CN105348251A - 3,4-methylenedioxy aniline preparation method - Google Patents
3,4-methylenedioxy aniline preparation method Download PDFInfo
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- CN105348251A CN105348251A CN201510882800.5A CN201510882800A CN105348251A CN 105348251 A CN105348251 A CN 105348251A CN 201510882800 A CN201510882800 A CN 201510882800A CN 105348251 A CN105348251 A CN 105348251A
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- methylene
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- dioxy
- mirbane
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- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- XGNXYCFREOZBOL-UHFFFAOYSA-N 1,3-benzodioxol-5-amine Chemical compound NC1=CC=C2OCOC2=C1 XGNXYCFREOZBOL-UHFFFAOYSA-N 0.000 title abstract 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims abstract description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
- 239000001257 hydrogen Substances 0.000 claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 238000001914 filtration Methods 0.000 claims abstract description 22
- 238000003756 stirring Methods 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910017604 nitric acid Inorganic materials 0.000 claims abstract description 12
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 11
- 238000004821 distillation Methods 0.000 claims abstract description 11
- 239000008213 purified water Substances 0.000 claims abstract description 11
- 239000000126 substance Substances 0.000 claims abstract description 11
- 238000005406 washing Methods 0.000 claims abstract description 11
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims abstract description 3
- 238000001816 cooling Methods 0.000 claims abstract description 3
- 238000001291 vacuum drying Methods 0.000 claims abstract description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 74
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 49
- -1 3,4-methylene Chemical group 0.000 claims description 32
- 150000005529 1,3-benzodioxoles Chemical class 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 229910052759 nickel Inorganic materials 0.000 claims description 21
- 238000005516 engineering process Methods 0.000 claims description 18
- 239000000428 dust Substances 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- 238000001035 drying Methods 0.000 claims description 12
- 238000011084 recovery Methods 0.000 claims description 11
- 238000009413 insulation Methods 0.000 claims description 10
- 238000000199 molecular distillation Methods 0.000 claims description 10
- 230000007935 neutral effect Effects 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 238000002791 soaking Methods 0.000 claims description 4
- 238000010790 dilution Methods 0.000 claims description 2
- 239000012895 dilution Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- 238000005984 hydrogenation reaction Methods 0.000 abstract description 9
- 239000003054 catalyst Substances 0.000 abstract description 4
- 239000003960 organic solvent Substances 0.000 abstract description 4
- 230000008901 benefit Effects 0.000 abstract description 3
- 239000002351 wastewater Substances 0.000 abstract description 2
- SNWQAKNKGGOVMO-UHFFFAOYSA-N 5-nitro-1,3-benzodioxole Chemical compound [O-][N+](=O)C1=CC=C2OCOC2=C1 SNWQAKNKGGOVMO-UHFFFAOYSA-N 0.000 abstract 3
- 238000010438 heat treatment Methods 0.000 abstract 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
- 238000004321 preservation Methods 0.000 abstract 1
- 238000011946 reduction process Methods 0.000 abstract 1
- 239000002910 solid waste Substances 0.000 abstract 1
- 238000005292 vacuum distillation Methods 0.000 abstract 1
- 239000002912 waste gas Substances 0.000 abstract 1
- 238000010792 warming Methods 0.000 description 19
- 239000002904 solvent Substances 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 11
- 150000001448 anilines Chemical class 0.000 description 7
- 239000002994 raw material Substances 0.000 description 6
- 239000006002 Pepper Substances 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000002566 Capsicum Nutrition 0.000 description 3
- 241000722363 Piper Species 0.000 description 3
- 235000016761 Piper aduncum Nutrition 0.000 description 3
- 235000017804 Piper guineense Nutrition 0.000 description 3
- 235000008184 Piper nigrum Nutrition 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 238000011020 pilot scale process Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- UIOFUWFRIANQPC-JKIFEVAISA-N Floxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl UIOFUWFRIANQPC-JKIFEVAISA-N 0.000 description 1
- KYGZCKSPAKDVKC-UHFFFAOYSA-N Oxolinic acid Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC2=C1OCO2 KYGZCKSPAKDVKC-UHFFFAOYSA-N 0.000 description 1
- LUSZGTFNYDARNI-UHFFFAOYSA-N Sesamol Natural products OC1=CC=C2OCOC2=C1 LUSZGTFNYDARNI-UHFFFAOYSA-N 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960004621 cinoxacin Drugs 0.000 description 1
- VDUWPHTZYNWKRN-UHFFFAOYSA-N cinoxacin Chemical compound C1=C2N(CC)N=C(C(O)=O)C(=O)C2=CC2=C1OCO2 VDUWPHTZYNWKRN-UHFFFAOYSA-N 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000001465 metallisation Methods 0.000 description 1
- 230000000802 nitrating effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229960000321 oxolinic acid Drugs 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 atoms of the carbocyclic ring
- C07D317/66—Nitrogen atoms not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A 3,4-methylenedioxy aniline preparation method applied to the field of chemosynthesis comprises the following steps: (1) adding dilute nitric acid into a reaction vessel for heating; (2) dropwise adding 1,2-methylenedioxy benzene into the reaction vessel slowly, carrying out intense stirring during the dropwise adding, and carrying out heat preservation after the dropwise adding is finished; (3) carrying out cooling and filtration to obtain a wet product of 3,4-methylenedioxy nitrobenzene, carrying out washing with purified water till the pH value of the wet product reaches 7, and carrying out vacuum drying to obtain 3,4-methylenedioxy nitrobenzene; (4) putting 3,4-methylenedioxy nitrobenzene, a nickel catalyst and one or more reaction solvents into a high-pressure reaction kettle for heating, injecting hydrogen, filtering out the nickel catalyst after the reaction is finished, carrying out high vacuum distillation after a low-boiling-point substance is removed through reduced pressure distillation, and collecting fractions to obtain 3,4-methylenedioxy aniline. The 3,4-methylenedioxy aniline preparation method has the advantages that nitrification reduction and hydrogenation reduction processes are adopted; less waste water, waste gas and solid waste are treated; the selectivity is high; the product treatment is easy; the product yield and the product quality are high; nitric acid, the hydrogenation catalyst and the hydrogenation organic solvents can be recovered for direct application.
Description
Technical field
The one that the present invention relates in the field of chemical synthesis is the method that 3,4-methylene dioxo group aniline prepared by raw material with 1,2-methylenedioxybenzenes.
Background technology
3,4-methylene dioxo group aniline, also known as pepper amine, molecular formula is C
7h
7nO
2pepper amine is a kind of very important dyestuff and medicine intermediate, with it for raw material can develop the derived product of multiple high added value, as synthetized oxidation preventive agent and pharmaceutical intermediate sesamol, prepare antimicrobial drug oxolinic acid and cinoxacin, the medicine of synthesis treatment hepatic diseases and anti-tumor drug, the application of pepper amine widely, all has the larger market requirement both at home and abroad.
The preparation of current pepper amine mainly contains two preparation were establisheds, and one is be that raw material is prepared through halogenation, diazotizing method with 1,2-methylenedioxybenzenes, and another kind is be that raw material is prepared through method that is nitrated, reduction with 1,2-methylenedioxybenzenes.But diazonium halide metallization processes is difficult to be separated with unreacted intermediate at the finished product of rear step, cannot realize industrialization, and current industrialization adopts nitrated, reducing process mostly, and Sodium Sulphide method yield in reducing process is low, under alkaline medium, aminocompound is easily oxidized, and application seldom; Metallic reducing environmental pollution is serious, and waste water and dregs process is very difficult.Therefore, the preparation method developing a kind of 3,4-methylene dioxo group aniline is new problem urgently to be resolved hurrily at present.
Summary of the invention
The object of the present invention is to provide a kind of 3, the preparation method of 4-methylene dioxo group aniline, the method is with 1,2-methylenedioxybenzenes is raw material, wherein nitration reaction adopts the slow feed of high temperature constant temperature and rapid stirring, reaction process is more gentle, avoid Yin Wendu to rise suddenly and sharply and the side reaction caused increases the disadvantageous effect with mass yield difference, the method yield is high, cost is low, simple to operate, the recovery that achieves nitric acid and hydrogenation catalyst and hydrogenation organic solvent, be applicable to industrialized production, 3, the 4-methylene dioxo group aniline content produced are high, impurity is few.
The object of the present invention is achieved like this: a kind of preparation method of 3,4-methylene dioxo group aniline, described method comprises the steps:
(1) dust technology is added in retort heat up;
(2) in above-mentioned retort, slowly drip 1,2-methylenedioxybenzenes, vigorous stirring, dropwises rear insulation simultaneously;
(3) after cooling, filtration obtains wet product 3,4-methylene-dioxy oil of mirbane, and purified water washing is neutral to pH value, and vacuum-drying, obtains 3,4-methylene-dioxy oil of mirbane;
(4) 3,4-methylene-dioxy oil of mirbane and nickel catalyzator, reaction solvent are dropped in autoclave, heat up, pass into hydrogen, reaction terminates rear filtration catalizer, and underpressure distillation carries out molecular distillation after removing low-boiling-point substance, collect cut, obtain 3,4-methylene dioxo group aniline;
In step (1), described dust technology concentration is 15%-30%, and preferred concentration is 20%-25%, and the temperature that described intensification reaches is 50-70 DEG C, and preferable temperature is 50-60 DEG C; 1,2-described methylenedioxybenzenes and the mol ratio 1:1.5-3 of nitric acid, the mol ratio 1:2.0-3 of preferred 1,2-methylenedioxybenzenes and nitric acid; In step (2), the speed of described slow dropping is 0.2-0.5g/min, and the speed preferably dripped is 0.3-0.4g/min; The speed of described vigorous stirring is 300-600r/min, and the speed of preferred vigorous stirring is 400-600r/min; Described soaking time is 0.3-1 hour, and preferred soaking time is 0.5 hour; In step (1), described dust technology is concentrated nitric acid dilution preparation or recovery, and what dust technology can be applied mechanically batch criticizes for 10-30; In step (3), described in be cooled to temperature range be 15-25 DEG C, be preferably cooled to 20 DEG C; Described drying for carry out drying under 40 DEG C of vacuum 0.09MPa; In step (4), described reaction solvent is selected from one or more in ethanol, acetone, toluene, ethyl acetate, and described reaction solvent is recyclable to be applied mechanically; In step (4), the temperature that described intensification reaches is 50-90 DEG C, and the temperature reached that preferably heats up is 60 DEG C, and described logical hydrogen is continue logical H-H reaction under a certain pressure, and then the logical hydrogen of interval is to hydrogen-pressure is constant; The described pressure continuing logical hydrogen is 1.5-4.0MPa, and preferred pressure is 2.5MPa; The described time continuing logical H-H reaction is 1.5-2.5 hour, preferably 2 hours; In step (4), described nickel catalyzator is skeletal nickel catalyst, described nickel catalyzator is the mixture of fresh nickel accelerant or upper batch of recovery nickel accelerant or fresh nickel accelerant and recovery nickel accelerant, and what described nickel catalyzator can be applied mechanically batch criticizes for 60-120; In step (4), described cut is the cut collected at 80-160Pa, 100-120 DEG C, described by 3, it is 3,4-methylene-dioxy oil of mirbane and nickel catalyzator, reaction solvent are dropped into successively in autoclave that 4-methylene-dioxy oil of mirbane and nickel catalyzator, reaction solvent drop in autoclave.
Main points of the present invention there are provided a kind of with 1,2-methylenedioxybenzenes is that raw material prepares 3, the method of 4-methylene dioxo group aniline, its principle is: the methylene-dioxy of (1) 1,2-methylenedioxybenzenes is first kind orientating group, reactive behavior is higher, can direct nitric acid nitrating, intermediate 3,4-methylene-dioxy oil of mirbane is directly separated out from reaction solution, reduce environmental pollution, the nitrated transformation efficiency more than 95% of dust technology; (2) nitration reaction, adopt the slow feed of high temperature constant temperature and rapid stirring, reaction process is more gentle, thus avoids that Yin Wendu rises suddenly and sharply and the side reaction that causes increases the disadvantageous effect with mass yield difference; (3) hydro-reduction, preferred low-cost skeleton nickel, effectively reduces costs, and improves active and environmental benefit; (4) achieve the recovery of nitric acid and hydrogenation catalyst and hydrogenation organic solvent, reduce costs further; (5) the method shows through pilot scale trial production, and pilot scale effect is suitable with lab scale effect, and after this patent is implemented, 3,4-methylene dioxo group aniline purity can reach more than 99%, and yield can reach more than 95%.
A kind of 3, the preparation method of 4-methylene dioxo group aniline compared with prior art, have and adopt nitrated, hydro-reduction technique, three-protection design is few, and yield is high, and selectivity is good, product easily processes, product yield is high and quality is good, and nitric acid and hydrogenation catalyst and the recyclable advantage such as to apply mechanically of hydrogenation organic solvent, will be widely used in the field of chemical synthesis.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of step reaction before the present invention.
Fig. 2 is the synthetic route chart walking reaction after the present invention.
Embodiment
Embodiment one
By scale 81.9g(1.3mol) 25% dust technology add in retort, be warming up to certain temperature, described in be warming up to the selection situation of certain temperature in table 1; Slowly 63.65g(0.52mol is dripped with 0.4g/min speed to retort) 1,2-methylenedioxybenzenes, simultaneously with the speed vigorous stirring of 400r/min, dropwise rear insulation 0.5 hour, be cooled to 20 DEG C of filtrations and obtain wet product 3,4-methylene-dioxy oil of mirbane, purified water washing is neutral to pH value, carries out drying, obtain 3 under 40 DEG C of vacuum 0.09MPa, 4-methylene-dioxy oil of mirbane intermediate, yield and purity situation are in table 1.By 3,4-methylene-dioxy oil of mirbane, skeletal nickel catalyst and ethanol drop into autoclave successively, and then exhausted air starts to pass into hydrogen when being warming up to 60 DEG C, logical H-H reaction 2h is continued under 2.5MPa pressure, then the logical hydrogen of interval is to hydrogen-pressure is constant, carries out underpressure distillation, steam and carry out molecular distillation again except after low-boiling-point substance water and solvent after filtration catalizer, collect 80-160Pa, 100-110 DEG C of cut, obtain finished product 3,4-methylene dioxo group aniline, yield and purity situation are in table 1.
Table 1: be warming up to the selection situation of certain temperature and 3,4-methylene-dioxy oil of mirbane, the yield of 3,4-methylene dioxo group anilines and purity situation
| Sequence number | Warming temperature DEG C | 3,4-methylene-dioxy oil of mirbane yield % | Purity % | 3,4-methylene dioxo group aniline molar yield % | Purity % |
| 1 | 30-35 | 75.6 | 98.4 | 72.6 | 98.50 |
| 2 | 40-45 | 80.2 | 98.7 | 77 | 98.60 |
| 3 | 50-60 | 99.8 | 99.2 | 95.9 | 99.40 |
| 4 | 65-70 | 94.8 | 98.5 | 90.7 | 98.20 |
Embodiment two
By scale 81.9g(1.3mol) 25% dust technology add in retort, be warming up to 50-60 DEG C, slowly drip 63.65g(0.52mol to retort with certain speed) 1,2-methylenedioxybenzenes, the selection situation of the speed of described dropping 1,2-methylenedioxybenzenes is in table 2; Simultaneously with the speed vigorous stirring of 400r/min, dropwise rear insulation 0.5 hour, be cooled to 20 DEG C of filtrations and obtain wet product 3,4-methylene-dioxy oil of mirbane, purified water washing is neutral to pH value, carries out drying, obtain 3 under 40 DEG C of vacuum 0.09MPa, 4-methylene-dioxy oil of mirbane intermediate, yield and purity situation are in table 2.By 3,4-methylene-dioxy oil of mirbane, skeletal nickel catalyst and ethanol drop into autoclave successively, and then exhausted air starts to pass into hydrogen when being warming up to 60 DEG C, logical H-H reaction 2h is continued under 2.5MPa pressure, then the logical hydrogen of interval is to hydrogen-pressure is constant, carries out underpressure distillation, steam and carry out molecular distillation again except after low-boiling-point substance water and solvent after filtration catalizer, collect 80-160Pa, 100-110 DEG C of cut, obtain finished product 3,4-methylene dioxo group aniline, yield and purity situation are in table 2.
Table 2: drip the selection situation of the speed of 1,2-methylenedioxybenzenes and 3,4-methylene-dioxy oil of mirbane, the yield of 3,4-methylene dioxo group anilines and purity
| Sequence number | Rate of addition g/min | 3,4-methylene-dioxy oil of mirbane yield % | Purity % | 3,4-methylene dioxo group aniline molar yield % | Purity % |
| 1 | 0.2 | 93.6 | 98.9 | 90.1 | 98.10 |
| 2 | 0.3 | 98.7 | 98.6 | 95 | 98.50 |
| 3 | 0.4 | 99.8 | 99.2 | 95.9 | 99.40 |
| 4 | 0.5 | 92.1 | 98.5 | 88.6 | 98.30 |
Embodiment three
By scale 81.9g(1.3mol) 25% dust technology add in retort, be warming up to 50-60 DEG C, slowly drip 63.65g(0.52mol to retort with 0.4g/min speed) 1,2-methylenedioxybenzenes, simultaneously with certain speed vigorous stirring, the selection situation of the speed of described stirring is in table 3; Dropwise rear insulation 0.5 hour, be cooled to 20 DEG C of filtrations and obtain wet product 3,4-methylene-dioxy oil of mirbane, purified water washing is neutral to pH value, carries out drying, obtain 3 under 40 DEG C of vacuum 0.09MPa, 4-methylene-dioxy oil of mirbane intermediate, yield and purity situation are in table 3.By 3,4-methylene-dioxy oil of mirbane, skeletal nickel catalyst and ethanol drop into autoclave successively, and then exhausted air starts to pass into hydrogen when being warming up to 60 DEG C, logical H-H reaction 2h is continued under 2.5MPa pressure, then the logical hydrogen of interval is to hydrogen-pressure is constant, carries out underpressure distillation, steam and carry out molecular distillation again except after low-boiling-point substance water and solvent after filtration catalizer, collect 80-160Pa, 100-110 DEG C of cut, obtain finished product 3,4-methylene dioxo group aniline, yield and purity situation are in table 3.
Table 3: the yield of the selection situation of the speed of stirring and 3,4-methylene-dioxy oil of mirbane, 3,4-methylene dioxo group anilines and purity
| Sequence number | The speed r/min stirred | 3,4-methylene-dioxy oil of mirbane yield % | Purity % | 3,4-methylene dioxo group aniline molar yield % | Purity % |
| 1 | 200 | 88.8 | 98.6 | 85.6 | 98.70 |
| 2 | 300 | 98.2 | 98.4 | 94.9 | 98.80 |
| 3 | 400 | 99.8 | 99.2 | 95.9 | 99.40 |
| 4 | 500 | 99.6 | 99.1 | 95.5 | 99.40 |
| 5 | 600 | 99.7 | 99.4 | 95.7 | 99.30 |
Embodiment four
By scale 81.9g(1.3mol) 25% dust technology add in retort, be warming up to 50-60 DEG C, slowly drip a certain amount of 1,2-methylenedioxybenzenes to retort with 0.4g/min speed, the selection situation situation of the different dripping quantity of described 1,2-methylenedioxybenzenes is in table 4; Simultaneously with the speed vigorous stirring of 400r/min, dropwise rear insulation 0.5 hour, be cooled to 20 DEG C of filtrations and obtain wet product 3,4-methylene-dioxy oil of mirbane, purified water washing is neutral to pH value, carries out drying, obtain 3 under 40 DEG C of vacuum 0.09MPa, 4-methylene-dioxy oil of mirbane intermediate, yield and purity situation situation are in table 4.By 3,4-methylene-dioxy oil of mirbane, skeletal nickel catalyst and ethanol drop into autoclave successively, and then exhausted air starts to pass into hydrogen when being warming up to 60 DEG C, logical H-H reaction 2h is continued under 2.5MPa pressure, then the logical hydrogen of interval is to hydrogen-pressure is constant, carries out underpressure distillation, steam and carry out molecular distillation again except after low-boiling-point substance water and solvent after filtration catalizer, collect 80-160Pa, 100-110 DEG C of cut, obtain finished product 3,4-methylene dioxo group aniline, yield and purity situation are in table 4.
The yield of the selection situation of the different dripping quantity of table 4:1,2-methylenedioxybenzenes and 3,4-methylene-dioxy oil of mirbane, 3,4-methylene dioxo group anilines and purity
| Sequence number | The different add-ons of 1,2-methylenedioxybenzenes | 3,4-methylene-dioxy oil of mirbane yield % | Purity % | 3,4-methylene dioxo group aniline molar yield % | Purity % |
| 1 | 105.84g，0.87mol（n=1.5） | 97.7 | 98.2 | 93.8 | 98.60 |
| 2 | 79.38g，0.65mol（n=2.0） | 99.2 | 98.7 | 95.1 | 99.00 |
| 3 | 63.65g，0.52mol（n=2.5） | 99.8 | 99.2 | 95.9 | 99.40 |
| 4 | 52.91g，0.43mol（n=3.0） | 99.3 | 99.4 | 95.1 | 98.90 |
| 5 | 39.69g，0.325mol（n=4.0） | 96.4 | 98.5 | 92.6 | 98.40 |
Embodiment five
By scale 81.9g(1.3mol) 25% dust technology add in retort, be warming up to 50-60 DEG C, slowly drip 63.65g(0.52mol to retort with 0.4g/min speed) 1,2-methylenedioxybenzenes; Simultaneously with the speed vigorous stirring of 400r/min, dropwise rear insulation 0.5 hour, be cooled to 20 DEG C of filtrations and obtain wet product 3,4-methylene-dioxy oil of mirbane, purified water washing is neutral to pH value, carries out drying, obtain 3 under 40 DEG C of vacuum 0.09MPa, 4-methylene-dioxy oil of mirbane intermediate, yield and purity situation situation are in table 5.By 3,4-methylene-dioxy oil of mirbane, skeletal nickel catalyst and solvent drop into autoclave successively, the selection situation of described solvent is in table 5, then exhausted air, start to pass into hydrogen when being warming up to 60 DEG C, logical H-H reaction 2h is continued under 2.5MPa pressure, then the logical hydrogen of interval is to hydrogen-pressure is constant, carry out underpressure distillation after filtration catalizer, steam and carry out molecular distillation again except after low-boiling-point substance water and solvent, collect 80-160Pa, 100-110 DEG C of cut, obtain finished product 3,4-methylene dioxo group aniline, yield and purity situation in Table, 5.
Table 5: the yield of the selection situation of solvent and 3,4-methylene-dioxy oil of mirbane, 3,4-methylene dioxo group anilines and purity
| Sequence number | The kind of solvent | 3,4-methylene-dioxy oil of mirbane yield % | Purity % | 3,4-methylene dioxo group aniline molar yield % | Purity % |
| 1 | Ethanol | 99.8 | 99.2 | 95.9 | 99.40% |
| 2 | Toluene | 99.8 | 99.2 | 95.1 | 99.20% |
Embodiment six
By scale 81.9g(1.3mol) 25% dust technology add in retort, be warming up to 50-60 DEG C, slowly drip 63.65g(0.52mol to retort with 0.4g/min speed) 1,2-methylenedioxybenzenes; Simultaneously with the speed vigorous stirring of 400r/min, dropwise rear insulation 0.5 hour, be cooled to 20 DEG C of filtrations and obtain wet product 3,4-methylene-dioxy oil of mirbane, purified water washing is neutral to pH value, carries out drying, obtain 3 under 40 DEG C of vacuum 0.09MPa, 4-methylene-dioxy oil of mirbane intermediate, yield and purity situation situation are in table 6.By 3,4-methylene-dioxy oil of mirbane, skeletal nickel catalyst and ethanol drop into autoclave successively, then exhausted air, start to pass into hydrogen when being warming up to 60 DEG C, continue logical H-H reaction 2h under a certain pressure, the selection situation of described pressure is in table 6, then the logical hydrogen of interval is to hydrogen-pressure is constant, underpressure distillation is carried out after filtration catalizer, steam and carry out molecular distillation again except after low-boiling-point substance water and solvent, collect 80-160Pa, 100-110 DEG C of cut, obtain finished product 3,4-methylene dioxo group aniline, yield and purity situation are in table 6.
Table 6: the yield of the selection situation of pressure and 3,4-methylene-dioxy oil of mirbane, 3,4-methylene dioxo group anilines and purity
| Sequence number | Pressure MPa | 3,4-methylene-dioxy oil of mirbane yield % | Purity % | 3,4-methylene dioxo group aniline molar yield % | Purity % |
| 1 | 2.5 | 99.8 | 99.2 | 95.9 | 99.40 |
| 2 | 3.0 | 99.8 | 99.2 | 95 | 99.20 |
| 3 | 3.5 | 99.8 | 99.2 | 95.1 | 99.30 |
Embodiment seven
By scale 81.9g(1.3mol) 25% dust technology add in retort, be warming up to 50-60 DEG C, slowly drip 63.65g(0.52mol to retort with 0.4g/min speed) 1,2-methylenedioxybenzenes; Simultaneously with the speed vigorous stirring of 400r/min, dropwise rear insulation 0.5 hour, be cooled to 20 DEG C of filtrations and obtain wet product 3,4-methylene-dioxy oil of mirbane, purified water washing is neutral to pH value, carries out drying, obtain 3 under 40 DEG C of vacuum 0.09MPa, 4-methylene-dioxy oil of mirbane intermediate, yield and purity situation situation are in table 7.By 3,4-methylene-dioxy oil of mirbane, skeletal nickel catalyst and ethanol drop into autoclave successively, then exhausted air, start to pass into hydrogen when being warming up to 60 DEG C, logical H-H reaction 2h is continued under 2.5MPa pressure, then the logical hydrogen of interval is to hydrogen-pressure is constant, underpressure distillation is carried out after filtration catalizer, steam and carry out molecular distillation again except after low-boiling-point substance water and solvent, collect cut, the selection situation of the pressure and temperature of described collection cut is in table 7, obtain finished product 3,4-methylene dioxo group aniline, yield and purity situation in Table, 7.
Table 7: collect the selection situation of pressure and temperature of cut and 3,4-methylene-dioxy oil of mirbane, the yield of 3,4-methylene dioxo group anilines and purity
| Sequence number | Collect the pressure and temperature of cut | 3,4-methylene-dioxy oil of mirbane yield % | Purity % | 3,4-methylene dioxo group aniline molar yield % | Purity % |
| 1 | 80-160Pa、100-110℃ | 99.8 | 99.2 | 95.9 | 99.40 |
| 2 | 90-150Pa、105-120℃ | 99.8 | 99.2 | 95.5 | 99.30 |
| 3 | 60-120Pa、100-105℃ | 99.8 | 99.2 | 95.1 | 99.10 |
Embodiment eight
Scale 81.9g(1.3mol by recovery) 25% dust technology add in retort, be warming up to 50-60 DEG C, slowly drip 63.65g(0.52mol to retort with 0.4g/min speed) 1,2-methylenedioxybenzenes; Simultaneously with the speed vigorous stirring of 400r/min, dropwise rear insulation 0.5 hour, be cooled to 20 DEG C of filtrations and obtain wet product 3,4-methylene-dioxy oil of mirbane, purified water washing is neutral to pH value, carries out drying, obtain 3 under 40 DEG C of vacuum 0.09MPa, 4-methylene-dioxy oil of mirbane intermediate, yield 99.1% and purity 99.1%.By 3,4-methylene-dioxy oil of mirbane, the skeletal nickel catalyst of recovery and the ethanol of recovery drop into autoclave successively, then exhausted air, start to pass into hydrogen when being warming up to 60 DEG C, logical H-H reaction 2h is continued under 2.5MPa pressure, then the logical hydrogen of interval is to hydrogen-pressure is constant, underpressure distillation is carried out after filtration catalizer, steam and carry out molecular distillation again except after low-boiling-point substance water and solvent, collect 80-160Pa, 100-110 DEG C of cut, obtain finished product 3,4-methylene dioxo group aniline, yield 95.2% and purity 99.1%.
Claims (10)
1. the preparation method of a methylene dioxo group aniline, is characterized in that, described method comprises the steps:
(1) dust technology is added in retort heat up;
(2) in above-mentioned retort, slowly drip 1,2-methylenedioxybenzenes, vigorous stirring, dropwises rear insulation simultaneously;
(3) after cooling, filtration obtains wet product 3,4-methylene-dioxy oil of mirbane, and purified water washing is neutral to pH value, and vacuum-drying, obtains 3,4-methylene-dioxy oil of mirbane;
(4) 3,4-methylene-dioxy oil of mirbane and nickel catalyzator, reaction solvent are dropped in autoclave, heat up, pass into hydrogen, reaction terminates rear filtration catalizer, and underpressure distillation carries out molecular distillation after removing low-boiling-point substance, collect cut, obtain 3,4-methylene dioxo group aniline.
2. the preparation method of one 3, the 4-methylene dioxo group aniline according to claims 1, is characterized in that, in step (1), described dust technology concentration is 15%-30%, and preferred concentration is 20%-25%, the temperature that described intensification reaches is 50-70 DEG C, and preferable temperature is 50-60 DEG C.
3. the preparation method of one 3, the 4-methylene dioxo group aniline according to claims 1, is characterized in that, 1,2-described methylenedioxybenzenes and the mol ratio 1:1.5-3 of nitric acid, the mol ratio 1:2.0-3 of preferred 1,2-methylenedioxybenzenes and nitric acid.
4. the preparation method of one 3, the 4-methylene dioxo group aniline according to claims 1, is characterized in that, in step (2), the speed of described slow dropping is 0.2-0.5g/min, and the speed preferably dripped is 0.3-0.4g/min; The speed of described vigorous stirring is 300-600r/min, and the speed of preferred vigorous stirring is 400-600r/min; Described soaking time is 0.3-1 hour, and preferred soaking time is 0.5 hour.
5. the preparation method of one 3, the 4-methylene dioxo group aniline according to claims 1, is characterized in that, in step (1), described dust technology is concentrated nitric acid dilution preparation or recovery, and what dust technology can be applied mechanically batch criticizes for 10-30.
6. the preparation method of one 3, the 4-methylene dioxo group aniline according to claims 1, is characterized in that, in step (3), described in be cooled to temperature range be 15-25 DEG C, be preferably cooled to 20 DEG C; Described drying for carry out drying under 40 DEG C of vacuum 0.09MPa.
7. the one 3 according to claims 1, the preparation method of 4-methylene dioxo group aniline, is characterized in that, in step (4), described reaction solvent is selected from one or more in ethanol, acetone, toluene, ethyl acetate, and described reaction solvent is recyclable to be applied mechanically.
8. the one 3 according to claims 1, the preparation method of 4-methylene dioxo group aniline, it is characterized in that, in step (4), the temperature that described intensification reaches is 50-90 DEG C, the temperature that preferred intensification reaches is 60 DEG C, and described logical hydrogen is continue logical H-H reaction under a certain pressure, and then the logical hydrogen of interval is to hydrogen-pressure is constant; The described pressure continuing logical hydrogen is 1.5-4.0MPa, and preferred pressure is 2.5MPa; The described time continuing logical H-H reaction is 1.5-2.5 hour, preferably 2 hours.
9. the one 3 according to claims 1, the preparation method of 4-methylene dioxo group aniline, it is characterized in that, in step (4), described nickel catalyzator is skeletal nickel catalyst, described nickel catalyzator is the mixture of fresh nickel accelerant or upper batch of recovery nickel accelerant or fresh nickel accelerant and recovery nickel accelerant, and what described nickel catalyzator can be applied mechanically batch criticizes for 60-120.
10. the one 3 according to claims 1, the preparation method of 4-methylene dioxo group aniline, it is characterized in that, in step (4), described cut is the cut collected at 80-160Pa, 100-120 DEG C, described 3,4-methylene-dioxy oil of mirbane and nickel catalyzator, reaction solvent being dropped in autoclave is 3,4-methylene-dioxy oil of mirbane and nickel catalyzator, reaction solvent are dropped into successively in autoclave.
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| CN101245060A (en) * | 2008-03-17 | 2008-08-20 | 武穴市龙翔药业有限公司 | Method for producing N-alkyl-(3,4-methylenedioxy) aniline |
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| US10633375B2 (en) | 2016-08-31 | 2020-04-28 | Jinagsu Hengrui Medicine Co., Ltd | Oxopicolinamide derivative, preparation method therefor and pharmaceutical use thereof |
| US11084808B2 (en) | 2016-08-31 | 2021-08-10 | Jiangsu Hengrui Medicine Co., Ltd. | Oxopicolinamide derivative, preparation method therefor and pharmaceutical use thereof |
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