CN108003114B - Preparation method of 3,3' -diphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine - Google Patents
Preparation method of 3,3' -diphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine Download PDFInfo
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- CN108003114B CN108003114B CN201711423100.5A CN201711423100A CN108003114B CN 108003114 B CN108003114 B CN 108003114B CN 201711423100 A CN201711423100 A CN 201711423100A CN 108003114 B CN108003114 B CN 108003114B
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- 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 the field of organic chemical synthesis and drug synthesis, and particularly relates to a preparation method of 3,3 '-diphenyl-2H, 2' H-2,2 '-dibenzo [1,4] thiazine, which comprises the steps of firstly sequentially adding 2, 2' -diaminodiphenyl disulfide, acetophenone, azodiisobutyronitrile and acetic acid into a round-bottom flask, putting the round-bottom flask into an oil bath, raising the temperature in the flask to 70-90 ℃, reacting for 16-36 hours, and then stopping heating; and then carrying out column chromatography on the product to obtain liquid, and carrying out rotary evaporation to obtain the product.
Description
Technical Field
The invention relates to a preparation method of 3,3' -diphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine, which belongs to the field of organic chemical synthesis and lays a foundation for the application of the organic chemical synthesis.
Background
Benzothiazine is a heterocyclic compound formed by combining benzene ring and six-membered sulfur-nitrogen heterocyclic ring, and is divided into the following six classes according to the difference of sulfur-nitrogen heteroatom positions: 3, 4-dihydro-1, 2-benzothiazine, 2, 4-dihydro-1, 3-benzothiazine, 2, 3-dihydro-1, 4-benzothiazine, 3, 4-dihydro-2, 1-benzothiazine, 1, 4-dihydro-2, 3-benzothiazine, 2, 4-dihydro-3, 1-benzothiazine. Researches find that the benzothiazine compound has biological activities of resisting bacteria, reducing blood fat, reducing blood pressure, expelling parasites, resisting viruses, resisting tumors, promoting urination and the like, and can be used for treating diseases such as schizophrenia, arrhythmia, rheumatoid arthritis and the like; in addition, the benzothiazine compound also has the effects of weeding, preventing corrosion of steel and the like.
In the case of 1, 4-benzothiazine derivatives, the compounds have a significant effect on the KCl-induced vasoconstriction function. Furthermore, antagonism of noradrenaline-induced vasoconstriction function by 1, 4-benzothiazine derivatives was also found. Hajela et al reported the synthesis of 3,3' -bis-phenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine using 1, 2-dibenzoyl acetylene and o-aminothiophenol with perchloric acid (J. heterocyclic. chem.,2011, 1336-. However, the reported synthetic method of the benzothiazine derivative is complex, the price of raw materials is expensive, the yield is low, and perchloric acid is used, so that the synthetic method is not in accordance with the green synthetic concept. Based on the documents, a preparation method of green 3,3' -diphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine is designed to lay a foundation for the application of the preparation method.
Through searching, no published patent literature relevant to the application of the invention is found.
Disclosure of Invention
The invention aims to find a concise synthesis method of 3,3' -diphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine. The method utilizes 2,2 '-diphenyl disulfide to react with acetophenone to synthesize the 3,3' -diphenyl-2H, 2'H-2, 2' -dibenzo [1,4] thiazine compound under an acidic condition, and has the advantages of simple method, easy operation, high yield and the like.
The scheme of the invention is that the preparation method of 3,3' -diphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine comprises the following steps; firstly, sequentially adding 2, 2' -diphenyl disulfide, acetophenone, a radical initiator and acetic acid into a round-bottom flask, putting the round-bottom flask into an oil bath, raising the temperature in the flask to 70-90 ℃, reacting for 16-36 h, and stopping heating; and then carrying out column layer separation on the product to obtain the product.
The molecular structure of 3,3' -bisphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine is as follows:
the NMR data of 3,3' -bisphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine are as follows:
1H NMR(400MHz,CDCl3):δ7.68-7.62(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 invention has the unique advantages that the synthesis method of the 3,3' -diphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine is simple and convenient, the perchloric acid with strong corrosivity is not needed, and the yield is higher.
Drawings
FIG. 1 shows the crystal structure of 3,3' -biphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine.
FIG. 2 shows the NMR spectrum of 13, 3' -biphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine.
FIG. 3 is a carbon nuclear magnetic resonance spectrum of the compound 13, 3' -biphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine.
Detailed Description
The present invention is described in detail below with reference to examples, but the scope of protection is not limited thereto.
A preparation method of 3,3' -diphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine comprises the following steps: firstly, sequentially adding 2, 2' -diaminodiphenyl disulfide (10-20 mmol), acetophenone (20-50 mmol), acetic acid (10-15 mL) and a free radical initiator (2-8 mmol) into a round-bottom flask, putting the round-bottom flask into an oil bath, raising the temperature in the flask to 75-85 ℃, and stopping heating. And (3) reacting for 16-24 hours, stopping the reaction, cooling to room temperature, and standing. And (5) performing column chromatography to obtain a product, wherein the yield is 60-85%.
The method mainly comprises the following steps:
(1) selecting the proportion of raw materials;
first, the reaction itself is a free radical reaction, and therefore, it is important to select a free radical initiator and its amount. If the free radical initiator is used in an excessive amount, a lot of difficulties are brought to the reaction, and through repeated experiments, the selected free radical initiator is azobisisobutyronitrile, and the specific reaction conditions are as follows: 2, 2' -diaminodiphenyl disulfide: acetophenone: the molar ratio of azodiisobutyronitrile is 10-20: 12-25: 2-8, the dosage of acetic acid is 10-15 mL, the reaction temperature is 75-85 ℃, and the reaction time is 16-24 hours, which is the best reaction condition.
(2) Researching reaction conditions;
how to increase the reaction speed and shorten the reaction time is also one of the important researches. Therefore, heating under normal pressure is used to reduce the reaction time and achieve higher yield. The reaction is carried out at the normal pressure of 75-85 ℃, and the yield of about 70-85% is obtained.
The first embodiment is as follows:
firstly, 2' -diaminodiphenyl disulfide (10mmol), acetophenone (20mmol), azobisisobutyronitrile (2mmol) and 10mL of acetic acid are sequentially added into a round-bottom flask, the round-bottom flask is placed in an oil bath, the temperature in the flask is increased to 75 ℃, the reaction is stopped for 16 hours, the flask is cooled to room temperature, and the flask is static. The product was obtained by column chromatography in 73% yield.
Example two:
firstly, 2' -diaminodiphenyl disulfide (10mmol), acetophenone (25mmol), azobisisobutyronitrile (2mmol) and 20mL of acetic acid are sequentially added into a round-bottom flask, the round-bottom flask is placed in an oil bath, the temperature in the flask is raised to 75 ℃, the reaction is stopped for 24 hours, the flask is cooled to room temperature and is static. The product is obtained by column chromatography with a yield of 84%.
Example three:
first, 2' -diaminodiphenyl disulfide (15mmol), acetophenone (24mmol), azobisisobutyronitrile (3mmol) and 15mL of acetic acid were sequentially added to a round-bottom flask, and the round-bottom flask was put in an oil bath to raise the temperature in the flask to 75 ℃ for 16 hours. Cooling to room temperature and standing. The product is obtained by column chromatography, and the yield is 78%.
Example four:
firstly, 2' -diaminodiphenyl disulfide (10mmol), acetophenone (22mmol), azobisisobutyronitrile (6mmol) and 15mL of acetic acid are sequentially added into a round-bottom flask, the round-bottom flask is placed in an oil bath, the temperature in the flask is raised to 85 ℃, the reaction is carried out for 16 hours, and the flask is cooled to room temperature and is static. The product is obtained by column chromatography, and the yield is 70%.
Example five:
firstly, 2' -diaminodiphenyl disulfide (10mmol), acetophenone (20mmol), azobisisobutyronitrile (8mmol) and 15mL of acetic acid are sequentially added into a round-bottom flask, the round-bottom flask is placed in an oil bath, the temperature in the flask is raised to 85 ℃, the reaction is carried out for 24 hours, and the flask is cooled to room temperature and is static. The product was obtained by column chromatography with a yield of 68%.
Example six:
firstly, 2' -diaminodiphenyl disulfide (10mmol), acetophenone (25mmol), azobisisobutyronitrile (5mmol) and 20mL of acetic acid are sequentially added into a round-bottom flask, the round-bottom flask is placed in an oil bath, the temperature in the flask is raised to 80 ℃, the reaction is stopped for 21 hours, the flask is cooled to room temperature, and the flask is static. The product is obtained by column chromatography, and the yield is 83 percent.
Example seven:
firstly, 2' -diaminodiphenyl disulfide (10mmol), acetophenone (22mmol), azobisisobutyronitrile (4mmol) and 15mL of acetic acid are sequentially added into a round-bottom flask, the round-bottom flask is placed in an oil bath, the temperature in the flask is raised to 80 ℃, the reaction is stopped for 24 hours, the flask is cooled to room temperature and is static. The product is obtained by column chromatography with a yield of 84%.
Taken together with examples 1-7, as shown in FIG. 1, it can be seen that this compound is of a symmetrical structure, containing two benzothiazines rings bonded by a single carbon-carbon bond to form a 3,3' -biphenyl-2H, 2' H-2, 2' -dibenzo [1,4] thiazine compound. The structure of this compound can be further confirmed by FIGS. 2 and 3. it can be seen from FIG. 2 that there is a single peak at 4.15ppm with two hydrogens, indicating that this hydrogen is a hydrogen atom bonded to two carbons of the two benzothiazines rings, and that the compound structure is exactly identical.
Claims (5)
1. The preparation method of thiazine compounds is characterized by comprising the following steps of firstly, sequentially adding 2, 2' -diaminodiphenyl disulfide, acetophenone, azobisisobutyronitrile and acetic acid into a round-bottom flask, putting the round-bottom flask into an oil bath, raising the temperature in the flask to 70-90 ℃, reacting for 16-36 hours, and stopping heating; and then carrying out column chromatography on the product to obtain liquid, and carrying out rotary evaporation to obtain the thiazine compound, wherein the molecular structural formula of the thiazine compound is as follows:
2. the method of claim 1, wherein: 2, 2' -diaminodiphenyl disulfide: acetophenone: the mass ratio of azobisisobutyronitrile is: 10-20: 12-25: 2 to 8.
3. The method according to claim 1, wherein the volume of acetic acid is 10 to 20 mL.
4. The method according to claim 3, wherein the volume of acetic acid is 10 to 15 mL.
5. The preparation method according to claim 1, characterized in that the reaction temperature is 75-85 ℃ and the reaction time is 16-24 h.
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