CN103613544A - 4-aminoantipyrene production technology and device thereof - Google Patents
4-aminoantipyrene production technology and device thereof Download PDFInfo
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- CN103613544A CN103613544A CN201310660063.5A CN201310660063A CN103613544A CN 103613544 A CN103613544 A CN 103613544A CN 201310660063 A CN201310660063 A CN 201310660063A CN 103613544 A CN103613544 A CN 103613544A
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- 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
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Abstract
The invention belongs to the field of pharmaceutical chemicals, and relates to a 4-aminoantipyrene production technology and a device thereof. The production technology comprises the steps of performing high-temperature methylation and hydrolysis on 1-phenyl-3-methyl-5 pyrazolone and dimethyl sulfate to generate hydrolysate; performing high-temperature methylation reaction, hydrolysis and alkali treatment on 1-phenyl-3-methyl-5 pyrazolone and dimethyl sulfate to produce antipyrine oil; preparing an antipyrine quaternary ammonium sulfate aqueous solution from hydrolysate and antipyrine oil; performing nitrosation, reduction and neutralization on the antipyrine quaternary ammonium sulfate aqueous solution to generate 4-aminoantipyrene, and cooling to 20 DEG C for later use. By adopting the production technology provided by the invention, the use of caustic soda liquid and sulfuric acid is greatly reduced, and the discharge of sodium sulfate and high-concentration wastewater is obviously reduced; the production technology is environment-friendly, simple in process and convenient to operate; the 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
Sulpyrine, pyramidon are important ntipyretic analgesic medicine, only the market scale of Sulpyrine is 20,000 tons of left and right, China is main in the world producing country and export State, in addition pyramidon market capacity is also 2500 tons of left and right, therefore the usage quantity of 4-AA is huge, so development and operation is simple, environmental friendliness, technique that atom utilization is high are extremely urgent.
Traditional technique take 1-phenyl-3-methyl-5-pyrazolone as starting material and methyl-sulfate high temperature methylates, quinizine oil is produced in hydrolysis, alkaline purification; 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; During by this explained hereafter, often produce 1 kilogram of 4-AA and need consume 0.5800 kilogram of liquid caustic soda, preparation quinizine quaternary ammonium sulfate consumes 0.2900 kilogram, sulfuric acid, generate 1.2672 kilograms, sodium sulfate, because of Sulpyrine, pyramidon series ntipyretic analgesic medicine market scale huge, huge to sodium sulfate, the high-COD waste water amount of the Nature discharge every year.
Summary of the invention
The object of this invention is to provide a kind of 4-AA production technique and device thereof, is antipyretic and analgesic Sulpyrine, the extremely important intermediate of pyramidon, and 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, easy to operate, and 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, are hydrolyzed generation hydrolyzed solution through high temperature;
(2) 1-phenyl-3-methyl-5 pyrazolone and methyl-sulfate are produced to obtain to quinizine oil through high temperature methylation reaction, hydrolysis and alkaline purification;
(3) hydrolyzed solution, quinizine oil are mixed with to the quinizine quaternary ammonium sulfate aqueous solution; Add water and make to contain in quinizine quaternary ammonium sulfate solution quinizine content 33.0-37.0% (g/g); Sulfuric acid content 9.0～12.0% (g/g); With the quinizine quaternary ammonium sulfate aqueous solution of preparation, through nitrosification, reduction, neutralization, generate 4-AA, temperature cooling 20 ℃ standby.
The object that adds water guarantees " in quinizine quaternary ammonium sulfate solution, to contain quinizine content 33.0-37.0% (g/g); 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 ℃.
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) 1-phenyl-3-methyl-5 pyrazolone, methyl-sulfate are mixed, being warmed up to interior temperature reaches after 160～180 ℃, temperature remains on 160～180 ℃ of methylation reaction 5-7 hour, after methylation reaction finishes, be cooled to after 100 ℃, under stirring, add 180-220L tap water, continue to be warming up to 105～110 ℃ of hydrolysis reaction 2-3 hour, hydrolysis reaction finishes to be cooled to 50-100 ℃ and obtains hydrolyzed solution;
(2) by 1-phenyl-3-methyl-5 pyrazolone, methyl-sulfate mixes, being warmed up to interior temperature reaches after 160～180 ℃, temperature remains on 160～180 ℃ of methylation reaction 5-7 hour, after methylation reaction finishes, be cooled to after 100 ℃, under stirring, add 200L tap water, continue to be warming up to 105～110 ℃ of hydrolysis reaction 2-3 hour, after hydrolysis reaction finishes, be cooled to after 70-90 ℃, 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 ℃, after reaction finishes, draw while hot reaction solution upper strata oil and obtain quinizine oil,
(3) hydrolyzed solution, quinizine oil are mixed, by water, regulate and control quinizine oil-contg, obtain quinizine quaternary ammonium sulfate;
(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, with starch potassium iodide test solution (inside adding a little FeSO4), check that terminal is micro-blueness, stir under icy salt solution cooling and carry out nitrosation reaction, reaction is controlled at 20-25 ℃, PH is controlled at 1.3-1.7, then nitroso-group quinizine carries out reduction reaction 2.5-3.5 hour at 80-85 ℃, survey reduction degree and be not less than 4.5ml,
(5) hydrolysis, neutralization: after reduction reaction finishes, be cooled to 75-95 ℃, 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 and be controlled at 80-90 ℃, be warming up to 100-120 ℃, hydrolysis 2-2.5 hour; After being hydrolyzed, be cooled to 70-80 ℃, logical liquefied ammonia is neutralized to PH7.1-7.3, after static 12-18 minute, obtains upper strata 4-AA.
The present invention often produces 1 kilogram of 4-AA need consume 0.29 kilogram of liquid caustic soda, preparation quinizine quaternary ammonium sulfate sulfuric acid consumption is 0, sodium sulfate generation reduces 0.4224 kilogram, because directly using hydrolyzed solution, discharges less 2.45 kilograms of high COD sodium sulfate wastewaters.
4-AA production equipment of the present invention, comprise the first pyrazolone feed bin, the first pyrazolone feed bin and the first methyl-sulfate test tank are connected by pipeline and first tank that methylates respectively, first tank that methylates is connected with the first hydrolytic decomposition pot, the first hydrolytic decomposition pot is connected with alkaline purification tank, and alkaline purification tank is connected with quinizine oil tank; The second pyrazolone feed bin and the second methyl-sulfate test tank are connected by pipeline and second tank that methylates respectively, second tank that methylates is connected with the second hydrolytic decomposition pot, the second hydrolytic decomposition pot, quinizine oil tank, the 3rd water metering are filled with and by pipeline, are connected with quinizine quaternary ammonium sulfate batch tank respectively, quinizine quaternary ammonium sulfate batch tank is connected with nitrosation reaction tank by pipeline respectively with Sodium Nitrite metering filling, nitrosation reaction tank is connected with reduction reaction can, and reduction reaction can is connected with hydrolysis neutralization tank; The first hydrolytic decomposition pot is filled with and is connected with liquid caustic soda metering by pipeline.
Hydrolysis neutralization tank is connected with 4-quinizine oil tank with ammonium sulfate liquor tank by pipeline respectively.
The first water metering is filled with and is connected with the first hydrolytic decomposition pot by pipeline.
The 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.
Valve is all set on each pipeline.
Every 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 is squeezed into the first methyl-sulfate test tank, and the pyrazolone of the first pyrazolone feed bin enters first tank that methylates, and closes the first tank pyrazolone charging opening that methylates; Open the first methyl-sulfate test tank bottom valve, the first tank feed valve that methylates, adds first tank that methylates by methyl-sulfate, finishes, close the first methyl-sulfate bottom valve, first tank feed valve that methylates, temperature reaction, reacts complete, opens the first tank bottom valve that methylates, the first hydrolytic decomposition pot feed valve, first liquid that methylates is put into the first hydrolytic decomposition pot, put completely, close the first tank bottom valve that methylates; Open the first water measuring tank bottom valve, the water of dosage is joined to the first hydrolytic decomposition pot, finish, close the first water measuring tank bottom valve and the first hydrolytic decomposition pot charging valve, reaction is hydrolyzed, 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 and collect, the upper strata quinizine oil of alkaline purification tank is put into quinizine oil tank, standby;
Pyrazolone is put into the second pyrazolone feed bin; Methyl-sulfate is squeezed into the second methyl-sulfate test tank, and the pyrazolone of the second pyrazolone feed bin enters second tank that methylates, and closes the second tank pyrazolone charging opening that methylates; Open the second methyl-sulfate test tank bottom valve, the second tank feed valve that methylates, adds second tank that methylates by methyl-sulfate, finishes, close the second methyl-sulfate bottom valve, second tank feed valve that methylates, temperature reaction, reacts complete, opens the second tank bottom valve that methylates, the second hydrolytic decomposition pot feed valve, second liquid that methylates is put into the second hydrolytic decomposition pot, put completely, close the second tank bottom valve that methylates; Open the second water measuring tank bottom valve, the water of dosage is joined to the second hydrolytic decomposition pot, finish, close the second water measuring tank bottom valve and the second hydrolytic decomposition pot charging valve, the reaction that is hydrolyzed, hydrolysis is finished, standby;
Open the second hydrolytic decomposition pot bottom valve, hydrolyzed solution is pressed into quinizine quaternary ammonium sulfate preparing tank, open quinizine oil tank bottom valve 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 to quinizine quaternary ammonium sulfate preparing tank, regulate quinizine content and sulfuric acid content in quinizine quaternary ammonium sulfate, quinizine quaternary ammonium sulfate is put into reduction reaction can with Sodium Nitrite and is reacted, and reaction is finished; Open reduction reaction can bottom valve, by pipeline, be transferred to hydrolysis, neutralization tank, be hydrolyzed, neutralization reaction.Standing, 4-AA oil is sucked to 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:
Technique of the present invention is simple, consumes liquid caustic soda few, and during preparation quinizine quaternary ammonium sulfate, without sulfuric acid, sodium sulfate generation reduces, and discharges high COD sodium sulfate wastewater few, and the usage quantity of liquid caustic soda, sulfuric acid greatly reduces; Sodium sulfate, hc effluent quantity discharged reduce obviously, meet environmental friendliness, Green Chemistry characteristic attribute, and product yield is high.Because Sulpyrine, pyramidon belong to large tonnage product in China, use after this invented technology economic benefit and social benefit obvious.
Accompanying drawing explanation
Fig. 1 production equipment figure of the present invention;
In figure, in figure, 1, the first methyl-sulfate test tank, 2, the first pyrazolone feed bin, 3, first tank that methylates, 4, liquid caustic soda metering is filled with, 5, the 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, the second hydrolytic decomposition pot, 18, second tank that methylates, 19, the second water metering is filled with, 20, the second methyl-sulfate test tank, 21, the second pyrazolone feed bin, 22, the 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, the first pyrazolone feed bin 2 and the first methyl-sulfate test tank 1 are connected by pipeline and first tank 3 that methylates respectively, first tank 3 that methylates is connected with the first hydrolytic decomposition pot 5, the first hydrolytic decomposition pot 5 is connected with alkaline purification tank 6, and alkaline purification tank 6 is connected with quinizine oil tank 8; The second pyrazolone feed bin 21 and the second methyl-sulfate test tank 20 are connected by pipeline and second tank 18 that methylates respectively, second tank 18 that methylates is connected with the second hydrolytic decomposition pot 17, the second hydrolytic decomposition pot 17, quinizine oil tank 8, water metering are filled with 16 and by pipeline, are connected with quinizine quaternary ammonium sulfate batch tank 15 respectively, quinizine quaternary ammonium sulfate batch tank 15 is connected with nitrosation reaction tank 10 by pipeline respectively 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; The first hydrolytic decomposition pot 5 is filled with 4 by pipeline with liquid caustic soda metering and is connected.
Hydrolysis neutralization tank 12 is connected with 4-quinizine oil tank 13 with ammonium sulfate liquor tank 11 by pipeline respectively.
The first water metering is filled with 22 and is connected with the first hydrolytic decomposition pot 5 by pipeline.
The second water metering is filled with 19 and 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 the first tank 3 pyrazolone charging openings that methylate, and pyrazolone is entered to first tank 3 that methylates, and closes the first tank 3 pyrazolone charging openings that methylate; Open the first methyl-sulfate test tank 1 bottom valve, the first tank 3 methyl-sulfate feed valves that methylate, methyl-sulfate is added to first tank 3 that methylates, finish, close the first methyl-sulfate tank 1 bottom valve, first tank 3 feed valves that methylate, temperature reaction is complete, open first tank 3 bottom valves that methylate, the first hydrolytic decomposition pot 5 feed valves, the liquid that will methylate is put into the first hydrolytic decomposition pot 5, put completely, close first tank 3 bottom valves that methylate; Open the first water measuring tank 22 bottom valves, water is joined to the first hydrolytic decomposition pot 5, finish, close the first water measuring tank 5 bottom valves and the first hydrolytic decomposition pot 5 charging valves, the reaction that is hydrolyzed, hydrolysis is finished, open the first hydrolytic decomposition pot 5 bottom valves, alkaline purification tank 6 bottom valves, put 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 to be collected, open quinizine oil tank 8 feed valves, the upper strata quinizine oil of alkaline purification tank 6 is put into quinizine oil tank 8, standby;
Pyrazolone is put into the second pyrazolone feed bin 21; The pyrazolone that methyl-sulfate is squeezed into the second methyl-sulfate test tank 20, the second pyrazolone feed bins 21 enters second tank 18 that methylates, and closes the second tank 18 pyrazolone charging openings that methylate; Open the second methyl-sulfate test tank 20 bottom valves, second tank 18 feed valves that methylate, add second tank 18 that methylates by methyl-sulfate, finish, close the second methyl-sulfate tank 20 bottom valves, second tank 18 feed valves that methylate, temperature reaction, reacts complete, opens second tank 18 bottom valves that methylate, the second hydrolytic decomposition pot 17 feed valves, second liquid that methylates is put into the second hydrolytic decomposition pot 17, put completely, close second tank 18 bottom valves that methylate; Open the second water measuring tank 19 bottom valves, water is joined to the second hydrolytic decomposition pot 17, finish, close the second water measuring tank 19 bottom valves and the second hydrolytic decomposition pot 17 charging valves, the reaction that is hydrolyzed, hydrolysis is finished, standby;
Open the second hydrolytic decomposition pot 17 bottom valves, hydrolyzed solution is pressed into quinizine quaternary ammonium sulfate preparing tank 15, open quinizine oil tank 8 bottom valves quinizine oil is put into quinizine quaternary ammonium sulfate preparing tank 15, finish, close quinizine oil tank 8 bottom valves, open the 3rd water measuring tank 16 bottom valves, water is added to quinizine quaternary ammonium sulfate preparing tank 15, regulate quinizine content and sulfuric acid content in quinizine quaternary ammonium sulfate, quinizine quaternary ammonium sulfate is put into reduction reaction can 14 with Sodium Nitrite and is reacted, and reaction is finished; Open reduction reaction can 14 bottom valves, by pipeline, be transferred to hydrolysis, neutralization tank 12, be hydrolyzed, neutralization reaction, standing, 4-AA oil is sucked to 4-AA oil tank 13 by valve tube, mother liquor proceeds to ammonium sulfate liquor tank 11.
4-AA production technique is as follows:
(1) by 180kg 1-phenyl-3-methyl-5 pyrazolone; Add the methyl-sulfate of 1.2 times of mol ratios to carry out methylation reaction, be warmed up to and when interior temperature reaches 160 ℃, start timing, temperature remains on 160 ± 2 ℃ of reactions 6 hours, then be cooled to after 100 ℃, under stirring state, slowly add 180L tap water, continue to heat up, 107 ± 2 ℃ of hydrolysis reaction 2.5 hours, after hydrolysis reaction finishes, be cooled to 50 ℃ and obtain hydrolyzed solution;
(2) by 180kg 1-phenyl-3-methyl-5 pyrazolone; Add the methyl-sulfate of 1.2 times of mol ratios to carry out methylation reaction, be warmed up to and when interior temperature reaches 160 ℃, start timing, temperature remains on 170 ± 2 ℃ of reactions 6 hours, be cooled to after 100 ℃, under stirring state, slowly add 200L tap water, continue to heat up, 107 ± 2 ℃ of hydrolysis reaction 2.5 hours, after hydrolysis reaction finishes, be cooled to 80 ℃, drip 110kg NaOH solution water solution, be warmed up to 102 ℃ and start clock reaction 2 hours, after reaction finishes, the upper strata oil extracting reaction solution while hot obtains quinizine oil;
(3) the quinizine oil that hydrolyzed solution step (1) being obtained obtains with step (2) and water are mixed together to react and obtain quinizine quaternary ammonium sulfate; Quinizine content 33.0% (g/g) in quinizine quaternary ammonium sulfate, sulfuric acid content 12.0% (g/g), temperature cooling 20 ℃ standby; Wherein, 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;
(4) nitrosification, reduction: the mixture that is 1.9:1 by the mass ratio of the ammonium bisulfite of getting 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 is controlled at 20 ℃, with starch potassium iodide test solution, (inside adds a little FeSO
4) checking that terminal is micro-blueness, PH is controlled at 1.5, and nitroso-group quinizine constantly flows into reduction reaction can 14 through pipeline, at 80 ℃, carries out reduction reaction 3 hours, surveys reduction degree and is not less than 4.5ml;
(5) hydrolysis, neutralization: after reduction reaction finishes, be cooled to 80 ℃ of left and right, by being 1.95 with sulfuric acid quinizine quaternary ammonium salt mol ratio, sulfuric acid slowly adds in reaction solution, add sulfuric acid temperature and be controlled at 90 ℃, add sulfuric acid complete, be warming up to 120 ℃, be hydrolyzed 2 hours, hydrolysis is complete is cooled to 70 ℃, 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 and using method are identical with embodiment 1,
4-AA production technique is as follows:
(1) by 180kg 1-phenyl-3-methyl-5 pyrazolone; The methyl-sulfate that adds 1.25 times of mol ratios, be warmed up to and when interior temperature reaches 170 ℃, start timing, temperature remains on 170 ℃ of reactions 7 hours, after methylation reaction finishes, be cooled to after 100 ℃, under stirring state, slowly add 200L tap water, continue to heat up, 105 ± 2 ℃ of hydrolysis reaction 3 hours, hydrolysis reaction finished to be cooled to 100 ℃ and obtains hydrolyzed solution;
(2) by 189kg 1-phenyl-3-methyl-5 pyrazolone; The methyl-sulfate that adds 1.25 times of mol ratios, be warmed up to and when interior temperature reaches 160 ℃, start timing, temperature remains on 160～180 ℃ of reactions 6 hours, after methylation reaction finishes, be cooled to after 100 ℃, under stirring state, slowly add 200L tap water, continue to heat up, 107 ± 2 ℃ of hydrolysis reaction 3 hours, after hydrolysis reaction finishes, be cooled to after 80 ℃, drip scale 110kgNaOH solution water solution, intensification degree to 110 ℃ starts clock reaction 2 hours, after reaction finishes, the upper strata oil extracting reaction solution while hot obtains quinizine oil;
(3) quinizine oil and water that hydrolyzed solution step (1) being obtained and step (2) obtain 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 cooling 20 ℃ standby, wherein, starting material 1-phenyl-3-methyl-5 pyrazolone that the hydrolyzed solution that step (1) obtains and step (2) are thrown is 1:1.5;
(4) nitrosification, reduction: the mixture that is 2.0:1 by the mass ratio of the ammonium bisulfite of getting 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, under the cooling of stirring icy salt solution, carry out nitrosation reaction, reaction is controlled at 25 ℃, with starch potassium iodide test solution, (inside adds a little FeSO
4) checking that terminal is micro-blueness, PH is controlled at 1.3, and nitroso-group quinizine constantly flows into reduction reaction can 14 through pipeline, at 85 ℃, carries out reduction reaction 3 hours, surveys reduction degree and is not less than 4.5ml;
(5) hydrolysis, neutralization: after reduction reaction finishes, be cooled to 80 ℃ of left and right, by being 1.90 with sulfuric acid quinizine quaternary ammonium salt mol ratio, sulfuric acid slowly adds in reaction solution, add sulfuric acid temperature and be controlled at 90 ℃, add sulfuric acid complete, be warming up to 110 ℃, be hydrolyzed 2 hours, the complete 70-80 ℃ that is cooled to of hydrolysis, 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 and using method are identical with embodiment 1,
4-AA production technique is as follows:
(1) by 180kg 1-phenyl-3-methyl-5 pyrazolone; The methyl-sulfate that adds 1.2 times of mol ratios, be warmed up to and when interior temperature reaches 180 ℃, start timing, temperature remains on 180 ℃ of reactions 5 hours, after methylation reaction finishes, be cooled to after 100 ℃, under stirring state, slowly add 220L tap water, continue to heat up, 110 ± 2 ℃ of hydrolysis reaction 2 hours, hydrolysis reaction finished to be cooled to 70 ℃ and obtains hydrolyzed solution;
(2) by 198kg (180 * 1.1 times) 1-phenyl-3-methyl-5 pyrazolone; The methyl-sulfate that adds 1.2 times of mol ratios, be warmed up to and when interior temperature reaches 160 ℃, start timing, temperature remains on 180 ℃ of reactions 7 hours, after methylation reaction finishes, be cooled to after 100 ℃, under stirring state, slowly add 200L tap water, continue to heat up, 105 ± 2 ℃ of hydrolysis reaction 2 hours, after hydrolysis reaction finishes, be cooled to after 80 ℃, drip scale 110kgNaOH solution water solution, intensification degree to 102 ℃ starts clock reaction 2 hours, after reaction finishes, the upper strata oil extracting reaction solution while hot obtains quinizine oil;
(3) the quinizine oil that hydrolyzed solution step (1) being obtained obtains with step (2) and water react and obtain quinizine quaternary ammonium sulfate, quinizine content 36.23% (g/g) in quinizine quaternary ammonium sulfate, sulfuric acid content 11.27% (g/g), temperature cooling 20 ℃ standby, wherein, starting material 1-phenyl-3-methyl-5 pyrazolone that the hydrolyzed solution that step (1) obtains and step (2) are thrown is 1:1.2;
(4) nitrosification, reduction: the mixture that is 1.9:1 by the mass ratio of the ammonium bisulfite of getting 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, under the cooling of stirring icy salt solution, carry out nitrosation reaction, reaction is controlled at 22 ℃, with starch potassium iodide test solution, (inside adds a little FeSO
4) checking that terminal is micro-blueness, PH is controlled at 1.7, and nitroso-group quinizine constantly flows into reduction reaction can 14 through pipeline, at 83 ℃, carries out reduction reaction 2.5 hours, surveys reduction degree and is not less than 4.5ml;
(5) hydrolysis, neutralization: after reduction reaction finishes, be cooled to 90 ℃ of left and right, by being 2.0 with sulfuric acid quinizine quaternary ammonium salt mol ratio, sulfuric acid slowly adds in reaction solution, add sulfuric acid temperature and be controlled at 85 ℃, add sulfuric acid complete, be warming up to 100 ℃, be hydrolyzed 2.5 hours, hydrolysis is complete is cooled to 75 ℃, 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 and using method are identical with embodiment 1,
4-AA production technique is as follows:
(1) by 180kg 1-phenyl-3-methyl-5 pyrazolone; The methyl-sulfate that adds 1.2 times of mol ratios, be warmed up to and when interior temperature reaches 165 ℃, start timing, temperature remains on 165 ℃ of reactions 6 hours, after methylation reaction finishes, be cooled to after 100 ℃, under stirring state, slowly add 200L tap water, continue to heat up, 110 ℃ of hydrolysis reaction 2.5 hours, hydrolysis reaction finished to be cooled to 90 ℃ and obtains hydrolyzed solution;
(2) by 207kg (180 * 1.15 times) 1-phenyl-3-methyl-5 pyrazolone; The methyl-sulfate that adds 1.2 times of mol ratios, be warmed up to and when interior temperature reaches 160 ℃, start timing, temperature remains on 160 ℃ of reactions 6 hours, after methylation reaction finishes, be cooled to after 100 ℃, under stirring state, slowly add 200L tap water, continue to heat up, 110 ℃ of hydrolysis reaction 2 hours, after hydrolysis reaction finishes, be cooled to after 80 ℃, drip scale 110kgNaOH solution water solution, intensification degree to 102 ℃ starts clock reaction 2 hours, after reaction finishes, the upper strata oil extracting reaction solution while hot obtains quinizine oil;
(3) the quinizine oil that hydrolyzed solution step (1) being obtained obtains with step (2) and water react and obtain quinizine quaternary ammonium sulfate, quinizine content 37.0% (g/g) in quinizine quaternary ammonium sulfate, sulfuric acid content 9.0% (g/g), temperature cooling 20 ℃ standby, wherein, starting material 1-phenyl-3-methyl-5 pyrazolone that the hydrolyzed solution that step (1) obtains and step (2) are thrown is 1:1.5;
(4) nitrosification, reduction: the mixture that is 2:1 by the mass ratio of the ammonium bisulfite of getting 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, under the cooling of stirring icy salt solution, carry out nitrosation reaction, reaction is controlled at 21 ℃, with starch potassium iodide test solution, (inside adds a little FeSO
4) checking that terminal is micro-blueness, PH is controlled at 1.5, and nitroso-group quinizine constantly flows into reduction reaction can 14 through pipeline, at 81 ℃, carries out reduction reaction 3.5 hours, surveys reduction degree and is not less than 4.5ml;
(5) hydrolysis, neutralization: after reduction reaction finishes, be cooled to 75 ℃ of left and right, by being 1.98 with sulfuric acid quinizine quaternary ammonium salt mol ratio, sulfuric acid slowly adds in reaction solution, add sulfuric acid temperature and be controlled at 83 ℃, add sulfuric acid complete, be warming up to 105 ℃, be hydrolyzed 2 hours, hydrolysis is complete is cooled to 76 ℃, 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 360kg 1-phenyl-3-methyl-5 pyrazolone; The methyl-sulfate that adds 1.2 times of mol ratios, be warmed up to and when interior temperature reaches 160 ℃, start timing, temperature remains on 160～180 ℃ of reactions 6 hours, after methylation reaction finishes, be cooled to after 100 ℃, under stirring state, slowly add 200L tap water, continue to heat up, 105～110 ℃ of hydrolysis reaction 2 hours, after hydrolysis reaction finishes, be cooled to after 80 ℃, drip scale 110kgNaOH solution water solution, intensification degree to 102 ℃ starts clock reaction 2 hours, after reaction finishes, the upper strata oil extracting reaction solution while hot obtains quinizine oil;
Quinizine quaternary ammonium sulfate preparation: quinizine oil is squeezed 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 cooling 20 ℃ standby;
Nitrosification, reduction: the reductive agent of getting ready is added in reduction reaction can, sulfuric acid quinizine quaternary ammonium salt and sodium nitrite in aqueous solution are fixed to count by one by header tank respectively and enter nitrosation reactor through spinner-type flowmeter, in stirring under icy salt solution cooling, carry out nitrosation reaction, Flow-rate adjustment is suitable, reaction is controlled at 20-25 ℃, with starch potassium iodide test solution (inside adding a little FeSO4), check that terminal should be micro-blueness, PH is controlled at 1.5 left and right, nitroso-group quinizine constantly flows into reduction reaction can through pipeline, at 80-85 ℃, carry out reduction reaction 3 hours, surveying reduction degree should be lower than 4.5ml,
Hydrolysis, neutralization: after reduction reaction finishes, be cooled to 80 ℃ of left and right, to slowly add in tank with the sulfuric acid of sulfuric acid quinizine quaternary ammonium salt 1.95 mol ratios, acid adding temperature is controlled at 80-90 ℃, and acid adding is complete, is warming up to 100-120 ℃, hydrolysis 2-2.5 hour, hydrolysis is complete is cooled to 70-80 ℃, and logical liquefied ammonia is neutralized to PH7.1-7.3, draws upper strata 4-AA (AA) oil and enter oil suction tank after static 15 minutes, 4-AA yield 91.34%, content 78.16% (g/g).
Claims (10)
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, are hydrolyzed generation hydrolyzed solution through high temperature;
(2) 1-phenyl-3-methyl-5 pyrazolone and methyl-sulfate are produced to obtain to quinizine oil through high temperature methylation reaction, hydrolysis and alkaline purification;
(3) hydrolyzed solution, quinizine oil are mixed with to the quinizine quaternary ammonium sulfate aqueous solution; Add water and make to contain in quinizine quaternary ammonium sulfate solution quinizine content 33.0-37.0% (g/g); Sulfuric acid content 9.0～12.0% (g/g); With the quinizine quaternary ammonium sulfate aqueous solution of preparation, through nitrosification, reduction, neutralization, generate 4-AA, the cooling product that obtains of temperature.
2. 4-AA production technique according to claim 1, is characterized in that, 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.
3. 4-AA production technique according to claim 1, is characterized in that, in step (1) and step (2), the mol ratio of phenyl-3-methyl-5 pyrazolone and methyl-sulfate is 1:1.20～1.25.
4. 4-AA production technique according to claim 1, is characterized in that, during preparation quinizine quaternary ammonium sulfate, hydrolyzed solution temperature is 50-100 ℃.
5. 4-AA production technique according to claim 1, is characterized in that, reductive agent is ammonium bisulfite and ammonium sulphite mixture.
6. 4-AA production technique according to claim 1, is characterized in that, the mass ratio of ammonium bisulfite and ammonium sulphite is 1.9-2.0:1.
7. a 4-AA production equipment claimed in claim 1, comprise the first pyrazolone feed bin (2), it is characterized in that, the first pyrazolone feed bin (2) and the first methyl-sulfate test tank (1) are connected by pipeline and first tank (3) that methylates respectively, first tank (3) that methylates is connected with the first hydrolytic decomposition pot (5), the first hydrolytic decomposition pot (5) is connected with alkaline purification tank (6), and alkaline purification tank (6) is connected with quinizine oil tank (8), the second pyrazolone feed bin (21) and the second methyl-sulfate test tank (20) are connected by pipeline and second tank (18) that methylates respectively, second tank (18) that methylates is connected with the second hydrolytic decomposition pot (17), the second hydrolytic decomposition pot (17), quinizine oil tank (8), the 3rd water measuring tank (16) is connected with quinizine quaternary ammonium sulfate batch tank (15) by pipeline respectively, quinizine quaternary ammonium sulfate batch tank (15) is connected with nitrosation reaction tank (10) by pipeline respectively 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, the first hydrolytic decomposition pot (5) is connected with liquid caustic soda test tank (4) by pipeline.
8. 4-AA production equipment according to claim 7, is characterized in that, hydrolysis, neutralization tank (12) are connected with 4-quinizine oil tank (13) with ammonium sulfate liquor tank (11) by pipeline respectively.
9. 4-AA production equipment according to claim 7, is characterized in that, the first water measuring tank (22) is connected with the first hydrolytic decomposition pot (5) by pipeline.
10. 4-AA production equipment according to claim 7, 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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