CN118718896B - Green synthesis process of high-content acethydrazide - Google Patents
Green synthesis process of high-content acethydrazide Download PDFInfo
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- CN118718896B CN118718896B CN202411206429.6A CN202411206429A CN118718896B CN 118718896 B CN118718896 B CN 118718896B CN 202411206429 A CN202411206429 A CN 202411206429A CN 118718896 B CN118718896 B CN 118718896B
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- OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical compound C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 title claims abstract description 60
- 238000000034 method Methods 0.000 title claims abstract description 48
- 230000008569 process Effects 0.000 title claims abstract description 28
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 27
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 141
- 239000003054 catalyst Substances 0.000 claims abstract description 62
- 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 60
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims abstract description 60
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 238000000746 purification Methods 0.000 claims abstract description 10
- 230000002439 hemostatic effect Effects 0.000 claims description 49
- 238000003756 stirring Methods 0.000 claims description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 27
- 238000010438 heat treatment Methods 0.000 claims description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 16
- 239000002808 molecular sieve Substances 0.000 claims description 16
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 16
- 239000011973 solid acid Substances 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 229920001971 elastomer Polymers 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 239000000047 product Substances 0.000 abstract description 18
- 239000002994 raw material Substances 0.000 abstract description 10
- 238000000926 separation method Methods 0.000 abstract description 9
- 230000008901 benefit Effects 0.000 abstract description 6
- 239000012535 impurity Substances 0.000 abstract description 6
- 238000001704 evaporation Methods 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 230000009471 action Effects 0.000 abstract description 3
- 239000012043 crude product Substances 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 3
- 238000005580 one pot reaction Methods 0.000 abstract description 3
- 230000008020 evaporation Effects 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000010025 steaming Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 239000002351 wastewater Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000010533 azeotropic distillation Methods 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000003889 chemical engineering Methods 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- ZRKSVHFXTRFQFL-UHFFFAOYSA-N isocyanomethane Chemical compound C[N+]#[C-] ZRKSVHFXTRFQFL-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- 241000522195 Dalbergia Species 0.000 description 1
- 206010044038 Tooth erosion Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000000152 carbamate pesticide Substances 0.000 description 1
- 239000013064 chemical raw material Substances 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000006698 hydrazinolysis reaction Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 238000005554 pickling Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 235000011225 shan shi Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
- B01J8/00—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes
- B01J8/08—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with moving particles
- B01J8/10—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with moving particles moved by stirrers or by rotary drums or rotary receptacles or endless belts
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D3/00—Distillation or related exchange processes in which liquids are contacted with gaseous media, e.g. stripping
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D3/00—Distillation or related exchange processes in which liquids are contacted with gaseous media, e.g. stripping
- B01D3/009—Distillation or related exchange processes in which liquids are contacted with gaseous media, e.g. stripping in combination with chemical reactions
-
- 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
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/14—Production of inert gas mixtures; Use of inert gases in general
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of organic synthesis, in particular to a green synthesis process of high-content acethydrazide, which adopts a one-pot method, the ethyl acetate and the hydrazine hydrate are heated to react under the action of a catalyst, then distilled at different temperatures respectively, various impurities in the crude product are gradually removed, and finally the acethydrazide is prepared. The method has the advantages that the intermediate steps and the separation and purification steps of the product are reduced, the higher raw material conversion rate and the product yield are maintained, the impurity removal rate can be improved by repeated evaporation, the loss of materials can be reduced by directly evaporating the acethydrazide from a reaction system, the product is not required to be transferred to another container for separation, the overall yield and the product purity can be improved, and the acethydrazide prepared by the method has the advantages of extremely high yield, extremely high purity and simple process, greatly saves the production cost and the labor cost, and has wide application prospect.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a green synthesis process of high-content acethydrazide.
Background
The acethydrazide is white crystal, has a melting point of 58-68 ℃ and is easy to dissolve in water, is an important chemical raw material, and can be used for synthesizing analgesic drugs, anticancer drugs, tooth corrosion inhibitors, platelet activity index inhibitors, antifogging agents of color fixing solutions, stabilizers, metal pickling preservatives and the like. Especially, the methyl isonitrile is used as the raw material to prepare the carbamate pesticide, which can avoid the toxicity to human body and environment caused by directly using methyl isonitrile.
At present, the synthesis method of the acethydrazide generally takes acetic acid, ethanol and hydrazine hydrate as raw materials and is prepared through two steps of reaction, wherein the first step is to carry out esterification reaction on the acetic acid and the ethanol under the action of a concentrated sulfuric acid catalyst to generate ethyl acetate, and the second step is to carry out hydrazinolysis reaction on the ethyl acetate and the hydrazine hydrate in an ethanol solvent by heating. The method for synthesizing the acethydrazide has the following defects that in the first-step esterification reaction, the used catalyst concentrated sulfuric acid has strong corrosiveness, high equipment requirement and can generate a large amount of acidic organic wastewater, the salt content and the COD content of the wastewater after the neutralization treatment by alkali are very high, and the problems of high treatment difficulty, high treatment cost, large discharge amount, easy environmental pollution and the like of the organic wastewater are solved.
In the optimization of the general synthesis method of the acethydrazide, as disclosed in patent technical document CN115466197A, the synthesis method of the acethydrazide comprises the following steps of adding hydrazine hydrate into a reactor, adding ethanol, adding ethyl acetate, then heating and refluxing under the protection of nitrogen, distilling under reduced pressure after the reaction until no liquid flows out, adding acetonitrile for continuous azeotropic distillation, then adding tetrahydrofuran and acetonitrile, dissolving, stirring, filtering, finally washing a filter cake with cold tetrahydrofuran, and vacuum drying the obtained filter cake to obtain the acethydrazide. The invention avoids using high-concentration hydrazine hydrate, reduces potential harm to operators and environment, but involves multiple azeotropic distillation in synthesis, and has complex process and high production cost.
Therefore, according to the related art, there is a need to develop a green synthesis process of high content of acethydrazide with simple process, high purity and high yield.
Disclosure of Invention
Therefore, the invention aims to provide a green synthesis process of high-content acethydrazide, which has the advantages of simple process, high purity and high yield.
Based on the above purpose, the invention provides a green synthesis process of high-content acethydrazide.
A green synthesis process of high-content acethydrazide comprises a reaction system and a purification system;
The reaction system comprises a three-necked flask which is used, wherein the three-necked flask comprises a first feed inlet, a second feed inlet and a third feed inlet which are respectively positioned at two sides of the three-necked flask, a condenser pipe is arranged above the second feed inlet and the third feed inlet through rubber pipes, a hemostatic clamp is arranged between the second feed inlet and the condenser pipe, and a hemostatic clamp is arranged between the third feed inlet and the condenser pipe;
The synthesis process comprises the following steps:
S1, under the protection of nitrogen, sequentially closing a hemostatic clamp at one side of a second feeding hole and a hemostatic clamp at one side of a third feeding hole, sequentially placing hydrazine hydrate, ethyl acetate and a catalyst into a flask, and heating and stirring to obtain a mixture A;
s2, opening a hemostatic clamp at one side of the second feed inlet, heating and stirring the mixture A, and changing the system temperature to T1 until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
S3, changing the system temperature to T2, and uniformly stirring until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
S4, closing a hemostatic clamp at one side of the second feeding port, opening a hemostatic clamp at one side of the third feeding port, changing the system temperature to T3 again, and uniformly stirring until the water level in the receiving container at the outlet of the condensing tube is not increased any more, thus obtaining the acethydrazide;
the molar ratio of the hydrazine hydrate to the ethyl acetate to the catalyst in the step S1 is 0.2:0.25-0.27:0.016-0.03.
Preferably, the catalyst in the step S1 is a mixture of an HY-type solid acid molecular sieve and EDCl, where the HY-type solid acid molecular sieve can adsorb water molecules in a product in its pore canal and has good thermal stability, and EDCl is a good catalyst in organic synthesis, and is dissolved in a byproduct ethanol, so that the reaction is facilitated to proceed forward.
Preferably, the mixture is obtained by mixing an HY type solid acid molecular sieve and EDCl in a molar ratio of 3-4:1.
Preferably, the hydrazine hydrate in the step S1 is 80% by mass, so that high-concentration hydrazine hydrate is avoided, and experimental safety and economic benefit are ensured.
Preferably, the temperature during heating and stirring in the step S1 is 58-63 ℃ and the stirring time is 3.5-4.5h.
Preferably, the temperature T1 in step S2 is 98-103 ℃, and the byproduct ethanol and water in the mixture a, EDCl in the catalyst, and ethyl acetate that is not completely reacted are removed.
Preferably, the temperature T2 in step S3 is 120-123 ℃, and the hydrazine hydrate that is not fully reacted in the solution is removed.
Preferably, in the step S4, the temperature T3 is 129-135 ℃, the product acethydrazide is distilled out from the reaction system, and the acethydrazide and the HY type solid acid molecular sieve catalyst are separated.
The invention has the beneficial effects that:
The invention provides a green synthesis process of high-content acethydrazide, which is characterized in that ethyl acetate and hydrazine hydrate are heated to react under the action of a catalyst by a one-pot method, then distilled at three different temperatures respectively, various impurities in a crude product are gradually removed, and finally the acethydrazide is prepared. The method has the advantages that the method reduces intermediate steps and separation and purification steps of products, is beneficial to maintaining higher raw material conversion rate and product yield, can improve impurity removal rate by repeated steaming, can reduce material loss by directly steaming the products out of a reaction system, improves overall yield and product purity, ensures that the prepared acethydrazide has extremely high yield and purity and simple process, greatly saves production cost and labor cost, and has wide application prospect.
Drawings
In order to more clearly illustrate the invention or the technical solutions of the prior art, the drawings which are used in the description of the embodiments or the prior art will be briefly described, it being obvious that the drawings in the description below are only of the invention and that other drawings can be obtained from them without inventive effort for a person skilled in the art.
FIG. 1 is a flow chart of the preparation of the acethydrazide in the invention;
FIG. 2 is a schematic diagram of the structure of a three-necked flask in the reaction system of the present invention;
The reference numerals indicate that 1, a first feed inlet, 2, a second feed inlet, 3, a third feed inlet;
FIG. 3 is a 1 H NMR spectrum of the acethydrazide prepared in example 2 of the present invention.
Detailed Description
The present invention will be further described in detail with reference to specific embodiments in order to make the objects, technical solutions and advantages of the present invention more apparent.
The sources and properties of part of raw materials adopted by the invention are as follows:
Ethyl acetate was purchased from shandong rui double chemical engineering limited, hydrazine hydrate with mass fraction of 80% was purchased from Huang Shanshi bas chemical engineering auxiliary agent limited, EDCl was purchased from shanghai maokang biotechnology limited, and HY type solid acid molecular sieve was purchased from dalbergia environmental protection technology limited.
Example 1:
A green synthesis process of high-content acethydrazide comprises a reaction system and a purification system;
The reaction system comprises a three-necked flask, wherein the three-necked flask comprises a first feed inlet 1, a second feed inlet 2 and a third feed inlet 3 which are respectively positioned at two sides of the first feed inlet, a condensing pipe is arranged above the second feed inlet 2 and the third feed inlet 3 through rubber pipes, a hemostatic clamp is arranged between the second feed inlet 2 and the condensing pipe, and a hemostatic clamp is arranged between the third feed inlet 3 and the condensing pipe.
Example 2A green synthesis process for high content of acethydrazide, comprising the following steps:
S1, under the protection of nitrogen, sequentially closing a hemostatic clamp on one side of a second feeding hole 2 and a hemostatic clamp on one side of a third feeding hole 3, sequentially putting hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (22.03 g,0.25 mol) and a catalyst (0.016 mol) with mass fraction of 80% into a flask, and heating and stirring for 4.5h at 58 ℃ to obtain a mixture A, wherein the molar ratio of HY type solid acid molecular sieve to EDCl in the catalyst is 3:1;
S2, opening a hemostatic clamp at one side of the second feeding hole 2, heating and stirring the mixture A, and changing the temperature of the system to 98 ℃ until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
s3, changing the temperature of the system to 120 ℃, and uniformly stirring until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
s4, closing a hemostatic clamp at one side of the second feeding hole 2, opening a hemostatic clamp at one side of the third feeding hole 3, changing the system temperature to 129 ℃ again, and uniformly stirring until the water level in the receiving container at the outlet of the condensing tube is not increased any more, thus obtaining the acethydrazide;
from the 1 H NMR spectrum of FIG. 3, it was confirmed that the synthesis of acethydrazide was successful.
Example 3A green synthesis process for high content of acethydrazide, comprising the following steps:
S1, under the protection of nitrogen, sequentially closing a hemostatic clamp on one side of a second feeding hole 2 and a hemostatic clamp on one side of a third feeding hole 3, sequentially putting hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (22.03 g,0.25 mol) and a catalyst (0.018 mol) with mass fraction of 80% into a flask, and heating and stirring for 4.5h at 59 ℃ to obtain a mixture A, wherein the molar ratio of HY type solid acid molecular sieve to EDCl in the catalyst is 3:1;
S2, opening a hemostatic clamp at one side of the second feeding hole 2, heating and stirring the mixture A, and changing the temperature of the system to 99 ℃ until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
s3, changing the temperature of the system to 121 ℃, and uniformly stirring until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
S4, closing the hemostatic clamp on one side of the second feeding hole 2, opening the hemostatic clamp on one side of the third feeding hole 3, changing the system temperature to 130 ℃ again, and stirring uniformly until the water level in the receiving container at the outlet of the condensing tube is not increased any more, thus obtaining the acethydrazide.
Example 4A green synthesis process for high content of acethydrazide, comprising the following steps:
S1, under the protection of nitrogen, sequentially closing a hemostatic clamp on one side of a second feeding hole 2 and a hemostatic clamp on one side of a third feeding hole 3, sequentially putting hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (22.91 g,0.26 mol) and a catalyst (0.02 mol) with mass fraction of 80% into a flask, and heating and stirring for 4 hours at 60 ℃ to obtain a mixture A, wherein the molar ratio of HY type solid acid molecular sieve to EDCl in the catalyst is 3.5:1;
s2, opening a hemostatic clamp at one side of the second feeding hole 2, heating and stirring the mixture A, and changing the temperature of the system to 100 ℃ until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
s3, changing the temperature of the system to 121 ℃, and uniformly stirring until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
S4, closing the hemostatic clamp on one side of the second feeding hole 2, opening the hemostatic clamp on one side of the third feeding hole 3, changing the system temperature to 132 ℃ again, and stirring uniformly until the water level in the receiving container at the outlet of the condensing tube is not increased any more, thus obtaining the acethydrazide.
Example 5A green synthesis process for high content of acethydrazide, comprising the following steps:
s1, under the protection of nitrogen, sequentially closing a hemostatic clamp on one side of a second feeding hole 2 and a hemostatic clamp on one side of a third feeding hole 3, sequentially putting hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (22.91 g,0.26 mol) and a catalyst (0.024 mol) with mass fraction of 80% into a flask, and heating and stirring for 4 hours at 61 ℃ to obtain a mixture A, wherein the molar ratio of HY type solid acid molecular sieve to EDCl in the catalyst is 3.5:1;
S2, opening a hemostatic clamp at one side of the second feeding hole 2, heating and stirring the mixture A, and changing the temperature of the system to 101 ℃ until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
s3, changing the temperature of the system to 122 ℃, and uniformly stirring until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
S4, closing the hemostatic clamp on one side of the second feeding hole 2, opening the hemostatic clamp on one side of the third feeding hole 3, changing the system temperature to 133 ℃ again, and stirring uniformly until the water level in the receiving container at the outlet of the condensing tube is not increased any more, thus obtaining the acethydrazide.
Example 6A green synthesis process for high content of acethydrazide, comprising the following steps:
s1, under the protection of nitrogen, sequentially closing a hemostatic clamp on one side of a second feeding hole 2 and a hemostatic clamp on one side of a third feeding hole 3, sequentially putting hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (23.79 g,0.27 mol) and a catalyst (0.028 mol) with mass fraction of 80% into a flask, and heating and stirring for 3.5h at 62 ℃ to obtain a mixture A, wherein the molar ratio of HY type solid acid molecular sieve to EDCl in the catalyst is 4:1;
s2, opening a hemostatic clamp at one side of the second feeding hole 2, heating and stirring the mixture A, and changing the temperature of the system to 102 ℃ until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
s3, changing the temperature of the system to 122 ℃, and uniformly stirring until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
S4, closing the hemostatic clamp on one side of the second feeding hole 2, opening the hemostatic clamp on one side of the third feeding hole 3, changing the system temperature to 134 ℃ again, and stirring uniformly until the water level in the receiving container at the outlet of the condensing tube is not increased any more, thus obtaining the acethydrazide.
Example 7A green synthesis process for high content of acethydrazide, comprising the following steps:
S1, under the protection of nitrogen, sequentially closing a hemostatic clamp on one side of a second feeding hole 2 and a hemostatic clamp on one side of a third feeding hole 3, sequentially putting hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (23.79 g,0.27 mol) and a catalyst (0.03 mol) with mass fraction of 80% into a flask, and heating and stirring for 3.5h at 63 ℃ to obtain a mixture A, wherein the molar ratio of HY type solid acid molecular sieve to EDCl in the catalyst is 4:1;
S2, opening a hemostatic clamp at one side of the second feeding hole 2, heating and stirring the mixture A, and changing the temperature of the system to 103 ℃ until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
s3, changing the temperature of the system to 123 ℃, and uniformly stirring until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
s4, closing the hemostatic clamp on one side of the second feeding hole 2, opening the hemostatic clamp on one side of the third feeding hole 3, changing the system temperature to 135 ℃ again, and stirring uniformly until the water level in the receiving container at the outlet of the condensing tube is not increased any more, thus obtaining the acethydrazide.
Comparative example 1:
In this comparative example, as compared with example 2, only "80% by mass of hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (22.03 g,0.25 mol), and catalyst (0.016 mol)" were adjusted to "80% by mass of hydrazine hydrate (5.01 g,0.1 mol), ethyl acetate (22.03 g,0.25 mol), and catalyst (0.016 mol)", and the other steps and parameters were the same, and the comparative example was not repeated, and finally, acetylhydrazine was obtained.
Comparative example 2:
In this comparative example, as compared with example 2, only "80% by mass of hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (22.03 g,0.25 mol), and catalyst (0.016 mol)" were adjusted to "80% by mass of hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (13.22 g,0.15 mol), and catalyst (0.016 mol)", and the other steps and parameters were the same, and the comparative example was not repeated, and finally, acetylhydrazine was obtained.
Comparative example 3:
In the comparative example, as compared with example 2, only "hydrazine hydrate (10.01 g,0.2 mol) with mass fraction of 80%, ethyl acetate (22.03 g,0.25 mol), catalyst (0.016 mol)" was adjusted to "hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (22.03 g,0.25 mol), catalyst (0.01 mol)" with mass fraction of 80%, and the other steps and parameters were the same, and the comparative example was not repeated to obtain the final product of the acetylhydrazine.
Comparative example 4:
In the comparative example, as compared with example 2, only "hydrazine hydrate (10.01 g,0.2 mol) with mass fraction of 80%, ethyl acetate (22.03 g,0.25 mol), catalyst (0.016 mol)" was adjusted to "hydrazine hydrate (15.02 g,0.3 mol), ethyl acetate (22.03 g,0.25 mol), catalyst (0.016 mol)" with mass fraction of 80%, and the rest steps and parameters are the same, and the comparative example will not be repeated, so that the acetylhydrazine is finally obtained.
Comparative example 5:
In the comparative example, as compared with example 2, only "hydrazine hydrate (10.01 g,0.2 mol) with mass fraction of 80%, ethyl acetate (22.03 g,0.25 mol), catalyst (0.016 mol)" was adjusted to "hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (35.25 g,0.4 mol), catalyst (0.016 mol)" with mass fraction of 80%, and the other steps and parameters were the same, and the comparative example was not repeated to obtain the final product of the acetylhydrazine.
Comparative example 6:
In the comparative example, as compared with example 2, only "hydrazine hydrate (10.01 g,0.2 mol) with the mass fraction of 80%, ethyl acetate (22.03 g,0.25 mol) and catalyst (0.016 mol)" were adjusted to "hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (22.03 g,0.25 mol) and catalyst (0.1 mol)" with the mass fraction of 80%, and the rest steps and parameters are the same, and the comparative example is not repeated, so that the acetylhydrazine is finally obtained.
Comparative example 7:
S1, under the protection of nitrogen, sequentially closing a hemostatic clamp on one side of a second feeding hole 2 and a hemostatic clamp on one side of a third feeding hole 3, sequentially putting hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (22.03 g,0.25 mol) and a catalyst (0.016 mol) with mass fraction of 80% into a flask, and heating and stirring for 4.5h at 58 ℃ to obtain a mixture A, wherein the molar ratio of HY type solid acid molecular sieve to EDCl in the catalyst is 3:1;
S2, opening a hemostatic clamp at one side of the second feeding hole 2, heating and stirring the mixture A, and changing the temperature of the system to 120 ℃ until the water level in the receiving container at the outlet of the condensing tube is not increased any more, so as to obtain a mixture B;
s3, pouring out and filtering the mixture B while the mixture B is hot, and cooling and crystallizing the filtrate, washing the filtrate with pure water and drying the filtrate in vacuum to obtain the acethydrazide.
Comparative example 8:
compared with the comparative example 2, the comparative example only replaces 'hydrazine hydrate with the mass fraction of 80% with' hydrazine hydrate with the mass fraction of 40%, the rest steps and parameters are the same, and repeated description is omitted, so that the acethydrazide is finally obtained.
Performance test:
yield:
Firstly, calculating theoretical yield, namely, assuming the quality of a product when the reaction is completely converted, respectively evaporating and crystallizing the acethydrazide prepared in the examples 2-7 and the comparative examples 1-8 slowly at 58 ℃ and weighing the quality of the acethydrazide actually obtained;
yield calculation formula:
Yield = (actual yield/theoretical yield) ×100%
Purity:
5g of the acethydrazide prepared in example 2-example 7 and comparative example 1-comparative example 8 were accurately weighed out, respectively, and dissolved in chloroform. A series of standard solutions of known concentrations of acetohydrazines were prepared and these solutions were analyzed by HPLC to construct a standard curve. The hydrazide solutions prepared in examples 2 to 7 and comparative examples 1 to 8 were injected into the HPLC system for analysis, the chromatograms of the hydrazides to be measured were recorded and compared with the standard curves, and the concentrations of the hydrazides prepared in examples 2 to 7 and comparative examples 1 to 8 were calculated, respectively.
Purity calculation formula:
Purity= (actual measured concentration/theoretical concentration) ×100%
Table 1 summary of raw material usage amounts for examples 2-7 and comparative examples 1-8
| Project | Hydrazine hydrate dosage/mol | Amount of ethyl acetate/mol | Catalyst amount/mol |
| Example 2 | 0.2 | 0.25 | 0.016 |
| Example 3 | 0.2 | 0.25 | 0.018 |
| Example 4 | 0.2 | 0.26 | 0.02 |
| Example 5 | 0.2 | 0.26 | 0.024 |
| Example 6 | 0.2 | 0.27 | 0.028 |
| Example 7 | 0.2 | 0.27 | 0.03 |
| Comparative example 1 | 0.1 | 0.25 | 0.016 |
| Comparative example 2 | 0.2 | 0.15 | 0.016 |
| Comparative example 3 | 0.2 | 0.25 | 0.01 |
| Comparative example 4 | 0.3 | 0.25 | 0.016 |
| Comparative example 5 | 0.2 | 0.4 | 0.016 |
| Comparative example 6 | 0.2 | 0.25 | 0.1 |
| Comparative example 7 | 0.2 | 0.25 | 0.016 |
| Comparative example 8 | 0.2 | 0.25 | 0.016 |
Table 2 summary of experimental data in example 2-example 7 and comparative example 1-comparative example 8
| Project | Yield/% | Purity/% |
| Example 2 | 99.1 | 99.0 |
| Example 3 | 99.2 | 99.1 |
| Example 4 | 99.5 | 99.4 |
| Example 5 | 99.5 | 99.4 |
| Example 6 | 99.3 | 99.3 |
| Example 7 | 99.0 | 99.1 |
| Comparative example 1 | 96.5 | 96.4 |
| Comparative example 2 | 97.0 | 97.0 |
| Comparative example 3 | 96.6 | 96.7 |
| Comparative example 4 | 98.2 | 98.1 |
| Comparative example 5 | 98.1 | 97.9 |
| Comparative example 6 | 97.8 | 97.5 |
| Comparative example 7 | 97.2 | 96.3 |
| Comparative example 8 | 97.6 | 97.3 |
Data analysis:
As can be seen from Table 2, the acethydrazide prepared by the method has higher yield and purity and simple process, which is probably due to the fact that the method adopts a one-pot method, reduces intermediate steps and separation and purification steps of products, improves the overall synthesis efficiency, is beneficial to maintaining higher raw material conversion rate and product yield, the catalyst used by the method is a mixture of HY type solid acid molecular sieve and EDCl, wherein the HY type solid acid molecular sieve can adsorb byproduct water molecules in pore channels and has good thermal stability, the method is beneficial to forward reaction, the EDCl is easy to dissolve in byproduct ethanol, and is likely to be beneficial to more effectively adsorbing reaction intermediates, reduces reaction energy barrier, accelerates forward reaction rate, reduces byproduct generation, simultaneously facilitates forward reaction, enables the final prepared acethydrazide to have high yield of 99.5%, and the method is distilled at three different temperatures to gradually remove various impurities in crude products and directly distill the products from a reaction system, so that the process is simple and the final prepared acethydrazide has high purity of 99.4%.
Comparative example 1 As a result of adjusting "80% by mass of hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (22.03 g,0.25 mol), catalyst (0.016 mol)" to "80% by mass of hydrazine hydrate (5.01 g,0.1 mol), ethyl acetate (22.03 g,0.25 mol), catalyst (0.016 mol)", it can be seen from Table 2 that the yield and purity of the obtained hydrazine hydrate were low, probably due to the fact that the amount of hydrazine hydrate used was too small and the theoretical amount of ethyl acetate and hydrazine hydrate was 1:1, but in experiments, an appropriate amount of one raw material was generally increased so that the other raw material could be reacted completely, thereby improving the yield, the amount of ethyl acetate unreacted with catalyst was relatively excessive, resulting in a decrease in purity, the yield and purity of comparative example 1 were inferior to those of example 2, and comparative example 2 as a result of "80% by mass of hydrazine hydrate (10.01 g,0.2 mol), Ethyl acetate (22.03 g,0.25 mol), catalyst (0.016 mol) "were adjusted to" 80% by mass of hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (13.22 g,0.15 mol), catalyst (0.016 mol) ", and it can be seen from Table 2 that the yield and purity of the hydrazine hydrate prepared by the method were low, probably due to the fact that the amount of ethyl acetate used was too small, the yield was reduced, the purity of the product in the reaction system was lowered, and thus the yield and purity of comparative example 2 were inferior to those of example 2, and comparative example 3 was due to the fact that" 80% by mass of hydrazine hydrate (10.01 g,0.2 mol), Ethyl acetate (22.03 g,0.25 mol), catalyst (0.016 mol) "were adjusted to" 80% by mass of hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (22.03 g,0.25 mol), catalyst (0.01 mol) ", and it can be seen from Table 2 that the hydrazine hydrate prepared by this method was low in yield and purity, probably due to the fact that the catalyst was too small in amount to be adsorbed by the reactant or product, the active site of the catalyst was likely to be saturated rapidly, the catalyst was deactivated, the catalytic effect was not exerted, the yield was reduced, and the amount of raw materials not involved in the reaction system was increased, so that the yield and purity of comparative example 3 were inferior to those of example 2, and comparative example 4 was prepared by using" 80% by mass of hydrazine hydrate (10.01 g,0.2 mol) " Ethyl acetate (22.03 g,0.25 mol), catalyst (0.016 mol) "were adjusted to" 80% by mass of hydrazine hydrate (15.02 g,0.3 mol), ethyl acetate (22.03 g,0.25 mol), catalyst (0.016 mol) ", and it can be seen from Table 2 that the hydrazine hydrate produced by this method was low in yield and purity, which may be due to the fact that the amount of hydrazine hydrate used was excessive, which may cause unnecessary waste, increased production cost, and separation and purification were not easy, and thus the yield and purity of comparative example 4 were inferior to that of example 2, and comparative example 5 was due to the fact that" 80% by mass of hydrazine hydrate (10.01 g,0.2 mol), Ethyl acetate (22.03 g,0.25 mol), catalyst (0.016 mol) "were adjusted to" 80% by mass of hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (35.25 g,0.4 mol), catalyst (0.016 mol) ", and it can be seen from Table 2 that the yield and purity of the hydrazine hydrate prepared by this method were low, probably due to the fact that the ethyl acetate was used too much, separation and purification were not easy and the reaction direction was likely to be affected, the yield of the hydrazine hydrate was reduced, and thus the yield and purity of comparative example 5 were inferior to those of example 2, and comparative example 6 was due to the fact that" 80% by mass of hydrazine hydrate (10.01 g,0.2 mol) ", Ethyl acetate (22.03 g,0.25 mol), catalyst (0.016 mol) "were adjusted to" 80% by mass of hydrazine hydrate (10.01 g,0.2 mol), ethyl acetate (22.03 g,0.25 mol), catalyst (0.1 mol) "from Table 2, it can be seen that the yield and purity of the hydrazide obtained by this method were low, probably due to excessive catalyst usage, excessive catalyst could cause aggregation or sedimentation between catalysts, thus reducing the total specific surface area of the catalyst, reducing the effective contact area of the catalyst with the reactants, resulting in reduced catalytic efficiency and less separation and purification, thus lowering yield and purity, and thus the yield and purity of comparative example 6 were inferior to those of example 2, and comparative example 7, because multiple re-evaporation separation and purification were not performed, it can be seen from Table 2 that the yield of the hydrazide obtained by this method, The purity is lower, this is probably because the impurity in the system can be effectively removed by repeated re-steaming, the pure acethydrazide is gradually separated by utilizing the vapor-liquid balance difference of different substances at different temperatures, so that the purity of the acethydrazide is improved, the loss of materials can be reduced by directly steaming out of the reaction system, the product is not required to be transferred into another container for separation, and the overall yield can be improved, thus the yield and purity of comparative example 7 are poorer than those of example 2, and the yield and purity of comparative example 8 are poorer than those of example 2 because the product is not required to be transferred into another container, and the yield of the acethydrazide prepared by the method can be seen from table 2, the lower purity may be due to the lower concentration of hydrazine hydrate which reduces the concentration of the effective reactant, resulting in a reduced reaction rate, and thus may require a longer reaction time or higher temperature to achieve the same conversion, thereby affecting the yield and purity of the reaction, and thus the yield and purity of comparative example 8 are inferior to those of example 2.
It will be appreciated by persons skilled in the art that the above discussion of any embodiment is merely exemplary and is not intended to imply that the scope of the invention is limited to these examples, that combinations of technical features in the above embodiments or in different embodiments may also be implemented in any order, and that many other variations of the different aspects of the invention as described above exist, which are not provided in detail for the sake of brevity.
The present invention is intended to embrace all such alternatives, modifications and variances which fall within the broad scope of the appended claims. Therefore, any omission, modification, equivalent replacement, improvement, etc. of the present invention should be included in the scope of the present invention.
Claims (3)
1. The green synthesis process of the high-content acethydrazide is characterized by comprising a reaction system and a purification system;
The reaction system comprises a three-necked flask which is used, wherein the three-necked flask comprises a first feeding port (1), a second feeding port (2) and a third feeding port (3) which are respectively positioned at two sides of the three-necked flask, a condensing pipe is arranged above the second feeding port (2) and the third feeding port (3) through rubber pipes, a hemostatic clamp is arranged between the second feeding port (2) and the condensing pipe, and a hemostatic clamp is arranged between the third feeding port (3) and the condensing pipe;
The synthesis process comprises the following steps:
S1, under the protection of nitrogen, sequentially closing a hemostatic clamp at one side of a second feeding hole (2) and a hemostatic clamp at one side of a third feeding hole (3), sequentially placing hydrazine hydrate, ethyl acetate and a catalyst into a flask, and heating and stirring to obtain a mixture A;
s2, opening a hemostatic clamp at one side of the second feed inlet (2), heating and stirring the mixture A, and changing the system temperature to T1 until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
S3, changing the system temperature to T2, and uniformly stirring until the water level in the receiving container at the outlet of the condensing tube is not increased any more;
S4, closing a hemostatic clamp at one side of the second feeding hole (2), opening a hemostatic clamp at one side of the third feeding hole (3), changing the system temperature to T3 again, and uniformly stirring until the water level in the receiving container at the outlet of the condensing tube is not increased any more, thus obtaining the acethydrazide;
The molar ratio of the hydrazine hydrate to the ethyl acetate to the catalyst in the step S1 is 0.2:0.25-0.27:0.016-0.03;
the temperature T1 in the step S2 is 98-103 ℃;
The temperature T2 in the step S3 is 120-123 ℃;
The temperature T3 in the step S4 is 129-135 ℃;
The catalyst in the step S1 is a mixture of HY type solid acid molecular sieve and EDCl;
the mixture is obtained by mixing an HY type solid acid molecular sieve and EDCl in a molar ratio of 3-4:1.
2. The green synthesis process of high-content acethydrazide as claimed in claim 1, wherein the hydrazine hydrate in the step S1 is 80% by mass of hydrazine hydrate.
3. The green synthesis process of high content of acethydrazide according to claim 1, wherein the temperature during heating and stirring in the step S1 is 58-63 ℃ and the stirring time is 3.5-4.5h.
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