CN110183397A - Bis cyclopentadienyl zirconium dichloride is catalyzed the method for preparing 1,5- benzo thiazides compounds - Google Patents
Bis cyclopentadienyl zirconium dichloride is catalyzed the method for preparing 1,5- benzo thiazides compounds Download PDFInfo
- Publication number
- CN110183397A CN110183397A CN201910547061.2A CN201910547061A CN110183397A CN 110183397 A CN110183397 A CN 110183397A CN 201910547061 A CN201910547061 A CN 201910547061A CN 110183397 A CN110183397 A CN 110183397A
- Authority
- CN
- China
- Prior art keywords
- zirconium dichloride
- cyclopentadienyl zirconium
- phenyl
- bis cyclopentadienyl
- thiazides compounds
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 35
- 239000003451 thiazide diuretic agent Substances 0.000 title claims abstract description 23
- 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 abstract description 18
- 238000000034 method Methods 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 25
- -1 aminobenzene sulfur alcohol compound Chemical group 0.000 claims abstract description 12
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 9
- 239000003446 ligand Substances 0.000 claims abstract description 9
- 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 group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 26
- 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 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 229960005190 phenylalanine Drugs 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 125000001544 thienyl group Chemical group 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
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 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
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- XNMQEEKYCVKGBD-UHFFFAOYSA-N 2-butyne Chemical group CC#CC XNMQEEKYCVKGBD-UHFFFAOYSA-N 0.000 claims 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 claims 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 claims 1
- 125000003963 dichloro group Chemical group Cl* 0.000 claims 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 229910052726 zirconium Inorganic materials 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 9
- 239000003054 catalyst Substances 0.000 abstract description 5
- 231100000252 nontoxic Toxicity 0.000 abstract description 3
- 230000003000 nontoxic effect Effects 0.000 abstract description 3
- 238000000926 separation method Methods 0.000 abstract description 3
- 238000004440 column chromatography Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 32
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 239000004305 biphenyl Substances 0.000 description 8
- 230000003595 spectral effect Effects 0.000 description 8
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
- CSKPAEFLXIWTSE-UHFFFAOYSA-N C1=CC=C(C=C1)C2C=C(C3=C(S2)C=CC=N3)C4=CC=CC=C4 Chemical compound C1=CC=C(C=C1)C2C=C(C3=C(S2)C=CC=N3)C4=CC=CC=C4 CSKPAEFLXIWTSE-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-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
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- QMZPQIVWTCTDIK-UHFFFAOYSA-N 2h-thiopyrano[3,2-b]pyridine Chemical group C1=CN=C2C=CCSC2=C1 QMZPQIVWTCTDIK-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
- 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 1
- 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 1
- 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 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 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
- 102000048238 Neuregulin-1 Human genes 0.000 description 1
- 108090000556 Neuregulin-1 Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000003340 retarding agent Substances 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
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 150000004897 thiazines Chemical class 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
Landscapes
- 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 kind of bis cyclopentadienyl zirconium dichloride catalysis preparations 1, the method of 5- benzo thiazides compounds, this method is using 3- crotonylene -one class compound and adjacent aminobenzene sulfur alcohol compound as raw material, using bis cyclopentadienyl zirconium dichloride as catalyst, under the promotion of the ligands such as L-phenylalanine, 3- nitrophthalic acid, 2- aminobenzenesulfonic acid, it can efficient, high yield preparation 1,5- benzo thiazides compounds.Used catalyst dosage of the present invention is few, it is inexpensive, nontoxic, to air-stable, reaction condition is mild, the time is short, it is easy to operate, Atom economy is high, only product need to be passed through simple column chromatography for separation after reaction, can be obtained 1,5- benzo thiazides compounds, new inexpensive, efficient approach is opened for the preparation of 1,5- benzo thiazides compounds, is had broad application prospects.
Description
Technical field
The invention belongs to the synthesis technical fields of 1,5- benzo thiazides compounds, and in particular to a kind of bis cyclopentadienyl zirconium dichloride is urged
Change 3- crotonylene -one class compound and adjacent aminobenzene sulfur alcohol compound reaction, efficiently prepares 1,5- benzo thiazides compounds
Method.
Background technique
1,5- benzothiazine skeleton is widely present in natural products, has been confirmed as the pharmacophoric group of a multiple-effect,
Derivative includes inverase and anticancer drug, angiotensin converting enzyme inhibitors, antibiotic and antifungal compound, calcium
Heregulin antagonist and Ca2+Retarding agent etc..Further, since many 1,5- benzo thiazides compounds have antimycotic, antibacterial,
Anti-inflammatory, analgesia and anti-convulsant activity, are of great significance in drug and organic synthesis.
And relative to stable five-membered ring, six-membered ring structure, researchers are to the appendicular research on heptatomic ring at present
At least, therefore specifically for the synthesis of the diversity of 1, the 5- benzo thiazides compounds of heptatomic ring lack very much.It develops more multistable
Fixed, cheap, efficient, mild condition catalysis process, is of great significance to the preparation of 1,5- benzo thiazides compounds.
Summary of the invention
The object of the present invention is to provide it is a kind of it is easy to operate, reaction condition is mild, efficiently prepare 2,4- diphenyl -1,5- benzene
And the method for thiazine derivative.
For above-mentioned purpose, the technical scheme adopted by the invention is that: by the -one class compound of 3- crotonylene shown in Formulas I and
The sulfur alcohol compound of neighbour's aminobenzene shown in Formula II is added in organic solvent, and bis cyclopentadienyl zirconium dichloride and ligand is added, in room temperature~60
It is stirred to react at DEG C 1~12 hour, isolates and purifies product, obtain formula III depicted 1,5- benzo thiazides compounds.
R in formula1And R2It is independent to represent aryl or substituted aryl, specifically such as: phenyl, C1~C4Alkyl-substituted phenyl,
C1~C4Alkoxy substituted phenyl, halogenophenyl, trifluoromethyl substituted-phenyl, nitro substituted-phenyl, thienyl etc.;R3、R4、R5、
R6It is independent to represent H, fluorine, chlorine, bromine, C1~C4Alkyl, C1~C4Any one in alkoxy.
Above-mentioned organic solvent is methylene chloride, tetrahydrofuran, any one in toluene, preferably methylene chloride.
Above-mentioned ligand is L-phenylalanine, 3- nitrophthalic acid, any one in 2- aminobenzenesulfonic acid, preferably L-
Phenylalanine.
In above-mentioned preparation method, the preferably described 3- crotonylene -one class compound rubs with adjacent aminobenzene sulfur alcohol compound
You are than being 1:1~1.5.
In above-mentioned preparation method, the additional amount 3- crotonylene -one class compound mole of the preferably described bis cyclopentadienyl zirconium dichloride
1%~6%.
In above-mentioned preparation method, the additional amount of the preferably described ligand be 3- crotonylene -one class compound mole 2%~
12%.
In above-mentioned preparation method, further preferably it is stirred to react at 40~50 DEG C 4~6 hours.
The present invention is using bis cyclopentadienyl zirconium dichloride as catalyst, with L-phenylalanine, 3- nitrophthalic acid, 2- aminobenzenesulfonic acid
It, can efficient catalytic 3- crotonylene -one class compound and adjacent aminobenzene sulfur alcohol compound reaction, preparation 1,5- for catalyst ligand
Benzo thiazides compounds.Used catalyst dosage of the present invention is few, it is inexpensive, nontoxic, to air-stable, reaction condition is mild, when
Between short, nontoxic solvent, it is easy to operate, after reaction only need to by product pass through simple column chromatography for separation, can be obtained has
1, the 5- benzo thiazides compounds of extensive bioactivity and medical value, are opened for the preparation of 1,5- benzo thiazides compounds
The approach for having warded off new low cost and green high-efficient, has broad application prospects.
Specific embodiment
Below with reference to embodiment, the present invention is described in more detail, but protection scope of the present invention is not limited only to these realities
Apply example.
Embodiment 1
The following 2,4- diphenyl -1,5- benzothiazine of preparation structure formula
The adjacent ammonia of 0.103g (0.5mmol) 1,4- diphenyl -3- crotonylene -one, 65 μ L (0.6mmol) is added into reaction tube
Base benzenethiol, 0.0074g (0.025mmol) bis cyclopentadienyl zirconium dichloride, 0.0083g (0.05mmol) L-phenylalanine, 1mL dichloromethane
Alkane, reflux is stirred to react 5h at 50 DEG C, stops reaction, and rotary evaporation removes methylene chloride, and with silica gel post separation, (eluant, eluent is
Petroleum ether and methylene chloride volume are than the mixed liquor for 2:1), 2,4- diphenyl -1,5- benzothiazine is obtained, yield is
97%, the spectral data of product are as follows:1H NMR(400MHz,CDCl3) δ 8.03 (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);13C NMR(101MHz,CDCl3)
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 embodiment 1, the tyrosine replacement of L-phenylalanine equimolar amounts used, other steps and embodiment 1
It is identical, obtain 2,4- diphenyl -1,5- benzothiazine, yield 37%.
Comparative example 2
In embodiment 1, the 5-sulphosalicylic acid replacement of L-phenylalanine equimolar amounts used, other steps and reality
It is identical to apply example 1, obtains 2,4- diphenyl -1,5- benzothiazine, yield 35%.
Embodiment 2
The following 2- of preparation structure formula (4- chlorphenyl) -4- phenyl -1,5- benzothiazine
In the present embodiment, used in equimolar 1- (4- chlorphenyl) -4- phenyl -3- crotonylene -one alternative embodiment 1
Isosorbide-5-Nitrae-diphenyl -3- crotonylene -one, other steps are same as Example 1, obtain 2- (4- chlorphenyl) -4- phenyl -1,5- benzo
Thiazine, yield 94%, the spectral data of product are as follows:1H NMR(400MHz,CDCl3) δ 7.88 (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);13C NMR(101MHz,CDCl3)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.
Embodiment 3
The following 2- of preparation structure formula (4- bromophenyl) -4- phenyl -1,5- benzothiazine
In the present embodiment, used in equimolar 1- (4- bromophenyl) -4- phenyl -3- crotonylene -one alternative embodiment 1
Isosorbide-5-Nitrae-diphenyl -3- crotonylene -one, other steps are same as Example 1, obtain 2- (4- bromophenyl) -4- phenyl -1,5- benzene
And thiazine, yield 91%, the spectral data of product are as follows:1H NMR(400MHz,CDCl3) δ 7.80 (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);13C NMR(101MHz,CDCl3)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.
Embodiment 4
The following 2- of preparation structure formula (4- fluorophenyl) -4- phenyl -1,5- benzothiazine
In the present embodiment, used in equimolar 1- (4- fluorophenyl) -4- phenyl -3- crotonylene -one alternative embodiment 1
Isosorbide-5-Nitrae-diphenyl -3- crotonylene -one, other steps are same as Example 1, obtain 2- (4- fluorophenyl) -4- phenyl -1,5- benzene
And thiazine, yield 97%, the spectral data of product are as follows:1H NMR(400MHz,CDCl3) δ 7.95 (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);13C NMR(101MHz,CDCl3)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.
Embodiment 5
The following 2- of preparation structure formula (4- aminomethyl phenyl) -4- phenyl -1,5- benzothiazine
In the present embodiment, with institute in equimolar 1- (4- aminomethyl phenyl) -4- phenyl -3- crotonylene -one alternative embodiment 1
Isosorbide-5-Nitrae-diphenyl-3- crotonylene -one, other steps are same as Example 1, obtain 2- (4- aminomethyl phenyl) phenyl-1-4-,
5- benzothiazine, yield 86%, the spectral data of product are as follows:1H NMR(400MHz,CDCl3) δ 7.99 (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);13C NMR(101MHz,CDCl3)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.
Embodiment 6
The following 2- of preparation structure formula (4- methoxyphenyl) -4- phenyl -1,5- benzothiazine
In the present embodiment, in equimolar 1- (4- methoxyphenyl) -4- phenyl -3- crotonylene -one alternative embodiment 1
Isosorbide-5-Nitrae used-diphenyl -3- crotonylene -one, other steps are same as Example 1, obtain 2- (4- methoxyphenyl) -4- benzene
Base -1,5- benzothiazine, yield 71%, the spectral data of product are as follows:1H NMR(400MHz,CDCl3) δ 7.92 (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);13C NMR(101MHz,CDCl3)δ
163.90,160.86,149.35,148.53,137.62,131.64,130.96,128.43,128.23,127.55,127.03,
126.42,125.19,125.16,123.39,112.82,54.39.
Embodiment 7
Following 2- phenyl -4- (4- the fluorophenyl) -1,5- benzothiazine of preparation structure formula
In the present embodiment, used in equimolar 1- phenyl -4- (4- fluorophenyl) -3- crotonylene -one alternative embodiment 1
Isosorbide-5-Nitrae-diphenyl -3- crotonylene -one, other steps are same as Example 1, obtain 2- phenyl -4- (4- fluorophenyl) -1,5- benzene
And thiazine, yield 98%, the spectral data of product are as follows:1H NMR(400MHz,CDCl3) δ 7.93 (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);13C NMR(101MHz,CDCl3)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.
Embodiment 8
Following 2- phenyl -4- (2- the thienyl) -1,5- benzothiazine of preparation structure formula
In the present embodiment, used in equimolar 1- phenyl -4- (2- thienyl) -3- crotonylene -one alternative embodiment 1
Isosorbide-5-Nitrae-diphenyl -3- crotonylene -one, other steps are same as Example 1, obtain 2- phenyl -4- (2- thienyl) -1,5- benzene
And thiazine, yield 87%, the spectral data of product are as follows:1H NMR(400MHz,CDCl3) δ 7.90 (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);13C NMR
(101MHz,CDCl3)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.
Embodiment 9
In the present embodiment, the L-phenylalanine used in equimolar 2- aminobenzenesulfonic acid alternative embodiment 1, other steps
It is same as Example 1, obtain 2,4- phenyl -1,5- benzothiazine, yield 71%.
Embodiment 10
In the present embodiment, the L-phenylalanine used in equimolar 3- nitrophthalic acid alternative embodiment 1 is other
Step is same as Example 1, obtains 2,4- phenyl -1,5- benzothiazine, yield 68%.
Embodiment 11
In the present embodiment, the methylene chloride used in isometric tetrahydrofuran alternative embodiment 1, other steps and implement
Example 1 is identical, obtains 2,4- phenyl -1,5- benzothiazine, yield 65%.
Embodiment 12
In the present embodiment, the methylene chloride used in isometric toluene alternative embodiment 1, other steps and embodiment 1
It is identical, obtain 2,4- phenyl -1,5- benzothiazine, yield 68%.
Claims (8)
1. a kind of method of bis cyclopentadienyl zirconium dichloride catalysis preparation 1,5- benzo thiazides compounds, it is characterised in that: by 3- shown in Formulas I
Neighbour's aminobenzene sulfur alcohol compound shown in crotonylene -one class compound and Formula II is added in organic solvent, and two cyclopentadienyl of dichloro is added
Zirconium and ligand are stirred to react 1~12 hour at room temperature~60 DEG C, isolate and purify product, obtain formula III depicted 1,5- benzo thiophene
Piperazine class compound;
R in formula1And R2It is independent to represent aryl or substituted aryl;R3、R4、R5、R6It is independent represent H, fluorine, chlorine, bromine,
C1~C4Alkyl, C1~C4Any one in alkoxy;
Above-mentioned organic solvent is methylene chloride, tetrahydrofuran, any one in toluene;
Above-mentioned ligand is L-phenylalanine, 3- nitrophthalic acid, any one in 2- aminobenzenesulfonic acid.
2. the method for bis cyclopentadienyl zirconium dichloride catalysis preparation 1,5- benzo thiazides compounds according to claim 1, feature
It is: the R1And R2It is independent to represent phenyl, C1~C4Alkyl-substituted phenyl, C1~C4Alkoxy substituted phenyl, halogen
For any one in phenyl, trifluoromethyl substituted-phenyl, nitro substituted-phenyl, thienyl.
3. the method for bis cyclopentadienyl zirconium dichloride catalysis preparation 1,5- benzo thiazides compounds according to claim 1 or 2, special
Sign is: the organic solvent is methylene chloride.
4. according to claim 1 or the bis cyclopentadienyl zirconium dichloride is catalyzed the method for preparing 1,5- benzo thiazides compounds, special
Sign is: the ligand is L-phenylalanine.
5. the method for bis cyclopentadienyl zirconium dichloride catalysis preparation 1,5- benzo thiazides compounds according to claim 1 or 2, special
Sign is: the molar ratio of the 3- crotonylene -one class compound and adjacent aminobenzene sulfur alcohol compound is 1:1~1.5.
6. the method for bis cyclopentadienyl zirconium dichloride catalysis preparation 1,5- benzo thiazides compounds according to claim 1 or 2, special
Sign is: the additional amount of the bis cyclopentadienyl zirconium dichloride is the 1%~6% of 3- crotonylene -one class compound mole.
7. the method for bis cyclopentadienyl zirconium dichloride catalysis preparation 1,5- benzo thiazides compounds according to claim 1 or 2, special
Sign is: the additional amount of the ligand is the 2%~12% of 3- crotonylene -one class compound mole.
8. the method for bis cyclopentadienyl zirconium dichloride catalysis preparation 1,5- benzo thiazides compounds according to claim 1 or 2, special
Sign is: being stirred to react at 40~50 DEG C 4~6 hours.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910547061.2A CN110183397B (en) | 2019-06-24 | 2019-06-24 | Method for preparing 1, 5-benzothiazine compound by catalysis of zirconocene dichloride |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910547061.2A CN110183397B (en) | 2019-06-24 | 2019-06-24 | Method for preparing 1, 5-benzothiazine compound by catalysis of zirconocene dichloride |
Publications (2)
Publication Number | Publication Date |
---|---|
CN110183397A true CN110183397A (en) | 2019-08-30 |
CN110183397B CN110183397B (en) | 2022-08-23 |
Family
ID=67722990
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910547061.2A Expired - Fee Related CN110183397B (en) | 2019-06-24 | 2019-06-24 | Method for preparing 1, 5-benzothiazine compound by catalysis of zirconocene dichloride |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110183397B (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3075968A (en) * | 1961-09-18 | 1963-01-29 | Olin Mathieson | Benzothiazepines |
GB1317475A (en) * | 1969-06-11 | 1973-05-16 | Boehringer Sohn Ingelheim | Benzodiazepines the preparation thereof and compositions containing the same |
AU2012251921A1 (en) * | 2008-06-20 | 2012-12-06 | Astrazeneca Ab | Dibenzothiazepine derivatives and use thereof |
-
2019
- 2019-06-24 CN CN201910547061.2A patent/CN110183397B/en not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3075968A (en) * | 1961-09-18 | 1963-01-29 | Olin Mathieson | Benzothiazepines |
GB1317475A (en) * | 1969-06-11 | 1973-05-16 | Boehringer Sohn Ingelheim | Benzodiazepines the preparation thereof and compositions containing the same |
AU2012251921A1 (en) * | 2008-06-20 | 2012-12-06 | Astrazeneca Ab | Dibenzothiazepine derivatives and use thereof |
Non-Patent Citations (5)
Title |
---|
GEMMA CABARROCAS ET AL.: "Synthesis of novel optically pure quinolyl-β-amino alcohol derivatives from 2-amino thiophenol and chiral α-acetylenic ketones and their IBX-mediated oxidative cleavage to N-Boc quinolyl carboxamides", 《TETRAHEDRON: ASYMMETRY》 * |
LINGAIAH NAGARAPU ET AL.: "BENZODIAZEPINE FUSED HETEROCYCLES IV : A CONVENIENT SYNTHESIS OF BENZO[b][1,5]THIAZEPINES USING MCM-41(H) ZEOLITE", 《HETEROCYCLIC COMMUNICATIOM》 * |
MINGMINGYANG ET AL.: "NaturalAminoAcid L-PhenylalanineCoordinatedZirconocene Complexas BifunctionalCatalystfor the Synthesisof 1,5-Benzothiazepines", 《ASIAN J. ORG. CHEM》 * |
廖云峰: "以芳基硫酚为原料的C-S键生成反应方法研究", 《中国优秀博硕士学位论文全文数据库(博士)工程科技Ⅰ辑》 * |
张艺扬 等: "SiO2微球负载的CeCl3·7H2O-NaI催化邻氨基苯硫酚与高位阻α,β-不饱和酮的Michael加成及其串联反应", 《有机化学》 * |
Also Published As
Publication number | Publication date |
---|---|
CN110183397B (en) | 2022-08-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105461624B (en) | A kind of method that sulfosalicylic acid collaboration cyclopentadienyl titanium dichloride water mutually efficiently prepares quinoline | |
EP0496692A1 (en) | 2-Methoxyphenylpiperazine derivatives | |
Yu et al. | Regioselective synthesis of highly substituted imidazoles via the sequential reaction of allenyl sulfonamides and amines | |
Sharma et al. | Organocatalytic enantioselective conjugate addition of pyrazolin-5-ones to arylomethylidene malonates | |
CN109867643A (en) | A kind of furane derivative derivative and its synthesis | |
CN102690227A (en) | Optical active tetrahydropyridine derivative and preparation method thereof | |
CN104447604A (en) | Synthetic method for chiral quaternary carbon oxazolidinone compound | |
BR0205683A (en) | Process for the preparation of piperazine derivatives, and mesylate of a compound | |
Prim et al. | Efficient synthesis of N, N-disubstituted 5-aminothiophene-2-carboxaldehydes by nucleophilic aromatic substitution in water | |
CN110183397A (en) | Bis cyclopentadienyl zirconium dichloride is catalyzed the method for preparing 1,5- benzo thiazides compounds | |
CN102070503B (en) | Method for preparing pyrrole derivative | |
CN111592544A (en) | Indoline aza eight-membered ring derivative and synthesis method thereof | |
Li et al. | Highly Enantioselective Synthesis of α‐Trifluoromethyldihydropyrans Using a Chiral Trifluoroethyl‐substituted Thiourea Catalyst Derived from Amino Acid | |
CN107573298B (en) | Preparation method for synthesizing 2, 5-disubstituted oxazole compound | |
CN109897033A (en) | A kind of method synthesizing imidazo containing iodine [1,2a] pyridine compounds and their | |
CN107868087A (en) | A kind of method for preparing pyrrolo-indole analog derivative | |
CN110698426B (en) | Method for preparing 1, 3-benzothiazole derivative by efficient catalysis of potassium tert-butoxide | |
CN101628904B (en) | Synthesis method of 2-nitro-3-aryl-2,3,5,7-tetrahydrobenzofuran-4-one derivative | |
CN109438288B (en) | N-nitrone substituted aromatic amide derivative and preparation method thereof | |
CN107445914B (en) | 2,2, 5-trisubstituted 1,3,4 oxadiazole derivative and synthetic method thereof | |
CN101372478A (en) | Compound containing 2- bromovinyl-1,2,3-triazole and preparation thereof | |
CN105272953A (en) | Method for synthesizing coumarone naphthoquinone derivative | |
CN105330565A (en) | Novel method for catalytically synthesizing cyanobenzene derivative through copper | |
CN110256365A (en) | The method that cyclopentadienyl titanium dichloride catalysis prepares Benzodiazepine derivative | |
CN109134402A (en) | A kind of chiral sulfonamide analog derivative and its preparation method and application |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20220823 |