CN113698348A - Preparation method of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate - Google Patents
Preparation method of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate Download PDFInfo
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- IBCDZZHMNXXYAP-UHFFFAOYSA-N 2-(4,5-diaminopyrazol-1-yl)ethanol;sulfuric acid Chemical compound OS(O)(=O)=O.NC=1C=NN(CCO)C=1N IBCDZZHMNXXYAP-UHFFFAOYSA-N 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 226
- 239000002994 raw material Substances 0.000 claims abstract description 53
- ANGDWNBGPBMQHW-UHFFFAOYSA-N methyl cyanoacetate Chemical compound COC(=O)CC#N ANGDWNBGPBMQHW-UHFFFAOYSA-N 0.000 claims abstract description 50
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 33
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 31
- GBHCABUWWQUMAJ-UHFFFAOYSA-N 2-hydrazinoethanol Chemical compound NNCCO GBHCABUWWQUMAJ-UHFFFAOYSA-N 0.000 claims abstract description 29
- 238000006114 decarboxylation reaction Methods 0.000 claims abstract description 29
- 238000006722 reduction reaction Methods 0.000 claims abstract description 22
- 238000006193 diazotization reaction Methods 0.000 claims abstract description 21
- 238000006386 neutralization reaction Methods 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 16
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 90
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 82
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 75
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 59
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 54
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 43
- 239000001632 sodium acetate Substances 0.000 claims description 43
- 235000017281 sodium acetate Nutrition 0.000 claims description 43
- 239000003054 catalyst Substances 0.000 claims description 37
- 239000000243 solution Substances 0.000 claims description 37
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
- 239000007864 aqueous solution Substances 0.000 claims description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 claims description 27
- 235000010288 sodium nitrite Nutrition 0.000 claims description 27
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 24
- 102000004190 Enzymes Human genes 0.000 claims description 21
- 108090000790 Enzymes Proteins 0.000 claims description 21
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 18
- 239000012452 mother liquor Substances 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 238000007363 ring formation reaction Methods 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 11
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 238000002425 crystallisation Methods 0.000 claims description 9
- 230000008025 crystallization Effects 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 238000005119 centrifugation Methods 0.000 claims description 7
- 238000000605 extraction Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000010413 mother solution Substances 0.000 claims description 2
- 238000005755 formation reaction Methods 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 22
- 238000004519 manufacturing process Methods 0.000 description 17
- 239000002351 wastewater Substances 0.000 description 15
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 14
- 238000010438 heat treatment Methods 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 230000000694 effects Effects 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000001816 cooling Methods 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- 238000004321 preservation Methods 0.000 description 7
- 230000035484 reaction time Effects 0.000 description 7
- 238000003860 storage Methods 0.000 description 7
- 230000007935 neutral effect Effects 0.000 description 6
- 239000007858 starting material Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000002699 waste material Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
- 230000009935 nitrosation Effects 0.000 description 1
- 238000007034 nitrosation reaction Methods 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/10—Nitrogen as only ring hetero atom
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Abstract
The invention discloses a preparation method of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate, belonging to the field of chemical intermediate synthesis. The method comprises the steps of using methyl cyanoacetate as a raw material, pretreating the methyl cyanoacetate as the raw material, cyclizing the pretreated product with 2-hydrazino ethanol to construct a pyrazole ring, subjecting the cyclized product to hydrolysis reaction, neutralization reaction, decarboxylation reaction, diazotization reaction, azo reaction and reduction reaction, and finally salifying the cyclized product with concentrated sulfuric acid.
Description
Technical Field
The invention relates to the technical field of chemical intermediate synthesis, and particularly relates to a preparation method of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate.
Background
In the synthesis method of the 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate, patent CN110423222A diethyl ethoxymethylene malonate is used as a raw material, patent CN106279026A uses 2-cyano-3-ethoxy ethyl acrylate as a starting material, and the two patents undergo the steps of cyclization of the starting material with 2-hydroxyethyl hydrazine, hydrolysis, acidification, decarboxylation, nitrosation, reduction and sulfuric acid salt formation to prepare a final target product. The raw materials used in the process have high reaction activity, are easy to oxidize and difficult to store, and high-concentration alkali solution is needed in the hydrolysis reaction, so that the three wastes are large and the production cost is high.
Disclosure of Invention
Aiming at the technical defects, the invention aims to provide the preparation method of the 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate, which uses stable methyl cyanoacetate as a starting material, uses high-efficiency enzyme catalysis reaction in hydrolysis reaction, reduces the discharge of three wastes and reduces the production cost.
In order to solve the technical problems, the invention adopts the following technical scheme: a preparation method of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate comprises the steps of pretreating raw material methyl cyanoacetate, cyclizing the pretreated product with 2-hydrazino ethanol to construct a pyrazole ring, subjecting the cyclized product to hydrolysis reaction, neutralization reaction, decarboxylation reaction, diazotization reaction, azo reaction and reduction reaction, and finally salifying with concentrated sulfuric acid to prepare the 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate.
Preferably, the pretreatment reaction temperature of the raw material methyl cyanoacetate pretreatment is-20-100 ℃, the cyclization reaction temperature in the subsequent steps is 50-100 ℃, the hydrolysis reaction temperature is 20-100 ℃, the neutralization reaction temperature is-10-40 ℃, the decarboxylation reaction temperature is 150-250 ℃, the diazotization reaction temperature is-20-30 ℃, the azo reaction temperature is-20-30 ℃, the reduction reaction temperature is 30-90 ℃, and the reaction temperature with the salt-forming concentrated sulfuric acid is 10-25 ℃.
Preferably, the method comprises the following steps:
(1) pretreatment: pretreatment of raw material methyl cyanoacetate: adding dimethyl sulfate into a reaction kettle, controlling the temperature to be 20-50 ℃, dropwise adding dimethyl formamide for 2-4 hours, controlling the temperature to be 30-70 ℃ after dropwise adding, and reacting for not less than 6 hours to obtain an intermediate A;
dropwise adding the intermediate A into a methanol solution of sodium methoxide, controlling the temperature to be-20 ℃, dropwise adding for 2-3 hours, reacting for 1-2 hours after dropwise adding, and centrifuging to obtain a mother solution B;
dropwise adding methyl cyanoacetate into the mother liquor B, controlling the temperature to be-10-20 ℃, dropwise adding for 1-3 hours, controlling the temperature to be-10-100 ℃ after dropwise adding, reacting for at least 6 hours, and obtaining an intermediate C through centrifugation, toluene extraction and drying;
(2) and (3) cyclization reaction: adding the intermediate C into a reaction kettle, dissolving the intermediate C with 95% ethanol, controlling the temperature to be-10-40 ℃, dropwise adding 2-hydrazino ethanol, controlling the temperature to be 50-100 ℃, and reacting for 4-6 hours to obtain an intermediate D;
(3) and (3) hydrolysis reaction: mixing the intermediate D, an La enzyme catalyst with the mass fraction of 0.2-0.8% based on the intermediate D and water, adjusting the pH value to 7-10 by using a sodium hydroxide solution, controlling the temperature to 20-100 ℃, reacting for 2-4 hours, and filtering to obtain an intermediate E;
(4) and (3) neutralization reaction: adding the intermediate E into a reaction kettle, dropwise adding hydrochloric acid to adjust the pH value to 7-8, controlling the temperature to be-10-40 ℃, reacting for 1-3 hours, and centrifuging to obtain an intermediate F;
(5) decarboxylation: adding the intermediate F into a reaction kettle, adding water and sodium acetate, stirring, controlling the temperature to be 150-250 ℃ and reacting for 2-4 hours to obtain an intermediate G;
(6) diazotization reaction: adding hydrochloric acid and water into a reaction kettle, controlling the temperature to be-20-30 ℃, dropwise adding aniline and sodium nitrite aqueous solution for 3 hours, and keeping the temperature for reaction for 1-3 hours after dropwise adding to obtain an intermediate H;
(7) and (3) azo reaction: adding the intermediate H and sodium acetate into a reaction kettle, controlling the temperature to be minus 20-30 ℃, dropwise adding the intermediate G for 4-5 hours, reacting for 1-2 hours after dropwise adding, and centrifuging to obtain an intermediate I;
(8) reduction reaction: adding the intermediate I, methanol and a palladium-carbon catalyst into a reaction kettle, introducing hydrogen, controlling the temperature to be 30-90 ℃ and reacting for 4-8 hours to obtain an intermediate J;
(9) salt forming reaction: and adding the intermediate J into a reaction kettle, dropwise adding concentrated sulfuric acid for 3 hours, stirring for 30 minutes after dropwise adding is finished, standing for crystallization, and filtering to obtain the 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate.
Preferably, in the step (1), the mass ratio of dimethyl sulfate to dimethylformamide is 1.5-3: 0.8-1; the mass ratio of the intermediate A to a 30-40% sodium methoxide methanol solution is 0.5-0.8: 1-1.5, wherein the mass ratio of the methyl cyanoacetate to the mother liquor B is 0.5-1: 2-3; in the step (2), the mass ratio of the intermediate C, 95% ethanol and 2-hydrazinoethanol is 1-1.5: 2-4: 0.8-1.5; in the step (5), the mass ratio of the intermediate F, water and sodium acetate is 1-2: 6-10: 2-4; in the step (6), the mass ratio of the hydrochloric acid, the water, the aniline and the sodium nitrite aqueous solution is 0.8-1.5: 0.8-1.2: 0.3-0.8: 0.8-1.5; in the step (7), the mass ratio of the intermediate H to the intermediate sodium acetate to the intermediate G is 0.5-1: 0.2-0.4: 1-2; in the step (8), the mass ratio of the intermediate I, the methanol and the palladium carbon catalyst is 0.5-1: 6-10: 0.02-0.05; in the step (9), the mass ratio of the intermediate J to concentrated sulfuric acid is 10-18: 2-4.
Preferably, the mass fraction of the methanol solution of sodium methoxide in the step (1) is 30-40%, the mass fraction of the sodium hydroxide aqueous solution in the step (3) is 20-40%, and the mass fraction of the sodium nitrite aqueous solution in the step (6) is 40-50%.
Preferably, the adding mass fraction of the La enzyme catalyst is 0.2-0.8% of the intermediate D.
Preferably, the pressure when the reaction is carried out and hydrogen is introduced is 3-5 MPa.
The invention has the beneficial effects that: 1. the methyl cyanoacetate is used as a starting material, double bonds do not exist in the raw material, the chemical property is more stable, the methyl cyanoacetate cannot be polymerized, is not easy to be oxidized and deteriorated by air, and is easy to store; 2. in the hydrolysis reaction, the biological enzyme is used as a catalyst, and the biological enzyme is a catalytic amount, so that the efficiency of the hydrolysis reaction is improved; the scheme integrally reduces the wastewater discharge, saves resources and further reduces the production cost.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
[ example 1]
A process for preparing 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate includes pretreating methyl cyanoacetate, cyclizing with 2-hydrazino alcohol, hydrolysis, neutralization, decarboxylation, diazotization, azo reaction, reduction and salifying with concentrated sulfuric acid to obtain 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate.
(1) Pretreatment: adding dimethyl sulfate into a reaction kettle, controlling the temperature to be 20-35 ℃, dropwise adding dimethylformamide, wherein the water content of the dimethylformamide can be changed, so that the mass ratio of the dimethyl sulfate to the dimethylformamide is 1.5-2.8:0.8-1, the dropwise adding time is 2-4 hours, and controlling the temperature to be 35-45 ℃ after the dropwise adding is finished, and reacting for 6 hours to obtain an intermediate A.
Preparing a 30-40% sodium methoxide methanol solution at room temperature, cooling the intermediate A obtained in the last step to 0-20 ℃, dropwise adding the intermediate A into the 30-40% sodium methoxide methanol solution, controlling the temperature to 0-20 ℃, and dropwise adding for 2-3 hours, wherein according to the actual solubility of sodium methoxide in methanol, the ratio of the intermediate A to the 30-40% sodium methoxide methanol solution is 0.5-0.8: 1-1.2, and reacting for 1-2 hours after the dropwise addition.
Dropwise adding methyl cyanoacetate into the obtained mother liquor B, controlling the temperature to be 0-20 ℃, dropwise adding for 2-3 hours, wherein the mass ratio of methyl cyanoacetate to the mother liquor B obtained in the last step is 0.5-1:2-2.7, gradually heating from 0-20 ℃ to 20-40 ℃ after dropwise adding, reacting for 6 hours, detecting the reaction progress of ethyl cyanoacetate serving as a raw material by using HPLC (high performance liquid chromatography), heating to 50-100 ℃ for continuous reaction when the raw material remains according to the reaction progress, stopping the reaction when 0.05% of methyl cyanoacetate remains, centrifuging, extracting with toluene, and drying to obtain an intermediate C. Methyl cyanoacetate is used as a raw material in the reaction, unsaturated bonds are not contained in the raw material, the raw material cannot be oxidized in storage and cannot be polymerized by itself, the reaction raw material is immediately put into the next production after being treated, and the reaction activity is high.
(2) And (3) cyclization reaction: adding the intermediate C and 95% ethanol into a reaction kettle, dissolving the intermediate C by 95%, controlling the temperature to be-10-5 ℃, dropwise adding 2-hydrazino ethanol for 2-3 hours, wherein the mass ratio of the intermediate C to the 95% ethanol to the 2-hydrazino ethanol is 1-1.4: 2-4: 0.8-1.5; and (3) changing the adding amount of the 2-hydrazinoethanol along with the amount of the intermediate C, and controlling the temperature to be 80-100 ℃ to react for 4-6 hours to obtain an intermediate D.
(3) And (3) hydrolysis reaction: adding the intermediate D, an La enzyme catalyst with the mass fraction of 0.2-0.8% calculated by the intermediate D and water into a reaction kettle, preparing 20-40% of sodium hydroxide solution, adjusting the pH value of a reaction system to 7-10, controlling the temperature to 20-40 ℃ for reaction for 3.5-4 hours, and filtering to obtain an intermediate E. The La enzyme catalyst is added, the reaction time is shortened, and the hydrolysis reaction efficiency of the reaction is improved.
(4) And (3) performing neutralization reaction, namely adding the intermediate E into a reaction kettle, dropwise adding hydrochloric acid to adjust the pH value to 7-8, controlling the temperature to be-10 ℃, reacting for 2-3 hours, and centrifuging to obtain an intermediate F.
(5) Decarboxylation: adding the intermediate F into a reaction kettle, adding water and sodium acetate, stirring, controlling the temperature to be 150-180 ℃, and reacting for 3-4 hours, wherein the mass ratio of the intermediate F to the water to the sodium acetate is 1-1.9: 6-10: 2-3.8, the amount of sodium acetate varies with the amount of hydrochloric acid used in the previous reaction to adjust the pH and the amount of water used in the decarboxylation reaction, to give intermediate G.
(6) Diazotization reaction: adding hydrochloric acid and water into a reaction kettle, controlling the temperature to be-20-0 ℃, dropwise adding aniline and 40-50% of sodium nitrite aqueous solution, wherein the mass ratio of the hydrochloric acid to the water to the aniline to the 40-50% of sodium nitrite aqueous solution is 0.9-1.5: 0.8-1.2: 0.3-0.8: 0.9-1.5, wherein the adding mass of the 40-50% sodium nitrite aqueous solution and the hydrochloric acid is consistent, the dripping time is 3 hours, and the heat preservation reaction is carried out for 2-3 hours after the dripping is finished, so as to obtain an intermediate H.
(7) And (3) azo reaction: adding the intermediate H and sodium acetate into a reaction kettle, controlling the temperature to be 0-15 ℃, and dropwise adding the intermediate G, wherein the ratio of the intermediate H to the sodium acetate to the intermediate G is 0.5-0.9: 0.2-0.4: 1-1.8, the dripping time is 4-5 hours, the reaction is carried out for 1-2 hours after the dripping is finished, and the intermediate I is obtained through centrifugation.
(8) Reduction reaction: adding the intermediate I into a reaction kettle, adding methanol for dissolving, adding a palladium carbon catalyst into the reaction kettle, introducing hydrogen, controlling the temperature to be 70-90 ℃ for reacting for 5-8 hours, wherein the hydrogen pressure is kept at 3-5 MPa in the reaction, and the ratio of the intermediate I, the methanol and the metal catalyst is 0.5-0.9: 6-10: 0.02-0.04 to obtain intermediate J.
(9) Salt forming reaction: adding the intermediate J into a reaction kettle, controlling the temperature to be 10-15 ℃, and dropwise adding concentrated sulfuric acid, wherein the ratio of the intermediate J to the concentrated sulfuric acid is 10-17: 2-4, the dropping time is 3 hours, the temperature is controlled to 15-25 ℃ after the dropping is finished, the mixture is stirred for 30 minutes, the mixture is kept stand for crystallization and filtered to obtain a product of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate, and the total yield is calculated by ethyl cyanoacetate: 82.8 percent and 99 percent of purity, and compared with the yield of 74 percent in the prior art, the yield of the scheme is improved. The method is used for preparing 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate products, 3000 tons of wastewater are generated, the scheme is not adopted, 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate are obtained, and the amount of the generated wastewater is more than 4000 tons.
[ example 2]
A process for preparing 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate includes pretreating methyl cyanoacetate, cyclizing with 2-hydrazino alcohol, hydrolysis, neutralization, decarboxylation, diazotization, azo reaction, reduction and salifying with concentrated sulfuric acid to obtain 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate.
(1) Pretreatment: adding dimethyl sulfate into a reaction kettle, controlling the temperature to be 20-30 ℃, dropwise adding dimethylformamide, wherein the water content of the dimethylformamide is changed, so that the mass ratio of the dimethyl sulfate to the dimethylformamide is 1.6-3:0.9-1, the dropwise adding time is 2-4 hours, and controlling the temperature to be 30-40 ℃ after the dropwise adding is finished to react for 6 hours to obtain an intermediate A.
Preparing a 30-40% sodium methoxide methanol solution at room temperature, cooling the intermediate A obtained in the last step to 0-20 ℃, dropwise adding the intermediate A into the 30-40% sodium methoxide methanol solution, controlling the temperature to 0-20 ℃, and dropwise adding for 2-3 hours, wherein according to the solubility of sodium methoxide in methanol, the ratio of the intermediate A to the 30-40% sodium methoxide methanol solution is 0.7-0.8: 1.3-1.5, the dripping time is 2-3 hours, and the reaction is 1-2 hours after the dripping is finished.
Dropwise adding methyl cyanoacetate into the obtained mother liquor B, controlling the temperature to be 0-20 ℃, dropwise adding for 2-3 hours, wherein the mass ratio of methyl cyanoacetate to the mother liquor B obtained in the last step is 0.5-0.9:2-2.8, gradually heating from 0-20 ℃ to 20-40 ℃ after dropwise adding, reacting for 6 hours, detecting the reaction progress of ethyl cyanoacetate serving as a raw material by using HPLC (high performance liquid chromatography), heating to 50-100 ℃ for continuous reaction when the raw material remains according to the reaction progress, stopping the reaction when 0.05% of methyl cyanoacetate remains, centrifuging, extracting with toluene, and drying to obtain an intermediate C. Methyl cyanoacetate is used as a raw material in the reaction, unsaturated bonds are not contained in the raw material, the raw material cannot be oxidized in storage and cannot be polymerized by itself, the reaction raw material is immediately put into the next production after being treated, and the reaction activity is high.
(2) And (3) cyclization reaction: adding the intermediate C and 95% ethanol into a reaction kettle, dissolving the intermediate C by 95%, controlling the temperature to be 5-25 ℃, dropwise adding 2-hydrazino ethanol for 2-4 hours, wherein the mass ratio of the intermediate C to the 95% ethanol to the 2-hydrazino ethanol is 1.1-1.5: 2-4: 0.9-1.5; and (3) the adding amount of the 2-hydrazinoethanol is changed along with the amount of the intermediate C, and the temperature is controlled to be 70-90 ℃ to react for 4-6 hours to obtain an intermediate D.
(3) And (3) hydrolysis reaction: adding the intermediate D, an La enzyme catalyst with the mass fraction of 0.2-0.8% calculated by the intermediate D and water into a reaction kettle, preparing 20-40% of sodium hydroxide solution, adjusting the pH value of a reaction system to 7-10, controlling the temperature to 80-100 ℃ for reaction for 2-3 hours, and filtering to obtain an intermediate E. The La enzyme catalyst is added, the reaction time is shortened, and the hydrolysis reaction efficiency of the reaction is improved.
(4) And (3) performing neutralization reaction, namely adding the intermediate E into a reaction kettle, dropwise adding hydrochloric acid to adjust the pH value to be neutral (the pH value is 7-8), controlling the temperature to be 30-40 ℃, reacting for 1-2 hours, and centrifuging to obtain an intermediate F.
(5) Decarboxylation: adding the intermediate F into a reaction kettle, adding water and sodium acetate, stirring, controlling the temperature to be 210-250 ℃ and reacting for 2-3 hours, wherein the mass ratio of the intermediate F to the water to the sodium acetate is 1.1-2: 6-10: 2.2-4, the amount of sodium acetate was varied by the amount of hydrochloric acid used for pH adjustment in the previous reaction and the amount of water used for decarboxylation reaction to give intermediate G.
(6) Diazotization reaction: adding hydrochloric acid and water into a reaction kettle, controlling the temperature to be 15-30 ℃, dropwise adding aniline and 40-50% of sodium nitrite aqueous solution, wherein the mass ratio of the hydrochloric acid to the water to the aniline to the 40-50% of sodium nitrite aqueous solution is 0.9-1.5: 0.8-1.2: 0.3-0.8: 0.9-1.5, wherein the adding mass of the 40-50% sodium nitrite aqueous solution and the hydrochloric acid is consistent, the dropwise adding time is 3 hours, and the heat preservation reaction is carried out for 1-2 hours after the dropwise adding is finished, so as to obtain an intermediate H.
(7) And (3) azo reaction: adding the intermediate H and sodium acetate into a reaction kettle, controlling the temperature to be 0-15 ℃, and dropwise adding the intermediate G, wherein the ratio of the intermediate H to the sodium acetate to the intermediate G is 0.5-0.9: 0.2-0.4: 1-1.8, the dripping time is 4-5 hours, the reaction is carried out for 1-2 hours after the dripping is finished, and the intermediate I is obtained through centrifugation.
(8) Reduction reaction: adding the intermediate I into a reaction kettle, adding methanol for dissolving, adding a palladium carbon catalyst into the reaction kettle, introducing hydrogen, controlling the temperature to be 60-70 ℃ for reacting for 7-8 hours, wherein the hydrogen pressure is kept at 3-5 MPa in the reaction, and the ratio of the intermediate I to the methanol to the metal catalyst is 0.5-1: 6-10: 0.02-0.05 to obtain an intermediate J.
(9) Salt forming reaction: adding the intermediate J into a reaction kettle, controlling the temperature to be 10-15 ℃, and dropwise adding concentrated sulfuric acid, wherein the ratio of the intermediate J to the concentrated sulfuric acid is 10-18: 2-4, the dropping time is 3 hours, the temperature is controlled to 15-25 ℃ after the dropping is finished, the mixture is stirred for 30 minutes, the mixture is kept stand for crystallization and filtered to obtain a product of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate, and the total yield is calculated by ethyl cyanoacetate: 82.5 percent and the purity is 99 percent. Compared with the yield of 74% in the prior art, the yield of the scheme is improved. The method is used for preparing 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate products, 3000 tons of wastewater are generated, the scheme is not adopted, 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate are obtained, and the amount of the generated wastewater is more than 4000 tons.
[ example 3]
A process for preparing 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate includes pretreating methyl cyanoacetate, cyclizing with 2-hydrazino alcohol, hydrolysis, neutralization, decarboxylation, diazotization, azo reaction, reduction and salifying with concentrated sulfuric acid to obtain 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate.
(1) Pretreatment: adding dimethyl sulfate into a reaction kettle, controlling the temperature to be 30-50 ℃, dropwise adding dimethylformamide, wherein the water content of the dimethylformamide is changed, so that the mass ratio of the dimethyl sulfate to the dimethylformamide is 1.7-3:0.9-1, the dropwise adding time is 3-4 hours, and controlling the temperature to be 50-70 ℃ to react for 6 hours after the dropwise adding is finished, thus obtaining an intermediate A.
Preparing a 30-40% sodium methoxide methanol solution at room temperature, cooling the intermediate A obtained in the last step to-20-0 ℃, dropwise adding the intermediate A into the 30-40% sodium methoxide methanol solution, controlling the temperature to-20-0 ℃, and dropwise adding for 1-2 hours, wherein according to the solubility of sodium methoxide in methanol, the ratio of the intermediate A to the 30-40% sodium methoxide methanol solution is 0.5-0.7: 1-1.3, and reacting for 1-2 hours after the dropwise addition.
Dropwise adding methyl cyanoacetate into the obtained mother liquor B, controlling the temperature to be-10 ℃, dropwise adding for 1-2 hours, wherein the mass ratio of methyl cyanoacetate to the mother liquor B obtained in the last step is 0.5-1:2.1-3, gradually heating from-10 ℃ to 40-60 ℃ after dropwise adding, reacting for 6 hours, detecting the reaction progress of ethyl cyanoacetate serving as a raw material by using HPLC (high performance liquid chromatography), heating to 60-100 ℃ for continuous reaction when the raw material remains according to the reaction progress, stopping the reaction when 0.05% of methyl cyanoacetate remains, centrifuging, extracting with toluene, and drying to obtain an intermediate C. Methyl cyanoacetate is used as a raw material in the reaction, unsaturated bonds are not contained in the raw material, the raw material cannot be oxidized in storage and cannot be polymerized by itself, the reaction raw material is immediately put into the next production after being treated, and the reaction activity is high.
(2) And (3) cyclization reaction: adding the intermediate C and 95% ethanol into a reaction kettle, dissolving the intermediate C by 95%, controlling the temperature to be 25-40 ℃, dropwise adding 2-hydrazino ethanol for 3-4 hours, wherein the mass ratio of the intermediate C to the 95% ethanol to the 2-hydrazino ethanol is 1-1.5: 2-4: 0.8 to 1.3; and (3) changing the adding amount of the 2-hydrazinoethanol along with the amount of the intermediate C, and controlling the temperature to be 50-70 ℃ to react for 4-6 hours to obtain an intermediate D.
(3) And (3) hydrolysis reaction: adding the intermediate D, an La enzyme catalyst with the mass fraction of 0.2-0.8% calculated by the intermediate D and water into a reaction kettle, preparing 20-40% of sodium hydroxide solution, adjusting the pH value of a reaction system to 7-10, controlling the temperature to 60-80 ℃ for reaction for 2-3 hours, and filtering to obtain an intermediate E. The La enzyme catalyst is added, the reaction time is shortened, and the hydrolysis reaction efficiency of the reaction is improved.
(4) And (3) neutralization reaction: and adding the intermediate E into a reaction kettle, dropwise adding hydrochloric acid to adjust the pH value to be neutral (the pH value is 7-8), controlling the temperature to be 10-20 ℃, reacting for 2-3 hours, and centrifuging to obtain an intermediate F.
(5) Decarboxylation: adding the intermediate F into a reaction kettle, adding water and sodium acetate, stirring, controlling the temperature to be 150-180 ℃, and reacting for 3-4 hours, wherein the mass ratio of the intermediate F to the water to the sodium acetate is 1-1.6: 6-10: 2-3.6, the amount of sodium acetate is changed with the change of hydrochloric acid used for adjusting pH in the previous step reaction and the amount of water used for decarboxylation reaction, thus obtaining an intermediate G.
(6) Diazotization reaction: adding hydrochloric acid and water into a reaction kettle, controlling the temperature to be-20-0 ℃, dropwise adding aniline and 40-50% of sodium nitrite aqueous solution, wherein the mass ratio of the hydrochloric acid to the water to the aniline to the 40-50% of sodium nitrite aqueous solution is 0.8-1.5: 0.8-1.2: 0.3-0.8: 0.8-1.5, wherein the adding mass of the 40-50% sodium nitrite aqueous solution and the hydrochloric acid is consistent, the dropwise adding time is 3 hours, and the heat preservation reaction is carried out for 2-3 hours after the dropwise adding is finished, so as to obtain an intermediate H.
(7) And (3) azo reaction: adding the intermediate H and sodium acetate into a reaction kettle, controlling the temperature to be 0-15 ℃, and dropwise adding the intermediate G, wherein the ratio of the intermediate H to the sodium acetate to the intermediate G is 0.5-0.9: 0.2-0.4: 1-1.8, the dripping time is 4-5 hours, the reaction is carried out for 1-2 hours after the dripping is finished, and the intermediate I is obtained through centrifugation.
(8) Reduction reaction: adding the intermediate I into a reaction kettle, adding methanol for dissolving, adding a palladium carbon catalyst into the reaction kettle, introducing hydrogen, controlling the temperature to be 60-70 ℃ for reacting for 7-8 hours, wherein the hydrogen pressure is kept at 3-5 MPa in the reaction, and the ratio of the intermediate I to the methanol to the metal catalyst is 0.5-1: 6-10: 0.02-0.05 to obtain an intermediate J.
(9) Salt forming reaction: adding the intermediate J into a reaction kettle, controlling the temperature to be 10-15 ℃, and dropwise adding concentrated sulfuric acid, wherein the ratio of the intermediate J to the concentrated sulfuric acid is 10-18: 2-4, the dropping time is 3 hours, the temperature is controlled to 15-25 ℃ after the dropping is finished, the mixture is stirred for 30 minutes, the mixture is kept stand for crystallization and filtered to obtain a product of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate, and the total yield is calculated by ethyl cyanoacetate: 83.2 percent and the purity is 99 percent. Compared with the yield of 74% in the prior art, the yield of the scheme is improved. The method is used for preparing 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate products, 3000 tons of wastewater are generated, the scheme is not adopted, 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate are obtained, and the amount of the generated wastewater is more than 4000 tons.
[ example 4]
A process for preparing 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate includes pretreating methyl cyanoacetate, cyclizing with 2-hydrazino alcohol, hydrolysis, neutralization, decarboxylation, diazotization, azo reaction, reduction and salifying with concentrated sulfuric acid to obtain 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate.
(1) Pretreatment: adding dimethyl sulfate into a reaction kettle, controlling the temperature to be 30-50 ℃, dropwise adding dimethylformamide, wherein the water content of the dimethylformamide is changed, so that the mass ratio of the dimethyl sulfate to the dimethylformamide is 1.5-2.8:0.8-1, the dropwise adding time is 3-4 hours, and controlling the temperature to be 50-70 ℃ to react for 6 hours after the dropwise adding is finished, thus obtaining an intermediate A.
Preparing a 30-40% sodium methoxide methanol solution at room temperature, cooling the intermediate A obtained in the last step to-20-0 ℃, dropwise adding the intermediate A into the 30-40% sodium methoxide methanol solution, controlling the temperature to-20-0 ℃, and dropwise adding for 1-2 hours, wherein according to the solubility of sodium methoxide in methanol, the ratio of the intermediate A to the 30-40% sodium methoxide methanol solution is 0.5-0.8: 1-1.5, and reacting for 2 hours after the dropwise addition.
Dropwise adding methyl cyanoacetate into the obtained mother liquor B, controlling the temperature to be-10 ℃, dropwise adding for 1-2 hours, wherein the mass ratio of methyl cyanoacetate to the mother liquor B obtained in the last step is 0.5-1:2-3, gradually heating from-10 ℃ to 40-60 ℃ after dropwise adding, reacting for 6 hours, detecting the reaction progress of ethyl cyanoacetate serving as a raw material by using HPLC (high performance liquid chromatography), heating to 60-100 ℃ for continuous reaction when the raw material remains according to the reaction progress, stopping the reaction when 0.05% of methyl cyanoacetate remains, centrifuging, extracting with toluene, and drying to obtain an intermediate C. Methyl cyanoacetate is used as a raw material in the reaction, unsaturated bonds are not contained in the raw material, the raw material cannot be oxidized in storage and cannot be polymerized by itself, the reaction raw material is immediately put into the next production after being treated, and the reaction activity is high.
(2) And (3) cyclization reaction: adding the intermediate C and 95% ethanol into a reaction kettle, dissolving the intermediate C by 95%, controlling the temperature to be 25-40 ℃, dropwise adding 2-hydrazino ethanol for 3-4 hours, wherein the mass ratio of the intermediate C to the 95% ethanol to the 2-hydrazino ethanol is 1-1.5: 2-3.8: 0.8-1.5; and (3) changing the adding amount of the 2-hydrazinoethanol along with the amount of the intermediate C, and controlling the temperature to be 50-70 ℃ to react for 4-6 hours to obtain an intermediate D.
(3) And (3) hydrolysis reaction: adding the intermediate D, an La enzyme catalyst with the mass fraction of 0.2-0.8% calculated by the intermediate D and water into a reaction kettle, preparing 20-40% of sodium hydroxide solution, adjusting the pH value of a reaction system to 7-10, controlling the temperature to 40-60 ℃ for reaction for 3-4 hours, and filtering to obtain an intermediate E. The La enzyme catalyst is added, the reaction time is shortened, and the hydrolysis reaction efficiency of the reaction is improved.
(4) And (3) performing neutralization reaction, namely adding the intermediate E into a reaction kettle, dropwise adding hydrochloric acid to adjust the pH value to be neutral (the pH value is 7-8), controlling the temperature to be 30-40 ℃, reacting for 1-2 hours, and centrifuging to obtain an intermediate F.
(5) Decarboxylation: adding the intermediate F into a reaction kettle, adding water and sodium acetate, stirring, controlling the temperature to be 210-250 ℃ and reacting for 2-3 hours, wherein the mass ratio of the intermediate F to the water to the sodium acetate is 1-2: 6-9: 2-4. the amount of sodium acetate is changed with the change of the amount of hydrochloric acid used for adjusting the pH in the previous reaction and the amount of water used for decarboxylation reaction, to obtain intermediate G.
(6) Diazotization reaction: adding hydrochloric acid and water into a reaction kettle, controlling the temperature to be-20-0 ℃, dropwise adding aniline and 40-50% of sodium nitrite aqueous solution, wherein the mass ratio of the hydrochloric acid to the water to the aniline to the 40-50% of sodium nitrite aqueous solution is 0.8-1.5: 0.8-1.2: 0.3-0.7: 0.8-1.5, wherein the adding mass of the 40-50% sodium nitrite aqueous solution and the hydrochloric acid is consistent, the dropwise adding time is 3 hours, and the heat preservation reaction is carried out for 2-3 hours after the dropwise adding is finished, so as to obtain an intermediate H.
(7) And (3) azo reaction: adding the intermediate H and sodium acetate into a reaction kettle, controlling the temperature to be minus 20-0 ℃, and dropwise adding the intermediate G, wherein the ratio of the intermediate H to the sodium acetate to the intermediate G is 0.5-1: 0.2-0.4: 1-2, the dripping time is 4 hours, the reaction is carried out for 1-2 hours after the dripping is finished, and the intermediate I is obtained through centrifugation.
(8) Reduction reaction: adding the intermediate I into a reaction kettle, adding methanol for dissolving, adding a palladium carbon catalyst into the reaction kettle, introducing hydrogen, controlling the temperature to be 60-70 ℃ for reacting for 7-8 hours, wherein the hydrogen pressure is kept at 3-5 MPa in the reaction, and the ratio of the intermediate I to the methanol to the metal catalyst is 0.5-1: 6-9: 0.02-0.05 to obtain an intermediate J.
(9) Salt forming reaction: adding the intermediate J into a reaction kettle, controlling the temperature to be 10-15 ℃, and dropwise adding concentrated sulfuric acid, wherein the ratio of the intermediate J to the concentrated sulfuric acid is 10-18: 2-4, the dropping time is 3 hours, the temperature is controlled to 15-25 ℃ after the dropping is finished, the mixture is stirred for 30 minutes, the mixture is kept stand for crystallization and filtered to obtain a product of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate, and the total yield is calculated by ethyl cyanoacetate: 82.7 percent and the purity is 99 percent. Compared with the yield of 74% in the prior art, the yield of the scheme is improved. The method is used for preparing 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate products, 3000 tons of wastewater are generated, the scheme is not adopted, 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate are obtained, and the amount of the generated wastewater is more than 4000 tons.
[ example 5]
A process for preparing 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate includes pretreating methyl cyanoacetate, cyclizing with 2-hydrazino alcohol, hydrolysis, neutralization, decarboxylation, diazotization, azo reaction, reduction and salifying with concentrated sulfuric acid to obtain 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate.
(1) Pretreatment: adding dimethyl sulfate into a reaction kettle, controlling the temperature to be 20-35 ℃, dropwise adding dimethylformamide, wherein the water content of the dimethylformamide is changed, so that the mass ratio of the dimethyl sulfate to the dimethylformamide is 1.5-2.5:0.8-0.9, the dropwise adding time is 2-4 hours, and controlling the temperature to be 30-40 ℃ after the dropwise adding is finished, and reacting for 6 hours to obtain an intermediate A.
Preparing a 30-40% sodium methoxide methanol solution at room temperature, cooling the intermediate A obtained in the last step to 0-20 ℃, dropwise adding the intermediate A into the 30-40% sodium methoxide methanol solution, controlling the temperature to 0-20 ℃, and dropwise adding for 2-3 hours, wherein according to the solubility of sodium methoxide in methanol, the ratio of the intermediate A to the 30-40% sodium methoxide methanol solution is 0.5-0.8: 1-1.5, the dripping time is 2-3 hours, and the reaction is carried out for 1-2 hours after the dripping is finished;
dropwise adding methyl cyanoacetate into the obtained mother liquor B, controlling the temperature to be 0-20 ℃, dropwise adding for 2-3 hours, wherein the mass ratio of methyl cyanoacetate to the mother liquor B obtained in the last step is 0.5-1:2-3, gradually heating from 0-20 ℃ to 20-40 ℃ after dropwise adding, reacting for 6 hours, detecting the reaction progress of ethyl cyanoacetate serving as a raw material by using HPLC (high performance liquid chromatography), heating to 50-100 ℃ for continuous reaction when the raw material is remained according to the reaction progress, stopping the reaction when 0.05% of methyl cyanoacetate remains, centrifuging, extracting with toluene, and drying to obtain an intermediate C. Methyl cyanoacetate is used as a raw material in the reaction, unsaturated bonds are not contained in the raw material, the raw material cannot be oxidized in storage and cannot be polymerized by itself, the reaction raw material is immediately put into the next production after being treated, and the reaction activity is high.
(2) And (3) cyclization reaction: adding the intermediate C and 95% ethanol into a reaction kettle, dissolving the intermediate C by 95%, controlling the temperature to be 25-40 ℃, dropwise adding 2-hydrazino ethanol for 3-4 hours, wherein the mass ratio of the intermediate C to the 95% ethanol to the 2-hydrazino ethanol is 1-1.5: 2-4: 0.8-1.5; and (3) changing the adding amount of the 2-hydrazinoethanol along with the amount of the intermediate C, and controlling the temperature to be 50-70 ℃ to react for 4-6 hours to obtain an intermediate D.
(3) And (3) hydrolysis reaction: adding the intermediate D, an La enzyme catalyst with the mass fraction of 0.2-0.8% calculated by the intermediate D and water into a reaction kettle, preparing 20-40% of sodium hydroxide solution, adjusting the pH value of a reaction system to 7-10, controlling the temperature to 40-60 ℃ for reaction for 3-4 hours, and filtering to obtain an intermediate E. The La enzyme catalyst is added, the reaction time is shortened, and the hydrolysis reaction efficiency of the reaction is improved.
(4) And (3) performing neutralization reaction, namely adding the intermediate E into a reaction kettle, dropwise adding hydrochloric acid to adjust the pH value to be neutral (the pH value is 7-8), controlling the temperature to be 30-40 ℃, reacting for 1-2 hours, and centrifuging to obtain an intermediate F.
(5) Decarboxylation: adding the intermediate F into a reaction kettle, adding water and sodium acetate, stirring, controlling the temperature to be 180-210 ℃, and reacting for 3-4 hours, wherein the mass ratio of the intermediate F to the water to the sodium acetate is 1-1.5: 6-8: 2-3. the amount of sodium acetate is changed with the change of the amount of hydrochloric acid used for adjusting the pH in the previous reaction and the amount of water used for decarboxylation reaction, to obtain intermediate G.
(6) Diazotization reaction: adding hydrochloric acid and water into a reaction kettle, controlling the temperature to be 15-30 ℃, dropwise adding aniline and 40-50% of sodium nitrite aqueous solution, wherein the mass ratio of the hydrochloric acid to the water to the aniline to the 40-50% of sodium nitrite aqueous solution is 0.8-1.5: 0.8-1.2: 0.3-0.8: 0.8-1.5, wherein the adding mass of the 40-50% sodium nitrite aqueous solution and the hydrochloric acid is consistent, the dropwise adding time is 3 hours, and the heat preservation reaction is carried out for 1-2 hours after the dropwise adding is finished, so as to obtain an intermediate H.
(7) And (3) azo reaction: adding the intermediate H and sodium acetate into a reaction kettle, controlling the temperature to be minus 20-0 ℃, and dropwise adding the intermediate G, wherein the ratio of the intermediate H to the sodium acetate to the intermediate G is 0.5-1: 0.2-0.4: 1-2, the dripping time is 4 hours, the reaction is carried out for 1-2 hours after the dripping is finished, and the intermediate I is obtained through centrifugation.
(8) Reduction reaction: adding the intermediate I into a reaction kettle, adding methanol for dissolving, adding a palladium carbon catalyst into the reaction kettle, introducing hydrogen, controlling the temperature to be 60-70 ℃ for reacting for 7-8 hours, wherein the hydrogen pressure is kept at 3-5 MPa in the reaction, and the ratio of the intermediate I to the methanol to the metal catalyst is 0.5-1: 6-10: 0.02-0.05 to obtain an intermediate J.
(9) Salt forming reaction: adding the intermediate J into a reaction kettle, controlling the temperature to be 10-15 ℃, and dropwise adding concentrated sulfuric acid, wherein the ratio of the intermediate J to the concentrated sulfuric acid is 10-18: 2-4, the dropping time is 3 hours, the temperature is controlled to 15-25 ℃ after the dropping is finished, the mixture is stirred for 30 minutes, the mixture is kept stand for crystallization and filtered to obtain a product of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate, and the total yield is calculated by ethyl cyanoacetate: 82.9 percent and the purity is 99 percent. Compared with the yield of 74% in the prior art, the yield of the scheme is improved. The method is used for preparing 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate products, 3000 tons of wastewater are generated, the scheme is not adopted, 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate are obtained, and the amount of the generated wastewater is more than 4000 tons.
[ example 6]
A process for preparing 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate includes pretreating methyl cyanoacetate, cyclizing with 2-hydrazino alcohol, hydrolysis, neutralization, decarboxylation, diazotization, azo reaction, reduction and salifying with concentrated sulfuric acid to obtain 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate.
(1) Pretreatment: adding dimethyl sulfate into a reaction kettle, controlling the temperature to be 20-35 ℃, dropwise adding dimethylformamide, wherein the water content of the dimethylformamide is changed, so that the mass ratio of the dimethyl sulfate to the dimethylformamide is 1.5-3:0.8-1, the dropwise adding time is 2-4 hours, and controlling the temperature to be 30-40 ℃ after the dropwise adding is finished to react for 6 hours to obtain an intermediate A.
Preparing a 30-40% sodium methoxide methanol solution at room temperature, cooling the intermediate A obtained in the last step to 0-20 ℃, dropwise adding the intermediate A into the 30-40% sodium methoxide methanol solution, controlling the temperature to 0-20 ℃, and dropwise adding for 2-3 hours, wherein according to the solubility of sodium methoxide in methanol, the ratio of the intermediate A to the 30-40% sodium methoxide methanol solution is 0.5-0.8: 1-1.5, the dripping time is 2-3 hours, and the reaction is carried out for 1-2 hours after the dripping is finished.
Dropwise adding methyl cyanoacetate into the obtained mother liquor B, controlling the temperature to be 0-20 ℃, dropwise adding for 2-3 hours, wherein the mass ratio of methyl cyanoacetate to the mother liquor B obtained in the last step is 0.5-1:2-3, gradually heating from 0-20 ℃ to 20-40 ℃ after dropwise adding, reacting for 6 hours, detecting the reaction progress of ethyl cyanoacetate serving as a raw material by using HPLC (high performance liquid chromatography), heating to 50-100 ℃ for continuous reaction when the raw material is remained according to the reaction progress, stopping the reaction when 0.05% of methyl cyanoacetate remains, centrifuging, extracting with toluene, and drying to obtain an intermediate C. Methyl cyanoacetate is used as a raw material in the reaction, unsaturated bonds are not contained in the raw material, the raw material cannot be oxidized in storage and cannot be polymerized by itself, the reaction raw material is immediately put into the next production after being treated, and the reaction activity is high.
(2) And (3) cyclization reaction: adding the intermediate C and 95% ethanol into a reaction kettle, dissolving the intermediate C by 95%, controlling the temperature to be 25-40 ℃, dropwise adding 2-hydrazino ethanol for 3-4 hours, wherein the mass ratio of the intermediate C to the 95% ethanol to the 2-hydrazino ethanol is 1-1.5: 2-4: 0.8-1.5; and (3) changing the adding amount of the 2-hydrazinoethanol along with the amount of the intermediate C, and controlling the temperature to be 50-70 ℃ to react for 4-6 hours to obtain an intermediate D.
(3) And (3) hydrolysis reaction: adding the intermediate D, an La enzyme catalyst with the mass fraction of 0.2-0.8% calculated by the intermediate D and water into a reaction kettle, preparing 20-40% of sodium hydroxide solution, adjusting the pH value of a reaction system to 7-10, controlling the temperature to 20-40 ℃ for reaction for 3.5-4 hours, and filtering to obtain an intermediate E. The La enzyme catalyst is added, the reaction time is shortened, and the hydrolysis reaction efficiency of the reaction is improved.
(4) And (3) performing neutralization reaction, namely adding the intermediate E into a reaction kettle, dropwise adding hydrochloric acid to adjust the pH value to be neutral (the pH value is 7-8), controlling the temperature to be 30-40 ℃, reacting for 1-2 hours, and centrifuging to obtain an intermediate F.
(5) Decarboxylation: adding the intermediate F into a reaction kettle, adding water and sodium acetate, stirring, controlling the temperature to be 150-180 ℃, and reacting for 3-4 hours, wherein the mass ratio of the intermediate F to the water to the sodium acetate is 1-2: 6-10: 2-4. the amount of sodium acetate is changed with the change of the amount of hydrochloric acid used for adjusting the pH in the previous reaction and the amount of water used for decarboxylation reaction, to obtain intermediate G.
(6) Diazotization reaction: adding hydrochloric acid and water into a reaction kettle, controlling the temperature to be-20-0 ℃, dropwise adding aniline and 40-50% of sodium nitrite aqueous solution, wherein the mass ratio of the hydrochloric acid to the water to the aniline to the 40-50% of sodium nitrite aqueous solution is 0.8-1.5: 0.8-1.2: 0.3-0.8: 0.8-1.5, wherein the adding mass of the 40-50% sodium nitrite aqueous solution and the hydrochloric acid is consistent, the dropwise adding time is 3 hours, and the heat preservation reaction is carried out for 2-3 hours after the dropwise adding is finished, so as to obtain an intermediate H.
(7) And (3) azo reaction: adding the intermediate H and sodium acetate into a reaction kettle, controlling the temperature to be 15-30 ℃, and dropwise adding the intermediate G, wherein the ratio of the intermediate H to the sodium acetate to the intermediate G is 0.5-1: 0.2-0.4: 1-2, dropwise adding for 4-5 hours, reacting for 4.5-5 hours after dropwise adding, and centrifuging to obtain an intermediate I.
(8) Reduction reaction: adding the intermediate I into a reaction kettle, adding methanol for dissolving, adding a palladium carbon catalyst into the reaction kettle, introducing hydrogen, controlling the temperature to be 30-60 ℃ for reaction for 7-8 hours, wherein the hydrogen pressure is kept at 3-5 MPa in the reaction, and the ratio of the intermediate I to the methanol to the metal catalyst is 0.5-1: 6-10: 0.02-0.05 to obtain an intermediate J.
(9) Salt forming reaction: adding the intermediate J into a reaction kettle, controlling the temperature to be 10-15 ℃, and dropwise adding concentrated sulfuric acid, wherein the ratio of the intermediate J to the concentrated sulfuric acid is 10-17: 2-3.9, the dripping time is 3 hours, the temperature is controlled to 15-25 ℃ after the dripping is finished, the mixture is stirred for 30 minutes, the mixture is kept stand for crystallization and filtered to obtain a product of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate, and the total yield is calculated by ethyl cyanoacetate: 82.6 percent and the purity is 99 percent. Compared with the yield of 74% in the prior art, the yield of the scheme is improved. The method is used for preparing 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate products, 3000 tons of wastewater are generated, the scheme is not adopted, 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate are obtained, and the amount of the generated wastewater is more than 4000 tons.
[ example 7]
A process for preparing 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate includes pretreating methyl cyanoacetate, cyclizing with 2-hydrazino alcohol, hydrolysis, neutralization, decarboxylation, diazotization, azo reaction, reduction and salifying with concentrated sulfuric acid to obtain 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate.
(1) Pretreatment: adding dimethyl sulfate into a reaction kettle, controlling the temperature to be 20-35 ℃, dropwise adding dimethylformamide, wherein the water content of the dimethylformamide is changed, so that the mass ratio of the dimethyl sulfate to the dimethylformamide is 1.5-3:0.8-1, the dropwise adding time is 2-4 hours, and controlling the temperature to be 30-40 ℃ after the dropwise adding is finished to react for 6 hours to obtain an intermediate A.
Preparing a 30-40% sodium methoxide methanol solution at room temperature, cooling the intermediate A obtained in the last step to 0-20 ℃, dropwise adding the intermediate A into the 30-40% sodium methoxide methanol solution, controlling the temperature to 0-20 ℃, and dropwise adding for 2-3 hours, wherein according to the solubility of sodium methoxide in methanol, the ratio of the intermediate A to the 30-40% sodium methoxide methanol solution is 0.5-0.8: 1-1.5, the dripping time is 2-3 hours, and the reaction is carried out for 1-2 hours after the dripping is finished.
Dropwise adding methyl cyanoacetate into the obtained mother liquor B, controlling the temperature to be 0-20 ℃, dropwise adding for 2-3 hours, wherein the mass ratio of methyl cyanoacetate to the mother liquor B obtained in the last step is 0.5-1:2-3, gradually heating from 0-20 ℃ to 20-40 ℃ after dropwise adding, reacting for 6 hours, detecting the reaction progress of ethyl cyanoacetate serving as a raw material by using HPLC (high performance liquid chromatography), heating to 50-100 ℃ for continuous reaction when the raw material is remained according to the reaction progress, stopping the reaction when 0.05% of methyl cyanoacetate remains, centrifuging, extracting with toluene, and drying to obtain an intermediate C. Methyl cyanoacetate is used as a raw material in the reaction, unsaturated bonds are not contained in the raw material, the raw material cannot be oxidized in storage and cannot be polymerized by itself, the reaction raw material is immediately put into the next production after being treated, and the reaction activity is high.
(2) And (3) cyclization reaction: adding the intermediate C and 95% ethanol into a reaction kettle, dissolving the intermediate C by 95%, controlling the temperature to be 25-40 ℃, dropwise adding 2-hydrazino ethanol for 3-4 hours, wherein the mass ratio of the intermediate C to the 95% ethanol to the 2-hydrazino ethanol is 1-1.5: 2-4: 0.8-1.5; and (3) changing the adding amount of the 2-hydrazinoethanol along with the amount of the intermediate C, and controlling the temperature to be 50-70 ℃ to react for 4-6 hours to obtain an intermediate D.
(3) And (3) hydrolysis reaction: adding the intermediate D, an La enzyme catalyst with the mass fraction of 0.2-0.8% calculated by the intermediate D and water into a reaction kettle, preparing 20-40% of sodium hydroxide solution, adjusting the pH value of a reaction system to 7-10, controlling the temperature to 60-80 ℃ for reaction for 2-3 hours, and filtering to obtain an intermediate E. The La enzyme catalyst is added, the reaction time is shortened, and the hydrolysis reaction efficiency of the reaction is improved.
(4) And (3) neutralization reaction: and adding the intermediate E into a reaction kettle, dropwise adding hydrochloric acid to adjust the pH value to be neutral (the pH value is 7-8), controlling the temperature to be 10-20 ℃, reacting for 2-3 hours, and centrifuging to obtain an intermediate F.
(5) Decarboxylation: adding the intermediate F into a reaction kettle, adding water and sodium acetate, stirring, controlling the temperature to be 150-180 ℃, and reacting for 3-4 hours, wherein the mass ratio of the intermediate F to the water to the sodium acetate is 1-2: 6-10: 2-4. the amount of sodium acetate is changed with the change of the amount of hydrochloric acid used for adjusting the pH in the previous reaction and the amount of water used for decarboxylation reaction, to obtain intermediate G.
(6) Diazotization reaction: adding hydrochloric acid and water into a reaction kettle, controlling the temperature to be 15-30 ℃, dropwise adding aniline and 40-50% of sodium nitrite aqueous solution, wherein the mass ratio of the hydrochloric acid to the water to the aniline to the 40-50% of sodium nitrite aqueous solution is 0.8-1.5: 0.8-1.2: 0.3-0.8: 0.8-1.5, wherein the adding mass of the 40-50% sodium nitrite aqueous solution and the hydrochloric acid is consistent, the dropwise adding time is 3 hours, and the heat preservation reaction is carried out for 1-2 hours after the dropwise adding is finished, so as to obtain an intermediate H.
(7) And (3) azo reaction: adding the intermediate H and sodium acetate into a reaction kettle, controlling the temperature to be 15-30 ℃, and dropwise adding the intermediate G, wherein the ratio of the intermediate H to the sodium acetate to the intermediate G is 0.5-1: 0.2-0.4: 1-2, dropwise adding for 4-5 hours, reacting for 4.5-5 hours after dropwise adding, and centrifuging to obtain an intermediate I.
(8) Reduction reaction: adding the intermediate I into a reaction kettle, adding methanol for dissolving, adding a palladium carbon catalyst into the reaction kettle, introducing hydrogen, controlling the temperature to be 60-70 ℃ for reacting for 7-8 hours, wherein the hydrogen pressure is kept at 3-5 MPa in the reaction, and the ratio of the intermediate I to the methanol to the metal catalyst is 0.5-1: 6-10: 0.02-0.05 to obtain an intermediate J.
(9) Salt forming reaction: adding the intermediate J into a reaction kettle, controlling the temperature to be 10-15 ℃, and dropwise adding concentrated sulfuric acid, wherein the ratio of the intermediate J to the concentrated sulfuric acid is 10-14: 2-3, the dropping time is 3 hours, the temperature is controlled to 15-25 ℃ after the dropping is finished, the mixture is stirred for 30 minutes, the mixture is kept stand for crystallization and filtered to obtain a product of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate, and the total yield is calculated by ethyl cyanoacetate: 83.1 percent and the purity is 99 percent. Compared with the yield of 74% in the prior art, the yield of the scheme is improved. The method is used for preparing 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate products, 3000 tons of wastewater are generated, the scheme is not adopted, 1700 tons of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate are obtained, and the amount of the generated wastewater is more than 4000 tons.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.
Claims (7)
1. A preparation method of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate is characterized in that raw material methyl cyanoacetate is pretreated, a pretreated product and 2-hydrazino ethanol are cyclized to construct a pyrazole ring, the cyclized product is subjected to hydrolysis reaction, neutralization reaction, decarboxylation reaction, diazotization reaction, azo reaction and reduction reaction, and finally salified with concentrated sulfuric acid to prepare the 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate.
2. The method for preparing 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate according to claim 1, wherein the pretreatment reaction temperature of the pretreatment of the raw material methyl cyanoacetate is-20 to 100 ℃, the cyclization reaction temperature in the subsequent steps is 50 to 100 ℃, the hydrolysis reaction temperature is 20 to 100 ℃, the neutralization reaction temperature is-10 to 40 ℃, the decarboxylation reaction temperature is 150 to 250 ℃, the diazotization reaction temperature is-20 to 30 ℃, the azo reaction temperature is-20 to 30 ℃, the reduction reaction temperature is 30 to 90 ℃, and the salt formation reaction temperature with concentrated sulfuric acid is 10 to 25 ℃.
3. The process for the preparation of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate according to claim 2, comprising the steps of:
(1) pretreatment: pretreatment of raw material methyl cyanoacetate: adding dimethyl sulfate into a reaction kettle, controlling the temperature to be 20-50 ℃, dropwise adding dimethyl formamide for 2-4 hours, controlling the temperature to be 30-70 ℃ after dropwise adding, and reacting for not less than 6 hours to obtain an intermediate A;
dropwise adding the intermediate A into a methanol solution of sodium methoxide, controlling the temperature to be-20 ℃, dropwise adding for 2-3 hours, reacting for 1-2 hours after dropwise adding, and centrifuging to obtain a mother solution B;
dropwise adding methyl cyanoacetate into the mother liquor B, controlling the temperature to be-10-20 ℃, dropwise adding for 1-3 hours, controlling the temperature to be-10-100 ℃ after dropwise adding, reacting for at least 6 hours, and obtaining an intermediate C through centrifugation, toluene extraction and drying;
(2) and (3) cyclization reaction: adding the intermediate C into a reaction kettle, dissolving the intermediate C with 95% ethanol, controlling the temperature to be-10-40 ℃, dropwise adding 2-hydrazino ethanol, controlling the temperature to be 50-100 ℃, and reacting for 4-6 hours to obtain an intermediate D;
(3) and (3) hydrolysis reaction: mixing an intermediate D, La enzyme catalyst with water, adjusting the pH value to 7-10 by using a sodium hydroxide solution, controlling the temperature to 20-100 ℃, reacting for 2-4 hours, and filtering to obtain an intermediate E;
(4) and (3) neutralization reaction: adding the intermediate E into a reaction kettle, dropwise adding hydrochloric acid to adjust the pH value to 7-8, controlling the temperature to be-10-40 ℃, reacting for 1-3 hours, and centrifuging to obtain an intermediate F;
(5) decarboxylation: adding the intermediate F into a reaction kettle, adding water and sodium acetate, stirring, controlling the temperature to be 150-250 ℃ and reacting for 2-4 hours to obtain an intermediate G;
(6) diazotization reaction: adding hydrochloric acid and water into a reaction kettle, controlling the temperature to be-20-30 ℃, dropwise adding aniline and sodium nitrite aqueous solution for 3 hours, and keeping the temperature for reaction for 1-3 hours after dropwise adding to obtain an intermediate H;
(7) and (3) azo reaction: adding the intermediate H and sodium acetate into a reaction kettle, controlling the temperature to be minus 20-30 ℃, dropwise adding the intermediate G for 4-5 hours, reacting for 1-2 hours after dropwise adding, and centrifuging to obtain an intermediate I;
(8) reduction reaction: adding the intermediate I, methanol and a palladium-carbon catalyst into a reaction kettle, introducing hydrogen, controlling the temperature to be 30-90 ℃ and reacting for 4-8 hours to obtain an intermediate J;
(9) salt forming reaction: and adding the intermediate J into a reaction kettle, dropwise adding concentrated sulfuric acid for 3 hours, stirring for 30 minutes after dropwise adding is finished, standing for crystallization, and filtering to obtain the 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate.
4. The process for producing 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate according to claim 3, wherein in the step (1), the mass ratio of dimethyl sulfate to dimethylformamide is 1.5 to 3:0.8 to 1; the mass ratio of the intermediate A to a methanol solution of sodium methoxide is 0.5-0.8: 1-1.5, wherein the mass ratio of the methyl cyanoacetate to the mother liquor B is 0.5-1: 2-3; in the step (2), the mass ratio of the intermediate C, 95% ethanol and 2-hydrazinoethanol is 1-1.5: 2-4: 0.8-1.5; in the step (5), the mass ratio of the intermediate F, water and sodium acetate is 1-2: 6-10: 2-4; in the step (6), the mass ratio of the hydrochloric acid, the water, the aniline and the sodium nitrite aqueous solution is 0.8-1.5: 0.8-1.2: 0.3-0.8: 0.8-1.5; in the step (7), the mass ratio of the intermediate H to the intermediate sodium acetate to the intermediate G is 0.5-1: 0.2-0.4: 1-2; in the step (8), the mass ratio of the intermediate I, the methanol and the palladium carbon catalyst is 0.5-1: 6-10: 0.02-0.05; in the step (9), the mass ratio of the intermediate J to concentrated sulfuric acid is 10-18: 2-4.
5. The process for producing 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate according to claim 3 or 4, wherein the mass fraction of sodium methoxide in methanol in step (1) is 30 to 40%, the mass fraction of sodium hydroxide in aqueous solution in step (3) is 20 to 40%, and the mass fraction of sodium nitrite in aqueous solution in step (6) is 40 to 50%.
6. The method for preparing 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate according to claim 3, wherein the added mass fraction of the La enzyme catalyst is 0.2-0.8% based on the intermediate D.
7. The process for producing 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate according to claim 3, wherein the pressure during the reaction is 3 to 5MPa when hydrogen gas is introduced.
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