CN110183397B - Method for preparing 1, 5-benzothiazine compound by catalysis of zirconocene dichloride - Google Patents
Method for preparing 1, 5-benzothiazine compound by catalysis of zirconocene dichloride Download PDFInfo
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- CN110183397B CN110183397B CN201910547061.2A CN201910547061A CN110183397B CN 110183397 B CN110183397 B CN 110183397B CN 201910547061 A CN201910547061 A CN 201910547061A CN 110183397 B CN110183397 B CN 110183397B
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- benzothiazine
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- zirconocene dichloride
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- -1 1, 5-benzothiazine compound Chemical class 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 25
- QMBQEXOLIRBNPN-UHFFFAOYSA-L zirconocene dichloride Chemical compound [Cl-].[Cl-].[Zr+4].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 QMBQEXOLIRBNPN-UHFFFAOYSA-L 0.000 title claims description 15
- 238000006555 catalytic reaction Methods 0.000 title description 2
- QMZPQIVWTCTDIK-UHFFFAOYSA-N 2h-thiopyrano[3,2-b]pyridine Chemical class C1=CN=C2C=CCSC2=C1 QMZPQIVWTCTDIK-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003446 ligand Substances 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 claims abstract description 5
- ZMCHBSMFKQYNKA-UHFFFAOYSA-N 2-aminobenzenesulfonic acid Chemical compound NC1=CC=CC=C1S(O)(=O)=O ZMCHBSMFKQYNKA-UHFFFAOYSA-N 0.000 claims abstract description 5
- KFIRODWJCYBBHY-UHFFFAOYSA-N 3-nitrophthalic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1C(O)=O KFIRODWJCYBBHY-UHFFFAOYSA-N 0.000 claims abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- 238000002360 preparation method Methods 0.000 claims description 17
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 230000003197 catalytic effect Effects 0.000 claims description 6
- 229960005190 phenylalanine Drugs 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 10
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical class NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 abstract description 3
- GWQYGDMKYIUOTM-UHFFFAOYSA-N 5-chlorocyclopenta-1,3-diene zirconium(2+) Chemical compound [Zr++].Cl[c-]1cccc1.Cl[c-]1cccc1 GWQYGDMKYIUOTM-UHFFFAOYSA-N 0.000 abstract description 3
- 231100000956 nontoxicity Toxicity 0.000 abstract description 3
- 238000004440 column chromatography Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract 1
- IWCMRVFONGZPMZ-UHFFFAOYSA-N 1,4-diphenylbut-3-yn-2-one Chemical compound C=1C=CC=CC=1C#CC(=O)CC1=CC=CC=C1 IWCMRVFONGZPMZ-UHFFFAOYSA-N 0.000 description 8
- 230000003595 spectral effect Effects 0.000 description 7
- CSKPAEFLXIWTSE-UHFFFAOYSA-N C1=CC=C(C=C1)C2C=C(C3=C(S2)C=CC=N3)C4=CC=CC=C4 Chemical class C1=CC=C(C=C1)C2C=C(C3=C(S2)C=CC=N3)C4=CC=CC=C4 CSKPAEFLXIWTSE-UHFFFAOYSA-N 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 3
- PUPRHKHGCVRFFJ-UHFFFAOYSA-N C1=CC=C(C=C1)C2=CC(SC3=C2N=CC=C3)C4=CC=C(C=C4)Br Chemical compound C1=CC=C(C=C1)C2=CC(SC3=C2N=CC=C3)C4=CC=C(C=C4)Br PUPRHKHGCVRFFJ-UHFFFAOYSA-N 0.000 description 2
- JMUWFIRDSBUAAN-UHFFFAOYSA-N C1=CC=C(C=C1)C2=CC(SC3=C2N=CC=C3)C4=CC=C(C=C4)F Chemical compound C1=CC=C(C=C1)C2=CC(SC3=C2N=CC=C3)C4=CC=C(C=C4)F JMUWFIRDSBUAAN-UHFFFAOYSA-N 0.000 description 2
- OOKLRYTZLFYCQA-UHFFFAOYSA-N COC1=CC=C(C=C1)C2C=C(C3=C(S2)C=CC=N3)C4=CC=CC=C4 Chemical compound COC1=CC=C(C=C1)C2C=C(C3=C(S2)C=CC=N3)C4=CC=CC=C4 OOKLRYTZLFYCQA-UHFFFAOYSA-N 0.000 description 2
- AGRXIAUKXSQDOL-UHFFFAOYSA-N ClC1=CC=C(C(C=C2C3=CC=CC=C3)SC3=C2N=CC=C3)C=C1 Chemical compound ClC1=CC=C(C(C=C2C3=CC=CC=C3)SC3=C2N=CC=C3)C=C1 AGRXIAUKXSQDOL-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 230000000843 anti-fungal effect Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- IZJCEPDBLOMILQ-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-phenylbut-3-yn-2-one Chemical compound C1=CC(F)=CC=C1CC(=O)C#CC1=CC=CC=C1 IZJCEPDBLOMILQ-UHFFFAOYSA-N 0.000 description 1
- BFJATBRDXLDYNR-UHFFFAOYSA-N 1-(4-methoxyphenyl)-4-phenylbut-3-yn-2-one Chemical compound C1=CC(OC)=CC=C1CC(=O)C#CC1=CC=CC=C1 BFJATBRDXLDYNR-UHFFFAOYSA-N 0.000 description 1
- QAHAYBDENBUIDT-UHFFFAOYSA-N 1-phenyl-4-thiophen-2-ylbut-3-yn-2-one Chemical compound C1=CC=C(C=C1)CC(=O)C#CC2=CC=CS2 QAHAYBDENBUIDT-UHFFFAOYSA-N 0.000 description 1
- AGRMCTHVMYHQJT-UHFFFAOYSA-N 4-(4-fluorophenyl)-1-phenylbut-3-yn-2-one Chemical compound C1=CC=C(C=C1)CC(=O)C#CC2=CC=C(C=C2)F AGRMCTHVMYHQJT-UHFFFAOYSA-N 0.000 description 1
- YCPXWRQRBFJBPZ-UHFFFAOYSA-N 5-sulfosalicylic acid Chemical compound OC(=O)C1=CC(S(O)(=O)=O)=CC=C1O YCPXWRQRBFJBPZ-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- NJQYYIBAJSTYMG-UHFFFAOYSA-N C1=CC(C)=CC=C1CC(=O)C#CC1=CC=CC=C1 Chemical compound C1=CC(C)=CC=C1CC(=O)C#CC1=CC=CC=C1 NJQYYIBAJSTYMG-UHFFFAOYSA-N 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- PLPHWCZYOVTRJJ-UHFFFAOYSA-N O=C(CC(C=C1)=CC=C1Br)C#CC1=CC=CC=C1 Chemical compound O=C(CC(C=C1)=CC=C1Br)C#CC1=CC=CC=C1 PLPHWCZYOVTRJJ-UHFFFAOYSA-N 0.000 description 1
- TWSSSXJWQALSBP-UHFFFAOYSA-N O=C(CC(C=C1)=CC=C1Cl)C#CC1=CC=CC=C1 Chemical compound O=C(CC(C=C1)=CC=C1Cl)C#CC1=CC=CC=C1 TWSSSXJWQALSBP-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000005059 halophenyl group Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a method for preparing 1, 5-benzothiazine compounds by catalyzing dichlorozirconocene, which takes 3-butyne-2-ketone compounds and o-aminobenzenethiol compounds as raw materials, takes dichlorozirconocene as a catalyst, and can prepare the 1, 5-benzothiazine compounds with high efficiency and high yield under the promotion of ligands such as L-phenylalanine, 3-nitrophthalic acid, 2-aminobenzenesulfonic acid and the like. The catalyst used in the invention has the advantages of low dosage, low price, no toxicity, stability to air, mild reaction conditions, short time, simple operation and high atom economy, and the 1, 5-benzothiazine compound can be obtained by separating the product through simple column chromatography after the reaction is finished, thereby opening up a new low-cost and high-efficiency way for preparing the 1, 5-benzothiazine compound and having wide application prospect.
Description
Technical Field
The invention belongs to the technical field of synthesis of 1, 5-benzothiazine compounds, and particularly relates to a method for efficiently preparing a 1, 5-benzothiazine compound by catalyzing a reaction between a 3-butyne-2-one compound and an o-aminobenzenethiol compound by using dichlorozirconocene.
Background
The 1, 5-benzothiazine skeleton is widely found in natural products and has been identified as a pleiotropic pharmacophore, and its derivatives include anti-HIV and anti-cancer drugs, angiotensin converting enzyme inhibitors, antibiotics and antifungal compounds, calmodulin antagonists and Ca 2+ Retarders, and the like. In addition, many 1, 5-benzothiazine compounds have antifungal, antibacterial, anti-inflammatory, analgesic, and anticonvulsant activities, and are of great significance in pharmaceutical and organic synthesis.
At present, researchers have the least research on the attachment on the seven-membered ring compared with the stable five-membered ring and six-membered ring structure, so that the diversity synthesis of the 1, 5-benzothiazine compound specially aiming at the seven-membered ring is very lacking. More stable, cheap, efficient and mild-condition catalytic methods are developed, and the method has important significance for preparing the 1, 5-benzothiazine compounds.
Disclosure of Invention
The invention aims to provide a method for efficiently preparing 2, 4-diphenyl-1, 5-benzothiazine derivatives, which is simple to operate and has mild reaction conditions.
Aiming at the purposes, the technical scheme adopted by the invention is as follows: adding a 3-butyne-2-ketone compound shown in a formula I and an o-aminobenzenethiol compound shown in a formula II into an organic solvent, adding zirconocene dichloride and a ligand, stirring and reacting for 1-12 hours at room temperature-60 ℃, and separating and purifying a product to obtain the 1, 5-benzothiazine compound shown in a formula III.
In the formula R 1 And R 2 Each independently represents aryl or substituted aryl, such as: phenyl radical, C 1 ～C 4 Alkyl-substituted phenyl, C 1 ～C 4 Alkoxy-substituted phenyl, halophenyl, trifluoromethyl-substituted phenyl, nitro-substituted phenyl, thienyl, etc.; r 3 、R 4 、R 5 、R 6 Each independently represents H, fluorine, chlorine, bromine, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Any one of alkoxy groups.
The organic solvent is any one of dichloromethane, tetrahydrofuran and toluene, preferably dichloromethane.
The ligand is any one of L-phenylalanine, 3-nitrophthalic acid and 2-aminobenzenesulfonic acid, and L-phenylalanine is preferred.
In the preparation method, the molar ratio of the 3-butyne-2-ketone compound to the o-aminobenzenethiol compound is preferably 1: 1-1.5.
In the preparation method, the addition amount of the zirconocene dichloride is preferably 1 to 6 percent of the molar amount of the 3-butyne-2-one compound.
In the preparation method, the adding amount of the ligand is preferably 2 to 12 percent of the molar weight of the 3-butyne-2-ketone compound.
In the above preparation method, it is further preferable that the reaction is carried out at 40 to 50 ℃ for 4 to 6 hours with stirring.
The invention takes zirconocene dichloride as a catalyst, takes L-phenylalanine, 3-nitrophthalic acid and 2-aminobenzenesulfonic acid as catalyst ligands, and can efficiently catalyze the reaction of 3-butyne-2-ketone compounds and o-aminobenzenethiol compounds to prepare the 1, 5-benzothiazine compounds. The catalyst used in the invention has the advantages of low dosage, low price, no toxicity, stability to air, mild reaction conditions, short time, no toxicity to solvent and simple operation, and the 1, 5-benzothiazine compound with wide biological activity and medicinal value can be obtained by only separating the product through simple column chromatography after the reaction is finished, thereby opening up a new low-cost, green and efficient way for preparing the 1, 5-benzothiazine compound and having wide application prospect.
Detailed Description
The present invention will be described in further detail with reference to examples, but the scope of the present invention is not limited to these examples.
Example 1
Preparation of 2, 4-diphenyl-1, 5-benzothiazine
To the reaction tube were added 0.103g (0.5mmol) of 1, 4-diphenyl-3-butyn-2-one, 65. mu.L (0.6mmol) of o-aminobenzenethiol, 0.0074g (0.025mmol) of zirconocene dichloride, 0.0083g (0.05mmol) of L-phenylalanine, 1mL of dichloromethane, the reaction was stirred under reflux at 50 ℃ for 5h, stopped, the dichloromethane was removed by rotary evaporation, and separated by a silica gel column (eluent was a mixture of petroleum ether and dichloromethane at a volume ratio of 2: 1) to give 2, 4-diphenyl-1, 5-benzothiazine in 97% yield, and the product had spectral data: 1 H NMR(400MHz,CDCl 3 )δ8.03(dd,J＝6.5,2.9Hz,2H),7.82(d,J＝7.3Hz,2H),7.48-7.32(m,9H),7.15(t,J＝7.6Hz,1H),6.85(s,1H)； 13 C NMR(101MHz,CDCl 3 )δ165.83,150.33,150.07,139.32,138.58,132.82,130.91,129.65,129.41,128.69,128.61,128.15,127.92,127.56,126.69,126.41,124.52.
comparative example 1
In example 1, L-phenylalanine used was replaced with an equimolar amount of tyrosine, and the other procedure was the same as in example 1 to obtain 2, 4-diphenyl-1, 5-benzothiazine in a yield of 37%.
Comparative example 2
In example 1, the L-phenylalanine used was replaced with an equimolar amount of 5-sulfosalicylic acid and the other procedure was the same as in example 1 to obtain 2, 4-diphenyl-1, 5-benzothiazine in a yield of 35%.
Example 2
Preparation of 2- (4-chlorophenyl) -4-phenyl-1, 5-benzothiazine
In this example, the equimolar amount of 1- (4-chlorophenyl) -4-phenyl-3-butyn-2-one was used instead of 1, 4-diphenyl-3-butyn-2-one used in example 1, and the other procedure was the same as in example 1 to obtain 2- (4-chlorophenyl) -4-phenyl-1, 5-benzothiazine in 94% yield, and spectral data of the product were: 1 H NMR(400MHz,CDCl 3 )δ7.88(d,J＝8.3Hz,2H),7.77-7.70(m,2H),7.35(dd,J＝7.9,4.9Hz,3H),7.29(dd,J＝6.9,4.9Hz,5H),7.10(dt,J＝8.4,4.3Hz,1H),6.73(s,1H)； 13 C NMR(101MHz,CDCl 3 )δ165.92,151.90,151.48,139.80,139.14,138.42,134.21,131.12,130.82,130.59,130.17,130.08,129.32,128.91,128.28,127.77,125.29.
example 3
Preparation of 2- (4-bromophenyl) -4-phenyl-1, 5-benzothiazine
In this example, the same procedure as in example 1 was repeated except for replacing 1, 4-diphenyl-3-butyn-2-one used in example 1 with equimolar 1- (4-bromophenyl) -4-phenyl-3-butyn-2-one to give 2- (4-bromophenyl) -4-phenyl-1, 5-benzothiazine in 91% yield, and the product had the spectral data: 1 H NMR(400MHz,CDCl 3 )δ7.80(d,J＝8.6Hz,2H),7.74-7.69(m,2H),7.49(d,J＝8.5Hz,2H),7.35(d,J＝7.7Hz,1H),7.32-7.24(m,5H),7.09(dt,J＝8.3,4.4Hz,1H),6.71(s,1H)； 13 C NMR(101MHz,CDCl 3 )δ166.02,151.94,151.48,139.79,139.58,134.22,133.13,131.13,130.83,130.81,130.09,129.31,128.91,128.31,127.76,126.92,125.22.
example 4
Preparation of 2- (4-fluorophenyl) -4-phenyl-1, 5-benzothiazine
In this example, the 1, 4-diphenyl-3-butyn-2-one used in example 1 was replaced with equimolar 1- (4-fluorophenyl) -4-phenyl-3-butyn-2-one and the other steps were the same as in example 1 to give 2- (4-fluorophenyl) -4-phenyl-1, 5-benzothiazine in 97% yield, and the product had the spectral data: 1 H NMR(400MHz,CDCl 3 )δ7.95(dd,J＝8.7,5.6Hz,2H),7.77-7.70(m,2H),7.36(d,J＝7.8Hz,1H),7.34-7.26(m,5H),7.08(qd,J＝8.5,3.0Hz,3H),6.75(s,1H)； 13 C NMR(101MHz,CDCl 3 )δ164.76,163.42,162.26,149.21,149.06,137.37,134.45,134.42,131.71,128.93,128.85,128.60,128.32,127.59,126.87,126.42,125.64,125.24,122.97,114.57,114.36.
example 5
Preparation of 2- (4-methylphenyl) -4-phenyl-1, 5-benzothiazine
In this example, the equimolar amount of 1- (4-methylphenyl) -4-phenyl-3-butyn-2-one was used instead of 1, 4-diphenyl-3-butyn-2-one used in example 1, and the other procedure was the same as in example 1 to give 2- (4-methylphenyl) -4-phenyl-1, 5-benzothiazine in a yield of 86%, and the product had spectral data of: 1 H NMR(400MHz,CDCl 3 )δ7.99(d,J＝8.1Hz,2H),7.92-7.85(m,2H),7.51(d,J＝7.8Hz,1H),7.44(q,J＝5.3Hz,5H),7.33(d,J＝8.0Hz,2H),7.25-7.19(m,1H),6.93(s,1H),2.47(s,3H)； 13 C NMR(101MHz,CDCl 3 )δ167.04,151.79,151.16,142.60,140.07,138.05,134.14,130.92,130.71,130.68,130.04,129.58,129.23,128.91,127.83,127.72,125.98,22.95.
example 6
Preparation of 2- (4-methoxyphenyl) -4-phenyl-1, 5-benzothiazine
In this example, the equimolar of 1- (4-methoxyphenyl) -4-phenyl-3-butyn-2-one was used instead of 1, 4-diphenyl-3-butyn-2-one used in example 1, and the other procedure was the same as in example 1 to obtain 2- (4-methoxyphenyl) -4-phenyl-1, 5-benzothiazine with a yield of 71%, and spectral data of the product were: 1 H NMR(400MHz,CDCl 3 )δ7.92(d,J＝8.5Hz,2H),7.78-7.72(m,2H),7.37(d,J＝7.8Hz,1H),7.29(q,J＝5.2,3.5Hz,5H),7.11-7.04(m,1H),6.90(d,J＝8.5Hz,2H),6.78(s,1H),3.78(s,3H)； 13 C NMR(101MHz,CDCl 3 )δ163.90,160.86,149.35,148.53,137.62,131.64,130.96,128.43,128.23,127.55,127.03,126.42,125.19,125.16,123.39,112.82,54.39.
example 7
Preparation of 2-phenyl-4- (4-fluorophenyl) -1, 5-benzothiazine
In this example, the equimolar amount of 1-phenyl-4- (4-fluorophenyl) -3-butyn-2-one was used instead of 1, 4-diphenyl-3-butyn-2-one used in example 1, and the other procedure was the same as in example 1 to obtain 2-phenyl-4- (4-fluorophenyl) -1, 5-benzothiazine in 98% yield: 1 H NMR(400MHz,CDCl 3 )δ7.93(dd,J＝6.6,3.0Hz,2H),7.51(d,J＝7.9Hz,1H),7.48-7.43(m,1H),7.39(d,J＝2.1Hz,2H),7.39-7.34(m,2H),7.29(dd,J＝6.4,3.2Hz,2H),7.27-7.21(m,1H),7.10(ddd,J＝8.3,6.2,2.7Hz,1H),6.97(td,J＝8.2,2.1Hz,1H),6.78(s,1H)； 13 C NMR(101MHz,CDCl 3 )δ165.44,164.09,161.63,150.12,148.38,148.36,140.80,140.73,139.07,132.73,130.98,130.19,130.11,129.50,128.61,127.82,127.72,126.80,126.44,125.29,123.12,123.09,116.56,116.35,114.64,114.41.
example 8
Preparation of 2-phenyl-4- (2-thienyl) -1, 5-benzothiazine
In this example, the equimolar amount of 1-phenyl-4- (2-thienyl) -3-butyn-2-one was used instead of 1, 4-diphenyl-3-butyn-2-one used in example 1, and the other procedure was the same as in example 1 to obtain 2-phenyl-4- (2-thienyl) -1, 5-benzothiazine with a yield of 87%, and the product had spectral data as follows: 1 H NMR(400MHz,CDCl 3 )δ7.90(dd,J＝6.6,2.9Hz,2H),7.53(d,J＝3.7Hz,1H),7.40-7.34(m,3H),7.34-7.25(m,3H),7.19(d,J＝5.1Hz,1H),7.06(td,J＝7.7,7.2,2.4Hz,1H),6.92(t,J＝4.4Hz,1H),6.75(s,1H)； 13 C NMR(101MHz,CDCl 3 )δ165.47,150.29,143.11,142.32,139.35,132.77,130.88,129.50,128.56,128.24,128.21,128.00,127.94,127.36,126.71,126.41,121.43.
example 9
In this example, the same procedure as in example 1 was repeated except for using 2-aminobenzenesulfonic acid in place of L-phenylalanine used in example 1 in an equimolar amount, to obtain 2, 4-phenyl-1, 5-benzothiazine in a yield of 71%.
Example 10
In this example, the same procedure as in example 1 was repeated except for replacing L-phenylalanine used in example 1 with equimolar 3-nitrophthalic acid to give 2, 4-phenyl-1, 5-benzothiazine in a yield of 68%.
Example 11
In this example, the same procedure as in example 1 was repeated except for replacing methylene chloride used in example 1 with the same volume of tetrahydrofuran to give 2, 4-phenyl-1, 5-benzothiazine in a yield of 65%.
Example 12
In this example, methylene chloride used in example 1 was replaced with an equal volume of toluene, and the other steps were the same as in example 1 to obtain 2, 4-phenyl-1, 5-benzothiazine in a yield of 68%.
Claims (7)
1. A method for preparing 1, 5-benzothiazine compounds by using zirconocene dichloride as a catalyst is characterized by comprising the following steps: adding a compound shown in a formula I and an o-aminobenzenethiol compound shown in a formula II into an organic solvent, adding zirconocene dichloride and a ligand, stirring and reacting for 1-12 hours at room temperature-60 ℃, and separating and purifying a product to obtain a 1, 5-benzothiazine compound shown in a formula III;
in the formula R 1 And R 2 Each independently represents phenyl, C 1 ～C 4 Alkyl-substituted phenyl, C 1 ～C 4 Any one of alkoxy substituted phenyl, halogenated phenyl, trifluoromethyl substituted phenyl, nitro substituted phenyl and thienyl; r 3 、R 4 、R 5 、R 6 Each independently represents H, fluorine, chlorine, bromine, C 1 ～C 4 Alkyl radical, C 1 ～C 4 Any one of alkoxy groups;
the organic solvent is any one of dichloromethane, tetrahydrofuran and toluene;
the ligand is any one of L-phenylalanine, 3-nitrophthalic acid and 2-aminobenzenesulfonic acid.
2. The process for the catalytic preparation of 1, 5-benzothiazine compounds by zirconocene dichloride according to claim 1, characterized in that: the organic solvent is dichloromethane.
3. The process for the catalytic preparation of 1, 5-benzothiazine compounds according to claim 1 or said zirconocene dichloride, characterized in that: the ligand is L-phenylalanine.
4. The process for the catalytic preparation of 1, 5-benzothiazine compounds by zirconocene dichloride according to claim 1, characterized in that: the molar ratio of the compound shown in the formula I to the o-aminobenzenethiol compound is 1: 1-1.5.
5. The process for the catalytic preparation of 1, 5-benzothiazine compounds by zirconocene dichloride according to claim 1, characterized in that: the addition amount of the zirconocene dichloride is 1 to 6 percent of the molar weight of the compound in the formula I.
6. The process for the catalytic preparation of 1, 5-benzothiazine compounds by zirconocene dichloride according to claim 1, characterized in that: the addition amount of the ligand is 2 to 12 percent of the molar weight of the compound in the formula I.
7. The method for preparing 1, 5-benzothiazine compound catalyzed by zirconocene dichloride according to claim 1, characterized in that: stirring and reacting for 4-6 hours at 40-50 ℃.
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