CN117247364A - N, N-diacetyl- [1,4,5] oxadiazepine and preparation method thereof - Google Patents
N, N-diacetyl- [1,4,5] oxadiazepine and preparation method thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 238000006243 chemical reaction Methods 0.000 claims abstract description 61
- UCFXDDIPFRIIFO-UHFFFAOYSA-N n-acetylacetohydrazide Chemical compound CC(=O)N(N)C(C)=O UCFXDDIPFRIIFO-UHFFFAOYSA-N 0.000 claims abstract description 40
- 238000000034 method Methods 0.000 claims abstract description 32
- ZNSMNVMLTJELDZ-UHFFFAOYSA-N Bis(2-chloroethyl)ether Chemical compound ClCCOCCCl ZNSMNVMLTJELDZ-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000002904 solvent Substances 0.000 claims abstract description 22
- 239000000203 mixture Substances 0.000 claims abstract description 20
- 239000003513 alkali Substances 0.000 claims abstract description 16
- 239000002585 base Substances 0.000 claims abstract description 13
- 238000002156 mixing Methods 0.000 claims abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 60
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 57
- 239000000047 product Substances 0.000 claims description 26
- 239000011259 mixed solution Substances 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 19
- 239000000243 solution Substances 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 238000010924 continuous production Methods 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000001103 potassium chloride Substances 0.000 claims description 5
- 235000011164 potassium chloride Nutrition 0.000 claims description 5
- 239000000758 substrate Substances 0.000 claims description 5
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- ARXJGSRGQADJSQ-UHFFFAOYSA-N 1-methoxypropan-2-ol Chemical compound COCC(C)O ARXJGSRGQADJSQ-UHFFFAOYSA-N 0.000 claims description 2
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical class 0.000 claims 5
- 150000001875 compounds Chemical class 0.000 claims 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- 230000001476 alcoholic effect Effects 0.000 claims 1
- 150000004703 alkoxides Chemical class 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- OTLYTKRAADUASA-UHFFFAOYSA-N oxadiazepane Chemical compound C1CCONNC1 OTLYTKRAADUASA-UHFFFAOYSA-N 0.000 claims 1
- 239000004009 herbicide Substances 0.000 abstract description 2
- 239000007806 chemical reaction intermediate Substances 0.000 abstract 1
- 230000002363 herbicidal effect Effects 0.000 abstract 1
- 239000012535 impurity Substances 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 9
- 239000000843 powder Substances 0.000 description 6
- 238000005086 pumping Methods 0.000 description 5
- 238000007599 discharging Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000005597 Pinoxaden Substances 0.000 description 2
- -1 alkaline earth metal carbonate Chemical class 0.000 description 2
- 150000001341 alkaline earth metal compounds Chemical class 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 2
- MGOHCFMYLBAPRN-UHFFFAOYSA-N pinoxaden Chemical compound CCC1=CC(C)=CC(CC)=C1C(C1=O)=C(OC(=O)C(C)(C)C)N2N1CCOCC2 MGOHCFMYLBAPRN-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 235000007320 Avena fatua Nutrition 0.000 description 1
- 241001647031 Avena sterilis Species 0.000 description 1
- 235000004535 Avena sterilis Nutrition 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 240000004585 Dactylis glomerata Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- 240000001348 Juncus inflexus Species 0.000 description 1
- 241000209082 Lolium Species 0.000 description 1
- 235000010086 Setaria viridis var. viridis Nutrition 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 244000230342 green foxtail Species 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- RYDICHIKLKVOEJ-UHFFFAOYSA-N oxadiazepine Chemical class O1C=CC=CN=N1 RYDICHIKLKVOEJ-UHFFFAOYSA-N 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
- C07D273/02—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having two nitrogen atoms and only one oxygen atom
- C07D273/06—Seven-membered rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention relates to the technical field of herbicide, and provides N, N-diacetyl- [1,4,5] oxadiazepine and a preparation method thereof, wherein the method is obtained by reacting N, N-diacetyl hydrazine and 2, 2-dichloro diethyl ether in the presence of alkali, and specifically comprises the following steps: further mixing a mixture of the N, N-diacetylhydrazine, the 2, 2-dichlorodiethyl ether and a solvent with a base to react the N, N-diacetylhydrazine in the reaction system at a mass concentration of 5% or less. The method can promote more intramolecular reactions, rather than intermolecular reactions, of the reaction intermediates, improves the selectivity of the reaction, and improves the yield of the N, N-diacetyl- [1,4,5] oxadiazepine.
Description
Technical Field
The invention relates to the technical field of herbicides, in particular to N, N-diacetyl- [1,4,5] oxadiazepine and a preparation method thereof.
Background
The pinoxaden is mainly used for preventing and removing annual gramineous weeds in wheat and barley fields after germination, such as alopecuroides, japanese alopecuroides, wild oat, ryegrass, green bristlegrass, hard grass, rush, and clavate grass. The key intermediate for preparing pinoxaden is N, N-diacetyl- [1,4,5] oxadiazepine, the structural formula of N, N-diacetyl- [1,4,5] oxadiazepine is as follows:
the current main synthesis of N, N-diacetyl- [1,4,5] oxadiazepine is that mentioned in patent CN1279032C, and is specifically: firstly adding potassium hydroxide powder into a mixture of N, N-diacetylhydrazine and a solvent, dissolving in a reaction kettle, slowly dripping 2, 2-dichloro diethyl ether in a heating state, reacting for a period of time in a heat-preserving mode, cooling, filtering, desolventizing mother liquor, crystallizing and the like, and finally obtaining the product. However, N-diacetyl- [1,4,5] oxadiazepine has the disadvantage of low yields.
In view of this, the present invention has been proposed.
Disclosure of Invention
The method mentioned in CN1279032C is that N, N-diacetyl hydrazine and potassium hydroxide are mixed and then 2, 2-dichloro diethyl ether is slowly added dropwise, in the reaction process, the N, N-diacetyl hydrazine and the 2, 2-dichloro diethyl ether form an intermediate, and the intermediate is subjected to intramolecular ring closure to form N, N-diacetyl- [1,4,5] oxa-diaza-oxo-cycloheptane, and the specific reaction process is as follows:
the invention further analyzes the obtained reaction product, and finds that the reaction product contains the following impurities:
from the above impurity structure, it can be seen that, in the reaction process, the intermediate formed by the N, N-diacetyl hydrazine and 2, 2-dichloro diethyl ether undergoes intramolecular ring closure to form N, N-diacetyl- [1,4,5] oxa-diazo-oxo-cycloheptane, and at the same time, intermolecular reaction also occurs to form impurities, thereby lowering the yield.
The invention provides N, N-diacetyl- [1,4,5] oxadiazepine and a preparation method thereof, which are used for solving the defect of low yield when N, N-diacetyl- [1,4,5] oxadiazepine is prepared by the prior art.
Specifically, the catalyst is obtained by reacting N, N-diacetylhydrazine and 2, 2-dichloro diethyl ether in the presence of a base, and comprises the following steps: the mixture of the N, N-diacetyl hydrazine, the 2, 2-dichloro diethyl ether and the solvent is further mixed with a base to react the N, N-diacetyl hydrazine in the reaction system at a mass concentration of 5% or less.
The 2, 2-dichlorodiethyl ether in the present invention is also referred to as 2, 2-dichlorodiethyl ether.
According to the invention, the N, N-diacetyl hydrazine and the 2, 2-dichloro diethyl ether are firstly mixed in the solvent and then mixed with the alkali, and the mass concentration of the N, N-diacetyl hydrazine is controlled below 5% during the reaction, so that the intermolecular reaction of the intermediate can be effectively avoided, and the product yield is improved.
Preferably, according to the preparation method of the N, N-diacetyl- [1,4,5] oxadiazepine provided by the invention, the alkali is an alkali metal and/or alkaline earth metal compound, and the alkaline earth metal compound is alkaline earth metal hydroxide, alkaline earth metal carbonate or alkaline earth metal alkoxide;
preferably, the base is one or more of potassium hydroxide, sodium hydroxide, potassium carbonate and potassium ethoxide, and when the base is potassium hydroxide, the following reaction formula is involved:
preferably, according to the present invention, there is providedN, N-diacetyl- [1,4,5] as described above]Process for the preparation of oxadiazepines, the solvent being DMSO ((CH) 3 ) 2 SO), sulfolane ((CH) 2 ) 4 SO 2 )、NMP((CH 2 ) 3 CONCH 3 ) And DMA (CH) 3 CON(CH 3 ) 2 ) More than one of them;
preferably, the solvent is one or more of DMSO, sulfolane, and DMA. In the test, it was found that when the solvent is DMSO, the substrate dispersion is more facilitated while the solubility to potassium hydroxide is optimized, thereby improving the yield, and therefore, it is further preferable that the solvent is DMSO.
Preferably, the preparation method of the N, N-diacetyl- [1,4,5] oxadiazepine provided by the invention comprises the following steps:
mixing N, N-diacetyl hydrazine, 2-dichloro diethyl ether and a solvent to ensure that the mass concentration of the N, N-diacetyl hydrazine is more than 5 percent, and heating the mixture to the temperature of a reaction system of more than 80 ℃, preferably more than 110 ℃, and more preferably 110-150 ℃;
the temperature of the reaction system is maintained above 110 ℃, and the mixed solution comprising the alkali and the solvent is added into the reaction system to enable the mass concentration of the N, N-diacetyl hydrazine to be below 5 percent for reaction for 0.05 to 0.2h, so as to obtain a first product containing the N, N-diacetyl- [1,4,5] oxa-diazo-oxo-cycloheptane.
The above-mentioned mixed solution is obtained by dissolving the above-mentioned alkali in a solvent in advance, and then adding the above-mentioned mixed solution to a reaction system, in addition to promoting the dispersion of the alkali in the system, the formation of impurities can be reduced to thereby improve the selectivity, generally, the mass concentration of the alkali in the mixed solution added to the reaction system is within 30%, and the mass ratio of the alkali to the N, N-diacetylhydrazine is not less than 2.156, preferably 2 to 3, when the reaction is carried out. In order to further avoid the intermolecular reaction of the intermediate from decreasing the formation of impurities and to increase the product yield, the mass concentration of the base in the mixed solution is preferably 5 to 15%.
Meanwhile, the alkali is added into the reaction system under the high-temperature condition, so that the reaction process can be accelerated, but the yield is reduced due to the excessively high temperature.
Preferably, according to the preparation method of the N, N-diacetyl- [1,4,5] oxadiazepine provided by the invention, the preparation method is carried out by adopting a continuous process, and in the continuous process, the mixed solution comprising alkali and solvent is added into a reaction system to enable the mass concentration of the N, N-diacetyl hydrazine to be less than 5 percent for reaction for 0.05 to 0.2 hour, and then the material is discharged.
In practice, it is found that the method mentioned in CN1279032C can result in large heat release, high reaction risk level and is very unfavorable for industrial production, while when the continuous process is adopted in the method of the present invention, the mixture of N, N-diacetylhydrazine, 2-dichloro diethyl ether and DMSO and the mixture containing alkali can be simultaneously fed into the tubular reactor to perform continuous reaction, and the continuous addition of alkali is more favorable for reducing the reaction concentration of the intermediate in the continuous reaction device, and at the reaction temperature of the present invention, more intramolecular reactions are promoted, thereby improving selectivity. Meanwhile, the method has the advantages of fast heat exchange, large flux, high production efficiency, intrinsic safety and low reaction risk level.
In addition, it was found in experiments that in continuous reactions, if the reaction time of the materials is prolonged, the amount of impurities is increased, which is disadvantageous for the improvement of the yield.
Preferably, according to the preparation method of the N, N-diacetyl- [1,4,5] oxadiazepine provided by the invention, the mass ratio of the N, N-diacetyl hydrazine to the 2, 2-dichloro diethyl ether is 1:1.85-2.5 during reaction.
In the method of the invention, the raw materials in the reaction system are controlled within the above range, which is more beneficial to the forward reaction and avoids the generation of impurities.
Preferably, the preparation method of the N, N-diacetyl- [1,4,5] oxadiazepine provided by the invention comprises the following steps:
filtering the product to remove potassium chloride solids;
desolventizing the filtered filtrate to recover solvent and 2, 2-dichlorodiethyl ether therein;
and adding the desolventized substrate into an alcohol solution for crystallization, filtering and drying to obtain a second product containing the N, N-diacetyl- [1,4,5] oxadiazepine, wherein the purity of the N, N-diacetyl- [1,4,5] oxadiazepine in the second product is more than or equal to 91%, and the main impurity is potassium chloride.
Preferably, according to the preparation method of the N, N-diacetyl- [1,4,5] oxadiazepine provided by the invention, the alcohol solution is an aqueous solution containing at least one of methanol, ethanol, propanol, isopropanol, methoxy isopropanol and ethoxyethanol; preferably, the alcohol concentration in the alcohol solution is 95% or more by volume.
The invention also provides a product prepared by the preparation method of the N, N-diacetyl- [1,4,5] oxadiazepine.
The N, N-diacetyl- [1,4,5] oxadiazepine and the preparation method thereof provided by the invention are characterized in that N, N-diacetyl hydrazine, 2-dichloro diethyl ether and a solvent are mixed and heated, and then alkali is added into a reaction system to enable the mass concentration of the N, N-diacetyl hydrazine to be below 5% for reaction.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the present invention more apparent, the technical solutions of the present invention will be clearly and completely described below, 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 specific techniques or conditions are not identified in the examples and are described in the literature in this field or are carried out in accordance with the product specifications. The reagents or equipment used were conventional products available for purchase by regular vendors without the manufacturer's attention. Wherein the content of potassium hydroxide in the potassium hydroxide powder is 91%, and the rest is impurities which do not affect the reaction.
The normal temperature in the invention is 20+/-15 ℃.
Example 1
A method for preparing N, N-diacetyl- [1,4,5] oxadiazepine, which comprises the following steps:
(1) Raw material preparation:
mixture a: consists of N, N-diacetyl hydrazine, 2-dichloro diethyl ether and DMSO, wherein the mass ratio of the N, N-diacetyl hydrazine to the 2, 2-dichloro diethyl ether is 50:92.5, and the mass concentration of the N, N-diacetyl hydrazine is 6.73%;
mixture B: is composed of potassium hydroxide powder and DMSO, wherein the mass concentration of potassium hydroxide is 12.63%.
(2) Preheating the mixture A to 120 ℃, pumping the mixture A into a continuous reaction device by a pump I, at the moment, preheating the mixture B to 120 ℃ at the temperature of 120 ℃ in a reaction system, pumping the mixture B into the reaction system by a pump II, maintaining the temperature of the reaction system at 120 ℃, controlling the pumping amount of the mixture A and the mixture B to ensure that the mass concentration of N, N-diacetylhydrazine in the reaction system is 4.1%, discharging after reacting for 0.1h, and collecting a product.
(3) Filtering the product obtained in the step (2) to remove potassium chloride solids in the product, and collecting filtrate.
(4) Desolventizing the filtrate obtained in the step (3), recovering DMSO and 2, 2-dichloro diethyl ether therein, and collecting a substrate; wherein, DMSO and 2, 2-dichloro diethyl ether can be recycled to the step (1) after dehydration.
(5) And (3) adding the substrate obtained in the step (4) into 95% ethanol solution, crystallizing at the temperature of minus 15 ℃, filtering, and drying a filter cake to obtain a product, wherein the purity of the N, N-diacetyl- [1,4,5] oxadiazepine is 95.2% (the impurity component is mainly potassium chloride), and the yield of the N, N-diacetyl- [1,4,5] oxadiazepine reaches 90.3%.
Example 2
A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine, which comprises substantially the same steps as in example 1, except that: the DMSO equivalent mass in step (1) is replaced by sulfolane.
Example 3
A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine, which comprises substantially the same steps as in example 1, except that: the DMSO equivalent mass in step (1) was replaced with NMP.
Example 4
A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine, which comprises substantially the same steps as in example 1, except that: the DMSO equivalent mass in step (1) is replaced with DMA.
Example 5
A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine, which comprises substantially the same steps as in example 1, except that: and (3) replacing the same mass of potassium hydroxide in the step (1) with sodium hydroxide.
Example 6
A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine, which comprises substantially the same steps as in example 1, except that: and (3) replacing the same mass of potassium hydroxide in the step (1) with potassium carbonate.
Example 7
A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine, which comprises substantially the same steps as in example 1, except that: and (3) replacing the same mass of potassium hydroxide in the step (1) with potassium ethoxide.
Example 8
A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine, which comprises substantially the same steps as in example 1, except that: the temperature of each material in the step (2) is always maintained at 150 ℃.
Example 9
A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine, which comprises substantially the same steps as in example 1, except that: and (3) reducing the mass concentration of the potassium hydroxide powder in the mixture B in the step (1) to 5%.
Example 10
A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine, which comprises substantially the same steps as in example 1, except that: and (3) maintaining the temperature of each material in the step (2) at 110 ℃ all the time.
Example 11
A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine, which comprises substantially the same steps as in example 1, except that: and (3) increasing the mass concentration of the N, N-diacetyl hydrazine in the mixture A in the step (1) to 10%.
Comparative example 1
A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine, which comprises substantially the same steps as in example 11, except that: in the step (2), the pumping amount of the mixture A and the mixture B is controlled to improve the mass concentration of the N, N-diacetyl hydrazine in the reaction system to 7 percent.
Comparative example 2
A method for preparing N, N-diacetyl- [1,4,5] oxadiazepine, which comprises the following steps:
(1) Adding potassium hydroxide powder into a mixed solution C of N, N-diacetylhydrazine and DMSO to obtain a mixed solution D;
(2) Adding 2, 2-dichloro diethyl ether into the mixed solution D with the temperature of 120 ℃ to obtain mixed solution E, maintaining the temperature of the mixed solution E at 120 ℃ for reaction for 0.1h, discharging, and collecting a product; wherein the contents of N, N-diacetylhydrazine, 2-dichlorodiethyl ether and base in the mixture E were the same as those in the reaction system of step (2) of example 1.
The resulting product was treated according to steps (3) to (5) in example 1.
Comparative example 3
A method for preparing N, N-diacetyl- [1,4,5] oxadiazepine, which comprises the following steps:
(1) Adding potassium hydroxide powder into a mixed solution F of 2, 2-dichloro diethyl ether and DMSO to obtain a mixed solution G;
(2) Adding N, N-diacetyl hydrazine into a mixed solution G with the temperature of 120 ℃ to obtain a mixed solution H, maintaining the temperature of the mixed solution H at 120 ℃ for reaction for 0.1H, discharging, and collecting a product; wherein the contents of N, N-diacetylhydrazine, 2-dichlorodiethyl ether and base in the mixed solution H were the same as those in the reaction system of step (2) of example 1.
The resulting product was treated according to steps (3) to (5) in example 1.
Comparative example 4
A method for preparing N, N-diacetyl- [1,4,5] oxadiazepine, which comprises the following steps:
(1) Simultaneously pumping a DMSO solution of N, N-diacetylhydrazine and a DMSO solution of 2, 2-dichloro diethyl ether into a DMSO solution of potassium hydroxide, wherein the temperature of each solution is 120 ℃, so that the contents of N, N-diacetylhydrazine, 2-dichloro diethyl ether and alkali in a reaction system are the same as those in the reaction system in the step (2) of the example 1, maintaining the temperature of the reaction system at 120 ℃, discharging after reaction for 0.25h, and collecting a product.
The resulting product was treated according to steps (3) to (5) in example 1.
The purity of the corresponding products and the yields of N, N-diacetyl- [1,4,5] oxadiazepine for the methods of examples 2 to 11 and comparative examples 1 to 4 are shown in the following table:
| purity (%) | Yield (%) | |
| Example 2 | 94.1 | 61 |
| Example 3 | 92.9 | 52 |
| Example 4 | 92.3 | 66 |
| Example 5 | 94.2 | 83 |
| Example 6 | 93.7 | 77 |
| Example 7 | 94.8 | 55 |
| Example 8 | 93 | 84.5 |
| Example 9 | 95.3 | 89 |
| Example 10 | 92 | 83.3 |
| Example 11 | 95.7 | 90.1 |
| Comparative example 1 | 92.2 | 70.3 |
| Comparative example 2 | 93.7 | 68.3 |
| Comparative example 3 | 90.2 | 71.1 |
| Comparative example 4 | 89.4 | 62.2 |
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims (10)
1. A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine, which comprises reacting N, N-diacetylhydrazine with 2, 2-dichlorodiethyl ether in the presence of a base, comprising: the mixture of the N, N-diacetyl hydrazine, the 2, 2-dichloro diethyl ether and the solvent is further mixed with a base to react the N, N-diacetyl hydrazine in the reaction system at a mass concentration of 5% or less.
2. The process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine according to claim 1, characterized in that the base is a compound of an alkali metal and/or an alkaline earth metal, the compound of an alkaline earth metal being a hydroxide of an alkaline earth metal, a carbonate of an alkaline earth metal, an alkoxide of an alkaline earth metal;
preferably, the alkali is one or more of potassium hydroxide, sodium hydroxide, potassium carbonate and potassium ethoxide, more preferably potassium hydroxide and/or potassium carbonate, still more preferably potassium hydroxide.
3. The method for producing N, N-diacetyl- [1,4,5] oxadiazepine according to claim 1 or 2, wherein the solvent is one or more of DMSO, sulfolane, NMP, and DMA;
preferably, the solvent is one or more of DMSO, sulfolane, and DMA;
further preferably, the solvent is DMSO.
4. A process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine according to any one of claims 1 to 3, comprising:
mixing the N, N-diacetyl hydrazine, 2-dichloro diethyl ether and a solvent, and heating to a reaction system temperature of T ℃, wherein the T ℃ is more than 80 ℃, preferably more than 110 ℃, and more preferably 110-150 ℃;
the temperature of the reaction system is maintained above T ℃, and the mixed solution comprising the alkali and the solvent is added into the reaction system to enable the mass concentration of the N, N-diacetyl hydrazine to be below 5 percent for reaction for 0.05 to 0.2h, so as to obtain a first product containing the N, N-diacetyl- [1,4,5] oxa-diazo-oxo-cycloheptane.
5. The method for producing N, N-diacetyl- [1,4,5] oxadiazepane according to claim 4, wherein the production is carried out by a continuous process, and wherein the mixed solution comprising the base and the solvent is fed into a reaction system in the continuous process, and the reaction is carried out for 0.05 to 0.2 hours at a mass concentration of the N, N-diacetylhydrazine of 5% or less.
6. The process for producing N, N-diacetyl- [1,4,5] oxadiazepine according to claim 4, wherein the mass ratio of N, N-diacetyl hydrazine to 2, 2-dichlorodiethyl ether is 1:1.85 to 2.5.
7. The process for producing N, N-diacetyl- [1,4,5] oxadiazepine according to any one of claims 4 to 6, wherein the mass concentration of the base in the mixed solution added to the reaction system is within 30%, more preferably within 5 to 15%.
8. The process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine according to any one of claims 4 to 7, characterized in that it comprises:
filtering the product to remove potassium chloride solids;
desolventizing the filtered filtrate to recover solvent and 2, 2-dichlorodiethyl ether therein;
and adding the desolventized substrate into an alcohol solution for crystallization, filtering and drying to obtain a second product containing the N, N-diacetyl- [1,4,5] oxadiazepine, wherein the purity of the N, N-diacetyl- [1,4,5] oxadiazepine in the second product is more than or equal to 91 percent.
9. The method for producing N, N-diacetyl- [1,4,5] oxadiazepine according to claim 8, wherein the alcoholic solution is an aqueous solution containing at least one of methanol, ethanol, propanol, isopropanol, methoxyisopropanol and ethoxyethanol; preferably, the alcohol concentration in the alcohol solution is 95% or more by volume.
10. A product according to any one of claims 1 to 9, produced by a process for the preparation of N, N-diacetyl- [1,4,5] oxadiazepine.
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