CN108003114A - One kind 3,3 '-bis- phenyl -2H, the preparation method of 2 ' H-2,2 '-dibenzo [1,4] thiazine - Google Patents
One kind 3,3 '-bis- phenyl -2H, the preparation method of 2 ' H-2,2 '-dibenzo [1,4] thiazine Download PDFInfo
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- CN108003114A CN108003114A CN201711423100.5A CN201711423100A CN108003114A CN 108003114 A CN108003114 A CN 108003114A CN 201711423100 A CN201711423100 A CN 201711423100A CN 108003114 A CN108003114 A CN 108003114A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/16—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
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Abstract
The invention belongs to organic chemical synthesis and pharmaceutical synthesis field, it is specifically related to the double phenyl 2H, 2'H 2 of 3,3' of one kind, 2 ' dibenzo [1,4] preparation method of thiazine, first by 2,2 ' diamino-diphenyl disulfides, acetophenone, azodiisobutyronitrile, acetic acid are added sequentially in round-bottomed flask, round-bottomed flask is placed in oil bath, pot temperature is risen to 70~90 DEG C, stops heating after reacting 16~36h；Then product is subjected to column chromatography, obtained liquid revolving, revolving gained is product, and the synthetic method that the present invention has widened benzothiazine is laid a good foundation for its application in terms of medicine.
Description
Technical field
The present invention relates to one kind 3,3 '-bis- phenyl -2H, 2 ' H-2, the preparation method of 2 '-dibenzo [Isosorbide-5-Nitrae] thiazine, belongs to
Organic chemical synthesis field, lays the foundation for its application.
Background technology
Benzothiazine is by phenyl ring and sulphur nitrogen hexa-member heterocycle and closes the heterocycle compound formed, former according to its sulphur azepine
Sub- position difference is divided into following six class：3,4- dihydro -1,2- benzothiazines, 2,4- dihydro -1,3- benzothiazines, 2,3- dihydros -
1,4- benzothiazines, 3,4- dihydro -2,1- benzothiazines and 1,4- dihydro -2,3- benzothiazines, 2,4- dihydro -3,1- benzos
Thiazine.Research finds that benzo thiazides compounds have antibacterial, reducing blood lipid, blood pressure lowering, expelling parasite, antiviral, antitumor, diuresis etc.
Bioactivity, available for diseases such as treatment schizophrenia, arrhythmia cordis and rheumatoid arthritis；In addition, benzothiazine
Compound also has weeding and prevents steel corrosion etc. from acting on.
For Isosorbide-5-Nitrae-benzothiazine derivative, such compound has notable shadow to KCl induction of vascular contractile functions
Ring.And it also found the antagonism for the vascular circle contractile function that 1,4- benzothiazine derivatives induce norepinephrine.
Hajela et al. reports using 1,2- dibenzoyls ethyl-acetylene and near amino thiophenols and to have synthesized 3,3 ' under perchloric acid effect-
Double phenyl -2H, 2 ' H-2,2 '-dibenzo [1,4] thiazine (J. Heterocycl.Chem., 2011,1336-1341).But its
The benzothiazine derivatives synthetic method of report is complex, and costly, yield is relatively low for cost of material, and uses high chlorine
Acid, does not meet the theory of green syt.On the basis of document above, a green 3,3 '-bis- phenyl -2H, 2 ' H- is designed
The preparation method of 2,2 '-dibenzo [1,4] thiazine lays the foundation for its application.
By retrieval, patent document related with the present patent application is not yet found.
The content of the invention
The purpose of this invention is discovery one 3,3 '-bis- phenyl -2H, and the succinct of 2 ' H-2,2 '-dibenzo [1,4] thiazine is closed
Into method.The present invention utilizes 2, and 2 '-Diphenyl disulfide ether is reacted with acetophenone, synthesize 3,3 ' in acid condition-it is bis-
Phenyl -2H, 2 ' H-2,2 '-dibenzo [Isosorbide-5-Nitrae] thiazine compounds, this method is simple with method, easy to operate, and yield is higher etc.
Advantage.
The solution of the present invention is one kind 3,3 '-bis- phenyl -2H, 2 ' H-2, the preparation method of 2 '-dibenzo [Isosorbide-5-Nitrae] thiazine,
Include the following steps；First by 2,2 '-Diphenyl disulfide ether, acetophenone, radical initiator, acetic acid are added sequentially to round bottom burning
In bottle, round-bottomed flask is placed in oil bath, pot temperature is risen to 70-90 DEG C, stops heating after reacting 16~36h；So
Product is subjected to chromatography afterwards, obtains product.
3,3 '-bis- phenyl -2H, the molecular structure of 2 ' H-2,2 '-dibenzo [1,4] thiazine are as follows：
3,3 '-bis- phenyl -2H, the hydrogen nuclear magnetic resonance modal data of 2 ' H-2,2 '-dibenzo [1,4] thiazine are as follows：
1H NMR(400MHz,CDCl3):δ 7.68-7.62 (m, 6H), 7.43-7.35 (m, 4H), 7.31 (t, J=
8.0Hz,4H),7.13(td,J1=8.0Hz, J2=1.6Hz, 2H), 6.91 (dd, J1=8.0Hz, J2=1.2Hz, 2H),
4.15(s,2H)；
13C NMR(100MHz,CDCl3):δ156.2,143.1,138.1,130.7,128.5,128.4, 128.0,
127.8,127.1,127.0,120.3,31.4。
The present invention has a unique advantage, 3,3 '-bis- phenyl -2H, 2 ' H-2, the synthesis side of 2 '-dibenzo [Isosorbide-5-Nitrae] thiazine
Method is easy, without using pollution, the strong perchloric acid of corrosivity, and yield is higher.
Brief description of the drawings
Fig. 1 is the crystal structure of double phenyl -2H, 2'H-2,2 '-dibenzo [1,4] thiazines of compound 3,3'-.
Fig. 2 is the nuclear magnetic resonance spectroscopy of double phenyl -2H, 2'H-2,2 '-dibenzo [1,4] thiazines of 1 3,3'- of compound.
Fig. 3 is the carbon-13 nmr spectra of double phenyl -2H, 2'H-2,2 '-dibenzo [1,4] thiazines of 1 3,3'- of compound.
Embodiment
With reference to embodiment, the present invention is described in detail, but protection domain is not limited by this.
One kind 3,3 '-bis- phenyl -2H, 2 ' H-2, the preparation method of 2 '-dibenzo [Isosorbide-5-Nitrae] thiazine, includes the following steps：It is first
First by 2,2 '-diamino-diphenyl disulfide (10~20mmol), acetophenone (20~50mmol), acetic acid (10~15mL), from
It is added sequentially to by base initiator (2~8mmol) in round-bottomed flask, round-bottomed flask is placed in oil bath, is made on pot temperature
75~85 DEG C are risen to, stops heating.When reaction 16~24 is small, stops reaction, be cooled to room temperature, it is static.Column chromatography obtains product, production
Rate is 60~85%.
This method it is main as follows to content：
(1) selection of raw material proportioning；
This reaction is a radical reaction in itself first, therefore screening radical initiator and its dosage are most important.
If excessive more using radical initiator, many difficulties are carried out to reaction zone, by repetition test, the free radical that we select draws
Hair agent is azodiisobutyronitrile, and specific reaction condition is as follows：2,2 '-diamino-diphenyl disulfide：Acetophenone：Two isobutyl of azo
Nitrile molar ratio is 10~20：12~25：2~8, acetic acid dosage is 10~15mL, and reaction temperature is 75~85 DEG C, and the reaction time is
16~24 be optimum reaction condition when small.
(2) research of reaction condition；
How reaction speed is improved, and it is also one of content of primary study to shorten the reaction time.Therefore add using under normal pressure
The method of heat reaches higher yield to reduce the reaction time.Using being reacted at 75~85 DEG C of normal pressure, obtain 70~
85% or so yield.
Embodiment one：
First by 2,2 '-diamino-diphenyl disulfide (10mmol), acetophenone (20mmol), azodiisobutyronitrile
(2mmol), acetic acid 10mL are added sequentially in round-bottomed flask, round-bottomed flask are placed in oil bath, rise to pot temperature
75 DEG C, when reaction 16 is small, stops reaction, be cooled to room temperature, it is static.Column chromatography obtains product, yield 73%.
Embodiment two：
First by 2,2 '-diamino-diphenyl disulfide (10mmol), acetophenone (25mmoI), azodiisobutyronitrile
(2mmol), acetic acid 20mL, is added sequentially in round-bottomed flask, and round-bottomed flask is placed in oil bath, rises to pot temperature
75 DEG C, when reaction 24 is small, stops reaction, be cooled to room temperature, it is static.Column chromatography obtains product, yield 84%.
Embodiment three：
First by 2,2 '-diamino-diphenyl disulfide (15mmol), acetophenone (24mmol), azodiisobutyronitrile
(3mmol), acetic acid 15mL are added sequentially in round-bottomed flask, round-bottomed flask are placed in oil bath, rise to pot temperature
75 DEG C, when reaction 16 is small.It is cooled to room temperature, it is static.Column chromatography obtains product, yield 78%.
Example IV：
First by 2,2 '-diamino-diphenyl disulfide (10mmol), acetophenone (22mmol), azodiisobutyronitrile
(6mmol), acetic acid 15mL, is added sequentially in round-bottomed flask, and round-bottomed flask is placed in oil bath, rises to pot temperature
85 DEG C, when reaction 16 is small, it is cooled to room temperature, it is static.Column chromatography obtains product, yield 70%.
Embodiment five：
First by 2,2 '-diamino-diphenyl disulfide (10mmol), acetophenone (20mmol), azodiisobutyronitrile
(8mmol), acetic acid 15mL, is added sequentially in round-bottomed flask, and round-bottomed flask is placed in oil bath, rises to pot temperature
85 DEG C, when reaction 24 is small, it is cooled to room temperature, it is static.Column chromatography obtains product, yield 68%.
Embodiment six：
First by 2,2 '-diamino-diphenyl disulfide (10mmol), acetophenone (25mmol), azodiisobutyronitrile
(5mmol), acetic acid 20mL are added sequentially in round-bottomed flask, round-bottomed flask are placed in oil bath, rise to pot temperature
80 DEG C, when reaction 21 is small, stops reaction, be cooled to room temperature, it is static.Column chromatography obtains product, yield 83%.
Embodiment seven：
First by 2,2 '-diamino-diphenyl disulfide (10mmol), acetophenone (22mmol), azodiisobutyronitrile
(4mmol), acetic acid 15mL are added sequentially in round-bottomed flask, round-bottomed flask are placed in oil bath, rise to pot temperature
80 DEG C, when reaction 24 is small, stops reaction, be cooled to room temperature, it is static.Column chromatography obtains product, yield 84%.
Comprehensive example 1-7, as shown in Figure 1, it can be seen that this compound is symmetrical structure, contains two benzothiazines
Ring, the two rings are by carbon-carbon single bond key even so as to form double phenyl -2H, 2'H-2,2 '-dibenzo [Isosorbide-5-Nitrae] thiazines of 3,3'-
Compound.The structure of this compound can also be further confirmed that further by Fig. 2, Fig. 3, figure it is seen that
Have unimodal at 4.15ppm, there are two hydrogen, illustrate that this hydrogen connects the hydrogen atom on two carbon of two benzothiazine rings for key, and
Compound structure just coincide.
Claims (5)
1. one kind 3, the preparation method of double phenyl -2H, 2'H-2, the 2'- biphenyl of 3'- simultaneously [Isosorbide-5-Nitrae] thiazine, it is characterised in that first will
2,2 '-diamino-diphenyl disulfide, acetophenone, azodiisobutyronitrile, acetic acid are added sequentially in round-bottomed flask, and round bottom is burnt
Bottle is placed in oil bath, pot temperature is risen to 70~90 DEG C, stops heating after reacting 16~36h；Then product is carried out
Column chromatography, obtained liquid revolving, revolving gained is product.
2. preparation method according to claim 1, it is characterised in that：2,2 '-diamino-diphenyl disulfide：Acetophenone：
The ratio between amount of material of azodiisobutyronitrile is：10~20：12~25：2~8.
3. preparation method according to claim 1, it is characterised in that the volume of acetic acid is 10~20mL (preferable, acetic acid
Volume be 10~15mL).
4. preparation method according to claim 1, it is characterised in that reaction temperature is 75~85 DEG C, the reaction time 16
~24h.
5. the preparation method as described in claim 1-4 is any, it is characterised in that gained 3, the double phenyl -2H, 2'H-2,2'- of 3'-
The molecular structural formula of biphenyl simultaneously [1,4] thiazine is as follows：
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| CN201711423100.5A CN108003114B (en) | 2017-12-25 | 2017-12-25 | Preparation method of 3,3' -diphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine |
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| CN201711423100.5A CN108003114B (en) | 2017-12-25 | 2017-12-25 | Preparation method of 3,3' -diphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4607006A (en) * | 1983-10-06 | 1986-08-19 | Fuji Photo Film Co., Ltd. | Silver halide photographic light-sensitive material containing non-spectral sensitizing electron donative silver halide adsorptive compound |
| CN106565571A (en) * | 2016-11-08 | 2017-04-19 | 聊城大学 | Preparation method for 2,2'-di(4-methyl benzene sulfoamino)diphenyl disulphide |
-
2017
- 2017-12-25 CN CN201711423100.5A patent/CN108003114B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4607006A (en) * | 1983-10-06 | 1986-08-19 | Fuji Photo Film Co., Ltd. | Silver halide photographic light-sensitive material containing non-spectral sensitizing electron donative silver halide adsorptive compound |
| CN106565571A (en) * | 2016-11-08 | 2017-04-19 | 聊城大学 | Preparation method for 2,2'-di(4-methyl benzene sulfoamino)diphenyl disulphide |
Non-Patent Citations (2)
| Title |
|---|
| XIANQIANG HUANG ET AL.,: "AIBN-Promoted Synthesis of Bibenzo[b][1,4]thiazines by the Condensation of 2,2′-Dithiodianiline with Methyl Aryl Ketones", 《ORG. LETT.》 * |
| 荣念新: "芳香酮及仲胺的C-H键、N-H键活化反应研究", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 * |
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