduction reaction stage:
In reaction kettle, drop into 200kg Sodium sulfhydrate and 500kg methyl alcohol, slowly be warming up to 70 ℃, reach reflux state; About reaction 15h, get and follow the tracks of appearance, whether react completely with the liquid-phase chromatographic analysis oxynitride; If tracking results is amount of nitrogen oxides＜0.1%, then can handle, if tracking results is amount of nitrogen oxides＞0.1%; Then need prolong the reaction times, carry out repetition measurement again.Till the reactant amount of nitrogen oxides reaches requirement.After reaction finished, logical water coolant was reduced to room temperature, feeds cold salt then and reduces to 5 ℃ again, is incubated 2 hours, and making the whole crystallizations of whole generation material is sodium salt, and the frame that re-packs then obtains the crystallisate sodium salt;
The acidification reaction stage:
The gained sodium salt is used 2000L, and the hot water dissolving about 60 ℃ changes still, adds the 50kg gac and under 60 ℃ of temperature, decolours 1 hour, and frame re-packs; Must filtrate, in reaction kettle, drip concentrated hydrochloric acid, temperature is being controlled at about 40 ℃; Rate of addition was controlled at about 1 hour, and the pH value of souring soln is 4-6, stirred after 1 hour; Still about 4-6, the frame that re-packs gets 2-chloro-6-hydroxyl quinoline woods to the pH value of repetition measurement solution, with the clarification of 60 ℃ of hot wash sheet frames to filtrating; The oven dry product, using liquid chromatography to survey content is 98.2%, yield is 92.5%.
Embodiment 2
The ring-closure reaction stage:
In the 3000L reaction kettle, drop into 180kg Pottasium Hydroxide solid and 800kg acetone soln, open stirring, be mixed with basic solvent; Logical cooling water temperature to 25 ± 5 ℃ drops into 260kg then to the adjacent nitro alpha.-acetylacetanilide of chlorine, reacts 3 hours down at 25 ± 5 ℃; Slowly be warming up to 60-65 ℃ then, reacted 2 hours, get and follow the tracks of appearance; With liquid-phase chromatographic analysis whether the adjacent nitro alpha.-acetylacetanilide of chlorine is reacted completely,, then can handle if tracking results is to the adjacent nitro alpha.-acetylacetanilide of chlorine content＜0.1%; If tracking results is to the adjacent nitro alpha.-acetylacetanilide of chlorine content＞0.1%, then need prolong the reaction times, follow the tracks of again.Till reactant reaches requirement to the adjacent nitro alpha.-acetylacetanilide of chlorine content.
The reduction reaction stage:
In reaction kettle, drop into 200kg Sodium sulfhydrate and 500kg acetone, slowly be warming up to 65 ℃, reach reflux state; About reaction 15h, after reaction finished, logical water coolant was reduced to room temperature; Feed cold salt then and reduce to 5 ℃ again, be incubated 2 hours, making the whole crystallizations of whole generation material is sodium salt; The frame that re-packs then obtains the crystallisate sodium salt.
The acidification reaction stage:
The gained sodium salt is used 2000L, and the hot water dissolving about 60 ℃ changes still, adds the 50Kg gac and under 60 ℃ of temperature, decolours 1 hour, and frame re-packs; Must filtrate, in reaction kettle, drip concentrated hydrochloric acid, temperature is being controlled at about 40 ℃; Rate of addition was controlled at about 1 hour, and the pH value of souring soln is 4-6, stirred after 1 hour; Still about 4-6, the frame that re-packs gets 2-chloro-6-hydroxyl quinoline woods to the pH value of repetition measurement solution, with the clarification of 60 ℃ of hot wash sheet frames to filtrating; The oven dry product, using liquid chromatography to survey content is 97.7%, yield is 91.5%.
Solvent cycle is utilized:
In the 5000L reaction kettle, drop into the 300kg sodium hydrate solid; The acetone mother liquor that 1000kg reclaims is opened stirring, is mixed with basic solvent, logical cooling water temperature to 25 ± 5 ℃; Drop into 400kg then to the adjacent nitro alpha.-acetylacetanilide of chlorine; Reacted 3 hours down at 25 ± 5 ℃, slowly be warming up to 60-65 ℃ then, reacted 2 hours.Following steps are with above-mentioned operation, and acetone mother liquor of the present invention can recycle, can overlap in the production of using next batch and go, and does not influence the content and the yield of product.
The recovery of solvent:
In the 3000L reaction kettle, drop into the waste water of reduction phase, the acetone solvent that atmospheric pressure or vacuum distillate out reclaims, and can overlap and use in the production.
Embodiment 3
The ring-closure reaction of preparation alkali lye:
In the 3000L reaction kettle, measure the 800Kg MTBE; Drive whisking appliance, drop into sodium hydroxide 150Kg, logical cooling water temperature is to 20-30 ℃; Drop into 400Kg again to the adjacent nitro alpha.-acetylacetanilide of chlorine; 20-30 ℃ of insulation reaction 3 hours, logical steam slowly was warming up to 50 ℃, insulation reaction 2 hours;
Reduction reaction:
In reaction kettle, drop into 500Kg MTBE and 150Kg POTASSIUM BOROHYDRIDE 97MIN, logical steam slowly is warming up to 60 ℃, and little back flow reaction 20 hours is cooled to and leads to cold salt again after the room temperature and reduce to 5 ℃, and the frame that re-packs filters out metal-salt;
The acidification reaction stage:
The acidification reaction stage adopts existing souring method to carry out acidifying, and using liquid chromatography to survey product content is 97.1%, and yield is 90.2%.
Comparative example (adopting the solvent of water) as reaction
The ring-closure reaction of preparation alkali lye:
In the 5000L reaction kettle, measure 1400L water, start to stir, drop into 375kg sodium hydroxide, be mixed with aqueous sodium hydroxide solution, logical cold salt was reduced to 25 ± 5 ℃, drops into 400kg then to the adjacent nitro alpha.-acetylacetanilide of chlorine, 25 ± 5 ℃ of insulation reaction 3 hours.It is 110 ℃ towards the material temperature that logical steam slowly is warming up to nature, insulation reaction 5 hours.
Reduction reaction:
Continuation drops into 800kg water and 300kg Sodium sulfhydrate in reaction kettle, logical steam is warming up to 115 ℃-118 ℃ insulations 18 hours, and sampling is surveyed and followed the tracks of; With liquid-phase chromatographic analysis whether the adjacent nitro alpha.-acetylacetanilide of chlorine is reacted completely; If tracking results is to the adjacent nitro alpha.-acetylacetanilide of chlorine content＜0.1, then can handle, if tracking results is to the adjacent nitro alpha.-acetylacetanilide of chlorine content＞0.1; Then need prolong the reaction times is 2 hours, follows the tracks of again.Till reactant reaches requirement to the adjacent nitro alpha.-acetylacetanilide of chlorine content.After reaction finished, logical water coolant was reduced to room temperature, feeds cold salt then and reduces to 5 ℃ again, is incubated 2 hours, and making the whole crystallizations of whole generation material is sodium salt, and the frame that re-packs then obtains the crystallisate sodium salt.
The acidification reaction stage:
The gained sodium salt is used 2000L, and the hot water dissolving about 60 ℃ changes still, adds the 50kg gac and under 60 ℃ of temperature, decolours 1 hour, and frame re-packs; Must filtrate, in reaction kettle, drip concentrated hydrochloric acid, temperature is being controlled at about 40 ℃; Rate of addition was controlled at about 1 hour, and the pH value of souring soln is 4-6, stirred after 1 hour; Still about 4-6, the frame that re-packs gets 2-chloro-6-hydroxyl quinoline woods to the pH value of repetition measurement solution, with the clarification of 60 ℃ of hot wash sheet frames to filtrating; The oven dry product, using liquid chromatography to survey content is 95.8%, yield is 80.7%.
Through the comparison of above embodiment and comparative example, all to be higher than with the aqueous solution be the reaction conditions of solvent for content, the yield of product when visible the present invention adopted organic solvent to be reaction solvent, and can recycle, reduces production cost, reduces quantity of wastewater effluent.
Claims (5)
1. the compound method of a 6-chloro-2-hydroxy quinoxaline comprises that it is characterized in that: described closed loop and reducing process are following to be closed loop, reduction and the acidification reaction of starting raw material to the adjacent nitro alpha.-acetylacetanilide of chlorine:
The first step: ring-closure reaction
In reactor drum, add the organic solvent that contains alkaline matter, add then to the adjacent nitro alpha.-acetylacetanilide of chlorine, under 20-30 ℃; Initiation reaction 2.5-3.5 hour; Be warmed up to 50 ℃-solvent boiling point temperature then and carry out ring-closure reaction, the reaction times is 2.5-3.5 hour, sampling; Follow the tracks of the adjacent nitro alpha.-acetylacetanilide of chlorine content with liquid chromatography; If tracking results is to the adjacent nitro alpha.-acetylacetanilide of chlorine content＜0.1%, then can descend the step to handle, if tracking results is to the adjacent nitro alpha.-acetylacetanilide of chlorine content＞0.1%; Then need prolong the reaction times, up to reactant to the adjacent nitro alpha.-acetylacetanilide of chlorine content＜step processing down in 0.1% o'clock;
Second step: reduction reaction
In above-mentioned reactor drum, add reductive agent, be warming up to about 50-150 ℃ insulation reaction 5-15 hour; Get and follow the tracks of appearance, whether react completely, if tracking results is amount of nitrogen oxides＜0.1% with the liquid-phase chromatographic analysis oxynitride; Then can carry out the back step handles; If tracking results is amount of nitrogen oxides＞0.1%, then need prolong the reaction times, carry out repetition measurement again till the reactant amount of nitrogen oxides reaches requirement; After reaction finished, logical water coolant was reduced to room temperature, feeds cold salt then and reduces to 5 ℃ again, is incubated 2 hours, and making the whole crystallizations of whole generation material is metal-salt, and the frame that re-packs then obtains the crystallisate metal-salt;
Wherein said mol ratio to the adjacent nitro alpha.-acetylacetanilide of chlorine, alkali and reductive agent is 1: 3-6: 1-2; Wherein the mole number with alkali is meant that the hydrogen-oxygen radical that is provided according to the monoatomic base metal converts, and is meant according to providing the reductive agent that shifts 1 mole of electronics to convert with the mol ratio of reductive agent;
Described organic solvent uses alcohols or ethers or ketone or its mixture, and wherein alcohols is selected from methyl alcohol or ethanol or propyl alcohol, and ethers is selected from ether or MTBE, and ketone is selected from acetone.
2. compound method according to claim 1 is characterized in that: described acidification reaction is:
To pass through the metal-salt that the reactant crystallisation by cooling of reduction reaction obtains, the hot water dissolving use in dry back, the adding activated carbon decolorizing; Get filtrating and carry out acidifying, in filtrating, drip acid solution, regulating the pH value is 4-6; The washing desalination, the filter cake oven dry promptly gets 6-chloro-2-hydroxy quinoxaline.
3. compound method according to claim 1 and 2 is characterized in that: described alkaline matter is selected from Pottasium Hydroxide or sodium hydroxide or salt of wormwood or its mixture.
4. compound method according to claim 1 and 2 is characterized in that: described reductive agent is sodium sulphite or sodium polysulphide or S-WAT or sodium sulfite anhy 96 or its mixture.
5. compound method according to claim 2 is characterized in that: described acid solution is the concentrated hydrochloric acid or the vitriol oil.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102644715A CN101941947B (en) | 2010-08-27 | 2010-08-27 | Synthesis method of 2-chloro-6-chloroquinoxaline |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102644715A CN101941947B (en) | 2010-08-27 | 2010-08-27 | Synthesis method of 2-chloro-6-chloroquinoxaline |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101941947A CN101941947A (en) | 2011-01-12 |
| CN101941947B true CN101941947B (en) | 2012-06-27 |
Family
ID=43434184
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102644715A Active CN101941947B (en) | 2010-08-27 | 2010-08-27 | Synthesis method of 2-chloro-6-chloroquinoxaline |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101941947B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107739343A (en) * | 2017-09-07 | 2018-02-27 | 京博农化科技股份有限公司 | A kind of environment-friendly type technique for producing Quizalotop-ethyl |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102180840A (en) * | 2011-03-15 | 2011-09-14 | 安徽丰乐农化有限责任公司 | New preparation process of 6-chloro-2-hydroxyquinoxaline |
| CN102108065B (en) * | 2011-03-23 | 2012-11-28 | 浙江禾田化工有限公司 | Method for preparing 2-quinoxalinol |
| CN102584723B (en) * | 2012-01-19 | 2015-03-04 | 江苏丰山集团股份有限公司 | Method for synthetizing 2,6-dichloroquinoxaline by using diketene |
| CN102675231A (en) * | 2012-05-15 | 2012-09-19 | 江苏丰山集团有限公司 | Method for removing sulfur content impurity in synthesis technology of 2, 6-dichloro-quinoxaline |
| CN102675233B (en) * | 2012-05-25 | 2016-03-09 | 安徽丰乐农化有限责任公司 | A kind of production technique of 6-chlorine-2-hydroxyl quinoxaline |
| CN113788786A (en) * | 2021-09-14 | 2021-12-14 | 京博农化科技有限公司 | Quizalofop-p-ethyl intermediate impurity and preparation method thereof |
| CN114369069B (en) * | 2022-01-21 | 2024-03-15 | 江苏丰山生化科技有限公司 | Preparation method of quizalofop-p-ethyl compound intermediate |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4636562A (en) * | 1982-05-07 | 1987-01-13 | E. I. Du Pont De Nemours And Company | Process for preparing 6-halo-2-chloroquinoxaline |
| JPS59216878A (en) * | 1983-05-25 | 1984-12-06 | Nippon Kayaku Co Ltd | Production of 2-quinoxalinol |
| IL86416A (en) * | 1987-06-19 | 1993-07-08 | Uniroyal Chem Co Inc | Process for the preparation of 2-quinoxalinol derivatives |
| US4814444A (en) * | 1987-06-19 | 1989-03-21 | Uniroyal Chemical Company, Inc. | Process for the selective reduction of 2-hydroxyquinoxaline-4-oxides |
-
2010
- 2010-08-27 CN CN2010102644715A patent/CN101941947B/en active Active
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107739343A (en) * | 2017-09-07 | 2018-02-27 | 京博农化科技股份有限公司 | A kind of environment-friendly type technique for producing Quizalotop-ethyl |
| CN107739343B (en) * | 2017-09-07 | 2020-06-19 | 京博农化科技股份有限公司 | Environment-friendly process for producing quizalofop-p-ethyl |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101941947A (en) | 2011-01-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101941947B (en) | Synthesis method of 2-chloro-6-chloroquinoxaline | |
| CN106748921B (en) | A kind of virtue sulfuryl difluoroacetic acid salt compounds, preparation method and applications | |
| CN102952043B (en) | Synthesis method of tert-butyl acrylamide sulfonate | |
| CN109111357A (en) | It is a kind of can volume production rhodium caprylate dimer synthetic method | |
| CN102161639A (en) | Method for synthesizing pyridinium hydroxy propyl sulfobetaine | |
| CN113683571A (en) | Preparation method of 2-methyl-5-bromopyrimidine | |
| CN111499517B (en) | Preparation method of m-nitrobenzotrifluoride | |
| CN115611803B (en) | Synthesis method of 2, 3-dichloropyridine | |
| CN111995640A (en) | Method for synthesizing (3-amino-3-cyano) propyl methyl butyl phosphite based on microchannel reactor | |
| CN104628653B (en) | The method of synthesizing rosuvastatin spit of fland calcium key intermediate | |
| CN116640047A (en) | Preparation method of 4-hydroxy biphenyl | |
| CN104892371A (en) | Method for producing glycol dimethyl ether | |
| CN112939893B (en) | Synthesis method of 4- (4-aminophenyl) -3-morpholinone | |
| CN104744352B (en) | A kind of method for preparing 4 substituted oxy phenol compounds | |
| CN108047033B (en) | Reaction device and method for preparing mandelic acid compound | |
| CN104387259B (en) | One is prepared the method for 2,4,5-trifluoro benzene acetic acid | |
| CN100391600C (en) | Catalyst for synthesizing methyl carbonate and method for preparing the same | |
| CN110577496A (en) | Preparation method of uracil | |
| CN101490013B (en) | Method for producing imidazolidine-2,4-dione compound and method for obtaining solid 4,5-dihydroxy-2-imidazolidinone compound | |
| CN109651266A (en) | A kind of preparation method of herbicide terbacil | |
| CN104649994B (en) | A kind of preparation method of 4-methyl-5-alkoxy-oxazole | |
| CN115073364B (en) | Preparation method of 6-nitropyridin-3-ol | |
| CN111825711B (en) | Vanadium pyridine catalyst for preparing 2, 5-dichlorophenol by catalytic oxidation and synthesis method and application thereof | |
| CN115260010B (en) | Method for preparing m-fluorophenol from 2, 6-difluorobenzonitrile | |
| CN110452097B (en) | Preparation method of 1-hydroxypyrene |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: SHANDONG CHAMBROAD HOLDING CO., LTD. Free format text: FORMER OWNER: SHANDONG JINGBO HOLDING DEVELOPMENT CO., LTD. Effective date: 20110822 Owner name: CHAMBROAD AGROCHEMICAL TECHNOLOGY CO., LTD. Free format text: FORMER OWNER: SHANDONG CHAMBROAD AGROCHEMICAL CO., LTD. |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 256505 BINZHOU, SHANDONG PROVINCE TO: 256500 BINZHOU, SHANDONG PROVINCE |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20110822 Address after: 256500 Shandong city of Binzhou province Hu Zhen Boxing County Chen Jingbo Industrial Park Applicant after: SHANDONG CHAMBROAD HOLDING Co.,Ltd. Co-applicant after: JINGBO AGROCHEMICALS TECHNOLOGY Co.,Ltd. Address before: 256505 Shandong city of Binzhou province Hu Zhen Boxing County Chen Jingbo Industrial Park Applicant before: SHANDONG JINGBO HOLDING DEVELOPMENT Co.,Ltd. Co-applicant before: Shandong Jingbo Agrochemicals Co.,Ltd. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Free format text: FORMER OWNER: CHAMBROAD AGROCHEMICAL TECHNOLOGY CO., LTD. Effective date: 20130426 Owner name: CHAMBROAD AGROCHEMICAL TECHNOLOGY CO., LTD. Free format text: FORMER OWNER: SHANDONG CHAMBROAD HOLDING CO., LTD. Effective date: 20130426 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20130426 Address after: 256500 Boxing Economic Development Zone, Binzhou, Shandong Patentee after: JINGBO AGROCHEMICALS TECHNOLOGY Co.,Ltd. Address before: 256500 Shandong city of Binzhou province Hu Zhen Boxing County Chen Jingbo Industrial Park Patentee before: SHANDONG CHAMBROAD HOLDING Co.,Ltd. Patentee before: JINGBO AGROCHEMICALS TECHNOLOGY Co.,Ltd. |
|
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 256500 Boxing County Economic Development Zone, Binzhou, Shandong Patentee after: JINGBO AGROCHEMICALS TECHNOLOGY Co.,Ltd. Address before: 256500 Boxing County Economic Development Zone, Binzhou, Shandong Patentee before: JINGBO AGROCHEMICALS TECHNOLOGY Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220728 Address after: 256500 Boxing Economic Development Zone, Shandong, Binzhou Patentee after: JINGBO AGROCHEMICALS TECHNOLOGY Co.,Ltd. Patentee after: Shandong Jingbo Biotechnology Co.,Ltd. Address before: 256500 Boxing Economic Development Zone, Shandong, Binzhou Patentee before: JINGBO AGROCHEMICALS TECHNOLOGY Co.,Ltd. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 256500 Boxing Economic Development Zone, Shandong, Binzhou Patentee after: Shandong Jingbo Agrochemical Technology Co.,Ltd. Patentee after: Shandong Jingbo Biotechnology Co.,Ltd. Address before: 256500 Boxing Economic Development Zone, Shandong, Binzhou Patentee before: JINGBO AGROCHEMICALS TECHNOLOGY Co.,Ltd. Patentee before: Shandong Jingbo Biotechnology Co.,Ltd. |
|
| CP01 | Change in the name or title of a patent holder |