CN114394916B - Preparation method of O-3-chloro-2-propenyl hydroxylamine - Google Patents
Preparation method of O-3-chloro-2-propenyl hydroxylamine Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims abstract description 32
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000003513 alkali Substances 0.000 claims abstract description 24
- 239000007788 liquid Substances 0.000 claims abstract description 23
- UOORRWUZONOOLO-OWOJBTEDSA-N (E)-1,3-dichloropropene Chemical compound ClC\C=C\Cl UOORRWUZONOOLO-OWOJBTEDSA-N 0.000 claims abstract description 20
- UOORRWUZONOOLO-UHFFFAOYSA-N telone II Natural products ClCC=CCl UOORRWUZONOOLO-UHFFFAOYSA-N 0.000 claims abstract description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 18
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims abstract description 17
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000004821 distillation Methods 0.000 claims abstract description 14
- 239000007864 aqueous solution Substances 0.000 claims abstract description 10
- 238000003756 stirring Methods 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 238000010992 reflux Methods 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 34
- 239000000243 solution Substances 0.000 claims description 20
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- ZNBNBTIDJSKEAM-UHFFFAOYSA-N 4-[7-hydroxy-2-[5-[5-[6-hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-3-methyloxolan-2-yl]-5-methyloxolan-2-yl]-2,8-dimethyl-1,10-dioxaspiro[4.5]decan-9-yl]-2-methyl-3-propanoyloxypentanoic acid Chemical compound C1C(O)C(C)C(C(C)C(OC(=O)CC)C(C)C(O)=O)OC11OC(C)(C2OC(C)(CC2)C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CC1 ZNBNBTIDJSKEAM-UHFFFAOYSA-N 0.000 claims description 8
- 229910000378 hydroxylammonium sulfate Inorganic materials 0.000 claims description 8
- 239000012153 distilled water Substances 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 239000002904 solvent Substances 0.000 abstract description 5
- 238000002156 mixing Methods 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 239000012535 impurity Substances 0.000 description 6
- 239000013067 intermediate product Substances 0.000 description 6
- NPEDVEDZDRRUJI-UHFFFAOYSA-N n-(3-chloroprop-2-enyl)hydroxylamine Chemical compound ONCC=CCl NPEDVEDZDRRUJI-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 238000005576 amination reaction Methods 0.000 description 4
- 238000006266 etherification reaction Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- FHKYMEGVIVZQAD-UHFFFAOYSA-N [N].ON Chemical compound [N].ON FHKYMEGVIVZQAD-UHFFFAOYSA-N 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- -1 ketone compound Chemical class 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000005497 Clethodim Substances 0.000 description 1
- NPEDVEDZDRRUJI-OWOJBTEDSA-N ONC\C=C\Cl Chemical compound ONC\C=C\Cl NPEDVEDZDRRUJI-OWOJBTEDSA-N 0.000 description 1
- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000005262 alkoxyamine group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- SILSDTWXNBZOGF-KUZBFYBWSA-N chembl111058 Chemical compound CCSC(C)CC1CC(O)=C(\C(CC)=N\OC\C=C\Cl)C(=O)C1 SILSDTWXNBZOGF-KUZBFYBWSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-N hydroperoxyl Chemical compound O[O] OUUQCZGPVNCOIJ-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- NXEMFEXLQSNTIY-UHFFFAOYSA-N sodium;n-oxidoacetamide Chemical compound [Na+].CC(=O)N[O-] NXEMFEXLQSNTIY-UHFFFAOYSA-N 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
- C07C239/08—Hydroxylamino compounds or their ethers or esters
- C07C239/20—Hydroxylamino compounds or their ethers or esters having oxygen atoms of hydroxylamino groups etherified
Abstract
The invention relates to a preparation method of O-3-chloro-2-propenyl hydroxylamine, which comprises the following steps: s1, adding hydroxylamine aqueous solution and methyl acetate into a flask, completely mixing, adding a 4-dimethylaminopyridine catalyst, and then dropwise adding alkali into the flask for reaction; s2, adding trans-1, 3 dichloropropene into the flask again, heating and maintaining the temperature for reaction; s3, adding hydrochloric acid, stirring, and then carrying out reflux reaction; s4, after the organic matters are separated by reduced pressure distillation, adding liquid alkali to adjust the pH; s5, extracting at room temperature, and then decompressing and distilling to remove the solvent to obtain the O-3-chloro-2-propenyl hydroxylamine.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method of O-3-chloro-2-propenyl hydroxylamine.
Background
O-3-chloro-2-propenyl hydroxylamine, also known as chloramine, trans-3-chloro-2-propenyl hydroxylamine, can be used as an alkylamine reagent, introduces an alkoxyamine group into a ketone compound (especially a steroid compound) in organic synthesis and new drug production, can be used as an intermediate in drug production, can also be used as an intermediate in the field of new medicine and new pesticide creation, and is an important intermediate in the production of clethodim.
The existing method for synthesizing the chloramine mainly comprises the following steps of hydrolyzing acetone oxime ether, reacting ketone and hydroxylamine in an alkaline environment to generate oxime, reacting with trans-1, 3-dichloropropene to generate oxime ether, and adding hydrochloric acid to hydrolyze the ketone to obtain the chloramine. The hydrolysis reaction is an equilibrium reaction, the generated acetone is required to be removed continuously to complete the reaction, and the operation is complicated. The other most commonly used method is an oxime method, in which hydroxylamine sulfate is used to react with methyl acetate under alkaline conditions to generate sodium acetylhydroxamate, hydroxylamine nitrogen is protected, then the hydroxylamine nitrogen reacts with trans-1, 3-dichloropropene to generate oxime ether, and nitrogen protecting groups are hydrolyzed to obtain the product chloramine.
The existing methods have the defects, and industrial mass production is highly demanded to develop more competitive preparation methods.
Disclosure of Invention
The invention aims to solve the defects in the prior art and provides a preparation method of O-3-chloro-2-propenyl hydroxylamine, which is realized by adopting the following technical scheme:
a preparation method of O-3-chloro-2-propenyl hydroxylamine comprises the following steps:
s1, adding hydroxylamine aqueous solution and methyl acetate into a flask in proportion, adding a 4-dimethylaminopyridine catalyst, and then dropwise adding alkali into the flask for reaction;
s2, adding trans-1, 3 dichloropropene into the flask again, heating and maintaining the temperature for reaction;
s3, adding hydrochloric acid and stirring after the reaction, and then carrying out reflux reaction;
s4, after the organic matters are separated by reduced pressure distillation, adding liquid alkali to adjust the pH;
s5, extracting for multiple times at room temperature, and removing the extractant by reduced pressure distillation again to obtain the O-3-chloro-2-propenyl hydroxylamine.
As a further improvement, the preparation method of the hydroxylamine aqueous solution comprises the following steps:
1) Distilled water and hydroxylamine sulfate are proportionally added into a flask;
2) And (5) dropwise adding alkali to prepare the hydroxylamine aqueous solution.
As a further improvement, the molar ratio of the aqueous hydroxylamine solution to methyl acetate and 4-dimethylaminopyridine is n (hydroxylamine): n (methyl acetate): n (4-dimethylaminopyridine) is 1:1.1:0.01-0.10.
As a further improvement, the liquid base is a 30% naoh aqueous solution, and the liquid base ratio n (hydroxylamine) added dropwise into the hydroxylamine aqueous solution: n (NaOH) is: 1:2.1.
as a further improvement, the ratio of the added trans-1, 3 dichloropropene to the aqueous hydroxylamine solution is n (trans-1, 3 dichloropropene): n (hydroxylamine) is 1:1.
as a further improvement, in the step S2, the temperature is raised and maintained at 50-70 ℃ for 5-7 hours.
As a further improvement, in the step S3, the reflux reaction maintains the temperature for 2 hours.
As a further improvement, in the step 34, a liquid alkali is added to adjust the pH to be more than 9.
The beneficial effects of the invention are as follows:
the synthetic route of the O-3-chloro-2-propenyl hydroxylamine is as follows:
the preparation of O-3-chloro-2-propenyl hydroxylamine can be divided into three parts, namely amination, etherification and hydrolysis, wherein the amination reaction is to produce sodium acetylhydroxamate by reacting hydroxylamine sulfate with methyl acetate in alkaline environment; the etherification reaction is to produce an intermediate product 3-chloro-2-propenyl hydroxylamine by reacting sodium acetylhydroxamate with trans-1, 3-dichloropropene; the hydrolysis reaction is that the intermediate product 3-chloro-2-propenyl hydroxylamine is hydrolyzed under an acidic medium to produce O-3-chloro-2-propenyl hydroxylamine.
By adopting the technical scheme, the prepared O-3-chloro-2-propenyl hydroxylamine has few impurities and does not influence the downstream product quality of the chloramine. By adopting the above technical scheme, the excess methyl acetate is added to obtain a larger yield of sodium acetohydroxamate, and the additional methyl acetate can be hydrolyzed in an alkaline solution. By adopting the technical scheme, experiments show that the addition of liquid alkali ensures the alkaline environment of the solution, trans-1, 3 dichloropropene preferentially reacts with hydroxyl oxygen in the alkaline environment to form an intermediate product 3-chloro-2-propenyl hydroxylamine, when the 3-chloro-2-propenyl hydroxylamine reaches a certain concentration, trans-1, 3 dichloropropene starts to react with the 3-chloro-2-propenyl hydroxylamine, the stronger the alkalinity of the reaction solution is, nitrogen is more easily combined with alkali metal to form salt, the more impurity precursors are produced, and the proportion is the optimal reaction condition that the intermediate product content is the largest and the impurity precursors are less.
By adopting the technical scheme, the reaction is incomplete due to the lower reaction temperature and shorter reaction time, a large amount of trans-1, 3-dichloropropene reactant remains, and the production of the intermediate product is promoted while the production of the impurity precursor is facilitated due to the higher reaction temperature and longer reaction time.
By adopting the technical scheme, excessive hydrochloric acid is added for mixing, so that the solution can be changed into an acidic environment while the rest liquid alkali is neutralized, and the intermediate product 3-chloro-2-propenyl hydroxylamine is hydrolyzed under the acidic environment to produce O-3-chloro-2-propenyl hydroxylamine. By adopting the technical scheme, after extraction, organic solvents such as methanol and part of impurities can be removed by reduced pressure distillation, and finally colorless transparent liquid, namely O-3-chloro-2-propenyl hydroxylamine, can be obtained.
The preparation of O-3-chloro-2-propenyl hydroxylamine can be divided into three parts, namely amination, etherification and hydrolysis in sequence. The invention surprisingly discovers that the 4-dimethylaminopyridine is added into a reaction system as a catalyst, has unexpected effects on the reactions of amination, etherification and hydrolysis, greatly improves the selectivity of the reaction, reduces the occurrence of side reactions, has simple operation and high yield, safely and effectively reduces the occurrence of impurities, and is suitable for large-scale industrial production. This is probably because 4-dimethylaminopyridine is a novel high-efficiency catalyst widely used in chemical synthesis in recent years, and its structural electron-donating dimethylamino group resonates with a parent ring (pyridine ring) and can strongly activate nitrogen atoms on the ring for nucleophilic substitution, and remarkably catalyze acylation (phosphorylation, sulfonylation, and carbo-acylation) reactions of alcohols and amines with high steric hindrance and low reactivity, and its activity is about 10 of pyridine 4-6 Multiple times.
Detailed Description
The technical scheme of the present invention will be further described in detail with reference to specific examples, but the scope of the present invention is not limited to the examples.
Example 1
Into the first three-necked flask, 71.0g of distilled water and 100g of hydroxylamine sulfate were successively added, followed by dropwise addition of 162.8g of liquid alkali to prepare 207.2g of an aqueous hydroxylamine solution. The prepared aqueous hydroxylamine solution was poured into a second three-necked flask, 99.6g of methyl acetate was further added, stirring was started, 1.5g of 4-dimethylaminopyridine catalyst was further added, 196g of 30% aqueous NaOH solution (liquid alkali) was then added dropwise, and the reaction was carried out at 20℃for 1 hour. 136g of trans-1, 3-dichloropropene was added to the second three-necked flask, and the temperature was raised to 50℃to conduct a reaction for 7 hours. The above raw material molar ratio n (hydroxylamine): n (methyl acetate): n (4-dimethylaminopyridine): n (NaOH): n (trans-1, 3-dichloropropene) is 1:1.1:0.01:2.1:1.
180g of hydrochloric acid are then added, and after stirring, the mixture is refluxed at 60℃for 2h. After the solvent is removed by reduced pressure distillation, liquid alkali is added to adjust the pH value to be more than 9, dichloromethane is used for extraction for 3 times at room temperature, and the dichloromethane is removed by reduced pressure distillation again, so that the target product O-3-chloro-2-propenyl hydroxylamine is obtained, and the yield is 96.5%.
Example 2
Into the first three-necked flask, 71.0g of distilled water and 100g of hydroxylamine sulfate were successively added, followed by dropwise addition of 162.8g of liquid alkali to prepare 207.2g of an aqueous hydroxylamine solution. The prepared aqueous hydroxylamine solution was poured into a second three-necked flask, 99.6g of methyl acetate was further added, stirring was started, 15.0g of 4-dimethylaminopyridine catalyst was further added, 196g of 30% aqueous NaOH solution (liquid alkali) was then added dropwise, and the reaction was carried out at 20℃for 1 hour. 136g of trans-1, 3-dichloropropene was added to the second three-necked flask, and the temperature was raised to 70℃to carry out a reaction for 5 hours. The above raw material molar ratio n (hydroxylamine): n (methyl acetate): n (4-dimethylaminopyridine): n (NaOH): n (trans-1, 3-dichloropropene) is 1:1.1:0.1:2.1:1.
180g of hydrochloric acid are then added, and after stirring, the mixture is refluxed at 60℃for 2h. After the solvent is removed by reduced pressure distillation, liquid alkali is added to adjust the pH value to be more than 9, dichloromethane is used for extraction for 3 times at room temperature, and the dichloromethane is removed by reduced pressure distillation again, so that the target product O-3-chloro-2-propenyl hydroxylamine is obtained, and the yield is 98.8%.
Example 3
Into the first three-necked flask, 71.0g of distilled water and 100g of hydroxylamine sulfate were successively added, followed by dropwise addition of 162.8g of liquid alkali to prepare 207.2g of an aqueous hydroxylamine solution. The prepared aqueous hydroxylamine solution was poured into a second three-necked flask, 99.6g of methyl acetate was further added, stirring was started, 7.5g of 4-dimethylaminopyridine catalyst was further added, 196g of 30% aqueous NaOH solution (liquid alkali) was then added dropwise, and the reaction was carried out at 20℃for 1 hour. 136g of trans-1, 3-dichloropropene was added to the second three-necked flask, and the temperature was raised to 60℃to carry out a reaction for 6 hours. The above raw material molar ratio n (hydroxylamine): n (methyl acetate): n (4-dimethylaminopyridine): n (NaOH): n (trans-1, 3-dichloropropene) is 1:1.1:0.05:2.1:1.
180g of hydrochloric acid are then added, and after stirring, the mixture is refluxed at 60℃for 2h. After the solvent is removed by reduced pressure distillation, liquid alkali is added to adjust the pH value to be more than 9, dichloromethane is used for extraction for 3 times at room temperature, and the dichloromethane is removed by reduced pressure distillation again, so that the target product O-3-chloro-2-propenyl hydroxylamine is obtained, and the yield is 99.2%.
Comparative example 1
Into the first three-necked flask, 71.0g of distilled water and 100g of hydroxylamine sulfate were successively added, followed by dropwise addition of 162.8g of liquid alkali, to prepare 207.2g of an aqueous hydroxylamine solution. The prepared aqueous hydroxylamine solution was poured into a second three-necked flask, 99.6g of methyl acetate was further added, magnetic stirring was started, 196g of 30% aqueous NaOH solution (liquid alkali) was added dropwise, and the temperature was kept at 20℃and the reaction was carried out for 1 hour. 136g of trans-1, 3-dichloropropene was added to the second three-necked flask, and the temperature was raised to 60℃to carry out a reaction for 6 hours. The above-mentioned dropwise molar ratio n (hydroxylamine): n (NaOH): n (trans-1, 3-dichloropropene) is 1:2.1:1.
180g of hydrochloric acid are then added, and after stirring, the mixture is refluxed at 60℃for 2h. After the solvent was removed by distillation under reduced pressure, pH was adjusted to more than 9 by addition of liquid alkali, extraction was performed 3 times with methylene chloride at room temperature, and the methylene chloride was removed by distillation under reduced pressure again to obtain the objective O-3-chloro-2-propenyl hydroxylamine in 82.5% yield.
As can be seen, the product yield was greatly reduced to 82.5% compared to comparative example 1 and example 3 due to the lack of catalysis by 4-dimethylaminopyridine.
Finally, it should also be noted that the above list is merely a specific example of the invention. Obviously, the invention is not limited to the above embodiment examples, but many variations are possible. All modifications directly derived or suggested to one skilled in the art from the present disclosure should be considered as being within the scope of the present invention.
Claims (8)
1. The preparation method of the O-3-chloro-2-propenyl hydroxylamine is characterized by comprising the following steps:
s1, adding hydroxylamine aqueous solution and methyl acetate into a flask in proportion, adding a 4-dimethylaminopyridine catalyst, and then dropwise adding alkali into the flask for reaction;
s2, adding trans-1, 3-dichloropropene into the flask again, heating and maintaining the temperature for reaction;
s3, adding hydrochloric acid and stirring after the reaction, and then carrying out reflux reaction;
s4, after the organic matters are separated by reduced pressure distillation, adding liquid alkali to adjust the pH;
s5, extracting for multiple times at room temperature, and removing the extractant by reduced pressure distillation again to obtain the O-3-chloro-2-propenyl hydroxylamine.
2. The method for preparing O-3-chloro-2-propenyl hydroxylamine according to claim 1, wherein the method for preparing the aqueous hydroxylamine solution comprises the following steps:
1) Distilled water and hydroxylamine sulfate are proportionally added into a flask;
2) And (5) dropwise adding alkali to prepare the hydroxylamine aqueous solution.
3. The method for preparing O-3-chloro-2-propenyl hydroxylamine according to claim 1, wherein in the step S1, hydroxylamine in the aqueous hydroxylamine solution comprises methyl acetate: the molar ratio of 4-dimethylaminopyridine is 1:1.1:0.01-0.10.
4. The method for preparing O-3-chloro-2-propenyl hydroxylamine according to claim 1, wherein in the step S1, the liquid alkali is 30% NaOH aqueous solution, and the molar ratio of hydroxylamine to NaOH in the hydroxylamine aqueous solution is: 1:2.1.
5. the method for preparing O-3-chloro-2-propenyl hydroxylamine according to claim 1, wherein in step S1, the molar ratio of trans-1, 3-dichloropropene added to hydroxylamine in the aqueous hydroxylamine solution is 1:1.
6. the method for producing O-3-chloro-2-propenylhydroxylamine according to claim 1 or 2 or 3 or 4 or 5, wherein in the step S2, the temperature is raised and maintained at 50 to 70 ℃ for a reaction time of 5 to 7 hours.
7. The method for producing O-3-chloro-2-propenyl hydroxylamine according to claim 6, wherein in the step S3, the reflux reaction is maintained at a temperature for 2 hours.
8. The method for producing O-3-chloro-2-propenyl hydroxylamine according to claim 1 or 2 or 3 or 4 or 5 or 7, wherein in step S4, the pH is adjusted to more than 9 by adding a liquid base.
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