CN101220005A - Method for producing benzo thiazides compounds - Google Patents
Method for producing benzo thiazides compounds Download PDFInfo
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- CN101220005A CN101220005A CNA2008100333150A CN200810033315A CN101220005A CN 101220005 A CN101220005 A CN 101220005A CN A2008100333150 A CNA2008100333150 A CN A2008100333150A CN 200810033315 A CN200810033315 A CN 200810033315A CN 101220005 A CN101220005 A CN 101220005A
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- electron
- alkynyl aniline
- lsothiocyanates
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Abstract
The invention belongs to the technical field of organic chemistry, in particular to a benzothiazole compound and a preparation method thereof. The structures of the compound is attributed and determined by the methods like <1>H NMR, <13>CNMR, IR, MS, elementary analysis, and single-crystal X-ray diffraction, etc. The invention uses silver triflate as a catalyst to prepare 4-methylene-1H-benzo[d] [1, 3] thiazine-2(4H)-imine framework compounds by mixing ortho-alkynyl aniline and isothiocyanate in tetrahydrofuran to react at room temperature. The benzothiazole compounds and the preparation method thereof of the invention has the advantages of mild reaction condition, simple operation, lower cost, fewer side effects and high purity of the product; thereby having a great application prospect.
Description
Technical field
The invention belongs to technical field of organic chemistry, be specifically related to a kind of preparation method of benzo thiazides compounds.
Background technology
1, the 4-benzo thiazides compounds is subjected to extensive studies (J.Med.Chem.1973 because of it has the anti-inflammatory isoreactivity on biology, 16,780), and 3, the synthetic method of 1-benzo thiazides compounds II and the research of biological activity aspect thereof also have report (Miller, B.L.Org.Lett.2000,2,3667; Swain, M.L.J.Chem.Soc., Perkin Trans.1 1975,922; Nishio, T.J.Org.Chem.1997,62,1106; Schmidt, R.R.J.Heterocycl.Chem.1999,36,153; Ress, C.W.Synlett 1997,704; Pazdera, P.Molecules 2000,7, and 96; Schmittel M.Synthesis2004,3,415).And the isomers I of benzo thiazides compounds II (4-methylene radical-1H-benzo [d] [1,3] research synthetic and the biological activity aspect thiazine-2 (4H)-imines) yet there are no report, based on research interest to relevant nitrogen-containing heterocycle compound, the present invention proposes the method for a kind of efficient acquisition 4-methylene radical-1H-benzo [d] [1,3] thiazine-2 (4H)-imines class framework compound.
R wherein
1Be H or 4-CH
3Etc. various electron-donating groups or 4-CF
3Etc. various electron-withdrawing groups; R
2Be Ph or 4-MeO-C
6H
4Deng containing various aromatic substituents for electron-withdrawing groups, also can be various aliphatic chain groups as n-Bu and cyclopropane base etc.; R
3Be Ph, 4-MeO-C
6H
4, 3-CF
3-C
6H
4, 3,5-(CF
3)
2-C
6H
3Or 4-NO
2-C
6H
4Deng, can be to contain various aromatic substituents for electron-withdrawing groups, also can be various aliphatic chain substituting groups as Et-, CH
3CH
2CH
2-or cyclohexyl etc.
Summary of the invention
The object of the invention is to provide the high preparation benzo thiophene of a kind of simple and effective product purity to chant in a loud voice the method for compound 4-methylene radical-1H-benzo [d] [1,3] thiazine-2 (4H)-imines class framework compound.
The present invention is under the silver trifluoromethanesulfonate catalytic condition, with adjacent alkynyl aniline and lsothiocyanates under the room temperature in tetrahydrofuran (THF) stirring reaction, the addition reaction of amine to lsothiocyanates promptly can take place, and intramolecular series connection cyclization takes place simultaneously, promptly obtain target product, yield is up to 98%.This method is easy and simple to handle, and the product purity height has extraordinary application prospect.
In the present invention, adjacent alkynyl aniline and lsothiocyanates and catalyzer silver trifluoromethanesulfonate three mol ratio are 1: 1.0～3.0: 0.01～0.05, the usage quantity of organic solvent tetrahydrofuran is relatively more crucial in reaction, controlling the volumetric molar concentration of adjacent alkynyl aniline in organic solvent tetrahydrofuran is 0.5-1.0M, and controlling reaction time is 8-36 hour.When concentration during, react the required time obviously to prolong, and reaction yield is also very low less than 0.1M.Under suitable concentration conditions, reaction can be carried out smoothly at ambient temperature.
The preferable reaction conditions of the present invention is:
(1) molar ratio of adjacent alkynyl aniline and lsothiocyanates is 1: 1.0～2.0;
(2) molar ratio of adjacent alkynyl aniline and catalyzer silver trifluoromethanesulfonate is 1: 0.01～0.03;
(3) volumetric molar concentration of adjacent alkynyl aniline in organic solvent tetrahydrofuran is 0.5～0.8M;
(4) temperature of reaction is 20-25 ℃;
(5) reaction times is 18～28 hours.
Operation of the present invention is easy, and the product yield height has extraordinary application prospect.
Embodiment
Embodiment 1 with 2-(2-phenylacetylene base) aniline (193.0mg, 1.0mmol), phenyl lsothiocyanates (405.0mg, 3.0mmol), silver trifluoromethanesulfonate (2.6mg, 0.01mmol), tetrahydrofuran (THF) (2mL) stirring reaction under room temperature, TLC follows the tracks of and detects to complete reaction about 24 hours.With the solvent evaporate to dryness, add entry (10mL), ethyl acetate extraction (20mL * 2), anhydrous sodium sulfate drying, the evaporating column chromatographic separation gets colourless object 321mg, and yield reaches 96%.
1H?NMR(400MHz，CDCl
3)δ7.06(t，J＝7.3Hz，1H)，7.17(s，1H)，7.19(dd，J＝1.5，7.8Hz，1H)，7.27-7.40(m，5H)，7.41-7.45(m，4H)，7.53-7.58(m，3H)；
13C?NMR(100MHz，CDCl
3)δ120.2，121.7，123.5，124.8，124.9，125.9，126.6，127.1，127.7，128.2，128.9，129.3，129.6，135.6，139.9，143.2，147.6；Ms(EI)m/z?328(M
+)；Elemental?analysis?calcd(％)for?C
21H
16N
2S：C?76.80，H?4.91，N?8.53；Found：C?76.64，H?4.92，N?8.62.
Embodiment 2
With 2-(2-phenylacetylene base) aniline (92.0mg, 0.5mmol), 4-nitro-phenyl lsothiocyanates (180.0mg, 2.0mmol), silver trifluoromethanesulfonate (6.5mg, 0.025mmol), tetrahydrofuran (THF) (1mL) stirring reaction under room temperature, TLC follows the tracks of and detects to complete reaction about 18 hours.With the solvent evaporate to dryness, add entry (10mL), ethyl acetate extraction (20mL * 2), anhydrous sodium sulfate drying, the evaporating column chromatographic separation gets colourless object 183mg, yield 98%.
1H?NMR(400MHz，DMSO)δ7.18-7.50(m，10H)，7.65(d，J＝7.3Hz，1H)，8.02(d，J＝8.0Hz，，2H)，8.13(d，J＝8.3Hz，2H)；
13C?NMR(100MHz，DMSO)δ119.2，121.3，125.4，125.8，126.4，127.3，128.3，128.8，129.7，130.4，135.8，141.7，142.9，146.7，147.3；Ms(EI)m/z?373(M
+)；Elemental?analysis?calcd(％)for?C
21H
15N
3O
2S：C?67.54，H?4.05，N?11.25；Found：C?67.82，H?3.98，N?10.97.
Embodiment 3
With 4-methyl-2-(2-phenylacetylene base) aniline (103.6mg, 0.5mmol), phenyl lsothiocyanates (135.0mg, 1.0mmol), silver trifluoromethanesulfonate (6.5mg, 0.025mmol), tetrahydrofuran (THF) (2mL) stirring reaction under room temperature, TLC follows the tracks of and detects to complete reaction 36 hours.With the solvent evaporate to dryness, add entry (10mL), ethyl acetate extraction (20mL * 2), drying, evaporating column chromatographic separation get colourless object 167.6mg, yield 98%.
1H?NMR(400MHz，CDCl
3)δ2.38(s，3H)，7.04(t，J＝7.3Hz，1H)，7.13-7.17(m，3H)，7.27-7.33(m，3H)，7.35(s，1H)，7.38-7.43(m，4H)，7.53(d，J＝8.3Hz，2H)；
13C?NMR(100MHz，CDCl
3)δ20.5，119.5，120.8，122.8，124.5，125.3，126.1，126.3，127.0，127.6，128.4，128.8，130.0，133.9，135.2，139.4，140.4，146.4；Ms(EI)m/z?328(M
+)；Elemental?analysis?calcd(％)forC
21H
16N
2S：C?76.80，H?4.91，N?8.53；Found：C?76.65，H?4.90，N?8.35.
Embodiment 4
With 4-trifluoromethyl-2-(2-phenylacetylene base) aniline (130.6mg, 0.5mmol), m-trifluoromethylphenyl lsothiocyanates (304mg, 1.5mmol), silver trifluoromethanesulfonate (6.5mg, 0.025mmol), tetrahydrofuran (THF) (2mL) stirring reaction under room temperature, TLC follows the tracks of and detects to complete reaction 8 hours.With the solvent evaporate to dryness, add entry (10mL), ethyl acetate extraction (20mL * 2), anhydrous sodium sulfate drying, the evaporating column chromatographic separation gets colourless object 220.5mg, yield 95%.
1H?NMR(400MHz，CDCl
3)δ6.85(br，1H)，7.20(s，1H)，7.26(d，J＝8.3Hz，1H)，7.31-7.44(m，7H)，7.56(d，J＝8.3Hz，1H)，7.61(d，J＝7.3Hz，1H)，7.76(s，1H)，7.92(s，1H)；
13C?NMR(100MHz，CDCl
3)δ117.3，120.4，122.2，122.3，123.4，123.8(q，
1J
CF＝270.2Hz)，124.1(q，
1J
CF＝270.5Hz)，124.4，125.7，126.2，126.3，126.9(q，
2J
CF＝32.4Hz)，128.3，129.4，129.5，131.4(q，
2J
CF＝32.4Hz)，134.9，140.2，145.4，149.6；Ms(EI)m/z?464(M
+)；Elementalanalysis?calcd(％)for?C
23H
14F
6N
2S：C?59.48，H?3.04，N?6.03；Found：C?59.35，H?2.90，N?6.15.
The invention is not restricted to above-mentioned example.In the described in front condition and range, all can obtain the target product of high yield.
Claims (10)
1. the preparation method of a benzo thiazides compounds, the structural formula of this compound is as follows:
Wherein, R
1Be electron-donating group or electron-withdrawing group, R
2For containing aromatic substituent for electron-withdrawing group, perhaps be the aliphatic chain group, R
3Be Ph, 4-MeO-C
6H
4, 3-CF
3-C
6H
4, 3,5-(CF
3)
2-C
6H
3Or 4-NO
2-C
6H
4, perhaps be Et-, CH
3CH
2CH
2-or cyclohexyl;
It is characterized in that concrete steps are as follows: under the silver trifluoromethanesulfonate catalytic condition, with adjacent alkynyl aniline and lsothiocyanates in tetrahydrofuran (THF), stirring under the room temperature, the addition reaction of amine to lsothiocyanates promptly takes place, and intramolecular series connection cyclization takes place simultaneously, promptly obtain target product: 4-methylene radical-1H-benzo [d] [1,3] thiazine-2 (4H)-imines skeleton compounds; Its reaction conditions is:
(1) mol ratio of adjacent alkynyl aniline and lsothiocyanates is 1: 1.0～3.0;
(2) mol ratio of adjacent alkynyl aniline and catalyzer silver trifluoromethanesulfonate is 1: 0.01～0.05;
(3) volumetric molar concentration of adjacent alkynyl aniline in organic solvent tetrahydrofuran is 0.5～1.0M;
(4) reaction times is 8～36 hours.
2. the method for claim 1, the mol ratio that it is characterized in that adjacent alkynyl aniline and lsothiocyanates is 1: 1.0～2.0;
3. the method for claim 1 is characterized in that adjacent alkynyl aniline and catalyzer silver trifluoromethanesulfonate mol ratio are 1: 0.01～0.03;
4. the method for claim 1 is characterized in that the volumetric molar concentration of adjacent alkynyl aniline in organic solvent tetrahydrofuran is 0.5～0.8M;
5. the method for claim 1 is characterized in that temperature of reaction is room temperature 20-25 ℃;
6. the method for claim 1 is characterized in that the reaction times is 18～28 hours.
7. the method for claim 1 is characterized in that R
1Be H or electron-donating group such as 4-CH
3, or electron-withdrawing group 4-CF
3
8. the method for claim 1 is characterized in that R
2Be aromatic group Ph or the 4-MeO-C that contains for electron-withdrawing group
6H
4, or fatty chain hydrocarbon n-Bu or cyclopropane base.
9. the method for claim 1 is characterized in that R
3Be the aromatic group Ph that electronic effect is arranged, 4-MeO-C
6H
4, 3-CF
3-C
6H
4, 3,5-(CF
3)
2-C
6H
3Or 4-NO
2-C
6H
4, or fatty chain hydrocarbon: Et-, CH
3CH
2CH
2-or cyclohexyl.
10. as the benzo thiazides compounds of method preparation as described in one of claim 1-9.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100333150A CN101220005A (en) | 2008-01-31 | 2008-01-31 | Method for producing benzo thiazides compounds |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100333150A CN101220005A (en) | 2008-01-31 | 2008-01-31 | Method for producing benzo thiazides compounds |
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|---|---|
| CN101220005A true CN101220005A (en) | 2008-07-16 |
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ID=39630116
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|---|---|---|---|
| CNA2008100333150A Pending CN101220005A (en) | 2008-01-31 | 2008-01-31 | Method for producing benzo thiazides compounds |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232410A (en) * | 2013-04-26 | 2013-08-07 | 苏州大学 | Method for preparing 2-amino benzothiazine |
| CN106187943A (en) * | 2016-07-13 | 2016-12-07 | 温州大学 | A kind of preparation method of 1,4 benzothiazines |
-
2008
- 2008-01-31 CN CNA2008100333150A patent/CN101220005A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232410A (en) * | 2013-04-26 | 2013-08-07 | 苏州大学 | Method for preparing 2-amino benzothiazine |
| CN103232410B (en) * | 2013-04-26 | 2014-12-10 | 苏州大学 | Method for preparing 2-amino benzothiazine |
| CN106187943A (en) * | 2016-07-13 | 2016-12-07 | 温州大学 | A kind of preparation method of 1,4 benzothiazines |
| CN106187943B (en) * | 2016-07-13 | 2018-06-15 | 温州大学 | A kind of preparation method of 1,4- benzothiazines |
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Open date: 20080716 |