CN115785010A - 一类硫代1,2,3-三氮唑及其高效合成方法 - Google Patents
一类硫代1,2,3-三氮唑及其高效合成方法 Download PDFInfo
- Publication number
- CN115785010A CN115785010A CN202211469959.0A CN202211469959A CN115785010A CN 115785010 A CN115785010 A CN 115785010A CN 202211469959 A CN202211469959 A CN 202211469959A CN 115785010 A CN115785010 A CN 115785010A
- Authority
- CN
- China
- Prior art keywords
- cdcl
- nmr
- 101mhz
- hrms
- 400mhz
- 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.)
- Pending
Links
- 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
- 150000001540 azides Chemical class 0.000 abstract description 16
- 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
- 230000001681 protective effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 97
- 238000002844 melting Methods 0.000 description 59
- 230000008018 melting Effects 0.000 description 59
- 239000007787 solid Substances 0.000 description 56
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 239000007788 liquid Substances 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- 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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 17
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 15
- 239000007864 aqueous solution Substances 0.000 description 15
- 238000001035 drying Methods 0.000 description 14
- 238000001914 filtration Methods 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- 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
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 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
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- JXYRIQRQKAUQIY-UHFFFAOYSA-N acetic acid;oxolane Chemical compound CC(O)=O.C1CCOC1 JXYRIQRQKAUQIY-UHFFFAOYSA-N 0.000 description 1
- 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
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 150000002898 organic sulfur compounds Chemical class 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 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
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Images
Abstract
本发明公开了一种硫代1,2,3‑三氮唑及其高效合成方法，该方法是在保护气氛下，以二苯基膦酰基硫代炔烃Ⅰ和叠氮化合物Ⅱ为原料，通过不同的反应，高效简便合成含硫1,2,3‑三氮唑化合物Ⅲ‑X的方法，具有产率高、官能团耐受范围广及操作简便等优点。
Description
技术领域
本发明涉及一种硫代1,2,3-三氮唑的合成方法，特别涉及二苯基膦酰基硫代炔烃为原料，通过铜催化其与叠氮化合物的环加成反应(CuAAC)，合成硫代1,2,3-三氮唑的方法，属于有机合成中的领域。
背景技术
有机硫化合物存在于很多天然产物和药物分子中，且容易被氧化而可用作抗氧化和抗辐射的药物。在生物活性分子中引入硫原子通常可以增加其生物活性或药效活性。1,2,3-三氮唑类化合物具有多种生物活性，是很多生物活性化合物、药物及农药分子的骨架结构。在1,2,3-三氮唑环不同位点引入不同的取代基可得到不同生物活性的分子。而在1,2,3-三氮唑环上引入硫取代基可得到具有特定生物活性的含硫1,2,3-三氮唑。
铜催化叠氮化合物与硫炔烃环加成反应(CuAAC)是构筑1,2,3-三氮唑骨架的常用方法。合成含硫1,2,3-三氮唑主要有下面两种方法：第一种方法是先合成1,2,3-三氮唑骨架，再通过SNAr反应合成含硫1,2,3-三氮唑；第二种方法是通过含硫底物与叠氮化合物环加成直接合成含硫1,2,3-三氮唑。虽然上述方法均有效地合成了含硫1,2,3-三氮唑，但亦具有以下缺陷：如碘代1,2,3-三氮唑需要在微波及180℃高温下转化为氟代1,2,3-三氮唑，再经过SNAr反应转化成目标含硫1,2,3-三氮唑)；需要使用贵金属如Ir、Ru催化剂；仅得到芳基硫1,2,3-三氮唑，底物范围有待进一步拓展。因此，发展一种新的含硫1,2,3-三氮唑高效合成方法具有较大的理论研究意义和实际应用价值。
发明内容
本发明的目的是在于提供一种在不同条件下，以二苯基膦酰基硫代炔烃Ⅰ和叠氮化合物Ⅱ为原料，通过不同的反应，高效简便合成含硫1,2,3-三氮唑化合物Ⅲ-X的方法。该方法具有产率高、官能团耐受范围广及操作简便等优点。
为了实现上述技术目的，本发明提供了在铜催化剂cat.1和碱试剂作用下，在苯基膦酰基硫代炔烃Ⅰ和叠氮化合物Ⅱ的THF、乙醇、丙醇、正丙醇、异丙醇、丁醇、异丁醇、叔丁醇、乙二醇二***、二乙二醇二***、1,4-二氧六环、DMF、DMSO或甲苯溶液体系中(或加入有机胺)，在特定温度T1下，反应一定时间t1，反应完毕，用常用有机溶剂萃取，干燥，过滤，通过柱层析即可得产物4-巯基-1,2,3-三氮唑Ⅲ。在间氯过氧苯甲酸(mCPBA)作用下，在4-巯基-1,2,3-三氮唑Ⅲ的THF、二氯甲烷、三氯甲烷、***、丙酮、乙醇、乙二醇二***、二乙二醇二***、1,4-二氧六环、DMF、DMSO或甲苯溶液体系中，在特定温度T2下，反应一定时间t2，反应完毕，用常用有机溶剂萃取，干燥，过滤，通过柱层析即可得产物4-砜基-1,2,3-三氮唑Ⅳ。在铜催化剂cat.2和抗坏血酸钠作用下，在苯基膦酰基硫代炔烃Ⅰ和叠氮化合物Ⅱ的THF、乙醇、丙醇、正丙醇、异丙醇、丁醇、异丁醇、叔丁醇、乙二醇二***、二乙二醇二***、1,4-dioxane、DMF、DMSO、NMP或甲苯溶液体系中，在特定温度T3下，反应一定时间t3，反应完毕，用常用有机溶剂萃取，干燥，过滤，通过柱层析即可得产物膦酰基和巯基取代1,2,3-三氮唑Ⅴ和Ⅵ。在mCPBA作用下，在二苯基膦酰基硫代炔烃Ⅰ的THF、二氯甲烷、三氯甲烷、***、丙酮、乙醇、乙二醇二***、二乙二醇二***、1,4-二氧六环、DMF、DMSO或甲苯溶液体系中，在特定温度T4下，反应一定时间t4，反应完毕，用常用有机溶剂萃取，干燥，过滤，旋干滤液得到粗产物，在此粗产物和叠氮化合物Ⅱ的THF、乙醇、丙醇、正丙醇、异丙醇、丁醇、异丁醇、叔丁醇、乙二醇二***、二乙二醇二***、DMF、DMSO或甲苯溶液体系中，在特定温度T5下，反应一定时间t5，反应完毕，用常用有机溶剂萃取，干燥，过滤，通过柱层析即可得产物膦酰基和巯基取代1,2,3-三氮唑Ⅶ和Ⅷ。在膦酰基和巯基取代1,2,3-三氮唑Ⅴ、苯基硅烷和醋酸的THF、乙醇、丙醇、正丙醇、异丙醇、丁醇、异丁醇、叔丁醇、乙二醇二***、二乙二醇二***、DMF、DMSO、甲苯或二甲苯溶液体系中，在特定温度T6下，反应一定时间t6，反应完毕，用常用有机溶剂萃取，干燥，过滤，通过柱层析即可得产物膦和巯基取代1,2,3-三氮唑Ⅸ。在膦酰基和巯基取代1,2,3-三氮唑Ⅴ和MeMgBr的THF、二氯甲烷、三氯甲烷、***、1,4-二氧六环、乙二醇二***、二乙二醇二***或甲苯溶液体系中，在特定温度T7下，反应一定时间t7，反应完毕，向此反应液中加入芳香醛，在特定温度T8下，反应一定时间t8，反应完毕，用常用有机溶剂萃取，干燥，过滤，通过柱层析即可得产物羟基和巯基取代1,2,3-三氮唑Ⅹ。在碱试剂作用下，在膦酰基和巯基取代1,2,3-三氮唑Ⅵ的THF、二氯甲烷、三氯甲烷、***、1,4-二氧六环、乙二醇二***、二乙二醇二***或甲苯溶液体系中，在特定温度T9下，反应一定时间t9，反应完毕，用常用有机溶剂萃取，干燥，过滤，通过柱层析即可得产物5-巯基-1,2,3-三氮唑Ⅺ。通过制备Ⅲ的步骤可得产物双4-巯基-1,2,3-三氮唑Ⅻ-1、Ⅻ-2、Ⅻ-3、Ⅻ-4。
其中所述R1、R2、R3为芳基或烷基等官能团。
上述合成方法中，炔基溴试剂是以下化合物：
上述合成方法中，苯基膦酰基硫代炔烃Ⅰ是以下化合物之一：
上述合成方法中，叠氮化合物Ⅱ是以下化合物之一：
上述合成方法中，铜催化剂cat.1是以下化合物之一：碘化亚铜(CuI)、六氟膦酸四乙腈铜(Cu(MeCN)4PF6)之一。
上述合成方法中，碱试剂是以下化合物之一：叔丁醇钾(tBuOK)。
上述合成方法中，有机胺是N,N'-二甲基乙二胺(DMEDA)。
上述合成方法中，铜催化剂cat.2是以下铜催化剂之一：CuI、Cu(MeCN)4BF4、CuI/CuSO4-5H2O之一。
上述合成方法中，芳香醛是以下化合物之一：
上述合成方法中，所述反应温度T1为50-140℃，T2为-20-60℃，T3为80-200℃，T4为-20-60℃，T5为50-180℃，T6为60-150℃，T7为-20-60℃，T8为-20-80℃，T9为-20-60℃。
上述合成方法中，所述反应时间t1为2-24h，t2为0.5-24h，t3为5-48h，t4为0.5-24h，t5为5-48h，t6为2-24h，t7为0.5-24h，t8为1-48h，t9为0.5-24h。
上述合成方法中，反应结束后萃取的常用有机溶剂是CH2Cl2、氯仿、甲苯、***、石油醚、正己烷、乙酸乙酯中的一种。
本发明所提供的合成方法为以二苯基膦酰基硫代炔烃为原料，通过铜催化其与叠氮化合物的环加成反应(CuAAC)，合成硫代1,2,3-三氮唑，开辟了硫代1,2,3-三氮唑新的合成途径，其优点在于：(1)无需分离中间体；(2)在温和反应条件进行、产率高、官能团耐受范围广；(3)操作简单。
附图说明
图1所示是本发明提供的二苯基膦酰基硫代炔烃与叠氮化合物的环加成反应(CuAAC)，合成硫代1,2,3-三氮唑路径图。
具体实施方式
为使本发明的上述特征、优点和目的能够更加明了易懂，下面结合附图对本发明的具体实施方式做详细的说明。在下面的描述中阐述了许多具体细节以便于充分理解本发明。但是本发明能够以很多不同于在此描述的其他方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似改进，因此本发明不受下面公开的具体实施的限制。
实施例1
目标产物结构式如下：
室温下，在10mL反应管中加入0.5mmolⅠ-1、0.6mmol叠氮化物Ⅱ-1、0.05mmol CuI、0.75mmol t-BuOK和2mLnPrOH，在110℃下进行反应12h，冷却至室温，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，通过柱层析得到产物1-苄基-4-(p-甲基苯基巯基)-1H-1,2,3-三氮唑Ⅲ-1，产率为82％。
Ⅲ-1为白色粉末。Meltingpoint(M.P.):98-100℃；1H NMR(400MHz,CDCl3)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).13CNMR(101MHz,CDCl3)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 C16H15N3S 281.0987；Found,281.0985.
实施例2
目标产物结构式如下：
步骤同实施例1，以Ⅰ-2和Ⅱ-1为原料。
Ⅲ-2为白色固体，产率84％。
Melting point(M.P.):157-159℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C15H12BrN3S 344.9935；Found,344.9934.
实施例3
目标产物结构式如下：
步骤同实施例1，以Ⅰ-3和Ⅱ-1为原料。
Ⅲ-3为白色固体，产率78％。
Melting point(M.P.):112-114℃；1H NMR(400MHz,CDCl3)δ7.56(s,1H),7.40-7.38(m,3H),7.29–7.27(m,2H),7.20(br,4H),5.55(s,2H).13C NMR(101MHz,CDCl3)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 C15H12ClN3S 301.0440；Found,301.0441.
实施例4
目标产物结构式如下：
步骤同实施例1，以Ⅰ-9和Ⅱ-1为原料。
Ⅲ-4为白色固体，产率85％。
Meltingpoint(M.P.):117-119℃；1H NMR(400MHz,CDCl3)δ7.52(s,1H),7.41–7.36(m,3H),7.28–7.23(m,6H),5.53(s,2H),1.27(s,9H).13C NMR(101MHz,CDCl3)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 C19H21N3S 323.1456；Found,323.1454.
实施例5
目标产物结构式如下：
步骤同实施例1，以Ⅰ-5和Ⅱ-1为原料。
Ⅲ-5为白色固体，产率82％。
Meltingpoint(M.P.):84-86℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C16H15N3OS 297.0936；Found,297.0935.
实施例6
目标产物结构式如下：
步骤同实施例1，以Ⅰ-6和Ⅱ-1为原料。
Ⅲ-6为白色固体，产率81％。
Melting point(M.P.):140-142℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C19H15N3S317.0987；Found,317.0988.
实施例7
目标产物结构式如下：
步骤同实施例1，以Ⅰ-13和Ⅱ-1为原料。
Ⅲ-7为白色固体，产率77％。
Melting point(M.P.):63-65℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C21H33N3S 359.2395；Found,359.2396.
实施例8
目标产物结构式如下：
步骤同实施例1，以Ⅰ-10和Ⅱ-1为原料。
Ⅲ-8为无色液体，产率74％。
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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]+CalcdforC13H17N3S 247.1143；Found,247.1142.
实施例9
目标产物结构式如下：
步骤同实施例1，以Ⅰ-1和Ⅱ-2为原料。
Ⅲ-9为白色固体，产率60％。
Melting point(M.P.):128-132℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 forC16H14BrN3S359.0092；Found,359.0093.
实施例10
目标产物结构式如下：
步骤同实施例1，以Ⅰ-1和Ⅱ-3为原料。
Ⅲ-10为白色固体，产率60％。
Melting point(M.P.):87-89℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C17H17N3S 295.1143；Found,295.1142.
实施例11
目标产物结构式如下：
步骤同实施例1，以Ⅰ-1和Ⅱ-4为原料。
Ⅲ-11为白色固体，产率88％。
Melting point(M.P.):102-104℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 forC17H17N3S 295.1143；Found,295.1144.
实施例12
目标产物结构式如下：
步骤同实施例1，以Ⅰ-1和Ⅱ-5为原料。
Ⅲ-12为白色固体，产率67％。
Melting point(M.P.):102-105℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C17H17N3OS311.1092；Found,311.1090.
实施例13
目标产物结构式如下：
步骤同实施例1，以Ⅰ-1和Ⅱ-6为原料。
Ⅲ-13为白色固体，产率83％。
Melting point(M.P.):137-139℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),53.65,20.94.19F NMR(376MHz,CDCl3)δ62.75.HRMS-ESI(m/z)[M+H]+Calcd for C17H14F3N3S 349.0861；Found,349.0860.
实施例14
目标产物结构式如下：
步骤同实施例1，以Ⅰ-1和Ⅱ-6为原料。
Ⅲ-14为白色固体，产率70％。
Meltingpoint(M.P.):102-107℃；1HNMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C22H19N3S 357.1300；Found,357.1303.
实施例15
目标产物结构式如下：
步骤同实施例1，以Ⅰ-1和Ⅱ-6为原料。
Ⅲ-15为白色固体，产率75％。
Melting point(M.P.):69-71℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C16H14BrN3S359.0092；Found,359.0091.
实施例15
目标产物结构式如下：
步骤同实施例1，以Ⅰ-1和Ⅱ-6为原料。
Ⅲ-16为白色固体，产率76％。
Melting point(M.P.):73-75℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C20H17N3S 331.1143；Found,331.1142.
实施例16
目标产物结构式如下：
步骤同实施例1，以Ⅰ-1和Ⅱ-6为原料。
Ⅲ-17为白色固体，产率74％。
Melting point(M.P.):177-182℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C24H19N3S 381.1300；Found,381.1303.
实施例17
目标产物结构式如下：
室温下，在10mL反应管中加入0.5mmolⅠ-1、0.6mmol叠氮化物Ⅱ-26、0.05mmolCuI、0.75mmol t-BuOK、0.05mmol DMEDA和2mL nPrOH，在室温下进行反应15h，冷却至室温，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，通过柱层析得到产物4-(p-甲基苯基巯基)-1-(4-三氟甲基苯基)1H-1,2,3-三氮唑，产率为83％。
4-(p-甲基苯基巯基)-1-(4-三氟甲基苯基)1H-1,2,3-三氮唑Ⅲ-18为白色粉末。
Melting point(M.P.):148-150℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),120.33,21.00.19FNMR(376MHz,CDCl3)δ62.66.HRMS-ESI(m/z)[M+H]+Calcd for C16H12F3N3S 335.0704；Found,335.0701.
实施例18
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-11为原料。
Ⅲ-19为黄色液体，产率79％。
Melting point(M.P.):149-150℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C15H21N3S 275.1456；Found,275.1455.
实施例19
目标产物结构式如下：
步骤同实施例17，以Ⅰ-2和Ⅱ-26为原料。
Ⅲ-20为白色固体，产率82％。
Melting point(M.P.):123-124℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),121.37,120.42.19F NMR(376MHz,CDCl3)δ62.69.HRMS-ESI(m/z)[M+H]+Calcd for C15H9BrF3N3S 398.9653；Found,398.9651.实施例20
目标产物结构式如下：
步骤同实施例17，以Ⅰ-3和Ⅱ-26为原料。
Ⅲ-21为白色固体，产率80％。
Meltingpoint(M.P.):119-122℃；1H NMR(400MHz,CDCl3)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).13CNMR(101MHz,CDCl3)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),120.42.19F NMR(376MHz,CDCl3)δ62.69.HRMS-ESI(m/z)[M+H]+Calcd for C15H9ClF3N3S 355.0158；Found,355.0157.
实施例21
目标产物结构式如下：
步骤同实施例17，以Ⅰ-6和Ⅱ-26为原料。
Ⅲ-22为白色固体，产率76％。
Melting point(M.P.):154-156℃；1H NMR(400MHz,CDCl3)δ8.12(s,1H),7.89(br,3H),7.82-7.74(m,5H),7.49-7.47(m,3H).13C NMR(101MHz,CDCl3)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),126.79,126.38,124.79,120.36.19F NMR(376MHz,CDCl3)δ62.65.HRMS-ESI(m/z)[M+H]+Calcd for C19H12F3N3S 371.0704；Found,371.0703.
实施例22
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-27为原料。
Ⅲ-23为白色固体，产率91％。
Melting point(M.P.):109-110℃；1H NMR(400MHz,CDCl3)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).13CNMR(101MHz,CDCl3)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 forC16H15N3S281.0987；Found,281.0985.
实施例23
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-28为原料。
Ⅲ-24为白色固体，产率88％。
Melting point(M.P.):101-103℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C17H17N3OS 311.1092；Found,311.1094.
实施例24
目标产物结构式如下：
步骤同实施例17，以Ⅰ-9和Ⅱ-39为原料。
Ⅲ-25为白色固体，产率68％。
Melting point(M.P.):123-125℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C18H18IN3S435.0266；Found,435.0265.
实施例25
目标产物结构式如下：
步骤同实施例17，以Ⅰ-9和Ⅱ-40为原料。
Ⅲ-26为白色固体，产率65％。
Melting point(M.P.):107-109℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C18H18ClN3S 343.0910；Found,343.0907.
实施例26
目标产物结构式如下：
步骤同实施例17，以Ⅰ-9和Ⅱ-29为原料。
Ⅲ-27为白色固体，产率72％。
Melting point(M.P.):100-102℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C20H21N3OS 351.1405；Found,351.1404.
实施例27
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-30为原料。
Ⅲ-28为白色固体，产率80％。
Melting point(M.P.):60-62℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C17H17N3S 295.1143；Found,295.1140.
实施例28
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-31为原料。
Ⅲ-29为白色固体，产率78％。
Melting point(M.P.):82-84℃；1H NMR(400MHz,CDCl3)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).13CNMR(101MHz,CDCl3)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 forC17H17N3O2S327.1041；Found,327.1040.
实施例29
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-32为原料。
Ⅲ-30为白色固体，产率62％。
Melting point(M.P.):156-161℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C22H17N3S355.1143；Found,355.1142.
实施例30
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-33为原料。
Ⅲ-31为黄色液体，产率73％。
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C19H15N3S 317.0987；Found,317.0986.
实施例31
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-34为原料。
Ⅲ-32为绿色液体，产率70％。
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C23H17N3S 367.1143；Found,367.1141.
实施例32
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-35为原料。
Ⅲ-33为白色固体，产率61％。
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C25H17N3S 391.1143；Found,391.1145.
实施例33
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-37为原料。
Ⅲ-34为白色固体，产率93％。
Melting point(M.P.):128-129℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C21H17N3S 343.1143；Found,343.1142.
实施例34
目标产物结构式如下：
步骤同实施例17，以Ⅰ-12和Ⅱ-37为原料。
Ⅲ-35为白色固体，产率62％。
Melting point(M.P.):95-97℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C22H27N3S 365.1926；Found,365.1925.
实施例35
目标产物结构式如下：
步骤同实施例17，以Ⅰ-13和Ⅱ-37为原料。
Ⅲ-36为白色固体，产率72％。
Melting point(M.P.):121-123℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 forC26H35N3S 421.2552；Found,421.2551.
实施例36
目标产物结构式如下：
步骤同实施例17，以Ⅰ-10和Ⅱ-37为原料。
Ⅲ-37为白色固体，产率74％。
Melting point(M.P.):85-87℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C19H21N3S 323.1456；Found,323.1455.
实施例37
目标产物结构式如下：
步骤同实施例17，以Ⅰ-11和Ⅱ-37为原料。
Ⅲ-38为白色固体，产率85％。
Melting point(M.P.):71-73℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C18H19N3S 309.1300；Found,309.1299.
实施例38
目标产物结构式如下：
步骤同实施例17，以Ⅰ-6和Ⅱ-12为原料。
Ⅲ-39为白色固体，产率41％。
Melting point(M.P.):79-82℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C17H19N3S 297.1300；Found,297.1298.
实施例39
目标产物结构式如下：
步骤同实施例17，以Ⅰ-2和Ⅱ-13为原料。
Ⅲ-40为白色固体，产率77％。
Melting point(M.P.):74-77℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C16H22BrN3S 367.0718；Found,367.0715.
实施例40
目标产物结构式如下：
步骤同实施例17，以Ⅰ-3和Ⅱ-14为原料。
Ⅲ-41为白色固体，产率82％。
Melting point(M.P.):84-86℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C17H16ClN3S 329.0753；Found,329.0752.
实施例41
目标产物结构式如下：
步骤同实施例17，以Ⅰ-9和Ⅱ-15为原料。
Ⅲ-42为白色固体，产率76％。
Melting point(M.P.):92-95℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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]+Calcdfor C20H23N3S337.1613；Found,337.1610.
实施例42
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-16为原料。
Ⅲ-43为白色固体，产率73％。
Melting point(M.P.):87-89℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C18H17N3S 307.1143；Found,307.1142.
实施例43
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-17为原料。
Ⅲ-44为无色液体，产率71％。
1H NMR(400MHz,CDCl3)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).13CNMR(101MHz,CDCl3)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 C19H25N3S 327.1769；Found,327.1768.
实施例44
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-18为原料。
Ⅲ-45为无色液体，产率76％。
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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]+Calcdfor C17H17N3S2327.0864；Found,327.0860.
实施例45
目标产物结构式如下：
步骤同实施例17，以Ⅰ-2和Ⅱ-38为原料。
Ⅲ-46为白色固体，产率75％。
Melting point(M.P.):133-135℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C25H30BrN3S 483.1344；Found,483.1346.
实施例46
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-19为原料。
Ⅲ-47为无色液体，产率72％。
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C14H17N3OS275.1092；Found,275.1090.
实施例47
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-20为原料。
Ⅲ-48为白色固体，产率78％。
Melting point(M.P.):98-101℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C19H19N3OS337.1249；Found,337.1248.实施例48
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-21为原料。
Ⅲ-49为白色固体，产率83％。
Melting point(M.P.):130-132℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C14H15N5S 285.1048；Found,285.1046.
实施例49
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-22为原料。
Ⅲ-50为白色固体，产率81％。
Melting point(M.P.):140-143℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C14H11BrN4S 345.9888；Found,345.9887.
实施例50
目标产物结构式如下：
步骤同实施例17，以Ⅰ-1和Ⅱ-23为原料。
Ⅲ-51为白色固体，产率79％。
Melting point(M.P.):130-132℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C14H11ClN4S 302.0393；Found,302.0392.
实施例51
目标产物结构式如下：
步骤同实施例17，以Ⅰ-9和Ⅱ-41为原料。
Ⅲ-52为黄色液体，产率63％。
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C20H23N3OS353.1562；Found,353.1561.
实施例52
目标产物结构式如下：
步骤同实施例17，以Ⅰ-9和Ⅱ-42为原料。
Ⅲ-53为白色固体，产率72％。
Melting point(M.P.):68-70℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C20H23N3O2S369.1511；Found,369.1510.
实施例53
目标产物结构式如下：
室温下，在10mL反应管中加入0.3mmolⅢ-52、0.9mmol mCPBA和1mL CH2Cl2，在室温下进行反应15h，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，通过柱层析得到产物Ⅳ-1，产率为90％。
Ⅳ-1为白色粉末。
Melting point(M.P.):124-126℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C20H23N3O3S 385.1460；Found,385.1459.
实施例54
目标产物结构式如下：
步骤同实施例53，以Ⅲ-53为原料。
Ⅳ-2为白色固体，产率87％。
Melting point(M.P.):151-154℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C20H23N3O4S401.1409；Found,401.1408.实施例55
目标产物结构式如下：
室温下，在10mL反应管中加入1.1mmolⅠ-8、0.5mmol叠氮化物Ⅱ-24、0.05mmolCuI、0.75mmol t-BuOK和2mL nPrOH，在110℃下进行反应12h，冷却至室温，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，通过柱层析得到产物Ⅻ-1，产率为76％。
产物Ⅻ-1为白色粉末。
Melting point(M.P.):132-135℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 forC26H24N6S2484.1504；Found,484.1503.
实施例56
目标产物结构式如下：
室温下，在10mL反应管中加入1.1mmolⅠ-1、0.5mmol叠氮化物Ⅱ-25、0.05mmolCuI、0.75mmol t-BuOK、0.05mmol DMEDA和2mL nPrOH，在室温下进行反应12h，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，通过柱层析得到产物Ⅻ-3，产率为76％。
产物Ⅻ-3为白色粉末，产率72％。
Meltingpoint(M.P.):120-122℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C24H28N6S2464.1817；Found,464.1815.
实施例57
目标产物结构式如下：
室温下，在10mL反应管中加入0.5mmolⅠ-2、0.6mmol叠氮化物Ⅱ-25、0.05mmolCuI、0.75mmol t-BuOK、0.05mmol DMEDA和2mL nPrOH，在室温下进行反应12h，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，通过柱层析得到中间体叠氮化合物。在10mL反应管中加入0.5mmolⅠ-8、中间体叠氮化合物、0.05mmol CuI、0.75mmol t-BuOK、0.05mmol DMEDA和2mLnPrOH，在室温下进行反应12h，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，通过柱层析得到产物Ⅻ-4。产率为59％。
Melting point(M.P.):101-103℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 forC23H25BrN6S2528.0765；Found,528.0764.
实施例58
目标产物结构式如下：
室温下，在10mL反应管中加入0.5mmolⅠ-3、0.6mmol叠氮化物Ⅱ-24、0.05mmolCuI、0.75mmol t-BuOK和2mL nPrOH，在室温下进行反应12h，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，通过柱层析得到中间体叠氮化合物。在10mL反应管中加入0.5mmolⅠ-2、中间体叠氮化合物、0.05mmol CuI、0.75mmol t-BuOK和2mL nPrOH，在室温下进行反应12h，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，通过柱层析得到产物Ⅻ-2。产率为60％。
Melting point(M.P.):226-229℃；1H 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).13C 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 C24H18BrClN6S2567.9906；Found,567.9904.
实施例59
目标产物结构式如下：
室温下，在10mL反应管中加入0.3mmolⅠ-1、0.45mmol叠氮化物Ⅱ-1、0.015mmol Cu(MeCN)4PF6、0.03mmol Na ascorbate和2mLDMF，在150℃下进行反应15h，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，通过柱层析得到产物Ⅴ-1和Ⅵ-1，产率分别为33％和54％。
Ⅴ-1:Melting point(M.P.):120-124℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),128.34,128.28,128.02,54.50,21.01.31P NMR(162MHz,CDCl3)δ19.41.HRMS-ESI(m/z)[M+H]+Calcdfor C28H24N3OPS481.1378；Found,481.1377.
Ⅵ-1:Meltingpoint(M.P.):93-95℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),130.37,129.98,128.74,128.37,128.25,128.01,52.03,20.95.31PNMR(162MHz,CDCl3)δ16.61.HRMS-ESI(m/z)[M+H]+Calcd for C28H24N3OPS481.1378；Found,481.1376.
实施例60
目标产物结构式如下：
步骤同实施例59，以Ⅰ-1和Ⅱ-6为原料。
Ⅴ-2为白色固体，产率32％。Ⅵ-2为黄色液体，产率52％。
Ⅴ-2:Melting point(M.P.):106-109℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),54.00,21.05.31P NMR(162MHz,CDCl3)δ19.33.19F NMR(376MHz,CDCl3)δ-62.76.HRMS-ESI(m/z)[M+H]+Calcd for C29H23F3N3OPS 549.1252；Found,549.1251.
Ⅵ-2:1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),51.32,20.78.31P NMR(162MHz,CDCl3)δ16.61.19F NMR(376MHz,CDCl3)δ-62.74.HRMS-ESI(m/z)[M+H]+Calcd forC29H23F3N3OPS 549.1252；Found,549.1250.
实施例61
目标产物结构式如下：
步骤同实施例59，以Ⅰ-3和Ⅱ-1为原料。
Ⅴ-3为白色固体，产率30％。Ⅵ-3为无色液体，产率51％。
Ⅴ-3:Melting point(M.P.):118-123℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),128.35,128.33,128.13,54.62.31P NMR(162MHz,CDCl3)δ19.28.HRMS-ESI(m/z)[M+H]+Calcd for C27H21ClN3OPS 501.0831；Found,501.0832.
Ⅵ-3:Melting point(M.P.):98-101℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),127.95,52.22.31P NMR(162MHz,CDCl3)δ16.40.HRMS-ESI(m/z)[M+H]+Calcd for C27H21ClN3OPS501.0831；Found,501.0830.
实施例62
目标产物结构式如下：
步骤同实施例59，以Ⅰ-6和Ⅱ-1为原料。
Ⅴ-4为白色固体，产率27％。Ⅵ-4为黄色液体，产率47％。
Ⅴ-4:Melting point(M.P.):85-87℃；1H NMR(400MHz,CDCl3)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).13CNMR(101MHz,CDCl3)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),128.47,128.35,128.33,128.11,127.90,127.63,127.27,126.79,126.55,126.12,54.65.31PNMR(162MHz,CDCl3)δ19.58.HRMS-ESI(m/z)[M+H]+Calcdfor C31H24N3OPS,517.1378；Found,517.1375.
Ⅵ-4:1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),128.01,127.56,127.39,126.69,126.65,126.48,52.21.31P NMR(162MHz,CDCl3)δ16.68.HRMS-ESI(m/z)[M+H]+Calcd forC31H24N3OPS,517.1378；Found,4517.1374.
实施例63
目标产物结构式如下：
步骤同实施例59，以Ⅰ-1和Ⅱ-15为原料。
Ⅴ-5为黄色固体，产率27％。Ⅵ-5为黄色液体，产率48％。
Ⅴ-5:Melting point(M.P.):96-98℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),128.51,126.75,52.49,37.12,20.99.31P NMR(162MHz,CDCl3)δ19.04.HRMS-ESI(m/z)[M+H]+Calcd for C29H26N3OPS,495.1534；Found,495.1532.
Ⅵ-5:1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),127.03,49.47,36.05,20.99.31P NMR(162MHz,CDCl3)δ16.81.HRMS-ESI(m/z)[M+H]+Calcd for C29H26N3OPS,495.1534；Found,495.1531.
实施例64
目标产物结构式如下：
步骤同实施例59，以Ⅰ-1和Ⅱ-14为原料。
Ⅴ-6为黄色液体，产率25％。Ⅵ-6为黄色液体，产率47％。
Ⅴ-6:1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),128.34,128.33,126.00,51.19,32.52,32.17,21.02.31P NMR(162MHz,CDCl3)δ18.75.HRMS-ESI(m/z)[M+H]+Calcd for C30H28N3OPS,509.1691；Found,509.1694.
Ⅵ-6:1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)δ140.04,138.17,131.96,131.95(d,J＝111.2Hz),131.93,131.75(d,J＝10.1Hz),130.66,130.10,128.43,128.39,128.32,128.27,126.19,47.87,32.49,30.87,20.95.31P NMR(162MHz,CDCl3)δ16.89.HRMS-ESI(m/z)[M+H]+Calcd for C30H28N3OPS,509.1691；Found,509.1693.
实施例65
目标产物结构式如下：
步骤同实施例59，以Ⅰ-7和Ⅱ-14为原料。
Ⅴ-7为黄色液体，产率26％。Ⅵ-7为黄色液体，产率45％。
Ⅴ-7:1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),128.36,128.33,127.86,126.43,126.02,51.26,32.54,32.22,21.23.31PNMR(162MHz,CDCl3)δ18.91.HRMS-ESI(m/z)[M+H]+Calcd for C30H28N3OPS,509.1691；Found,509.1696.
Ⅵ-7:1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),128.26,126.82,126.71,47.86,32.43,30.80,21.09.31PNMR(162MHz,CDCl3)δ16.78.HRMS-ESI(m/z)[M+H]+Calcd for C30H28N3OPS,509.1691；Found,509.1697.
实施例66
目标产物结构式如下：
步骤同实施例59，以Ⅰ-12和Ⅱ-1为原料。
Ⅴ-8为黄色液体，产率28％。Ⅵ-8为黄色液体，产率49％。
Ⅴ-8:1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),125.37,124.25,54.31,32.84,31.71,29.36,29.07,28.97,28.60,22.56,14.03.31P NMR(162MHz,CDCl3)δ18.74.HRMS-ESI(m/z)[M+H]+Calcd for C29H34N3OPS503.2160；Found,503.2159.
Ⅵ-8:1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),127.90,51.86,37.13,31.62,29.46,28.95,28.85,28.39,22.51,14.00.31P NMR(162MHz,CDCl3)δ16.89.HRMS-ESI(m/z)[M+H]+Calcd for C29H34N3OPS503.2160；Found,503.2161.
实施例67
目标产物结构式如下：
步骤同实施例59，以Ⅰ-11和Ⅱ-1为原料。
Ⅴ-9为黄色液体，产率30％。Ⅵ-9为黄色液体，产率47％。
Ⅴ-9:1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),54.33,44.52,29.46,20.43,11.11.31P NMR(162MHz,CDCl3)δ19.12.HRMS-ESI(m/z)[M+H]+Calcd for C25H26N3OPS 447.1534；Found,447.1533.
Ⅵ-9:1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),127.99,51.71,48.42,29.57,19.85,10.89.31P NMR(162MHz,CDCl3)δ16.69.HRMS-ESI(m/z)[M+H]+Calcd for C25H26N3OPS447.1534；Found,447.1530.
实施例68
目标产物结构式如下：
室温下，在10mL反应管中加入0.3mmolⅠ-1、0.9mmol mCPBA和2mL CH2Cl2，在室温下进行反应15h，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，干燥过滤，得到中间体粗产物。室温下，在10mL反应管中加入上述中间体粗产物、0.45mmolⅡ-1和1mLDMF，在120℃下进行反应30h，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，干燥过滤，通过柱层析得到产物Ⅶ-1白色固体和Ⅷ-1白色固体，产率分别为30％和52％。
Ⅶ-1:Melting point(M.P.):187-189℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),128.36,128.29,55.06,21.62.31PNMR(162MHz,CDCl3)δ22.15.HRMS-ESI(m/z)[M+H]+Calcd for C28H24N3O3PS 513.1276；Found,513.1275.
Ⅷ-1:Melting point(M.P.):167-169℃；1HNMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),127.58,53.85,21.64.31P NMR(162MHz,CDCl3)δ18.13.HRMS-ESI(m/z)[M+H]+Calcd for C28H24N3O3PS 513.1276；Found,513.1273.
实施例69
目标产物结构式如下：
步骤同实施例68，以Ⅰ-11和Ⅱ-9为原料。
Ⅶ-2为白色固体，产率32％。Ⅷ-2为白色固体，产率39％。
Ⅶ-2:Melting point(M.P.):192-194℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),125.94,124.82,123.28,52.70,21.66.31P NMR(162MHz,CDCl3)δ21.84.HRMS-ESI(m/z)[M+H]+Calcd forC32H26N3O3PS 563.1432；Found,563.1431.
Ⅷ-2:Melting point(M.P.):174-176℃；1HNMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),127.09,126.31,125.08,124.89,122.27,51.25,21.62.31P NMR(162MHz,CDCl3)δ18.42.HRMS-ESI(m/z)[M+H]+Calcd for C32H26N3O3PS563.1432；Found,563.1429.
实施例70
目标产物结构式如下：
室温下，在10mL反应管中加入0.3mmol V-1、1.2mmol PhSiH3、3.0mmol醋酸和2mL甲苯，在120℃下进行反应12h，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，干燥过滤，通过柱层析得到产物Ⅸ。
Ⅸ，白色固体，产率为91％。Melting point(M.P.):105-108℃；1HNMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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),21.00.31P NMR(162MHz,CDCl3)δ-34.99.HRMS-ESI(m/z)[M+H]+Calcd for C28H24N3PS 465.1429；Found,465.1427.
实施例71
目标产物结构式如下：
室温下，在10mL反应管中加入0.3mmol V-1、0.33mmol MeMgBr(3.0M in EthylEther)和1mL THF，在室温下进行反应5h，向反应液中加入芳香醛1(0.45mmol)的THF(1mL)溶液，在室温下进行反应15h，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，干燥过滤，通过柱层析得到产物Ⅹ-1。
Ⅹ-1，白色固体，产率为66％。Melting point(M.P.):150-152℃；1HNMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C27H23N3OS437.1562；Found,437.1561.
实施例72
目标产物结构式如下：
步骤同实施例71，以Ⅴ-1和芳香醛2为原料。
Ⅹ-2为白色固体，产率52％。
Ⅹ-2:Melting point(M.P.):163-165℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 C31H28N4OS 504.1984；Found,504.1983.
实施例73
目标产物结构式如下：
室温下，在10mL反应管中加入0.3mmolⅥ-1、2mLTHF和0.33mmol MeMgBr(3.0MinEthyl Ether)，在室温下进行反应10h，加入饱和氯化铵水溶液和10mL乙酸乙酯萃取分离，干燥过滤，通过柱层析得到产物Ⅺ-1。
Ⅺ-1，无色液体，产率为92％。1H NMR(400MHz,CDCl3)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).13CNMR(101MHz,CDCl3)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 C16H15N3S281.0987；Found,281.0988.
实施例74
目标产物结构式如下：
步骤同实施例73，以Ⅵ-8为原料。
Ⅺ-2为黄色液体，产率90％。
Ⅺ-2：1H NMR(400MHz,CDCl3)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).13CNMR(101MHz,CDCl3)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 C17H25N3S 303.1769；Found,303.1767.
实施例75
目标产物结构式如下：
步骤同实施例73，以Ⅵ-9为原料。
Ⅺ-3为白色固体，产率86％。
Ⅺ-3：Melting point(M.P.):61-63℃；1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 forC13H17N3S 247.1143；Found,247.1142.
Claims (9)
1.一类硫代1,2,3-三氮唑及其高效合成方法，其特征在于：以二苯基膦酰基硫代炔烃Ⅰ和叠氮化合物Ⅱ为原料，通过不同的反应，高效简便合成含硫1,2,3-三氮唑化合物Ⅲ-Ⅻ的方法。结构式如下：
2.根据权利要求1所述的合成方法，其特征在于，苯基膦酰基硫代炔烃Ⅰ是以下化合物：
3.根据权利要求1所述的合成方法，其特征在于，叠氮化合物Ⅱ是以下化合物之一：
4.根据权利要求1所述的合成方法，其特征在于，铜催化剂cat.1是以下化合物之一：碘化亚铜(CuI)、六氟膦酸四乙腈铜(Cu(MeCN)4PF6)之一。
5.根据权利要求1所述的合成方法，其特征在于，碱试剂是叔丁醇钾(tBuOK)。
6.根据权利要求1所述的合成方法，其特征在于，有机胺是N,N'-二甲基乙二胺(DMEDA)。
7.根据权利要求1所述的合成方法，其特征在于，铜催化剂cat.2是以下铜催化剂之一：CuI、Cu(MeCN)4BF4、CuI/CuSO4-5H2O之一。
8.根据权利要求1所述的合成方法，其特征在于，格氏试剂是甲基溴化镁(MeMgBr)。
9.根据权利要求1所述的合成方法，其特征在于，芳香醛是以下化合物之一：
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211469959.0A CN115785010A (zh) | 2022-11-23 | 2022-11-23 | 一类硫代1,2,3-三氮唑及其高效合成方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211469959.0A CN115785010A (zh) | 2022-11-23 | 2022-11-23 | 一类硫代1,2,3-三氮唑及其高效合成方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115785010A true CN115785010A (zh) | 2023-03-14 |
Family
ID=85440245
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211469959.0A Pending CN115785010A (zh) | 2022-11-23 | 2022-11-23 | 一类硫代1,2,3-三氮唑及其高效合成方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115785010A (zh) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108503601A (zh) * | 2014-12-19 | 2018-09-07 | 河南师范大学 | 1-烷基-5-芳硫基-1,2,3-三氮唑类化合物的合成方法 |
| CN110746365A (zh) * | 2019-11-04 | 2020-02-04 | 大连理工大学 | 一种新型4-硫氰基-1,4,5-三取代的1,2,3-***的制备方法 |
| WO2022167457A1 (en) * | 2021-02-02 | 2022-08-11 | Liminal Biosciences Limited | Gpr84 antagonists and uses thereof |
-
2022
- 2022-11-23 CN CN202211469959.0A patent/CN115785010A/zh active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108503601A (zh) * | 2014-12-19 | 2018-09-07 | 河南师范大学 | 1-烷基-5-芳硫基-1,2,3-三氮唑类化合物的合成方法 |
| CN110746365A (zh) * | 2019-11-04 | 2020-02-04 | 大连理工大学 | 一种新型4-硫氰基-1,4,5-三取代的1,2,3-***的制备方法 |
| WO2022167457A1 (en) * | 2021-02-02 | 2022-08-11 | Liminal Biosciences Limited | Gpr84 antagonists and uses thereof |
Non-Patent Citations (5)
| Title |
|---|
| ERIC GODIN ET AL.: "General Cu-Catalyzed Csp–S Coupling", ORGANIC LETTERS, vol. 22, no. 15, 15 July 2020 (2020-07-15), pages 5905 - 5909 * |
| LANA A. SLUTSKY SMITH ET AL.: "Modifiable bidentate systems via N–C rearrangement in triazoles", CHEM. COMMUN., vol. 47, 23 August 2010 (2010-08-23), pages 319 - 321 * |
| ONKAR S. NAYAL ET AL.: "Green and efficient CuI NPs catalytic cross-coupling approach for the synthesis of tertiary-3-aminopropenoates, ciprofloxacin and triazoles", ASIAN JOURNAL OF ORGANIC CHEMISTRY, vol. 7, no. 4, 1 February 2018 (2018-02-01), pages 776 - 780 * |
| YASUHIRO OKUDA ET AL.: "Process-Controlled Regiodivergent Copper-Catalyzed Azide−AlkyneCycloadditions: Tailor-made Syntheses of 4- and 5‑Bromotriazolesfrom Bromo(phosphoryl)ethyne", ORG. LETT., vol. 22, 11 June 2020 (2020-06-11), pages 5099 - 5103 * |
| YASUHIRO OKUDA ET AL.: "Synthesis of Ph2P(O)-stabilized Ynamines via C(sp)–N Bond Formation and Their Dephosphorylative Copper-catalyzed Click Reaction", CHEMISTRY LETTERS, vol. 48, no. 12, 21 September 2019 (2019-09-21), pages 1484 - 1487 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20180100313A (ko) | 4-((6-(2-(2,4-디플루오로페닐)-1,1-디플루오로-2-히드록시-3-(1h-1,2,4-트리아졸-1-일)프로필)피리딘-3-일)옥시)벤조니트릴 및 제조방법 | |
| CN104387326B (zh) | 1,4,5-三取代-2-氨基咪唑类化合物的制备方法 | |
| EP2246348A1 (en) | Coupling reactions useful in the preparation of (1h-tetrazol-5-yl)-biphenyl derivatives | |
| Sá et al. | Synthesis of allylic thiocyanates and novel 1, 3-thiazin-4-ones from 2-(bromomethyl) alkenoates and S-nucleophiles in aqueous medium | |
| CN111303028B (zh) | 一种4-氰基-2-二氟甲基取代的喹啉类化合物及合成方法 | |
| WO2013108024A1 (en) | Aromatic compounds and methods of making the same | |
| KR20180088724A (ko) | 3차 아릴 아민의 제조를 위한 부흐발트-하르트비히 아릴화 방법 | |
| CN115785010A (zh) | 一类硫代1,2,3-三氮唑及其高效合成方法 | |
| CN112876488B (zh) | 螺环吲哚啉衍生物及其制备方法和应用 | |
| CN103910657A (zh) | 氮杂环丙烷化合物的开环方法 | |
| WO2016073276A1 (en) | Telescoping synthesis of 2-methoxymethyl-p-phenylenediamine | |
| Pokhvisneva et al. | Synthesis of high energy nitroguanidine derivatives | |
| KR102500124B1 (ko) | 1-[5-(2-플루오로페닐)-1-(피리딘-3-일술포닐)-1h-피롤-3-일]-n-메틸메탄아민모노푸마르산염의 제조법 | |
| US10336704B2 (en) | Method for preparing indenoisoquinoline derivatives | |
| CN107814757B (zh) | 一种合成多取代吡咯衍生物的方法 | |
| CN103910655A (zh) | 一种氮杂环丙烷化合物开环的方法 | |
| CN105085495B (zh) | N－炔基苯并咪唑衍生物的制备方法 | |
| CN108530368B (zh) | 有机碱催化巴比妥酸与二烯二腈加成反应的方法 | |
| CN108250127B (zh) | 一种异二氢吲哚酮类化合物及其衍生物的制备方法 | |
| US10662206B2 (en) | Method for preparing silane derivatives from furan derivatives in presence of borane catalyst | |
| KR20110042095A (ko) | ３，４-디아릴-４，５-디하이드로-（１ｈ）-피라졸-１-카복스아미딘 유도체의 합성 | |
| KR101170024B1 (ko) | 아조세미드 제조방법 | |
| Verma et al. | Synthesis of new 2, 3-disubstituted pyridines containing a 1, 2, 3-triazole in the side-chain via one-pot copper-catalyzed azide-alkyne cycloaddition | |
| KR101957989B1 (ko) | 유기붕소 촉매를 이용한 안티-(2-알킬)사이클로프로필 실란 화합물의 제조방법 | |
| Moskalenko et al. | Reaction of acetylferrocene with dimethylformamide dimethyl acetal and some transformations of the reaction product |
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 |