CN101602742A - A kind of 1, the synthetic method of 2-benzo isothiazole compound - Google Patents
A kind of 1, the synthetic method of 2-benzo isothiazole compound Download PDFInfo
- Publication number
- CN101602742A CN101602742A CNA2009101001886A CN200910100188A CN101602742A CN 101602742 A CN101602742 A CN 101602742A CN A2009101001886 A CNA2009101001886 A CN A2009101001886A CN 200910100188 A CN200910100188 A CN 200910100188A CN 101602742 A CN101602742 A CN 101602742A
- Authority
- CN
- China
- Prior art keywords
- phenyl cyanide
- cyanide
- methylthio group
- benzo isothiazole
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Thiazole And Isothizaole Compounds (AREA)
Abstract
The present invention relates to a kind of suc as formula 1 of the last unsubstituted of the N shown in (II), the synthetic method of 2-benzo isothiazole compound, described method is being raw material suc as formula 2-(alkylthio) phenyl cyanide, hydrogen peroxide, the hydrogenchloride shown in (I),-20 ℃ to 170 ℃ prepared in reaction 1,2-benzo isothiazole compound, wherein R
1Representative contains the alkyl of 1 to 4 carbon atom, R
2Represent hydrogen atom, contain the alkyl of 1 to 4 carbon atom, the alkoxyl group that contains 1 to 4 carbon atom, nitro, carboxyl or its ester, and halogen atom.Operational path advanced person of the present invention, processing condition are reasonable, got rid of the use of halogenating agents such as chlorine, sulfuryl chloride, have the characteristics of simpler, economic, convenient, safety, environmental protection.
Description
Technical field
The present invention relates to a kind of is raw material with 2-(alkylthio) phenyl cyanide, substitutes halogenating agent preparation 1, the novel method of 2-benzisothiazole-3-ketone with hydrogen peroxide and hydrogenchloride.
Background technology
1,2-benzisothiazole-3-ketone is the compound that can be used as sterilant and anti-mycotic agent.
Known 1, the preparation method of 2-benzisothiazole-3-ketone have following several:
(A)、Bull.Chem.Soc.Jap.，55，1183-1187(1982)
In this method; earlier prepare 2-(methylthio group) benzamide by the chloride of 2-(methylthio group) phenylformic acid, amidation; become 2-(methylsulfinyl) benzamide with periodate oxidation then, cyclisation generates 1 in the presence of thionyl chloride at last, 2-benzisothiazole-3-ketone.Reaction equation is as follows, and wherein the productive rate of Y is 80～98%.
(B)、Org.Prep.Proced.Int.，15，315-319(1983)
This method is a starting raw material with the dithio-salicylic acid, makes 1 by four-step reaction, 2-benzisothiazole-3-ketone.Reaction equation is as follows, and wherein, d is for the productive rate of b: 84～96%).
(C)、Ger.Offen.3500577(1986)
This method with dithio-salicylic acid as starting raw material after chloride, amidation, and in the end cyclisation step uses sodium hydroxide required 1 to make, 2-benzisothiazole-3-ketone.The productive rate of this reaction is 94%.
(D)、J.Org.Chem.40(14)，2029-2032(1975)
By the 2-Thiosalicylic acid after esterification, thioetherification, amination again with highly basic reaction produce required 1,2-benzisothiazole-3-ketone.Reaction equation is as follows, and wherein the productive rate of Y is 82-93%
(E)、Japaness Patent Application No.5-350932(1993)，No.6-151476(1994)
Produce corresponding adjacent alkylthio benzamide by ortho position substituted benzamide and paraffinic hydrocarbons thiol reactant, after the halogenating agent reaction, produce 1,2-benzisothiazole-3-ketone again.
(F)、Japaness Patent Application No.6-301348(1994)
By producing 1,2-benzisothiazole-3-ketone through the halogenating agent reaction again behind adjacent alkylthio phenyl aldehyde and the azanol reaction.
Yet there is following defective in all these ordinary methods:
Among the method A, need to use expensive Periodic acid and comprise many reactions steps, dangerous property when its meso-periodic acid is handled.
Method B and C need to use expensive dithio-salicylic acid as starting raw material, and comprise many reactions steps, prices of raw and semifnished materials height.
Method D need use expensive Thiosalicylic acid to make raw material, uses the highly basic cyclization, and will pass through polystep reaction, and this method is unsuitable for industrial use.
Method E is changing form of above-mentioned ordinary method.
Method F need use expensive 2-(alkylthio) phenyl aldehyde, prices of raw and semifnished materials height, and this method is unsuitable for industrial use.
As mentioned above, all these currently known methodss all are unsuitable for being prepared on the technical scale.
Japanese Patent JP6-301348 has invented with 2-(alkylthio) phenyl cyanide one step acquisition 1, the method for 2-benzisothiazole-3-ketone,
Halogenating agent is chlorine, SULPHURYL CHLORIDE etc. in this invention, and these halogenating agent toxicity are very high, and production, storage, transportation and use all are subjected to strict restriction.
Summary of the invention
Technical problem to be solved by this invention provides 1 of a kind of simpler, economic, convenient, safety, environmental protection, the synthetic method of 2-benzo isothiazole compound.For this reason, the present invention is by the following technical solutions: 1, the synthetic method of 2-benzo isothiazole compound, described 1, the 2-benzo isothiazole compound is gone up 1 of unsubstituted for the N with general formula (II) expression, and the 2-benzo isothiazole compound is characterized in that described synthetic method is is raw material with 2-(alkylthio) phenyl cyanide, hydrogen peroxide, the hydrogenchloride shown in the general formula (I), on-20 ℃ to the 170 ℃ described N of prepared in reaction 1 of unsubstituted, the 2-benzo isothiazole compound;
R in the formula (I)
1Representative contains the alkyl of 1 to 4 carbon atom, R in formula (I) and the formula (II)
2Represent hydrogen atom, contain the alkyl of 1 to 4 carbon atom, the alkoxyl group that contains 1 to 4 carbon atom, nitro, carboxyl or its ester, and halogen atom.
The present invention proposes and use hydrogen peroxide and hydrogenchloride as halogenating agent preparation 1,2-benzisothiazole-3-ketone, its reaction equation is:
According to method of the present invention, can be under the condition of not using expensive starting raw material, easily by brief step with produced in high yields 1,2-benzisothiazole-this class of 3-ketone can be made the compound of sterilant and anti-mycotic agent.
Below the present invention is described in detail by embodiment of the present invention:
The invention is characterized in that substituting halogenating agent with hydrogen peroxide and hydrogenchloride produces 1,2-benzisothiazole-3-ketone by the cyclisation of 2-(alkylthio) phenyl cyanide.2-(alkylthio) phenyl cyanide can be made by 2-halogenophenyl cyanogen and the generation of paraffinic hydrocarbons thiol reactant in the presence of alkali, also can make by other method.
In the formula (I), R
1Representative contains the alkyl of 1 to 4 carbon atom.R
1Represent the example of alkyl that methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl and the tertiary butyl are arranged, wherein preferable methyl, ethyl, n-propyl and the tertiary butyl.
Formula (I) (II) in R
2Represent hydrogen atom, contain the alkyl of 1 to 4 carbon atom, the alkoxyl group that contains 1 to 4 carbon atom, nitro, carboxyl or its ester, and halogen atom.R
2The example of the alkyl of representative has methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl and the tertiary butyl.R
2The example of the alkoxyl group of representative has methoxyl group, oxyethyl group, propoxy-, butoxy.R
2The example of the carboxyl ester of representative has methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, butoxy carbonyl.R
2Represent the example of halogen atom that chlorine atom and bromine atoms are arranged.Preferred R
2Example comprise hydrogen atom, methyl, ethyl, the tertiary butyl, methoxyl group, methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, chlorine atom and nitro:
The example of 2-(alkylthio) phenyl cyanide of general formula (I) comprising:
2-(methylthio group) phenyl cyanide, 2-(ethylmercapto group) phenyl cyanide, 2-(positive rosickyite base) phenyl cyanide, 2-(uncle's butylthio) phenyl cyanide, 3-methyl-2-(ethylmercapto group) phenyl cyanide, 5-butyl-2-(methylthio group) phenyl cyanide, 4-methoxyl group-2-(methylthio group) phenyl cyanide and 4-chloro-2-(methylthio group) phenyl cyanide.
Consider preferred 2-(methylthio group) phenyl cyanide, 2-(ethylmercapto group) phenyl cyanide, 2-(positive rosickyite base) phenyl cyanide and 2-(uncle's butylthio) phenyl cyanide in above-mentioned example from the high fungicidal activity of raw material sources and products therefrom.
Although to the method for 2-(alkylthio) phenyl cyanide of preparation general formula (I) without limits, preferably adopt 2-(alkylthio) phenyl cyanide that the generation of 2-halogenophenyl cyanogen and paraffinic hydrocarbons thiol reactant is made.Specifically, be exactly in the presence of alkali, in heterogeneous solvent system, make 2-halogenophenyl cyanogen and paraffinic hydrocarbons thiol reactant prepare 2-(alkylthio) phenyl cyanide.
To narrate below by 2-(alkylthio) phenyl cyanide preparation 1, the reaction of 2-benzisothiazole-3-ketone.Spendable hydrogen peroxide comprises reagent and the industrial goods of 20-50% in the reaction, and the example of spendable hydrogenchloride comprises the aqueous solution and the hydrogen chloride gas of hydrogenchloride in the reaction
Every mole of 2-(alkylthio) phenyl cyanide, the consumption of hydrogen peroxide are generally 0.8 to 3.0 mole, are advisable for preferred 1.0 to 2.0 moles.When the hydrogen peroxide consumption was less than 0.8 mole, unconverted 2-(alkylthio) phenyl cyanide amount increased; On the other hand, the hydrogen peroxide consumption surpasses 3.0 moles, side reaction then takes place cause productive rate to descend.The hydrogenchloride consumption is generally 0.8 to 4.0 mole, and preferred 1.0 to 3.0 moles, when the hydrogenchloride consumption was less than 0.8 mole, unconverted 2-(alkylthio) phenyl cyanide amount increased; On the other hand, the hydrogenchloride consumption surpasses 4.0 moles, side reaction then takes place cause productive rate to descend.
Generate 1, used solvent does not have special restriction in 2-benzisothiazole-3-ketone process, as long as they are inertia for reaction.The example of the solvent that can be used for reacting comprises such as alkane and aromatic hydrocarbons such as normal hexane, normal heptane, hexanaphthene, methylcyclohexane, benzene, toluene and dimethylbenzene; And such as methylene dichloride, 1, halogenated hydrocarbons such as 2-ethylene dichloride and chlorobenzene.The solvent usage quantity generally is 0.5 to 30 times of 2-(alkylthio) phenyl cyanide weight.
The temperature of reaction of this process is generally-20 ℃ to 170 ℃, and preferred 0 ℃ to 100 ℃, temperature of reaction is higher than 170 ℃ can cause that side reaction produces.Otherwise when temperature of reaction was lower than-20 ℃, then speed of response can be reduced to the level that reaction can't be carried out.Reaction times is depended on temperature of reaction and reaction solvent kind, is generally 1 to 50 hour.
Generally can adopt the conventional crystallization technique or the first technology of extraction recrystallize, from reaction mixture segregation and purify with aforesaid method obtain 1,2-benzisothiazole-3-ketone also can adopt other technologies.
The N of the general formula (II) that makes with method of the present invention goes up 1 of unsubstituted, and the example of 2-benzo isothiazole compound comprises:
1,2-benzisothiazole-3-ketone, 7-methyl isophthalic acid, 2-benzisothiazole-3-ketone, 5-butyl-1,2-benzisothiazole-3-ketone, 6-methoxyl group-1,2-benzisothiazole-3-ketone and 6-chloro-1,2-benzisothiazole-3-ketone.
Embodiment
The invention will be further described by following working example, and these embodiment only are used to the present invention is described but not limit the scope of the invention.
Resulting product proton nmr spectra (
1HNMR) or mass spectrum identify to confirm whether to obtain desirable material.
Embodiment 1: synthesize 1,2-benzisothiazole-3-ketone.
In the 500ml four neck flasks that agitator, thermometer and prolong are housed, add 59.6g (0.4mol) 2-(methylthio group) phenyl cyanide, 100g chlorobenzene and 45.3g 30% (0.4mol) hydrogen peroxide, under 5-15 ℃ of stirring, in flask, add 44.6g 36% (0.44mol) hydrochloric acid, be heated to 70-80 ℃ of reaction 1 hour then.Reaction is cooled to room temperature with reaction mixture after finishing, and separates out white crystals.Crystallisate washs with chlorobenzene, and drying obtains 55.6g 1,2-benzisothiazole-3-ketone (fusing point: 157-158 ℃).Product is 92% for the productive rate of initial 2-(methylthio group) phenyl cyanide.
Embodiment 2: synthesize 1,2-benzisothiazole-3-ketone
Adopt the method identical to make 58.0g1 with embodiment 1,2-benzisothiazole-3-ketone, difference is that present embodiment is with in the 19.0g hydrogen chloride gas feeding reaction mixture.Product is 96% for the productive rate of initial 2-(methylthio group) phenyl cyanide.
Embodiment 3 to 9: synthesize 1,2-benzisothiazole-3-ketone
Adopt the method preparation 1 identical with embodiment 2,2-benzisothiazole-3-ketone, difference is that 2-(alkylthio) phenyl cyanide in the usefulness table 1 is as initial substance.Table 1:
| Embodiment | 2-(alkylthio) phenyl cyanide class | 1,2-benzisothiazole-3-ketone | Productive rate (%) |
| 3 | 2-(ethylmercapto group) phenyl cyanide | 1,2-benzisothiazole-3-ketone | 95 |
| 4 | 2-(positive rosickyite base) phenyl cyanide | 1,2-benzisothiazole-3-ketone | 95 |
| 5 | 2-(uncle's butylthio) phenyl cyanide | 1,2-benzisothiazole-3-ketone | 92 |
| 6 | 3-methyl-2-(ethylmercapto group) phenyl cyanide | The 7-methyl isophthalic acid, 2-benzisothiazole-3-ketone | 90 |
| 7 | 5-butyl-2-(methylthio group) phenyl cyanide | 5-butyl-1,2-benzisothiazole-3-ketone | 90 |
| 8 | 4-methoxyl group-2-(methylthio group) phenyl cyanide | 6-methoxyl group-1,2-benzisothiazole-3-ketone | 89 |
| 9 | 4-chloro-2-(methylthio group) phenyl cyanide | 6-chloro-1,2-benzisothiazole-3-ketone | 89 |
In table 1, described productive rate is 1, and 2-benzisothiazole-3-ketone is for the productive rate of 2-(alkylthio) phenyl cyanide.
Claims (3)
1. one kind 1, the synthetic method of 2-benzo isothiazole compound, described 1, the 2-benzo isothiazole compound is gone up 1 of unsubstituted for the N with general formula (II) expression, the 2-benzo isothiazole compound, it is characterized in that described synthetic method is is raw material with 2-(alkylthio) phenyl cyanide, hydrogen peroxide, the hydrogenchloride shown in the general formula (I), on-20 ℃ to the 170 ℃ described N of prepared in reaction 1 of unsubstituted, the 2-benzo isothiazole compound;
R in the formula (I)
1Representative contains the alkyl of 1 to 4 carbon atom, R in formula (I) and the formula (II)
2Represent hydrogen atom, contain the alkyl of 1 to 4 carbon atom, the alkoxyl group that contains 1 to 4 carbon atom, nitro, carboxyl or its ester, and halogen atom.
2. N as claimed in claim 1 goes up 1 of unsubstituted, and the synthetic method of 2-benzo isothiazole compound is characterized in that described hydrogenchloride can be that hydrogen chloride gas also can be a hydrochloride aqueous solution.
3. a kind of N as claimed in claim 1 or 2 goes up 1 of unsubstituted, and the synthetic method of 2-benzo isothiazole compound is characterized in that the compound of general formula (I) is selected from:
2-(methylthio group) phenyl cyanide, 2-(ethylmercapto group) phenyl cyanide, 2-(positive rosickyite base) phenyl cyanide, 2-(uncle's butylthio) phenyl cyanide, 3-methyl-2-(ethylmercapto group) phenyl cyanide, 5-butyl-2-(methylthio group) phenyl cyanide, 4-methoxyl group-2-(methylthio group) phenyl cyanide, 2-methylthio group-3-cyanide-nitrophenyl, 4-chloro-2-(methylthio group) phenyl cyanide, 4-carboxyl-2-(methylthio group) phenyl cyanide and 4-methoxycarbonyl-2-(methylthio group) phenyl cyanide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2009101001886A CN101602742A (en) | 2009-07-02 | 2009-07-02 | A kind of 1, the synthetic method of 2-benzo isothiazole compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2009101001886A CN101602742A (en) | 2009-07-02 | 2009-07-02 | A kind of 1, the synthetic method of 2-benzo isothiazole compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101602742A true CN101602742A (en) | 2009-12-16 |
Family
ID=41468654
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2009101001886A Pending CN101602742A (en) | 2009-07-02 | 2009-07-02 | A kind of 1, the synthetic method of 2-benzo isothiazole compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101602742A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013043881A (en) * | 2011-08-26 | 2013-03-04 | Sumitomo Seika Chem Co Ltd | Method for producing 1,2-benzisothiazolin-3-one compound |
| CN102952093A (en) * | 2011-08-26 | 2013-03-06 | 住友精化株式会社 | Method for preparing 1,2 benzo-isothiazolin-3-ketone compound |
| CN103130736A (en) * | 2011-12-05 | 2013-06-05 | 海南大学 | Structure and antibacterial activity of ethoxy benzo isothiazolone aromatic acid ester |
| CN103429579A (en) * | 2011-03-18 | 2013-12-04 | 住友精化株式会社 | 1,2-benzisothiazol-3-one compound production method |
| CN115974809A (en) * | 2023-03-21 | 2023-04-18 | 北京探微精细化工科技有限公司 | Method for preparing benzo [ d ] isothiazoline-3 (2H) -ketone by oxygen transfer reaction |
-
2009
- 2009-07-02 CN CNA2009101001886A patent/CN101602742A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103429579A (en) * | 2011-03-18 | 2013-12-04 | 住友精化株式会社 | 1,2-benzisothiazol-3-one compound production method |
| US8802862B2 (en) | 2011-03-18 | 2014-08-12 | Sumitomo Seika Chemicals Co., Ltd. | 1,2-benzisothiazol-3-one compound production method |
| JP2013043881A (en) * | 2011-08-26 | 2013-03-04 | Sumitomo Seika Chem Co Ltd | Method for producing 1,2-benzisothiazolin-3-one compound |
| CN102952093A (en) * | 2011-08-26 | 2013-03-06 | 住友精化株式会社 | Method for preparing 1,2 benzo-isothiazolin-3-ketone compound |
| CN102952094A (en) * | 2011-08-26 | 2013-03-06 | 住友精化株式会社 | Method of preparing 1,2-benzisothiazole-3-ketone compound |
| CN103130736A (en) * | 2011-12-05 | 2013-06-05 | 海南大学 | Structure and antibacterial activity of ethoxy benzo isothiazolone aromatic acid ester |
| CN115974809A (en) * | 2023-03-21 | 2023-04-18 | 北京探微精细化工科技有限公司 | Method for preparing benzo [ d ] isothiazoline-3 (2H) -ketone by oxygen transfer reaction |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101602742A (en) | A kind of 1, the synthetic method of 2-benzo isothiazole compound | |
| KR20100101649A (en) | Sulfenamide, vulcanization accelerator containing the sulfenamide for rubber, and process for producing the same | |
| DK149623B (en) | PROCEDURE FOR THE PREPARATION OF ALFA-HYDROXYCARBOXYLIC ACIDAMIDS | |
| CN103429579A (en) | 1,2-benzisothiazol-3-one compound production method | |
| CN102952093A (en) | Method for preparing 1,2 benzo-isothiazolin-3-ketone compound | |
| Rostamizadeh et al. | Aqueous NaHSO 4 catalyzed regioselective and versatile synthesis of 2-thiazolamines | |
| CN106674040A (en) | Method for preparing N-aryl amide without solvent and catalyst | |
| CN108440417B (en) | 1- methyl thio phenyl benzimidazole and its derivative synthesizing process | |
| CN107759450A (en) | α, the method for beta unsaturated ketone class compound are synthesized by dimethyl sulfoxide (DMSO) and ketone compounds | |
| US6960668B2 (en) | Process for the production of substituted thioxanthones | |
| CN104860856A (en) | Alkali-free green synthetic method for isothiocyanate | |
| SU677657A3 (en) | Method of producing n-formylated compounds | |
| CN108017594B (en) | Preparation method of mercapto-substituted nitrogen heterocyclic compound | |
| ES2413015T3 (en) | Procedure for the preparation of substituted 2-alkoxycarbonyl-3-aminothiophenes | |
| KR101477407B1 (en) | Process for the preparation of 4,4'-bis(2-benzoxazolyl)stilbene | |
| JPS5840546B2 (en) | 2- Benzimidazole carbamic acid alkyl ester | |
| JP2016108332A (en) | Method for producing amino compound | |
| CN106866544B (en) | 2- (2-hydroxyphenyl) -1H-benzimidazole and derivative, synthetic method and application thereof | |
| JPS58216153A (en) | Manufacture of thiobisphenol | |
| JP5142241B2 (en) | Method for producing nicotinic acid ester compound | |
| KR101214005B1 (en) | Novel indene derivatives and its preparation method | |
| CN1951914A (en) | Process for synthesis of symmetrical aryl urea compound | |
| CN105175286B (en) | A kind of preparation method of hydrochloric acid alkyl guanidine salt | |
| JPWO2007020797A1 (en) | (E) -N-monoalkyl-3-oxo-3- (2-thienyl) propenamine and process for producing the same, and (E, Z) -N-monoalkyl-3-oxo-3- (2-thienyl) Propeneamine production method | |
| JP5370990B2 (en) | Novel sulfenamide compound and process for producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20091216 |