CN101774929A - Preparation method of 2-methyl-4-nitrophenylamine - Google Patents
Preparation method of 2-methyl-4-nitrophenylamine Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- XTTIQGSLJBWVIV-UHFFFAOYSA-N 2-methyl-4-nitroaniline Chemical compound CC1=CC([N+]([O-])=O)=CC=C1N XTTIQGSLJBWVIV-UHFFFAOYSA-N 0.000 title abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 126
- 239000007787 solid Substances 0.000 claims abstract description 54
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 38
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229910017604 nitric acid Inorganic materials 0.000 claims abstract description 21
- 239000002994 raw material Substances 0.000 claims abstract description 18
- 239000012065 filter cake Substances 0.000 claims abstract description 14
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 13
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 5
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 4
- 230000007062 hydrolysis Effects 0.000 claims abstract description 4
- 230000001105 regulatory effect Effects 0.000 claims abstract description 3
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 claims description 68
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 19
- 238000001035 drying Methods 0.000 claims description 15
- 238000001953 recrystallisation Methods 0.000 claims description 15
- 238000010992 reflux Methods 0.000 claims description 13
- 125000003368 amide group Chemical group 0.000 claims description 5
- 230000000802 nitrating effect Effects 0.000 claims description 4
- 238000006396 nitration reaction Methods 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 230000001143 conditioned effect Effects 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 18
- 238000001914 filtration Methods 0.000 abstract description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract description 6
- 230000010933 acylation Effects 0.000 abstract description 3
- 238000005917 acylation reaction Methods 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 125000003277 amino group Chemical group 0.000 abstract 1
- 230000001546 nitrifying effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 13
- 238000001816 cooling Methods 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 238000010792 warming Methods 0.000 description 11
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 2-methyl-4-nitrophenylamine, which sequentially comprises the following steps of: (1) protecting acylation amino group by using ortho-toludiene as a raw material and using acetic acid as an acylation agent; (2) carrying out nitrification reaction on the reaction liquid obtained in the step (1) by using concentrated nitric acid as a nitrifying agent to obtain a nitrified solid; (3) carrying out hydrolysis reaction on the nitrified solid by using concentrated hydrochloric acid as a hydrolysis reagent; and (4) regulating the pH of the reaction liquid obtained in the step (3) to1-2, and filtering and recrystallizing an obtained filter cake to obtain the 2-methyl-4-nitrophenylamine. The 2-methyl-4-nitrophenylamine prepared by using the method has the characteristics of concise process and low cost.
Description
Technical field
The present invention relates to a kind of synthetic method of organic compound, particularly the synthetic method of 2-methyl-4-N-methyl-p-nitroaniline (2-methyl-4-nitroaniline).
Background technology
2-methyl-4-N-methyl-p-nitroaniline, its molecular formula are C
7H
8N
2O
2, its structure is shown in S-1, and pure product are the yellow-green colour crystal, and 130～131 ℃ of fusing points are a kind of medium-to-high grade glacial dye, requisite dyestuff when it is velveteen, pleuche, corduroy dyeing.
The comprehensive literature report, following method is adopted in the preparation of 2-methyl-4-N-methyl-p-nitroaniline at present: 1, report among report PB74027 of United States Federal Government bureau of publication and the PB25625, the employing Ortho Toluidine is a raw material, with the Tosyl chloride is acylating agent, through acidylate, nitrated, hydrolysis, neutralization and filtration drying and get, yield is 95.0%; 2, adopting o-toluidine is raw material, utilizes the formic acid acidylate, and again through mixed acid nitrification, sulphuric acid hydrolysis and getting is 89105407.3 Chinese patent " a kind of production methods of glacial dye " as application number, and yield is 70.0%; 3, document (synthetic process for red base RL is improved, chemical reagent, 2006,28 (11), 671-673) in, be raw material with the o-toluidine, utilize acetic anhydride acylation, again through mixed acid nitrification, sulphuric acid hydrolysis and getting, yield is 78.4%.Adopt the Tosyl chloride method, auxiliary material is more, complex process, and also the Tosyl chloride price is higher, and production cost is bigger.Utilize the formic acid acidylate, the acylating agent ability a little less than, reaction conditions is had relatively high expectations, and side reaction is more, and utilizes the vitriol oil nitrated as solvent, produces a large amount of acid-bearing wastewaters, is difficult to administer.Utilize diacetyl oxide and mixed acid nitrification, diacetyl oxide is easily system drugs and price height, and reaction generates a large amount of acetic acid, can not recycle, after again through mixed acid nitrification, last handling process need consume a large amount of alkali lye, the production cost height, waste water is many.So all there are some defectives in more existing 2-methyl-4-N-methyl-p-nitroaniline preparation method, have to be solved.
Summary of the invention
The technical problem to be solved in the present invention provides the preparation method of 2-methyl-4-N-methyl-p-nitroaniline that a kind of technology is succinct, cost is low.
In order to solve the problems of the technologies described above, the invention provides the preparation method of a kind of 2-methyl-4-N-methyl-p-nitroaniline, may further comprise the steps successively:
1), acetate acidylate amido protecting
With the o-toluidine is raw material, is that acylating agent carries out the acidylate amido protecting with acetate, and temperature of reaction is 80 ℃～120 ℃, and in 1～5 hour reaction times, the mol ratio of acetate and o-toluidine is 2.0～4.0: 1;
2), nitrated
The reaction solution that with the concentrated nitric acid is nitrating agent and step 1) gained carries out nitration reaction, and temperature of reaction is 10～40 ℃, and the reaction times, the mol ratio of nitric acid and o-toluidine was 1.0～1.2: 1 at 3～6 hours; Get nitrated back solid;
3), hydrolysis
Be the reaction that is hydrolyzed of hydrolysing agent and nitrated back solid with the concentrated hydrochloric acid, the mol ratio of concentrated hydrochloric acid and o-toluidine is 2.5: 1, reacts under reflux state 2～3 hours;
4), separate purification
Regulating step 3) reaction solution of gained filters to PH=1～2, and gained filter cake recrystallization obtains 2-methyl-4-N-methyl-p-nitroaniline.
Improvement as the preparation method of 2-methyl of the present invention-4-N-methyl-p-nitroaniline: adopt the sodium hydroxide solution conditioned reaction liquid of mass concentration 10%～50% in the step 4), with mass concentration 50%～90% aqueous ethanolic solution recrystallization.
Further improvement as the preparation method of 2-methyl of the present invention-4-N-methyl-p-nitroaniline: after nitration reaction step 2) finishes, the gained reaction solution poured in 0～10 ℃ the cold water, with the solid drying of separating out, nitrated back solid.
In the present invention, concentrated nitric acid is meant that mass concentration is about 65% salpeter solution, and concentrated hydrochloric acid is meant that mass concentration is 35%～37% hydrochloric acid soln.
The present invention is raw material with the Ortho Toluidine at first, carries out amido protecting through the peracetic acid acetylize; Then direct adding concentrated nitric acid carries out nitrated, adopts hydrochloric acid to be hydrolyzed then, regulates pH value by alkali lye again, separates obtaining 2-methyl-4-N-methyl-p-nitroaniline.
Reaction equation of the present invention is as follows:
2-methyl of the present invention-4-N-methyl-p-nitroaniline preparation method has following advantage:
1, utilize acetate as acylating agent, the o-toluidine acetylize is generated ortho-methylacetanilid, thereby protection is amino.This invention has solved the formic acid poor activity, and Tosyl chloride and the high shortcoming of diacetyl oxide cost.
2, adopt concentrated nitric acid as nitrating agent: after acetylization reaction finishes, directly add concentrated nitric acid, compare, reduced the discharging of spent acid with utilizing mixed acid nitrification as nitrating agent, environmentally friendly.Acidylate and nitratedly carry out has continuously been saved the production time, and a little less than the oxidisability of acetate and nitric acid system, can have been reduced the generation of by product.
3, utilize alkali lye to regulate pH value, separated product 2-methyl-4-N-methyl-p-nitroaniline and its isomer, easy to operation.
Embodiment
The preparation method of embodiment 1, a kind of 2-methyl-4-N-methyl-p-nitroaniline is a starting raw material with the o-toluidine, carries out following steps successively:
(1) 45g (0.75mol) acetate is joined in the 250ml there-necked flask, drip 32.1g (0.3mol) o-toluidine, the control charge temperature is no more than 60 ℃.After dropwising, be warming up to 100 ℃ of reactions, reaction process constantly steams the water of generation, stopped reaction behind the 4h.
(2) with 32g (0.33mol) concentrated nitric acid (65%, Wt%, down with) slowly splash in the reaction solution of above-mentioned steps (1) gained, drip process water-bath cooling, maintain the temperature at below 30 ℃.Then at 30 ℃ of following isothermal reaction 5h; After reaction finishes, reaction solution is poured in 10 ℃ of cold water, separated out yellow solid, filtration, drying get nitrated back solid.
(3) with the 75ml concentrated hydrochloric acid (35%, Wt%, down with) join in the there-necked flask of 250ml, the nitrated back solid with step (2) gained adds then, at 90 ℃ of following heating reflux reaction 3h.
(4) after reaction finishes, in reaction solution, drip 30% (Wt%, down together) sodium hydroxide solution, be adjusted to PH=1.5, separate out yellow solid, separate out fully after, filter, filter cake is with 80% (Wt%, down together) aqueous ethanolic solution recrystallization, filtration drying, obtain 2-methyl-4-N-methyl-p-nitroaniline product 40.2g, yield 88.2% is analyzed through HPLC, purity 99%, fusing point are 130～131 ℃.
The preparation method of embodiment 2, a kind of 2-methyl-4-N-methyl-p-nitroaniline is a starting raw material with the o-toluidine, carries out following steps successively:
(1) 45g (0.75mol) acetate is joined in the 250ml there-necked flask, drip 32.1g (0.3mol) o-toluidine, the control charge temperature is no more than 60 ℃.After dropwising, be warming up to 100 ℃ of reactions, reaction process constantly steams the water of generation, stopped reaction behind the 4h.
(2) 32g (0.33mol) concentrated nitric acid (65%) is slowly splashed in the above-mentioned reaction solution, drip the cooling of process ice-water bath, the control charge temperature is no more than 10 ℃.At 10 ℃ of following isothermal reaction 5h, after reaction finishes, reaction solution is poured in 10 ℃ of cold water then, separated out yellow solid, filtration, drying get nitrated back solid.
(3) 75ml concentrated hydrochloric acid (35%) is joined in the there-necked flask of 250ml, then nitrated back solid is added, at 90 ℃ of following heating reflux reaction 3h.
(4) after reaction finishes, in reaction solution, drip 10% sodium hydroxide solution, drop to PH=2.0, separate out yellow solid, separate out fully, filter, filter cake obtains 2-methyl-4-N-methyl-p-nitroaniline product 36.0g with 50% aqueous ethanolic solution recrystallization, yield reaches 78.9%, analyze through HPLC, purity 97%, fusing point is 129～131 ℃.
The preparation method of embodiment 3, a kind of 2-methyl-4-N-methyl-p-nitroaniline is a starting raw material with the o-toluidine, carries out following steps successively:
(1) 45g (0.75mol) acetate is joined in the 250ml there-necked flask, drip 32.1g (0.3mol) o-toluidine, the control charge temperature is no more than 60 ℃.After dropwising, be warming up to 100 ℃ of reactions, reaction process constantly steams the water of generation, stopped reaction behind the 4h.
(2) 32g (0.33mol) concentrated nitric acid (65%) is slowly splashed in the above-mentioned reaction solution, drip process water-bath cooling, the control charge temperature is no more than 40 ℃.At 40 ℃ of following isothermal reaction 5h, after reaction finishes, reaction solution is poured in 10 ℃ of cold water then, separated out yellow solid, filtration, drying get nitrated back solid.
(3) with 75ml concentrated hydrochloric acid (35%), join in the there-necked flask of 250ml, then nitrated back solid is added, at 90 ℃ of following heating reflux reaction 3h.
(4) after reaction finishes, Dropwise 5 0% sodium hydroxide solution drops to PH=1.0 in reaction solution, separates out yellow solid, separate out fully, filter, filter cake obtains 2-methyl-4-N-methyl-p-nitroaniline product 38.1g with 90% aqueous ethanolic solution recrystallization, yield reaches 83.6%, analyze through HPLC, purity 98%, fusing point is 129～130 ℃.
The preparation method of embodiment 4, a kind of 2-methyl-4-N-methyl-p-nitroaniline is a starting raw material with the o-toluidine, carries out following steps successively:
(1) 36g (0.6mol) acetate is joined in the 250ml there-necked flask, drip 32.1g (0.3mol) o-toluidine, the control charge temperature is no more than 60 ℃.After dropwising, be warming up to 100 ℃ of reactions, reaction process constantly steams the water of generation, stopped reaction behind the 4h.
(2) 32g (0.33mol) concentrated nitric acid (65%) is slowly splashed in the above-mentioned reaction solution, drip process water-bath cooling, the control charge temperature is no more than 30 ℃.At 30 ℃ of isothermal reaction 5h, after reaction finishes, reaction solution is poured in 10 ℃ of cold water then, separated out yellow solid, filtration, drying get nitrated back solid.
(3) with 75ml concentrated hydrochloric acid (35%), join in the there-necked flask of 250ml, then nitrated back solid is added, at 90 ℃ of following heating reflux reaction 3h.
(4) after reaction finishes, in reaction solution, drip 30% sodium hydroxide solution, drop to PH=1.5, separate out yellow solid, separate out fully, filter, filter cake obtains 2-methyl-4-N-methyl-p-nitroaniline product 37.2g with 80% aqueous ethanolic solution recrystallization, yield reaches 81.6%, analyze through HPLC, purity 98%, fusing point is 129～130 ℃.
The preparation method of embodiment 5, a kind of 2-methyl-4-N-methyl-p-nitroaniline is a starting raw material with the o-toluidine, carries out following steps successively:
(1) 72g (1.2mol) acetate is joined in the 250ml there-necked flask, drip 32.1g (0.3mol) o-toluidine, the control charge temperature is no more than 60 ℃.After dropwising, be warming up to 100 ℃ of reactions, reaction process constantly steams the water of generation, stopped reaction behind the 3h
(2) 32g (0.33mol) concentrated nitric acid (65%) is slowly splashed in the above-mentioned reaction solution, drip process water-bath cooling, the control charge temperature is no more than 30 ℃.At 30 ℃ of isothermal reaction 5h, after reaction finishes, reaction solution is poured in 10 ℃ of cold water then, separated out yellow solid, filtration, drying get nitrated back solid.
(3) 75ml concentrated hydrochloric acid (35%) is joined in the there-necked flask of 250ml, then nitrated back solid is added, at 90 ℃ of following heating reflux reaction 3h.
(4) after reaction finishes, in reaction solution, drip 30% sodium hydroxide solution, drop to PH=1.5, separate out yellow solid, separate out fully, filter, filter cake obtains 2-methyl-4-N-methyl-p-nitroaniline product 40.5g with 80% aqueous ethanolic solution recrystallization, yield reaches 88.8%, analyze through HPLC, purity 99%, fusing point is 130～131 ℃.
The preparation method of embodiment 6, a kind of 2-methyl-4-N-methyl-p-nitroaniline is a starting raw material with the o-toluidine, carries out following steps successively:
(1) 45g (0.75mol) acetate is joined in the 250ml there-necked flask, drip 32.1g (0.3mol) o-toluidine, the control charge temperature is no more than 60 ℃.After dropwising, be warming up to 100 ℃ of reactions, reaction process constantly steams the water of generation, stopped reaction behind the 5h.
(2) 29.1g (0.3mol) concentrated nitric acid (65%) is slowly splashed in the above-mentioned reaction solution, drip process water-bath cooling, the control charge temperature is no more than 30 ℃.At 30 ℃ of isothermal reaction 5h, after reaction finishes, reaction solution is poured in 10 ℃ of cold water then, separated out yellow solid, filtration, drying get nitrated back solid.
(3) with 75ml concentrated hydrochloric acid (35%), join in the there-necked flask of 250ml, then nitrated back solid is added, at 90 ℃ of following heating reflux reaction 3h.
(4) after reaction finishes, in reaction solution, drip 30% sodium hydroxide solution, drop to PH=1.5, separate out yellow solid, separate out fully, filter, filter cake obtains 2-methyl-4-N-methyl-p-nitroaniline product 36.4g with 80% aqueous ethanolic solution recrystallization, yield reaches 79.8%, analyze through HPLC, purity 98%, fusing point is 129～130 ℃.
The preparation method of embodiment 7, a kind of 2-methyl-4-N-methyl-p-nitroaniline is a starting raw material with the o-toluidine, carries out following steps successively:
(1) 45g (0.75mol) acetate is joined in the 250ml there-necked flask, drip 32.1g (0.3mol) o-toluidine, the control charge temperature is no more than 60 ℃.After dropwising, be warming up to 100 ℃ of reactions, reaction process constantly steams the water of generation, stopped reaction behind the 4h.
(2) 34.9g (0.36mol) concentrated nitric acid (65%) is slowly splashed in the above-mentioned reaction solution, drip process water-bath cooling, the control charge temperature is no more than 30 ℃.At 30 ℃ of isothermal reaction 5h, after reaction finishes, reaction solution is poured in 10 ℃ of cold water then, separated out yellow solid, filtration, drying get nitrated back solid.
(3) 75ml concentrated hydrochloric acid (35%) is joined in the there-necked flask of 250ml, then nitrated back solid is added, at 90 ℃ of following heating reflux reaction 3h.
(4) after reaction finishes, in reaction solution, drip 30% sodium hydroxide solution, drop to PH=1.5, separate out yellow solid, separate out fully, filter, filter cake obtains 2-methyl-4-N-methyl-p-nitroaniline product 37.9g with 80% aqueous ethanolic solution recrystallization, yield reaches 83.1%, analyze through HPLC, purity 99%, fusing point is 130～131 ℃.
The preparation method of embodiment 8, a kind of 2-methyl-4-N-methyl-p-nitroaniline is a starting raw material with the o-toluidine, carries out following steps successively:
(1) 45g (0.75mol) acetate is joined in the 250ml there-necked flask, drip 32.1g (0.3mol) o-toluidine, the control charge temperature is no more than 60 ℃.After dropwising, be warming up to 80 ℃ of reactions, stopped reaction behind the 5h.
(2) 32g (0.33mol) concentrated nitric acid (65%) is slowly splashed in the above-mentioned reaction solution, drip process water-bath cooling, the control charge temperature is no more than 30 ℃.At 30 ℃ of isothermal reaction 3h, after reaction finishes, reaction solution is poured in 10 ℃ of cold water then, separated out yellow solid, filtration, drying get nitrated back solid.
(3) with 75ml concentrated hydrochloric acid (35%), join in the there-necked flask of 250ml, then nitrated back solid is added, at 90 ℃ of following heating reflux reaction 3h.After reaction finishes, in reaction solution, drip 30% sodium hydroxide solution, drop to PH=1.5, separate out yellow solid, separate out fully, filter, filter cake obtains 2-methyl-4-N-methyl-p-nitroaniline product 37.1g with 80% aqueous ethanolic solution recrystallization, yield reaches 81.4%, analyze purity 97%, 127～129 ℃ of fusing points through HPLC.
The preparation method of embodiment 9, a kind of 2-methyl-4-N-methyl-p-nitroaniline is a starting raw material with the o-toluidine, carries out following steps successively:
(1) 45g (0.75mol) acetate is joined in the 250ml there-necked flask, drip 32.1g (0.3mol) o-toluidine, the control charge temperature is no more than 60 ℃.After dropwising, be warming up to 100 ℃ of reactions, reaction process constantly steams the water of generation, stopped reaction behind the 2h.
(2) 32g (0.33mol) concentrated nitric acid (65%) is slowly splashed in the above-mentioned reaction solution, drip process water-bath cooling, the control charge temperature is no more than 30 ℃.At 30 ℃ of isothermal reaction 6h, after reaction finishes, reaction solution is poured in 10 ℃ of cold water then, separated out yellow solid, filtration, drying get nitrated back solid.
(3) 75ml concentrated hydrochloric acid (35%) is joined in the there-necked flask of 250ml, then nitrated back solid is added, at 90 ℃ of following heating reflux reaction 3h.
(4) after reaction finishes, in reaction solution, drip 30% sodium hydroxide solution, drop to PH=1.5, separate out yellow solid, separate out fully, filter, filter cake obtains 2-methyl-4-N-methyl-p-nitroaniline product 37.3g with 80% aqueous ethanolic solution recrystallization, yield reaches 81.8%, analyze through HPLC, purity 98%, fusing point is 129～130 ℃.
The preparation method of embodiment 10, a kind of 2-methyl-4-N-methyl-p-nitroaniline is a starting raw material with the o-toluidine, carries out following steps successively:
(1) 45g (0.75mol) acetate is joined in the 250ml there-necked flask, drip 32.1g (0.3mol) o-toluidine, the control charge temperature is no more than 60 ℃.After dropwising, be warming up to 120 ℃ of reactions, reaction process constantly steams the water of generation, stopped reaction behind the 1.5h.
(2) 32g (0.33mol) concentrated nitric acid (65%) is slowly splashed in the above-mentioned reaction solution, drip process water-bath cooling, the control charge temperature is no more than 30 ℃.At 30 ℃ of following isothermal reaction 5h, after reaction finishes, reaction solution is poured in 10 ℃ of cold water then, separated out yellow solid, filtration, drying get nitrated back solid.
(3) 75ml concentrated hydrochloric acid (35%) is joined in the there-necked flask of 250ml, then nitrated back solid is added, at 90 ℃ of following heating reflux reaction 3h.
(4) after reaction finishes, in reaction solution, drip 30% sodium hydroxide solution, drop to PH=1.5, separate out yellow solid, separate out fully, filter, filter cake obtains 2-methyl-4-N-methyl-p-nitroaniline product 35.7g with 80% aqueous ethanolic solution recrystallization, yield reaches 78.3%, analyze through HPLC, purity 97%, fusing point is 125～127 ℃.
The preparation method of embodiment 11, a kind of 2-methyl-4-N-methyl-p-nitroaniline is a starting raw material with the o-toluidine, carries out following steps successively:
(1) 45g (0.75mol) acetate is joined in the 250ml there-necked flask, drip 32.1g (0.3mol) o-toluidine, the control charge temperature is no more than 60 ℃.After dropwising, be warming up to 100 ℃ of reactions, reaction process constantly steams the water of generation, stopped reaction behind the 5h.
(2) 32g (0.33mol) concentrated nitric acid (65%) is slowly splashed in the above-mentioned reaction solution, drip process water-bath cooling, the control charge temperature is no more than 30 ℃.At 30 ℃ of following isothermal reaction 5h, after reaction finishes, reaction solution is poured in 10 ℃ of cold water then, separated out yellow solid, filtration, drying get nitrated back solid.
(3) 75ml concentrated hydrochloric acid (35%) is joined in the there-necked flask of 250ml, then nitrated back solid is added, at 90 ℃ of following heating reflux reaction 3h.
(4) after reaction finishes, in reaction solution, drip 30% sodium hydroxide solution, drop to PH=1.5, separate out yellow solid, separate out fully, filter, filter cake obtains 2-methyl-4-N-methyl-p-nitroaniline product 38.4g with 80% aqueous ethanolic solution recrystallization, yield reaches 84.2%, analyze through HPLC, purity 99%, fusing point is 130～131 ℃.
At last, it is also to be noted that what more than enumerate only is several specific embodiments of the present invention.Obviously, the invention is not restricted to above embodiment, many distortion can also be arranged.All distortion that those of ordinary skill in the art can directly derive or associate from content disclosed by the invention all should be thought protection scope of the present invention.
Claims (3)
1. the preparation method of 2-methyl-4-N-methyl-p-nitroaniline is characterized in that may further comprise the steps successively:
1), acetate acidylate amido protecting
With the o-toluidine is raw material, is that acylating agent carries out the acidylate amido protecting with acetate, and temperature of reaction is 80 ℃～120 ℃, and in 1～5 hour reaction times, the mol ratio of described acetate and o-toluidine is 2.0～4.0: 1;
2), nitrated
The reaction solution that with the concentrated nitric acid is nitrating agent and step 1) gained carries out nitration reaction, and temperature of reaction is 10～40 ℃, and the reaction times, the mol ratio of described nitric acid and o-toluidine was 1.0～1.2: 1 at 3～6 hours; Get nitrated back solid;
3), hydrolysis
Be the reaction that is hydrolyzed of hydrolysing agent and nitrated back solid with the concentrated hydrochloric acid, the mol ratio of concentrated hydrochloric acid and o-toluidine is 2.5: 1, reacts under reflux state 2～3 hours;
4), separate purification
Regulating step 3) reaction solution of gained filters to PH=1～2, and gained filter cake recrystallization obtains 2-methyl-4-N-methyl-p-nitroaniline.
2. the preparation method of 2-methyl according to claim 1-4-N-methyl-p-nitroaniline is characterized in that: adopt the sodium hydroxide solution conditioned reaction liquid of mass concentration 10%～50% in the described step 4), with mass concentration 50%～90% aqueous ethanolic solution recrystallization.
3. the preparation method of 2-methyl according to claim 2-4-N-methyl-p-nitroaniline is characterized in that: step 2) nitration reaction finish after, the gained reaction solution poured in 0～10 ℃ the cold water, with the solid drying of separating out, nitrated back solid.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102070466A (en) * | 2010-12-28 | 2011-05-25 | 天津市筠凯化工科技有限公司 | Preparation method of 5-chiorine-2-nitroaniline |
| CN105218375A (en) * | 2015-10-31 | 2016-01-06 | 丁玉琴 | A kind of synthetic method of 2-methyl-4-nitrobenzoic acid |
| CN109776337A (en) * | 2019-03-07 | 2019-05-21 | 福建振新化学有限公司 | The preparation method of 2- methoxyl group -4- nitroaniline |
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| CN113429309A (en) * | 2021-06-28 | 2021-09-24 | 浙江闰土股份有限公司 | Preparation method of 3,3 '-dinitro-4, 4' -diacetyl amino diphenyl ether |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102070466A (en) * | 2010-12-28 | 2011-05-25 | 天津市筠凯化工科技有限公司 | Preparation method of 5-chiorine-2-nitroaniline |
| CN105218375A (en) * | 2015-10-31 | 2016-01-06 | 丁玉琴 | A kind of synthetic method of 2-methyl-4-nitrobenzoic acid |
| CN109851127A (en) * | 2019-02-01 | 2019-06-07 | 山东世纪阳光科技有限公司 | A kind of processing method of large red-based g spent acid |
| CN109776337A (en) * | 2019-03-07 | 2019-05-21 | 福建振新化学有限公司 | The preparation method of 2- methoxyl group -4- nitroaniline |
| CN109942434A (en) * | 2019-03-26 | 2019-06-28 | 山东世纪阳光科技有限公司 | A kind of production method of large red-based g |
| CN113429309A (en) * | 2021-06-28 | 2021-09-24 | 浙江闰土股份有限公司 | Preparation method of 3,3 '-dinitro-4, 4' -diacetyl amino diphenyl ether |
| US11851387B2 (en) | 2021-08-18 | 2023-12-26 | Yuanhan Materials Inc. | Para-phenylenediamine derivative, 1,4-cyclohexyldiamine derivative, and fabricating method for 1,4-diamine cyclic compound derivative |
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