CN114394916A - 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
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 239000003513 alkali Substances 0.000 claims abstract description 27
- 239000007788 liquid Substances 0.000 claims abstract description 27
- 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
- 239000007864 aqueous solution Substances 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 15
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 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 36
- 239000000243 solution Substances 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- 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
- 238000004519 manufacturing process Methods 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
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 abstract description 5
- 238000002156 mixing Methods 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 230000006872 improvement Effects 0.000 description 7
- 239000013067 intermediate product Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 5
- NPEDVEDZDRRUJI-UHFFFAOYSA-N n-(3-chloroprop-2-enyl)hydroxylamine Chemical compound ONCC=CCl NPEDVEDZDRRUJI-UHFFFAOYSA-N 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 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
- 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
- -1 ketone compound Chemical class 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 230000035484 reaction time Effects 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
- 230000000052 comparative effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000000694 effects Effects 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
- 239000002547 new drug Substances 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 239000005497 Clethodim Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- NPEDVEDZDRRUJI-OWOJBTEDSA-N ONC\C=C\Cl Chemical compound ONC\C=C\Cl NPEDVEDZDRRUJI-OWOJBTEDSA-N 0.000 description 1
- FHKYMEGVIVZQAD-UHFFFAOYSA-N [N].ON Chemical compound [N].ON FHKYMEGVIVZQAD-UHFFFAOYSA-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
- 238000005917 acylation reaction Methods 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
- 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
- 239000012295 chemical reaction liquid Substances 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
- 239000003814 drug Substances 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
- 238000000605 extraction 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
- 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
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 150000003431 steroids Chemical class 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pyridine Compounds (AREA)
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 4-dimethylaminopyridine catalyst, and then adding liquid 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 carrying out reflux reaction; s4, after organic matters are separated by reduced pressure distillation, adding liquid alkali to adjust the pH value; s5 is extracted at room temperature, and then the solvent is removed by reduced pressure distillation, so that the O-3-chloro-2-propenyl hydroxylamine is obtained.
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 chloroamine, trans-3-chloro-2-propenyl hydroxylamine, can be used as an alkylamido reagent, can be used as an intermediate for drug production by introducing an alkoxyamine group to a ketone compound (particularly a steroid) in organic synthesis and new drug production, can also be used as an intermediate in the fields of new drugs and new pesticide creation, and is an important intermediate for producing clethodim.
The current methods for synthesizing the chloramine mainly comprise a plurality of methods, one method is a method for hydrolyzing acetone oxime ether, ketone and hydroxylamine react in an alkaline environment to generate oxime, the oxime ether is generated by reacting with trans-1, 3-dichloropropene, hydrochloric acid is added to hydrolyze the ketone, and the chloramine can be obtained. The hydrolysis reaction of the method is an equilibrium reaction, and the acetone generated in the hydrolysis reaction needs to be continuously removed to completely react, so the operation is complicated. The other method is the oxime method, wherein hydroxylamine sulfate reacts with methyl acetate under alkaline condition to generate sodium acetoxy oximate, hydroxylamine nitrogen is protected, then the sodium acetoxy oximate reacts with trans-1, 3-dichloropropene to generate oxime ether, and the nitrogen protecting group is hydrolyzed to obtain the product of chloramine.
The existing methods have defects, and the development of a more competitive preparation method is urgently needed for industrial mass production.
Disclosure of Invention
In order to solve the defects in the prior art, the invention 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 according to a proportion, adding a 4-dimethylaminopyridine catalyst, and then adding liquid alkali into the flask for reaction;
s2, adding trans-1, 3-dichloropropene into the flask again, heating and maintaining the temperature for reaction;
s3, after the reaction, adding hydrochloric acid, stirring, and then carrying out reflux reaction;
s4, after organic matters are separated by reduced pressure distillation, adding liquid alkali to adjust the pH value;
s5, extracting for many times at room temperature, and removing the extracting agent 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 is as follows:
1) adding distilled water and hydroxylamine sulfate into a flask according to a proportion;
2) and dropwise adding liquid 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) to n (methyl acetate): n (4-dimethylaminopyridine) is 1: 1.1: 0.01-0.10.
As a further improvement, the liquid alkali is a 30% NaOH aqueous solution, and the liquid alkali proportion n (hydroxylamine) added dropwise to the hydroxylamine aqueous solution: n (NaOH) is: 1: 2.1.
as a further improvement, the ratio of the added trans-1, 3 dichloropropene to 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 increased and maintained at 50-70 ℃, and the reaction time is 5-7 h.
As a further improvement, in said step S3, the reflux reaction is maintained at temperature for 2 h.
As a further improvement, in step 34, a liquid alkali is added to adjust the pH to greater than 9.
The invention has the following beneficial effects:
the synthetic route of O-3-chloro-2-propenyl hydroxylamine is as follows:
the preparation of the O-3-chloro-2-propenyl hydroxylamine can be totally divided into three parts, namely amination, etherification and hydrolysis, wherein the amination is to react hydroxylamine sulfate with methyl acetate in an alkaline environment to produce sodium acetoxy oxime; the etherification reaction is to react sodium acetoxymate with trans-1, 3-dichloropropene to produce an intermediate product, namely 3-chloro-2-propenyl hydroxylamine; the hydrolysis reaction is to hydrolyze the intermediate product 3-chloro-2-propenyl hydroxylamine in 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 less impurities, and the quality of downstream products of the chloroamine is not influenced. By adopting the technical scheme, the excess methyl acetate is added to obtain larger yield of the sodium acetoxy oxime, 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 to form an intermediate product 3-chloro-2-propenyl hydroxylamine in the alkaline environment, the trans-1, 3-dichloropropene starts to react with the intermediate product after the 3-chloro-2-propenyl hydroxylamine reaches a certain concentration, the stronger the alkalinity of the reaction liquid is, the more the nitrogen is combined with alkali metal to form salt, the more the impurity precursors are produced, and the proportion is the optimal reaction condition with the largest content of the intermediate product and the smaller content of the impurity precursors.
By adopting the technical scheme, incomplete reaction is often caused by lower reaction temperature and shorter reaction time, a large amount of trans-1, 3 dichloropropene reactant is remained, and the generation of impurity precursors is promoted while the production of intermediate products is facilitated by higher reaction temperature and longer reaction time.
By adopting the technical scheme, excessive hydrochloric acid is added and mixed, the solution can be changed into an acidic environment while the residual liquid alkali is neutralized, and the intermediate product 3-chloro-2-propenyl hydroxylamine is hydrolyzed under the acidic environment to produce the O-3-chloro-2-propenyl hydroxylamine. By adopting the technical scheme, after extraction, organic solvents such as methanol and the like and part of impurities can be removed through reduced pressure distillation, and finally colorless transparent liquid, namely O-3-chloro-2-propenyl hydroxylamine, can be obtained.
The preparation of the O-3-chloro-2-propenyl hydroxylamine can be totally divided into three parts, namely amination, etherification and hydrolysis respectively. The invention has the advantages that the addition of 4-dimethylamino pyridine as a catalyst in a reaction system has unexpected effects on amination, etherification and hydrolysis, greatly improves the selectivity of the reaction, reduces the occurrence of side reactions,simple operation, high yield, safe reaction, effective reduction of impurities and suitability for large-scale industrial production. This is probably because 4-dimethylaminopyridine is a novel highly efficient catalyst widely used in chemical synthesis in recent years, and its resonance of structurally electron-donating dimethylamino group with a parent ring (pyridine ring) strongly activates nitrogen atoms on the ring to perform nucleophilic substitution, remarkably catalyzes acylation (phosphorylation, sulfonylation, carboacylation) reaction of alcohol and amine with high steric hindrance and low reactivity, and has an activity of about 10 of pyridine4-6And (4) doubling.
Detailed Description
The technical solution 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 were successively charged 71.0g of distilled water, 100g of hydroxylamine sulfate, followed by dropwise addition of 162.8g of a liquid alkali to prepare 207.2g of an aqueous hydroxylamine solution. The prepared hydroxylamine aqueous solution was poured into a second three-necked flask, 99.6g of methyl acetate was added thereto, stirring was started, 1.5g of 4-dimethylaminopyridine catalyst was added thereto, 196g of a 30% NaOH aqueous solution (liquid alkali) was added dropwise thereto, and the reaction was carried out at 20 ℃ for 1 hour. 136g of trans-1, 3-dichloropropene are added into the second three-neck flask, the temperature is raised to 50 ℃, and the reaction is carried out for 7 hours. The molar ratio n (hydroxylamine) of the raw materials is as follows: 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 subsequently added, stirred and then refluxed for 2h at 60 ℃. Removing the solvent by reduced pressure distillation, adding liquid alkali to adjust the pH to be more than 9, extracting for 3 times by using dichloromethane at room temperature, and removing the dichloromethane by reduced pressure distillation again to obtain the target product O-3-chloro-2-propenyl hydroxylamine with the yield of 96.5%.
Example 2
Into the first three-necked flask were successively charged 71.0g of distilled water, 100g of hydroxylamine sulfate, followed by dropwise addition of 162.8g of a liquid alkali to prepare 207.2g of an aqueous hydroxylamine solution. Pouring the prepared hydroxylamine aqueous solution into a second three-neck flask, adding 99.6g of methyl acetate, starting stirring, adding 15.0g of 4-dimethylaminopyridine catalyst, then adding 196g of 30% NaOH aqueous solution (liquid alkali) dropwise, keeping the temperature at 20 ℃, and carrying out reaction for 1 h. 136g of trans-1, 3-dichloropropene are added into the second three-neck flask, the temperature is raised to 70 ℃, and the reaction is carried out for 5 hours. The molar ratio n (hydroxylamine) of the raw materials is as follows: 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 subsequently added, stirred and then refluxed for 2h at 60 ℃. Removing the solvent by reduced pressure distillation, adding liquid alkali to adjust the pH to be more than 9, extracting for 3 times by using dichloromethane at room temperature, and removing the dichloromethane by reduced pressure distillation again to obtain the target product O-3-chloro-2-propenyl hydroxylamine with the yield of 98.8%.
Example 3
Into the first three-necked flask were successively charged 71.0g of distilled water, 100g of hydroxylamine sulfate, followed by dropwise addition of 162.8g of a liquid alkali to prepare 207.2g of an aqueous hydroxylamine solution. The prepared hydroxylamine aqueous solution was poured into a second three-necked flask, 99.6g of methyl acetate was added thereto, stirring was started, 7.5g of 4-dimethylaminopyridine catalyst was added thereto, 196g of a 30% NaOH aqueous solution (liquid alkali) was added dropwise thereto, and the reaction was carried out at 20 ℃ for 1 hour. 136g of trans-1, 3-dichloropropene are added into the second three-neck flask, the temperature is raised to 60 ℃, and the reaction is carried out for 6 hours. The molar ratio n (hydroxylamine) of the raw materials is as follows: 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 subsequently added, stirred and then refluxed for 2h at 60 ℃. Removing the solvent by reduced pressure distillation, adding liquid alkali to adjust the pH to be more than 9, extracting for 3 times by using dichloromethane at room temperature, and removing the dichloromethane by reduced pressure distillation again to obtain the target product O-3-chloro-2-propenyl hydroxylamine with the yield of 99.2%.
Comparative example 1
In a first three-necked flask, 71.0g of distilled water and 100g of hydroxylamine sulfate were sequentially charged, followed by dropwise addition of 162.8g of a liquid alkali to prepare 207.2g of an aqueous hydroxylamine solution. Pouring the prepared hydroxylamine aqueous solution into a second three-neck flask, adding 99.6g of methyl acetate, starting magnetic stirring, dropwise adding 196g of 30% NaOH aqueous solution (liquid alkali), keeping the temperature at 20 ℃, and reacting for 1 h. 136g of trans-1, 3-dichloropropene are added into the second three-neck flask, the temperature is raised to 60 ℃, and the reaction is carried out for 6 hours. The above-mentioned dropwise addition molar ratio n (hydroxylamine): n (NaOH): n (trans-1, 3-dichloropropene) is 1: 2.1: 1.
180g of hydrochloric acid are subsequently added, stirred and then refluxed for 2h at 60 ℃. Removing the solvent by reduced pressure distillation, adding liquid alkali to adjust the pH to be more than 9, extracting for 3 times by using dichloromethane at room temperature, and removing the dichloromethane by reduced pressure distillation again to obtain the target product O-3-chloro-2-propenyl hydroxylamine with the yield of 82.5%.
It can be seen that the product yield is greatly reduced to 82.5% compared with the 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 only a specific implementation example of the present invention. It is obvious that the invention is not limited to the above embodiment examples, but that many variations are possible. All modifications which can be derived or suggested by a person skilled in the art from the disclosure of the present invention are to be considered within the scope of the invention.
Claims (8)
1. A preparation method of O-3-chloro-2-propenyl hydroxylamine is characterized by comprising the following steps:
s1, adding hydroxylamine aqueous solution and methyl acetate into a flask according to a proportion, adding a 4-dimethylaminopyridine catalyst, and then adding liquid alkali into the flask for reaction;
s2, adding trans-1, 3-dichloropropene into the flask again, heating and maintaining the temperature for reaction;
s3, after the reaction, adding hydrochloric acid, stirring, and then carrying out reflux reaction;
s4, after organic matters are separated by reduced pressure distillation, adding liquid alkali to adjust the pH value;
s5, extracting for many times at room temperature, and removing the extracting agent by reduced pressure distillation again to obtain the O-3-chloro-2-propenyl hydroxylamine.
2. The method for producing O-3-chloro-2-propenylhydroxylamine as claimed in claim 1, wherein said aqueous hydroxylamine solution is produced by the following method:
1) adding distilled water and hydroxylamine sulfate into a flask according to a proportion;
2) and dropwise adding liquid alkali to prepare the hydroxylamine aqueous solution.
3. The method for producing O-3-chloro-2-propenylhydroxylamine as claimed in claim 1, wherein in the step S1, the ratio of hydroxylamine in the aqueous solution of hydroxylamine to methyl acetate: the molar ratio of the 4-dimethylamino pyridine is 1: 1.1: 0.01-0.10.
4. The method of claim 1, wherein the aqueous alkali solution is 30% aqueous NaOH solution, and the molar ratio of hydroxylamine to NaOH in the aqueous hydroxylamine solution is: 1: 2.1.
5. the method of producing O-3-chloro-2-propenylhydroxylamine as claimed in claim 1, wherein the molar ratio of trans-1, 3-dichloropropene added to hydroxylamine in the aqueous solution of hydroxylamine in step S1 is 1: 1.
6. the method for producing O-3-chloro-2-propenylhydroxylamine according to claim 1, 2, 3, 4 or 5, wherein in the step of S2, the temperature is raised and maintained at 50 to 70 ℃ for 5 to 7 hours.
7. The method of producing O-3-chloro-2-propenylhydroxylamine as claimed in claim 6, wherein the reflux reaction is maintained at a temperature for 2 hours in step S3.
8. The method for producing O-3-chloro-2-propenylhydroxylamine according to claim 1, 2, 3, 4, 5 or 7, wherein in the step S4, a liquid alkali is added to adjust the pH to more than 9.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202111632298.4A CN114394916B (en) | 2021-12-29 | 2021-12-29 | Preparation method of O-3-chloro-2-propenyl hydroxylamine |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202111632298.4A CN114394916B (en) | 2021-12-29 | 2021-12-29 | Preparation method of O-3-chloro-2-propenyl hydroxylamine |
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| Publication Number | Publication Date |
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| CN114394916A true CN114394916A (en) | 2022-04-26 |
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