CN106496158B - 一种1,2,4-苯并噻二嗪系列化合物的制备方法 - Google Patents
一种1,2,4-苯并噻二嗪系列化合物的制备方法 Download PDFInfo
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- -1 1,2, 4-benzothiadiazine series compounds Chemical class 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 110
- 239000003054 catalyst Substances 0.000 claims abstract description 44
- 239000000758 substrate Substances 0.000 claims abstract description 9
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- 230000035484 reaction time Effects 0.000 claims abstract description 8
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 6
- 150000003624 transition metals Chemical class 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical group CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 claims description 62
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 52
- 239000012046 mixed solvent Substances 0.000 claims description 43
- 229910052709 silver Inorganic materials 0.000 claims description 24
- 239000004332 silver Substances 0.000 claims description 24
- 229910021584 Cobalt(II) iodide Inorganic materials 0.000 claims description 23
- AVWLPUQJODERGA-UHFFFAOYSA-L cobalt(2+);diiodide Chemical compound [Co+2].[I-].[I-] AVWLPUQJODERGA-UHFFFAOYSA-L 0.000 claims description 23
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 10
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- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
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- 239000011737 fluorine Substances 0.000 claims description 6
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
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- 238000006555 catalytic reaction Methods 0.000 claims description 5
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- 239000000460 chlorine Substances 0.000 claims description 5
- QGHDLJAZIIFENW-UHFFFAOYSA-N 4-[1,1,1,3,3,3-hexafluoro-2-(4-hydroxy-3-prop-2-enylphenyl)propan-2-yl]-2-prop-2-enylphenol Chemical group C1=C(CC=C)C(O)=CC=C1C(C(F)(F)F)(C(F)(F)F)C1=CC=C(O)C(CC=C)=C1 QGHDLJAZIIFENW-UHFFFAOYSA-N 0.000 claims description 4
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- 125000000304 alkynyl group Chemical group 0.000 claims description 4
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- TYMWDZKTHYZJBV-UHFFFAOYSA-N cyclopenta-2,4-dien-1-ylidenemethanone Chemical compound O=C=C1C=CC=C1 TYMWDZKTHYZJBV-UHFFFAOYSA-N 0.000 description 21
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- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
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- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
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- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
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- OTEKOJQFKOIXMU-UHFFFAOYSA-N 1,4-bis(trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=C(C(Cl)(Cl)Cl)C=C1 OTEKOJQFKOIXMU-UHFFFAOYSA-N 0.000 description 1
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- ASWCZHASOIYNRH-UHFFFAOYSA-N 2-(2-aminophenyl)sulfinylaniline Chemical compound NC1=CC=CC=C1S(=O)C1=CC=CC=C1N ASWCZHASOIYNRH-UHFFFAOYSA-N 0.000 description 1
- QRKDOAWSBBGNLE-UHFFFAOYSA-N 2h-1,2,4-benzothiadiazine Chemical compound C1=CC=C2N=CNSC2=C1 QRKDOAWSBBGNLE-UHFFFAOYSA-N 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
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- PYYACAUVAHXWIZ-UHFFFAOYSA-N [Rh].ClC1(C=CC=C1)Cl Chemical compound [Rh].ClC1(C=CC=C1)Cl PYYACAUVAHXWIZ-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
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- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
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- 239000002249 anxiolytic agent Substances 0.000 description 1
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- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
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- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
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- 125000000524 functional group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
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- KNPJTNDEHOFWKA-UHFFFAOYSA-N imino-oxo-diphenyl-$l^{6}-sulfane Chemical compound C=1C=CC=CC=1S(=O)(=N)C1=CC=CC=C1 KNPJTNDEHOFWKA-UHFFFAOYSA-N 0.000 description 1
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- OHZZTXYKLXZFSZ-UHFFFAOYSA-I manganese(3+) 5,10,15-tris(1-methylpyridin-1-ium-4-yl)-20-(1-methylpyridin-4-ylidene)porphyrin-22-ide pentachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Mn+3].C1=CN(C)C=CC1=C1C(C=C2)=NC2=C(C=2C=C[N+](C)=CC=2)C([N-]2)=CC=C2C(C=2C=C[N+](C)=CC=2)=C(C=C2)N=C2C(C=2C=C[N+](C)=CC=2)=C2N=C1C=C2 OHZZTXYKLXZFSZ-UHFFFAOYSA-I 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
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- 244000045947 parasite Species 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
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- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/15—Six-membered rings
- C07D285/16—Thiadiazines; Hydrogenated thiadiazines
- C07D285/18—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines
- C07D285/20—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems
- C07D285/22—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D285/24—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Abstract
一种1,2,4‑苯并噻二嗪系列化合物的制备方法,该方法采用亚砜磺酰亚胺和3‑芳(烷)基‑1,4,2‑二唑‑5‑酮作为反应底物,在过渡金属催化剂和共催化剂的共同催化作用下,利用微波反应器加热(反应温度为100‑120℃,反应时间为2~3小时)或油浴加热(反应温度为110‑130℃,反应时间为15~18小时)的条件发生反应,通过C‑H/N‑H键的双官能团化形成含苯并亚砜和双氮的杂环化合物,即制得1,2,4‑苯并噻二嗪系列化合物。本方法所得的副产物仅为二氧化碳和水,便于分离提纯;反应的化学选择性高,底物适用性广;无须额外的惰性气体保护作为反应环境,便于操作简便;微波条件下的反应时间短,成本极低、副产物少,可适用于较大规模的制备。
Description
技术领域
本发明涉及一种含硫和双氮杂环药物骨架的衍生物,具体涉及1,2,4-苯并噻二嗪类化合物的制备方法。
背景技术
亚砜磺酰亚胺是一类重要的具有生物活性的有机分子。早在上世纪70年代,二苯基亚砜磺酰亚胺(diphenylsulfoximine)即被当作药效团用于临床药物开发研究。目前,含有此类亚砜磺酰亚胺骨架并成功上市应用于临床的药物有:用于治疗喘息平喘的药物Suloxifen(舒洛昔芬);用于解除痉挛使用的药物HE-HK 52[(a)Satzinger,G.Drug NewsPerspect.2001,14,197.(b)Pothmann,R.Drugs Future 1982,7,478.];驱虫杀虫剂Sulfoxaflor(氟啶虫胺腈);抗过敏药Sudexanox(RU 31156,舒地古诺);依赖于细胞周期蛋白(CDKs)致活酶的pan-CDK抑制剂ZK 304709[G.Siemeister,U.Luecking,C.Wagner,K.Detjen,C.McCoy,K.Bosslet,Biomed.Pharmacother.2006,60,269.];以及用于预防淋巴细胞HIV逆转录酶抑制剂的药物NSC 287474[P.Stoss,G.Satzinger,Chem.Ber.1972,105,2575.]等。
苯并[e][1,2,4]噻二唑-1-氧衍生物含有苯并亚砜磺酰亚胺的杂环骨架结构,含有此类结构的分子被视作药物研发的“优势骨架(privileged structure)”。含有该核心结构的化合物广泛存在于各类天然产物,或者具有重要生理药理活性的有机分子当中。此外,在农药和材料科学领域也有大量的有机分子含有苯并[e][1,2,4]噻二唑的结构[(a)U.Lücking,Angew.Chem.Int.Ed.2013,52,9399-9408.(b)R.W.Buckheit Jr.,V.Fliakas-Boltz,W.D.Decker,J.L.Roberson,T.L.Stup,C.A.Pyle,E.L.White,J.B.McMahon,M.J.Currens,M.R.Boyd,J.P.Bader,Antiviral Res.1995,26,117.(c)A.Hizi,R.Tal,M.Shaharabany,M.J.Currens,M.R.Boyd,S.H.Hughes,J.B.McMahon,Antimicrob.AgentsChemother.1993,37,1037.(d)R.W.Buckheit,Jr.,V.-F.Boltz,W.D.Decker,J.L.Robertson,C.A.Pyle,E.L.White,B.J.Bowdon,J.B.McMahon,M.R.Boyd,J.P.Bader,D.G.Nickell,H.Barth,T.K.Antonucci,Antiviral Res.1994,25,43.(e)R.D.Dillard,T.T.Yen,P.Stark,D.E.Pavey,J.Med.Chem.1980,23,717.]。目前,已经临床使用的特效抗焦虑和抗惊厥的药物4962是一种基于苯并亚硫砜二氮杂的受体拮抗药,其有效成分即含有苯并[e][1,2,4]噻二唑1-氧的结构骨架[(a)Bartoszyk,G.;Dooley,D.;Barth,H.;Hartenstein,J.;Satzinger,G.J.Pharm.Pharmacol.1987,39,407.(b)Bartoszyk,G.;Schoenherr,U.Behavioral&Neural Biology,1987,48(2):317-319]。另外一种含有双硫代1-苯基苯并[e][1,2,4]噻二唑-1-氧的衍生物是一种优良的逆转录酶抑制剂,可用于保护血液和淋巴液中的淋巴细胞,因而可用于潜在的抗HIV药物,引起了药物化学家的关注[(a)G.Satzinger,Drug News Perspect.2001,14,197.(b)G.Satzinger(GodeckeAktiengesellschaft),US 5321024,1994.]。因此,发展一些高效快捷的方法合成含1-氧噻二唑结构的化合物具有十分重要的意义。
早在1964年,Wagner课题组首次报道了合成1-氧噻二唑骨架分子的方法[A.W.Wagner,G.Liebigs Ann.Chem.1964,675,189.],通过该方法合虽然能够构建噻二唑基本骨架,但是转化的效率却不是很理想。1971年和1973年,Williams相继报道了利用亚磺酰亚胺经过多步反应制备1-氧噻二唑的方法[(a)T.R.Williams,D.J.Cram,J.Am.Chem.Soc.1971,93,7333;(b)T.R.Williams,D.J.Cram,J.Org.Chem.1973,38,20.]。虽然此方法未使用过渡金属,但其步骤繁多,整体收率低。同样,1976年,Satzinger等报道了3号位各种取代的1-氧噻二唑衍生物方法[P.Stoss,G.Satzinger,Chem.Ber.1976,109,2097.]。此方法要用到不易制备的邻氨基苯基亚砜亚磺酰胺,以及毒性较重的氰化溴(BrCN)和五氯化磷(PCl5)作为化工原料,因而大规模制备时对设备的要求较严格,生产成本高。
以上这些方法,为合成含亚砜磺酰亚胺结构的1,2,4-苯并噻二嗪类化合物提供了可供选择的途径。然而,经过文献调研我们发现,目前还没有一种很有效的方法一步合成1,2,4-苯并噻二嗪类化合物。基于亚砜磺酰亚胺衍生物所具有的强效的生物或药物活性,我们预计开发有效的方法合成含有该结构特征的化合物将具有十分强大的可转化能力,以及十分广阔的应用前景。
基于此,本发明旨在通过发展一类短周期过渡金属催化的高选择性C-H/N-H活化反应,使用价格便宜而且低毒性的钴配合物作为催化剂,结构上廉价易得的小分子化合物作为原料,在简单的反应条件下高效率、高化学选择性地合成含1,2,4-苯并噻二嗪类化合物。本发明方法对于各类基团如卤素(氟、氯、溴、碘),不饱和基团(烯基、炔基),氰基、酯基、硝基等敏感基团具有良好的兼容性,这些基团本身具有良好的反应活性,因此所得产物能够通过其他的有机化学反应发生进一步的转化,从而在1,2,4-苯并噻二嗪类化合物的骨架上引入更多的官能团,同时还可构建其他一些新型结构的化合物。
发明内容
本发明的目的在于提供一种1,2,4-苯并噻二嗪类化合物的制备方法,该方法化学选择性高,底物适用性广,操作简便,副产物少,适用于较大规模的制备。
本发明是这样实现的,在有机混合溶剂中,采用亚砜磺酰亚胺和3-芳(烷)基-1,4,2-二唑-5-酮作为反应底物,在过渡金属催化剂和共催化剂的共同催化作用下,在一定温度下反应一段时间得到产物1,2,4-苯并噻二嗪类化合物。反应通式如下:
其中R1、R2、R3为H或烷基、烷氧基、环烷基等各种供电子的基团,或氟、氯、溴、碘、酯基、硝基、氰基、酰胺基等各种吸电子的基团,或呋喃基、噻吩基、吡啶基、烯基、炔基、硅基等。
其中,所述的有机混合溶剂为叔戊醇/一氯甲烷、叔戊醇/二氯甲烷、叔戊醇/三氯甲烷、叔戊醇/四氯甲烷、叔丁醇/三氯甲烷或叔丁醇/1,2-二氯甲烷,其中,以叔戊醇/三氯甲烷为最佳。
所述的过渡金属催化剂为环戊二烯二氯化钴、一羰基环戊二烯基碘化钴、二(乙腈)环戊二烯基二(六氟碲酸银)化钴、二氯环戊二烯化铑或二氯环戊二烯化铱,其中,以一羰基环戊二烯碘化钴为最佳。
所述的共催化剂为六氟碲酸银、三氟甲磺酸银、双三氟甲基磺酰亚胺银、四氟硼酸银。
反应的温度控制可以采用微波反应器加热、油浴加热等加热方式,采用微波反应器加热时,反应温度为100~120℃,反应时间为2~3小时;采用油浴加热时,反应温度为110~130℃,反应时间为15~18小时。
反应无须额外的惰性气体保护作为反应环境,并且副产物仅为二氧化碳和水。
由上述方法制得的1-芳(烷)基1,2,4-苯并噻二嗪类化合物分子中,骨架上1-位的芳基可以为各种带有供电子基团的芳基、各种带有吸电子基团的芳基、呋喃基、噻吩基、吡啶基;所述供电子基团有烷基、烷氧基、环烷基;所述吸电子基团有氟、氯、溴、碘、酯基、硝基、氰基、酰胺基;骨架上3-位的取代基可以为各种烷基、烷氧基、环烷基、芳基、萘基、呋喃基、噻吩基、吡啶基、硅基或卤素基团。
本发明的有益效果是:反应物亚砜磺酰亚胺与催化剂的比例为1:0.05就能非常顺利地进行,所得的副产物仅为二氧化碳和水,不仅便于产物的分离提纯,而且体现出良好的绿色化;反应的化学选择性高,底物适用性广,产物收率高;无须额外的惰性气体保护作为反应环境,操作简便,微波条件下的反应时间短,成本极低,可适用于较大规模的制备;由于产物对于卤素(氟、氯、溴、碘),不饱和基团(烯基、炔基),氰基、酯基、硝基等敏感基团具有良好的兼容性,这些基团本身具有良好的反应活性,因此所得产物能够通过其他的有机化学反应发生进一步的转化,构建其他一些新型的含亚砜磺酰亚胺结构的化合物,具有潜在的生物或药物活性,在生物医药、农药和材料科学等领域具有非常好的应用前景。
附图说明
图1是根据本发明方法所得产物1,2,4-苯并噻二嗪类化合物的结构通式。
图2是本发明实施例1的产物1,3-二苯基-1,2,4-苯并噻二嗪类化合物3a的单晶结构示意图。
图3是本发明实施例1的产物1,3-二苯基-1,2,4-苯并噻二嗪类化合物3a的化学结构式。
具体实施方式
下面的实施例是对本发明的进一步说明,而不是限制本发明的范围。
实施例一:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在Biotage微波反应器加热到110℃,再滴加反应物二苯基亚磺酰亚胺(43.4mg,0.2mmol)以及3-苯基-1,4,2-二唑-5-酮(64mg,0.4mmol)和混合溶剂(1.0mL)至反应体系中,于空气氛围下继续反应2小时,TLC检测完全反应。后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3a。产率:85%。以下是产物3a的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ:8.47-8.40(m,2H),7.88(dd,J=5.4Hz,3.6Hz,2H),7.70-7.54(m,5H),7.49-7.41(m,4H),7.26(m,1H).
13C NMR(100MHz,CDCl3)δ:158.1,147.3,140.7,137.6,134.4,133.9,131.0,129.3,128.7,128.7,128.2,126.3,124.8,113.8.
实施例二:
空气氛围下将催化剂一羰基环戊二烯碘化钴(230mg,0.25mmol)双三氟甲基磺酰亚胺银(400mg,0.5mmol)溶于混合溶剂叔戊醇/三氯甲烷(25mL,v:v=1:1)中,在Biotage微波反应器加热到110℃,再滴加反应物二苯基亚磺酰亚胺(1.09g,5.0mmol)以及3-苯基-1,4,2-二唑-5-酮(1.6g,10mmol)至反应体系中,于空气氛围下继续反应3小时,TLC检测完全反应。后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3a。产率:80%。以下是产物3a的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ:8.47-8.40(m,2H),7.88(dd,J=5.4Hz,3.6Hz,2H),7.70-7.54(m,5H),7.49-7.41(m,4H),7.26(m,1H).
13C NMR(100MHz,CDCl3)δ:158.1,147.3,140.7,137.6,134.4,133.9,131.0,129.3,128.7,128.7,128.2,126.3,124.8,113.8.
实施例三:
空气氛围下将催化剂一羰基环戊二烯碘化钴(230mg,0.25mmol)双三氟甲基磺酰亚胺银(400mg,0.5mmol)溶于混合溶剂叔戊醇/三氯甲烷(25mL,v:v=1:1)中,在油浴反应器中加热到120℃,再滴加反应物二苯基亚磺酰亚胺(1.09g,5.0mmol)以及3-苯基-1,4,2-二唑-5-酮(1.6g,10mmol)至反应体系中,于空气氛围下继续反应16小时,TLC检测完全反应。后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3a。产率:69%。以下是产物3a的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ:8.47-8.40(m,2H),7.88(dd,J=5.4Hz,3.6Hz,2H),7.70-7.54(m,5H),7.49-7.41(m,4H),7.26(m,1H).
13C NMR(100MHz,CDCl3)δ:158.1,147.3,140.7,137.6,134.4,133.9,131.0,129.3,128.7,128.7,128.2,126.3,124.8,113.8.
实施例四:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在Biotage微波反应器加热到110℃,再滴加反应物二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-(4-甲基)苯基-1,4,2-二唑-5-酮(71mg,0.4mmol)混合溶剂(1.0mL)溶至反应体系中,于空气氛围下继续反应2小时,TLC板检测完全反应。后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3b。产率:87%。以下是产物3b的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.33(d,J=8.2Hz,2H),7.88(d,J=7.6Hz,2H),7.68-7.52(m,5H),7.44(d,J=7.9Hz,1H),7.29-7.19(m,3H),2.41(s,3H).
13C NMR(100MHz,CDCl3)δ158.2,147.5,141.4,140.9,134.9,134.3,133.8,129.3,128.9,128.7,128.6,126.0,124.8,113.7,21.6.
实施例五:
空气氛围下将催化剂一羰基环戊二烯碘化钴(230mg,0.25mmol)双三氟甲基磺酰亚胺银(400mg,0.5mmol)溶于混合溶剂叔戊醇/三氯甲烷(25mL,v:v=1:1)中,在Biotage微波反应器加热到110℃,再滴加反应物二苯基亚磺酰亚胺(1.09g,5.0mmol)以及3-苯基-1,4,2-二唑-5-酮(1.78g,10mmol)至反应体系中,于空气氛围下继续反应3小时,TLC检测完全反应。后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3b。产率:81%。以下是产物3b的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ:8.47-8.40(m,2H),7.88(dd,J=5.4Hz,3.6Hz,2H),7.70-7.54(m,5H),7.49-7.41(m,4H),7.26(m,1H).
13C NMR(100MHz,CDCl3)δ:158.1,147.3,140.7,137.6,134.4,133.9,131.0,129.3,128.7,128.7,128.2,126.3,124.8,113.8.
实施例六:
空气氛围下将催化剂一羰基环戊二烯碘化钴(230mg,0.25mmol)双三氟甲基磺酰亚胺银(400mg,0.5mmol)溶于混合溶剂叔戊醇/三氯甲烷(25mL,v:v=1:1)中,在油浴反应器加热到120℃,再滴加反应物二苯基亚磺酰亚胺(1.09g,5.0mmol)以及3-苯基-1,4,2-二唑-5-酮(1.78g,10mmol)至反应体系中,于空气氛围下继续反应18小时,TLC检测完全反应。后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3b。产率:72%。以下是产物3b的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ:8.47-8.40(m,2H),7.88(dd,J=5.4Hz,3.6Hz,2H),7.70-7.54(m,5H),7.49-7.41(m,4H),7.26(m,1H).
13C NMR(100MHz,CDCl3)δ:158.1,147.3,140.7,137.6,134.4,133.9,131.0,129.3,128.7,128.7,128.2,126.3,124.8,113.8.
实施例七:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)以及三甲基乙酸(40mg,0.4mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在Biotage微波反应器加热到110℃,再滴加反应物二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-(4-甲氧基)苯基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应2小时,TLC检测至完全反应。后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3c。产率:69%。以下是产物3c的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.41-8.38(m,2H),7.91-7.84(m,2H),7.60(m,5H),7.42(d,J=7.7Hz,1H),7.26-7.19(m,1H),6.97-6.92(m,2H),3.85(s,3H).
13C NMR(100MHz,CDCl3)δ162.2,157.8,147.6,140.9,134.3,133.8,130.4,130.2,129.3,128.6,128.5,125.8,124.8,113.6,113.5,55.4.
实施例八:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)以及三甲基乙酸(40mg,0.4mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在Biotage微波反应器加热到100℃,再滴加反应物二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-(4-甲氧基)苯基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应4小时,TLC检测至完全反应。后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3c。产率:61%。以下是产物3c的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.41-8.38(m,2H),7.91-7.84(m,2H),7.60(m,5H),7.42(d,J=7.7Hz,1H),7.26-7.19(m,1H),6.97-6.92(m,2H),3.85(s,3H).
13C NMR(100MHz,CDCl3)δ162.2,157.8,147.6,140.9,134.3,133.8,130.4,130.2,129.3,128.6,128.5,125.8,124.8,113.6,113.5,55.4.
实施例九:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)以及三甲基乙酸(40mg,0.4mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在油浴反应器加热到130℃,再滴加反应物二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-(4-甲氧基)苯基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应15小时,TLC检测至完全反应。后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3c。产率:60%。以下是产物3c的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.41-8.38(m,2H),7.91-7.84(m,2H),7.60(m,5H),7.42(d,J=7.7Hz,1H),7.26-7.19(m,1H),6.97-6.92(m,2H),3.85(s,3H).
13C NMR(100MHz,CDCl3)δ162.2,157.8,147.6,140.9,134.3,133.8,130.4,130.2,129.3,128.6,128.5,125.8,124.8,113.6,113.5,55.4.
实施例十:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)以及三甲基乙酸(40mg,0.4mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在Biotage微波反应器加热到110℃,滴加反应物二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-(4-氟)苯基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应2小时,TLC检测至完全反应。反应完毕,后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3d。产率:71%。以下是产物3d的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.51-8.38(m,2H),7.88(d,J=7.5Hz,2H),7.65-7.55(m,5H),7.44(d,J=7.9Hz,1H),7.33-7.21(m,1H),7.17-7.07(m,2H).
13C NMR(100MHz,CDCl3)δ166.1,163.6,157.0,147.2,140.6,134.5,133.9,130.9,130.8,129.4,126.3,124.8,115.2,115.0,113.7.
实施例十一:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)以及三甲基乙酸(40mg,0.4mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在Biotage微波反应器加热到110℃,滴加反应物二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-(4-溴)苯基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应2小时,TLC检测至完全反应。反应完毕,后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3e。产率:52%。以下是产物3e的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.31(d,J=8.6Hz,2H),7.91-7.85(m,2H),7.70-7.53(m,7H),7.44(d,J=7.8Hz,1H),7.33-7.23(m,1H).
13C NMR(100MHz,CDCl3)δ157.1,147.1,140.6,136.6,134.5,134.0,131.3,130.3,129.4,128.7,128.6,126.5,125.8,124.8,113.8.
实施例十二:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)以及三甲基乙酸(40mg,0.4mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在Biotage微波反应器加热到110℃,滴加反应物二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-(4-碘)苯基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应2小时,TLC检测至完全反应。反应完毕,后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3f。产率:48%。以下是产物3f的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.16(d,J=8.5Hz,2H),7.87(d,J=7.7Hz,2H),7.78(d,J=8.4Hz,2H),7.67-7.53(m,5H),7.44(d,J=7.8Hz,1H),7.27(m,1H).
13C NMR(100MHz,CDCl3)δ157.2,147.1,140.6,137.4,137.2,134.5,134.0,130.3,129.4,128.7,128.6,126.5,124.8,113.8,98.2.
实施例十三:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)以及三甲基乙酸(40mg,0.4mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在Biotage微波反应器加热到110℃,滴加反应物二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-萘基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应2小时,TLC检测至完全反应。反应完毕,后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3g。产率:73%。以下是产物3g的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.95(s,1H),8.57(dd,J=8.7Hz,1.2Hz,1H),8.00-7.82(m,5H),7.76-7.44(m,8H),7.28(dd,J=13.6Hz,5.8Hz,1H).
13C NMR(100MHz,CDCl3)δ158.0,147.4,140.8,135.0,134.9,134.4,133.9,133.1,129.4,129.3,128.8,128.7,127.7,127.7,127.2,126.3,126.1,125.4,124.9,113.9.
实施例十四:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)以及三甲基乙酸(40mg,0.4mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在微波炉110℃于磁力搅拌器中滴加含有二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-苯乙烯基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应2小时,TLC板检测至完全反应。反应完毕,后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3h。产率:72%。以下是产物3h的核磁共振实验数据:
1H NMR·(400MHz,CDCl3)δ7.87(t,J=12.0Hz,3H),7.66-7.57(m,7H),7.42(d,J=7.9Hz,1H),7.38-7.29(m,3H),7.24(dd,J=11.0,5.0Hz,1H),7.06(d,J=15.8Hz,1H).
13C NMR(100MHz,CDCl3)δ158.5,147.2,140.7,139.7,135.9,134.5,133.9,129.4,129.2,128.8,128.7,128.2,127.8,126.3,125.0,114.4.
实施例十五:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)以及三甲基乙酸(40mg,0.4mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在微波炉110℃于磁力搅拌器中滴加含有二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-噻吩基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应2小时,TLC板检测至完全反应。反应完毕,后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3i。产率:35%。以下是产物3i的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.96-7.87(m,3H),7.70-7.55(m,5H),7.48(dd,J=5.0,1.2Hz,1H),7.42(d,J=8.3Hz,1H),7.25-7.19(m,1H),7.11(dd,J=5.0,3.8Hz,1H).
13C NMR(100MHz,CDCl3)δ154.4,134.4,133.9,130.3,130.1,129.3,129.3,128.7,128.6,128.3,127.8,127.8,125.9,124.8,114.0.
实施例十六:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)以及三甲基乙酸(40mg,0.4mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在微波炉110℃于磁力搅拌器中滴加含有4,4-二氯二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-苯基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应2-3小时,TLC板检测至完全反应。反应完毕,后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3j。产率:77%。以下是产物3j的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.41(dd,J=8.1,1.4Hz,2H),7.82-7.75(m,2H),7.67(d,J=2.0Hz,1H),7.56-7.42(m,5H),7.35(d,J=8.6Hz,1H),7.26-7.19(m,1H).
13C NMR(100MHz,CDCl3)δ159.0,148.6,141.1,140.8,139.0,137.0,131.5,130.0,129.8,128.8,128.3,128.2,126.9,126.0,111.8.
实施例十七:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在微波炉110℃于磁力搅拌器中滴加含有4,4-二氯二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-(4-甲氧基)苯基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应2小时,TLC板检测至完全反应。反应完毕,后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3k。产率:83%。以下是产物3k的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.36(d,J=9.0Hz,2H),7.83-7.75(m,2H),7.63(d,J=2.0Hz,1H),7.53(d,J=8.7Hz,2H),7.34(d,J=8.6Hz,1H),7.18(dd,J=8.6,2.0Hz,1H),6.99-6.91(m,2H),3.86(s,3H).13C NMR(100MHz,CDCl3)δ162.6,158.7,148.9,141.0,140.7,139.2,130.6,129.9,129.7,129.5,128.0,126.4,126.0,113.6,111.6,55.4.
实施例十八:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在微波炉110℃于磁力搅拌器中滴加含有4,4-二甲基二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-(4-甲氧基)苯基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应2小时,TLC板检测至完全反应。反应完毕,后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3l。产率:84%。以下是产物3l的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.45-8.38(m,2H),7.73(d,J=8.3Hz,2H),7.45(dd,J=7.3,6.5Hz,4H),7.33(dd,J=8.2,1.9Hz,3H),7.07(d,J=8.2Hz,1H),2.42(s,6H).
13C NMR(100MHz,CDCl3)δ158.2,147.4,145.3,144.9,138.2,137.8,130.8,129.9,128.6,128.5,128.3,128.1,127.6,124.6,111.5,21.8,21.6.
实施例十九:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在微波炉110℃于磁力搅拌器中滴加含有4,4-二甲基二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-(4-甲基)苯基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应2小时,TLC板检测至完全反应。反应完毕,后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3m。产率:80%。以下是产物3m的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.31(d,J=8.2Hz,2H),7.73(d,J=8.3Hz,2H),7.44(s,1H),7.32(dd,J=8.2,2.2Hz,3H),7.24(d,J=7.9Hz,2H),7.04(d,J=8.2Hz,1H),2.41(s,3H),2.40(s,3H).
13C NMR(100MHz,CDCl3)δ158.3,147.5,145.2,144.8,141.2,138.3,135.1,129.9,128.9,128.6,128.5,128.2,127.4,124.6,111.4,21.8,21.6,21.5.
实施例二十:
空气氛围下将催化剂一羰基环戊二烯碘化钴(9.2mg,0.01mmol)双三氟甲基磺酰亚胺银(16mg,0.02mmol)溶于混合溶剂叔戊醇/三氯甲烷(1.0mL,v:v=1:1)中,在微波炉110℃于磁力搅拌器中滴加含有4,4-二甲基二苯基亚磺酰亚胺(43.4mg,0.2mmol)及3-萘基-1,4,2-二唑-5-酮(64mg,0.04mmol)混合溶剂(1.0mL)溶液至反应体系中,于空气氛围下继续反应2小时,TLC板检测至完全反应。反应完毕,后处理时先通过装有硅胶的砂芯漏斗抽滤除掉催化剂,所得滤液通过快速柱层析分离得纯净的产品1,3-二苯基苯并[e][1,2,4]噻二唑1-氧化合物3n。产率:57%。以下是产物3n的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.94(s,1H),8.56(dd,J=8.7,1.5Hz,1H),7.98-7.83(m,3H),7.77(d,J=8.3Hz,2H),7.53-7.45(m,3H),7.34(dd,J=7.9,6.3Hz,3H),7.07(d,J=8.1Hz,1H),2.43(s,3H),2.41(s,3H).
13C NMR(100MHz,CDCl3)δ158.1,147.4,145.4,144.9,138.2,135.2,134.9,133.1,129.9,129.3,129.2,128.6,128.3,127.7,127.7,127.1,126.1,125.4,124.6,118.2,111.6,21.8,21.6.
Claims (2)
1.一种1,2,4-苯并噻二嗪类化合物的制备方法,包括以下步骤:在有机混合溶剂中,采用结构如式I的化合物和结构如式II的化合物作为反应底物,在过渡金属催化剂和共催化剂的共同催化作用下,在一定温度条件下反应一段时间,得到结构如式III的产物1,2,4-苯并噻二嗪类化合物;
其中R1、R2、R3为H、烷基、烷氧基、环烷基、氟、氯、溴、碘、酯基、硝基、氰基、酰胺基、呋喃基、噻吩基、吡啶基、烯基、炔基、或硅基;
所述的有机混合溶剂为叔戊醇/一氯甲烷、叔戊醇/二氯甲烷、叔戊醇/三氯甲烷、叔戊醇/四氯甲烷、叔丁醇/三氯甲烷、或叔丁醇/1,2-二氯甲烷;
所述的过渡金属催化剂为环戊二烯二氯化钴、一羰基环戊二烯基碘化钴、或二(乙腈)环戊二烯基二(六氟碲酸银)化钴;
所述的共催化剂为六氟碲酸银、三氟甲磺酸银、双三氟甲基磺酰亚胺银、或四氟硼酸银;
反应的温度采用微波反应器加热控制,反应温度为100~120℃,反应时间为2~3小时;或者,反应的温度采用油浴加热控制,反应温度为110~130℃,反应时间为15~18小时。
2.根据权利要求1所述的1,2,4-苯并噻二嗪类化合物的制备方法,其特征在于:反应在空气环境下进行。
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