CN110878036A - 一种[(1,2-双磺酰基)乙基]芳烃类化合物的制备方法 - Google Patents
一种[(1,2-双磺酰基)乙基]芳烃类化合物的制备方法 Download PDFInfo
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 150000001491 aromatic compounds Chemical class 0.000 title description 3
- -1 alkyl halohydrocarbon Chemical class 0.000 claims abstract description 38
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims abstract description 17
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910000077 silane Inorganic materials 0.000 claims abstract description 6
- 239000003513 alkali Substances 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 238000004440 column chromatography Methods 0.000 claims description 7
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical group CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000012044 organic layer Substances 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 4
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 4
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical group [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 4
- RWPGFSMJFRPDDP-UHFFFAOYSA-L potassium metabisulfite Chemical group [K+].[K+].[O-]S(=O)S([O-])(=O)=O RWPGFSMJFRPDDP-UHFFFAOYSA-L 0.000 claims description 3
- 229940043349 potassium metabisulfite Drugs 0.000 claims description 3
- 235000010263 potassium metabisulphite Nutrition 0.000 claims description 3
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
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- 229910052786 argon Inorganic materials 0.000 claims description 2
- 238000001514 detection method Methods 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 4
- 239000002585 base Substances 0.000 claims 2
- 239000003208 petroleum Substances 0.000 claims 2
- WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 claims 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims 1
- 229940001584 sodium metabisulfite Drugs 0.000 claims 1
- 235000010262 sodium metabisulphite Nutrition 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 10
- 150000001336 alkenes Chemical class 0.000 abstract description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 abstract description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 abstract description 6
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- 125000000524 functional group Chemical group 0.000 abstract description 3
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- 230000007547 defect Effects 0.000 abstract 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 150000003457 sulfones Chemical class 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 6
- 238000001035 drying Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 4
- 229910000397 disodium phosphate Inorganic materials 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 3
- 238000005694 sulfonylation reaction Methods 0.000 description 3
- 230000001588 bifunctional effect Effects 0.000 description 2
- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 150000005826 halohydrocarbons Chemical class 0.000 description 2
- DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- HDBWAWNLGGMZRQ-UHFFFAOYSA-N p-Vinylbiphenyl Chemical compound C1=CC(C=C)=CC=C1C1=CC=CC=C1 HDBWAWNLGGMZRQ-UHFFFAOYSA-N 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical class C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 1
- JWVTWJNGILGLAT-UHFFFAOYSA-N 1-ethenyl-4-fluorobenzene Chemical compound FC1=CC=C(C=C)C=C1 JWVTWJNGILGLAT-UHFFFAOYSA-N 0.000 description 1
- PSWDQTMAUUQILQ-UHFFFAOYSA-N 2-[(6-methoxy-4-methylquinazolin-2-yl)amino]-5,6-dimethyl-1h-pyrimidin-4-one Chemical class N1=C(C)C2=CC(OC)=CC=C2N=C1NC1=NC(=O)C(C)=C(C)N1 PSWDQTMAUUQILQ-UHFFFAOYSA-N 0.000 description 1
- ORNUPNRNNSVZTC-UHFFFAOYSA-N 2-vinylthiophene Chemical compound C=CC1=CC=CS1 ORNUPNRNNSVZTC-UHFFFAOYSA-N 0.000 description 1
- CQVWOJSAGPFDQL-UHFFFAOYSA-N 3-iodopropan-1-ol Chemical compound OCCCI CQVWOJSAGPFDQL-UHFFFAOYSA-N 0.000 description 1
- RYYXDZDBXNUPOG-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine;dihydrochloride Chemical compound Cl.Cl.C1C(N)CCC2=C1SC(N)=N2 RYYXDZDBXNUPOG-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 238000005579 Julia olefination reaction Methods 0.000 description 1
- 239000005578 Mesotrione Substances 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical class C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 229940125796 compound 3d Drugs 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- OTLDLQZJRFYOJR-LJQANCHMSA-N eletriptan Chemical compound CN1CCC[C@@H]1CC1=CN=C2[C]1C=C(CCS(=O)(=O)C=1C=CC=CC=1)C=C2 OTLDLQZJRFYOJR-LJQANCHMSA-N 0.000 description 1
- 229960002472 eletriptan Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- RLZFVPPGVAHZPE-UHFFFAOYSA-N ethyl 4-iodobutanoate Chemical compound CCOC(=O)CCCI RLZFVPPGVAHZPE-UHFFFAOYSA-N 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
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- 150000002576 ketones Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- KPUREKXXPHOJQT-UHFFFAOYSA-N mesotrione Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)C)=CC=C1C(=O)C1C(=O)CCCC1=O KPUREKXXPHOJQT-UHFFFAOYSA-N 0.000 description 1
- 238000003328 mesylation reaction Methods 0.000 description 1
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- 238000006452 multicomponent reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000007342 radical addition reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 238000006175 van Leusen reaction Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/02—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to acyclic carbon atoms
- C07C317/10—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B61/00—Other general methods
- C07B61/02—Generation of organic free radicals; Organic free radicals per se
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/18—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/18—Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/03—Free radicals
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Abstract
本发明属有机化学技术领域，具体为一种[(1，2‑双磺酰基)乙基]芳烃类化合物的制备方法。在有机溶剂中(如DMF)，在当量硅烷和碱的作用下，烷基卤代烃，芳基烯烃与焦亚硫酸盐反应，制得[(1，2‑双磺酰基)乙基]芳烃类化合物。该类化合物的结构经1H NMR、13C NMR、HRMR、单晶X衍射等方法表征并得以确认。本发明方法在温和简单的条件下，利用简单烯烃为基本载体，实现了烯烃的双官能团化反应，一步高效构建了1，2‑双磺酰基取代的化合物，极大提高了该类化合物的合成效率，并且丰富了其官能团的多样性；该反应原料易得，成本较低，操作简单且避免了传统的1，2‑双磺酰基类化合物合成方法中步骤繁冗、可操作性不强、产率低的缺点，可适用于较大规模的制备，具有很好的应用前景。
Description
技术领域
本发明属有机化学技术领域，具体涉及一种[(1，2-双磺酰基)乙基]芳烃类化合物的制备方法。
背景技术
磺酰基片段是一个非常重要的基团，常见的含磺酰基的化合物有磺酰胺、砜、磺酸以及磺酸酯类化合物等，并且该结构片段广泛存在于药物分子、农药分子及材料分子当中[M.Bartholow，Top 200 Drug of 2011.Pharmacy Times.http：//www.pharmacytimes.com/publications/issue/2012/July2012/Top-200-Drugs-of-2011，accessed on Jan 9，2013；P.S.Santos，M.T.S.Mello，J.Mol.Struc.1988，178，121；El-Hibri，M.J.；Weinberg，S.A.In Encyclopedia of Polymer Scienceand Technology，Ed.Mark，H.F.Wiley：New York，2014，179]。其中，砜类化合物是一种很重要的磺酰类化合物，比如说，含砜基取代的药物如Eletriptan被用来治疗偏头痛，Mesotrione是一种除草剂。此外，砜类化合物也是非常有用的有机合成中间体，比如人名反应Ramberg-
反应，Van Leusen反应和Julia-Lythgoe烯烃化都是基于砜类化合物的转化。但从合成角度来讲，最传统的合成砜类化合物的方式主要有两种，一种是硫醚或者亚砜的氧化，另一种是亚磺酸盐与卤代烷烃的烷基化反应。在氧化制备砜类化合物的方法中，硫醚一般具有难闻的恶臭气味，还需要使用很强的氧化剂。而在取代的方法中，亚磺酸盐的来源不方便，一般是通过磺酰氯制备，而磺酰氯的制备过程往往需要苛刻的条件，还需要使用有毒和具有腐蚀性的氯化试剂，且底物限制性很大。但是由于砜类化合物具有一定的生物活性和潜在应用价值，所以，近几年来化学家不断努力去开发更高效绿色的新方法。其中通过二氧化硫的直接插入合成砜类化合物的策略吸引着化学家们的关注，发表了很多工作[for reviews：Org.Chem.Front.2018，5，691；Org.Biomol.Chem.2015，13，1592；electronicEncyclopedia of Reagents for Organic Synthesis，2018；Book：“Sulfur DioxideInsertion Reactions for Organic Synthesis”，Nature Springer：Berlin，2017；Chem.Eur.J.2018，24，1；Chem.Commun.2019，55，1013；Chem.Commun.2018，54，10405]。从中不难看出，使用稳定，易操作，易定量的二氧化硫代替品，如DABCO.(SO2)2，焦亚硫酸盐，吊白块，二氧化硫脲等来构建系列磺酰类化合物已是一种趋势，这些替代品有效避免了二氧化硫气体的直接使用，符合绿色化学的发展要求。
目前合成1，2-双磺酰基类化合物还主要通过相应硫醇底物氧化，或者通过烯烃磺酰化硫化反应，再进一步氧化构建。2019年，Tsai小组报道了以α-磺酰基取代的酮为底物与二甲基亚砜反应实现酮羰基α位的甲磺酰化反应构建了α，β-双磺酰类产物[Org.Lett.2019，21，1832]，此方法条件温和，但底物官能团取代限制性大。
烯烃双官能团化策略是一个非常高效的手段，能同时将两个官能团引入到分子中，从而一步实现复杂分子的构建。近年来，利用烯烃双官能团化策略合成砜类化合物已经发展了很多工作[Angew.Chem.Int.Ed.2013，52，7156；Fora review：Chem.Commun.2018，54，12561]。但这些方法仅仅限于单磺酰基化，而并未实现双磺酰基化反应。
发明内容
本发明目的在于提供一种简便、高效快速的[(1，2-双磺酰基)乙基]芳烃类化合物的制备方法。本发明选用便宜易得的焦亚硫酸盐作为二氧化硫的来源，利用烯烃双官能团化和二氧化硫插入策略，实现烷基卤代烃、芳基烯烃、焦亚硫酸盐和硅烷的多组分反应，一步构建1，2-双磺酰基类化合物，丰富了1，2-双磺酰基类化合物的多样性，并且提供一种简单快速得到1，2-双磺酰基类化合物的新方法，为材料领域和医药领域的研究奠定方法基础。
在极性溶剂中，硅烷和焦亚硫酸盐作用还原卤代烃产生烷基自由基，继而跟焦亚硫酸盐释放的二氧化硫分子结合产生磺酰基自由基，然后对芳基烯烃进行双自由基加成，得到1，2-双磺酰基类化合物3。
具体而言，本发明方法是在有机溶剂(如DMF)中，在加热条件下(如50℃)，磷酸二氢钠作为碱，三异丙基硅烷和焦亚硫酸盐还原卤代烃产生烷基自由基，继而跟二氧化硫分子结合产生磺酰基自由基，然后对烯烃进行双自由基加成，得到[(1，2-双磺酰基)乙基]芳烃类化合物3，其反应式为：
其中，R1为烷基；所述烷基为一级烷基和二级烷基；
Ar为苯基、含有供电子基团或吸电子基团的芳香取代基；其中，含有供电子基团的芳香取代基是对甲基苯基、对甲氧基苯基、对叔丁基苯基、邻甲基苯基、邻甲氧基苯基、间甲基苯基或者间甲氧基苯基以及噻吩环；含有吸电子基团的芳香取代基是对氯苯基、对氟苯基、对溴苯基、对三氟甲基苯基、邻氯苯基、邻氟苯基、邻溴苯基、邻三氟甲基苯基、间氯苯基、间氟苯基、间溴苯基或邻三氟甲基苯基。
R2为烷基或者氢。
本发明方法的具体步骤如下：
(1)在反应管中依次加入焦亚硫酸钾(3.0当量)、芳基烯烃(0.2mmol)、烷基卤代烃(4.0当量)，磷酸二氢钠(2.0当量)，三异丙基硅烷(2.0当量)以及有机溶剂DMF(2mL)，在惰性气体氮气或氩气保护下，于50℃搅拌24小时左右，至TLC检测完全反应；
(2)反应液用乙酸乙酯稀释，分别水和饱和食盐水萃取，有机层干燥、浓缩并柱层析分离，得到相应的[(1，2-双磺酰基)乙基]芳烃类化合物。
上述反应收率达20-80％。
该类化合物的结构经1H NMR、13C NMR、HRMS、单晶X衍射等方法表征并得以确认。
本发明中，反应体系所使用的有机溶剂优选为N，N-二甲基甲酰胺(DMF)。
本发明中，以烯烃为1.0当量，卤代烃用量为4.0当量，反应体系中焦亚硫酸钾用量为3.0当量，磷酸二氢钠为2.0当量，三异丙基硅烷为2.0当量。
本发明中，反应体系反应温度优选为50℃；反应时间为24小时左右。
本发明反应在温和简单的条件下，利用焦亚硫酸盐作为二氧化硫来源，卤代烃作为烷基来源，直接实现了烯烃的双磺酰基化反应，构建了[(1，2-双磺酰基)乙基]芳烃类化合物；该方法简单高效，底物兼容性好，原料简单易得，成本较低，且避免了传统合成方法中具有恶臭气味的硫醇类中间体的使用和氧化剂的使用，可适用于较大规模的制备，具有非常好的应用前景。
具体实施方式
实施例1
在反应管中依次加入K2S2O5(3.0当量)和Na2HPO4(2.0当量)，把试管中的空气置换成高纯度氮气后加入2mLDMF作为溶剂。然后用微量进样器依次加入对氟苯乙烯(0.2mmol)、1-碘丁烷(4.0当量)，三异丙基硅烷(2.0当量)，于50℃搅拌24小时。反应完后，反应液用EA稀释，分别用水和饱和食盐水萃取，随后有机层干燥，浓缩并柱层析分离，以57％收率得到相应的1，2-双砜基取代的化合物3a。
1H NMR(400MHz，CDCl3)δ(ppm)7.56(dd，J＝8.4，5.2Hz，2H)，7.17(t，J＝8.4Hz，2H)，4.74(dd，J＝10.7，2.1Hz，1H)，3.95(dd，J＝14.4，1.9Hz，1H)，3.69(dd，J＝14.3，10.9Hz，1H)，2.89-2.58(m，4H)，1.79-1.68(m，4H)，1.43-1.27(m，4H)，0.91-0.85(m，6H)；19FNMR(376MHz，CDCl3)δ-109.9--110.0(m)；13C NMR(100MHz，CDCl3)δ(ppm)163.6(d，1JCF＝251.3Hz)，131.4(d，3JCF＝8.2Hz)，127.1，116.7(d，2JCF＝21.8Hz)，61.7，54.5，50.6，50.3，23.8，23.5，21.6，21.5，13.4，13.4；HRMS(ESI)calcd for C16H29FNO4S+：382.1517(M+NH4 +)，found：382.1519.
实施例2
在反应管中依次加入K2S2O5(3.0当量)和Na2HPO4(2.0当量)，把试管中的空气置换成高纯度氮气后加入2mLDMF作为溶剂。然后用微量进样器依次加入2-乙烯基噻吩(0.2mmol)、1-碘丁烷(4.0当量)，三异丙基硅烷(2.0当量)，于50℃搅拌24小时。反应完后，反应液用EA稀释，分别用水和饱和食盐水萃取，随后有机层干燥，浓缩并柱层析分离，以70％收率得到相应的1，2-双砜基取代的化合物3b。
1H NMR(400MHz，CDCl3)δ(ppm)7.48(d，J＝5.0Hz，1H)，7.32(d，J＝3.3Hz，1H)，7.10(dd，J＝4.9，3.8Hz，1H)，5.00(dd，J＝10.9，2.3Hz，1H)，3.92(dd，J＝14.6，2.2Hz，1H)，3.67(dd，J＝14.5，11.0Hz，1H)，2.98-2.68(m，2H)，2.63-2.48(m，2H)，1.85-1.60(m，4H)，1.44-1.20(m，4H)，0.91-0.82(m，6H).13C NMR(100MHz，CDCl3)δ(ppm)132.4，130.2，128.7，127.8，58.5，54.3，51.4，50.0，23.8，23.7，21.6，21.5，13.4，13.3；HRMS(ESI)calcd forC14H28NO4S3 +：370.1175(M+NH4 +)，found：370.1188.
实施例3
在反应管中依次加入K2S2O5(3.0当量)，Na2HPO4(2.0当量)和对苯基苯乙烯(0.2mmol)，把试管中的空气置换成高纯度氮气后加入2mLDMF作为溶剂。然后用微量进样器依次加入4-碘丁酸乙酯(4.0当量)，三异丙基硅烷(2.0当量)，于50℃搅拌24小时。反应完后，反应液用EA稀释，分别用水和饱和食盐水萃取，随后有机层干燥，浓缩并柱层析分离，以58％收率得到相应的1，2-双砜基取代的化合物3c。
1HNMR(400MHz，CDCl3)δ(ppm)7.72-7.61(m，6H)，7.48(t，J＝7.5Hz，2H)，7.40(t，J＝7.2Hz，1H)，4.80(d，J＝10.4Hz，1H)，4.16-3.98(m，5H)，3.81(dd，J＝14.4，10.9Hz，1H)，3.08-2.73(m，4H)，2.54-2.31(m，4H)，2.18-1.97(m，4H)，1.22(t，J＝7.1Hz，6H)；13C NMR(100MHz，CDCl3)δ(ppm)171.9，171.8，143.1，139.6，130.0，129.6，129.0，128.2，128.1，127.1，62.6，60.8，53.6，50.8，49.6，32.2，32.1，17.5，17.3，14.2；HRMS(ESI)calcd forC26H35O8S2 +：539.1768(M+H+)，found：539.1750.
实施例4
在反应管中依次加入K2S2O5(3.0当量)，Na2HPO4(2.0当量)和对苯基苯乙烯(0.2mmol)，把试管中的空气置换成高纯度氮气后加入2mLDMF作为溶剂。然后用微量进样器依次加入3-碘丙醇(4.0当量)，三乙基硅烷(2.0当量)，于50℃搅拌24小时。反应完后，反应液用EA稀释，分别用水和饱和食盐水萃取，随后有机层干燥，浓缩并柱层析分离，以40％收率得到相应的1，2-双砜基取代的化合物3d。
1H NMR(400MHz，DMSO)δ(ppm)7.75-7.65(m，6H)，7.48(t，J＝7.6Hz，2H)，7.38(t，J＝7.3Hz，1H)，5.02(d，J＝9.8Hz，1H)，4.66-4.61(m，2H)，4.19(dd，J＝14.4，11.4Hz，1H)，3.89(d，J＝13.1Hz，1H)，3.45-3.21(m，5H)，3.05-2.92(m，3H)，1.84-1.66(m，4H).；13C NMR(100MHz，DMSO)δ(ppm)141.2，139.7，131.2，130.9，129.4，128.2，127.2，127.2，61.6，59.3，59.2，50.9，50.2，47.3，25.0，24.4；HRMS(ESI)calcd for C20H26NaO6S2 +：449.1063(M+Na+)，found：449.1052.
Claims (9)
1.一种[(1，2-双磺酰基)乙基]芳烃类化合物，其特征在于，其结构式如下：
其中，R1为烷基；
Ar为苯基、含有供电子基团或吸电子基团的芳香取代基；其中，含有供电子基团的芳香取代基是对甲基苯基、对甲氧基苯基、对叔丁基苯基、邻甲基苯基、邻甲氧基苯基、间甲基苯基或者间甲氧基苯基以及噻吩环；含有吸电子基团的芳香取代基是对氯苯基、对氟苯基、对溴苯基、对三氟甲基苯基、邻氯苯基、邻氟苯基、邻溴苯基、邻三氟甲基苯基、间氯苯基、间氟苯基、间溴苯基或邻三氟甲基苯基；
R2为烷基或者氢；所述烷基为一级烷基。
2.一种权利要求1所述[(1，2-双磺酰基)乙基]芳烃类化合物的制备方法，其特征在于，具体步骤如下：
(1)在反应管中依次加入一定量的焦亚硫酸盐、芳基烯烃、烷基卤代烃、碱、硅烷以及有机溶剂，在惰性气体氮气或氩气保护下，于45-55℃搅拌20-28小时，至TLC检测完全反应；
(2)反应液用乙酸乙酯稀释，分别用水和饱和食盐水萃取，有机层干燥、浓缩并柱层析分离，得到相应的[(1，2-双磺酰基)乙基]芳烃类化合物。
3.根据权利要求2所述的制备方法，其特征在于，所述有机溶剂为DMF、DMSO、NMP或DME。
4.根据权利要求3所述的制备方法，其特征在于，所述有机溶剂为DMF。
5.根据权利要求2所述的制备方法，其特征在于，所述硅烷为三异丙基硅烷。
6.根据权利要求2所述的制备方法，其特征在于，所述碱为磷酸二氢钠。
7.根据权利要求2所述的制备方法，其特征在于，所述焦亚硫酸盐为焦亚硫酸钾或焦亚硫酸钠。
8.根据权利要求2所述的制备方法，其特征在于，以芳基烯烃为1.0当量计，焦亚硫酸盐用量为3.0当量，烷基卤代烃用量为4.0当量，碱的用量为2.0当量，硅烷的用量为2.0当量，以烯烃量计有机溶剂用量为0.1M，体系反应温度为50℃；反应时间为24h左右。
9.根据权利要求2所述的制备方法，其特征在于，柱层析采用的流动相为石油醚和乙酸乙酯，石油醚和乙酸乙酯体积比例为4∶1-2∶1。
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