CN115785010A - Thio-1, 2, 3-triazole and efficient synthesis method thereof - Google Patents
Thio-1, 2, 3-triazole and efficient synthesis method thereof Download PDFInfo
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- 238000001308 synthesis method Methods 0.000 title claims abstract description 19
- PWWSSIYVTQUJQQ-UHFFFAOYSA-N distearyl thiodipropionate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CCSCCC(=O)OCCCCCCCCCCCCCCCCCC PWWSSIYVTQUJQQ-UHFFFAOYSA-N 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 84
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- -1 1,2, 3-triazole compound Chemical class 0.000 claims abstract description 20
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000011593 sulfur Substances 0.000 claims abstract description 11
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 11
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 7
- BVLCUZLVOPMLGD-UHFFFAOYSA-N 2h-triazole-4-sulfonic acid Chemical compound OS(=O)(=O)C1=CNN=N1 BVLCUZLVOPMLGD-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 239000010949 copper Substances 0.000 claims description 13
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical group [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 10
- 229910052802 copper Inorganic materials 0.000 claims description 10
- 239000003054 catalyst Substances 0.000 claims description 9
- 150000000177 1,2,3-triazoles Chemical class 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 5
- 150000003934 aromatic aldehydes Chemical class 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical group [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 3
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical group CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 claims description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 2
- 239000007818 Grignard reagent Substances 0.000 claims 1
- 150000004795 grignard reagents Chemical class 0.000 claims 1
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- 125000000524 functional group Chemical group 0.000 abstract description 4
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 abstract description 3
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- 239000007788 liquid Substances 0.000 description 22
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 18
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- 238000001035 drying Methods 0.000 description 14
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- 239000003960 organic solvent Substances 0.000 description 9
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 8
- RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- 229940019778 diethylene glycol diethyl ether Drugs 0.000 description 8
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 125000003396 thiol group Chemical group [H]S* 0.000 description 7
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- 238000000926 separation method Methods 0.000 description 6
- LLCOQBODWBFTDD-UHFFFAOYSA-N 1h-triazol-1-ium-4-thiolate Chemical compound SC1=CNN=N1 LLCOQBODWBFTDD-UHFFFAOYSA-N 0.000 description 5
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
- 229960001701 chloroform Drugs 0.000 description 5
- 238000006352 cycloaddition reaction Methods 0.000 description 5
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 101001053401 Arabidopsis thaliana Acid beta-fructofuranosidase 3, vacuolar Proteins 0.000 description 2
- 101001053395 Arabidopsis thaliana Acid beta-fructofuranosidase 4, vacuolar Proteins 0.000 description 2
- 101100132433 Arabidopsis thaliana VIII-1 gene Proteins 0.000 description 2
- 101100459319 Arabidopsis thaliana VIII-2 gene Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- UQVNQVMNIKJMBR-UHFFFAOYSA-N 4-fluoro-2h-triazole Chemical compound FC1=CN=NN1 UQVNQVMNIKJMBR-UHFFFAOYSA-N 0.000 description 1
- RWPISZUNOCYFHY-UHFFFAOYSA-N 4-iodo-2h-triazole Chemical compound IC1=CNN=N1 RWPISZUNOCYFHY-UHFFFAOYSA-N 0.000 description 1
- YYYYGCMMBVVYLF-UHFFFAOYSA-N 4-sulfonyltriazole Chemical compound O=S(=O)=C1C=NN=N1 YYYYGCMMBVVYLF-UHFFFAOYSA-N 0.000 description 1
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 1
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- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000003471 anti-radiation Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
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- 230000000975 bioactive effect Effects 0.000 description 1
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- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
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- 125000001424 substituent group Chemical group 0.000 description 1
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Images
Abstract
The invention discloses sulfo-1, 2, 3-triazole and an efficient synthesis method thereof, which are a method for efficiently and simply synthesizing a sulfur-containing 1,2, 3-triazole compound III-X by taking diphenyl phosphono sulfo-alkyne I and azide compound II as raw materials through different reactions under a protective atmosphere, and have the advantages of high yield, wide functional group tolerance range, simplicity and convenience in operation and the like.
Description
Technical Field
The invention relates to a method for synthesizing sulfo-1, 2, 3-triazole, in particular to a method for synthesizing sulfo-1, 2, 3-triazole by taking diphenylphosphonyl sulfo-alkyne as a raw material and catalyzing cycloaddition reaction (CuAAC) of the diphenyl phosphono sulfo-alkyne and azide by copper, belonging to the field of organic synthesis.
Background
Organosulfur compounds are present in many natural products and drug molecules and are readily oxidized and useful as anti-oxidant and anti-radiation drugs. Introduction of sulfur atoms into biologically active molecules generally increases their biological or pharmacodynamic activity. The 1,2, 3-triazole compound has various biological activities and is a skeleton structure of a plurality of bioactive compounds, medicines and pesticide molecules. Different substituents are introduced into different sites of the 1,2, 3-triazole ring to obtain molecules with different biological activities. And sulfur substituent groups are introduced to the 1,2, 3-triazole ring to obtain the sulfur-containing 1,2, 3-triazole with specific biological activity.
Copper-catalyzed cycloaddition reaction (CuAAC) of azide and thioalkyne is a common method for constructing a 1,2, 3-triazole skeleton. The following two methods are mainly used for synthesizing the sulfur-containing 1,2, 3-triazole: the first method is to synthesize a 1,2, 3-triazole skeleton, and then synthesize the sulfur-containing 1,2, 3-triazole through SNAr reaction; the second method is to directly synthesize the sulfur-containing 1,2, 3-triazole by cycloaddition of a sulfur-containing substrate and an azide compound. Although the above methods are effective in synthesizing sulfur-containing 1,2, 3-triazole, they have the following drawbacks: for example, iodo-1, 2, 3-triazole needs to be converted into fluoro-1, 2, 3-triazole under microwave and high temperature of 180 ℃, and then is converted into the target sulfur-containing 1,2, 3-triazole through SNAr reaction); the use of noble metals such as Ir, ru catalysts is required; only the aryl sulfur 1,2, 3-triazole is obtained, and the substrate range needs to be further expanded. Therefore, the development of a novel high-efficiency synthesis method of the sulfur-containing 1,2, 3-triazole has great theoretical research significance and practical application value.
Disclosure of Invention
The invention aims to provide a method for efficiently, simply and conveniently synthesizing a sulfur-containing 1,2, 3-triazole compound III-X by taking diphenylphosphonyl thioalkyne I and an azide compound II as raw materials through different reactions under different conditions. The method has the advantages of high yield, wide functional group tolerance range, simple and convenient operation and the like.
In order to achieve the technical purpose, the invention provides a method for preparing 4-mercapto-1, 2, 3-triazole III by reacting in a THF (tetrahydrofuran), ethanol, propanol, n-propanol, isopropanol, butanol, isobutanol, tert-butanol, ethylene glycol diethyl ether, diethylene glycol diethyl ether, 1,4-dioxane, DMF (dimethyl formamide), DMSO or toluene solution system (or adding organic amine) of phenylphosphonothioalkyne I and azide II at a specific temperature T1 for a certain time T1 under the action of a copper catalyst cat.1 and an alkali reagent, extracting with a common organic solvent after the reaction is finished, drying, filtering, and carrying out column chromatography to obtain the product 4-mercapto-1, 2, 3-triazole III. Under the action of m-chloroperoxybenzoic acid (mCPBA), reacting for a certain time T2 in a THF, dichloromethane, trichloromethane, diethyl ether, acetone, ethanol, ethylene glycol diethyl ether, diethylene glycol diethyl ether, 1,4-dioxane, DMF, DMSO or toluene solution system of 4-mercapto-1, 2, 3-triazole III at a specific temperature T2, extracting with a common organic solvent after the reaction is finished, drying, filtering, and carrying out column chromatography to obtain the product 4-sulfonyl-1, 2, 3-triazole IV. Under the action of a copper catalyst cat.2 and sodium ascorbate, reacting in a THF, ethanol, propanol, n-propanol, isopropanol, butanol, isobutanol, tert-butanol, ethylene glycol diethyl ether, diethylene glycol diethyl ether, 1,4-dioxane, DMF, DMSO, NMP or toluene solution system of phenylphosphonothioalkyne I and azide compound II at a specific temperature T3 for a certain time T3, extracting with a common organic solvent after the reaction is finished, drying, filtering, and performing column chromatography to obtain phosphono and mercapto substituted 1,2, 3-triazole V and VI products. Under the action of mCPBA, reacting for a certain time T4 in a THF, dichloromethane, chloroform, diethyl ether, acetone, ethanol, ethylene glycol diethyl ether, diethylene glycol diethyl ether, 1,4-dioxane, DMF, DMSO or toluene solution system of diphenylphosphonothioalkyne I at a specific temperature T4, extracting by using a common organic solvent after the reaction is finished, drying, filtering, and spin-drying the filtrate to obtain a crude product, reacting for a certain time T5 in the crude product and a THF, ethanol, propanol, n-propanol, isopropanol, butanol, isobutanol, tert-butanol, ethylene glycol diethyl ether, diethylene glycol diethyl ether, DMF, DMSO or toluene solution system of azide II at a specific temperature T5, extracting by using a common organic solvent after the reaction is finished, drying, filtering, and performing column chromatography to obtain products of phosphono and mercapto substituted 1,2, 3-triazole VII and VIII. Reacting for a certain time T6 at a specific temperature T6 in a phosphono and mercapto substituted 1,2, 3-triazole V, phenyl silane and acetic acid THF, ethanol, propanol, n-propanol, isopropanol, butanol, isobutanol, tert-butanol, ethylene glycol diethyl ether, diethylene glycol diethyl ether, DMF, DMSO, toluene or xylene solution system, extracting by using a common organic solvent after the reaction is finished, drying, filtering, and carrying out column chromatography to obtain a product phosphine and mercapto substituted 1,2, 3-triazole IX. In a phosphono and mercapto substituted 1,2, 3-triazole V and MeMgBr solution system of THF, dichloromethane, trichloromethane, diethyl ether, 1,4-dioxane, ethylene glycol diethyl ether, diethylene glycol diethyl ether or toluene, reacting for a certain time T7 at a specific temperature T7, after the reaction is finished, adding aromatic aldehyde into the reaction solution, reacting for a certain time T8 at a specific temperature T8, after the reaction is finished, extracting with a common organic solvent, drying, filtering, and performing column chromatography to obtain the product, namely the hydroxy and mercapto substituted 1,2, 3-triazole X. Under the action of an alkali reagent, reacting for a certain time T9 in a phosphono and mercapto substituted 1,2, 3-triazole VI solution system of THF, dichloromethane, trichloromethane, diethyl ether, 1,4-dioxane, ethylene glycol diethyl ether, diethylene glycol diethyl ether or toluene at a specific temperature T9, extracting with a common organic solvent after the reaction is finished, drying, filtering, and carrying out column chromatography to obtain the product 5-mercapto-1, 2, 3-triazole XI. Products of bis 4-mercapto-1, 2, 3-triazole XII-1, XII-2, XII-3 and XII-4 can be obtained through the step of preparing III.
Wherein said R 1 、R 2 、R 3 Is functional group such as aryl or alkyl.
In the above synthesis method, the alkynyl bromide reagent is the following compound:
in the above synthesis method, the phenylphosphonothioalkyne i is one of the following compounds:
in the above synthesis method, the azide compound ii is one of the following compounds:
in the above synthesis method, the copper catalyst cat.1 is one of the following compounds: copper iodide (CuI), copper tetra-acetonitrile hexafluorophosphate (Cu (MeCN) 4 PF 6 ) One of them.
In the above synthesis method, the alkali reagent is one of the following compounds: potassium tert-butoxide (tBuOK).
In the above synthesis method, the organic amine is N, N' -dimethylethylenediamine (DMEDA).
In the above synthesis method, the copper catalyst cat.2 is one of the following copper catalysts: cuI, cu (MeCN) 4 BF 4 、CuI/CuSO 4 -5H 2 One of O.
In the above synthesis method, the aromatic aldehyde is one of the following compounds:
in the synthesis method, the reaction temperature T1 is 50-140 ℃, T2 is-20-60 ℃, T3 is 80-200 ℃, T4 is-20-60 ℃, T5 is 50-180 ℃, T6 is 60-150 ℃, T7 is-20-60 ℃, T8 is-20-80 ℃ and T9 is-20-60 ℃.
In the above synthesis method, the reaction time t1 is 2-24h, t2 is 0.5-24h, t3 is 5-48h, t4 is 0.5-24h, t5 is 5-48h, t6 is 2-24h, t7 is 0.5-24h, t8 is 1-48h, and t9 is 0.5-24h.
In the above synthesis method, the common organic solvent for extraction after the reaction is CH 2 Cl 2 And one of chloroform, toluene, diethyl ether, petroleum ether, n-hexane and ethyl acetate.
The synthesis method provided by the invention is characterized in that diphenylphosphonothioalkyne is used as a raw material, and the cycloaddition reaction (CuAAC) of diphenylphosphonothioalkyne and azide is catalyzed by copper to synthesize the sulfo-1, 2, 3-triazole, so that a new synthesis way of the sulfo-1, 2, 3-triazole is developed, and the synthesis method has the advantages that: (1) without isolation of intermediates; (2) The method is carried out under mild reaction conditions, the yield is high, and the tolerance range of functional groups is wide; and (3) the operation is simple.
Drawings
FIG. 1 is a schematic diagram of a cycloaddition reaction (CuAAC) of diphenylphosphonothioalkyne and an azide to synthesize thio-1, 2, 3-triazole.
Detailed Description
In order to make the aforementioned features, advantages and objects of the present invention comprehensible, embodiments accompanied with figures are described in detail below. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein, but rather should be construed as broadly as the present invention is capable of modification in various respects, all without departing from the spirit and scope of the present invention.
Example 1
The target product has the following structural formula:
at room temperature, 0.5mmol of I-1, 0.6mmol of azide II-1, 0.05mmol of CuI, 0.75mmol of t-BuOK and 2mLnPrOH are added into a 10mL reaction tube, the reaction is carried out for 12H at the temperature of 110 ℃, the reaction is cooled to the room temperature, saturated ammonium chloride aqueous solution and 10mL of ethyl acetate are added for extraction and separation, and the products 1-benzyl-4- (p-methylphenyl mercapto) -1H-1,2, 3-triazole III-1 are obtained through column chromatography, wherein the yield is 82%.
III-1 is a white powder. Meltingpoint (M.P.) 98-100 deg.C; 1 H NMR(400MHz,CDCl 3 )δ7.50(s,1H),7.37(br,3H),7.26–7.22(m,4H),7.06(d,J＝8.0Hz,2H),5.52(s,2H),2.29(s,3H). 13 CNMR(101MHz,CDCl 3 )δ139.76,136.96,134.12,131.53,129.81,129.68,129.15,128.88,128.09,126.74,54.43,20.94.HRMS-ESI(m/z)[M+H] + Calcd for C 16 H 15 N 3 S 281.0987；Found,281.0985.
example 2
The target product has the following structural formula:
the procedure is as in example 1, starting from I-2 and II-1.
III-2 is a white solid in 84% yield.
Melting point(M.P.):157-159℃； 1 H NMR(400MHz,CDCl 3 )δ7.57(s,1H),7.38–7.34(m,5H),7.29–7.27(m,2H),7.14(d,J＝8.4Hz,2H),5.55(s,2H). 13 C NMR(101MHz,CDCl 3 )δ137.96,134.73,133.90,132.02,130.21,129.23,129.01,128.15,127.49,120.58,54.56.HRMS-ESI(m/z)[M+H] + Calcd for C 15 H 12 BrN 3 S 344.9935；Found,344.9934.
Example 3
The target product has the following structural formula:
the procedure is as in example 1, starting from I-3 and II-1.
III-3 is a white solid in 78% yield.
Melting point(M.P.):112-114℃； 1 H NMR(400MHz,CDCl 3 )δ7.56(s,1H),7.40-7.38(m,3H),7.29–7.27(m,2H),7.20(br,4H),5.55(s,2H). 13 C NMR(101MHz,CDCl 3 )δ138.17,133.98,133.92,132.70,130.06,129.23,129.12,129.01,128.15,127.40,54.55.HRMS-ESI(m/z)[M+H] + Calcd for C 15 H 12 ClN 3 S 301.0440；Found,301.0441.
Example 4
The target product has the following structural formula:
the procedure is as in example 1, starting from I-9 and II-1.
III-4 is a white solid in 85% yield.
Meltingpoint(M.P.):117-119℃； 1 H NMR(400MHz,CDCl 3 )δ7.52(s,1H),7.41–7.36(m,3H),7.28–7.23(m,6H),5.53(s,2H),1.27(s,9H). 13 C NMR(101MHz,CDCl 3 )δ149.98,139.24,134.08,131.61,129.07,129.04,128.78,128.03,127.02,126.05,77.32,77.00,76.69,53.77,34.35,31.12.HRMS-ESI(m/z)[M+H] + Calcd for C 19 H 21 N 3 S 323.1456；Found,323.1454.
Example 5
The target product has the following structural formula:
the procedure is as in example 1, starting from I-5 and II-1.
III-5 is a white solid in 82% yield.
Meltingpoint(M.P.):84-86℃； 1 H NMR(400MHz,CDCl 3 )δ7.43(s,1H),7.37-7.35(m,5H),7.24(d,J＝7.4Hz,2H),6.81(d,J＝8.8Hz,2H),5.49(s,2H),3.77(s,3H). 13 C NMR(101MHz,CDCl 3 )δ159.32,141.14,134.13,132.72,129.15,128.87,128.09,125.85,125.04,114.73,55.32,54.41.HRMS-ESI(m/z)[M+H] + Calcd for C 16 H 15 N 3 OS 297.0936；Found,297.0935.
Example 6
The target product has the following structural formula:
the procedure is as in example 1, starting from I-6 and II-1.
III-6 is a white solid in 81% yield.
Melting point(M.P.):140-142℃； 1 H NMR(400MHz,CDCl 3 )δ7.77-7.67(m,4H),7.58(s,1H),7.47–7.38(m,6H),7.29–7.27(m,2H),5.59(s,2H). 13 C NMR(101MHz,CDCl 3 )δ138.74,134.05,133.55,132.73,131.98,129.51,128.88,128.69,128.06,127.63,127.42,127.32,127.21,126.65,126.58,125.98,54.46.HRMS-ESI(m/z)[M+H] + Calcd for C 19 H 15 N 3 S 317.0987；Found,317.0988.
Example 7
The structural formula of the target product is as follows:
the procedure is as in example 1, starting from I-13 and II-1.
III-7 is a white solid in 77% yield.
Melting point(M.P.):63-65℃； 1 H NMR(400MHz,CDCl 3 )δ7.38(d,J＝6.8Hz,4H),7.26(t,J＝4.3Hz,2H),5.51(s,2H),2.90(t,J＝7.4Hz,2H),1.59(q,J＝7.5Hz,2H),1.34-1.38(m,2H),1.24(br,16H),0.88(t,J＝6.7Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ140.91,134.37,129.15,128.84,128.07,124.74,54.34,34.95,31.90,29.71,29.62,29.56,29.48,29.33,29.13,28.56,22.67,14.09.HRMS-ESI(m/z)[M+H] + Calcd for C 21 H 33 N 3 S 359.2395；Found,359.2396.
Example 8
The target product has the following structural formula:
the procedure is as in example 1, starting from I-10 and II-1.
III-8 is a colorless liquid, 74% yield.
1 H NMR(400MHz,CDCl 3 )δ7.44(s,1H),7.39-7.37(m,3H),7.26(d,J＝8.0Hz,2H),5.52(s,2H),3.12(q,J＝8.0Hz,1H),1.66-1.59(m,1H),1.54-1.47(m,1H),1.24(d,J＝6.8Hz,3H),0.99(t,J＝8.0Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ139.28,134.33,129.13,128.81,128.00,126.67,54.27,45.68,29.57,20.77,11.40.HRMS-ESI(m/z)[M+H] + Calcd forC 13 H 17 N 3 S 247.1143；Found,247.1142.
Example 9
The target product has the following structural formula:
the procedure is as in example 1, starting from I-1 and II-2.
III-9 is a white solid with a yield of 60%.
Melting point(M.P.):128-132℃； 1 H NMR(400MHz,CDCl 3 )δ7.52(s,1H),7.49(d,J＝4.0Hz,2H),7.24(d,J＝8.0Hz,2H),7.13(d,J＝8.0Hz,2H),7.07(d,J＝8.0Hz,2H),5.46(s,2H),2.29(s,3H). 13 C NMR(101MHz,CDCl 3 )δ140.33,137.19,133.16,132.38,131.29,129.96,129.88,129.69,126.51,123.13,53.74,20.99.HRMS-ESI(m/z)[M+H] + Calcd for C 16 H 14 BrN 3 S359.0092；Found,359.0093.
Example 10
The target product has the following structural formula:
the procedure is as in example 1, starting from I-1 and II-3.
III-10 is a white solid with a yield of 60%.
Melting point(M.P.):87-89℃； 1 H NMR(400MHz,CDCl 3 )δ7.39(s,1H),7.30-7.26(m,1H),7.23-7.19(m,4H),7.15(d,J＝8Hz,1H),7.05(d,J＝8Hz,2H),5.53(s,2H),2.28(s,3H),2.26(s,3H). 13 C NMR(101MHz,CDCl 3 )δ139.32,136.87,136.84,131.97,131.69,131.06,129.77,129.45,129.26,126.72,126.67,51.99,20.47,18.39.HRMS-ESI(m/z)[M+H] + Calcd for C 17 H 17 N 3 S 295.1143；Found,295.1142.
Example 11
The target product has the following structural formula:
the procedure is as in example 1, starting from I-1 and II-4.
III-11 is a white solid in 88% yield.
Melting point(M.P.):102-104℃； 1 H NMR(400MHz,CDCl 3 )δ7.47(s,1H),7.22–7.15(m,6H),7.05(d,J＝7.8Hz,2H),5.47(s,2H),2.35(s,3H),2.29(s,3H). 13 C NMR(101MHz,CDCl 3 )δ139.43,138.78,136.83,131.57,131.03,129.75,129.51,128.10,126.73,77.32,77.00,76.68,54.18,21.08,20.91.HRMS-ESI(m/z)[M+H] + Calcd for C 17 H 17 N 3 S 295.1143；Found,295.1144.
Example 12
The target product has the following structural formula:
the procedure is as in example 1, starting from I-1 and II-5.
III-12 is a white solid, 67% yield.
Melting point(M.P.):102-105℃； 1 H NMR(400MHz,CDCl 3 )δ7.46(s,1H),7.23-7.20(m,4H),7.05(d,J＝8.0Hz,2H),6.89(d,J＝8.0Hz,2H),5.45(s,2H),3.81(s,3H),2.29(s,3H). 13 C NMR(101MHz,CDCl 3 )δ160.02,139.55,136.92,131.63,129.80,129.74,129.62,126.60,126.02,114.52,55.33,54.03,20.98.HRMS-ESI(m/z)[M+H] + Calcd for C 17 H 17 N 3 OS 311.1092；Found,311.1090.
Example 13
The structural formula of the target product is as follows:
the procedure is as in example 1, starting from I-1 and II-6.
III-13 is a white solid in 83% yield.
Melting point(M.P.):137-139℃； 1 H NMR(400MHz,CDCl 3 )δ7.64(d,J＝8.0Hz,2H),
7.52(s,1H),7.37(d,J＝8.0Hz,2H),7.25(d,J＝8.0Hz,2H),7.08(d,J＝4Hz,2H),5.58(s,2H),2.30(s,3H). 13 C NMR(101MHz,CDCl 3 )δ140.41,138.12(q,J＝1.0Hz),137.23,131.11,131.06(q,J＝32.8Hz),129.92,129.88,128.21,126.71,126.10(q,J＝4.0Hz),123.68(q,J＝273.7Hz),53.65,20.94. 19 F NMR(376MHz,CDCl 3 )δ62.75.HRMS-ESI(m/z)[M+H] + Calcd for C 17 H 14 F 3 N 3 S 349.0861；Found,349.0860.
Example 14
The target product has the following structural formula:
the procedure is as in example 1, starting from I-1 and II-6.
III-14 is a white solid with a yield of 70%.
Meltingpoint(M.P.):102-107℃； 1 HNMR(400MHz,CDCl 3 )δ7.49(s,1H),7.36-7.35(m,7H),7.21(d,J＝8.0Hz,2H),7.11–7.05(m,6H),2.28(s,3H). 13 C NMR(101MHz,CDCl 3 )δ
138.87,137.75,136.80,131.79,129.80,129.31,128.98,128.69,128.01,127.17,68.55,20.93.HRMS-ESI(m/z)[M+H] + Calcd for C 22 H 19 N 3 S 357.1300；Found,357.1303.
Example 15
The target product has the following structural formula:
the procedure is as in example 1, starting from I-1 and II-6.
III-15 is a white solid in 75% yield.
Melting point(M.P.):69-71℃； 1 H NMR(400MHz,CDCl 3 )δ7.55(s,1H),7.39-7.34(m,5H),7.28(d,J＝7.5Hz,2H),7.12(d,J＝8.5Hz,2H),5.82(q,J＝8.0Hz,1H),2.00(d,J＝8.0Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ139.21,137.37,134.90,132.02,130.10,129.16,128.83,126.53,120.50,60.85,21.20.HRMS-ESI(m/z)[M+H] + Calcd for C 16 H 14 BrN 3 S 359.0092；Found,359.0091.
Example 15
The target product has the following structural formula:
the procedure is as in example 1, starting from I-1 and II-6.
III-16 is a white solid in 76% yield.
Melting point(M.P.):73-75℃； 1 H NMR(400MHz,CDCl 3 )δ7.91-7.89(m,3H),7.53–7.41(m,4H),7.36(s,1H),7.13(d,J＝8.0Hz,2H),7.00(d,J＝8.0Hz,2H),5.96(s,2H),2.25(s,3H). 13 C NMR(101MHz,CDCl 3 )δ139.26,136.72,133.87,131.61,131.00,130.14,129.70,129.30,128.92,127.94,127.28,126.96,126.38,125.26,122.67,52.59,20.87.HRMS-ESI(m/z)[M+H] + Calcd for C 20 H 17 N 3 S 331.1143；Found,331.1142.
Example 16
The structural formula of the target product is as follows:
the procedure is as in example 1, starting from I-1 and II-6.
III-17 is a white solid in 74% yield.
Melting point(M.P.):177-182℃； 1 H NMR(400MHz,CDCl 3 )δ8.59(s,1H),8.27(d,J＝8.0Hz,2H),8.08(d,J＝8.0Hz,2H),7.61(t,J＝8.0Hz,2H),7.53(t,J＝8.0Hz,2H),7.20(s,1H),7.09(d,J＝8.0Hz,2H),6.97(d,J＝8.0Hz,2H),6.55(s,2H),2.24(s,3H). 13 C NMR(101MHz,CDCl 3 )δ138.83,136.69,131.68,131.44,130.78,130.09,129.69,129.54,129.23,127.80,126.79,125.45,123.23,122.79,46.81,20.92.HRMS-ESI(m/z)[M+H] + Calcd for C 24 H 19 N 3 S 381.1300；Found,381.1303.
Example 17
The structural formula of the target product is as follows:
at room temperature, 0.5mmol of I-1, 0.6mmol of azide II-26, 0.05mmol of CuI, 0.75mmol of t-BuOK, 0.05mmol of DMDEA and 2mL of nPrOH are added into a 10mL reaction tube, reaction is carried out for 15H at room temperature, cooling to room temperature is carried out, saturated ammonium chloride aqueous solution and 10mL of ethyl acetate are added for extraction and separation, and the product 4- (p-methylphenyl mercapto) -1- (4-trifluoromethylphenyl) 1H-1,2, 3-triazole is obtained by column chromatography, wherein the yield is 83%.
The 4- (p-methylphenyl mercapto) -1- (4-trifluoromethyl phenyl) 1H-1,2, 3-triazole III-18 is white powder.
Melting point(M.P.):148-150℃； 1 H NMR(400MHz,CDCl 3 )δ8.03(s,1H),7.87(d,J＝8.0Hz,2H),7.80(d,J＝8.0Hz,2H),7.36(d,J＝8.0Hz,2H),7.12(d,J＝8.0Hz,2H),2.32(s,3H). 13 C NMR(101MHz,CDCl 3 )δ141.87,139.03,137.72,130.92(q,J＝33.3Hz),130.60,130.50,130.05,127.12(q,J＝4.0Hz),124.15,123.44(q,J＝273.7Hz),120.33,21.00. 19 F NMR(376MHz,CDCl 3 )δ62.66.HRMS-ESI(m/z)[M+H] + Calcd for C 16 H 12 F 3 N 3 S 335.0704；Found,335.0701.
Example 18
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-1 and II-11.
III-19 is a yellow liquid, yield 79%.
Melting point(M.P.):149-150℃； 1 H NMR(400MHz,CDCl 3 )δ7.57(s,1H),7.24(d,J＝8.0Hz,2H),7.07(d,J＝8.0Hz,2H),4.34(t,J＝7.2Hz,2H),2.30(s,3H),1.89(q,J＝7.2Hz,2H),1.31(br,6H),0.91-0.85(m,3H). 13 C NMR(101MHz,CDCl 3 )δ139.18,136.90,131.85,129.83,129.59,126.72,50.67,31.06,30.10,26.07,22.36,20.97,13.87.HRMS-ESI(m/z)[M+H] + Calcd for C 15 H 21 N 3 S 275.1456；Found,275.1455.
Example 19
The target product has the following structural formula:
the procedure is as in example 17, starting from I-2 and II-26.
III-20 is a white solid, yield 82%.
Melting point(M.P.):123-124℃； 1 H NMR(400MHz,CDCl 3 )δ1H NMR 8.15(s,1H),7.90(d,J＝8.0Hz,2H),7.82(d,J＝8.0Hz,2H),7.41(d,J＝8.0Hz,2H),7.27(d,J＝8.0Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ140.00,138.93,137.74,132.31,131.20(q,J＝34.3Hz),131.12,127.24(q,J＝4.0Hz),125.01,123.40(q,J＝275.7Hz),121.37,120.42. 19 F NMR(376MHz,CDCl 3 )δ62.69.HRMS-ESI(m/z)[M+H] + Calcd for C 15 H 9 BrF 3 N 3 S398.9653; fountain, 398.9651, example 20
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-3 and II-26.
III-21 is a white solid with a yield of 80%.
Meltingpoint(M.P.):119-122℃； 1 H NMR(400MHz,CDCl 3 )δ8.14(s,1H),7.90(d,J＝8.0Hz,2H),7.82(d,J＝8.0Hz,2H),7.34(d,J＝8.0Hz,2H),7.26(d,J＝8.0Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ140.22,138.94,133.48,133.00,131.20(q,J＝32.3Hz),130.99,129.39,127.24(q,J＝4.0Hz),124.92,123.42(q,J＝273.7Hz),120.42. 19 F NMR(376MHz,CDCl 3 )δ62.69.HRMS-ESI(m/z)[M+H] + Calcd for C 15 H 9 ClF 3 N 3 S 355.0158；Found,355.0157.
Example 21
The target product has the following structural formula:
the procedure is as in example 17, starting from I-6 and II-26.
III-22 is a white solid, 76% yield.
Melting point(M.P.):154-156℃； 1 H NMR(400MHz,CDCl 3 )δ8.12(s,1H),7.89(br,3H),7.82-7.74(m,5H),7.49-7.47(m,3H). 13 C NMR(101MHz,CDCl 3 )δ140.95,138.99,133.63,132.30,131.62,131.04(q,J＝33.3Hz),129.04,128.63,127.73,127.62(q,J＝265.6Hz),127.39,127.31,127.17(q,J＝4.0Hz),126.79,126.38,124.79,120.36. 19 F NMR(376MHz,CDCl 3 )δ62.65.HRMS-ESI(m/z)[M+H] + Calcd for C 19 H 12 F 3 N 3 S 371.0704；Found,371.0703.
Example 22
The target product has the following structural formula:
the procedure is as in example 17, starting from I-1 and II-27.
III-23 is a white solid, 91% yield.
Melting point(M.P.):109-110℃； 1 H NMR(400MHz,CDCl 3 )δ7.96(s,1H),7.58(d,J＝8.0Hz,2H),7.31(t,J＝8.0Hz,4H),7.09(d,J＝8.0Hz,2H),2.41(s,3H),2.30(s,3H). 13 C NMR(101MHz,CDCl 3 )δ140.38,139.15,137.23,134.38,131.23,130.24,130.08,129.90,124.72,120.29,77.32,77.00,76.68,21.05,20.97.HRMS-ESI(m/z)[M+H] + Calcd for C 16 H 15 N 3 S281.0987；Found,281.0985.
Example 23
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-1 and II-28.
III-24 is a white solid in 88% yield.
Melting point(M.P.):101-103℃； 1 H NMR(400MHz,CDCl 3 )δ7.92(s,1H),7.58(d,J＝8.5Hz,2H),7.32(d,J＝7.8Hz,2H),7.09(d,J＝7.8Hz,2H),6.99(d,J＝8.6Hz,2H),4.07(q,J＝7.0Hz,2H),2.30(s,3H),1.44(t,J＝7.0Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ159.36,140.22,136.27,131.97,130.04,129.94,129.90,124.88,122.04,115.26,77.32,77.00,76.68,63.90,20.98,14.65.HRMS-ESI(m/z)[M+H] + Calcd for C 17 H 17 N 3 OS 311.1092；Found,311.1094.
Example 24
The target product has the following structural formula:
the procedure is as in example 17, starting from I-9 and II-39.
III-25 is a white solid in 68% yield.
Melting point(M.P.):123-125℃； 1 H NMR(400MHz,CDCl 3 )δ7.99(s,1H),7.85(d,J＝8.8Hz,2H),7.48(d,J＝8.8Hz,2H),7.36(d,J＝8.6Hz,2H),7.31(d,J＝8.6Hz,2H),1.28(s,9H). 13 C NMR(101MHz,CDCl 3 )δ150.71,141.10,138.92,136.33,130.91,130.00,126.32,124.38,121.91,93.92,34.53,31.21.HRMS-ESI(m/z)[M+H] + Calcd for C 18 H 18 IN 3 S 435.0266；Found,435.0265.
Example 25
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-9 and II-40.
III-26 is a white solid with a yield of 65%.
Melting point(M.P.):107-109℃； 1 H NMR(400MHz,CDCl 3 )δ7.99(s,1H),7.67(d,J＝8.8Hz,2H),7.49(d,J＝8.8Hz,2H),7.37(d,J＝8.6Hz,2H),7.31(d,J＝8.5Hz,2H),1.29(s,9H). 13 C NMR(101MHz,CDCl 3 )δ150.70,141.06,135.19,134.84,130.94,130.00,126.32,124.56,121.60,34.53,31.20.HRMS-ESI(m/z)[M+H] + Calcd for C 18 H 18 ClN 3 S 343.0910；Found,343.0907.
Example 26
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-9 and II-29.
III-27 is a white solid, yield 72%.
Melting point(M.P.):100-102℃； 1 H NMR(400MHz,CDCl 3 )δ8.26(s,1H),8.10(s,1H),8.00(t,J＝7.5Hz,2H),7.65(t,J＝7.4Hz,1H),7.38(d,J＝8.0Hz,2H),7.32(d,J＝8.0Hz,2H),2.66(s,3H),1.29(s,9H). 13 C NMR(101MHz,CDCl 3 )δ196.51,150.75,141.34,138.53,137.12,130.83,130.29,130.10,128.64,126.34,124.65,124.59,119.60,34.52,31.19,26.70.HRMS-ESI(m/z)[M+H] + Calcd for C 20 H 21 N 3 OS 351.1405；Found,351.1404.
Example 27
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-1 and II-30.
III-28 is a white solid in 80% yield.
Melting point(M.P.):60-62℃； 1 H NMR(400MHz,CDCl 3 )δ7.97(s,1H),7.31(t,J＝4.0Hz,4H),7.11(s,1H),7.08(d,J＝7.8Hz,2H),2.39(s,6H),2.31(s,3H). 13 C NMR(101MHz,CDCl 3 )δ140.36,139.77,137.22,136.61,131.35,130.60,130.07,129.92,124.87,118.24,21.26,21.00.HRMS-ESI(m/z)[M+H] + Calcd for C 17 H 17 N 3 S 295.1143；Found,295.1140.
Example 28
The target product has the following structural formula:
the procedure is as in example 17, starting from I-1 and II-31.
III-29 is a white solid in 78% yield.
Melting point(M.P.):82-84℃； 1 H NMR(400MHz,CDCl 3 )δ7.96(s,1H),7.32(d,J＝8.0Hz,3H),7.16-7.06(m,3H),6.94(d,J＝8.6Hz,1H),3.94(d,J＝6.5Hz,6H),2.31(s,3H). 13 CNMR(101MHz,CDCl 3 )δ149.86,149.64,140.35,137.26,131.32,130.30,130.08,129.92,124.98,112.42,111.23,104.93,56.25,56.19,20.98.HRMS-ESI(m/z)[M+H] + Calcd for C 17 H 17 N 3 O 2 S327.1041；Found,327.1040.
Example 29
The target product has the following structural formula:
the procedure is as in example 17, starting from I-1 and II-32.
III-30 is a white solid, 62% yield.
Melting point(M.P.):156-161℃； 1 H NMR(400MHz,CDCl 3 )δ8.05(s,1H),7.92(s,1H),7.88(d,J＝8.2Hz,1H),7.83(d,J＝7.5Hz,1H),7.69(d,J＝8.3Hz,1H),7.59(d,J＝7.4Hz,1H),7.43(t,J＝7.5Hz,1H),7.36(dd,J＝11.4,7.5Hz,3H),7.12(d,J＝7.8Hz,2H),3.99(s,2H),2.32(s,3H). 13 C NMR(101MHz,CDCl 3 )δ144.87,143.51,142.69,140.68,140.29,137.38,135.33,131.28,130.25,130.00,127.60,127.17,125.22,124.86,120.72,120.34,119.42,117.56,37.07,21.05.HRMS-ESI(m/z)[M+H] + Calcd for C 22 H 17 N 3 S 355.1143；Found,355.1142.
Example 30
The target product has the following structural formula:
the procedure is as in example 17, starting from I-1 and II-33.
III-31 is a yellow liquid, 73% yield.
1 H NMR(400MHz,CDCl 3 )δ8.03-8.01(m,1H),7.96-7.94(m,2H),7.60-7.56(m,5H),7.40(d,J＝8.0Hz,2H),2.32(s,3H). 13 C NMR(101MHz,CDCl 3 )δ140.01,137.38,134.10,133.26,131.11,130.60,130.28,129.99,129.02,128.29,127.99,127.11,124.91,123.53,122.06,21.01.HRMS-ESI(m/z)[M+H] + Calcd for C 19 H 15 N 3 S 317.0987；Found,317.0986.
Example 31
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-1 and II-34.
III-32 is a green liquid with a yield of 70%.
1 H NMR(400MHz,CDCl 3 )δ8.78(d,J＝8.0Hz,1H),8.74(d,J＝8.0Hz,1H),7.99(s,1H),7.93(d,J＝7.9Hz,1H),7.88(s,1H),7.80–7.74(m,2H),7.68(d,J＝8.0Hz,1H),7.62(d,J＝8.0Hz,1H),7.56(d,J＝8.0Hz,1H),7.42(d,J＝12.0Hz,2H),7.15(d,J＝8.0Hz,2H),2.33(s,3H). 13 C NMR(101MHz,CDCl 3 )δ140.08,137.45,132.06,131.13,130.75,130.34,130.17,130.04,129.30,129.24,128.46,127.94,127.82,127.65,127.24,124.92,123.14,123.00,122.85,21.06.HRMS-ESI(m/z)[M+H] + Calcd for C 23 H 17 N 3 S 367.1143；Found,367.1141.
Example 32
The target product has the following structural formula:
the procedure is as in example 17, starting from I-1 and II-35.
III-33 is a white solid, 61% yield.
1 H NMR(400MHz,CDCl 3 )δ8.29(d,J＝7.6Hz,1H),8.25(d,J＝7.9Hz,2H),8.18(t,J＝9.4Hz,2H),8.13(s,1H),8.10(d,J＝8.2Hz,1H),8.07(s,1H),8.03(d,J＝8.1Hz,1H),7.83(d,J＝9.3Hz,1H),7.45(d,J＝7.9Hz,2H),7.16(d,J＝7.9Hz,2H),2.34(s,3H). 13 C NMR(101MHz,CDCl 3 )δ140.21,137.44,132.39,131.23,131.11,130.61,130.37,130.05,129.98,129.88,129.49,129.09,126.94,126.83,126.52,126.18,126.06,125.02,124.69,124.11,123.26,120.84,21.06.HRMS-ESI(m/z)[M+H] + Calcd for C 25 H 17 N 3 S 391.1143；Found,391.1145.
Example 33
The target product has the following structural formula:
the procedure is as in example 17, starting from I-1 and II-37.
III-34 is a white solid in 93% yield.
Melting point(M.P.):128-129℃； 1 H NMR(400MHz,CDCl 3 )δ8.03(s,1H),7.80–7.73(m,4H),7.62(d,J＝8.0Hz,2H),7.48(t,J＝8.0Hz,2H),7.42-7.34(m,3H),7.12(d,J＝8.0Hz,2H),2.32(s,3H). 13 C NMR(101MHz,CDCl 3 )δ141.91,140.75,139.40,137.33,135.68,131.07,129.94,128.94,128.30,127.97,127.00,124.54,120.62,20.98.HRMS-ESI(m/z)[M+H] + Calcd for C 21 H 17 N 3 S 343.1143；Found,343.1142.
Example 34
The target product has the following structural formula:
the procedure is as in example 17, starting from I-12 and II-37.
III-35 is a white solid, 62% yield.
Melting point(M.P.):95-97℃； 1 H NMR(400MHz,CDCl 3 )δ7.96(s,1H),7.80(d,J＝8.0Hz,2H),7.74(d,J＝8.0Hz,2H),7.62(d,J＝8.0Hz,2H),7.48(t,J＝8.0Hz,2H),7.40(t,J＝8.0Hz,1H),3.01(d,J＝8.0Hz,2H),1.70(p,J＝8.0Hz,2H),1.43(t,J＝8.0Hz,2H),1.27(br,8H),0.87(t,J＝8.0Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ141.82,141.50,139.51,135.85,128.97,128.34,127.96,127.04,122.76,120.61,34.94,31.75,29.77,29.14,29.07,28.58,22.60,14.06.HRMS-ESI(m/z)[M+H] + Calcd for C 22 H 27 N 3 S 365.1926；Found,365.1925.
Example 35
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-13 and II-37.
III-36 is a white solid, yield 72%.
Melting point(M.P.):121-123℃； 1 H NMR(400MHz,CDCl 3 )δ7.96(s,1H),7.80(d,J＝8.0Hz,2H),7.74(d,J＝8.0Hz,2H),7.62(d,J＝8.0Hz,2H),7.48(t,J＝8.0Hz,2H),7.40(t,J＝8.0Hz,1H),3.01(t,J＝8.0Hz,2H),1.73-1.65(m,2H),1.43(t,J＝8.0Hz,2H),1.25(br,16H),0.88(t,J＝8.0Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ141.87,141.53,139.55,135.88,128.98,128.37,127.98,127.06,122.75,120.65,34.96,31.89,29.80,29.63,29.61,29.57,29.51,29.32,29.13,28.59,22.66,14.09.HRMS-ESI(m/z)[M+H] + Calcd for C 26 H 35 N 3 S 421.2552；Found,421.2551.
Example 36
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-10 and II-37.
III-37 is a white solid, 74% yield.
Melting point(M.P.):85-87℃； 1 H NMR(400MHz,CDCl 3 )δ7.95(s,1H),7.80-7.78(m,2H),7.75-7.73(m,2H),7.62(d,J＝8.0Hz,2H),7.48(t,J＝8.0Hz,2H),7.42-7.38(m,1H),3.10-3.05(m,1H),2.91-2.85(m,1H),1.72-1.68(m,1H),1.58-1.54(m,1H),1.30-1.26(m,1H),1.05(d,J＝8.0Hz,3H),0.91(t,J＝8.0Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ142.01,141.78,139.50,135.84,128.95,128.31,127.94,127.02,122.36,120.58,41.94,34.85,28.46,18.57,11.17.HRMS-ESI(m/z)[M+H] + Calcd for C 19 H 21 N 3 S 323.1456；Found,323.1455.
Example 37
The target product has the following structural formula:
the procedure is as in example 17, starting from I-11 and II-37.
III-38 is a white solid in 85% yield.
Melting point(M.P.):71-73℃； 1 H NMR(400MHz,CDCl 3 )δ8.02(s,1H),7.83-7.81(m,2H),7.77-7.74(m,2H),7.64-7.61(m,2H),7.51-7.48(m,2H),7.43-7.40(m,1H),3.28-3.22(m,1H),1.76-1.60(m,2H),1.34(t,J＝8.0Hz,3H),1.08-1.03(m,3H). 13 C NMR(101MHz,CDCl 3 )δ141.75,139.92,139.44,135.76,128.93,128.28,127.93,126.98,124.57,120.56,45.79,29.63,20.83,11.40.HRMS-ESI(m/z)[M+H] + Calcd for C 18 H 19 N 3 S 309.1300；Found,309.1299.
Example 38
The target product has the following structural formula:
the procedure is as in example 17, starting from I-6 and II-12.
III-39 is a white solid, 41% yield.
Melting point(M.P.):79-82℃； 1 H NMR(400MHz,CDCl 3 )δ7.84–7.66(m,5H),7.47-7.42(m,2H),7.38(d,J＝8.0Hz,1H),4.70(q,J＝8.0Hz,1H),1.96–1.81(m,2H),1.59(s,2H),1.35–1.19(m,3H),0.92(t,J＝8.0Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ137.86,133.62,133.17,131.99,128.72,127.69,127.26,127.09,126.61,126.56,125.96,125.52,57.79,39.17,21.28,19.15,13.54.HRMS-ESI(m/z)[M+H] + Calcd for C 17 H 19 N 3 S 297.1300；Found,297.1298.
Example 39
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-2 and II-13.
III-40 is a white solid, 77% yield.
Melting point(M.P.):74-77℃； 1 H NMR(400MHz,CDCl 3 )δ7.65(s,1H),7.34(d,J＝8.0Hz,2H),7.15(d,J＝8.0Hz,2H),4.37(t,J＝8.0Hz,2H),1.92(t,J＝8.0Hz,2H),1.31–1.26(m,10H),0.88(t,J＝8.0Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ137.36,135.04,132.04,130.11,127.46,120.51,50.79,31.63,30.12,28.98,28.86,26.40,22.56,14.03.HRMS-ESI(m/z)[M+H] + Calcd for C 16 H 22 BrN 3 S 367.0718；Found,367.0715.
Example 40
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-3 and II-14.
III-41 is a white solid in 82% yield.
Melting point(M.P.):84-86℃； 1 H NMR(400MHz,CDCl 3 )δ7.61(s,1H),7.30(t,J＝8.0Hz,2H),7.24(br,5H),7.15(d,J＝8.0Hz,2H),4.37(t,J＝8.0Hz,2H),2.66(t,J＝8.0Hz,2H),2.30–2.23(m,2H). 13 C NMR(101MHz,CDCl 3 )δ139.78,137.75,134.13,132.73,130.08,129.15,128.65,128.35,127.45,126.45,49.87,32.40,31.43.HRMS-ESI(m/z)[M+H] + Calcd for C 17 H 16 ClN 3 S 329.0753；Found,329.0752.
EXAMPLE 41
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-9 and II-15.
III-42 is a white solid, 76% yield.
Melting point(M.P.):92-95℃； 1 H NMR(400MHz,CDCl 3 )δ7.28–7.26(m,6H),7.18(d,J＝8.0Hz,2H),7.06(d,J＝8.0Hz,2H),4.59(t,J＝8.0Hz,2H),3.21(t,J＝8.0Hz,2H),1.28(s,9H). 13 C NMR(101MHz,CDCl 3 )δ149.95,138.51,136.68,131.86,128.98,128.79,128.61,127.62,127.09,126.05,51.90,36.54,34.40,31.18.HRMS-ESI(m/z)[M+H] + Calcd for C 20 H 23 N 3 S337.1613；Found,337.1610.
Example 42
The target product has the following structural formula:
the procedure is as in example 17, starting from I-1 and II-16.
III-43 is a white solid, 73% yield.
Melting point(M.P.):87-89℃； 1 H NMR(400MHz,CDCl 3 )δ7.64(s,1H),7.39-7.26(m,7H),7.07(d,J＝8.0Hz,2H),6.67(d,J＝12.0Hz,1H),6.36-6.29(m,1H),5.13(d,J＝8.0Hz,2H),2.29(s,3H). 13 C NMR(101MHz,CDCl 3 )δ139.91,137.09,135.89,135.31,131.57,129.94,129.87,128.76,128.68,126.74,126.53,121.32,52.69,20.99.HRMS-ESI(m/z)[M+H] + Calcd for C 18 H 17 N 3 S 307.1143；Found,307.1142.
Example 43
The target product has the following structural formula:
the procedure is as in example 17, starting from I-1 and II-17.
III-44 is a colorless liquid, 71% yield.
1 H NMR(400MHz,CDCl 3 )δ7.57(s,1H),7.23(d,J＝8.0Hz,2H),7.06(d,J＝8.0Hz,2H),5.41(d,J＝8.0Hz,1H),5.06(d,J＝8.0Hz,1H),4.94(d,J＝8.0Hz,2H),2.29(s,3H),2.19(d,J＝8.0Hz,2H),2.13(t,J＝8.0Hz,2H),1.80(s,3H),1.67(s,3H),1.59(s,3H). 13 C NMR(101MHz,CDCl 3 )δ143.66,139.02,136.81,132.78,131.95,129.77,129.56,126.40,123.04,117.35,48.04,32.07,26.20,25.67,23.34,20.95,17.65.HRMS-ESI(m/z)[M+H] + Calcd for C 19 H 25 N 3 S 327.1769；Found,327.1768.
Example 44
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-1 and II-18.
III-45 is a colorless liquid, yield 76%.
1 H NMR(400MHz,CDCl 3 )δ7.58(s,1H),7.37-7.28(m,4H),7.26(d,J＝3.2Hz,1H),7.23(d,J＝8.2Hz,2H),7.07(d,J＝7.9Hz,2H),4.51(t,J＝6.8Hz,2H),3.38(t,J＝6.8Hz,2H),2.30(s,3H). 13 C NMR(101MHz,CDCl 3 )δ139.39,137.04,133.59,131.56,130.58,129.86,129.79,129.37,127.48,127.37,49.61,34.15,20.98.HRMS-ESI(m/z)[M+H] + Calcd for C 17 H 17 N 3 S 2 327.0864；Found,327.0860.
Example 45
The target product has the following structural formula:
the procedure is as in example 17, starting from I-2 and II-38.
III-46 is a white solid, 75% yield.
Melting point(M.P.):133-135℃； 1 H NMR(400MHz,CDCl 3 )δ8.05(s,1H),7.62(d,J＝8.0Hz,2H),7.40-7.35(m,4H),7.23(d,J＝8.0Hz,2H),2.54(t,J＝12.2Hz,1H),1.96–1.86(m,4H),1.52–1.41(m,2H),1.35-1.21(m,10H),1.12-1.05(m,2H),0.90(t,J＝8.0Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ149.41,138.52,134.57,134.48,132.17,130.57,128.19,125.53,120.87,120.47,44.27,37.28,37.22,34.24,33.42,32.17,26.61,22.69,14.09.HRMS-ESI(m/z)[M+H] + Calcd for C 25 H 30 BrN 3 S 483.1344；Found,483.1346.
Example 46
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-1 and II-19.
III-47 is a colorless liquid, 72% yield.
1 H NMR(400MHz,CDCl 3 )δ7.79(s,1H),7.23(d,J＝8.0Hz,2H),7.06(d,J＝7.9Hz,2H),4.53(dd,J＝14.1,3.3Hz,1H),4.37(dd,J＝14.1,6.0Hz,1H),4.22(qd,J＝6.9,3.3Hz,1H),3.77(m,2H),2.29(s,3H),2.09-2.00(m,1H),1.86(dq,J＝14.4,7.2Hz,1H),1.77-1.69(m,1H),1.59(dq,J＝12.5,7.5Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ139.14,136.83,131.91,129.78,129.59,128.33,76.96,68.57,53.23,28.43,25.64,20.95.HRMS-ESI(m/z)[M+H] + Calcd for C 14 H 17 N 3 OS275.1092；Found,275.1090.
Example 47
The target product has the following structural formula:
the procedure is as in example 17, starting from I-1 and II-20.
III-48 is a white solid in 78% yield.
Melting point(M.P.):98-101℃； 1 H NMR(400MHz,CDCl 3 )δ7.30(s,1H),7.14(d,J＝8.0Hz,2H),7.05(d,J＝8.0Hz,2H),6.86(s,1H),6.76(d,J＝8.0Hz,1H),6.64(d,J＝8.0Hz,1H),4.53-4.50(m,4H),3.12-3.08(m,4H),2.28(s,3H). 13 C NMR(101MHz,CDCl 3 )δ159.14,138.53,136.69,131.79,129.69,129.28,128.47,128.12,127.54,127.42,125.09,109.25,71.12,52.22,35.90,29.98,20.85.HRMS-ESI(m/z)[M+H] + Calcd for C 19 H 19 N 3 OS 337.1249; found,337.1248 EXAMPLE 48
The target product has the following structural formula:
the procedure is as in example 17, starting from I-1 and II-21.
III-49 is a white solid, 83% yield.
Melting point(M.P.):130-132℃； 1 H NMR(400MHz,CDCl 3 )δ7.56(d,J＝1.9Hz,1H),7.13(d,J＝8.0Hz,2H),7.06–7.03(m,3H),7.00(s,1H),6.13(s,1H),4.88–4.84(m,2H),4.60–4.58(m,2H),2.30(s,3H). 13 C NMR(101MHz,CDCl 3 )δ140.77,139.37,136.96,131.36,130.54,129.75,129.67,127.96,105.85,51.37,49.99,20.92.HRMS-ESI(m/z)[M+H] + Calcd for C 14 H 15 N 5 S 285.1048；Found,285.1046.
Example 49
The structural formula of the target product is as follows:
the procedure is as in example 17, starting from I-1 and II-22.
III-50 is a white solid, 81% yield.
Melting point(M.P.):140-143℃； 1 H NMR(400MHz,CDCl 3 )δ8.52(d,J＝5.5Hz,1H),8.02(s,1H),7.89(d,J＝1.9Hz,1H),7.68(dd,J＝5.5,1.9Hz,1H),7.36(d,J＝8.0Hz,2H),7.13(d,J＝8.0Hz,2H),2.33(s,3H). 13 C NMR(101MHz,CDCl 3 )δ151.77,143.92,143.51,143.34,138.20,131.16,130.19,129.68,123.06,117.67,112.78,21.07.HRMS-ESI(m/z)[M+H] + Calcd for C 14 H 11 BrN 4 S 345.9888；Found,345.9887.
Example 50
The target product has the following structural formula:
the procedure is as in example 17, starting from I-1 and II-23.
III-51 is a white solid in 79% yield.
Melting point(M.P.):130-132℃； 1 H NMR(400MHz,CDCl 3 )δ8.54(d,J＝5.5Hz,1H),8.02(s,1H),7.74(d,J＝1.9Hz,1H),7.64(dd,J＝5.5,1.9Hz,1H),7.36(d,J＝8.0Hz,2H),7.13(d,J＝8.0Hz,2H),2.33(s,3H). 13 C NMR(101MHz,CDCl 3 )δ153.32,151.45,144.41,143.37,138.22,131.19,130.20,129.68,123.05,114.02,112.44,21.08.HRMS-ESI(m/z)[M+H] + Calcd for C 14 H 11 ClN 4 S 302.0393；Found,302.0392.
Example 51
The target product has the following structural formula:
the procedure is as in example 17, starting from I-9 and II-41.
III-52 is a yellow liquid in 63% yield.
1 H NMR(400MHz,CDCl 3 )δ8.25(s,1H),7.66(s,1H),7.30(s,4H),7.21(d,J＝8.3Hz,1H),6.97(d,J＝8.5Hz,1H),3.86(s,3H),2.36(s,3H),1.28(s,9H). 13 C NMR(101MHz,CDCl 3 )δ149.94,148.69,138.00,132.13,131.04,130.57,129.55,128.91,126.12,125.62,125.48,112.21,56.06,34.46,31.23,20.36.HRMS-ESI(m/z)[M+H] + Calcd for C 20 H 23 N 3 OS 353.1562；Found,353.1561.
Example 52
The target product has the following structural formula:
the procedure is as in example 17, starting from I-9 and II-42.
III-53 as white solid in 72% yield.
Melting point(M.P.):68-70℃； 1 H NMR(400MHz,CDCl 3 )δ8.32(s,1H),7.47(s,1H),7.31(s,4H),7.02–6.95(m,2H),3.83(d,J＝3.1Hz,6H),1.29(s,10H). 13 C NMR(101MHz,CDCl 3 )δ153.86,149.94,144.58,138.15,131.95,129.44,128.93,126.08,115.80,113.58,109.84,56.46,55.91,34.40,31.17.HRMS-ESI(m/z)[M+H] + Calcd for C 20 H 23 N 3 O 2 S 369.1511；Found,369.1510.
Example 53
The target product has the following structural formula:
at room temperature, 0.3mmol of III-52, 0.9mmol of mCPBA and 1mL of CH were added to a 10mL reaction tube 2 Cl 2 Reacting for 15h at room temperature, adding saturated ammonium chloride aqueous solution and 10mL ethyl acetate, extracting and separating, and obtaining a product IV-1 through column chromatography, wherein the yield is 90%.
IV-1 is white powder.
Melting point(M.P.):124-126℃； 1 H NMR(400MHz,CDCl 3 )δ8.69(s,1H),8.05(d,J＝8.7Hz,2H),7.60–7.56(m,3H),7.24(d,J＝8.5Hz,1H),6.99(d,J＝8.5Hz,1H),3.89(s,3H),2.35(s,3H),1.33(s,9H). 13 C NMR(101MHz,CDCl 3 )δ157.83,148.73,148.58,137.25,131.31,131.14,127.98,127.71,126.34,125.52,124.72,112.24,56.12,35.27,31.02,20.32.HRMS-ESI(m/z)[M+H] + Calcd for C 20 H 23 N 3 O 3 S 385.1460；Found,385.1459.
Example 54
The target product has the following structural formula:
the procedure is as in example 53, starting from III-53.
IV-2 is a white solid with a yield of 87%.
Melting point(M.P.):151-154℃； 1 H NMR(400MHz,CDCl 3 )δ8.76(s,1H),8.06(d,J＝8.6Hz,2H),7.57(d,J＝8.6Hz,2H),7.40(d,J＝2.9Hz,1H),7.04(d,J＝9.1Hz,1H),6.99(dd,J＝9.1,2.9Hz,1H),3.88(s,3H),3.80(s,3H),1.33(s,9H). 13 C NMR(101MHz,CDCl 3 )δ157.86,153.89,148.87,144.58,137.21,127.99,127.70,126.33,125.26,116.53,113.57,110.13,56.52,55.98,35.26,29.99.HRMS-ESI(m/z)[M+H] + Calcd for C 20 H 23 N 3 O 4 S401.1409; found,401.1408 example 55
The structural formula of the target product is as follows:
at room temperature, adding 1.1mmol of I-8, 0.5mmol of azide II-24, 0.05mmol of CuI, 0.75mmol of t-BuOK and 2mL of nPrOH into a 10mL reaction tube, reacting at 110 ℃ for 12 hours, cooling to room temperature, adding saturated ammonium chloride aqueous solution and 10mL of ethyl acetate, extracting and separating, and obtaining a product XII-1 by column chromatography, wherein the yield is 76%.
The product XII-1 is a white powder.
Melting point(M.P.):132-135℃； 1 H NMR(400MHz,CDCl 3 )δ7.49(s,2H),7.28(s,4H),7.16(dd,J＝7.7,1.3Hz,2H),7.13–7.10(m,2H),7.10–7.03(m,4H),5.53(s,4H),2.42(s,6H). 13 C NMR(101MHz,CDCl 3 )δ139.29,137.44,135.11,134.24,130.41,129.61,128.78,127.02,126.98,126.65,53.89,20.33.HRMS-ESI(m/z)[M+H] + Calcd for C 26 H 24 N 6 S 2 484.1504；Found,484.1503.
Example 56
The target product has the following structural formula:
at room temperature, adding 1.1mmol of I-1, 0.5mmol of azide II-25, 0.05mmol of CuI, 0.75mmol of t-BuOK, 0.05mmol of DMDEA and 2mL of nPrOH into a 10mL reaction tube, reacting for 12 hours at room temperature, adding saturated ammonium chloride aqueous solution and 10mL of ethyl acetate, extracting and separating, and obtaining a product XII-3 by column chromatography, wherein the yield is 76%.
The product XII-3 is a white powder with a yield of 72%.
Meltingpoint(M.P.):120-122℃； 1 H NMR(400MHz,CDCl 3 )δ7.55(s,2H),7.25(d,J＝7.9
Hz,4H),7.07(d,J＝7.9Hz,4H),4.31(t,J＝7.1Hz,4H),2.29(s,6H),1.90–1.87(m,4H),1.36–1.32(m,4H). 13 C NMR(101MHz,CDCl 3 )δ139.59,137.10,131.59,129.87,126.61,50.29,29.84,25.71,20.99.HRMS-ESI(m/z)[M+H] + Calcd for C 24 H 28 N 6 S 2 464.1817；Found,464.1815.
Example 57
The target product has the following structural formula:
at room temperature, 0.5mmol of I-2, 0.6mmol of azide II-25, 0.05mmol of CuI, 0.75mmol of t-BuOK, 0.05mmol of DMDEA and 2mL of nPrOH are added into a 10mL reaction tube, reaction is carried out for 12h at room temperature, saturated ammonium chloride aqueous solution and 10mL of ethyl acetate are added for extraction and separation, and the intermediate azide compound is obtained through column chromatography. Adding 0.5mmol of I-8, the intermediate azide compound, 0.05mmol of CuI, 0.75mmol of t-BuOK, 0.05mmol of DMDEA and 2mLnPrOH into a 10mL reaction tube, reacting at room temperature for 12h, adding a saturated ammonium chloride aqueous solution and 10mL of ethyl acetate, extracting and separating, and obtaining a product XII-4 through column chromatography. The yield was 59%.
Melting point(M.P.):101-103℃； 1 H NMR(400MHz,CDCl 3 )δ7.63(s,1H),7.55(s,1H),7.37(d,J＝8.0Hz,2H),7.18–7.15(m,3H),7.13–7.04(m,3H),4.35(td,J＝7.1,1.5Hz,4H),2.45(s,3H),1.95-1.88(m,4H),1.38-1.34(m,4H). 13 C NMR(101MHz,CDCl 3 )δ138.42,137.66,137.26,134.81,134.50,132.06,130.33,129.36,127.41,127.02,126.88,126.60,120.65,50.37,50.29,29.82,25.68,20.30.HRMS-ESI(m/z)[M+H] + Calcd for C 23 H 25 BrN 6 S 2 528.0765；Found,528.0764.
Example 58
The structural formula of the target product is as follows:
at room temperature, adding 0.5mmol of I-3, 0.6mmol of azide II-24, 0.05mmol of CuI, 0.75mmol of t-BuOK and 2mL of nPrOH into a 10mL reaction tube, reacting for 12 hours at room temperature, adding saturated ammonium chloride aqueous solution and 10mL of ethyl acetate, extracting and separating, and obtaining the intermediate azide compound through column chromatography. Adding 0.5mmol of I-2, the intermediate azide compound, 0.05mmol of CuI, 0.75mmol of t-BuOK and 2mL of nPrOH into a 10mL reaction tube, reacting at room temperature for 12 hours, adding a saturated ammonium chloride aqueous solution and 10mL of ethyl acetate, extracting and separating, and obtaining a product XII-2 through column chromatography. The yield was 60%.
Melting point(M.P.):226-229℃； 1 H NMR(400MHz,DMSO)δ8.60(d,J＝1.3Hz,2H),7.50(d,J＝8.6Hz,2H),7.38–7.34(m,6H),7.19(d,J＝8.0Hz,2H),7.12(d,J＝8.0Hz,2H),5.64(s,4H). 13 C NMR(101MHz,DMSO)δ135.67,135.32,135.17,134.73,134.52,132.14,131.27,130.71,130.64,130.56,130.07,130.03,129.48,129.27,128.51,119.52,52.96.HRMS-ESI(m/z)[M+H] + Calcd for C 24 H 18 BrClN 6 S 2 567.9906；Found,567.9904.
Example 59
The target product has the following structural formula:
0.3mmol of I-1, 0.45mmol of azide II-1, 0.015mmol of Cu (MeCN) were added to a 10mL reaction tube at room temperature 4 PF 6 0.03mmol of Na ascorbate and 2mL of DMF, reacting for 15h at 150 ℃, adding saturated ammonium chloride aqueous solution and 10mL of ethyl acetate for extraction and separation, and obtaining products V-1 and VI-1 by column chromatography, wherein the yield is 33 percent and 54 percent respectively.
Ⅴ-1:Melting point(M.P.):120-124℃； 1 H NMR(400MHz,CDCl 3 )δ7.52-7.47(m,6H),7.35-7.31(m,4H),7.19(d,J＝8.0Hz,2H),7.11-7.06(m,3H),6.99(d,J＝8.0Hz,2H),6.93(d,J＝8.0Hz,2H),6.10(s,2H),2.28(s,3H). 13 C NMR(101MHz,CDCl 3 )δ145.24(d,J＝16.2Hz),137.43,134.87,137.74(d,J＝3.0Hz),131.82(d,J＝11.1Hz),130.45,130.14(d,J＝114.2Hz),129.63,129.18,128.52(d,J＝13.1Hz),128.41(d,J＝111.2Hz),128.34,128.28,128.02,54.50,21.01. 31 P NMR(162MHz,CDCl 3 )δ19.41.HRMS-ESI(m/z)[M+H] + Calcd for C 28 H 24 N 3 OPS481.1378；Found,481.1377.
Ⅵ-1:Meltingpoint(M.P.):93-95℃； 1 H NMR(400MHz,CDCl 3 )δ7.79(m,4H),7.49(t,J＝7.4Hz,2H),7.43-7.38(m,4H),7.26-7.21(m,3H),7.16-7.14(m,2H),6.90(d,J＝8.1Hz,2H),6.83(d,J＝8.0Hz,2H),5.52(s,2H),2.21(s,3H). 13 C NMR(101MHz,CDCl 3 )δ144.72(d,J＝130.4Hz),137.92,136.37(d,J＝24.3Hz),133.96,132.00(d,J＝112.1Hz),131.90,131.78(d,J＝10.1Hz),130.37,129.98,128.74,128.37,128.25,128.01,52.03,20.95. 31 PNMR(162MHz,CDCl 3 )δ16.61.HRMS-ESI(m/z)[M+H] + Calcd for C 28 H 24 N 3 OPS 481.1378；Found,481.1376.
Example 60
The structural formula of the target product is as follows:
the procedure is as in example 59, starting from I-1 and II-6.
V-2 is a white solid with a yield of 32%. VI-2 is yellow liquid, and the yield is 52 percent.
Ⅴ-2:Melting point(M.P.):106-109℃； 1 H NMR(400MHz,CDCl 3 )δ7.51-7.42(m,6H),7.35–7.26(m,6H),7.23(d,J＝8.0Hz,2H),7.02(d,J＝8.0Hz,2H),6.97(d,J＝8.0Hz,2H),6.15(s,2H),2.30(s,3H). 13 C NMR(101MHz,CDCl 3 )δ145.96(d,J＝15.2Hz),138.66,137.77,132.95(d,J＝2.0Hz),131.72(d,J＝11.1Hz),130.82,129.78(d,J＝115.2Hz),129.74,129.48(d,J＝112.2Hz),129.21,128.78,128.67,128.54(d,J＝2.0Hz),126.56(q,J＝261.8Hz),125.20(q,J＝4.0Hz),54.00,21.05. 31 P NMR(162MHz,CDCl 3 )δ19.33. 19 F NMR(376MHz,CDCl 3 )δ-62.76.HRMS-ESI(m/z)[M+H] + Calcd for C 29 H 23 F 3 N 3 OPS 549.1252；Found,549.1251.
Ⅵ-2: 1 H NMR(400MHz,CDCl 3 )δ7.86-7.79(m,4H),7.52(t,J＝7.4Hz,2H),7.47-7.40(m,6H),7.15(d,J＝8.0Hz,2H),6.83(d,J＝8.3Hz,2H),6.78(d,J＝8.1Hz,2H),5.59(s,2H),2.19(s,3H). 13 C NMR(101MHz,CDCl 3 )δ145.35(d,J＝131.4Hz),138.10,137.62,136.38(d,J＝23.2Hz),132.49,132.02,131.79(d,J＝111.2Hz),131.76(d,J＝10.1Hz),130.78(q,J＝36.4Hz),130.06(d,J＝19.2Hz),128.67(d,J＝14.2Hz),128.38(d,J＝12.1Hz),127.98,125.56(d,J＝4.0Hz),123.77(d,J＝275.7Hz),51.32,20.78. 31 P NMR(162MHz,CDCl 3 )δ16.61. 19 F NMR(376MHz,CDCl 3 )δ-62.74.HRMS-ESI(m/z)[M+H] + Calcd for C 29 H 23 F 3 N 3 OPS 549.1252；Found,549.1250.
Example 61
The target product has the following structural formula:
the procedure is as in example 59, starting from I-3 and II-1.
V-3 is a white solid with a yield of 30%. VI-3 is colorless liquid, and the yield is 51 percent.
Ⅴ-3:Melting point(M.P.):118-123℃； 1 H NMR(400MHz,CDCl 3 )δ7.51-7.45(m,6H),7.30-7.34(m,4H),7.20(d,J＝7.5Hz,2H),7.13-7.07(m,5H),6.87(d,J＝8.6Hz,2H),6.12(s,2H). 13 C NMR(101MHz,CDCl 3 )δ143.53(d,J＝16.2Hz),134.69,133.12,132.84(d,J＝4.0Hz),131.74(d,J＝11.1Hz),130.53,129.93(d,J＝115.2Hz),129.58(d,J＝109.2Hz),128.90,128.54(d,J＝14.2Hz),128.35,128.33,128.13,54.62. 31 P NMR(162MHz,CDCl 3 )δ19.28.HRMS-ESI(m/z)[M+H] + Calcd for C 27 H 21 ClN 3 OPS 501.0831；Found,501.0832.
Ⅵ-3:Melting point(M.P.):98-101℃； 1 H NMR(400MHz,CDCl 3 )δ7.79-7.74(m,4H),7.51(t,J＝7.8Hz,2H),7.44-7.40(m,4H),7.26-7.22(m,3H),7.15(d,J＝7.0Hz,2H),6.92(d,J＝8.8Hz,2H),6.85(d,J＝6.7Hz,2H),5.59(s,2H). 13 C NMR(101MHz,CDCl 3 )δ145.24(d,J＝131.4Hz),135.46,133.80(d,J＝16.2Hz),132.27,132.06,131.69(d,J＝10.1Hz),131.14,129.86(d,J＝128.4Hz),128.85,128.52,128.40(d,J＝12.1Hz),127.95,52.22. 31 P NMR(162MHz,CDCl 3 )δ16.40.HRMS-ESI(m/z)[M+H] + Calcd for C 27 H 21 ClN 3 OPS 501.0831；Found,501.0830.
Example 62
The target product has the following structural formula:
the procedure is as in example 59, starting from I-6 and II-1.
V-4 is a white solid with a yield of 27%. VI-4 is yellow liquid, and the yield is 47%.
Ⅴ-4:Melting point(M.P.):85-87℃； 1 H NMR(400MHz,CDCl 3 )δ7.75-7.73(m,1H),7.63-7.58(m,2H),7.51-7.41(m,8H),7.31(s,1H),7.25-7.20(m,6H),7.13-7.04(m,4H),6.15(s,2H). 13 CNMR(101MHz,CDCl 3 )δ143.96(d,J＝15.2Hz),134.85,132.76(d,J＝3.0Hz),132.74(d,J＝124.4Hz),131.80(d,J＝11.1Hz),130.73,130.34,129.98(d,J＝114.2Hz),129.26,128.50(d,J＝13.1Hz),128.47,128.35,128.33,128.11,127.90,127.63,127.27,126.79,126.55,126.12,54.65. 31 PNMR(162MHz,CDCl 3 )δ19.58.HRMS-ESI(m/z)[M+H] + Calcd for C 31 H 24 N 3 OPS,517.1378；Found,517.1375.
Ⅵ-4: 1 H NMR(400MHz,CDCl 3 )δ7.79-7.74(m,4H),7.68(d,J＝8.0Hz,1H),7.47(d,J＝8.7Hz,1H),7.45-7.38(m,5H),7.34-7.30(m,5H),7.17(s,5H),6.99(d,J＝10.5Hz,1H),5.58(s,2H). 13 C NMR(101MHz,CDCl 3 )δ145.23(d,J＝133.5Hz),135.62(d,J＝23.2Hz),133.79,132.76(d,J＝108.2Hz),131.89,131.67(d,J＝10.1Hz),131.11,129.23,129.01,128.92,128.69,128.41,128.24(d,J＝13.1Hz),128.01,127.56,127.39,126.69,126.65,126.48,52.21. 31 P NMR(162MHz,CDCl 3 )δ16.68.HRMS-ESI(m/z)[M+H] + Calcd for C 31 H 24 N 3 OPS,517.1378；Found,4517.1374.
Example 63
The target product has the following structural formula:
the procedure is as in example 59, starting from I-1 and II-15.
V-5 is a yellow solid, yield 27%. VI-5 is a yellow liquid in 48% yield.
Ⅴ-5:Melting point(M.P.):96-98℃； 1 H NMR(400MHz,CDCl 3 )δ7.66-7.56(m,6H),7.44-7.42(m,4H),7.23-7.16(m,5H),6.98(d,J＝4.0Hz,2H),6.88(d,J＝12.0Hz,2H),5.09(t,J＝8.0Hz,2H),3.17(t,J＝8.0Hz,2H),2.29(s,3H). 13 C NMR(101MHz,CDCl 3 )δ144.48(d,J＝16.2Hz),137.22,136.93,132.96(d,J＝3.0Hz),131.90(d,J＝11.1Hz),130.42(d,J＝114.2Hz),129.99,129.61,128.99,128.98(d,J＝110.2Hz),128.74(d,J＝13.1Hz),128.51,126.75,52.49,37.12,20.99. 31 P NMR(162MHz,CDCl 3 )δ19.04.HRMS-ESI(m/z)[M+H] + Calcd for C 29 H 26 N 3 OPS,495.1534；Found,495.1532.
Ⅵ-5: 1 H NMR(400MHz,CDCl 3 )δ7.82-7.77(m,4H),7.55-7.49(m,2H),7.46-7.41(m,4H),7.28-7.22(m,3H),7.05(d,J＝5.8Hz,2H),7.01(d,J＝8.2Hz,2H),6.93(d,J＝8.0Hz,2H),4.54(t,J＝8.0Hz,2H),3.07(t,J＝8.0Hz,2H),2.24(s,3H). 13 C NMR(101MHz,CDCl 3 )δ144.46(d,J＝134.5Hz),138.13,136.63,136.18(d,J＝23.2Hz),132.04(d,J＝111.2Hz),131.95,131.80(d,J＝10.1Hz),130.30(d,J＝27.3Hz),128.72,128.52,128.34(d,J＝13.1Hz),127.03,49.47,36.05,20.99. 31 P NMR(162MHz,CDCl 3 )δ16.81.HRMS-ESI(m/z)[M+H] + Calcd for C 29 H 26 N 3 OPS,495.1534；Found,495.1531.
Example 64
The target product has the following structural formula:
the procedure is as in example 59, starting from I-1 and II-14.
V-6 is a yellow liquid with a yield of 25%. VI-6 is yellow liquid, and the yield is 47%.
Ⅴ-6: 1 H NMR(400MHz,CDCl 3 )δ7.68-7.63(m,4H),7.60–7.57(m,2H),7.47-7.42(m,4H),7.24-7.21(m,2H),7.17-7.16(m,1H),7.04(d,J＝4.0Hz,2H),7.00(d,J＝8.0Hz,2H),6.94(d,J＝8.0Hz,2H),4.86(t,J＝8.0Hz,2H),2.55(t,J＝8.0Hz,2H),2.28(s,3H),2.17-2.09(m,2H). 13 C NMR(101MHz,CDCl 3 )δ144.95(d,J＝16.2Hz),140.58,137.42,133.02(d,J＝3.0Hz),131.92(d,J＝11.1Hz),130.40(d,J＝114.2Hz),130.39,129.67,129.39,128.80(d,J＝13.1Hz),128.66(d,J＝111.2Hz),128.34,128.33,126.00,51.19,32.52,32.17,21.02. 31 P NMR(162MHz,CDCl 3 )δ18.75.HRMS-ESI(m/z)[M+H] + Calcd for C 30 H 28 N 3 OPS,509.1691；Found,509.1694.
Ⅵ-6: 1 H NMR(400MHz,CDCl 3 )δ7.86-7.81(m,4H),7.52(t,J＝6.7Hz,2H),7.46-7.42(m,4H),7.28-7.24(m,2H),7.19(t,J＝7.3Hz,1H),7.09(d,J＝8.8Hz,2H),6.97(d,J＝8.3Hz,2H),6.91(d,J＝8.1Hz,2H),4.30(t,J＝7.4Hz,2H),2.57(t,J＝7.6Hz,2H),2.23(s,3H),2.05(q,J＝8.0Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ140.04,138.17,131.96,131.95(d,J＝111.2Hz),131.93,131.75(d,J＝10.1Hz),130.66,130.10,128.43,128.39,128.32,128.27,126.19,47.87,32.49,30.87,20.95. 31 P NMR(162MHz,CDCl 3 )δ16.89.HRMS-ESI(m/z)[M+H] + Calcd for C 30 H 28 N 3 OPS,509.1691；Found,509.1693.
Example 65
The structural formula of the target product is as follows:
the procedure is as in example 59, starting from I-7 and II-14.
V-7 is a yellow liquid, 26% yield. VI-7 is yellow liquid, and the yield is 45 percent.
Ⅴ-7: 1 H NMR(400MHz,CDCl 3 )δ7.67-7.61(m,4H),7.56(t,J＝8.0Hz,2H),7.44-7.40(m,4H),7.25-7.21(m,2H),7.16((t,J＝8.0Hz,1H),7.06-7.03(m,3H),6.96(d,J＝8.0Hz,1H),6.77(d,J＝8.0Hz,1H),6.73(s,1H),4.89(t,J＝8.0Hz,2H),2.56(t,J＝8.0Hz,2H),2.22(s,3H),2.19-2.11(m,2H). 13 C NMR(101MHz,CDCl 3 )δ143.93(d,J＝16.2Hz),140.56,138.61,133.18,132.96(d,J＝3.0Hz),131.90(d,J＝11.1Hz),130.32(d,J＝114.2Hz),129.88,129.62(d,J＝110.2Hz),128.74(d,J＝13.1Hz),128.36,128.33,127.86,126.43,126.02,51.26,32.54,32.22,21.23. 31 PNMR(162MHz,CDCl 3 )δ18.91.HRMS-ESI(m/z)[M+H] + Calcd for C 30 H 28 N 3 OPS,509.1691；Found,509.1696.
Ⅵ-7: 1 H NMR(400MHz,CDCl 3 )δ7.87-7.82(m,4H),7.52(t,J＝7.8Hz,2H),7.47-7.42(m,4H),7.28-7.25(m,4H),7.19(t,J＝7.3Hz,1H),7.10(d,J＝7.4Hz,2H),7.01(t,J＝7.6Hz,1H),6.94(d,J＝7.6Hz,1H),6.83(d,J＝7.6Hz,1H),6.77(s,1H),4.30(t,J＝7.4Hz,2H),2.59(t,J＝7.6Hz,2H),2.13(s,3H),2.11-2.05(m,2H). 13 C NMR(101MHz,CDCl 3 )δ139.97,139.29,131.97,131.94,131.92(d,J＝111.2Hz),131.72(d,J＝10.1Hz),130.22,129.10,128.58,128.40,128.30(d,J＝12.1Hz),128.26,126.82,126.71,47.86,32.43,30.80,21.09. 31 PNMR(162MHz,CDCl 3 )δ16.78.HRMS-ESI(m/z)[M+H] + Calcd for C 30 H 28 N 3 OPS,509.1691；Found,509.1697.
Example 66
The target product has the following structural formula:
the procedure is as in example 59, starting from I-12 and II-1.
V-8 is a yellow liquid, yield 28%. VI-8 is a yellow liquid in 49% yield.
Ⅴ-8: 1 H NMR(400MHz,CDCl 3 )δ7.56-7.51(m,6H),7.41-7.37(m,4H),7.18(d,J＝7.8Hz,2H),7.14-7.04(m,3H),6.04(s,2H),2.93(t,J＝7.4Hz,2H),1.46(q,J＝7.2Hz,2H),1.21(br,10H),0.87(t,J＝6.9Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ148.14(d,J＝16.2Hz),134.96,132.68(d,J＝3.0Hz),131.86(d,J＝11.1Hz),130.26(d,J＝115.2Hz),128.52(d,J＝13.1Hz),128.29,128.08(d,J＝29.3Hz),125.37,124.25,54.31,32.84,31.71,29.36,29.07,28.97,28.60,22.56,14.03. 31 P NMR(162MHz,CDCl 3 )δ18.74.HRMS-ESI(m/z)[M+H] + Calcd for C 29 H 34 N 3 OPS503.2160；Found,503.2159.
Ⅵ-8: 1 H NMR(400MHz,CDCl 3 )δ7.88-7.82(m,4H),7.52(t,J＝7.3Hz,2H),7.47-7.46(m,4H),7.30(br,5H),5.65(s,2H),2.76(t,J＝7.6Hz,2H),1.23-1.14(m,8H),1.04(br,4H),0.87(t,J＝7.1Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ143.66(d,J＝136.5Hz),138.25(d,J＝24.3Hz),134.54,132.23(d,J＝117.3Hz),131.93,131.70(d,J＝11.1Hz),128.80,128.32(d,J＝13.1Hz),127.90,51.86,37.13,31.62,29.46,28.95,28.85,28.39,22.51,14.00. 31 P NMR(162MHz,CDCl 3 )δ16.89.HRMS-ESI(m/z)[M+H] + Calcd for C 29 H 34 N 3 OPS 503.2160；Found,503.2161.
Example 67
The structural formula of the target product is as follows:
the procedure is as in example 59, starting from I-11 and II-1.
V-9 is a yellow liquid with a yield of 30%. VI-9 is a yellow liquid in 47% yield.
Ⅴ-9: 1 H NMR(400MHz,CDCl 3 )δ7.55-7.51(m,6H),7.41-7.36(m,4H),7.19(d,J＝7.1Hz,2H),7.12-7.06(m,3H),6.06(s,2H),3.52-3.44(m,1H),1.50(dq,J＝13.9,7.0Hz,1H),1.40(dq,J＝14.1,7.0Hz,1H),1.10(d,J＝6.8Hz,3H),0.82(t,J＝7.4Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ147.72(d,J＝16.2Hz),135.09,132.66(d,J＝3.0Hz),131.92(dd,J＝11.1,4.0Hz),130.34(dd,J＝114.2,2.0Hz),128.47(dd,J＝13.1,2.0Hz),128.29,128.09(d,J＝32.3Hz),125.64(d,J＝125.6Hz),54.33,44.52,29.46,20.43,11.11. 31 P NMR(162MHz,CDCl 3 )δ19.12.HRMS-ESI(m/z)[M+H] + Calcd for C 25 H 26 N 3 OPS 447.1534；Found,447.1533.
Ⅵ-9: 1 H NMR(400MHz,CDCl 3 )δ7.88-7.83(m,4H),7.52-7.50(m,2H),7.47-7.43(m,4H),7.30(br,5H),5.64(s,2H),3.55(q,J＝6.7Hz,1H),1.44-1.29(m,2H),0.96(d,J＝6.8Hz,3H),0.76(t,J＝7.4Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ143.66(d,J＝136.5Hz),138.02(d,J＝23.2Hz),133.70(d,J＝168.8Hz),131.91(d,J＝2.0Hz),131.70(dd,J＝10.1,5.0Hz),128.77,128.42,128.32(dd,J＝13.1,5.0Hz),127.99,51.71,48.42,29.57,19.85,10.89. 31 P NMR(162MHz,CDCl 3 )δ16.69.HRMS-ESI(m/z)[M+H] + Calcd for C 25 H 26 N 3 OPS 447.1534；Found,447.1530.
Example 68
The target product has the following structural formula:
at room temperature, 0.3mmol of I-1, 0.9mmol of mCPBA and 2mL of CH were added to a 10mL reaction tube 2 Cl 2 Reacting at room temperature for 15h, adding saturated ammonium chloride aqueous solution and 10mL ethyl acetate, extracting and separating, drying and filtering to obtain an intermediate crude product. And (2) adding the intermediate crude product, 0.45mmol of II-1 and 1mL of DMMF into a 10mL reaction tube at room temperature, reacting for 30 hours at 120 ℃, adding a saturated ammonium chloride aqueous solution and 10mL of ethyl acetate, extracting, separating, drying, filtering, and performing column chromatography to obtain a VII-1 white solid and a VIII-1 white solid, wherein the yield is 30% and 52% respectively.
Ⅶ-1:Melting point(M.P.):187-189℃； 1 H NMR(400MHz,CDCl 3 )δ7.71-7.65(m,4H),7.59(br,2H),7.44–7.42(m,4H),7.34–7.32(m,2H),7.18(br,4H),7.14–7.03(m,3H),6.25(s,2H),2.39(s,3H). 13 C NMR(101MHz,CDCl 3 )δ152.42(d,J＝13.1Hz),145.10,136.29,134.42,132.94(d,J＝3.0Hz),132.42(d,J＝11.1Hz),129.62(d,J＝117.3Hz),129.51,129.16(d,J＝96.0Hz),128.44,128.46(d,J＝13.1Hz),128.36,128.29,55.06,21.62. 31 P NMR(162MHz,CDCl 3 )δ22.15.HRMS-ESI(m/z)[M+H] + Calcd for C 28 H 24 N 3 O 3 PS 513.1276；Found,513.1275.
Ⅷ-1:Melting point(M.P.):167-169℃； 1 HNMR(400MHz,CDCl 3 )δ7.90(d,J＝8.0Hz,2H),7.79–7.74(m,4H),7.54-7.53(m,2H),7.49-7.45(m,4H),7.29(d,J＝8.0Hz,1H),7.22(d,J＝8.0Hz,2H),7.08-7.04(m,4H),5.97(s,2H),2.32(s,3H). 13 C NMR(101MHz,CDCl 3 )δ145.65,144.12(d,J＝125.4Hz),142.15(d,J＝20.2Hz),135.75,133.64,132.06(d,J＝3.0Hz),131.98(d,J＝111.4Hz),131.88(d,J＝10.1Hz),129.62,129.09,128.84,128.41,128.32(d,J＝13.1Hz),127.58,53.85,21.64. 31 P NMR(162MHz,CDCl 3 )δ18.13.HRMS-ESI(m/z)[M+H] + Calcd for C 28 H 24 N 3 O 3 PS 513.1276；Found,513.1273.
Example 69
The structural formula of the target product is as follows:
the procedure is as in example 68, starting from I-11 and II-9.
VII-2 was a white solid with a yield of 32%. VIII-2 is a white solid with a yield of 39%.
Ⅶ-2:Melting point(M.P.):192-194℃； 1 H NMR(400MHz,CDCl 3 )δ8.18–8.15(m,1H),7.79-7.77(m,1H),7.71–7.65(m,4H),7.63–7.56(m,3H),7.49-7.45(m,2H),7.43-7.38(m,6H),7.19(d,J＝8.0Hz,2H),7.01(d,J＝8.0Hz,1H),6.90(d,J＝7.1Hz,1H),6.73(s,2H),2.39(s,3H). 13 C NMR(101MHz,CDCl 3 )δ152.38(d,J＝12.1Hz),145.16,136.23,133.50,133.02,132.42(d,J＝11.1Hz),130.79,130.31,129.40(d,J＝117.3Hz),129.06,128.96(d,J＝114.2Hz),128.48,128.47(d,J＝14.2Hz),126.68(d,J＝6.1Hz),125.94,124.82,123.28,52.70,21.66. 31 P NMR(162MHz,CDCl 3 )δ21.84.HRMS-ESI(m/z)[M+H] + Calcd for C 32 H 26 N 3 O 3 PS 563.1432；Found,563.1431.
Ⅷ-2:Melting point(M.P.):174-176℃； 1 HNMR(400MHz,CDCl 3 )δ7.92(d,J＝9.1Hz,1H),7.88(d,J＝9.1Hz,1H),7.83(d,J＝7.5Hz,2H),7.80(d,J＝7.8Hz,4H),7.72(d,J＝8.3Hz,1H),7.59-7.55(m,4H),7.52-7.48(m,4H),7.02(t,J＝7.7Hz,1H),6.90(d,J＝8.0Hz,2H),6.41(s,2H),6.34(d,J＝7.2Hz,1H),2.27(s,3H). 13 C NMR(101MHz,CDCl 3 )δ145.71,135.03,132.98(d,J＝109.2Hz),132.12,131.85(d,J＝10.1Hz),130.80(d,J＝101.1Hz),129.57,129.04,128.88,128.76(d,J＝10.1Hz),128.36(d,J＝13.1Hz),127.09,126.31,125.08,124.89,122.27,51.25,21.62. 31 P NMR(162MHz,CDCl 3 )δ18.42.HRMS-ESI(m/z)[M+H] + Calcd for C 32 H 26 N 3 O 3 PS563.1432；Found,563.1429.
Example 70
The structural formula of the target product is as follows:
0.3mmol V-1, 1.2mmol PhSiH was added to a 10mL reaction tube at room temperature 3 Reacting 3.0mmol of acetic acid and 2mL of toluene at 120 ℃ for 12h, adding saturated ammonium chloride aqueous solution and 10mL of ethyl acetate for extraction and separation, drying and filtering, and carrying out column chromatography to obtain a product IX.
Ix, white solid, 91% yield. 105-108 ℃ in Melting point (M.P.); 1 HNMR(400MHz,CDCl 3 )δ7.29–7.25(m,2H),7.21-7.14(m,11H),7.10(d,J＝8.0Hz,2H),6.99–6.94(m,4H),5.72(s,2H),2.26(s,3H). 13 C NMR(101MHz,CDCl 3 )δ146.38,136.83,135.00,133.20(d,J＝25.3Hz),133.08(d,J＝20.2Hz),131.72(d,J＝4.0Hz),130.41,129.95(d,J＝99.1Hz),128.64(d,J＝108.2Hz),128.55,128.78,128.77,53.65(d,J＝10.1Hz),21.00. 31 P NMR(162MHz,CDCl 3 )δ-34.99.HRMS-ESI(m/z)[M+H] + Calcd for C 28 H 24 N 3 PS 465.1429；Found,465.1427.
example 71
The structural formula of the target product is as follows:
at room temperature, adding 0.3mmol V-1, 0.33mmol MeMgBr (3.0M in Ethyl Ether) and 1mL THF into a 10mL reaction tube, reacting at room temperature for 5h, adding a THF (1 mL) solution of aromatic aldehyde 1 (0.45 mmol) into the reaction solution, reacting at room temperature for 15h, adding a saturated ammonium chloride aqueous solution and 10mL Ethyl acetate, extracting and separating, drying and filtering, and obtaining the product X-1 by column chromatography.
X-1, white solid, 66% yield. Melting point (M.P.) at 150-152 deg.C; 1 HNMR(400MHz,CDCl 3 )δ7.75(d,J＝8.0Hz,1H),7.62(d,J＝8.0Hz,1H),7.55(d,J＝8.0Hz,1H),7.48–7.41(m,3H),7.20(d,J＝8.0Hz,2H),7.11–7.06(m,4H),7.01–6.97(m,4H),6.43(s,1H),5.46–5.36(m,2H),2.25(s,3H). 13 C NMR(101MHz,CDCl 3 )δ140.44,137.01,136.16,134.51,132.90,132.83,131.67,129.89,129.45,128.51,128.47,128.05,128.03,127.57,127.53,126.32,124.62,123.39,66.18,53.14,20.94.HRMS-ESI(m/z)[M+H] + Calcd for C 27 H 23 N 3 OS 437.1562；Found,437.1561.
example 72
The structural formula of the target product is as follows:
the procedure is as in example 71, starting from V-1 and aromatic aldehyde 2.
X-2 is a white solid with a yield of 52%.
Ⅹ-2:Melting point(M.P.):163-165℃； 1 H NMR(400MHz,CDCl 3 )δ7.80(d,J＝8.0Hz,1H),7.61(s,1H),7.46(t,J＝8.0Hz,1H),7.39(d,J＝8.0Hz,1H),7.24-7.20(m,3H),7.19(s,1H),7.16(d,J＝1.8Hz,1H),7.14-7.11(m,3H),7.03-6.99(m,4H),6.44(s,1H),5.43(s,2H),4.32(q,J＝7.2Hz,2H),2.22(s,3H),1.41(t,J＝7.2Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ141.18,140.22,139.49,137.06,136.90,134.71,131.83,129.86,129.35,128.53,128.02,127.59,125.94,123.42,122.89,122.53,120.55,118.95,117.90,108.51,108.43,66.91,53.09,37.56,20.90,13.79.HRMS-ESI(m/z)[M+H] + Calcd for C 31 H 28 N 4 OS 504.1984；Found,504.1983.
Example 73
The target product has the following structural formula:
0.3mmol of VI-1, 2mmol of LTHF and 0.33mmol of MeMgBr (3.0 Min Ethyl Ether) are added into a 10mL reaction tube at room temperature, reaction is carried out for 10h at room temperature, saturated ammonium chloride aqueous solution and 10mL of Ethyl acetate are added for extraction separation, and the product XI-1 is obtained through drying filtration and column chromatography.
XI-1 as colorless liquid in 92% yield. 1 H NMR(400MHz,CDCl 3 )δ7.76(s,1H),7.25(s,2H),7.18-7.17(m,2H),7.02(d,J＝8.0Hz,2H),6.97(d,J＝8.1Hz,2H),5.51(s,2H),2.29(s,3H). 13 CNMR(101MHz,CDCl 3 )δ139.24,137.80,134.53,130.21,129.25,129.08,129.00,128.68,128.18,127.86,51.89,20.95.HRMS-ESI(m/z)[M+H] + Calcd for C 16 H 15 N 3 S 281.0987；Found,281.0988.
Example 74
The target product has the following structural formula:
the procedure is as in example 73, starting from VI-8.
XI-2 is a yellow liquid with a yield of 90%.
Ⅺ-2： 1 H NMR(400MHz,CDCl 3 )δ7.67(s,1H),7.35-7.29(m,3H),7.28-7.24(m,2H),5.58(s,2H),2.52(t,J＝7.4Hz,2H),1.49-1.42(m,2H),1.27-1.21(m,10H),0.88(t,J＝6.9Hz,3H). 13 CNMR(101MHz,CDCl 3 )δ137.46,135.02,130.01,128.76,128.25,127.67,51.66,35.36,31.65,29.14,28.99,28.86,28.29,22.53,14.00.HRMS-ESI(m/z)[M+H] + Calcd for C 17 H 25 N 3 S 303.1769；Found,303.1767.
Example 75
The structural formula of the target product is as follows:
the procedure is as in example 73, starting from VI-9.
XI-3 was a white solid in 86% yield.
Ⅺ-3：Melting point(M.P.):61-63℃； 1 H NMR(400MHz,CDCl 3 )δ7.70(s,1H),7.35-7.28(m,5H),5.61(s,2H),2.66(q,J＝6.7Hz,1H),1.56-1.40(m,2H),1.13(d,J＝6.7Hz,3H),0.91(t,J＝7.4Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ138.96,135.22,129.37,128.79,128.28,127.73,51.64,47.01,29.41,20.36,11.22.HRMS-ESI(m/z)[M+H] + Calcd for C 13 H 17 N 3 S 247.1143；Found,247.1142.
Claims (9)
1. A kind of sulfo-1, 2, 3-triazole and a high-efficiency synthesis method thereof are characterized in that: the method for efficiently and simply synthesizing the sulfur-containing 1,2, 3-triazole compounds III-XII by taking diphenylphosphonyl thioalkyne I and azide compounds II as raw materials through different reactions. The structural formula is as follows:
2. the synthesis process as claimed in claim 1, characterized in that phenylphosphonothioalkyne i is the following compound:
3. the method of claim 1, wherein the azide compound ii is one of the following compounds:
4. the synthesis process according to claim 1, characterized in that the copper catalyst cat.1 is one of the following compounds: copper iodide (CuI), copper tetra-acetonitrile hexafluorophosphate (Cu (MeCN) 4 PF 6 ) One of them.
5. The method of claim 1, wherein the base reagent is potassium tert-butoxide (tBuOK).
6. The synthesis method according to claim 1, characterized in that the organic amine is N, N' -dimethylethylenediamine (DMDEA).
7. The synthesis process according to claim 1, characterized in that the copper catalyst cat.2 is one of the following copper catalysts: cuI, cu (MeCN) 4 BF 4 、CuI/CuSO 4 -5H 2 One of O.
8. The method of synthesis according to claim 1, wherein the grignard reagent is methyl magnesium bromide (MeMgBr).
9. The method of claim 1, wherein the aromatic aldehyde is one of the following compounds:
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| CN108503601A (en) * | 2014-12-19 | 2018-09-07 | 河南师范大学 | The synthetic method of 1- alkyl -5- arylthio -1,2,3- triazole compounds |
| CN110746365A (en) * | 2019-11-04 | 2020-02-04 | 大连理工大学 | Preparation method of novel 4-thiocyano-1, 4, 5-trisubstituted 1,2, 3-triazole |
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