CN111377838A - 一种大位阻烷基-烷基砜类化合物及其合成方法和应用 - Google Patents
一种大位阻烷基-烷基砜类化合物及其合成方法和应用 Download PDFInfo
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- CN111377838A CN111377838A CN202010157412.1A CN202010157412A CN111377838A CN 111377838 A CN111377838 A CN 111377838A CN 202010157412 A CN202010157412 A CN 202010157412A CN 111377838 A CN111377838 A CN 111377838A
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- Prior art keywords
- alkyl
- cycloalkyl
- straight
- hydrogen
- ester
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Links
- 238000010189 synthetic method Methods 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 68
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims abstract description 26
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 14
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 5
- 239000000463 material Substances 0.000 claims abstract description 5
- 239000000575 pesticide Substances 0.000 claims abstract description 5
- 238000001308 synthesis method Methods 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 3
- 150000002148 esters Chemical class 0.000 claims description 108
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 98
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 96
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 91
- 125000000217 alkyl group Chemical group 0.000 claims description 89
- -1 aryl C1-C10 alkyl Chemical group 0.000 claims description 87
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 claims description 53
- 239000002904 solvent Substances 0.000 claims description 51
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 50
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 50
- 230000002829 reductive effect Effects 0.000 claims description 49
- 239000011592 zinc chloride Substances 0.000 claims description 49
- 235000005074 zinc chloride Nutrition 0.000 claims description 49
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 47
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 44
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 42
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 16
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 15
- 239000000654 additive Substances 0.000 claims description 14
- 230000000996 additive effect Effects 0.000 claims description 13
- 235000010269 sulphur dioxide Nutrition 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 11
- 125000004344 phenylpropyl group Chemical group 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 230000009471 action Effects 0.000 claims description 4
- 125000004946 alkenylalkyl group Chemical group 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
- 125000005038 alkynylalkyl group Chemical group 0.000 claims description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 4
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 4
- 239000012039 electrophile Substances 0.000 claims description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 4
- PQXKHYXIUOZZFA-UHFFFAOYSA-M lithium fluoride Chemical compound [Li+].[F-] PQXKHYXIUOZZFA-UHFFFAOYSA-M 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 claims description 4
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 claims description 4
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- VFTFKUDGYRBSAL-UHFFFAOYSA-N 15-crown-5 Chemical compound C1COCCOCCOCCOCCO1 VFTFKUDGYRBSAL-UHFFFAOYSA-N 0.000 claims description 2
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims description 2
- CMNQIVHHHBBVSC-UHFFFAOYSA-N 5-hydroxy-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=C1C=CC=C2O CMNQIVHHHBBVSC-UHFFFAOYSA-N 0.000 claims description 2
- 229920000858 Cyclodextrin Polymers 0.000 claims description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 2
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 150000004996 alkyl benzenes Chemical class 0.000 claims description 2
- 150000001347 alkyl bromides Chemical class 0.000 claims description 2
- 229940077388 benzenesulfonate Drugs 0.000 claims description 2
- CHQVQXZFZHACQQ-UHFFFAOYSA-M benzyl(triethyl)azanium;bromide Chemical compound [Br-].CC[N+](CC)(CC)CC1=CC=CC=C1 CHQVQXZFZHACQQ-UHFFFAOYSA-M 0.000 claims description 2
- DSTSOVPKKRBGSU-UHFFFAOYSA-M benzyl(triethyl)azanium;fluoride Chemical compound [F-].CC[N+](CC)(CC)CC1=CC=CC=C1 DSTSOVPKKRBGSU-UHFFFAOYSA-M 0.000 claims description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 2
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019797 dipotassium phosphate Nutrition 0.000 claims description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 2
- HQRPHMAXFVUBJX-UHFFFAOYSA-M lithium;hydrogen carbonate Chemical compound [Li+].OC([O-])=O HQRPHMAXFVUBJX-UHFFFAOYSA-M 0.000 claims description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 2
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 claims description 2
- MOVBJUGHBJJKOW-UHFFFAOYSA-N methyl 2-amino-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1N MOVBJUGHBJJKOW-UHFFFAOYSA-N 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- RWPGFSMJFRPDDP-UHFFFAOYSA-L potassium metabisulfite Chemical compound [K+].[K+].[O-]S(=O)S([O-])(=O)=O RWPGFSMJFRPDDP-UHFFFAOYSA-L 0.000 claims description 2
- 229940043349 potassium metabisulfite Drugs 0.000 claims description 2
- 235000010263 potassium metabisulphite Nutrition 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 claims description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- DDFYFBUWEBINLX-UHFFFAOYSA-M tetramethylammonium bromide Chemical compound [Br-].C[N+](C)(C)C DDFYFBUWEBINLX-UHFFFAOYSA-M 0.000 claims description 2
- RXMRGBVLCSYIBO-UHFFFAOYSA-M tetramethylazanium;iodide Chemical compound [I-].C[N+](C)(C)C RXMRGBVLCSYIBO-UHFFFAOYSA-M 0.000 claims description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims description 2
- 229940102001 zinc bromide Drugs 0.000 claims description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 238000013086 organic photovoltaic Methods 0.000 claims 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 229910052751 metal Inorganic materials 0.000 abstract description 5
- 239000002184 metal Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 3
- 125000000524 functional group Chemical group 0.000 abstract description 3
- 150000002894 organic compounds Chemical class 0.000 abstract description 2
- 239000002699 waste material Substances 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 190
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 141
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 96
- 239000012074 organic phase Substances 0.000 description 92
- 229910052757 nitrogen Inorganic materials 0.000 description 48
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 47
- 238000005160 1H NMR spectroscopy Methods 0.000 description 47
- 238000004440 column chromatography Methods 0.000 description 47
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 45
- 238000012544 monitoring process Methods 0.000 description 40
- 238000010791 quenching Methods 0.000 description 40
- 230000000171 quenching effect Effects 0.000 description 40
- BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 38
- YYEROYLAYAVZNW-UHFFFAOYSA-N 2-methyl-2-phenylpropanoic acid Chemical compound OC(=O)C(C)(C)C1=CC=CC=C1 YYEROYLAYAVZNW-UHFFFAOYSA-N 0.000 description 20
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 19
- 238000002390 rotary evaporation Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- WVLBCYQITXONBZ-UHFFFAOYSA-N trimethyl phosphate Chemical compound COP(=O)(OC)OC WVLBCYQITXONBZ-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 4
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 3
- JIMXXGFJRDUSRO-UHFFFAOYSA-N adamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC2CC1(C(=O)O)C3 JIMXXGFJRDUSRO-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- IJCUWQJHCMMQRC-UHFFFAOYSA-N 1-tert-butyl-4-methylsulfonylbenzene Chemical compound CC(C)(C)C1=CC=C(S(C)(=O)=O)C=C1 IJCUWQJHCMMQRC-UHFFFAOYSA-N 0.000 description 2
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 2
- OFJWFSNDPCAWDK-UHFFFAOYSA-N 2-phenylbutyric acid Chemical compound CCC(C(O)=O)C1=CC=CC=C1 OFJWFSNDPCAWDK-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- UAXOELSVPTZZQG-UHFFFAOYSA-N tiglic acid Natural products CC(C)=C(C)C(O)=O UAXOELSVPTZZQG-UHFFFAOYSA-N 0.000 description 2
- CNBUSIJNWNXLQQ-NSHDSACASA-N (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical class CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CNBUSIJNWNXLQQ-NSHDSACASA-N 0.000 description 1
- KEJGAYKWRDILTF-JDDHQFAOSA-N (3ar,5s,6s,6ar)-5-[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-6-ol Chemical class O1C(C)(C)OC[C@@H]1[C@@H]1[C@H](O)[C@H]2OC(C)(C)O[C@H]2O1 KEJGAYKWRDILTF-JDDHQFAOSA-N 0.000 description 1
- VDLWTJCSPSUGOA-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)CCCC2=C1 VDLWTJCSPSUGOA-UHFFFAOYSA-N 0.000 description 1
- IDMKVUTYPXAVHL-UHFFFAOYSA-N 1-(3-methoxypropyl)cyclohexane-1-carboxylic acid Chemical compound COCCCC1(C(O)=O)CCCCC1 IDMKVUTYPXAVHL-UHFFFAOYSA-N 0.000 description 1
- BYJIXWOWTNEVFO-UHFFFAOYSA-N 1-(4-bromophenyl)cyclopropane-1-carboxylic acid Chemical compound C=1C=C(Br)C=CC=1C1(C(=O)O)CC1 BYJIXWOWTNEVFO-UHFFFAOYSA-N 0.000 description 1
- VMKOFRJSULQZRM-UHFFFAOYSA-N 1-bromooctane Chemical compound CCCCCCCCBr VMKOFRJSULQZRM-UHFFFAOYSA-N 0.000 description 1
- YZWKKMVJZFACSU-UHFFFAOYSA-N 1-bromopentane Chemical compound CCCCCBr YZWKKMVJZFACSU-UHFFFAOYSA-N 0.000 description 1
- REHQLKUNRPCYEW-UHFFFAOYSA-N 1-methylcyclohexane-1-carboxylic acid Chemical compound OC(=O)C1(C)CCCCC1 REHQLKUNRPCYEW-UHFFFAOYSA-N 0.000 description 1
- PRPINYUDVPFIRX-UHFFFAOYSA-N 1-naphthaleneacetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CC=CC2=C1 PRPINYUDVPFIRX-UHFFFAOYSA-N 0.000 description 1
- RHPCYZLXNNRRMB-UHFFFAOYSA-N 1-phenylcyclopentane-1-carboxylic acid Chemical compound C=1C=CC=CC=1C1(C(=O)O)CCCC1 RHPCYZLXNNRRMB-UHFFFAOYSA-N 0.000 description 1
- IWWCCNVRNHTGLV-UHFFFAOYSA-N 1-phenylcyclopropane-1-carboxylic acid Chemical compound C=1C=CC=CC=1C1(C(=O)O)CC1 IWWCCNVRNHTGLV-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
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- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
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- SISAYUDTHCIGLM-UHFFFAOYSA-N bromine dioxide Inorganic materials O=Br=O SISAYUDTHCIGLM-UHFFFAOYSA-N 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- FLHFTXCMKFVKRP-UHFFFAOYSA-N bromomethylcyclobutane Chemical compound BrCC1CCC1 FLHFTXCMKFVKRP-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000001723 carbon free-radicals Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
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- 238000003776 cleavage reaction Methods 0.000 description 1
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- 229960003627 gemfibrozil Drugs 0.000 description 1
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- 229960001680 ibuprofen Drugs 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- 238000006452 multicomponent reaction Methods 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
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- 238000005580 one pot reaction Methods 0.000 description 1
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- WUPVYJJCKYSGCR-UHFFFAOYSA-M sodium;3-oxoisoindol-1-olate Chemical compound [Na+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 WUPVYJJCKYSGCR-UHFFFAOYSA-M 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000004291 sulphur dioxide Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
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- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
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Abstract
本发明属于有机化合物合成及应用技术领域,公开了一种如式(4)所示的大位阻烷基‑烷基砜类化合物及其合成方法,以羧酸衍生的氧化还原酯、还原性二氧化硫源以及烷基亲电试剂为原料,三组分一锅法得到一系列大位阻的烷基‑烷基砜类化合物。本发明合成方法原料来源广泛、廉价易得;反应操作简单;官能团耐受性强;该反应中还原性二氧化硫源的使用避免了额外当量金属还原试剂的加入,经济实用,避免了对环境的废金属污染。本发明还公开了所述烷基‑烷基砜类化合物在制备药物、农药、有机光电材料等中的应用。本发明具有较强的实用价值和广泛的应用前景。
Description
技术领域
本发明属于有机化合物合成及应用技术领域,涉及一种大位阻烷基-烷基砜类化合物及其合成方法和应用。
背景技术
砜类化合物是一类非常重要的含硫化合物,其广泛存在于药物、农药、有机光电材料及天然产物中。因此,从廉价易得、来源广泛的商业原料出发高效环保地构建砜类化合物显得尤为重要。
传统合成砜类化合物的方法主要是由硫醇在过渡金属催化下构建硫醚类化合物,随后在强氧化剂作用下制备得到。然而现有方法存在的缺陷包括:(1)不可避免使用到有毒、恶臭、易被氧化的硫醇(硫酚);(2)强氧化剂的使用使其原子经济性、官能团兼容性较差;(3)需要多步合成,步骤经济性较差。因此,发展一种简洁高效、操作简便的构建砜类化合物的方法具有重要意义。
发明内容
为了克服现有技术的上述缺陷,本发明创新性地提出了一种以商业可得、广泛存在的式(1)氧化还原酯(羧酸衍生的/羧酸原料制备的氧化还原酯)为底物,以式(2)为还原性二氧化硫源,以式(3)烷基亲电试剂为烷基源,在溶剂中,在添加剂(添加剂1、添加剂2)、碱的作用下三组分一锅法合成一系列式(4)大位阻烷基-烷基砜类化合物。本发明避免了有毒、恶臭的硫醇的使用,避免了在反应后期使用强氧化剂调整氧化态。本发明合成方法反应操作简单,原料廉价易得,来源广泛,底物普适性广,官能团耐受性强;该反应中还原性二氧化硫源的使用避免了额外当量金属还原试剂的加入,经济实用,避免了对环境的废金属污染;产率(30%-85%)高;本发明具有较强的实用价值和广泛的应用前景。
所述反应过程如下反应式(A)所示:
其中,R1,R2,R3是各种烷基化合物基团。R也是各类烷基化合物基团。
优选地,R1为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R2为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R3为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢。R为直链烷基、环烷基、烷氧基烷基、芳基烷基、烯基烷基、炔基烷基。
进一步优选地,R1为C1-C10直链烷基、C1-C10环烷基、芳基C1-C10烷基、含不饱和键的C1-C10烷基或氢;R2为C1-C10直链烷基、C1-C10环烷基、芳基C1-C10烷基、含不饱和键的C1-C10烷基或氢;R3为C1-C10直链烷基、C1-C10环烷基、芳基C1-C10烷基、含不饱和键的C1-C10烷基或氢。R为C1-C10直链烷基、C1-C10环烷基、烷氧基C1-C10烷基、芳基C1-C10烷基、烯基C1-C10烷基、炔基C1-C10烷基。
进一步优选地,R1为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R2为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R3为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢。R为甲基、乙基、正戊基、正庚基、正辛基、苯丙基、苯丁基、甲基环丁基、苯氧基乙基、正戊烯基、正丁炔基、噻吩乙基等。
进一步优选地,R1,R2,R3,R4分别独立地选自甲基、乙基、正戊基、正庚基、正辛基、苯丙基、苯丁基、甲基环丁基、苯氧基乙基、正戊烯基、正丁炔基、噻吩乙基等。
本发明中,所述反应温度为60-140℃;优选地,反应温度为120℃。
本发明中,所述反应的时间为6-20小时;优选地,反应时间为2-20小时;进一步优选地,反应时间为15小时。
本发明中,所述溶剂选自N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲亚砜、N-甲基吡咯烷酮、乙腈、水、四氢呋喃、1,4-二氧六环、环戊基甲醚、乙醚、叔丁基甲醚等中的一种或多种;优选地,反应溶剂为N,N-二甲基甲酰胺:乙腈(2:1)。
本发明中,所述还原性二氧化硫源选自连二亚硫酸钠(保险粉)、焦亚硫酸钠、焦亚硫酸钾、二氧化硫脲、甲醛合次硫酸氢钠等中的一种或多种;优选地,二氧化硫源为连二亚硫酸钠。
本发明中,烷基亲电试剂为烷基溴、烷基苯磺酸酯(OTs)、烷基磷酸酯等中的一种或多种。
本发明中,所述式(1)氧化还原酯与所述式(2)还原性二氧化硫源、所述式(3)烷基亲电试剂的摩尔比用量为1:(1-8):(1-8);优选地,为1:2:3。
本发明中,所述碱选自碳酸钾、碳酸钠、碳酸锂、碳酸氢钾、碳酸氢钠、碳酸氢锂、磷酸钾、磷酸氢钾、氢氧化钾、氢氧化钠、三乙胺、N,N’-二异丙基乙胺、N,N’-二甲基乙二胺等中的一种或多种;优选地,为N,N’-二异丙基乙胺。本发明中,所述式(1)氧化还原酯与所述碱的摩尔比为1:(1-5);优选地,为1:2。
本发明中,所述添加剂1选自氯化镁、氯化锌、氯化锂、溴化锌、碘化锌、氯化锡、氯化铝、氟化锂等中的一种或多种;优选地,为氯化锌。本发明中,所述式(1)氧化还原酯与所述添加剂1的摩尔比为1:(1-5);优选地,为1:0.5。
本发明中,所述添加剂2选自四甲基氟化铵、四甲基氯化铵、四甲基溴化铵、四甲基碘化铵、四丁基氟化铵、四丁基氯化铵、四丁基溴化铵、四丁基碘化铵、四丁基四氟硼酸铵、四丁基六氟磷酸铵、苄基三乙基氟化铵、苄基三乙基氯化铵、苄基三乙基溴化铵、苄基三乙基碘化铵、15-冠-5、18-冠-6、环糊精、聚乙二醇等中的一种或多种;优选地,为四丁基溴化铵。本发明中,所述式(1)氧化还原酯与所述添加剂2的摩尔比为1:(1-5);优选地,为1:1.5。
本发明中,所述反应优选在氮气保护下进行。
本发明中,当采用氧化还原酯、还原性二氧化硫源、磷酸酯为反应原料,在碱性催化剂、添加剂的作用下,反应机理如反应式(B)所示:
首先,连二亚硫酸钠均裂,提供了两个二氧化硫自由基阴离子7。羧基衍生的氧化还原活性酯1经过单电子转移形成中间体8,并且氯化锌会与其发生螯合作用。中间体8的裂解通过在氯化锌的帮助下脱掉一分子二氧化碳,得到了碳自由基9和邻苯二甲酰亚胺钠盐(NaNPhth)。通过碳自由基9捕获另一个二氧化硫自由基阴离子7,得到磺酰基阴离子10和亚磺酸盐10'。最后,与中间体10的“软”配偶进行烷基化偶联,得到所需的砜产物3。
在一个具体的实施方式中:所述反应过程如下反应式(A’)所示。
其中,R1,R2,R3是各种烷基化合物基团。R也是各类烷基化合物基团。
优选地,R1为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R2为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R3为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢。R为直链烷基、环烷基、烷氧基烷基、芳基烷基、烯基烷基、炔基烷基。
进一步优选地,R1为C1-C10直链烷基、C1-C10环烷基、芳基C1-C10烷基、含不饱和键的C1-C10烷基或氢;R2为C1-C10直链烷基、C1-C10环烷基、芳基C1-C10烷基、含不饱和键的C1-C10烷基或氢;R3为C1-C10直链烷基、C1-C10环烷基、芳基C1-C10烷基、含不饱和键的C1-C10烷基或氢。R为C1-C10直链烷基、C1-C10环烷基、烷氧基C1-C10烷基、芳基C1-C10烷基、烯基C1-C10烷基、炔基C1-C10烷基。
进一步优选地,R1为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R2为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R3为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢。R为甲基、乙基、正戊基、正庚基、正辛基、苯丙基、苯丁基、甲基环丁基、苯氧基乙基、正戊烯基、正丁炔基、噻吩乙基等。
进一步优选地,R1,R2,R3,R4分别独立地选自甲基、乙基、正戊基、正庚基、正辛基、苯丙基、苯丁基、甲基环丁基、苯氧基乙基、正戊烯基、正丁炔基、噻吩乙基等。
本发明还提出了如式(4)所示的烷基-烷基砜类化合物
其中,R1,R2,R3是各种烷基化合物基团。R也是各类烷基化合物基团。
优选地,R1为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R2为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R3为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢。R为直链烷基、环烷基、烷氧基烷基、芳基烷基、烯基烷基、炔基烷基。
进一步优选地,R1为C1-C10直链烷基、C1-C10环烷基、芳基C1-C10烷基、含不饱和键的C1-C10烷基或氢;R2为C1-C10直链烷基、C1-C10环烷基、芳基C1-C10烷基、含不饱和键的C1-C10烷基或氢;R3为C1-C10直链烷基、C1-C10环烷基、芳基C1-C10烷基、含不饱和键的C1-C10烷基或氢。R为C1-C10直链烷基、C1-C10环烷基、烷氧基C1-C10烷基、芳基C1-C10烷基、烯基C1-C10烷基、炔基C1-C10烷基。
进一步优选地,R1为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R2为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R3为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢。R为甲基、乙基、正戊基、正庚基、正辛基、苯丙基、苯丁基、甲基环丁基、苯氧基乙基、正戊烯基、正丁炔基、噻吩乙基等。
进一步优选地,R1,R2,R3,R4分别独立地选自甲基、乙基、正戊基、正庚基、正辛基、苯丙基、苯丁基、甲基环丁基、苯氧基乙基、正戊烯基、正丁炔基、噻吩乙基等。
本发明还提出了由上述合成方法制备得到的如式(4)所示的烷基-烷基砜类化合物。
本发明还提出了所述式(4)所示的烷基-烷基砜类化合物在制备药物、农药、有机光电材料等中的应用。
本发明的有益效果在于:本发明创新性地提出了一种无需额外引发剂,一步直接由氧化还原酯、还原性二氧化硫源、烷基亲电试剂的多组分反应高效构建烷基-烷基砜类化合物的方法。该方法避免了传统方法中有毒、恶臭的硫醇的使用,同时无需使用强氧化剂调整氧化态;且在该反应中,创新性地使用还原性二氧化硫源,无需加入当量金属还原试剂即可顺利发生反应。本发明制备的烷基-烷基砜类化合物在药物、农药、有机光电材料等领域具有广泛的应用。
具体实施方式
结合以下具体实施例,对本发明作进一步的详细说明,本发明的保护内容不局限于以下实施例。在不背离发明构思的精神和范围下,本领域技术人员能够想到的变化和优点都被包括在本发明中,并且以所附的权利要求书为保护范围。实施本发明的过程、条件、试剂、实验方法等,除以下专门提及的内容之外,均为本领域的普遍知识和公知常识,本发明没有特别限制内容。以下实施例所给出的数据包括具体操作和反应条件及产物。产物纯度通过核磁鉴定。
实施例1
化合物3a的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3a(34.6mg),收率为73%。1H NMR(400MHz,CDCl3)δ7.68–7.59(m,2H),7.42–7.34(m,3H),2.61–2.51(m,2H),1.84(s,6H),1.66–1.57(m,2H),1.33–1.25(m,2H),0.82(t,J=7.3Hz,3H).13C NMR(100MHz,CDCl3)δ137.7,128.5,128.5,127.9,64.7,46.1,22.7,22.5,21.8,13.4.IRν2960,2873,1467,1450,1290,1271,1118,1095,777,698,661cm-1;HRMS(EI)for C13H20O2S Calculated:240.1184,found:240.1180.
实施例2
化合物3b的合成:
向反应管中加入1-苯基-1-环丙羧酸衍生的氧化还原酯(61.5mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3b(36.2mg),收率为76%。1H NMR(400MHz,CDCl3)δ7.56(dd,J=6.5,3.0Hz,2H),7.40–7.35(m,3H),2.88–2.80(m,2H),1.82–1.79(m,2H),1.78–1.71(m,2H),1.41–1.32(m,2H),1.28–1.24(m,2H),0.89(t,J=7.3Hz,3H).13C NMR(100MHz,CDCl3)δ134.6,131.7,129.0,128.7,49.9,44.7,23.6,21.7,13.5,11.7.IRν2962,2873,1494,1448,1415,1298,1130,933,808,700,665cm-1;HRMS(EI)for C13H18O2S Calculated:238.1028,found:238.1031.
实施例3
化合物3c的合成:
向反应管中加入1-(4-溴苯基)环丙甲酸衍生的氧化还原酯(77.2mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3b(38.7mg),收率为61%。1H NMR(400MHz,CDCl3)δ7.54–7.48(m,2H),7.47–7.40(m,2H),2.84–2.80(m,2H),1.82–1.79(m,2H),1.76–1.71(m,2H),1.42–1.33(m,2H),1.25–1.21(m,2H),0.89(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ133.7,133.2,132.0,123.4,50.0,44.1,23.6,21.7,13.5,11.7.IRν2960,2873,1490,1396,1309,1296,1131,1091,1010,835,713,686,597cm-1;HRMS(EI)for C13H17BrO2S Calculated:316.0133,found:316.0130.
实施例4
化合物3d的合成:
向反应管中加入1-(2,2-二氟苯并[D][1,3]二氧杂环戊烯-5-基)环丙烷甲酸衍生的氧化还原酯(77.5mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3d(31.8mg),收率为50%。1H NMR(400MHz,CDCl3)δ7.26(d,J=1.7Hz,1H),7.21–7.19(m,1H),6.98(d,J=8.0Hz,1H),2.80–2.76(m,2H),1.77–1.74(m,2H),1.71–1.67(m,2H),1.37–1.28(m,2H),1.19–1.17(m,2H),0.84(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ144.2,143.8,131.7(t,J=255Hz),130.7,127.0,113.2,109.4,49.9,44.4,23.5,21.7,13.5,12.2.19F NMR(376MHz,CDCl3)δ-49.81.IRν2966,2877,1500,1440,1240,1157,1126,1033,906,896,821,705,626cm-1;HRMS(EI)for C14H16F2O4S Calculated:318.0737,found:318.0742.
实施例5
化合物3e的合成:
向反应管中加入1-苯基环戊烷羧酸衍生的氧化还原酯(67.1mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3e(41.0mg),收率为77%。1H NMR(400MHz,CDCl3)δ7.58(dd,J=8.1,1.3Hz,2H),7.41–7.32(m,3H),2.78–2.71(m,2H),2.57–2.53(m,2H),2.43–2.37(m,2H),2.03–1.92(m,2H),1.73–1.64(m,2H),1.63–1.54(m,2H),1.31–1.25(m,2H),0.82(t,J=7.3Hz,3H).13CNMR(100MHz,CDCl3)δ137.7,129.0,128.5,128.4,76.1,47.6,33.8,24.6,22.8,21.8,13.5.IRν2958,2873,1448,1282,1269,1120,756,700,607cm-1;HRMS(ESI)for C15H22O2SNa+Calculated:289.1233,[M+Na]+found:289.1229.
实施例6
化合物3f的合成:
向反应管中加入金刚烷甲酸衍生的氧化还原酯(65.0mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3f(35.9mg),收率为70%。1H NMR(400MHz,CDCl3)δ7.88(d,J=8.6Hz,2H),7.72(d,J=8.6Hz,2H),7.51(s,1H),3.04(s,3H),2.23(s,3H).13C NMR(100MHz,CDCl3)δ168.6,142.7,135.2,128.7,119.5,44.6,24.8.IRν3026,1683,1643,1587,1529,1417,1363,1224,964,821,765cm-1;HRMS(EI)for C9H11NO3S Calculated:213.0460,found:213.0461.
实施例7
化合物3g的合成:
向反应管中加入1-(3-甲氧基丙基)环己烷-1-甲酸衍生地氧化还原酯(69.0mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3g(35.9mg),收率为65%。1H NMR(400MHz,CDCl3)δ3.39(t,J=5.7Hz,2H),3.32(s,3H),2.89–2.85(m,2H),1.97–1.89(m,2H),1.87–1.79(m,8H),1.75–1.66(m,3H),1.51–1.40(m,4H),1.27–1.19(m,1H),0.95(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ72.6,64.9,58.5,46.1,28.3,26.9,24.9,23.8,22.5,22.1,21.2,13.6;IRν2931,2872,2827,1462,1286,1267,1118,1097,852,705,678cm-1;HRMS(EI)for C14H28O3SCalculated:276.1759,found:276.1752.
实施例8
化合物3h的合成:
向反应管中加入1-甲基-1-环已羧酸衍生的氧化还原酯(57.4mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3h(29.7mg),收率为68%。1H NMR(400MHz,CDCl3)δ2.84(m,2H),1.90–1.80(m,4H),1.76–1.65(m,5H),1.50–1.36(m,7H),1.18(d,J=11.2Hz,1H),0.93(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ62.3,44.8,29.3,25.0,22.3,22.0,21.2,17.1,13.6;IRν2937,2870,2850,1465,1263,1136,1091,975,856,790,727,680cm-1;HRMS(EI)forC11H22O2S Calculated:218.1341,found:218.1345.
实施例9
化合物3i的合成:
向反应管中加入特戊酸衍生的氧化还原酯(49.5mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3i(20.7mg),收率为58%。1H NMR(400MHz,CDCl3)δ2.93–2.87(m,2H),1.92–1.83(m,2H),1.53–1.45(m,2H),1.41(s,9H),0.97(t,J=7.3Hz,3H).13C NMR(100MHz,CDCl3)δ58.8,45.3,23.5,22.5,22.1,13.6.IRν2960,2857,1465,1288,1269,1112,808,756,713,657cm-1;HRMS(ESI)for C8H18O2SH+Calculated:179.1112,[M+H]+found:179.1098.
实施例10
化合物3j的合成:
向反应管中加入环己基甲酸衍生的氧化还原酯(55.0mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3j(22.0mg),收率为54%。1H NMR(400MHz,CDCl3)δ2.92–2.86(m,2H),2.85–2.78(m,1H),2.14(d,J=11.4Hz,2H),1.92(d,J=13.1Hz,2H),1.84–1.77(m,2H),1.74(s,1H),1.59–1.51(m,2H),1.49–1.43(m,2H),1.34–1.20(m,3H),0.95(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ60.8,49.1,25.0(7),25.0(5),25.0,23.3,21.9,13.5.IRν2935,2858,1452,1361,1298,1265,1222,1130,1111,894,823,700cm-1;HRMS(EI)for C10H20O2SCalculated:204.1184,found:204.1181.
实施例11
化合物3k的合成:
向反应管中加入1,2,3,4-四氢-1-萘甲酸衍生的氧化还原酯(64.3mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3k(25.2mg),收率为50%。1H NMR(400MHz,CDCl3)δ7.47(d,J=7.6Hz,1H),7.23–7.17(m,1H),7.12(dd,J=16.3,7.7Hz,2H),4.27–4.20(m,1H),2.87–2.67(m,4H),2.48–2.39(m,1H),2.18–2.07(m,2H),1.75–1.64(m,3H),1.38–1.29(m,2H),0.84(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ139.5,131.0,129.7,128.6,127.2,126.1,62.9,49.9,28.8,23.9,23.3,21.9,19.7,13.6.IRν2958,2937,2873,1452,1294,1122,815,773,738,569cm-1;HRMS(EI)for C14H20O2S Calculated:252.1184,found:252.1186.
实施例12
化合物3l的合成:
向反应管中加入2-茚羧酸衍生的氧化还原酯(61.5mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3l(25.0mg),收率为52%。1H NMR(400MHz,CDCl3)δ7.26–7.18(m,4H),3.97–3.88(m,1H),3.55–3.49(m,2H),3.37–3.31(m,2H),2.94–2.88(m,2H),1.90–1.81(m,2H),1.51–1.42(m,2H),0.95(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ139.4,127.3,124.5,60.7,50.8,33.4,23.4,21.8,13.5.IRν2958,2931,2873,1460,1313,1267,1244,1124,997,738,628cm-1;HRMS(EI)for C13H18O2S Calculated:238.1028,found:238.1023.
实施例13
化合物3m的合成:
向反应管中加入2-苯基丁酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3m(28.8mg),收率为60%。1H NMR(400MHz,CDCl3)δ7.47–7.32(m,5H),3.90(dd,J=11.3,3.7Hz,1H),2.70–2.55(m,2H),2.52–2.42(m,1H),2.16–2.14(m,1H),1.73–1.63(m,2H),1.35–1.28(m,2H),0.90–0.83(m,6H).13CNMR(100MHz,CDCl3)δ133.1,129.4,129.0,129.0,70.1,50.4,23.5,21.7,20.7,13.4,11.4.IR(film)ν2935,2875,1454,1313,1288,1132,802,700,611cm-1;HRMS(EI)for C13H20O2S Calculated:240.1184,found:240.1187.
实施例14
化合物3n的合成:
向反应管中加入2-甲基丁酸衍生的氧化还原酯(49.5mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3n(23.9mg),收率为65%。1H NMR(400MHz,CDCl3)δ2.97–2.88(m,2H),2.87–2.81(m,1H),2.15–2.01(m,1H),1.86–1.78(m,2H),1.61–1.52(m,1H),1.52–1.43(m,2H),1.37(d,J=6.9Hz,3H),1.05(t,J=7.5Hz,3H),0.96(t,J=7.3Hz,3H).13C NMR(100MHz,CDCl3)δ58.9,49.3,23.3,22.1,21.9,13.5,12.3,11.2.IRν2966,2875,1465,1296,1132,962,914,850,800cm-1;HRMS(EI)for C8H18O2S Calculated:178.1028,found:178.1027.
实施例15
化合物3o的合成:
向反应管中加入萘乙酸衍生的氧化还原酯(66.3mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3o(16.3mg),收率为31%。1H NMR(400MHz,CDCl3)δ8.13(d,J=8.5Hz,1H),7.90(dd,J=8.1,3.1Hz,2H),7.64–7.56(m,2H),7.56–7.47(m,2H),4.74(s,2H),2.91–2.85(m,2H),1.83–1.75(m,2H),1.42–1.33(m,2H),0.88(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ134.1,132.1,130.3,130.0,129.0,127.0,126.3,125.3,124.4,123.7,56.7,51.4,23.6,21.7,13.4.IR(film)ν3049,2960,2922,2873,1313,1271,1126,808,779,648cm-1;HRMS(EI)for C15H18O2S Calculated:262.1028,found:262.1025.
实施例16
化合物3p的合成:
向反应管中加入布洛芬衍生的氧化还原酯(67.1mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3p(32.2mg),收率为57%。1H NMR(400MHz,CDCl3)δ7.33(d,J=8.1Hz,2H),7.16(d,J=8.1Hz,2H),4.15(q,J=7.2Hz,1H),2.74–2.62(m,2H),2.47(d,J=7.2Hz,2H),1.89–1.82(m,1H),1.76(d,J=7.2Hz,3H),1.73–1.62(m,2H),1.37–1.30(m,2H),0.89(dd,J=6.6,0.7Hz,6H),0.85(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ142.8,131.7,129.7,128.6,63.0,49.6,45.0,30.1,23.5,22.3,21.7,13.6,13.4.IRν2958,1512,1467,1315,1132,852,806,760cm-1;HRMS(EI)for C16H26O2S Calculated:282.1654,found:282.1659.
实施例17
化合物3q的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),乙基溴(65.4mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3q(30.2mg),收率为71%。1H NMR(400MHz,CDCl3)δ7.64(dd,J=8.1,1.2Hz,2H),7.43–7.33(m,3H),2.61(q,J=7.5Hz,2H),1.85(s,6H),1.16(t,J=7.5Hz,3H).13C NMR(100MHz,CDCl3)δ137.71,128.53,128.49,127.92,64.56,40.89,22.53,5.21.IR(film)ν2983,1498,1450,1292,1159,1118,1095,1045,777,698,578cm-1;HRMS(EI)for C11H16O2S Calculated:212.0871,found:212.0874.
实施例18
化合物3r的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正戊基溴(90.6mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3r(37.0mg),收率为73%。1H NMR(400MHz,CDCl3)δ7.67–7.60(m,2H),7.37(m,3H),2.60–2.52(m,2H),1.84(s,6H),1.67–1.59(m,2H),1.27–1.18(m,4H),0.87–0.77(m,3H).13C NMR(100MHz,CDCl3)δ137.7,128.5,128.4,127.9,64.7,46.4,30.7,22.5,22.1,20.4,13.6.IR(film)ν2956,2872,1465,1450,1288,1118,1095,1031,923,777,696,663cm-1;HRMS(EI)for C14H22O2S Calculated:254.1341,found:254.1345.
实施例19
化合物3s的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),1-溴辛烷(115.9mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3s(45.0mg),收率为76%。1H NMR(400MHz,CDCl3)δ7.68–7.59(m,2H),7.44–7.32(m,3H),2.61–2.52(m,2H),1.84(s,6H),1.68–1.57(m,2H),1.28–1.16(m,10H),0.84(t,J=7.0Hz,3H).13C NMR(100MHz,CDCl3)δ137.7,128.5,128.5,127.9,64.7,52.7,46.5,31.6,28.9,28.8,28.6,22.5,20.7,14.0.IR(film)ν2953,2924,2854,1286,1159,1118,1095,1031,777,696,663cm-1;HRMS(EI)for C17H28O2S Calculated:296.1810,found:296.1812.
实施例20
化合物3t的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),4-苯基-1-丁基溴(128.0mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3t(42.4mg),收率为67%。1H NMR(400MHz,CDCl3)δ7.61(dd,J=8.1,1.5Hz,2H),7.41–7.35(m,3H),7.25(dd,J=9.6,5.0Hz,2H),7.17(d,J=7.3Hz,1H),7.08(d,J=7.0Hz,2H),2.59–2.50(m,4H),1.83(s,6H),1.71–1.56(m,4H).13C NMR(100MHz,CDCl3)δ141.4,137.7,128.5(3),128.5(1),128.3(3),128.2(7),127.9,125.9,64.8,46.3,35.3,30.3,22.5,20.5.IR(film)ν2941,2858,1496,1452,1286,1159,1118,1095,777,746,698,663cm-1;HRMS(EI)for C19H24O2S Calculated:316.1497,found:316.1500.
实施例21
化合物3u的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),(5-溴正戊基)苯(136.0mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3u(43.7mg),收率为66%。1H NMR(400MHz,CDCl3)δ7.66(dd,J=8.0,1.6Hz,2H),7.42(m,3H),7.31–7.26(m,2H),7.17(m,3H),2.65–2.49(m,4H),1.87(s,6H),1.74–1.52(m,4H),1.37–1.27(m,2H).13C NMR(100MHz,CDCl3)δ142.0,137.7,128.6,128.5,128.3(0),128.2(6),127.9,125.7,64.8,46.3,35.4,30.7,28.2,22.5,20.7.IR(film)ν2931,2856,1496,1452,1286,1159,1118,1095,779,698,663cm-1;HRMS(EI)for C20H26O2SCalculated:330.1654,found:330.1658.
实施例22
化合物3v的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),9-(2-溴乙基)-9H-咔唑(165.0mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3v(37.7mg),收率为50%。1H NMR(400MHz,CDCl3)δ7.95(d,J=7.7Hz,2H),7.56(dd,J=8.0,1.5Hz,2H),7.37–7.29(m,5H),7.16–7.10(m,4H),4.43–4.37(m,2H),3.01–2.95(m,2H),1.77(s,6H).13C NMR(100MHz,CDCl3)δ139.4,137.0,129.0,128.9,128.0,126.0,123.2,120.5,119.6,108.2,65.7,44.6,35.7,22.3.IR(film)ν3053,1597,1485,1454,1327,1300,1236,1155,1118,1095,777,752,725,700cm-1;HRMS(EI)forC23H23NO2S Calculated:377.1449,found:377.1446.
实施例23
化合物3w的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),3-(2-溴乙基)噻吩(115.0mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3w(39.9mg),收率为68%。1H NMR(400MHz,CDCl3)δ7.65(dd,J=8.2,1.4Hz,2H),7.40(m,3H),7.22(dd,J=4.9,3.0Hz,1H),6.88(d,J=2.0Hz,1H),6.79(dd,J=4.9,1.1Hz,1H),2.96–2.82(m,4H),1.87(s,6H).13C NMR(100MHz,CDCl3)δ138.2,137.4,128.7,128.6,128.0,127.6,126.1,121.5,65.0,47.3,22.5,21.7.IR(film)ν3095,2987,1734,1714,1450,1284,1267,1116,1093,783,700,626,590cm-1;HRMS(EI)forC15H18O2S2 Calculated:294.0748,found:294.0753.
实施例24
化合物3x的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),2-苯氧乙基溴(120.0mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3x(47.9mg),收率为79%。1H NMR(400MHz,CDCl3)δ7.63–7.55(m,2H),7.37–7.28(m,3H),7.20–7.13(m,2H),6.89–6.85(m,1H),6.70(d,J=7.9Hz,2H),4.03(t,J=7.0Hz,2H),3.05(t,J=7.0Hz,2H),1.80(s,6H).13C NMR(100MHz,CDCl3)δ157.7,137.1,129.5,128.8,128.7,128.1,121.4,114.5,65.6,60.5,46.7,22.3.IR(film)ν2997,1598,1587,1496,1388,1300,1240,1118,1095,1031,777,754,692cm-1;HRMS(EI)forC17H20O3SCalculated:304.1133,found:304.1130.
实施例25
化合物3y的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),4-溴正丁炔(79.8mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3y(33.0mg),收率为70%。1H NMR(400MHz,CDCl3)δ7.63(dd,J=8.1,1.5Hz,2H),7.45–7.35(m,3H),2.83–2.79(m,2H),2.49–2.41(m,2H),1.97(t,J=2.7Hz,1H),1.86(s,6H).13C NMR(100MHz,CDCl3)δ137.1,128.8,128.7,128.0,80.1,70.2,65.1,45.3,22.4,11.5.IR(film)ν3275,2997,1498,1450,1300,1269,1159,1116,1095,1031,985,777,696,657cm-1;HRMS(EI)for C13H16O2SCalculated:236.0871,found:236.0866.
实施例26
化合物3z的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),5-溴-1-戊烯(89.4mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3z(47.9mg),收率为79%。1H NMR(400MHz,CDCl3)δ7.63(dd,J=8.2,1.4Hz,2H),7.43–7.33(m,3H),5.72–5.52(m,1H),5.00–4.87(m,2H),2.60–2.55(m,2H),2.03(q,J=7.1Hz,2H),1.84(s,6H),1.76–1.67(m,2H).13C NMR(100MHz,CDCl3)δ137.6,136.4,128.5,127.9,116.1,64.8,45.6,32.3,22.5,20.0.IR(film)ν3076,2997,1641,1498,1450,1290,1118,1095,921,777,698cm-1;HRMS(EI)for C14H20O2SCalculated:252.1184,found:252.1187.
实施例27
化合物3aa的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),溴甲基环丁烷(89.4mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3aa(39.3mg),收率为78%。1H NMR(400MHz,CDCl3)δ7.65–7.58(m,2H),7.43–7.33(m,3H),2.81–2.71(m,1H),2.66(d,J=7.3Hz,2H),2.15–2.08(m,2H),1.96–1.86(m,1H),1.82(s,6H),1.78–1.66(m,3H).13C NMR(100MHz,CDCl3)δ137.7,128.5,128.4,127.9,64.8,51.8,28.7,28.5,22.4,19.3.IR(film)ν2980,2939,1498,1448,1290,1155,1118,1095,1031,923,779,696,667cm-1;HRMS(EI)for C14H20O2SCalculated:252.1184,found:252.1181.
实施例28
化合物3ab的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),2-溴丁烷(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3ab(24.0mg),收率为50%。1H NMR(400MHz,CDCl3)δ7.66(dd,J=8.1,1.4Hz,2H),7.43–7.34(m,3H),2.89–2.77(m,1H),1.84(s,6H),1.66–1.56(m,2H),0.96(d,J=7.0Hz,3H),0.80(t,J=7.5Hz,3H).13C NMR(100MHz,CDCl3)δ138.1128.5,128.5,127.9,66.0,55.5,23.5,23.3,13.8,11.0.IR(film)ν2980,1450,1284,1157,1118,1093,925,775,698,590cm-1;HRMS(EI)for C13H20O2SCalculated:240.1184,found:240.1186.
实施例29
化合物3ac的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),伊索克酸衍生物(189.7mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3ac(65.6mg),收率为78%。1H NMR(400MHz,CDCl3)δ7.92–7.84(m,2H),7.65(dd,J=8.2,1.4Hz,2H),7.57–7.52(m,1H),7.48–7.41(m,2H),7.41–7.33(m,3H),7.18(dd,J=8.4,2.4Hz,1H),6.93(d,J=8.4Hz,1H),5.13(s,2H),2.87(s,4H),1.87(s,6H).13C NMR(100MHz,CDCl3)δ190.7,160.1,140.2,137.2,135.6,135.5,132.8,131.8,131.2,129.4,129.2,128.7(0),128.6(5),128.0,127.8,125.2,121.1,73.5,65.0,47.9,26.2,22.5.IR(film)ν2993,1647,1610,1489,1411,1300,1118,1095,1014,831,760,698,642cm-1;HRMS(EI)for C25H24O4SCalculated:420.1395,found:420.1400.
实施例30
化合物3ad的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),香茅醇衍生物(75.6mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3ad(32.2mg),收率为50%。1H NMR(400MHz,CDCl3)δ7.64(dd,J=8.2,1.4Hz,2H),7.42–7.35(m,3H),5.03–4.96(m,1H),2.64–2.49(m,2H),1.93–1.82(m,8H),1.69–1.62(m,4H),1.55(s,3H),1.46–1.34(m,2H),1.23–1.13(m,1H),1.11–1.02(m,1H),0.75(d,J=6.4Hz,3H).13C NMR(100MHz,CDCl3)δ137.7,131.5,128.5,127.9,124.2,64.8,44.7,36.5,31.7,27.3,25.7,25.2,22.5,18.9,17.6.IR(film)ν2962,2918,1450,1381,1300,1159,1118,1097,921,779,736,698,588cm-1;HRMS(EI)for C18H28O2SCalculated:322.1967,found:322.1961.
实施例31
化合物3ae的合成:
向反应管中加入金刚烷甲酸衍生的氧化还原酯(65.0mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),磷酸三甲酯(84.0mg,0.6mmol),三乙胺(40.5mg,0.4mmol),四丁基溴化铵(96.7mg,0.3mmol),水(70μL),DMA(2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3ae(31.0mg),收率为79%。1H NMR(400MHz,CDCl3)δ2.72(s,3H),2.18(s,3H),2.01(d,J=2.8Hz,6H),1.73(q,J=12.5Hz,6H).13C NMR(100MHz,CDCl3)δ59.9,35.7,34.7,33.1,28.0.IRν2908,2862,1327,1278,1259,1139,1049,968,837,752cm-1;HRMS(EI)for C11H18O2S Calculated:214.1028,found:214.1026.
实施例32
化合物3af的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),磷酸三甲酯(84.0mg,0.6mmol),三乙胺(40.5mg,0.4mmol),四丁基溴化铵(96.7mg,0.3mmol),水(70μL),DMA(2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3af(33.7mg),收率为85%。1H NMR(400MHz,CDCl3)δ7.64(dd,J=8.2,1.4Hz,2H),7.46–7.31(m,3H),2.50(s,3H),1.85(s,6H).13C NMR(100MHz,CDCl3)δ137.6,128.6(0),128.5(6),127.9,64.6,34.6,22.3.IR(film)ν2920,2850,1469,1450,1286,1161,1118,1095,952,779,721,696cm-1;HRMS(ESI)for C10H14O2SNa+Calculated:221.0607,[M+Na]+found:221.0602.
实施例33
化合物3ag的合成:
向反应管中加入特戊酸衍生的氧化还原酯(49.5mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),磷酸三甲酯(84.0mg,0.6mmol),三乙胺(40.5mg,0.4mmol),四丁基溴化铵(96.7mg,0.3mmol),水(70μL),DMA(2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3ag(15.0mg),收率为55%。1H NMR(400MHz,CDCl3)δ2.80(s,3H),1.42(s,9H).13C NMR(100MHz,CDCl3)δ58.6,34.1,23.4.IRν2985,2935,1280,1116,956,808,758,603cm-1;HRMS(ESI)for C5H12O2SNa+Calculated:159.0450,[M+Na]+found:159.0448.
实施例34
化合物3ah的合成:
向反应管中加入环己基甲酸衍生的氧化还原酯(55.0mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),磷酸三甲酯(84.0mg,0.6mmol),三乙胺(40.5mg,0.4mmol),四丁基溴化铵(96.7mg,0.3mmol),水(70μL),DMA(2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3ah(23.5mg),收率为73%。1H NMR(400MHz,CDCl3)δ2.86–2.74(m,4H),2.22–2.16(m,2H),1.98–1.88(m,2H),1.76–1.68(m,1H),1.50(qd,J=12.4,3.2Hz,2H),1.36–1.18(m,3H).13C NMR(100MHz,CDCl3)δ62.4,37.2,25.4,25.0(0),24.9(7).IRν2933,2858,1452,1296,1267,1134,1111,960,761cm-1;HRMS(ESI)forC7H14O2SH+Calculated:163.0787,[M+H]+found:163.0785.
实施例35
化合物3ai的合成:
向反应管中加入2-甲基丁酸衍生的氧化还原酯(49.5mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),磷酸三甲酯(84.0mg,0.6mmol),三乙胺(40.5mg,0.4mmol),四丁基溴化铵(96.7mg,0.3mmol),水(70μL),DMA(2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3ai(20.4mg),收率为75%。1H NMR(400MHz,CDCl3)δ2.89–2.82(m,1H),2.81(s,3H),2.14–2.05(m,1H),1.58–1.50(m,1H),1.39(d,J=6.9Hz,3H),1.06(t,J=7.5Hz,3H).13C NMR(100MHz,CDCl3)δ60.6,37.2,22.6,12.7,11.2.IRν2978,2937,1465,1296,1136,1118,954,759cm-1;HRMS(ESI)for C5H12O2SH+Calculated:137.0631,[M+H]+found:137.0629.
实施例36
化合物3aj的合成:
向反应管中加入1-苯基环戊烷羧酸衍生的氧化还原酯(67.1mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),磷酸三乙酯(109.3mg,0.6mmol),三乙胺(40.5mg,0.4mmol),四丁基溴化铵(96.7mg,0.3mmol),水(70μL),DMA(2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3aj(33.3mg),收率为70%。1H NMR(400MHz,CDCl3)δ7.59(dd,J=8.2,1.4Hz,2H),7.42–7.33(m,3H),2.83–2.70(m,2H),2.59(q,J=7.5Hz,2H),2.46–2.37(m,2H),2.03–1.93(m,2H),1.73–1.62(m,2H),1.15(t,J=7.5Hz,3H).13C NMR(100MHz,CDCl3)δ137.6,129.0,128.5,128.4,75.8,42.3,33.9,24.5,5.3.IRν2966,2875,1494,1448,1294,1120,1035,779,700,603cm-1;HRMS(ESI)forC13H18O2SNa+ Calculated:261.0920,[M+Na]+found:261.0914.
实施例37
化合物3ak的合成:
向反应管中加入金刚烷甲酸衍生的氧化还原酯(65.0mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),对甲苯磺酸正庚酯(162.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3ak(40.6mg),收率为68%。1H NMR(400MHz,CDCl3)δ2.83–2.79(m,2H),2.16(s,3H),2.01(d,J=2.7Hz,6H),1.89–1.81(m,2H),1.72(q,J=12.5Hz,6H),1.46–1.37(m,2H),1.34–1.23(m,6H),0.86(t,J=6.8Hz,3H).13C NMR(100MHz,CDCl3)δ60.2,44.5,35.8,34.8,31.5,28.8(4),28.8(3),28.1,22.5,20.2,14.0.IRν2910,2854,1454,1284,1138,1105,1049,975,837,758,603cm-1;HRMS(EI)for C17H30O2S Calculated:298.1967,found:298.1962.
实施例38
化合物3al的合成:
向反应管中加入2-苯基丁酸衍生的氧化还原酯(61.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),对甲苯磺酸乙酯(60.8mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物3al(30.2mg),收率为71%。1H NMR(400MHz,CDCl3)δ7.42–7.36(m,5H),3.92(dd,J=11.3,3.7Hz,1H),2.75–2.59(m,2H),2.51–2.42(m,1H),2.16–2.06(m,1H),1.24(t,J=7.5Hz,3H),0.88(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ133.0,129.3,129.1,129.0,69.5,45.0,20.6,11.3,6.0.IR(film)ν3018,1454,1307,1132,1045,759,707,575cm-1;HRMS(EI)for C11H16O2S Calculated:212.0871,found:212.0868.
实施例39
化合物4a的合成:
向反应管中加入萘普生衍生的氧化还原酯(75.0mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物4a(32.5mg),收率为53%。1H NMR(400MHz,CDCl3)δ7.77(m,3H),7.52(dd,J=8.5,1.6Hz,1H),7.22–7.10(m,2H),4.31(q,J=7.1Hz,1H),3.93(s,3H),2.77–2.63(m,2H),1.86(d,J=7.1Hz,3H),1.79–1.68(m,2H),1.36–1.27(m,2H),0.84(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ158.4,134.7,129.6,129.5,128.7,128.2,127.6,126.5,119.6,105.6,63.3,55.4,49.7,23.4,21.7,13.8,13.5.IR(film)ν2962,1606,1485,1394,1265,1234,1130,1029,923,854,810cm-1;HRMS(EI)for C17H22O3SCalculated:306.1290,found:306.1295.
实施例40
化合物4b的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(67.1mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),布洛芬衍生物(187.9mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物4b(69.9mg),收率为82%。1H NMR(400MHz,CDCl3)δ7.57–7.54(m,2H),7.42–7.35(m,3H),7.12(q,J=8.2Hz,4H),4.01(t,J=6.0Hz,2H),3.62(q,J=7.2Hz,1H),2.52(td,J=7.1,3.6Hz,2H),2.46(d,J=7.2Hz,2H),1.91–1.83(m,3H),1.79(s,6H),1.43(d,J=7.2Hz,3H),0.91(d,J=6.6Hz,6H).13C NMR(100MHz,CDCl3)δ174.2,140.5,137.5,137.2,129.3,128.6,128.5,127.9,127.0,64.8,62.5,45.0,44.9,43.1,30.1,22.3(3),22.2(8),20.6,18.2.IRν2954,2868,1498,1276,1157,1118,1095,923,850,777,698cm-1;HRMS(EI)for C25H34O4S Calculated:430.2178,found:430.2182.
实施例41
化合物4c的合成:
向反应管中加入吉非罗齐衍生的氧化还原酯(79.0mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物4c(40.0mg),收率为62%。1H NMR(400MHz,CDCl3)δ7.01(d,J=7.5Hz,1H),6.67(d,J=7.5Hz,1H),6.61(s,1H),3.98(t,J=5.6Hz,2H),2.94–2.90(m,2H),2.31(s,3H),2.17(s,3H),2.01–1.86(m,6H),1.52–1.47(m,2H),1.42(s,6H),0.98(t,J=7.4Hz,3H).13C NMR(100MHz,CDCl3)δ156.7,136.6,130.4,123.5,121.0,112.0,67.4,61.8,45.7,32.2,24.2,22.5,22.1,21.4,20.7,15.8,13.6.IR(film)ν2958,2872,1614,1585,1508,1462,1286,1269,1111,1041,804cm-1;HRMS(EI)for C18H30O3SCalculated:326.1916,found:326.1920.
实施例42
化合物4d的合成:
向反应管中加入松香酸衍生的氧化还原酯(89.9mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),正丁基溴(82.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物4d(37.8mg),收率为50%。1H NMR(400MHz,CDCl3)δ5.77(s,1H),5.43–5.32(m,1H),2.94–2.77(m,3H),2.66–2.58(m,1H),2.24–2.16(m,2H),2.10–2.04(m,2H),1.91–1.77(m,7H),1.50(s,3H),1.48–1.44(m,2H),1.25–1.19(m,2H),1.15–1.06(m,2H),1.01–0.93(m,9H),0.86(s,3H).13C NMR(100MHz,CDCl3)δ145.2,134.7,122.2,120.3,67.1,50.5,45.9,41.9,37.7,35.8,34.8,34.4,27.3,25.3,22.6,22.1,21.4,20.8,18.2,15.2,14.2,13.6.IR(film)ν2958,2872,1710,1361,1267,1220,1118,1091,827,759,736cm-1;HRMS(EI)forC23H38O2SCalculated:378.2593,found:378.2596.
实施例43
化合物4e的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(89.1mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),Boc-L-酪氨酸衍生物(430.3mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物4e(75.9mg),收率为71%。1H NMR(400MHz,CDCl3)δ7.63(dd,J=8.1,1.5Hz,2H),7.40–7.33(m,3H),7.00(d,J=8.4Hz,2H),6.71(d,J=8.5Hz,2H),4.96(d,J=7.8Hz,1H),4.52(d,J=7.1Hz,1H),3.83(t,J=5.7Hz,2H),3.70(s,3H),3.08–2.90(m,2H),2.72–2.63(m,2H),1.85(s,7H),1.80–1.72(m,3H),1.41(s,9H).13C NMR(100MHz,CDCl3)δ172.3,157.7,155.0,137.6,130.2,128.6,128.5,127.9,114.4,79.8,66.9,64.8,54.5,52.1,46.0,37.4,28.3,28.1,22.4,18.2.IR(film)ν2976,1708,1512,1438,1363,1286,1244,1161,1118,1095,1053,831,777,698,663cm-1;HRMS(EI)forC28H39NO7SCalculated:533.2447,found:533.2453.
实施例44
化合物4f的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(89.1mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),果糖二丙酮衍生物(237.2mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物4f(65.7mg),收率为66%。1H NMR(400MHz,CDCl3)δ7.66–7.58(m,2H),7.41–7.32(m,3H),4.57(dd,J=7.9,2.6Hz,1H),4.29(d,J=2.6Hz,1H),4.22–4.18(m,1H),3.87(dd,J=12.9,1.7Hz,1H),3.69(d,J=12.9Hz,1H),3.50–3.34(m,4H),2.62–2.57(m,2H),1.82(s,6H),1.74–1.67(m,2H),1.60–1.52(m,2H),1.50(s,3H),1.44(s,3H),1.33(d,J=11.2Hz,6H).13C NMR(100MHz,CDCl3)δ137.6,128.5(0),
128.4(8),127.9,108.8,108.4,102.5,72.2,71.0,70.1,69.9,64.7,60.9,46.1,28.3,26.5,25.8,25.3,24.0,22.4,18.0.IR(film)ν2989,2935,1714,1381,1371,1290,1251,1205,1116,1068,889,777,700cm-1;HRMS(EI)for C25H38O8SCalculated:498.2287,found:498.2280.
实施例45
化合物4g的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(89.1mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),双丙酮葡萄糖衍生物(237.1mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物4g(67.9mg),收率为68%。1H NMR(400MHz,CDCl3)δ7.61(d,J=7.0Hz,2H),7.42–7.33(m,3H),5.78(d,J=3.5Hz,1H),4.43(d,J=3.6Hz,1H),4.21–4.16(m,1H),4.07–3.99(m,2H),3.95–3.91(m,1H),3.76(d,J=2.9Hz,1H),3.53–3.42(m,2H),2.62–2.50(m,2H),1.82(s,6H),1.76–1.68(m,2H),1.59–1.51(m,2H),1.46(s,3H),1.38(s,3H),1.29(d,J=5.4Hz,6H).13C NMR(100MHz,CDCl3)δ137.6,128.5,127.9,111.7,108.9,105.1,82.4,82.1,81.0,72.3,69.7,67.2,64.7,45.9,28.5,26.7,26.1,25.3,22.4,17.9.IR(film)ν2989,1710,1361,1290,1220,1165,1120,1072,1018,848,779,700cm-1;HRMS(EI)for C25H38O8SCalculated:498.2287,found:498.2292.
实施例46
化合物4h的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(89.1mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),胆固醇衍生物(304mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物4h(78.2mg),收率为64%。1H NMR(400MHz,CDCl3)δ7.64(dd,J=8.2,1.3Hz,2H),7.42–7.34(m,3H),5.30(d,J=5.1Hz,1H),3.44(t,J=5.9Hz,2H),3.07–2.97(m,1H),2.76–2.68(m,2H),2.24–2.18(m,1H),2.11–1.95(m,3H),1.85(s,10H),1.69–1.41(m,7H),1.38–1.23(m,6H),1.20–1.05(m,6H),0.97(s,6H),0.91(d,J=6.5Hz,4H),0.86(dd,J=6.6,1.7Hz,6H),0.67(s,3H).13C NMR(100MHz,CDCl3)δ140.7,137.6,128.5,128.0,121.6,78.9,65.7,64.8,56.7,56.1,50.1,43.5,42.3,39.7,39.5,39.0,37.1,36.8,36.2,35.7,31.8(8),31.8(5),28.3,28.2,28.0,24.3,23.8,22.8,22.5(2),22.4(6),21.9,21.0,19.3,18.7,11.8.IR(film)ν2933,2900,2848,2110,1720,1606,1560,1365,1224,1107,1093,696,599cm-1;HRMS(ESI)for C39H62O3SNa+Calculated:633.4312[M+Na]+found:633.4305.
实施例47
化合物4i的合成:
向反应管中加入二甲基苯乙酸衍生的氧化还原酯(89.1mg,0.2mmol),连二亚硫酸钠(69.6mg,0.4mmol),雌酚酮衍生物(234.8mg,0.6mmol),N,N’-二异丙基乙胺(51.7mg,0.4mmol),氯化锌(13.6mg,0.1mmol),四丁基溴化铵(96.7mg,0.3mmol),水(60μL),DMF/CH3CN(2:1,2mL),在氮气保护下于120℃反应15h,点板监测至氧化还原酯消耗完全,移至室温,加水淬灭,乙酸乙酯萃取,收集有机相。有机相用无水硫酸钠干燥,减压旋除溶剂,柱层析分离得到产物4(70.6mg),收率为71%。1H NMR(400MHz,CDCl3)δ7.64(dd,J=8.2,1.4Hz,2H),7.43–7.34(m,3H),7.16(d,J=8.6Hz,1H),6.61(dd,J=8.6,2.6Hz,1H),6.55(d,J=2.5Hz,1H),3.92(t,J=5.8Hz,2H),2.89–2.78(m,4H),2.50(dd,J=18.8,8.6Hz,1H),2.42–2.34(m,1H),2.28–2.21(m,1H),2.16–1.93(m,6H),1.87(s,6H),1.66–1.42(m,6H),0.90(s,3H).13C NMR(100MHz,CDCl3)δ156.4,137.7,137.4,132.4,128.6,127.9,126.3,114.4,112.1,65.8,64.9,50.3,47.9,43.9,43.5,38.3,35.8,31.5,29.6,26.4,25.9,22.4,21.5,21.3,13.8.IR(film)ν2922,2854,1734,1498,1365,1251,1118,1095,779,700cm-1;HRMS(EI)for C30H38O4SCalculated:494.2491,found:494.2498.
本发明的保护内容不局限于以上实施例。在不背离发明构思的精神和范围下,本领域技术人员能够想到的变化和优点都被包括在本发明中,并且以所附的权利要求书为保护范围。
Claims (17)
2.如权利要求1所述的合成方法,其特征在于,所述R1为C1-C10直链烷基、C1-C10环烷基、芳基C1-C10烷基、含不饱和键的C1-C10烷基或氢;R2为C1-C10直链烷基、C1-C10环烷基、芳基C1-C10烷基、含不饱和键的C1-C10烷基或氢;R3为C1-C10直链烷基、C1-C10环烷基、芳基C1-C10烷基、含不饱和键的C1-C10烷基或氢;R为C1-C10直链烷基、C1-C10环烷基、烷氧基C1-C10烷基、芳基C1-C10烷基、烯基C1-C10烷基、炔基C1-C10烷基。
3.如权利要求1所述的合成方法,其特征在于,R1为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R2为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R3为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R为甲基、乙基、正戊基、正庚基、正辛基、苯丙基、苯丁基、甲基环丁基、苯氧基乙基、正戊烯基、正丁炔基、噻吩乙基。
4.如权利要求1所述的合成方法,其特征在于,所述R1,R2,R3,R4分别独立地选自甲基、乙基、正戊基、正庚基、正辛基、苯丙基、苯丁基、甲基环丁基、苯氧基乙基、正戊烯基、正丁炔基或噻吩乙基。
5.如权利要求1所述的合成方法,其特征在于,所述溶剂为N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲亚砜、N-甲基吡咯烷酮、乙腈、水、四氢呋喃、1,4-二氧六环、环戊基甲醚、乙醚、叔丁基甲醚之任意一种或多种。
6.如权利要求1所述的合成方法,其特征在于,所述反应温度为60-140℃。
7.如权利要求1所述的合成方法,其特征在于,所述反应时间为6-20h。
8.如权利要求1所述的合成方法,其特征在于,所述还原性二氧化硫源为连二亚硫酸钠(保险粉)、焦亚硫酸钠、焦亚硫酸钾、二氧化硫脲、甲醛合次硫酸氢钠之任意一种或多种。
9.如权利要求1所述的合成方法,其特征在于,所述烷基亲电试剂为烷基溴、烷基苯磺酸酯、烷基磷酸酯中的一种或多种。
10.如权利要求1所述的合成方法,其特征在于,所述式(1)氧化还原酯、式(2)还原性二氧化硫源及式(3)烷基亲电试剂的摩尔比为1:(1-8):(1-8)。
11.如权利要求1所述的合成方法,其特征在于,所述添加剂1选自氯化镁、氯化锌、氯化锂、溴化锌、碘化锌、氯化锡、氯化铝、氟化锂之任意一种或多种;所述式(1)氧化还原酯与所述添加剂1的用量摩尔比为1:(1-5)。
12.如权利要求1所述的合成方法,其特征在于,所述碱选自碳酸钾、碳酸钠、碳酸锂、碳酸氢钾、碳酸氢钠、碳酸氢锂、磷酸钾、磷酸氢钾、氢氧化钾、氢氧化钠、三乙胺、N,N’-二异丙基乙胺、N,N’-二甲基乙二胺中的一种或多种;所述式(1)氧化还原酯与所述碱的用量摩尔比为1:(1-5)。
13.如权利要求1所述的合成方法,其特征在于,所述添加剂2为四甲基氟化铵、四甲基氯化铵、四甲基溴化铵、四甲基碘化铵、四丁基氟化铵、四丁基氯化铵、四丁基溴化铵、四丁基碘化铵、四丁基四氟硼酸铵、四丁基六氟磷酸铵、苄基三乙基氟化铵、苄基三乙基氯化铵、苄基三乙基溴化铵、苄基三乙基碘化铵、15-冠-5、18-冠-6、环糊精、聚乙二醇之任意一种或多种;所述式(1)氧化还原酯与所述添加剂2的用量摩尔比为1:(1-5)。
15.如权利要求14所述的大位阻烷基-烷基砜类化合物,其特征在于,R1为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R2为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢;R3为直链烷基、环烷基、芳基烷基、含不饱和键的烷基或氢。R为甲基、乙基、正戊基、正庚基、正辛基、苯丙基、苯丁基、甲基环丁基、苯氧基乙基、正戊烯基、正丁炔基、噻吩乙基等。
16.如权利要求14所述的大位阻烷基-烷基砜类化合物,其特征在于,所述R1,R2,R3,R4分别独立地选自甲基、乙基、正戊基、正庚基、正辛基、苯丙基、苯丁基、甲基环丁基、苯氧基乙基、正戊烯基、正丁炔基或噻吩乙基。
17.如权利要求14-16之任一项所述的大位阻烷基-烷基砜类化合物在制备药物、农药、有机光电材料等中的应用。
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