CN117843523A - Preparation method of trimethyl acethydrazide - Google Patents
Preparation method of trimethyl acethydrazide Download PDFInfo
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- CN117843523A CN117843523A CN202311670178.2A CN202311670178A CN117843523A CN 117843523 A CN117843523 A CN 117843523A CN 202311670178 A CN202311670178 A CN 202311670178A CN 117843523 A CN117843523 A CN 117843523A
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- OARJXUPBZNUYBG-UHFFFAOYSA-N 2,2-dimethylpropanehydrazide Chemical compound CC(C)(C)C(=O)NN OARJXUPBZNUYBG-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000011968 lewis acid catalyst Substances 0.000 claims abstract description 23
- 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 claims abstract description 19
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims abstract description 19
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000010992 reflux Methods 0.000 claims abstract description 15
- 239000002808 molecular sieve Substances 0.000 claims abstract description 7
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims description 42
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 28
- 239000000047 product Substances 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000002244 precipitate Substances 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 9
- 238000005406 washing Methods 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- FSSPGSAQUIYDCN-UHFFFAOYSA-N 1,3-Propane sultone Chemical compound O=S1(=O)CCCO1 FSSPGSAQUIYDCN-UHFFFAOYSA-N 0.000 claims description 6
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 5
- 238000000967 suction filtration Methods 0.000 claims description 5
- 238000012544 monitoring process Methods 0.000 claims description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000003760 magnetic stirring Methods 0.000 claims description 2
- 230000001376 precipitating effect Effects 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 9
- 238000006297 dehydration reaction Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 19
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 12
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 8
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 4
- 238000004321 preservation Methods 0.000 description 4
- 239000004408 titanium dioxide Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- RKEWSXXUOLRFBX-UHFFFAOYSA-N pimavanserin Chemical compound C1=CC(OCC(C)C)=CC=C1CNC(=O)N(C1CCN(C)CC1)CC1=CC=C(F)C=C1 RKEWSXXUOLRFBX-UHFFFAOYSA-N 0.000 description 3
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- HHEIMYAXCOIQCJ-UHFFFAOYSA-N ethyl 2,2-dimethylpropanoate Chemical compound CCOC(=O)C(C)(C)C HHEIMYAXCOIQCJ-UHFFFAOYSA-N 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 description 1
- 239000005588 Oxadiazon Substances 0.000 description 1
- CHNUNORXWHYHNE-UHFFFAOYSA-N Oxadiazon Chemical compound C1=C(Cl)C(OC(C)C)=CC(N2C(OC(=N2)C(C)(C)C)=O)=C1Cl CHNUNORXWHYHNE-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical class C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C241/00—Preparation of compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C241/04—Preparation of hydrazides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0244—Nitrogen containing compounds with nitrogen contained as ring member in aromatic compounds or moieties, e.g. pyridine
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a preparation method of trimethyl acethydrazide, which takes pivalic acid and hydrazine hydrate as raw materials, and reflux is carried out in toluene solution in the presence of Lewis acid catalyst and 4A molecular sieve, and trimethyl acethydrazide is obtained through dehydration reaction>95%) of the target product was obtained.
Description
Technical Field
The invention relates to the technical field of organic chemistry, in particular to a preparation method of trimethyl acethydrazide.
Background
Trimethyl acethydrazide is a common raw material and is widely used for synthesis in the field of medicines or agriculture, for example, 5-tertiary butyl-1, 3, 4-oxadiazole-2 (3H) -ketone can be prepared by the reaction of trimethyl acethydrazide and solid phosgene, and can be used for synthesis of pesticide herbicide oxadiazon.
The preparation methods of the conventional trimethylacethydrazide mainly comprise three methods:
first kind: using trimethylacetyl chloride and hydrazine hydrate as raw materials, for example: the method of dropwise adding trimethylacetyl chloride into a mixed solution formed by an aqueous solution of sodium hydroxide and an aqueous solution of hydrazine hydrate under low temperature condition is adopted by Bryan Li et al, the reaction solution is concentrated by distillation, filtered, then toluene is added, distillation and dehydration are carried out again, concentration and filtration are carried out, and finally pure product of trimethylacetyl hydrazine is obtained by recrystallization, the purity is 97%, and the yield is 72% (Bryan Li, preparation of pivaloyl hydrazine in water, organic Syntheses,2005, 81:254-261). However, the post-treatment process of the method is complex, and the yield is not high.
Second kind: starting from trimethylacetic acid and hydrazine hydrate, for example: verbruge, pieter Adriaan et al adopts sec-butyl alcohol as a solvent, tetraisopropyl titanate, trimethylacetic acid and hydrazine hydrate are added into a reactor, the amorphous titanium dioxide generated by the decomposition of the tetraisopropyl titanate is catalyzed and reacted at a temperature which can reach 96 percent (Verbruge, pieter Adriaan, process and catalyst for the preparation of pivaloyl hydrazide from water-containing solutions of hydrazine and pivalic acid and EP653415,1994-10-28), the existence form of the titanium dioxide with the catalytic effect in the method directly influences the reaction effect, and when the more common industrial crystalline titanium dioxide is adopted as a catalyst in the patent, the reaction yield is reduced to below 80 percent. Thereafter, urban, frank John used the same method as Verbruge, pieter Adriaan in 88% yield (Urban, frank John, pyrozolopyridino, EP1380585,2000-4-7); the reaction was scaled up to 75% in kg using essentially the same method as Verbruge, pieter Adriaan (Bong Chan Kim, development of a kilogram-scale synthesis of cis-LC15-0133 tartrate,a potent dipeptidyl peptidase IV inhibitor,Organic Process Research&Development,2008,12:626-631), which suggests that it is not easy to obtain high yields by this method, probably because amorphous titania produced after the decomposition of tetraisopropyl titanate is unstable and the catalytic effect is poor when crystalline titania is formed in part more easily; in addition, the solvent (such as isobutanol), isopropanol generated by the decomposition of tetraisopropyl titanate, titanium dioxide and the like exist in the reaction system at the same time, so that the components of the reaction solution are complex, and the separation is difficult.
Third kind: methyl or ethyl trimethylacetate and hydrazine or hydrazine hydrate are used as raw materials, for example, schostarez, heinrich Josef adopts methyl trimethylacetate to react with anhydrous hydrazine, the yield is 90 percent (Schostarez, heinrich Josef, method for treating alzheimer's disease using quinaldoyl-amine derivatives of oxo-and hydroxyl-substituted hydrocarbons, WO03020370,2002-8-28), thibault, thomas Delor adopts methyl trimethylacetate to react with pure hydrazine hydrate for 4 days, the yield is 85 percent (Thibault, 2-tert-butyl-5-methylamine-1, 3, 4-thiodiazoles, DE2541115,1975-9-15), helmut, quast et al adopts ethyl trimethylacetate to react with pure hydrazine hydrate in a pressure kettle for 24 hours, the yield is 63 percent (Helmut, quast, thermal decomposition of isomeric dihydro-1,3,4-thiodiazole 1,1-dioxides, chemische Berichte,1981, 3-4-thiodiazoles, and 3, 114) and the industrial hydrazine is not stable in use, and the industrial value is not provided because of the high stability of the hydrazine hydrate is not provided; tao et al use methyl trimethylacetate and 80% hydrazine hydrate aqueous solution reflux reaction for 28 hours, get the yield 79% of trimethyl acethydrazide after post-treatment, purity 98% (Tao, solid phosgene method synthetic 5-tertiary butyl-1, 3, 4-oxadiazole-2 (3H) -ketone, chemical reagent, 2013,35 (5): 457-460), the method is easy to operate, raw materials are easy to obtain, but the reaction time is long, the yield is lower.
In summary, the preparation method of the prior art has the problems of unstable catalyst, difficult acquisition of raw materials, high price, complex operation, low yield and the like, so that the preparation method of the trimethylacethydrazide with easy acquisition of raw materials, simple operation and high yield is needed to be provided.
Disclosure of Invention
The invention aims to provide a preparation method of trimethyl acethydrazide, which aims to solve the problems of unstable catalyst, difficult acquisition of raw materials, high price, complex operation, low yield and the like in the prior art.
In order to solve the technical problems, the invention provides a preparation method of trimethyl acethydrazide, which comprises the following synthetic route:
the method comprises the following specific steps: 1) Taking pivalic acid and hydrazine hydrate as raw materials, refluxing in toluene solution in the presence of a Lewis acid catalyst and a 4A molecular sieve, and obtaining trimethyl acethydrazide through dehydration reaction;
as a preferable technical scheme of the invention, the method comprises the following steps: 1) Adding toluene solution into a reaction bottle, starting stirring, sequentially adding pivalic acid, a Lewis acid catalyst and a 4A molecular sieve, controlling the reaction temperature below 35 ℃, slowly dripping hydrazine hydrate, slowly heating the reaction solution to reflux after dripping, keeping the temperature for reflux reaction for 6-12h, performing TLC monitoring reaction, cooling the reaction system to 0-5 ℃ after the reaction is finished, precipitating solids, performing suction filtration, and drying to obtain a target product trimethylacethydrazide;
as a preferable technical scheme of the invention, the molar ratio of the pivalic acid to the hydrazine hydrate in the step 1) is 1:1 to 1.5;
as a preferable technical scheme of the invention, the structure of the Lewis acid catalyst in the step 1) is as follows:
as a preferred technical scheme of the invention, the molar ratio of the Lewis acid catalyst to the pivalic acid in the step 1) is 0.05-0.08:1, a step of; preferably, the molar ratio of the Lewis acid catalyst to the pivalic acid in step 1) is 0.05:1, a step of;
as a preferable technical scheme of the invention, the time of the heat preservation reflux reaction in the step 1) is 6-12h, preferably 6-8h; more preferably 6h;
the invention also provides a preparation method of the Lewis acid catalyst, which comprises the following steps: prepared by the method of patent CN 105435842B;
the specific synthesis steps are as follows: a) Firstly, adding a certain amount of 1, 2-diimidazole ethane and 1, 3-propane sultone into a 100mL round bottom flask, adding 30-50mL of acetonitrile, reacting for 24 hours at 80 ℃ under magnetic stirring, washing the generated white powder precipitate with ethanol, drying in vacuum, adding water into the white powder, dripping into a metered hydrochloric acid solution, reacting for 12 hours at 60 ℃, concentrating the obtained solution under reduced pressure, adding a certain amount of toluene to extract and separate oily precipitate, repeatedly washing the oily precipitate with acetonitrile and ethyl acetate, drying under reduced pressure to obtain a pale yellow oily product, adding a certain amount of pale yellow oily product and metered copper chloride into a 100mL volumetric flask, adding 50-100mL of ethanol, reacting for 12 hours at 80 ℃, cooling, and washing the obtained oily product with acetonitrile for times to obtain the required Lewis acid catalyst.
As a preferred embodiment of the present invention, the molar ratio of 1, 2-diimidazole ethane to 1, 3-propane sultone in the step A) is 1:2-3.
The invention has the beneficial effects that:
1) The preparation method adopts the novel Lewis acid catalyst, so that the catalyst dosage is low, the water diversion step is not needed, the operation method is simple, and the target product can be obtained in high yield (more than 95%).
Detailed Description
The technical solutions of the present invention will be clearly and completely described in connection with the embodiments, and it is apparent that the described embodiments are 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 making any inventive effort, are intended to be within the scope of the invention.
The invention is further illustrated with reference to specific embodiments.
Example 1
Synthesis of Lewis acid catalyst:
the preparation is carried out by the method of patent CN 105435842B: 1.78g of 1, 2-diimidazole ethane and 2.4g of 1, 3-propane sultone are firstly added into a 100mL round bottom flask, 30mL of acetonitrile is added, the mixture is reacted for 24 hours at 80 ℃, the generated white powder precipitate is washed by ethanol and dried in vacuum, 10mL of hydrochloric acid solution with the concentration of 5M is added dropwise after the white powder is dissolved into 10mL of water, the mixture is reacted for 12 hours at 60 ℃, 50mL of toluene is added after the obtained solution is concentrated under reduced pressure to extract and separate oily precipitate, the oily precipitate is repeatedly washed by acetonitrile and ethyl acetate and dried under reduced pressure to prepare a pale yellow oily product, 3g of pale yellow oily product and 1g of copper chloride are added into a 100mL volumetric flask to react for 12 hours at 80 ℃, and the obtained oily substance is washed by acetonitrile for times to prepare the required Lewis acid catalyst after the cooling.
EXAMPLE 1 preparation of trimethylacethydrazide
The synthetic route is as follows:
1) 100mL of toluene solution is added into a reaction bottle, stirring is started, pivalic acid (2 mmol,0.21 g), a Lewis acid catalyst (0.1 mmol,61.4 mg) and a 4A molecular sieve (200 mg) are sequentially added, the reaction temperature is controlled below 35 ℃, hydrazine hydrate (2 mmol,0.1 g) is slowly added dropwise, the reaction solution is slowly heated to reflux after the dropwise addition, the reflux reaction is carried out for 6h under heat preservation, after the TLC monitoring reaction is finished, the reaction system is cooled to 0 ℃, solids are separated out, suction filtration, washing and drying are carried out, and 0.22g of target product trimethylacethydrazide is obtained, and the yield is 95%.
EXAMPLE 2 preparation of trimethylacethydrazide
The synthetic route is as follows:
1) 100mL of toluene solution is added into a reaction bottle, stirring is started, pivalic acid (2 mmol,0.20 g), a Lewis acid catalyst (0.16 mmol,98.2 mg) and a 4A molecular sieve (200 mg) are sequentially added, the reaction temperature is controlled below 35 ℃, hydrazine hydrate (2 mmol,0.11 g) is slowly added dropwise, the reaction solution is slowly heated to reflux after the dropwise addition, the reflux reaction is carried out for 6h under heat preservation, after the TLC monitoring reaction is finished, the reaction system is cooled to 0 ℃, solids are separated out, suction filtration, washing and drying are carried out, and 0.225g of target product trimethylacethydrazide is obtained, and the yield is 97%.
Comparative example 1
Synthesis of Lewis acid catalyst 2:
the preparation is carried out by the method of patent CN 105435842B: first, 1.77g of 1, 2-diimidazole ethane and 2.4g of 1, 3-propane sultone are added into a 100mL round bottom flask, 30mL of acetonitrile is added, the mixture is reacted for 24 hours at 80 ℃ under stirring, the generated white powder precipitate is washed by ethanol and dried in vacuum, 10mL of hydrochloric acid solution with the concentration of 5M is added dropwise after the white powder is dissolved into 10mL of water, the mixture is reacted for 12 hours at 60 ℃, 50mL of toluene is added after the obtained solution is concentrated under reduced pressure to extract and separate oily precipitate, and the oily precipitate is repeatedly washed by acetonitrile and ethyl acetate and dried under reduced pressure to prepare a light yellow oily product Lewis acid catalyst 2.
Comparative example 2 preparation of trimethylacethydrazide
The synthetic route is as follows:
1) 100mL of toluene solution is added into a reaction bottle, stirring is started, pivalic acid (2 mmol,0.20 g), lewis acid catalyst 2 (0.1 mmol,48 mg) and 4A molecular sieve (200 mg) are sequentially added, the reaction temperature is controlled below 35 ℃, hydrazine hydrate (2 mmol,0.11 g) is slowly added dropwise, the reaction solution is slowly heated to reflux after the dripping, the reflux reaction is carried out for 6h under heat preservation, the TLC monitors the reaction, the reaction system is cooled to 0 ℃ after the reaction is finished, solid is separated out, suction filtration, washing and drying are carried out, and 0.135g of target product trimethylacethydrazide is obtained, and the yield is 58%.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (9)
1. A preparation method of trimethyl acethydrazide is characterized by comprising the following synthetic route:
the method comprises the following specific steps: 1) Adding toluene solution into a reaction bottle, starting stirring, sequentially adding pivalic acid, a Lewis acid catalyst and a 4A molecular sieve, controlling the reaction temperature below 35 ℃, slowly dripping hydrazine hydrate, slowly heating the reaction liquid to reflux after dripping, keeping the temperature for reflux reaction for 6-12h, monitoring the reaction by TLC, cooling the reaction system to 0-5 ℃ after the reaction is finished, precipitating solids, carrying out suction filtration, and drying to obtain the target product trimethylacethydrazide.
2. The method according to claim 1, wherein the molar ratio of pivalic acid to hydrazine hydrate in step 1) is 1:1-1.5.
3. The method according to claim 2, wherein the molar ratio of pivalic acid to hydrazine hydrate in step 1) is 1:1.
4. the method according to claim 1, wherein the Lewis acid catalyst in step 1) has the structure:
5. the process according to claim 1, wherein the molar ratio of Lewis acid catalyst to pivalic acid in step 1) is from 0.05 to 0.08:1.
6. the process of claim 5, wherein the molar ratio of Lewis acid catalyst to pivalic acid in step 1) is 0.05:1.
7. the method according to claim 1, wherein the time for the heat-retaining reflux reaction in step 1) is 6 to 8 hours.
8. The method for preparing a Lewis acid catalyst according to claim 1, characterized by comprising the steps of: a) Firstly, adding a certain amount of 1, 2-diimidazole ethane and 1, 3-propane sultone into a 100mL round bottom flask, adding 30-50mL of acetonitrile, reacting for 24 hours at 80 ℃ under magnetic stirring, washing the generated white powder precipitate with ethanol, drying in vacuum, adding water into the white powder, dripping into a metered hydrochloric acid solution, reacting for 12 hours at 60 ℃, concentrating the obtained solution under reduced pressure, adding a certain amount of toluene to extract and separate oily precipitate, repeatedly washing the oily precipitate with acetonitrile and ethyl acetate, drying under reduced pressure to obtain a pale yellow oily product, adding a certain amount of pale yellow oily product and metered copper chloride into a 100mL volumetric flask, adding 50-100mL of ethanol, reacting for 12 hours at 80 ℃, cooling, and washing the obtained oily product with acetonitrile for times to obtain the required Lewis acid catalyst.
9. The method for preparing a Lewis acid catalyst according to claim 8 wherein the molar ratio of 1, 2-diimidazole ethane to 1, 3-propane sultone in step A) is 1:2-3.
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