CN115572263B - Method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt - Google Patents
Method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt Download PDFInfo
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- pyrazoline
- ketazine
- hydrazine salt
- hydrazine
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- 150000002429 hydrazines Chemical class 0.000 title claims abstract description 45
- 238000000034 method Methods 0.000 title claims abstract description 43
- PFLUPZGCTVGDLV-UHFFFAOYSA-N acetone azine Chemical compound CC(C)=NN=C(C)C PFLUPZGCTVGDLV-UHFFFAOYSA-N 0.000 title claims abstract description 37
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 238000007363 ring formation reaction Methods 0.000 title claims abstract description 29
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 29
- 238000006243 chemical reaction Methods 0.000 claims abstract description 48
- 239000003054 catalyst Substances 0.000 claims abstract description 42
- -1 pyrazoline compound Chemical class 0.000 claims abstract description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 59
- 229910052757 nitrogen Inorganic materials 0.000 claims description 31
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 16
- QQZOPKMRPOGIEB-UHFFFAOYSA-N 2-Oxohexane Chemical compound CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- ZMJZYXKPJWGDGR-UHFFFAOYSA-N aminosulfamic acid Chemical compound NNS(O)(=O)=O ZMJZYXKPJWGDGR-UHFFFAOYSA-N 0.000 claims description 8
- XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 claims description 8
- WTDVBCFDCDLEPI-UHFFFAOYSA-N aminoazanium;2,2,2-trifluoroacetate Chemical compound [NH3+]N.[O-]C(=O)C(F)(F)F WTDVBCFDCDLEPI-UHFFFAOYSA-N 0.000 claims description 5
- BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 3
- 229910017464 nitrogen compound Inorganic materials 0.000 claims description 3
- 150000002830 nitrogen compounds Chemical class 0.000 claims description 3
- FUSNOPLQVRUIIM-UHFFFAOYSA-N 4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-n-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide Chemical compound O=C1NC(C)(C)CN1C(N=C1N)=NC=C1C(=O)NC1=CC=CC(C(F)(F)F)=C1 FUSNOPLQVRUIIM-UHFFFAOYSA-N 0.000 claims description 2
- 239000003570 air Substances 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 229910052734 helium Inorganic materials 0.000 claims description 2
- 239000001307 helium Substances 0.000 claims description 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 2
- 229910000377 hydrazine sulfate Inorganic materials 0.000 claims description 2
- 239000012493 hydrazine sulfate Substances 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000005260 corrosion Methods 0.000 abstract description 5
- 230000007797 corrosion Effects 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 5
- 238000002360 preparation method Methods 0.000 abstract description 4
- 238000001308 synthesis method Methods 0.000 abstract description 3
- 239000003380 propellant Substances 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 239000002699 waste material Substances 0.000 abstract description 2
- 230000003321 amplification Effects 0.000 abstract 1
- 238000003199 nucleic acid amplification method Methods 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 230000003197 catalytic effect Effects 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
- 239000000047 product Substances 0.000 description 12
- SBYYIROHHZRLBX-UHFFFAOYSA-N 3,5-diethyl-5-methyl-1,4-dihydropyrazole Chemical compound CCC1=NNC(C)(CC)C1 SBYYIROHHZRLBX-UHFFFAOYSA-N 0.000 description 11
- 238000011156 evaluation Methods 0.000 description 10
- 238000001228 spectrum Methods 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- MEVTUZFUVAZEPY-UHFFFAOYSA-N 3,5,5-trimethyl-1,4-dihydropyrazole Chemical compound CC1=NNC(C)(C)C1 MEVTUZFUVAZEPY-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 description 4
- CGUBRJOKFDZAHA-UHFFFAOYSA-N CCCC1(C)NN=C(CCC)C1 Chemical compound CCCC1(C)NN=C(CCC)C1 CGUBRJOKFDZAHA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000010813 internal standard method Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000007791 liquid phase Substances 0.000 description 3
- 150000003219 pyrazolines Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- HVCFCNAITDHQFX-UHFFFAOYSA-N 1-cyclopropylethanone Chemical compound CC(=O)C1CC1 HVCFCNAITDHQFX-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 238000007036 catalytic synthesis reaction Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000005474 detonation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940072185 drug for treatment of tuberculosis Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011949 solid catalyst Substances 0.000 description 1
- 238000009270 solid waste treatment Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Abstract
The invention provides a method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt, belongs to the technical field of organic chemical synthesis, and aims to solve the technical problems of low selectivity and yield of a pyrazoline compound synthesized by a ketazine internal cyclization method, difficult separation of a catalyst and a product and easy equipment corrosion. According to the invention, the ketazine compound and the hydrazine salt catalyst are mixed and then reacted to obtain the pyrazoline compound. The synthesis method has simple process conditions and high reaction yield, the selectivity of the synthesis method is up to 99.6%, and the yield is up to 98.2%; after the hydrazine salt catalyst is repeatedly used for 5 times, the selectivity of pyrazoline can still reach more than 95 percent, and the yield can reach 75 percent. And the hydrazine salt catalyst has simple preparation process, is easy to separate from products, generates less three wastes in the synthesis process, is suitable for industrial amplification, and the obtained target product can meet the requirement of pyrazoline as a medical intermediate, is also a key intermediate for synthesizing a novel aerospace propellant, and has very wide industrial application prospect.
Description
Technical Field
The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt.
Background
Pyrazoline compounds are known to be effective corrosion inhibitors in the field of corrosion-resistant materials as an important class of five-membered nitrogen heterocyclic substances; in the field of biological medicine, pyrazoline derivatives have high biological activity and are generally used as anti-cancer, anti-depression and anti-tuberculosis medicines, so that the method has important significance in the synthesis research of pyrazoline compounds.
The pyrazoline compound ring contains N-N, C =N and C-N bonds, has larger ring tension, and has higher formation enthalpy. The nitrogen element on the pyrazole ring is decomposed to generate nitrogen, a large amount of energy can be generated in the release process, and the pyrazoline compound has good detonation performance and stability and good compatibility with other energetic materials. Pyrazoline is used as a raw material, and various compounds applied to the fields of explosives and propellants can be synthesized through nitration, amination, denitrification and the like, so that the application value of the military is not quite small.
According to the previous investigation and a large number of experimental bases, the synthesis of pyrazoline by ketazine cyclization needs a specific acid environment, and most of the currently adopted acid is strong acid such as oxalic acid, hydrochloric acid and the like, the strong acid catalyst can not only corrode equipment, but also only adopt a water washing process when being separated from products, so that a large amount of waste water can be generated, and the concept of environmental protection is not met; the subject group also adopts a Lewis acid catalyst (transition metal salt) to provide an acidic environment, and can reduce corrosion of acid to equipment, but the reaction yield is not high, in addition, after the reaction is finished, the transition metal salt and the product pyrazoline form a complex, the combination effect is strong, the separation is difficult, and the catalyst can only be used as solid waste treatment at the follow-up, so that certain problems exist in the catalysts at present.
Disclosure of Invention
Aiming at the technical problems of low selectivity and yield and easy equipment corrosion of the pyrazoline compound synthesized by the ketazine internal cyclization method, the invention provides a method for synthesizing pyrazoline by catalyzing ketazine cyclization by hydrazine salt, which can provide an acidic environment required by reaction, and after the reaction is finished, a catalyst can be recovered by simple filtering operation, can be recycled after the catalyst is recovered, reduces the cost of the catalyst, has higher selectivity and yield than acid and transition metal catalysts, and has very wide industrial application prospect.
In order to achieve the above purpose, the technical scheme of the invention is realized as follows:
a method for synthesizing pyrazoline by catalyzing ketazine with hydrazine salt is characterized in that a ketazine compound and a hydrazine salt catalyst are placed in a device to react to obtain the pyrazoline compound.
The ketone-linked nitrogen compound is any one of acetone-linked nitrogen, 2-butanone-linked nitrogen, 2-pentanone-linked nitrogen, methyl isopropyl ketone-linked nitrogen, 2-hexanone-linked nitrogen or cyclopropyl methyl ketone-linked nitrogen.
The pyrazoline product obtained by the reaction is any one of 3, 5-trimethyl-2-pyrazoline, 3, 5-diethyl-5-methyl-2-pyrazoline, 3, 5-dipropyl-5-methyl-2-pyrazoline, 3, 5-diisopropyl-5-methyl-2-pyrazoline, 3, 5-dibutyl-5-methyl-2-pyrazoline or 3, 5-dicyclohexyl-5-methyl-2-pyrazoline.
The hydrazine salt catalyst is self-made and is any one of hydrazine hydrochloride, hydrazine sulfate, hydrazine sulfonate or trifluoroacetic acid hydrazine salt, and the hydrazine salt catalyst can provide an acidic environment required by the reaction.
The molar ratio of the ketazine compound to the hydrazine salt catalyst is 1: (0.002 to 0.05), preferably 1: (0.005-0.02).
The reaction temperature in the reaction device is 60-140 ℃, preferably 80-120 ℃; the reaction time is 0.5 to 12 hours, preferably 6 to 10 hours.
The reaction is carried out in one or more atmospheres of air, nitrogen, argon or helium, and the reaction pressure is normal pressure, preferably in a nitrogen atmosphere.
The structural formulas of the ketazine and the pyrazoline are shown as a formula a and a formula b respectively:
reaction route
The path of synthesizing pyrazoline by catalyzing ketazine cyclization by hydrazine salt is shown as the formula:
the invention has the beneficial effects that: the method has the characteristics that the hydrazine salt catalyst synthesized by the method has the characteristics of high selectivity, and the hydrazine salt anion is taken as a nucleophilic part to act with ketazine to further rearrange into a ring, and the nucleophilic part can leave in time while providing an acidic environment required by the reaction, so that the reaction is controlled to be carried out towards the direction of synthesizing the pyrazoline, and the selectivity of the product is up to 99.6 percent and the yield is up to 98.2 percent aiming at the acetone continuous nitrogen synthesis reaction; the hydrazine salt catalyst synthesized in the method can catalyze a series of ketazine compounds, not single ketazine, and has universal applicability; the self-made hydrazine salt catalyst has a longer service life, can avoid the problem of catalyst deactivation in the synthesis process, and has a pyrazoline selectivity of more than 95% and a yield of 75% after the hydrazine salt catalyst is repeatedly used for 5 times.
The hydrazine salt catalytic ketazine reaction can be carried out under normal pressure, the process condition is simple, and the harsh requirement on the reaction condition in the existing synthesis method is avoided. Meanwhile, hydrazine salt is weak acid salt, the pH is about 2-4, the consumption is small, the acid environment required by the reaction can be provided, and the influence on equipment is very little. Thereby reducing the requirements on reaction equipment, being suitable for industrial production, simultaneously generating less three wastes, avoiding the problem of environmental pollution and conforming to the green development concept.
Drawings
In order to more clearly illustrate the embodiments of the invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, it being obvious that the drawings in the following description are only some embodiments of the invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 shows the nuclear magnetic H spectra (1 a) and C spectra (1 b) of 3, 5-diethyl-5-methyl-2-pyrazoline prepared in example 1.
FIG. 2 shows the nuclear magnetic H spectra (2 a) and C spectra (2 b) of 3, 5-dipropyl-5-methyl-2-pyrazoline prepared in example 5.
FIG. 3 shows the nuclear magnetic H spectra (3 a) and C spectra (3 b) of 3, 5-dibutyl-5-methyl-2-pyrazoline prepared in example 6.
FIG. 4 shows the nuclear magnetic H spectra (4 a) and C spectra (4 b) of 3, 5-trimethyl-2-pyrazoline prepared in example 11.
FIG. 5 shows the nuclear magnetic H-spectrum (5 a) and C-spectrum (5 b) of 3, 5-diisopropyl-5-methyl-2-pyrazoline prepared in example 15.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without any inventive effort, are intended to be within the scope of the invention.
Example 1
A method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt comprises the following steps:
(1.1) preparation of the catalyst
And (3) dripping a certain amount of hydrazine hydrate into a three-neck flask filled with sulfonic acid through a separating funnel, using an ice water bath to enable the temperature of the feed liquid to be lower than 30 ℃, reacting for a period of time after dripping, standing a reaction product for more than 12 hours, generating crystals, flushing the crystals with absolute ethyl alcohol for a plurality of times after suction filtration, and placing the crystals in a blast drying oven for drying treatment to finally obtain the hydrazine sulfonate catalyst.
(1.2) catalytic Synthesis reaction
1mol of 2-butanone is taken and placed in a 500mL three-neck flask, the stirring speed of a heating sleeve is set to be 500rpm, then 0.01mol of hydrazine sulfonate catalyst is added, the air in the flask is replaced by nitrogen, then the temperature is raised to 100 ℃, the reaction is stopped after 7 hours, the product is filtered by suction, the liquid phase is taken for analysis, and the solid catalyst is recycled after washing. The raw materials and the products are detected and analyzed by Agilent gas chromatography, specifically an HP-5 column is adopted, and the content of each compound is calculated by an internal standard method according to a standard curve. The obtained pyrazoline product is distilled and purified, and then: nuclear magnetic resonance spectroscopy further confirms the structure of the compound as shown in figure 1: 1 H NMR(600MHz,DMSO)δ＝2.36-2.32(m,1H,CH 2 ),2.21(dd,J＝13.9,7.4Hz,1H,CH 2 ),2.19-2.13(m,2H,CH 2 ),1.46-1.39(m,2H,CH 2 ),1.04(s,3H,CH 3 ),1.01(t,J＝7.5Hz,3H,CH 3 ),0.81ppm(dd,J＝8.4,6.6Hz,3H,CH 3 ). 13 C NMR(151MHz,DMSO)δ＝153.9(C＝N),64.6(C-N),45.9(CH 2 ),33.1(CH 2 ),25.2(CH 2 ),23.7(CH 3 ),11.5(CH 3 ),9.7ppm(CH 3 ). The conversion of 2-butanone and the selectivity of 3, 5-diethyl-5-methyl-2-pyrazoline are 80.6%, 99.0% and 79.8%.
Example 2
Unlike example 1, the reaction time in step (1.2) was 8h. The catalytic performance evaluation shows that the conversion rate of 2-butanone and nitrogen is 83.4%, the selectivity of 3, 5-diethyl-5-methyl-2-pyrazoline is 98.5%, and the yield is 82.1%.
Example 3
A method for synthesizing pyrazoline by catalyzing ketazine cyclization by hydrazine salt is different from that in the embodiment 2 in that the amount of hydrazine sulfonate catalyst in the step (1.2) is 0.02mol. The catalytic performance evaluation shows that the conversion rate of 2-butanone and nitrogen is 87.9%, the selectivity of 3, 5-diethyl-5-methyl-2-pyrazoline is 98.3%, and the yield is 86.4%.
Example 4
A method for synthesizing pyrazoline by catalyzing ketazine cyclization by hydrazine salt, which is different from example 2 in that the reaction temperature in the step (1.2) is 90 ℃. The catalytic performance evaluation shows that the conversion rate of 2-butanone and nitrogen is 86.0%, the selectivity of 3, 5-diethyl-5-methyl-2-pyrazoline is 98.6%, and the yield is 84.8%.
Example 5
Unlike example 3, the method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt is characterized in that 2-butanone azine in the step (1.2) is replaced by 2-pentanone azine to prepare 3, 5-dipropyl-5-methyl-2-pyrazoline. Characterization was performed using a nuclear magnetic resonance spectrometer, as shown in fig. 2: 1 H NMR(600MHz,DMSO)δ＝2.32(d,J＝16.3Hz,1H,CH 2 ),2.21(d,J＝16.3Hz,1H,CH 2 ),2.12(t,J＝7.4Hz,2H,CH 2 ),1.46(dd,J＝14.8,7.4Hz,2H,CH 2 ),1.39(dd,J＝9.3,7.4Hz,2H,CH 2 ),1.28-1.21(m,2H,CH 2 ),1.04(s,3H,CH 3 ),0.88-0.86(m,3H,CH 3 ),0.86-0.85ppm(m,3H,CH 3 ). 13 C NMR(151MHz,DMSO)δ＝152.6(C＝N),64.3(C-N),46.5(CH 2 ),43.2(CH 2 ),32.4(CH 2 ),25.5(CH 2 ),19.9(CH 2 ),18.3(CH 3 ),15.1(CH 3 ),14.2ppm(CH 3 ). The catalytic performance evaluation shows that the conversion rate of 2-pentanone to nitrogen is 78.0%, the selectivity of 3, 5-dipropyl-5-methyl-2-pyrazoline is 98.5%, and the yield is 76.8%.
Example 6
Unlike example 3, the method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt is characterized in that 2-butanone azine in the step (1.2) is replaced by 2-hexanone azine to prepare 3, 5-dibutyl-5-methyl-2-pyrazoline. Characterization was performed using a nuclear magnetic resonance spectrometer, as shown in fig. 3: 1 H NMR(600MHz,DMSO)δ＝2.49-2.47(m,1H,CH 2 ),2.37(d,J＝16.6Hz,1H,CH 2 ),2.21(t,J＝7.5Hz,2H,CH 2 ),1.45(dd,J＝7.7,5.1Hz,2H,CH 2 ),1.42(dd,J＝13.4,5.9Hz,2H,CH 2 ),1.29-1.25(m,2H,CH 2 ),1.25-1.22(m,2H,CH 2 ),1.20(ddd,J＝13.9,6.9,3.5Hz,2H,CH 2 ),1.08(s,3H,CH 3 ),0.87-0.85(m,3H,CH 3 ),0.85-0.82ppm(m,3H,CH 3 ). 13 C NMR(151MHz,DMSO)δ＝160.8(C＝N),64.9(C-N),47.2(CH 2 ),30.1(CH 2 ),28.4(CH 2 ),27.1(CH 2 ),24.8(CH 2 ),23.1(CH 2 ),22.3(CH 3 ),14.4(CH 3 ),14.1ppm(CH 3 ). The catalytic performance evaluation shows that the conversion rate of 2-hexanone and nitrogen is 66.7%, the selectivity of 3, 5-dibutyl-5-methyl-2-pyrazoline is 90.6%, and the yield is 60.4%.
Example 7
A method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt comprises the following steps:
(7.1) preparation of catalyst
And (3) dripping hydrazine hydrate into a three-neck flask filled with trifluoroacetic acid through a separating funnel, using an ice water bath to enable the temperature of the feed liquid to be lower than 30 ℃, reacting for 2 hours after the dripping is finished, distilling off water by distillation, adding a hydrazine trifluoroacetate seed crystal into a product, and slowly growing the seed crystal to finally obtain the hydrazine trifluoroacetate catalyst.
(7.2) catalytic Synthesis reaction
1mol of 2-butanone is taken and placed in a 500mL three-neck flask, a heating sleeve is arranged, the stirring speed is set to be 500rpm, then 0.01mol of hydrazine trifluoroacetate catalyst is added, the air in the flask is replaced by nitrogen, then the temperature is raised to 80 ℃, the reaction is stopped after 7 hours, and the liquid phase is taken for analysis after the product is filtered by suction. The raw materials and the products are detected and analyzed by Agilent gas chromatography, specifically an HP-5 column is adopted, and the content of each compound is calculated by an internal standard method according to a standard curve. The conversion of 2-butanone and nitrogen is 88.3%, the selectivity of 3, 5-diethyl-5-methyl-2-pyrazoline is 98.6%, and the yield is 87.1%.
Example 8
Unlike example 7, the reaction time in step (7.2) was 9h. The catalytic performance evaluation shows that the conversion rate of 2-butanone and the nitrogen is 89.6%, the selectivity of 3, 5-diethyl-5-methyl-2-pyrazoline is 98.1%, and the yield is 87.9%.
Example 9
A method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt is different from that in the embodiment 8 in that the amount of hydrazine sulfonate catalyst in the step (7.2) is 0.02mol. The catalytic performance evaluation shows that the conversion rate of 2-butanone and nitrogen is 94.6%, the selectivity of 3, 5-diethyl-5-methyl-2-pyrazoline is 93.6%, and the yield is 88.5%.
Example 10
Unlike example 8, the reaction temperature in step (7.2) is 115 ℃. The catalytic performance evaluation shows that the conversion rate of 2-butanone and the nitrogen is 95.3%, the selectivity of 3, 5-diethyl-5-methyl-2-pyrazoline is 91.6%, and the yield is 87.3%.
Example 11
Method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt and method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine saltThe difference between example 10 and the substitution of 2-butanone azine as reactant in step (7.2) with acetone azine at a reaction temperature of 105℃yields 3, 5-trimethyl-2-pyrazoline. Characterization by nuclear magnetic resonance spectroscopy, as shown in figure 4, 1 H NMR(600MHz,DMSO)δ＝2.28(d,J＝1.1Hz,2H,CH 2 ),1.81(t,J＝1.0Hz,3H,CH 3 ),1.11ppm(s,6H,CH 3 )； 13 C NMR(151MHz,DMSO)δ＝149.45(C＝N),61.83(C-N),49.96(CH 2 ),27.64(CH 3 ),16.51ppm(CH 3 ). The catalytic performance is evaluated, the conversion rate of acetone to nitrogen is 99.6%, the selectivity of 3, 5-trimethyl-2-pyrazoline is 99.4%, and the yield is 99.0%.
Example 12
Unlike example 10, the method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt is characterized in that 2-butanone diazonium in the step (7.2) is replaced by cyclopropyl methyl ketazine to prepare 3, 5-dicyclohexyl-5-methyl-2-pyrazoline. The catalytic performance evaluation shows that the conversion rate of cyclopropylmethyl ketone to nitrogen is 62.3%, the selectivity of 3, 5-dicyclohexyl-5-methyl-2-pyrazoline is 93.5%, and the yield is 58.2%.
Example 13
A method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt comprises the following steps:
(13.1) catalyst preparation
And (3) adding absolute ethanol into a certain amount of hydrazine hydrate to dilute, slowly adding concentrated hydrochloric acid, using an ice-water bath to enable the temperature of the feed liquid to be lower than 30 ℃, reacting for 2 hours after the dripping is finished, and standing a reaction product for more than 12 hours. Heating in water bath, concentrating, evaporating ethanol, cooling, precipitating crystals, filtering, dissolving crystals with deionized water, concentrating the filtrate under reduced pressure, cooling, filtering, washing with a little absolute ethanol, and drying in a forced air drying oven to obtain hydrazine hydrochloride catalyst.
(13.2) Synthesis reaction
1mol of acetone is placed in a 500mL three-neck flask with continuous nitrogen, a heating sleeve is arranged, the stirring speed is 500rpm, then 0.01mol of hydrazine hydrochloride catalyst is added, the air in the flask is replaced by nitrogen, then the temperature is raised to 90 ℃, the reaction is stopped after 9 hours, and a liquid phase is taken for analysis after the product is filtered by suction. The raw materials and the products are detected and analyzed by Agilent gas chromatography, specifically an HP-5 column is adopted, and the content of each compound is calculated by an internal standard method according to a standard curve. The conversion rate of acetone to nitrogen is 98.6%, the selectivity of 3, 5-trimethyl-2-pyrazoline is 99.6%, and the yield is 98.2%.
Example 14
A method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt is different from that in the embodiment 13 in that the amount of hydrazine hydrochloride catalyst in the step (13.2) is 0.03mol. The catalytic performance is evaluated, the conversion rate of 2-acetone with nitrogen is 99.3%, the selectivity of 3, 5-trimethyl-2-pyrazoline is 99.7%, and the yield is 96.6%.
Example 15
Unlike example 14, the method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt is characterized in that acetone diazonium in the step (13.2) is replaced by methyl isopropyl ketazine to prepare 3, 5-diisopropyl-5-methyl-2-pyrazoline. Characterization was performed using a nuclear magnetic resonance spectrometer, as shown in fig. 5: 1 H NMR(600MHz,DMSO)δ＝2.33(d,J＝7.1Hz,2H,CH 2 ),2.02-1.95(m,1H,CH),1.66(dd,J＝15.3,8.9Hz,1H,CH),1.27(s,3H,CH 3 ),0.95-0.90ppm(m,12H,CH 3 ). 13 C NMR(151MHz,DMSO)δ＝158.40(C＝N),66.60(C-N),50.16(CH),45.76(CH),25.77(CH 3 ),24.80(CH 3 ),23.94(CH 3 ),23.51(CH 3 ),22.74(CH 3 ),22.69ppm(CH 3 ). The catalytic performance evaluation shows that the conversion rate of methyl isopropyl ketone to nitrogen is 32.7%, the selectivity of 3, 5-diisopropyl-5-methyl-2-pyrazoline is 86.0%, and the yield is 28.1%.
Example 16
Number of catalyst cycles
The hydrazine sulfonate catalyst in the example 2 is filtered after reaction, the solid is washed with absolute ethyl alcohol for 2-3 times, and the solid is dried for 12 hours at 80 ℃ in a blast drying oven, thus obtaining the hydrazine sulfonate catalyst. After repeated use for 5 times, the catalyst still has higher catalytic activity, and the selectivity of 3, 5-diethyl-5-methyl-2-pyrazoline can be kept at 95.2 percent, and the yield can reach 75.4 percent.
TABLE 1 influence of catalyst cycle times on butanone pyrazoline yield
| Number of cycles | 1 | 2 | 3 | 4 | 5 |
| Conversion/% | 83.4 | 82.6 | 80.8 | 80.0 | 79.2 |
| Selectivity/% | 98.5 | 98.3 | 97.6 | 96.8 | 95.2 |
| Yield/% | 82.1 | 81.1 | 78.9 | 77.4 | 75.4 |
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.
Claims (7)
1. A method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt is characterized in that: mixing a ketazine compound and a hydrazine salt catalyst, and then reacting to obtain a pyrazoline compound; the synthetic route is shown in the following formula:
；
the ketazine compound is any one of acetone azine, 2-butanone azine, 2-pentanone azine, methyl isopropyl ketazine, 2-hexanone azine or cyclopropyl methyl ketazine;
the hydrazine salt catalyst is any one of hydrazine hydrochloride, hydrazine sulfate, hydrazine sulfonate or hydrazine trifluoroacetate.
2. The method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt according to claim 1, wherein the method comprises the following steps: the molar ratio of the ketone-linked nitrogen compound to the hydrazine salt catalyst is 1: (0.002 to 0.05).
3. The method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt according to any one of claim 2, wherein the method comprises the following steps: the molar ratio of the ketone-linked nitrogen compound to the hydrazine salt catalyst is 1: (0.005-0.02).
4. The method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt according to claim 3, wherein the method comprises the following steps: the reaction temperature of the reaction is 60-140 ℃ and the reaction time is 0.5-12 h.
5. The method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt according to claim 4, wherein the method comprises the following steps: the reaction temperature of the reaction is 80-120 ℃ and the reaction time is 6-10 h.
6. The method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt according to claim 5, wherein the method comprises the following steps: the reaction atmosphere is any one or more than two of air, nitrogen, argon or helium, and the reaction pressure is normal pressure.
7. The method for synthesizing pyrazoline by catalyzing ketazine cyclization with hydrazine salt according to claim 6, wherein the method comprises the following steps: and filtering and washing the hydrazine salt catalyst after the reaction is finished, and reusing the hydrazine salt catalyst.
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| CN107381523A (en) * | 2017-09-07 | 2017-11-24 | 盐城顺恒化工有限公司 | A kind of preparation method of hydrazine sulfate |
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