CN103613544B - 4-AA production technique and device thereof - Google Patents
4-AA production technique and device thereof Download PDFInfo
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- CN103613544B CN103613544B CN201310660063.5A CN201310660063A CN103613544B CN 103613544 B CN103613544 B CN 103613544B CN 201310660063 A CN201310660063 A CN 201310660063A CN 103613544 B CN103613544 B CN 103613544B
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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Abstract
The invention belongs to field of medicine and chemical technology, relate to a kind of 4-AA production technique and device thereof, step is as follows: 1-phenyl-3-methyl-5 pyrazolone and methyl-sulfate are methylated through high temperature, are hydrolyzed generation hydrolyzed solution; 1-phenyl-3-methyl-5 pyrazolone and methyl-sulfate are produced to obtain quinizine oil through high temperature methylation reaction, hydrolysis and alkaline purification; Hydrolyzed solution, quinizine oil are mixed with quinizine quaternary ammonium salt brine solution; Quinizine quaternary ammonium salt brine solution through nitrosification, reduction, neutralization generate 4-AA, temperature cool 20 DEG C for subsequent use.The usage quantity of liquid caustic soda of the present invention, sulfuric acid greatly reduces; Sodium sulfate, hc effluent quantity discharged reduce obviously, environmental friendliness, and technique is simple, and easy to operate, product yield is high.
Description
Technical field
The invention belongs to field of medicine and chemical technology, particularly a kind of 4-AA production technique and device thereof.
Background technology
The ntipyretic analgesic medicine that Sulpyrine, pyramidon system are important, only the market scale of Sulpyrine is at about 20,000 tons, China is producing country main in the world and export State, in addition pyramidon market capacity is also at about 2500 tons, therefore the usage quantity of 4-AA is huge, and the technique that therefore development and operation is simple, environmental friendliness, atom utilization are high is extremely urgent.
Traditional technique is that starting material and methyl-sulfate high temperature methylate, are hydrolyzed, quinizine oil is produced in alkaline purification with 1-phenyl-3-methyl-5-pyrazolone; Quinizine oil is made into quinizine quaternary ammonium sulfate in the proper ratio with the vitriol oil, water, and quinizine quaternary ammonium sulfate generates 4-AA through nitrosification, reduction, hydrolysis and neutralization; Liquid caustic soda 0.5800 kilogram need be consumed with often producing 1 kilogram of 4-AA during this explained hereafter, preparation quinizine quaternary ammonium sulfate consumes 0.2900 kilogram, sulfuric acid, generate 1.2672 kilograms, sodium sulfate, because Sulpyrine, pyramidon series ntipyretic analgesic medicine market scale are huge, huge to the sodium sulfate of the Nature discharge, high-COD waste water amount every year.
Summary of the invention
The object of this invention is to provide a kind of 4-AA production technique and device thereof, be antipyretic and analgesic Sulpyrine, the extremely important intermediate of pyramidon, the usage quantity of liquid caustic soda of the present invention, sulfuric acid greatly reduces; Sodium sulfate, hc effluent quantity discharged reduce obviously, environmental friendliness, and technique is simple, and easy to operate, product yield is high.
4-AA production technique of the present invention, step is as follows:
(1) 1-phenyl-3-methyl-5 pyrazolone and methyl-sulfate are methylated through high temperature, are hydrolyzed generation hydrolyzed solution;
(2) 1-phenyl-3-methyl-5 pyrazolone and methyl-sulfate are produced to obtain quinizine oil through high temperature methylation reaction, hydrolysis and alkaline purification;
(3) hydrolyzed solution, quinizine oil are mixed with quinizine quaternary ammonium salt brine solution; Add water and make in quinizine quaternary ammonium salts solution containing quinizine content 33.0-37.0% (g/g); Sulfuric acid content 9.0 ~ 12.0% (g/g); With preparation quinizine quaternary ammonium salt brine solution through nitrosification, reduction, neutralization generate 4-AA, temperature cool 20 DEG C for subsequent use.
The object added water ensures " containing quinizine content 33.0-37.0% (g/g) in quinizine quaternary ammonium salts solution; Sulfuric acid content 9.0 ~ 12.0% (g/g).
Starting material 1-phenyl-3-methyl-5 pyrazolone that the hydrolyzed solution that described step (1) obtains and step (2) are thrown is 1:1.0 ~ 1.15.
In step (1) and step (2), the mol ratio of 1-phenyl-3-methyl-5 pyrazolone and methyl-sulfate is 1:1.20 ~ 1.25.
During preparation quinizine quaternary ammonium sulfate, hydrolyzed solution temperature is 50-100 DEG C.
Reductive agent is ammonium bisulfite and ammonium sulphite mixture.
The mass ratio of ammonium bisulfite and ammonium sulphite is 1.9-2.0:1.
4-AA production craft step of the present invention is as follows:
(1) by 1-phenyl-3-methyl-5 pyrazolone, methyl-sulfate mixing, be warmed up to after interior temperature reaches 160 ~ 180 DEG C, temperature remains on 160 ~ 180 DEG C of methylation reaction 5-7 hour, after methylation reaction terminates, after being cooled to 100 DEG C, under stirring, add 180-220L tap water, continue to be warming up to 105 ~ 110 DEG C of hydrolysis reaction 2-3 hour, hydrolysis reaction terminates to be cooled to 50-100 DEG C and obtains hydrolyzed solution;
(2) by 1-phenyl-3-methyl-5 pyrazolone, methyl-sulfate mixes, be warmed up to after interior temperature reaches 160 ~ 180 DEG C, temperature remains on 160 ~ 180 DEG C of methylation reaction 5-7 hour, after methylation reaction terminates, after being cooled to 100 DEG C, under stirring, add 200L tap water, continue to be warming up to 105 ~ 110 DEG C of hydrolysis reaction 2-3 hour, after hydrolysis reaction terminates, after being cooled to 70-90 DEG C, drip the NaOH aqueous solution, wherein, the mol ratio of NaOH and 1-phenyl-3-methyl-5 pyrazolone is 2.6-2.8:1, intensification degree starts clock reaction 2-3 hour to 100-110 DEG C, after reaction terminates, draw reaction solution upper strata oil while hot and obtain quinizine oil,
(3) by hydrolyzed solution, the mixing of quinizine oil, by water regulable control quinizine oil-contg, quinizine quaternary ammonium sulfate is obtained;
(4) nitrosification, reduction: reductive agent is added in reduction reaction can, the weight ratio of reductive agent and sulfuric acid quinizine quaternary ammonium salt is 1.60 ~ 1.70:1, sulfuric acid quinizine quaternary ammonium salt and sodium nitrite in aqueous solution, the consumption of Sodium Nitrite is as the criterion with reaction end, (inside adds a little FeSO with starch potassium iodide test solution
4) check that terminal is micro-blueness, carry out nitrosation reaction under stirring icy salt solution cooling, reaction controlling controls at 1.3-1.7 at 20-25 DEG C, PH, and then nitroso-group quinizine carries out reduction reaction 2.5-3.5 hour at 80-85 DEG C, surveys reduction degree and is not less than 4.5ml;
(5) be hydrolyzed, neutralize: after reduction reaction terminates, be cooled to 75-95 DEG C, by with sulfuric acid quinizine quaternary ammonium salt: the sulfuric acid of sulfuric acid=1:1.9 ~ 2.0 mol ratio slowly adds in tank, add sulfuric acid temperature to control, at 80-90 DEG C, to be warming up to 100-120 DEG C, hydrolysis 2-2.5 hour; Be cooled to 70-80 DEG C after being hydrolyzed, logical liquefied ammonia is neutralized to PH7.1-7.3, obtains upper strata 4-AA after static 12-18 minute.
The present invention often produces 1 kilogram of 4-AA need consume liquid caustic soda 0.29 kilogram, preparation quinizine quaternary ammonium sulfate sulfuric acid consumption is 0, sodium sulfate generation reduces 0.4224 kilogram, because directly using hydrolyzed solution, discharges high COD sodium sulfate wastewater 2.45 kilograms less.
4-AA production equipment of the present invention, comprise the first pyrazolone feed bin, first pyrazolone feed bin and the first methyl-sulfate test tank are connected respectively by pipeline and first tank that methylates, first tank that methylates is connected with the first hydrolytic decomposition pot, first hydrolytic decomposition pot is connected with alkaline purification tank, and alkaline purification tank is connected with quinizine oil tank; Second pyrazolone feed bin and the second methyl-sulfate test tank are connected respectively by pipeline and second tank that methylates, second tank that methylates is connected with the second hydrolytic decomposition pot, second hydrolytic decomposition pot, quinizine oil tank, the 3rd water metering are filled with and are connected with quinizine quaternary ammonium sulfate batch tank respectively by pipeline, quinizine quaternary ammonium sulfate batch tank is filled with Sodium Nitrite metering and is connected with nitrosation reaction tank respectively by pipeline, nitrosation reaction tank is connected with reduction reaction can, and reduction reaction can is connected with hydrolysis neutralization tank; First hydrolytic decomposition pot measures to fill with by pipeline and liquid caustic soda and is connected.
Hydrolysis neutralization tank is connected with ammonium sulfate liquor tank and 4-quinizine oil tank respectively by pipeline.
First water metering is filled with and is connected with the first hydrolytic decomposition pot by pipeline.
Second water metering is filled with and is connected with the second hydrolytic decomposition pot by pipeline.
Alkaline purification tank is connected with sodium sulfate mother liquor tank by pipeline.
Each pipeline all arranges valve.
Every root pipeline has twice valve, is respectively bottom valve and material feeding valve.
Using method:
Pyrazolone is put into the first pyrazolone feed bin; Methyl-sulfate squeezes into the first methyl-sulfate test tank, and the pyrazolone of the first pyrazolone feed bin enters first and to methylate tank, closes first and to methylate tank pyrazolone charging opening; Open the first methyl-sulfate test tank bottom valve, first methylates tank feed valve, methyl-sulfate is added first and to methylate tank, finish, close the first methyl-sulfate bottom valve, first to methylate tank feed valve, temperature reaction, reacts complete, opens first and to methylate tank bottom valve, first hydrolytic decomposition pot feed valve, the liquid that methylates first puts into the first hydrolytic decomposition pot, puts complete, closes first and to methylate tank bottom valve; Open the first water measuring tank bottom valve, the water of dosage is joined the first hydrolytic decomposition pot, finish, close the first water measuring tank bottom valve and the first hydrolytic decomposition pot charging valve, be hydrolyzed reaction, hydrolysis is finished, and opens the first hydrolytic decomposition pot bottom valve, alkaline purification tank feed valve, hydrolysis material is put into alkaline purification tank, open alkali lye metering and fill with valve, put into the reaction of alkaline purification tank, reaction is finished, open quinizine oil tank feed valve, lower floor's solution is put into sodium sulfate mother liquor tank to collect, the upper strata quinizine oil of alkaline purification tank is put into quinizine oil tank, for subsequent use;
Pyrazolone is put into the second pyrazolone feed bin; Methyl-sulfate squeezes into the second methyl-sulfate test tank, and the pyrazolone of the second pyrazolone feed bin enters second and to methylate tank, closes second and to methylate tank pyrazolone charging opening; Open the second methyl-sulfate test tank bottom valve, second methylates tank feed valve, methyl-sulfate is added second and to methylate tank, finish, close the second methyl-sulfate bottom valve, second to methylate tank feed valve, temperature reaction, reacts complete, opens second and to methylate tank bottom valve, second hydrolytic decomposition pot feed valve, the liquid that methylates second puts into the second hydrolytic decomposition pot, puts complete, closes second and to methylate tank bottom valve; Open the second water measuring tank bottom valve, the water of dosage is joined the second hydrolytic decomposition pot, finishes, close the second water measuring tank bottom valve and the second hydrolytic decomposition pot charging valve, be hydrolyzed reaction, and hydrolysis is finished, for subsequent use;
Open the second hydrolytic decomposition pot bottom valve, hydrolyzed solution press-in quinizine quaternary ammonium sulfate preparing tank, open quinizine oil tank bottom valve and quinizine oil is put into quinizine quaternary ammonium sulfate preparing tank, finish, close quinizine oil tank bottom valve, open the 3rd water measuring tank bottom valve, water is added quinizine quaternary ammonium sulfate preparing tank, regulate quinizine content and sulfuric acid content in quinizine quaternary ammonium sulfate, quinizine quaternary ammonium sulfate and Sodium Nitrite are put into reduction reaction can and are reacted, and reaction is finished; Open reduction reaction can bottom valve, be transferred to hydrolysis, neutralization tank by pipeline, be hydrolyzed, neutralization reaction.Leave standstill, 4-AA oil is sucked 4-AA oil tank by stainless-steel vacuum pipe.Mother liquor proceeds to ammonium sulfate liquor tank.
Beneficial effect of the present invention is as follows:
Present invention process is simple, consumes liquid caustic soda few, and without the need to sulfuric acid during preparation quinizine quaternary ammonium sulfate, sodium sulfate generation reduces, and discharge high COD sodium sulfate wastewater few, the usage quantity of liquid caustic soda, sulfuric acid greatly reduces; Sodium sulfate, hc effluent quantity discharged reduce obviously, and meet environmental friendliness, Green Chemistry characteristic attribute, product yield is high.Because Sulpyrine, pyramidon belong to large tonnage product in China, use economic benefit and social benefit after this invented technology obvious.
Accompanying drawing explanation
Fig. 1 production equipment figure of the present invention;
In figure, 1, first methyl-sulfate test tank, 2, first pyrazolone feed bin, 3, first methylates tank, 4, liquid caustic soda metering is filled with, 5, first hydrolytic decomposition pot, 6, alkaline purification tank, 7, sodium sulfate mother liquor tank, 8, quinizine oil tank, 9, Sodium Nitrite metering is filled with, 10, nitrosation reaction tank, 11, ammonium sulfate liquor tank, 12, hydrolysis, neutralization tank, 13, 4-quinizine oil tank, 14, reduction reaction can, 15, quinizine quaternary ammonium sulfate batch tank, 16, water metering is filled with, 17, second hydrolytic decomposition pot, 18, second methylates tank, 19, second water metering is filled with, 20, second methyl-sulfate test tank, 21, second pyrazolone feed bin, 22, first water metering is filled with.
Embodiment
Below in conjunction with embodiment, the invention will be further described.
Embodiment 1
As Fig. 1, the present embodiment 4-AA production equipment, comprise the first pyrazolone feed bin 2, first pyrazolone feed bin 2 and the first methyl-sulfate test tank 1 are connected respectively by pipeline and first tank 3 that methylates, first tank 3 that methylates is connected with the first hydrolytic decomposition pot 5, first hydrolytic decomposition pot 5 is connected with alkaline purification tank 6, and alkaline purification tank 6 is connected with quinizine oil tank 8; Second pyrazolone feed bin 21 and the second methyl-sulfate test tank 20 are connected respectively by pipeline and second tank 18 that methylates, second tank 18 that methylates is connected with the second hydrolytic decomposition pot 17, second hydrolytic decomposition pot 17, quinizine oil tank 8, water metering filling 16 is connected with quinizine quaternary ammonium sulfate batch tank 15 respectively by pipeline, quinizine quaternary ammonium sulfate batch tank 15 is connected with nitrosation reaction tank 10 respectively by pipeline with Sodium Nitrite metering filling 9, nitrosation reaction tank 10 is connected with reduction reaction can 14, and reduction reaction can 14 is connected with hydrolysis neutralization tank 12; First hydrolytic decomposition pot 5 measures filling 4 by pipeline and liquid caustic soda and is connected.
Hydrolysis neutralization tank 12 is connected with ammonium sulfate liquor tank 11 and 4-quinizine oil tank 13 respectively by pipeline.
First water metering filling 22 is connected with the first hydrolytic decomposition pot 5 by pipeline.
Second water metering filling 19 is connected with the second hydrolytic decomposition pot 17 by pipeline.
Alkaline purification tank 6 is connected with sodium sulfate mother liquor tank 7 by pipeline.
Using method:
Pyrazolone is put into the first pyrazolone feed bin 2; Methyl-sulfate drops into the first methyl-sulfate test tank 1, opens first and to methylate tank 3 pyrazolone charging opening, pyrazolone is entered first and to methylate tank 3, closes first and to methylate tank 3 pyrazolone charging opening; Open the first methyl-sulfate test tank 1 bottom valve, first methylates tank 3 methyl-sulfate feed valve, methyl-sulfate is added first to methylate tank 3, finish, close the first methyl-sulfate tank 1 bottom valve, first and to methylate tank 3 feed valve, temperature reaction is complete, open first to methylate tank 3 bottom valve, the first hydrolytic decomposition pot 5 feed valve, the liquid that will methylate puts into the first hydrolytic decomposition pot 5, put complete, close first and to methylate tank 3 bottom valve; Open the first water measuring tank 22 bottom valve, water is joined the first hydrolytic decomposition pot 5, finish, close the first water measuring tank 5 bottom valve and the first hydrolytic decomposition pot 5 charging valve, be hydrolyzed reaction, and hydrolysis is finished, open the first hydrolytic decomposition pot 5 bottom valve, alkaline purification tank 6 bottom valve, puts into alkaline purification tank 6 by hydrolysis material and liquid caustic soda, and reaction is finished, lower floor's solution is put into sodium sulfate mother liquor tank 7 collect, open quinizine oil tank 8 feed valve, the upper strata quinizine oil of alkaline purification tank 6 is put into quinizine oil tank 8, for subsequent use;
Pyrazolone is put into the second pyrazolone feed bin 21; The pyrazolone that methyl-sulfate squeezes into the second methyl-sulfate test tank 20, second pyrazolone feed bin 21 enters second and to methylate tank 18, closes second and to methylate tank 18 pyrazolone charging opening; Open the second methyl-sulfate test tank 20 bottom valve, second methylates tank 18 feed valve, methyl-sulfate is added second and to methylate tank 18, finish, close the second methyl-sulfate tank 20 bottom valve, second to methylate tank 18 feed valve, temperature reaction, reacts complete, opens second and to methylate tank 18 bottom valve, second hydrolytic decomposition pot 17 feed valve, the liquid that methylates second puts into the second hydrolytic decomposition pot 17, puts complete, closes second and to methylate tank 18 bottom valve; Open the second water measuring tank 19 bottom valve, water is joined the second hydrolytic decomposition pot 17, finish, close the second water measuring tank 19 bottom valve and the second hydrolytic decomposition pot 17 charging valve, be hydrolyzed reaction, and hydrolysis is finished, for subsequent use;
Open the second hydrolytic decomposition pot 17 bottom valve, hydrolyzed solution press-in quinizine quaternary ammonium sulfate preparing tank 15, open quinizine oil tank 8 bottom valve and quinizine oil is put into quinizine quaternary ammonium sulfate preparing tank 15, finish, close quinizine oil tank 8 bottom valve, open the 3rd water measuring tank 16 bottom valve, water is added quinizine quaternary ammonium sulfate preparing tank 15, regulate quinizine content and sulfuric acid content in quinizine quaternary ammonium sulfate, quinizine quaternary ammonium sulfate and Sodium Nitrite are put into reduction reaction can 14 and are reacted, and reaction is finished; Open reduction reaction can 14 bottom valve, be transferred to hydrolysis, neutralization tank 12 by pipeline, be hydrolyzed, neutralization reaction, leave standstill, 4-AA oil is sucked 4-AA oil tank 13 by valve tube, and mother liquor proceeds to ammonium sulfate liquor tank 11.
4-AA production technique is as follows:
(1) by 180kg1-phenyl-3-methyl-5 pyrazolone; The methyl-sulfate adding mol ratio 1.2 times carries out methylation reaction, be warmed up to when interior temperature reaches 160 DEG C and start timing, temperature remains on 160 ± 2 DEG C of reactions 6 hours, then after being cooled to 100 DEG C, under stirring state, slowly add 180L tap water, continue to heat up, 107 ± 2 DEG C of hydrolysis reaction 2.5 hours, be cooled to 50 DEG C after hydrolysis reaction terminates and obtain hydrolyzed solution;
(2) by 180kg1-phenyl-3-methyl-5 pyrazolone; The methyl-sulfate adding mol ratio 1.2 times carries out methylation reaction, be warmed up to when interior temperature reaches 160 DEG C and start timing, temperature remains on 170 ± 2 DEG C of reactions 6 hours, after being cooled to 100 DEG C, under stirring state, slowly add 200L tap water, continue to heat up, 107 ± 2 DEG C of hydrolysis reaction 2.5 hours, be cooled to 80 DEG C after hydrolysis reaction terminates, drip 110kgNaOH solution water solution, be warmed up to 102 DEG C and start clock reaction 2 hours, after reaction terminates, the upper strata oil extracted reaction solution while hot obtains quinizine oil;
(3) the quinizine oil that hydrolyzed solution step (1) obtained and step (2) obtain and water are mixed together and are obtained by reacting quinizine quaternary ammonium sulfate; Quinizine content 33.0% (g/g) in quinizine quaternary ammonium sulfate, sulfuric acid content 12.0% (g/g), temperature cool 20 DEG C for subsequent use; Wherein, starting material 1-phenyl-3-methyl-5 pyrazolone that the hydrolyzed solution that obtains of step (1) and step (2) are thrown is 1:1.0;
(4) nitrosification, reduction: the mixture being 1.9:1 by the mass ratio of the ammonium bisulfite got ready and ammonium sulphite adds in reduction reaction can 14, sulfuric acid quinizine quaternary ammonium salt and sodium nitrite in aqueous solution carry out nitrosation reaction under the cooling of stirring icy salt solution, reaction controlling, at 20 DEG C, (inside adds a little FeSO with starch potassium iodide test solution
4) checking that terminal is micro-blueness, PH controls 1.5, and nitroso-group quinizine constantly flows into reduction reaction can 14 through pipeline, carries out reduction reaction 3 hours at 80 DEG C, surveys reduction degree and is not less than 4.5ml;
(5) be hydrolyzed, neutralize: after reduction reaction terminates, be cooled to about 80 DEG C, by being 1.95 with sulfuric acid quinizine quaternary ammonium salt mol ratio, sulfuric acid slowly adds in reaction solution, adding sulfuric acid temperature controls at 90 DEG C, add sulfuric acid complete, be warming up to 120 DEG C, be hydrolyzed 2 hours, hydrolysis is complete is cooled to 70 DEG C, logical liquefied ammonia is neutralized to PH7.1, draws upper strata 4-AA (AA) oil after static 15 minutes.
4-AA yield 92.23%, content 78.5% (g/g).
Embodiment 2
The apparatus structure of the present embodiment is identical with embodiment 1 with using method,
4-AA production technique is as follows:
(1) by 180kg1-phenyl-3-methyl-5 pyrazolone; Add the methyl-sulfate of mol ratio 1.25 times, be warmed up to when interior temperature reaches 170 DEG C and start timing, temperature remains on 170 DEG C of reactions 7 hours, after methylation reaction terminates, after being cooled to 100 DEG C, under stirring state, slowly add 200L tap water, continue to heat up, 105 ± 2 DEG C of hydrolysis reaction 3 hours, hydrolysis reaction terminated to be cooled to 100 DEG C and obtains hydrolyzed solution;
(2) by 189kg1-phenyl-3-methyl-5 pyrazolone; Add the methyl-sulfate of mol ratio 1.25 times, be warmed up to when interior temperature reaches 160 DEG C and start timing, temperature remains on 160 ~ 180 DEG C of reactions 6 hours, after methylation reaction terminates, after being cooled to 100 DEG C, under stirring state, slowly add 200L tap water, continue to heat up, 107 ± 2 DEG C of hydrolysis reaction 3 hours, after hydrolysis reaction terminates, after being cooled to 80 DEG C, drip scale 110kgNaOH solution water solution, intensification degree starts clock reaction 2 hours to 110 DEG C, after reaction terminates, the upper strata oil extracted reaction solution while hot obtains quinizine oil;
(3) the quinizine oil that hydrolyzed solution step (1) obtained and step (2) obtain and water are mixed to get quinizine quaternary ammonium sulfate, quinizine content 34.43% (g/g) in quinizine quaternary ammonium sulfate, sulfuric acid content 10.79% (g/g), temperature cool 20 DEG C for subsequent use, wherein, starting material 1-phenyl-3-methyl-5 pyrazolone that the hydrolyzed solution that obtains of step (1) and step (2) are thrown is 1:1.5;
(4) nitrosification, reduction: the mixture being 2.0:1 by the mass ratio of the ammonium bisulfite got ready and ammonium sulphite adds in reduction reaction can 14, sulfuric acid quinizine quaternary ammonium salt and sodium nitrite in aqueous solution enter nitrosation reactor, nitrosation reaction is carried out under the cooling of stirring icy salt solution, reaction controlling, at 25 DEG C, (inside adds a little FeSO with starch potassium iodide test solution
4) checking that terminal is micro-blueness, PH controls 1.3, and nitroso-group quinizine constantly flows into reduction reaction can 14 through pipeline, carries out reduction reaction 3 hours at 85 DEG C, surveys reduction degree and is not less than 4.5ml;
(5) be hydrolyzed, neutralize: after reduction reaction terminates, be cooled to about 80 DEG C, by being 1.90 with sulfuric acid quinizine quaternary ammonium salt mol ratio, sulfuric acid slowly adds in reaction solution, adding sulfuric acid temperature controls at 90 DEG C, add sulfuric acid complete, be warming up to 110 DEG C, be hydrolyzed 2 hours, hydrolysis is complete is cooled to 70-80 DEG C, logical liquefied ammonia is neutralized to PH7.2, draws upper strata 4-AA (AA) oil after static 18 minutes.
4-AA yield 92.87%, content 78.35% (g/g).
Embodiment 3
The apparatus structure of the present embodiment is identical with embodiment 1 with using method,
4-AA production technique is as follows:
(1) by 180kg1-phenyl-3-methyl-5 pyrazolone; Add the methyl-sulfate of mol ratio 1.2 times, be warmed up to when interior temperature reaches 180 DEG C and start timing, temperature remains on 180 DEG C of reactions 5 hours, after methylation reaction terminates, after being cooled to 100 DEG C, under stirring state, slowly add 220L tap water, continue to heat up, 110 ± 2 DEG C of hydrolysis reaction 2 hours, hydrolysis reaction terminated to be cooled to 70 DEG C and obtains hydrolyzed solution;
(2) by 198kg (180 × 1.1 times) 1-phenyl-3-methyl-5 pyrazolone; Add the methyl-sulfate of mol ratio 1.2 times, be warmed up to when interior temperature reaches 160 DEG C and start timing, temperature remains on 180 DEG C of reactions 7 hours, after methylation reaction terminates, after being cooled to 100 DEG C, under stirring state, slowly add 200L tap water, continue to heat up, 105 ± 2 DEG C of hydrolysis reaction 2 hours, after hydrolysis reaction terminates, after being cooled to 80 DEG C, drip scale 110kgNaOH solution water solution, intensification degree starts clock reaction 2 hours to 102 DEG C, after reaction terminates, the upper strata oil extracted reaction solution while hot obtains quinizine oil;
(3) the quinizine oil that hydrolyzed solution step (1) obtained and step (2) obtain and water are obtained by reacting quinizine quaternary ammonium sulfate, quinizine content 36.23% (g/g) in quinizine quaternary ammonium sulfate, sulfuric acid content 11.27% (g/g), temperature cool 20 DEG C for subsequent use, wherein, starting material 1-phenyl-3-methyl-5 pyrazolone that the hydrolyzed solution that obtains of step (1) and step (2) are thrown is 1:1.2;
(4) nitrosification, reduction: the mixture being 1.9:1 by the mass ratio of the ammonium bisulfite got ready and ammonium sulphite adds in reduction reaction can 14, sulfuric acid quinizine quaternary ammonium salt and sodium nitrite in aqueous solution enter nitrosation reactor, nitrosation reaction is carried out under the cooling of stirring icy salt solution, reaction controlling, at 22 DEG C, (inside adds a little FeSO with starch potassium iodide test solution
4) checking that terminal is micro-blueness, PH controls 1.7, and nitroso-group quinizine constantly flows into reduction reaction can 14 through pipeline, carries out reduction reaction 2.5 hours at 83 DEG C, surveys reduction degree and is not less than 4.5ml;
(5) be hydrolyzed, neutralize: after reduction reaction terminates, be cooled to about 90 DEG C, by being 2.0 with sulfuric acid quinizine quaternary ammonium salt mol ratio, sulfuric acid slowly adds in reaction solution, adding sulfuric acid temperature controls at 85 DEG C, add sulfuric acid complete, be warming up to 100 DEG C, be hydrolyzed 2.5 hours, hydrolysis is complete is cooled to 75 DEG C, logical liquefied ammonia is neutralized to PH7.3, draws upper strata 4-AA (AA) oil after static 16 minutes.
4-AA yield 93.27%, content 78.65% (g/g).
Embodiment 4
The apparatus structure of the present embodiment is identical with embodiment 1 with using method,
4-AA production technique is as follows:
(1) by 180kg1-phenyl-3-methyl-5 pyrazolone; Add the methyl-sulfate of mol ratio 1.2 times, be warmed up to when interior temperature reaches 165 DEG C and start timing, temperature remains on 165 DEG C of reactions 6 hours, after methylation reaction terminates, after being cooled to 100 DEG C, under stirring state, slowly add 200L tap water, continue to heat up, 110 DEG C of hydrolysis reaction 2.5 hours, hydrolysis reaction terminated to be cooled to 90 DEG C and obtains hydrolyzed solution;
(2) by 207kg (180 × 1.15 times) 1-phenyl-3-methyl-5 pyrazolone; Add the methyl-sulfate of mol ratio 1.2 times, be warmed up to when interior temperature reaches 160 DEG C and start timing, temperature remains on 160 DEG C of reactions 6 hours, after methylation reaction terminates, after being cooled to 100 DEG C, under stirring state, slowly add 200L tap water, continue to heat up, 110 DEG C of hydrolysis reaction 2 hours, after hydrolysis reaction terminates, after being cooled to 80 DEG C, drip scale 110kgNaOH solution water solution, intensification degree starts clock reaction 2 hours to 102 DEG C, after reaction terminates, the upper strata oil extracted reaction solution while hot obtains quinizine oil;
(3) the quinizine oil that hydrolyzed solution step (1) obtained and step (2) obtain and water are obtained by reacting quinizine quaternary ammonium sulfate, quinizine content 37.0% (g/g) in quinizine quaternary ammonium sulfate, sulfuric acid content 9.0% (g/g), temperature cool 20 DEG C for subsequent use, wherein, starting material 1-phenyl-3-methyl-5 pyrazolone that the hydrolyzed solution that obtains of step (1) and step (2) are thrown is 1:1.5;
(4) nitrosification, reduction: the mixture being 2:1 by the mass ratio of the ammonium bisulfite got ready and ammonium sulphite adds in reduction reaction can 14, sulfuric acid quinizine quaternary ammonium salt and sodium nitrite in aqueous solution enter nitrosation reactor, nitrosation reaction is carried out under the cooling of stirring icy salt solution, reaction controlling, at 21 DEG C, (inside adds a little FeSO with starch potassium iodide test solution
4) checking that terminal is micro-blueness, PH controls 1.5, and nitroso-group quinizine constantly flows into reduction reaction can 14 through pipeline, carries out reduction reaction 3.5 hours at 81 DEG C, surveys reduction degree and is not less than 4.5ml;
(5) be hydrolyzed, neutralize: after reduction reaction terminates, be cooled to about 75 DEG C, by being 1.98 with sulfuric acid quinizine quaternary ammonium salt mol ratio, sulfuric acid slowly adds in reaction solution, adding sulfuric acid temperature controls at 83 DEG C, add sulfuric acid complete, be warming up to 105 DEG C, be hydrolyzed 2 hours, hydrolysis is complete is cooled to 76 DEG C, logical liquefied ammonia is neutralized to PH7.3, draws upper strata 4-AA (AA) oil after static 12 minutes.
4-AA yield 92.33%, content 78.87% (g/g).
Comparative example 1
By 360kg1-phenyl-3-methyl-5 pyrazolone; Add the methyl-sulfate of mol ratio 1.2 times, be warmed up to when interior temperature reaches 160 DEG C and start timing, temperature remains on 160 ~ 180 DEG C of reactions 6 hours, after methylation reaction terminates, after being cooled to 100 DEG C, under stirring state, slowly add 200L tap water, continue to heat up, 105 ~ 110 DEG C of hydrolysis reaction 2 hours, after hydrolysis reaction terminates, after being cooled to 80 DEG C, drip scale 110kgNaOH solution water solution, intensification degree starts clock reaction 2 hours to 102 DEG C, after reaction terminates, the upper strata oil extracted reaction solution while hot obtains quinizine oil;
Quinizine quaternary ammonium sulfate is prepared: quinizine oil squeezes into quinizine quaternary ammonium sulfate preparing tank with dosage sulfuric acid together with water, quinizine content 34.56% (g/g) in quinizine quaternary ammonium sulfate, sulfuric acid content 10.78% (g/g), temperature cool 20 DEG C for subsequent use;
Nitrosification, reduction: the reductive agent got ready is added in reduction reaction can, sulfuric acid quinizine quaternary ammonium salt and sodium nitrite in aqueous solution respectively by header tank by one fix number enter nitrosation reactor through spinner-type flowmeter, nitrosation reaction is carried out under the cooling of stirring icy salt solution, Flow-rate adjustment is suitable, reaction controlling is at 20-25 DEG C, check that terminal should be micro-blueness with starch potassium iodide test solution (inside adding a little FeSO4), PH controls about 1.5, nitroso-group quinizine constantly flows into reduction reaction can through pipeline, reduction reaction is carried out 3 hours at 80-85 DEG C, surveying reduction degree should lower than 4.5ml,
Hydrolysis, neutralization: after reduction reaction terminates, be cooled to about 80 DEG C, sulfuric acid with sulfuric acid quinizine quaternary ammonium salt 1.95 mol ratio is slowly added in tank, acid adding temperature controls at 80-90 DEG C, acid adding is complete, be warming up to 100-120 DEG C, hydrolysis 2-2.5 hour, hydrolysis is complete is cooled to 70-80 DEG C, logical liquefied ammonia is neutralized to PH7.1-7.3, draw upper strata 4-AA (AA) oil after static 15 minutes and enter oil suction tank, 4-AA yield 91.34%, content 78.16% (g/g).
Claims (8)
1. a 4-AA production technique, is characterized in that, step is as follows:
(1) 1-phenyl-3-methyl-5 pyrazolone and methyl-sulfate are methylated through high temperature, are hydrolyzed generation hydrolyzed solution;
(2) 1-phenyl-3-methyl-5 pyrazolone and methyl-sulfate are produced to obtain quinizine oil through high temperature methylation reaction, hydrolysis and alkaline purification;
(3) hydrolyzed solution, quinizine oil are mixed with quinizine quaternary ammonium salt brine solution; Add water and make in quinizine quaternary ammonium salts solution containing quinizine content g/g33.0-37.0%; Sulfuric acid content g/g9.0 ~ 12.0%; Generate 4-AA with the quinizine quaternary ammonium salt brine solution of preparation through nitrosification, reduction, neutralization, temperature cools to obtain product;
Starting material 1-phenyl-3-methyl-5 pyrazolone that the hydrolyzed solution that step (1) obtains and step (2) are thrown is 1:1.0 ~ 1.15;
In step (1) and step (2), the mol ratio of 1-phenyl-3-methyl-5 pyrazolone and methyl-sulfate is 1:1.20 ~ 1.25.
2. 4-AA production technique according to claim 1, is characterized in that, during preparation quinizine quaternary ammonium sulfate, hydrolyzed solution temperature is 50-100 DEG C.
3. 4-AA production technique according to claim 1, is characterized in that, reductive agent is ammonium bisulfite and ammonium sulphite mixture.
4. 4-AA production technique according to claim 3, is characterized in that, the mass ratio of ammonium bisulfite and ammonium sulphite is 1.9-2.0:1.
5. a 4-AA production technique production equipment according to claim 1, comprise the first pyrazolone feed bin (2), it is characterized in that, first pyrazolone feed bin (2) and the first methyl-sulfate test tank (1) are connected respectively by pipeline and first tank (3) that methylates, first tank (3) that methylates is connected with the first hydrolytic decomposition pot (5), first hydrolytic decomposition pot (5) is connected with alkaline purification tank (6), and alkaline purification tank (6) is connected with quinizine oil tank (8), second pyrazolone feed bin (21) and the second methyl-sulfate test tank (20) are connected respectively by pipeline and second tank (18) that methylates, second tank (18) that methylates is connected with the second hydrolytic decomposition pot (17), second hydrolytic decomposition pot (17), quinizine oil tank (8), 3rd water measuring tank (16) is connected with quinizine quaternary ammonium sulfate batch tank (15) respectively by pipeline, quinizine quaternary ammonium sulfate batch tank (15) is connected with nitrosation reaction tank (10) respectively by pipeline with Sodium Nitrite test tank (9), nitrosation reaction tank (10) is connected with reduction reaction can (14), reduction reaction can (14) and hydrolysis, neutralization tank (12) connects, first hydrolytic decomposition pot (5) is connected with liquid caustic soda test tank (4) by pipeline.
6. 4-AA production technique production equipment according to claim 5, is characterized in that, hydrolysis, neutralization tank (12) are connected with ammonium sulfate liquor tank (11) and 4-quinizine oil tank (13) respectively by pipeline.
7. 4-AA production technique production equipment according to claim 5, is characterized in that, the first water measuring tank (22) is connected with the first hydrolytic decomposition pot (5) by pipeline.
8. 4-AA production technique production equipment according to claim 5, is characterized in that, the second water measuring tank (19) is connected with the second hydrolytic decomposition pot (17) by pipeline; Alkaline purification tank (6) is connected with sodium sulfate mother liquor tank (7) by pipeline.
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| CN110526869B (en) * | 2019-08-29 | 2022-06-28 | 青岛科技大学 | Continuous production system of 4-aminoantipyrine |
| CN113058529B (en) * | 2021-03-30 | 2023-01-31 | 河北冀衡药业股份有限公司 | Continuous preparation method of 4-nitrosoantipyrine |
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