CN116621792A - Method for preparing N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide - Google Patents
Method for preparing N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide Download PDFInfo
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- CN116621792A CN116621792A CN202310551734.8A CN202310551734A CN116621792A CN 116621792 A CN116621792 A CN 116621792A CN 202310551734 A CN202310551734 A CN 202310551734A CN 116621792 A CN116621792 A CN 116621792A
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- benzisothiazolin
- butyl
- oxide
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- 238000000034 method Methods 0.000 title claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000012363 selectfluor Substances 0.000 claims abstract description 20
- 239000000654 additive Substances 0.000 claims abstract description 9
- 238000000926 separation method Methods 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 230000000996 additive effect Effects 0.000 claims description 7
- 238000004821 distillation Methods 0.000 claims description 5
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 5
- -1 N-butyl-1, 2-benzisothiazolin-3-one-1-oxide Chemical compound 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 3
- LUYIHWDYPAZCNN-UHFFFAOYSA-N 2-butyl-1,2-benzothiazol-3-one Chemical compound C1=CC=C2C(=O)N(CCCC)SC2=C1 LUYIHWDYPAZCNN-UHFFFAOYSA-N 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000007788 liquid Substances 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 5
- 239000007810 chemical reaction solvent Substances 0.000 abstract description 3
- 238000003889 chemical engineering Methods 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 238000000605 extraction Methods 0.000 abstract description 2
- 239000012847 fine chemical Substances 0.000 abstract description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- 230000002194 synthesizing effect Effects 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OEEHSSKRJOGQMP-UHFFFAOYSA-N 2-[(2-carbamoylphenyl)disulfanyl]benzamide Chemical compound NC(=O)C1=CC=CC=C1SSC1=CC=CC=C1C(N)=O OEEHSSKRJOGQMP-UHFFFAOYSA-N 0.000 description 1
- MJNPHLBKHKJDEF-UHFFFAOYSA-N 2h-1$l^{4},2-benzothiazine 1-oxide Chemical compound C1=CC=C2S(=O)NC=CC2=C1 MJNPHLBKHKJDEF-UHFFFAOYSA-N 0.000 description 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000872931 Myoporum sandwicense Species 0.000 description 1
- PFRUBEOIWWEFOL-UHFFFAOYSA-N [N].[S] Chemical compound [N].[S] PFRUBEOIWWEFOL-UHFFFAOYSA-N 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940126731 protein tyrosine phosphatase inhibitor Drugs 0.000 description 1
- 239000003806 protein tyrosine phosphatase inhibitor Substances 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical class C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to the technical field of fine chemical engineering, and discloses a method for preparing N-N-butyl-1, 3-benzisothiazolin-3-one-1-oxide. The method comprises the following specific steps: N-N-butyl-1, 2-benzisothiazolin-3-one is taken as a raw material, selectfluor and DMF are taken as important additives, and the target product N-N-butyl-1, 3-benzisothiazolin-3-one-1-oxide is obtained after reaction in a solvent. The method is simple and convenient to operate, water can be used as a reaction solvent for reaction, and the target compound can be obtained through simple extraction and liquid separation, thereby conforming to the category of green chemistry and having potential application value.
Description
Technical Field
The invention belongs to the field of fine chemical engineering, and relates to a method for preparing N-N-butyl-1, 3-benzisothiazolin-3-one-1-oxide.
Background
N-N-butyl-1, 3-benzisothiazolin-3-one-1-oxide is an important sulfur-nitrogen-containing six-membered heterocyclic compound, is also an important organic synthesis intermediate, has potential biological activity, can be used as a protein tyrosine phosphatase inhibitor, an anxiolytic agent and the like, and can be used as a precursor for synthesizing saccharin derivatives.
At present, no literature reports a method for synthesizing N-N-butyl-1, 3-benzisothiazolin-3-one-1-oxide, and 3 methods for synthesizing analogues 1, 3-benzisothiazolin-3-one-1-oxide are available: (1) Synthesizing 1, 3-benzisothiazolin-3-one-1-oxide by taking benzothiazinone as a raw material and sodium periodate as an oxidant, wherein the yield is 71% (Tetrahedron, 1988,44,2985); (2) 2-carbamoylphenyl disulfide is used as a raw material, sodium periodate is used as an oxidant, and 1, 3-benzisothiazolin-3-one-1-oxide is synthesized with the yield of 72 percent (Magyar Kemiai Folyoirat,1989,95,455); (3) 2-carbamoylbenzene sulfinic acid is used as raw material, trimethyl chlorosilane is used as raw material, 1, 3-benzisothiazolin-3-one-1-oxide is synthesized, and the yield is 79% (Japanese patent JP 2011162465).
The method uses N-N-butyl-1, 2-benzisothiazolin-3-one, selectfluor and DMF as additives to quickly and efficiently construct N-N-butyl-1, 3-benzisothiazolin-3-one-1-oxide.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a high-efficiency synthesis method of N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide.
In order to achieve the purpose of the invention, the preparation method of the N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide comprises the following steps: reacting N-N-butyl-1, 2-benzisothiazolin-3-one, selectfluor and an additive in a solvent, and purifying after the reaction is finished to obtain N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide;
the additive is DMF, and the mole ratio of DMF to N-N-butyl-1, 2-benzisothiazolin-3-one is 1-5:1-1, preferably 2-4:1;
the molar ratio of SelectFluor to N-N-butyl-1, 2-benzisothiazolin-3-one is 1-3:1.
The solvent is any one or more of water, DMF and MeCN.
Further, the purification method comprises the following steps: after the reaction, ethyl acetate extraction and separation are sequentially carried out, and the ethyl acetate is removed by reduced pressure distillation. The method realizes that the target compound can be separated by simple extraction and liquid separation, and accords with the category of green chemistry.
Further, in the invention, the molar ratio of N-N-butyl-1, 2-benzisothiazolin-3-one, selectFluor and DMF is 1.0:1.0:2.5.
further, the reaction temperature is at least 0 ℃, and the reaction time is 0.5-6.0 h.
Compared with the prior art, the invention provides a preparation method of N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide, which has the characteristics of simplicity and high efficiency.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a product obtained in the example;
FIG. 2 is a nuclear magnetic resonance spectrum of the product obtained in the example.
Detailed Description
The invention is further described in detail below in connection with the examples:
example 1
The synthesis method of the N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide comprises the following steps: to a 25 mL-sealed tube were successively added water (2 mL), N-N-butyl-1, 2-benzisothiazolin-3-one (0.2 mmol), selectFluor (0.2 mmol) and DMF (0.5 mmol), the reaction temperature was controlled at 25℃and the reaction was vigorously stirred for 1 hour. And after the reaction is finished, sequentially extracting and separating liquid by ethyl acetate, and distilling under reduced pressure to remove ethyl acetate to obtain the N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide, wherein the separation yield is 90%.
Nuclear magnetic data and mass spectrum data of target products:
1 H NMR(300MHz,CDCl 3 )δ7.92(d,J＝7.3Hz,1H),7.83(d,J＝7.1Hz,1H),7.76–7.66(m,2H),3.93–3.83(m,1H),3.75–3.65(m,1H),1.75–1.69(m,2H),1.37–1.32(m,2H),0.90(t,J＝7.3Hz,3H). 13 C NMR(75MHz,CDCl 3 )δ165.38,145.56,134.10,133.21,128.43,126.11,125.07,41.07,31.36,20.09,13.67.MS(EI)＝223.0[M] + .
on the basis of this example, only the reaction time was adjusted, and the yields of the reactions for 0.5h and 6.0h were 83% and 81%, respectively.
On the basis of the present example, only the reaction temperature was adjusted, and the yields at 0 degrees celsius and 50 degrees celsius were 70% and 88%, respectively.
Example 2 (SelectFluor usage screening)
Acetonitrile (2 mL), N-N-butyl-1, 2-benzisothiazolin-3-one (0.2 mmol), selectFluor (0.6 mmol), DMF (0.5 mmol) were added in this order to a 25mL vial, the reaction temperature was controlled at 25℃and the reaction was vigorously stirred for 1 hour. After the reaction is finished, ethyl acetate extraction and liquid separation are sequentially carried out, and the ethyl acetate is removed by reduced pressure distillation, and the specific conditions are as follows:
(1) The dosage of SelectFluor is 0, and the yield of the target product is 0%;
(2) The amount of SelectFluor used was 0.1mmol, and the yield of the target product was 44%;
(3) The amount of SelectFluor used was 0.2mmol, and the yield of the target product was 90%;
(4) The amount of SelectFluor used was 0.3mmol, and the yield of the target product was 81%;
(5) The amount of SelectFluor used was 0.4mmol, and the yield of the target product was 80%;
(6) The amount of SelectFluor used was 0.6mmol, and the yield of the target product was 80%;
example 3 (dosage screening of DMF)
Acetonitrile (2 mL), N-butyl-1, 2-benzisothiazolin-3-one (0.2 mmol), selectfluor (0.2 mmol), DMF (0-0.8 mmol) were added in this order to a 25mL vial, the reaction temperature was controlled at 25 degrees celsius, and the reaction was vigorously stirred for 1 hour. After the reaction is finished, ethyl acetate extraction and liquid separation are sequentially carried out, and the ethyl acetate is removed by reduced pressure distillation, and the specific conditions are as follows:
(1) The DMF consumption is 0, and the yield of the target product is 40%;
(2) The dosage of DMF is 0.2mmol, and the yield of the target product is 62%;
(3) The dosage of DMF is 0.4mmol, and the yield of the target product is 80%;
(4) The dosage of DMF is 0.5mmol, and the yield of the target product is 90%;
(5) The dosage of DMF is 0.6mmol, and the yield of the target product is 85%;
(6) The consumption of DMF is 0.8mmol, and the yield of the target product is 80%;
example 4 (screening of different reaction solvents)
To a 25 mL-sealed tube were successively added different reaction solvents (2 mL), N-N-butyl-1, 2-benzisothiazolin-3-one (0.2 mmol), selectFluor (0.2 mmol), DMF (0.5 mmol), the reaction temperature was controlled at 25℃and the reaction was vigorously stirred for 1 hour. After the reaction is finished, ethyl acetate extraction and liquid separation are sequentially carried out, and the ethyl acetate is removed by reduced pressure distillation, and the specific conditions are as follows:
(1) Using DMF as solvent, the yield of target product is 85%;
(2) The yield of the target product was 80% using MeCN as solvent;
(3) The target product cannot be separated by using DCM, DCE, THF, 1,4-Dioxane, DMSO, toluene and methanol as solvents.
Example 5 (use of sodium periodate instead of SelectFluor)
Water (2 mL), N-N-butyl-1, 2-benzisothiazolin-3-one (0.2 mmol), and NaIO were added in this order to a 25mL vial 4 (0.2 mmol), DMF (0.5 mmol), the reaction temperature was controlled at 25℃and the reaction was stirred vigorously for 1 hour. And after the reaction is finished, sequentially extracting and separating liquid by ethyl acetate, distilling under reduced pressure to remove ethyl acetate, and separating by column chromatography to obtain a target product N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide, wherein the separation yield is 25%.
The foregoing describes alternative embodiments of the present invention to teach those skilled in the art how to implement and reproduce the invention. Some conventional technical aspects have been simplified and omitted in order to teach the inventive solution. Those skilled in the art will appreciate variations from this aspect that fall within the scope of the invention.
Claims (5)
1. The preparation method of the N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide is characterized by comprising the following steps: reacting N-N-butyl-1, 2-benzisothiazolin-3-one, selectfluor and an additive in a solvent, and purifying after the reaction is finished to obtain N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide;
the additive is DMF, and the mol ratio of the additive DMF to N-N-butyl-1, 2-benzisothiazolin-3-one is 1-5:1-1;
the molar ratio of SelectFluor to N-N-butyl-1, 2-benzisothiazolin-3-one is 1-3:1;
the solvent is any one or more of water, DMF and MeCN.
2. The method for producing N-butyl-1, 2-benzisothiazolin-3-one-1-oxide according to claim 1, characterized in that the purification method comprises the steps of: after the reaction, ethyl acetate extraction and separation are sequentially carried out, and the ethyl acetate is removed by reduced pressure distillation.
3. The method for preparing N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide according to claim 1, wherein the molar ratio of N-N-butyl-1, 2-benzisothiazolin-3-one, selectfluor and additive DMF is 1.0:1.0:2.5.
4. the process for the preparation of N-butyl-1, 2-benzisothiazolin-3-one-1-oxide according to claim 1, characterized in that the molar ratio of additive DMF to N-butyl-1, 2-benzisothiazolin-3-one is 2-4:1.
5. The method for producing N-butyl-1, 2-benzisothiazolin-3-one-1-oxide according to claim 1, wherein the reaction temperature is at least 0 ℃ and the reaction time is 0.5 to 6.0 hours.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310551734.8A CN116621792A (en) | 2023-05-16 | 2023-05-16 | Method for preparing N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310551734.8A CN116621792A (en) | 2023-05-16 | 2023-05-16 | Method for preparing N-N-butyl-1, 2-benzisothiazolin-3-one-1-oxide |
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| CN116621792A true CN116621792A (en) | 2023-08-22 |
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- 2023-05-16 CN CN202310551734.8A patent/CN116621792A/en active Pending
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