CN110015952B - Diaryl methane compound and preparation method and application thereof - Google Patents
Diaryl methane compound and preparation method and application thereof Download PDFInfo
- Publication number
- CN110015952B CN110015952B CN201810023238.4A CN201810023238A CN110015952B CN 110015952 B CN110015952 B CN 110015952B CN 201810023238 A CN201810023238 A CN 201810023238A CN 110015952 B CN110015952 B CN 110015952B
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- Prior art keywords
- group
- radical
- alkyl
- preparation
- alkynyl
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- -1 Diaryl methane compound Chemical class 0.000 title claims abstract description 194
- 238000002360 preparation method Methods 0.000 title claims abstract description 94
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 53
- 238000006243 chemical reaction Methods 0.000 claims abstract description 49
- 239000003054 catalyst Substances 0.000 claims abstract description 25
- 238000004519 manufacturing process Methods 0.000 claims abstract description 19
- 229940126062 Compound A Drugs 0.000 claims abstract description 13
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003513 alkali Substances 0.000 claims abstract description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 59
- 125000000304 alkynyl group Chemical group 0.000 claims description 54
- 125000003118 aryl group Chemical group 0.000 claims description 43
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 34
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 24
- 239000004327 boric acid Substances 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 17
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000004434 sulfur atom Chemical group 0.000 claims description 15
- 125000006735 (C1-C20) heteroalkyl group Chemical group 0.000 claims description 12
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 150000003459 sulfonic acid esters Chemical class 0.000 claims description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 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
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 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
- RYCLIXPGLDDLTM-UHFFFAOYSA-J tetrapotassium;phosphonato phosphate Chemical compound [K+].[K+].[K+].[K+].[O-]P([O-])(=O)OP([O-])([O-])=O RYCLIXPGLDDLTM-UHFFFAOYSA-J 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 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
- 235000019797 dipotassium phosphate Nutrition 0.000 claims description 2
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 2
- 235000019800 disodium phosphate Nutrition 0.000 claims description 2
- 150000002391 heterocyclic compounds Chemical group 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
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 claims description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 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
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- 235000011008 sodium phosphates Nutrition 0.000 claims description 2
- QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 claims description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 2
- 239000000047 product Substances 0.000 abstract description 72
- 238000000034 method Methods 0.000 abstract description 28
- 230000015572 biosynthetic process Effects 0.000 abstract description 12
- 238000003786 synthesis reaction Methods 0.000 abstract description 11
- 230000008569 process Effects 0.000 abstract description 10
- 239000008204 material by function Substances 0.000 abstract description 8
- 239000012450 pharmaceutical intermediate Substances 0.000 abstract description 5
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 238000006555 catalytic reaction Methods 0.000 abstract description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 abstract description 2
- 150000001543 aryl boronic acids Chemical class 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 description 133
- 125000005842 heteroatom Chemical group 0.000 description 28
- 125000003545 alkoxy group Chemical group 0.000 description 26
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 26
- VINBEKQZAXWGCO-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]-2,4-dimethylbenzene Chemical compound C1=CC(OC)=CC=C1CC1=CC=C(C)C=C1C VINBEKQZAXWGCO-UHFFFAOYSA-N 0.000 description 23
- PECXPZGFZFGDRD-UHFFFAOYSA-N 2-(chloromethyl)-1,4-dimethylbenzene Chemical compound CC1=CC=C(C)C(CCl)=C1 PECXPZGFZFGDRD-UHFFFAOYSA-N 0.000 description 23
- 238000012512 characterization method Methods 0.000 description 23
- 238000004440 column chromatography Methods 0.000 description 23
- 239000000706 filtrate Substances 0.000 description 23
- 125000003342 alkenyl group Chemical group 0.000 description 22
- 238000007405 data analysis Methods 0.000 description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 21
- 238000009987 spinning Methods 0.000 description 21
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 20
- 125000000392 cycloalkenyl group Chemical group 0.000 description 15
- 229910052757 nitrogen Inorganic materials 0.000 description 15
- 239000007787 solid Substances 0.000 description 14
- 125000003107 substituted aryl group Chemical group 0.000 description 14
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 238000000926 separation method Methods 0.000 description 11
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 10
- 125000005100 aryl amino carbonyl group Chemical group 0.000 description 10
- 125000004104 aryloxy group Chemical group 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 125000002950 monocyclic group Chemical group 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 125000005129 aryl carbonyl group Chemical group 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 150000003384 small molecules Chemical class 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 125000005103 alkyl silyl group Chemical group 0.000 description 8
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 8
- 229940073608 benzyl chloride Drugs 0.000 description 8
- 239000000376 reactant Substances 0.000 description 8
- 230000003197 catalytic effect Effects 0.000 description 7
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 125000003860 C1-C20 alkoxy group Chemical group 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 125000001931 aliphatic group Chemical group 0.000 description 6
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 150000002430 hydrocarbons Chemical group 0.000 description 6
- 125000003367 polycyclic group Chemical group 0.000 description 6
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 125000003282 alkyl amino group Chemical group 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 5
- 229910052710 silicon Inorganic materials 0.000 description 5
- 239000010703 silicon Substances 0.000 description 5
- 125000000547 substituted alkyl group Chemical group 0.000 description 5
- 239000011593 sulfur Substances 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- 238000006069 Suzuki reaction reaction Methods 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 150000004982 aromatic amines Chemical class 0.000 description 4
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 150000002240 furans Chemical class 0.000 description 4
- 125000005553 heteroaryloxy group Chemical group 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 229930192474 thiophene Natural products 0.000 description 4
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 3
- 125000001769 aryl amino group Chemical group 0.000 description 3
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
- 125000005981 pentynyl group Chemical group 0.000 description 3
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- AQFCCDXDSQEHKT-UHFFFAOYSA-N (4-benzylphenoxy)-tert-butyl-dimethylsilane Chemical compound C(C)(C)(C)[Si](OC1=CC=C(CC2=CC=CC=C2)C=C1)(C)C AQFCCDXDSQEHKT-UHFFFAOYSA-N 0.000 description 2
- LEIRCQBDSGHKOJ-UHFFFAOYSA-N 1-benzyl-2-chloro-4-methoxybenzene Chemical compound ClC1=CC(OC)=CC=C1CC1=CC=CC=C1 LEIRCQBDSGHKOJ-UHFFFAOYSA-N 0.000 description 2
- KDWAWSSREPAGEG-UHFFFAOYSA-N 1-benzyl-3,5-dimethoxybenzene Chemical compound COC1=CC(OC)=CC(CC=2C=CC=CC=2)=C1 KDWAWSSREPAGEG-UHFFFAOYSA-N 0.000 description 2
- LFDLONXAKQLOMQ-UHFFFAOYSA-N 1-benzyl-4-phenoxybenzene Chemical compound C=1C=C(OC=2C=CC=CC=2)C=CC=1CC1=CC=CC=C1 LFDLONXAKQLOMQ-UHFFFAOYSA-N 0.000 description 2
- KKPSLFBGGFDGRE-UHFFFAOYSA-N 1-bromo-3-[(4-methoxyphenyl)methyl]benzene Chemical compound C1=CC(OC)=CC=C1CC1=CC=CC(Br)=C1 KKPSLFBGGFDGRE-UHFFFAOYSA-N 0.000 description 2
- BTVIMPCUUKOJGI-UHFFFAOYSA-N 1-bromo-4-[(4-methoxyphenyl)methyl]benzene Chemical compound C1=CC(OC)=CC=C1CC1=CC=C(Br)C=C1 BTVIMPCUUKOJGI-UHFFFAOYSA-N 0.000 description 2
- YXIZFLAFDDDYLM-UHFFFAOYSA-N 1-methoxy-4-[(4-phenylphenyl)methyl]benzene Chemical group C1=CC(OC)=CC=C1CC1=CC=C(C=2C=CC=CC=2)C=C1 YXIZFLAFDDDYLM-UHFFFAOYSA-N 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- MMYPHRAOQIYWON-UHFFFAOYSA-N 2-benzyl-1,10-phenanthroline Chemical compound C=1C=C2C=CC3=CC=CN=C3C2=NC=1CC1=CC=CC=C1 MMYPHRAOQIYWON-UHFFFAOYSA-N 0.000 description 2
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 2
- HDZKIDYVJLGONY-UHFFFAOYSA-N 4-[(4-methoxyphenyl)methyl]benzonitrile Chemical compound C1=CC(OC)=CC=C1CC1=CC=C(C#N)C=C1 HDZKIDYVJLGONY-UHFFFAOYSA-N 0.000 description 2
- FZOGMSMEMWORBS-UHFFFAOYSA-N 4-benzyl-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1CC1=CC=CC=C1 FZOGMSMEMWORBS-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- XTGLEMXWWDQXOM-UHFFFAOYSA-N C(C1=CC=CC=C1)C=1C=C2CCN(C2=CC1)S(=O)(=O)C1=CC=C(C)C=C1 Chemical compound C(C1=CC=CC=C1)C=1C=C2CCN(C2=CC1)S(=O)(=O)C1=CC=C(C)C=C1 XTGLEMXWWDQXOM-UHFFFAOYSA-N 0.000 description 2
- CYAVFSNQWUVNOA-UHFFFAOYSA-N CC(C=C1)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(CC(C=C2OC)=CC(OC)=C2OC)C=C1 Chemical compound CC(C=C1)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(CC(C=C2OC)=CC(OC)=C2OC)C=C1 CYAVFSNQWUVNOA-UHFFFAOYSA-N 0.000 description 2
- FEAGEDXRTHUKDA-UHFFFAOYSA-N COC1=CC=C(CC2=CC=C(C=C2)SC)C=C1 Chemical compound COC1=CC=C(CC2=CC=C(C=C2)SC)C=C1 FEAGEDXRTHUKDA-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000000033 alkoxyamino group Chemical group 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 125000005264 aryl amine group Chemical group 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 2
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 2
- JKWMSGQKBLHBQQ-UHFFFAOYSA-N diboron trioxide Chemical compound O=BOB=O JKWMSGQKBLHBQQ-UHFFFAOYSA-N 0.000 description 2
- JTTXRFNOFFGPFI-UHFFFAOYSA-N ethyl 4-(chloromethyl)benzoate Chemical compound CCOC(=O)C1=CC=C(CCl)C=C1 JTTXRFNOFFGPFI-UHFFFAOYSA-N 0.000 description 2
- JFRPWHSKUZXHFF-UHFFFAOYSA-N ethyl 4-[(4-methoxyphenyl)methyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CC1=CC=C(OC)C=C1 JFRPWHSKUZXHFF-UHFFFAOYSA-N 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C15/00—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts
- C07C15/20—Polycyclic condensed hydrocarbons
- C07C15/27—Polycyclic condensed hydrocarbons containing three rings
- C07C15/30—Phenanthrenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/43—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C211/54—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to two or three six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/54—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/18—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/205—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/205—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring
- C07C43/2055—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring containing more than one ether bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/225—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
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Abstract
The invention discloses a diaryl methane compound and a preparation method and application thereof. The general formula of the molecular structure of the diarylmethane compound is shown in the general formula (I) in the specification. The preparation method of the diarylmethane compound comprises the step of adding the benzyl halogenated hydrocarbon compound A and the arylboronic acid B into a reaction system containing an organic small molecular catalyst, an alkali reagent and a solvent for reaction preparation. The diarylmethane compound contains an electron-withdrawing group and an electron-donating group substituted diarylmethane basic skeleton, and can be widely used for synthesis of pharmaceutical intermediates, particularly polysubstituted methane compounds, and preparation of functional materials. The preparation method has the advantages of simple process, low requirement on reaction conditions, safe and controllable reaction process, high atom utilization rate and production efficiency, high efficiency, capability of ensuring the regional and stereoselectivity of the product, introduction of the scientific organic micromolecule catalysis concept at the same time, and environmental friendliness.
Description
Technical Field
The invention belongs to the technical field of organic compound synthesis, and particularly relates to a diarylmethane compound, a preparation method thereof and application of the diarylmethane compound.
Background
The diarylmethane compounds refer to compounds in which two aromatic substituents are simultaneously connected to the same substituted carbon atom. Diarylmethane compounds not only widely exist in bioactive compounds such as natural products, drug molecules and intermediates, but also widely used in industrial production, for example, as dyes, heat transfer fluids, solvents, and the like. The synthesis of such compounds is therefore an important aspect of current organic chemistry.
The traditional method for synthesizing diaryl methane compounds comprises Friedel-Crafts reaction, reduction reaction of diaryl ketone or diaryl methanol, and Suzuki cross-coupling reaction catalyzed by transition metal. However, these methods have a number of disadvantages and limitations, for example 1) the Friedel-Crafts reaction requires a stronger Lewis acid or
The acid is used as an accelerant, the reaction condition is severe, the regioselectivity is poor, and the byproducts are more; 2) reducing diaryl ketone or diaryl methanol requires hazardous reducing agents such as hydrogen, sodium borohydride and the like, and raw materials need to be prepared in multiple steps; 3) the catalyst palladium or nickel usually used in the coupling reaction catalyzed by the transition metal has high toxicity and is not environment-friendly, so that the application range of the catalyst in the production of medicaments is greatly reduced; 4) in general, there are great restrictions on the functional groups of the reaction substrates, for example both basic groups of the Friedel-Crafts reactionThe compatibility is low, diaryl ketones or diaryl carbinols have low compatibility with aldehydes, ketones, esters, alkenes, alkynes, etc., while transition metal catalyzed coupling reactions have low tolerance for aryl halogens, especially carbon-bromine and carbon-iodine bonds.
Therefore, there is a need for a new diarylmethane compound and method to overcome the above-mentioned deficiencies in the prior art. In recent years, the development of the field of organic small molecule catalytic chemistry is changing day by day, and a new path is provided for the construction of diarylmethane compounds.
Disclosure of Invention
The invention aims to overcome the defects in the prior art, and provides a diarylmethane compound and a preparation method thereof, so as to solve the technical problems of harsh preparation conditions, low yield, complex process, environmental friendliness, limited application range and the like of the conventional diarylmethane compound.
Furthermore, the invention also provides application of the diarylmethane compound.
In order to achieve the above object, according to one aspect of the present invention, a diarylmethane compound is provided. The general molecular structure formula of the diarylmethane compound is as follows (I):
R 1 is C 1 -C 20 Alkyl radical, C 1 -C 20 Heteroalkyl group, C 3 -C 20 Cycloalkyl radical, C 3 -C 20 Heterocycloalkyl radical, C 2 -C 20 Alkenyl radical, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl radical, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl, C 3 -C 20 Heterocycloalkynyl, C 1 -C 20 Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, aryl C 1 -C 20 Alkyl, heteroaryl C 1 -C 20 Alkyl radical, C 2 -C 20 Alkenyl radical C 1 -C 20 Alkyl radical, C 2 -C 20 Alkynyl C 1 -C 20 Alkyl, cyano C 1 -C 20 Any one of an alkyl group, an alkyloxycarbonylalkyl group, and a hydrogen atom substituent;
said R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is C 1 -C 20 Alkyl radical, C 1 -C 20 Heteroalkyl group, C 3 -C 20 Cycloalkyl radical, C 3 -C 20 Heterocycloalkyl, C 2 -C 20 Alkenyl radical, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl radical, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl group, C 3 -C 20 Heterocycloalkynyl, C 1 -C 20 Alkoxy, amino, C 1 -C 20 Alkylamino radical, C 3 -C 20 Arylamino, C 1 -C 20 Alkyloxyboron radical, C 1 -C 20 Alkylsilyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C 1 -C 20 Alkyl, heteroaryl C 1 -C 20 Alkyl, cyano C 1 -C 20 Alkyl radical, C 1 -C 20 Alkyloxycarbonyl group C 1 -C 20 Alkyl radical, C 1 -C 20 Alkyloxycarbonyl, C 3 -C 20 Aryloxycarbonyl, C 1 -C 20 Alkylcarbonyl group, C 3 -C 20 Aryl carbonyl group, C 1 -C 20 Alkylaminocarbonyl radical, C 3 -C 20 Any one of arylaminocarbonyl, nitro, cyano, halogen and hydrogen atom substituent.
As another aspect of the present invention, there is provided a method for producing the diarylmethane compounds, comprising the steps of:
providing a sulfonic acid ester compound A of benzyl halogenated hydrocarbon or benzyl alcohol, a boric acid or boric anhydride compound B respectively represented by the following structural formula:
A、
B、
adding the sulfonic ester compound A of benzyl halogenated hydrocarbon or benzyl alcohol and the boric acid or boric anhydride compound B into a reaction system containing an organic micromolecule catalyst, an alkali reagent and a solvent to react at the temperature of 30-110 ℃ to obtain the diarylmethane compound shown as the following structural general formula (I):
wherein, the compound A, B and the R in the structural formula of the (I) 1 Are all made of
C 1 -C 20 Alkyl radical, C 1 -C 20 Heteroalkyl group, C 3 -C 20 Cycloalkyl radical, C 3 -C 20 Heterocycloalkyl radical, C 2 -C 20 Alkenyl radical, C 2 -C 20 Heteroalkenyl radical, C 3 -C 20 Cycloalkenyl radical, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl, C 3 -C 20 Heterocycloalkynyl, C 1 -C 20 Alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, aryl C 1 -C 20 Alkyl, heteroaryl C 1 -C 20 Alkyl radical, C 2 -C 20 Alkenyl radical C 1 -C 20 Alkyl radical, C 2 -C 20 Alkynyl C 1 -C 20 Alkyl, cyano C 1 -C 20 Any one of an alkyl group, an alkyloxycarbonylalkyl group, and a hydrogen atom substituent;
said R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is C 1 -C 20 Alkyl radical, C 1 -C 20 Heteroalkyl group, C 3 -C 20 Cycloalkyl radical, C 3 -C 20 Heterocycloalkyl radical, C 2 -C 20 Alkenyl radical, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl radical, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl group, C 3 -C 20 Heterocycloalkynyl, C 1 -C 20 Alkoxy, amino, C 1 -C 20 Alkylamino radical, C 3 -C 20 Arylamino, C 1 -C 20 Alkyloxyboron radical, C 1 -C 20 Alkylsilyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl C 1 -C 20 Alkyl, heteroaryl C 1 -C 20 Alkyl, cyano C 1 -C 20 Alkyl radical, C 1 -C 20 Alkyloxycarbonyl group C 1 -C 20 Alkyl radical, C 1 -C 20 Alkyloxycarbonyl, C 3 -C 20 Aryloxycarbonyl, C 1 -C 20 Alkylcarbonyl group, C 3 -C 20 Aryl carbonyl group, C 1 -C 20 Alkylaminocarbonyl radical, C 3 -C 20 Any one of arylaminocarbonyl, nitro, cyano, halogen and hydrogen atom substituent;
wherein X is a halogen atom or a sulfonyloxy group. As still another aspect of the present invention, the present invention provides use of the diarylmethane compounds of the present invention described above or the diarylmethane compounds prepared by the method for preparing diarylmethane compounds of the present invention described above in synthesis of pharmaceutical intermediates and preparation of industrial raw materials.
Compared with the prior art, the diarylmethane compound has a typical high-functional group structure, such as structures containing electron-withdrawing groups, electron-donating groups, halogens, heterocycles and the like, so the diarylmethane compound has the same characteristics as other diarylmethane compounds, can be widely used for synthesis of drug intermediates and preparation of functional materials, and enhances the application of the diarylmethane compound in the field of drugs.
Compared with the prior art, the preparation method of the diarylmethane compound has the following advantages:
1. the organic micromolecules are used as catalysts, so that strict transition-free metallization of the whole reaction system can be realized, the reaction process is safe and controllable, and the operation in the preparation production process is simplified;
2. based on a thioether compound, a sulfonic ester substrate of benzyl halohydrocarbon or benzyl alcohol is subjected to nucleophilic substitution under an alkaline condition to form a sulfur ylide intermediate, and then aryl boric acid or boric anhydride substrate is subjected to complexation to generate 1, 2-migration reaction, so that the circulation of a catalyst is realized, and a target product with specific regioselectivity and an extremely wide range is efficiently and greenly prepared;
3. the invention is similar to Suzuki reaction in the net result of the reaction, so the atom utilization rate of the reaction is high, and the by-product is nontoxic boric acid.
4. The benzyl halogenated hydrocarbon and the common aryl boric acid which are simple and commercially available are selected as reactants in the reaction, the raw materials are low in price and very easy to obtain, and the reactants before the reaction are not required to be subjected to additional modification protection and can be directly used for preparation production, so that the operation steps are simplified, and the reaction route is shortened; the forward reaction rate is high, and the production efficiency is obviously improved;
5. due to the advantages of the 1 st to the 4 th, the method has the advantages of simple process, low requirement on reaction conditions, safe and controllable reaction process, high atom utilization rate and production efficiency and low environmental pollution pressure, the method obviously reduces the production cost for preparing the diarylmethane compounds, and greatly expands the designability and application prospect of the compounds.
The diarylmethane compound has a typical high-functional group structure and the advancement of the preparation method, so that the diarylmethane compound can be widely used for synthesis of drug intermediates and preparation of functional materials, can effectively reduce the economic cost for preparation of the drug intermediates and the functional materials, and is environment-friendly.
Detailed Description
In order to make the technical problems, technical solutions and beneficial effects to be solved by the present invention more clearly apparent, the present invention is further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The compounds and derivatives thereof referred to in the examples of the present invention are named according to IUPAC (International Union of pure and applied chemistry) or CAS (chemical Abstract service society, Columbus, Ohio) naming system. Accordingly, the groups of compounds specifically referred to in the examples of the present invention are illustrated and described as follows:
with respect to "hydrocarbon group", the minimum and maximum values of the carbon atom content in a hydrocarbon group are indicated by a prefix, e.g., the prefix (C) a -C b ) Alkyl represents any alkyl group containing "a" to "b" carbon atoms. Thus, for example, (C) 1 -C 6 ) Alkyl refers to alkyl groups containing one to six carbon atoms.
"alkoxy" refers to a straight or branched, monovalent, saturated aliphatic chain bonded to an oxygen atom and includes, but is not limited to, groups such as methoxy, ethoxy, propoxy, butoxy, isobutoxy, t-butoxy, and the like. (C) a -C b ) Alkoxy means any straight or branched, monovalent, saturated aliphatic chain of an alkyl group containing from "a" to "b" carbon atoms bonded to an oxygen atom.
"alkyl" refers to a straight or branched, monovalent, saturated aliphatic chain including, but not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl, and the like.
"heteroalkyl" means a straight or branched, monovalent, saturated aliphatic chain attached to at least one heteroatom, such as, but not limited to, methylaminoethyl or other similar groups.
"alkenyl" refers to straight or branched chain hydrocarbons with one or more double bonds, including but not limited to, groups such as ethenyl, propenyl, and the like.
"Heteroalkenyl" means a straight or branched chain hydrocarbon with one or more double bonds attached to at least one heteroatom, including but not limited to, for example, vinylaminoethyl or other similar groups.
"alkynyl" refers to a straight or branched chain hydrocarbon with one or more triple bonds, including but not limited to, for example, ethynyl, propynyl, and the like.
"Heteroalkynyl" means a straight or branched chain hydrocarbon with one or more triple bonds attached to at least one heteroatom, including but not limited to, groups such as ethynyl, propynyl, and the like.
"aryl" refers to a cyclic aromatic hydrocarbon including, but not limited to, groups such as phenyl, naphthyl, anthryl, phenanthryl, and the like.
"heteroaryl" refers to a monocyclic or polycyclic or fused aromatic hydrocarbon in which one or more carbon atoms have been replaced with a heteroatom such as nitrogen, oxygen, or sulfur. If the heteroaryl group contains more than one heteroatom, these heteroatoms may be the same or different. Heteroaryl groups include, but are not limited to, groups such as benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzopyranyl, furanyl, imidazolyl, indazolyl, indolizinyl, indolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, oxazinyl, oxazolyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridine [3,4-b ] indolyl, pyridyl, pyrimidinyl, pyrrolyl, quinolizinyl, quinolyl, quinoxalinyl, thiadiazolyl, thiatriazolyl, thiazolyl, thienyl, triazinyl, triazolyl, xanthenyl, and the like.
"cycloalkyl" refers to a saturated monocyclic or polycyclic alkyl group, possibly fused to an aromatic hydrocarbon group. Cycloalkyl groups include, but are not limited to, groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indanyl, tetrahydronaphthyl, and the like.
"Heterocycloalkyl" means a saturated monocyclic or polycyclic alkyl group, possibly fused to an aromatic hydrocarbon group, in which at least one carbon atom has been replaced by a heteroatom such as nitrogen, oxygen or sulfur. If the heterocycloalkyl group contains more than one heteroatom, these heteroatoms may be the same or different. Heterocycloalkyl groups include, but are not limited to, groups such as azepanyl, azetidinyl, indolinyl, morpholinyl, pyrazinyl, piperidinyl, pyrrolidinyl, tetrahydrofuryl, tetrahydroquinolinyl, tetrahydroindazolyl, tetrahydroindolyl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydroquinoxalinyl, tetrahydrothiopyranyl, thiazolidinyl, thiomorpholinyl, thioxanthyl, and the like.
"cycloalkenyl" refers to an unsaturated, monocyclic or polycyclic alkenyl group with one or more double bonds, possibly fused to an aromatic hydrocarbon group, including but not limited to cycloethenyl, cyclopropenyl, or other similar groups.
"Heterocycloalkenyl" means an unsaturated, monocyclic or polycyclic alkenyl radical having one or more double bonds, possibly condensed with an aromatic hydrocarbon radical, in which at least one carbon atom is replaced by a heteroatom such as nitrogen, oxygen or sulfur. If the heterocycloalkyl group contains more than one heteroatom, these heteroatoms may be the same or different.
"cycloalkynyl" refers to an unsaturated, monocyclic or polycyclic alkynyl group having one or more triple bonds, possibly fused to an aromatic hydrocarbon group, including, but not limited to, cycloalkynyl, cyclopropynyl, or the like.
"Heterocycloalkynyl" means an unsaturated, monocyclic or polycyclic alkynyl radical having one or more triple bonds, possibly condensed with an aromatic hydrocarbon radical, in which at least one carbon atom has been replaced by a heteroatom such as nitrogen, oxygen or sulfur. If the heterocycloalkyl group contains more than one heteroatom, these heteroatoms may be the same or different.
“C 2 -C 20 Alkynyl (C) 1 -C 20 ) Alkyl "and" C 2 -C 20 Alkynyl C 1 -C 20 The same meaning of alkyl is intended to mean a mixture of alkynyl groups containing two to twenty carbon atoms and alkyl groups containing one to twenty carbon atoms, the latter statement being intended primarily to avoid ambiguity which may arise between parentheses when forming the claim.
In one aspect, the embodiment of the present invention provides a diarylmethane compound, whose molecular structural general formula is as follows (I):
wherein R in the molecular structure general formula (I) 1 Is C 1 -C 20 Alkyl radical, C 1 -C 20 Heteroalkyl group, C 3 -C 20 Cycloalkyl, C 3 -C 20 Heterocycloalkyl radical, C 2 -C 20 Alkenyl radical, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl radical, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl group, C 3 -C 20 Heterocycloalkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C 3 -C 20 Arylalkyl radical, C 3 -C 20 Heteroaryl (C) 1 -C 20 ) Alkyl radical, C 2 -C 20 Alkenyl (C) 1 -C 20 ) Alkyl radical, C 2 -C 20 Alkynyl (C) 1 -C 20 ) Alkyl, cyano (C) 1 -C 20 ) Any one of an alkyl group, an alkyloxycarbonylalkyl group, and a hydrogen atom substituent;
when R is 1 Is (C) 1 -C 20 ) When it is an alkyl group, in one embodiment, the group (C) 1 -C 20 ) The alkyl group may be (C) 1 -C 10 ) Alkyl, (C) 1 -C 5 ) Alkyl, (C) 1 -C 4 ) Alkyl, (C) 1 -C 3 ) Alkyl, (C) 1 -C 2 ) Alkyl groups, and the like. In certain embodiments, (C) 1 -C 20 ) The alkyl group may be methyl, ethyl, propyl, butyl,Isobutyl, pentyl, isopentyl, and the like.
When R is 1 Is (C) 1 -C 20 ) When it is heteroalkyl, in one embodiment, (C) is 1 -C 20 ) The heteroalkyl group may be (C) 1 -C 10 ) Heteroalkyl group, (C) 1 -C 5 ) Heteroalkyl group, (C) 1 -C 4 ) Heteroalkyl group, (C) 1 -C 3 ) Heteroalkyl group, (C) 1 -C 2 ) Heteroalkyl groups and the like. In certain embodiments, the heteroatom in the heteroalkyl group may be a halogen, nitrogen atom, sulfur atom, or the like.
When R is 1 Is (C) 3 -C 20 ) Cycloalkyl, in one embodiment, the (C) 3 -C 20 ) The cycloalkyl group may be (C) 3 -C 10 ) Cycloalkyl group, (C) 3 -C 5 ) Cycloalkyl group, (C) 3 -C 4 ) Cycloalkyl groups, and the like. In certain embodiments, (C) 3 -C 20 ) Cycloalkyl groups may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.
When R is 1 Is (C) 3 -C 20 ) When it is heterocycloalkyl, in one embodiment, the group (C) 3 -C 20 ) The heterocycloalkyl group may be (C) 3 -C 10 ) Heterocycloalkyl group, (C) 3 -C 10 ) Heterocycloalkyl group, (C) 3 -C 5 ) Heterocycloalkyl group, (C) 3 -C 4 ) Heterocycloalkyl, and the like. In certain embodiments, the heteroatoms in the heterocycloalkyl group can be halogens, nitrogen atoms, sulfur atoms, and the like.
When R is 1 Is (C) 2 -C 20 ) Alkenyl, in one embodiment, the (C) 2 -C 20 ) The alkenyl group may be (C) 3 -C 10 ) Alkenyl, (C) 3 -C 5 ) Alkenyl, (C) 3 -C 4 ) Alkenyl, (C) 2 -C 3 ) Alkenyl groups, and the like. In certain embodiments, (C) 2 -C 20 ) The alkenyl group may be ethenyl, propenyl, butenyl, pentenyl, etc.
When R is 1 Is (C) 2 -C 20 ) When it is heteroalkenyl, the group (C) 2 -C 20 ) Heteroalkenyl can be (C) 2 -C 10 ) Heteroalkenyl, (C) 3 -C 10 ) Heteroalkenyl, (C) 3 -C 5 ) Heteroalkenyl, (C) 3 -C 4 ) Heteroalkenyl, (C) 2 -C 3 ) Heteroalkenyl and the like. In certain embodiments, the heteroatom in the heteroalkenyl can be a halogen, a nitrogen atom, a sulfur atom, and the like.
When R is 1 Is (C) 3 -C 20 ) Cycloalkenyl group of the formula (C) 3 -C 20 ) Cycloalkenyl can be (C) 3 -C 10 ) Cycloalkenyl group, (C) 3 -C 5 ) Cycloalkenyl group, (C) 3 -C 4 ) Cycloalkenyl groups and the like. In certain embodiments, (C) 3 -C 20 ) Cycloalkenyl can be cyclopropenyl, cyclobutenyl, cyclopentenyl and the like.
When R is 1 Is (C) 3 -C 20 ) When it is heterocycloalkenyl, the compound (C) 3 -C 20 ) The heterocycloalkenyl group may be (C) 3 -C 10 ) Heterocycloalkenyl, (C) 3 -C 5 ) Heterocycloalkenyl, (C) 3 -C 4 ) Heterocycloalkenyl, and the like. In certain embodiments, the heteroatom in the heterocycloalkenyl can be a halogen, a nitrogen atom, a sulfur atom, and the like.
When R is 1 Is (C) 2 -C 20 ) Alkynyl, the (C) 2 -C 20 ) Alkynyl may be (C) 2 -C 10 ) Alkynyl, (C) 3 -C 10 ) Alkynyl, (C) 3 -C 5 ) Alkynyl, (C) 3 -C 4 ) Alkynyl, (C) 2 -C 3 ) Alkynyl and the like. In certain embodiments, (C) 2 -C 20 ) The alkynyl group may be ethynyl, propynyl, butynyl, pentynyl, etc.
When R is 1 Is (C) 2 -C 20 ) When it is heteroalkynyl, (C) 2 -C 20 ) Heteroalkynyl can be (C) 2 -C 10 ) Heteroalkynyl, (C) 3 -C 10 ) Heteroalkynyl, (C) 3 -C 5 ) Heteroalkynyl, (C) 3 -C 4 ) Heteroalkynyl, (C) 2 -C 3 ) Heteroalkynyl, and the like. In certain embodiments, the heteroatom in the heteroalkynyl group can be a halogen, nitrogen atom, sulfur atom, and the like.
When R is 1 Is (C) 3 -C 20 ) Cycloalkynyl radicalWhen (C) is present 3 -C 20 ) The cycloalkynyl group can be (C) 3 -C 10 ) Cycloalkynyl, (C) 3 -C 5 ) Cycloalkynyl, (C) 3 -C 4 ) Cycloalkynyl, and the like. In certain embodiments, (C) 2 -C 20 ) The cycloalkynyl group may be cyclopropynyl, cyclobutynyl, cyclopentynyl, or the like.
When R is 1 Is (C) 3 -C 20 ) When the heterocyclic ring is alkynyl, the compound (C) 3 -C 20 ) The heterocycloalkynyl can be (C) 3 -C 10 ) Heterocycloalkynyl, (C) 3 -C 5 ) Heterocycloalkynyl, (C) 3 -C 4 ) Heterocycloalkynyl, and the like. In certain embodiments, the heteroatom in the heterocyclic alkynyl group can be a halogen, nitrogen atom, sulfur atom, or the like.
When R is 1 Is (C) 1 -C 20 ) Alkoxy, in one embodiment, the (C) 1 -C 20 ) The alkoxy group may be (C) 1 -C 10 ) Alkoxy group, (C) 1 -C 8 ) Alkoxy group, (C) 1 -C 6 ) Alkoxy group, (C) 1 -C 4 ) Alkoxy group, (C) 1 -C 3 ) Alkoxy group, (C) 1 -C 2 ) An alkoxy group. In certain embodiments, this (C) 1 -C 20 ) Alkoxy groups may be, but are not limited to, methyloxy, ethyloxy, propyloxy, and the like.
When R is 1 When aryl, the aryl group can be, but is not limited to, monocyclic aryl, polycyclic aryl, fused ring aryl. In one embodiment, the aryl group is a monocyclic aryl group. In certain embodiments, aryl is phenyl, substituted phenyl, and the like.
When R is 1 When substituted aryl, the substituted aryl may be, but is not limited to, phenyl substituted singly or multiply in the ortho, meta, or para positions. Substituents in substituted aryl include, but are not limited to, alkyl, substituted alkyl, halo, alkoxyamino, nitro, -NR 16 R 17 、-NR 16 -CO-NR 17 、-OCONR 16 、-PR 16 R 17 、-SOR 16 、-SO 2 -R 16 、-SiR 16 R 17 R 18 、-BR 16 R 17 Wherein R is 16 、R 17 、R 18 Which may be the same or different is as R above 1 、R 2 The groups shown. Wherein, when the substituent is an alkyl group, the alkyl group is exemplified by, but not limited to, methyl, ethyl, propyl, butyl, isobutyl; when the substituent is a substituted alkyl group, such as, but not limited to, trifluoromethyl, trichloromethyl, trifluoroethyl, trichloroethyl; when the substituent is halogen, such as, but not limited to, fluorine, chlorine, bromine, iodine; when the substituent is an alkoxy group, the alkoxy group is, for example, but not limited to, methyloxy, ethyloxy, propyloxy. The substituted aryl group may also be cyano (C) 1 -C 10 ) Alkyl radical (C) 3 -C 8 ) Aryl, substituted (C) 3 -C 8 ) And (4) an aryl group.
When R is 1 When heteroaryl, the heteroaryl may be (C) 3 -C 8 ) Heteroaryl, furan, thiophene.
When R is 1 When heteroaryl, the substituted heteroaryl may be substituted (C) 3 -C 8 ) Heteroaryl, alkoxy substituted furan, (C) 3 -C 8 ) Heteroaryl substituted furans, aliphatic chain substituted thiophenes.
When R is 1 When it is aryloxy, the aryloxy may be phenoxy, naphthoxy, anthracenoxy, phenanthroxy.
When R is 1 Is aryl (C) 1 -C 20 ) When it is an alkyl group, the aryl group (C) 1 -C 20 ) The alkyl group may be aryl (C) 1 -C 10 ) Alkyl, phenyl (C) 1 -C 10 ) Alkyl, phenyl (C) 1 -C 5 ) Alkyl, phenyl (C) 1 -C 4 ) Alkyl, phenyl (C) 1 -C 3 ) Alkyl, phenyl (C) 1 -C 2 ) Alkyl groups, and the like. In certain embodiments, aryl (C) 1 -C 20 ) The alkyl group may be phenylmethyl, phenylethyl, phenylpropyl, phenylbutyl, phenylisobutyl, phenylpentyl, phenylisoamyl, phenylneopentyl.
When R is 1 Is heteroaryl (C) 1 -C 20 ) When it is alkyl, the heteroaryl group (C) 1 -C 20 ) The alkyl group may be heteroaryl (C) 1 -C 10 ) Alkyl, heteroaryl (C) 1 -C 10 ) Alkyl, heteroaryl (C) 1 -C 5 ) Alkyl, heteroaryl (C) 1 -C 4 ) Alkyl, heteroaryl (C) 1 -C 3 ) Alkyl, heteroaryl (C) 1 -C 2 ) Alkyl groups, and the like. Wherein the heteroaryl group may be (C) 3 -C 8 ) Heteroaryl, furan, pyridine, and the like.
When R is 1 Is (C) 2 -C 20 ) Alkenyl (C) 1 -C 20 ) Alkyl group of the (C) 2 -C 20 ) Alkenyl (C) 1 -C 20 ) The alkyl group may be (C) 2 -C 10 ) Alkenyl (C) 1 -C 10 )、(C 2 -C 5 ) Alkenyl (C) 1 -C 3 ). In certain embodiments, the (C) 2 -C 20 ) Alkenyl (C) 1 -C 20 ) The alkyl group may be a 2-butenyl group, 2-pentenyl group, 3-hexenyl group, 3-heptenyl group, or the like.
When R is 1 Is (C) 2 -C 20 ) Alkynyl (C) 1 -C 20 ) When it is an alkyl group, in one embodiment, the group (C) 2 -C 20 ) Alkynyl (C) 1 -C 20 ) The alkyl group may be (C) 2 -C 10 ) Alkynyl (C) 1 -C 10 ) Alkyl, (C) 2 -C 5 ) Alkynyl (C) 1 -C 3 ) An alkyl group. In certain embodiments, the (C) 2 -C 20 ) Alkynyl (C) 1 -C 20 ) The alkyl group may be 2-butynyl, 2-pentynyl, 3-hexynyl, 3-heptynyl, etc.
When R is 1 Is cyano (C) 1 -C 20 ) Alkyl, in one embodiment, the cyano (C) 1 -C 20 ) The alkyl group may be cyano (C) 1 -C 10 ) Alkyl, cyano (C) 1 -C 5 ) Alkyl, cyano (C) 1 -C 4 ) Alkyl, cyano (C) 1 -C 3 ) Alkyl, cyano (C) 1 -C 2 ) Alkyl groups, and the like. In certain embodiments, cyano (C) 1 -C 20 ) The alkyl group may be cyanomethyl, cyanoethyl, cyanopropyl, cyanobutyl, cyanopentyl, or the like.
When R is 1 When it is an alkyloxycarbonylalkyl group, in one embodiment, the alkyloxycarbonylalkyl group can be (C) 1 -C 10 ) Alkyloxycarbonyl (C) 1 -C 10 ) Alkyl, (C) 1 -C 5 ) Alkyloxycarbonyl (C) 1 -C 5 ) Alkyl, (C) 1 -C 4 ) Alkyloxycarbonyl (C) 1 -C 4 ) Alkyl, (C) 1 -C 3 ) Alkyloxycarbonyl (C) 1 -C 3 ) Alkyl, (C) 1 -C 2 ) Alkyloxycarbonyl (C) 1 -C 2 ) Alkyl groups, and the like. In certain embodiments, the alkyloxycarbonylalkyl group can be an ethoxycarbonylethyl group, ethoxycarbonylmethyl group, methoxycarbonylethyl group, methoxycarbonylmethyl group, propoxycarbonylpropyl group, propoxycarbonylethyl group, propoxycarbonylmethyl group, and the like.
Based on the above examples, R in the above general molecular structural formula (I) 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is C 1 -C 20 Alkyl radical, C 1 -C 20 Heteroalkyl group, C 3 -C 20 Cycloalkyl, C 3 -C 20 Heterocycloalkyl radical, C 2 -C 20 Alkenyl radical, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl radical, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl, C 3 -C 20 Heterocycloalkynyl, C 1 -C 20 Alkoxy, amino, alkyl (C) 1 -C 20 ) Amino group, C 6 -C 20 Arylamine, (C) 1 -C 20 ) Alkyloxyboron group, (C) 1 -C 20 ) Alkylsilyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl (C) 1 -C 20 ) Alkyl, heteroaryl (C) 1 -C 20 ) Alkyl, cyano (C) 1 -C 20 ) Alkyl, (C) 1 -C 20 ) Alkyloxycarbonyl group (a)C 1 -C 20 ) Alkyl, (C) 1 -C 20 ) Alkyloxycarbonyl, (C) 6 -C 20 ) Aryloxy carbonyl group, (C) 1 -C 20 ) Alkylcarbonyl group, (C) 6 -C 20 ) Aryl carbonyl group, (C) 1 -C 20 ) Alkylaminocarbonyl, (C) 6 -C 20 ) Any one of arylaminocarbonyl, nitro, cyano, halogen and hydrogen atom substituent.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different (C) 1 -C 20 ) When it is an alkyl group, in one embodiment, the group (C) 1 -C 20 ) The alkyl group may be (C) 1 -C 10 ) Alkyl, (C) 1 -C 5 ) Alkyl, (C) 1 -C 4 ) Alkyl, (C) 1 -C 3 ) Alkyl, (C) 1 -C 2 ) Alkyl groups, and the like. In certain embodiments, (C) 1 -C 20 ) The alkyl group may be methyl, ethyl, propyl, butyl, isobutyl, pentyl, isopentyl, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different (C) 1 -C 20 ) When it is heteroalkyl, in one embodiment, the (C) 1 -C 20 ) The heteroalkyl radical may be (C) 1 -C 10 ) Heteroalkyl group, (C) 1 -C 5 ) Heteroalkyl group, (C) 1 -C 4 ) Heteroalkyl group, (C) 1 -C 3 ) Heteroalkyl group, (C) 1 -C 2 ) Heteroalkyl groups and the like. In certain embodiments, the heteroatom in the heteroalkyl group may be a halogen, nitrogen atom, sulfur atom, or the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different (C) 3 -C 20 ) Cycloalkyl, in one embodiment, the (C) 3 -C 20 ) The cycloalkyl group may be (C) 3 -C 10 ) Cycloalkyl group, (C) 3 -C 5 ) Cycloalkyl, (C) 3 -C 4 ) Cycloalkyl groups, and the like. In certain embodiments, (C) 3 -C 20 ) Cycloalkyl groups may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are the same or different (C) 3 -C 20 ) When it is heterocycloalkyl, in one embodiment, (C) is 3 -C 20 ) The heterocycloalkyl group may be (C) 3 -C 10 ) Heterocycloalkyl group, (C) 3 -C 10 ) Heterocycloalkyl, (C) 3 -C 5 ) Heterocycloalkyl group, (C) 3 -C 4 ) Heterocycloalkyl, and the like. In certain embodiments, the heteroatom in the heterocycloalkyl group can be a halogen, nitrogen atom, sulfur atom, or the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different (C) 2 -C 20 ) When an alkenyl group is present, the group (C) 2 -C 20 ) The alkenyl group may be (C) 2 -C 10 ) Alkenyl, (C) 3 -C 10 ) Alkenyl, (C) 3 -C 5 ) Alkenyl, (C) 3 -C 4 ) Alkenyl, (C) 2 -C 3 ) Alkenyl groups, and the like. In certain embodiments, (C) 2 -C 20 ) The alkenyl group may be ethenyl, propenyl, butenyl, pentenyl, or the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different (C) 2 -C 20 ) When it is heteroalkenyl, the group (C) 2 -C 20 ) The heteroalkenyl group can be (C) 2 -C 10 ) Heteroalkenyl, (C) 3 -C 10 ) Heteroalkenyl, (C) 3 -C 5 ) Heteroalkenyl, (C) 3 -C 4 ) Heteroalkenyl, (C) 2 -C 3 ) Heteroalkenyl and the like. In some embodimentsThe hetero atom in the heteroalkenyl group may be any of a halogen atom, a nitrogen atom, a sulfur atom, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different (C) 2 -C 20 ) When an alkenyl group is present, the group (C) 2 -C 20 ) Heteroalkenyl can be (C) 2 -C 10 ) Heteroalkenyl, (C) 3 -C 10 ) Heteroalkenyl, (C) 3 -C 5 ) Heteroalkenyl, (C) 3 -C 4 ) Heteroalkenyl, (C) 2 -C 3 ) Heteroalkenyl and the like. In certain embodiments, the heteroatom in the heteroalkenyl group can be a halogen, a nitrogen atom, a sulfur atom, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are the same or different (C) 2 -C 20 ) Cycloalkenyl group of the formula (C) 2 -C 20 ) Cycloalkenyl can be (C) 2 -C 10 ) Cycloalkenyl, (C) 3 -C 10 ) Cycloalkenyl, (C) 3 -C 5 ) Cycloalkenyl group, (C) 3 -C 4 ) Cycloalkenyl group, (C) 2 -C 3 ) Cycloalkenyl groups, and the like. In certain embodiments, (C) 2 -C 20 ) Cycloalkenyl can be cyclopropenyl, cyclobutenyl, cyclopentenyl and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different (C) 2 -C 20 ) Alkynyl, the (C) 2 -C 20 ) Alkynyl may be (C) 2 -C 10 ) Alkynyl, (C) 3 -C 10 ) Alkynyl, (C) 3 -C 5 ) Alkynyl, (C) 3 -C 4 ) Alkynyl, (C) 2 -C 3 ) Alkynyl and the like. In certain embodiments, (C) 2 -C 20 ) The alkynyl group may be an ethynyl group, propynyl group, butynyl group, pentynyl group or the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is (C) 3 -C 20 ) When it is heterocycloalkenyl, the compound (C) 3 -C 20 ) The heterocycloalkenyl group may be (C) 3 -C 10 ) Heterocycloalkenyl, (C) 3 -C 5 ) Heterocycloalkenyl, (C) 3 -C 4 ) Heterocycloalkenyl, and the like. In certain embodiments, the heteroatom in the heterocycloalkenyl can be a halogen, a nitrogen atom, a sulfur atom, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is (C) 2 -C 20 ) Alkynyl, the (C) 2 -C 20 ) Alkynyl may be (C) 2 -C 10 ) Alkynyl, (C) 3 -C 10 ) Alkynyl, (C) 3 -C 5 ) Alkynyl, (C) 3 -C 4 ) Alkynyl, (C) 2 -C 3 ) Alkynyl and the like. In certain embodiments, (C) 2 -C 20 ) The alkynyl group may be an ethynyl group, propynyl group, butynyl group, pentynyl group or the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is (C) 2 -C 20 ) When it is heteroalkynyl, (C) 2 -C 20 ) Heteroalkynyl can be (C) 2 -C 10 ) Heteroalkynyl, (C) 3 -C 10 ) Heteroalkynyl, (C) 3 -C 5 ) Heteroalkynyl, (C) 3 -C 4 ) Heteroalkynyl, (C) 2 -C 3 ) Heteroalkynyl, and the like. In certain embodiments, the heteroatom in the heteroalkynyl group can be a halogen, nitrogen atom, sulfur atom, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is (C) 8 -C 20 ) Cycloalkynyl group, the (C) 3 -C 20 ) The cycloalkynyl group can be (C) 3 -C 10 ) Cycloalkynyl, (C) 3 -C 5 ) Cycloalkynyl, (C) 3 -C 4 ) Cycloalkynyl, and the like. In certain embodiments, (C) 2 -C 20 ) The cycloalkynyl group can be cyclooctynyl group, cyclononynyl group, etc.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is (C) 3 -C 20 ) Heterocyclic alkynyl, the (C) 3 -C 20 ) The heterocycloalkynyl can be (C) 3 -C 10 ) Heterocycloalkynyl, (C) 3 -C 5 ) Heterocycloalkynyl, (C) 3 -C 4 ) Heterocycloalkynyl, and the like. In certain embodiments, the heteroatoms in the heterocyclic alkynyl group can be halogens, nitrogen atoms, sulfur atoms, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is (C) 1 -C 20 ) Alkoxy, in one embodiment, the (C) 1 -C 20 ) The alkoxy group may be (C) 1 -C 10 ) Alkoxy group, (C) 1 -C 8 ) Alkoxy group, (C) 1 -C 6 ) Alkoxy group, (C) 1 -C 4 ) Alkoxy group, (C) 1 -C 3 ) Alkoxy group, (C) 1 -C 2 ) An alkoxy group. In certain embodiments, this (C) 1 -C 20 ) Alkoxy groups may be, but are not limited to, methyloxy, ethyloxy, propyloxy, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is (C) 1 -C 20 ) Alkylamino, in one embodiment, (C) is 1 -C 20 ) The alkylamino group can be (C) 1 -C 10 ) Alkylamino radical, (C) 1 -C 8 ) Alkylamino radical, (C) 1 -C 6 ) Alkylamino radical, (C) 1 -C 4 ) Alkylamino radical, (C) 1 -C 3 ) Alkylamino radical, (C) 1 -C 2 ) An alkylamino group. In certain embodiments, this (C) 1 -C 20 ) The alkylamino group can be, but is not limited to, methylamino, ethylamino, propylamino, dimethylamino, diethylamino, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is (C) 3 -C 22 ) Arylamino, in one embodiment, (C) 3 -C 22 ) The arylamine group may be (C) 3 -C 18 ) Arylamine, (C) 3 -C 14 ) Arylamine, (C) 3 -C 10 ) An arylamine group. In certain embodiments, this (C) 3 -C 22 ) Alkylamino can be, but is not limited to, phenylamino, naphthylamino, diphenylamino, dinaphthylamino, difuranylamino, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is (C) 1 -C 20 ) An alkyloxyboron group, in one embodiment, the (C) 1 -C 20 ) The alkyloxyboron group may be alkyl (C) 1 -C 10 ) Oxyboronyl, alkyl (C) 1 -C 8 ) Oxyboronyl, alkyl (C) 1 -C 6 ) Oxyboronyl, alkyl (C) 1 -C 4 ) Oxyboronyl, alkyl (C) 1 -C 3 ) Oxyboronyl, alkyl (C) 1 -C 2 ) An oxyboronyl group. In certain embodiments, the alkyl (C) 1 -C 20 ) The oxyboronyl group may be, but is not limited to, a dimethoxyboryl group, a diethoxyboronyl group, a pinacolboronyl group, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is (C) 1 -C 20 ) When alkylsilyl, in one embodiment, (C) is 1 -C 20 ) The alkylsilyl group may be (C) 1 -C 10 ) Alkylsilyl (C) 1 -C 8 ) Alkyl silicon base, (C) 1 -C 6 ) Alkyl silicon base, (C) 1 -C 4 ) Alkyl silicon base、(C 1 -C 3 ) Alkyl silicon base, (C) 1 -C 2 ) And alkyl silicon base. In certain embodiments, this (C) 1 -C 20 ) The alkylsilyl group may be, but is not limited to, trimethylsilyl, triethylsilyl, triisopropylsilyl, dimethyl-t-butylsilyl, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 When the aryl groups are the same or different, the aryl groups may be, but are not limited to, monocyclic aryl groups, polycyclic aryl groups, and fused ring aryl groups. In one embodiment, the aryl group is a monocyclic aryl group. In certain embodiments, aryl is phenyl, substituted phenyl, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 When the same or different substituted aryl groups are present, the substituted aryl groups may be, but are not limited to, phenyl groups substituted singly or multiply in the ortho, meta, or para positions. Substituents include, but are not limited to, alkyl, substituted alkyl, halo, alkoxyamino, nitro, substituted amino, substituted boryl, substituted phosphino, substituted silyl, substituted thio, and the like. Wherein, when the substituent is an alkyl group, the alkyl group is exemplified by, but not limited to, methyl, ethyl, propyl, butyl, isobutyl; when the substituent is a substituted alkyl group, such as, but not limited to, trifluoromethyl, trichloromethyl, trifluoroethyl, trichloroethyl; when the substituent is halogen, such as, but not limited to, fluorine, chlorine, bromine, iodine; when the substituent is an alkoxy group, the alkoxy group is, for example, but not limited to, methyloxy, ethyloxy, propyloxy. The substituted aryl group may also be cyano (C) 1 -C 10 ) Alkyl radical (C) 3 -C 8 ) Aryl, substituted (C) 3 -C 8 ) And (4) an aryl group.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 When the same or different heteroaryl groups are present, the heteroaryl groups may be, but are not limited toIs limited to (C) 3 -C 8 ) Heteroaryl, furan, thiophene.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 In the case of identical or different substituted hetaryl, the substituted hetaryl may be substituted (C) 3 -C 8 ) Heteroaryl, alkoxy substituted furan, (C) 3 -C 8 ) Heteroaryl substituted furans, aliphatic chain substituted thiophenes.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 When the same or different aryloxy groups, the aryloxy groups may be, but are not limited to, phenoxy, naphthoxy, anthracenoxy, phenanthroxy.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different aryl radicals (C) 1 -C 20 ) When it is an alkyl group, the aryl group (C) 1 -C 20 ) The alkyl group may be aryl (C) 1 -C 10 ) Alkyl, phenyl (C) 1 -C 10 ) Alkyl, phenyl (C) 1 -C 5 ) Alkyl, phenyl (C) 1 -C 4 ) Alkyl, phenyl (C) 1 -C 3 ) Alkyl, phenyl (C) 1 -C 2 ) Alkyl groups, and the like. In certain embodiments, aryl (C) 1 -C 20 ) Alkyl groups may be, but are not limited to, phenylmethyl, phenylethyl, phenylpropyl, phenylbutyl, phenylisobutyl, phenylpentyl, phenylisopentyl, phenylneopentyl.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different heteroaryl (C) 1 -C 20 ) When it is alkyl, the heteroaryl group (C) 1 -C 20 ) The alkyl group may be heteroaryl (C) 1 -C 10 ) Alkyl, heteroaryl (C) 1 -C 8 ) Alkyl radicalHeteroaryl (C) 1 -C 5 ) Alkyl, heteroaryl (C) 1 -C 4 ) Alkyl, heteroaryl (C) 1 -C 3 ) Alkyl, heteroaryl (C) 1 -C 2 ) Alkyl groups, and the like. Wherein the heteroaryl may be, but is not limited to, (C) 3 -C 8 ) Heteroaryl, furan, pyridine, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different cyano groups (C) 1 -C 20 ) When it is alkyl, the cyano group (C) 1 -C 20 ) The alkyl group may be cyano (C) 1 -C 10 ) Alkyl, cyano (C) 1 -C 8 ) Alkyl, cyano (C) 1 -C 6 ) Alkyl, cyano (C) 1 -C 4 ) Alkyl, cyano (C) 1 -C 3 ) Alkyl, cyano (C) 1 -C 2 ) Alkyl groups, and the like. Wherein the cyano group (C) 1 -C 20 ) Alkyl groups may be, but are not limited to, cyanomethyl, cyanoethyl, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 When the alkyl groups are the same or different alkyl oxycarbonylalkyl groups, in one embodiment, the alkyl oxycarbonylalkyl groups may be (C) 1 -C 10 ) Alkyloxycarbonyl (C) 1 -C 10 ) Alkyl, (C) 1 -C 5 ) Alkyloxycarbonyl (C) 1 -C 5 ) Alkyl, (C) 1 -C 4 ) Alkyloxycarbonyl (C) 1 -C 4 ) Alkyl, (C) 1 -C 3 ) Alkyloxycarbonyl (C) 1 -C 3 ) Alkyl, (C) 1 -C 2 ) Alkyloxycarbonyl (C) 1 -C 2 ) Alkyl groups, and the like. In certain embodiments, the alkyloxycarbonylalkyl group can be, but is not limited to, ethoxycarbonylethyl, ethoxycarbonylmethyl, methoxycarbonylethyl, methoxycarbonylmethyl, propoxycarbonylpropyl, propoxycarbonylethyl, propoxycarbonylmethyl, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different (C) 1 -C 20 ) Alkyloxycarbonyl, in one embodiment, the (C) 1 -C 20 ) Alkane (C) 1 -C 20 ) The oxycarbonyl group can be (C) 1 -C 10 ) Alkyloxycarbonyl, (C) 1 -C 5 ) Alkyloxycarbonyl, (C) 1 -C 4 ) Alkyloxycarbonyl, (C) 1 -C 3 ) Alkyloxycarbonyl, (C) 1 -C 2 ) Alkyloxycarbonyl, and the like. In certain embodiments, the alkyloxycarbonyl group may be, but is not limited to, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different (C) 3 -C 20 ) Aryloxy carbonyl group, in one embodiment, the (C) 3 -C 20 ) The aryloxycarbonyl group may be aryl (C) 3 -C 10 ) Oxycarbonyl, aryl (C) 3 -C 8 ) Oxycarbonyl, and the like. In certain embodiments, aryl (C) 3 -C 20 ) The oxycarbonyl group can be, but is not limited to, phenyloxycarbonyl, naphthyloxycarbonyl, anthracenoxycarbonyl, thiophenoxycarbonyl, pyrazolyloxycarbonyl, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are identical or different (C) 1 -C 20 ) Alkyl carbonyl, in one embodiment, the (C) 1 -C 20 ) The alkylcarbonyl group may be (C) 1 -C 10 ) Alkylcarbonyl, (C) 1 -C 5 ) Alkylcarbonyl group, (C) 1 -C 4 ) Alkylcarbonyl, (C) 1 -C 3 ) Alkylcarbonyl group, (C) 1 -C 2 ) Alkylcarbonyl and the like. In certain embodiments, the alkyloxycarbonyl group may be, but is not limited to, methylcarbonyl, ethylcarbonyl, propylcarbonyl, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are the same or different (C) 3 -C 20 ) Aryl carbonyl, in one embodiment, the group (C) 3 -C 20 ) The arylcarbonyl group may be (C) 3 -C 10 ) Aryl carbonyl group, (C) 3 -C 8 ) Arylcarbonyl, and the like. In certain embodiments, (C) 3 -C 20 ) Arylcarbonyl can be, but is not limited to, phenylcarbonyl, naphthylcarbonyl, anthracenylcarbonyl, pyridylcarbonyl, thienylcarbonyl, pyrazolylcarbonyl, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are the same or different (C) 1 -C 20 ) In the case of alkylaminocarbonyl, in one embodiment, (C) is 1 -C 20 ) The alkylaminocarbonyl radical may be (C) 1 -C 10 ) Alkylaminocarbonyl, (C) 1 -C 8 ) Alkylaminocarbonyl, (C) 1 -C 6 ) Alkylaminocarbonyl, (C) 1 -C 4 ) Alkylaminocarbonyl, (C) 1 -C 3 ) Alkylaminocarbonyl, (C) 1 -C 2 ) Alkylaminocarbonyl, and the like. In certain embodiments, (C) 1 -C 20 ) The alkylaminocarbonyl group may be, but is not limited to, methylaminocarbonyl, ethylaminocarbonyl, dimethylaminocarbonyl, piperidinylcarbonyl, and the like.
When R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Are the same or different (C) 3 -C 20 ) Arylaminocarbonyl, in one embodiment, (C) is 3 -C 20 ) The arylaminocarbonyl group may be (C) 3 -C 10 ) Arylaminocarbonyl, (C) 3 -C 8 ) Arylaminocarbonyl, (C) 3 -C 6 ) Arylaminocarbonyl, and the like. In certain embodiments, (C) 3 -C 20 ) The arylaminocarbonyl group may be, but is not limited toBut are not limited to phenylaminocarbonyl, naphthylaminocarbonyl, diphenylaminocarbonyl, dinaphthylaminocarbonyl, and the like.
Therefore, the diarylmethane compounds with the molecular structure general formula (I) in the embodiments can be widely applied to the synthesis of drug intermediates, particularly heterocyclic compounds, and the preparation of functional materials.
On the other hand, on the basis of the diarylmethane compounds of the above embodiments of the present invention, the embodiments of the present invention also provide a preparation method of the diarylmethane compounds of the above general molecular structure formula (I). The method comprises the following steps:
s01: providing a sulfonic acid ester compound A of benzyl halogenated hydrocarbon or benzyl alcohol, a boric acid or boric anhydride compound B respectively represented by the following structural formula:
A、
B、
s02: adding the sulfonic ester compound A of benzyl halogenated hydrocarbon or benzyl alcohol and the boric acid or boric anhydride compound B into a reaction system containing an organic micromolecule catalyst, an alkali reagent and a solvent to react at the temperature of 30-110 ℃ to obtain the diarylmethane compound shown as the following structural general formula (I):
specifically, in the step S01, R in the molecular structural formula of the sulfonic acid ester compound A of benzyl halohydrocarbon or benzyl alcohol 1 、R 2 、R 3 、R 4 、R 5 、R 6 The group is represented as R in the general formula (I) of the molecular structure of the diarylmethane compound in the embodiment of the invention 1 、R 2 、R 3 、R 4 、R 5 、R 6 The groups represented are the same. Boric acid or boronR in molecular structural formula of anhydride compound B 7 、R 8 、R 9 、R 10 、R 11 The group is as R in the structural general formula (I) of the diarylmethane compound 7 、R 8 、R 9 、R 10 、R 11 The groups represented are the same. X is halogen and hydroxy sulfonate. For economy of disclosure, further description is omitted here.
The sulfonic acid ester compound a of benzyl halohydrocarbon or benzyl alcohol and the boric acid or boric anhydride compound B of step S01 can be prepared according to a method conventionally used in the art, and can be obtained commercially.
In step S02, according to the structural formulas of the reaction substrates, i.e., the benzyl halohydrocarbon or benzyl alcohol sulfonate compound a and the boric acid or boric anhydride compound B, a is coupled as an electrophilic reagent and B is coupled as an affinity reagent, so that the two reactants undergo a formal Suzuki coupling reaction. Thus, not only the atom utilization rate of the reactant is effectively improved, but also the byproducts are inorganic salt with five toxins and boric acid. And the transition metal catalyst obtained in the traditional Suzuki coupling reaction is effectively avoided by combining the form of organic micromolecule catalysis, so that the target product diarylmethane compound with high regioselectivity and extremely wide range is efficiently and greenly prepared.
The coupling reaction formula of the sulfonic acid ester compound a of benzyl halohydrocarbon or benzyl alcohol and the boric acid or boric acid anhydride compound B in step S02 in the reaction environment and system in step S02 is as follows:
in the chemical reaction formula, the organic small molecular catalyst and the alkali reagent act synergistically, so that the catalytic system is low in toxicity, the reaction efficiency is improved, and the by-products are few and non-toxic. Meanwhile, the reaction process is safe and controllable, and the operation in the preparation production process is simplified. The alkali reagent deprotonates an intermediate formed by the organic small-molecular catalyst and the compound A, catalytic circulation of the reaction can be synergistically promoted within a certain load range, and the reaction has high catalytic efficiency under the condition of a proportion within a certain range, so that a target product with an almost single absolute configuration is obtained.
In order to make the catalytic system exert more effective catalytic action, in one embodiment, the molar ratio of the organic small molecule catalyst, the alkali agent, the boric acid or the boric anhydride compound B is (0.1-20): 1-200): 1-150, preferably (0.1-20):200: 150.
In one embodiment, the addition amount of the organic small molecule catalyst, the alkali agent, the boric acid or the boric anhydride compound B in the reaction system is controlled to be (0.2-20): 1-200): 1-150): 1-100 molar ratio with the sulfonic acid ester compound A of the benzyl halogenated hydrocarbon or benzyl alcohol.
In one embodiment, the organic small-molecule catalyst is one of thioether, thianthrene, phenoxathiin and phenothiazine. In specific experiments, the organic small molecule catalyst listed as the preferable organic small molecule catalyst can catalyze the reaction more efficiently. As in the specific example, the organic small molecule catalyst is the following compound C:
C：
y in the structural general formula C is a sulfur atom or an oxygen atom; in the structural general formula C, R 12 、R 13 、R 14 、R 15 Are identical or different and are C 1 -C 20 Alkyl radical, C 1 -C 20 Heteroalkyl group, C 3 -C 20 Cycloalkyl radical, C 3 -C 20 Heterocycloalkyl radical, C 1 -C 20 Perfluoro substituted alkyl group, C 2 -C 20 Alkenyl radical, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl radical, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl group, C 3 -C 20 Heterocycloalkynyl, C 1 -C 20 Alkoxy, amino、(C 1 -C 20 ) Alkylamino radical, (C) 3 -C 20 ) Arylamine, (C) 1 -C 20 ) Alkyloxyboron group, (C) 1 -C 20 ) Alkylsilyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aryloxy, heteroaryloxy, aryl (C) 1 -C 20 ) Alkyl, heteroaryl (C) 1 -C 20 ) Alkyl, cyano (C) 1 -C 20 ) Alkyl, (C) 1 -C 20 ) Alkyloxycarbonyl (C) 1 -C 20 ) Alkyl, (C) 1 -C 20 ) Alkyloxycarbonyl, (C) 3 -C 20 ) Aryloxy carbonyl group, (C) 1 -C 20 ) Alkylcarbonyl, (C) 3 -C 20 ) Aryl carbonyl group, (C) 1 -C 20 ) Alkylaminocarbonyl, (C) 3 -C 20 ) Any one of arylaminocarbonyl, nitro, cyano, halogen and hydrogen atom substituent. And/or
In one embodiment, the base reagent is at least one of lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, potassium pyrophosphate, 1-azabicyclo [2.2.2] octane, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 1,5, 7-triazabicyclo (4.4.0) dec-5-ene, triethylamine, diisopropylethylamine, sodium methoxide, sodium ethoxide, and sodium ethylmercaptide. The alkali agent can efficiently promote the formation of ylide intermediates (sulfonium salt intermediates formed in situ after nucleophilic substitution of benzyl halohydrocarbon or benzyl alcohol sulfonate compounds A and organic small molecule catalysts C), promote the reaction with boric acid or boric anhydride B compounds, and realize high regioselectivity reaction.
Under the action of the organic small molecule catalyst, the reaction system is carried out at a heating temperature, and the applicable reaction temperature range is 20-140 ℃.
In order to further improve the reaction efficiency, in one embodiment, the reaction temperature of the reaction system is 80 to 110 ℃.
In another embodiment, the reaction temperature of the reaction system is 110-140 ℃. The reaction time in the environment of the temperature of each preferred reaction should be such that the above reactants are sufficiently reacted, for example, the reaction time may be 6 to 48 hours, or longer.
In the above reaction system, a certain amount of solvent is optionally added. Such solvents include, but are not limited to, acetonitrile, tetrahydrofuran, 1, 4-dioxane. Alternative solvents will be readily selected by those of ordinary skill in the art based on the reactions and disclosure described herein. In one embodiment, the solvent is added in an amount such that the molar ratio of solvent to catalyst is (50-1000000): 1.
therefore, the preparation method of the diarylmethane compound uses the organic small molecular catalyst, so that the catalytic system has low toxicity, high atom utilization rate and production efficiency, safe and controllable reaction process, and simplified operation in the preparation production process. Meanwhile, the toxicity of the reaction residues is reduced to the minimum, the pollution to the environment in the production process is reduced, and the steps and the operation for removing the residues after the reaction are simplified. In addition, the reactant raw materials are very easy to obtain, and the reactant can be directly used for preparation production without additional modification before reaction, so that the operation steps are simplified, and the reaction route is shortened; obviously reduces the production cost. Secondly, the method can also flexibly adjust the proportion and the addition amount among the organic small molecular catalyst, the alkali reagent and the reactant, further improve the utilization rate and the production efficiency of the atoms and reduce the production of byproducts.
In another aspect, based on the diarylmethane compounds and the preparation method thereof, the embodiment of the invention provides the application range of the diarylmethane compounds. In one embodiment, the diarylmethane compounds are used in the synthesis of pharmaceutical intermediates and in the preparation of functional materials. Thus, since the diarylmethane compound has a typical high-functional structure as described above and the preparation method thereof is advanced, it can be widely used for the synthesis of pharmaceutical intermediates and the preparation of functional materials, and can effectively reduce the economic cost for the preparation of pharmaceutical intermediates and functional materials and provide environmental friendliness.
For example, the synthesis and modification of the drug molecule and the natural active molecule, the synthesis of the celecoxib drug modified derivative (example 20), the bazedoxifene drug modified derivative (example 21), the natural product active molecule epiandrosterone modified derivative (example 22), and the hypolipidemic drug beclofibrate (example 23), etc., all prove the utility of the invention.
The present invention will now be described in further detail with reference to examples.
Example 1
This example provides 1- (4-methoxybenzyl) -2, 4-dimethylbenzene and a process for its preparation. The structural formula of the 1- (4-methoxybenzyl) -2, 4-dimethyl is shown as the following molecular structural formula I1:
the preparation method comprises the following steps:
2-methoxy-10- (4-methoxyphenyl) -10H-phenothiazine catalyst (0.1mmol,0.2eq), potassium pyrophosphate (1.0mmol,2.0eq), 4-methoxyphenylboronic acid (0.75mmol,1.5eq) and 0.5mL of anhydrous acetonitrile were added to a dry 10mL sealed tube, argon was substituted three times, 0.5mmol of 2- (chloromethyl) -1, 4-dimethylbenzene was added, argon was substituted again three times, the reaction tube was sealed and stirred at 110 ℃ for 48H.
After the reaction is finished, the filtrate is dried by spinning, and is separated by column chromatography, so that the target product is obtained, and is colorless oily liquid, and the yield is 66%.
The result of the correlation characterization analysis is as follows: 1 H NMR(400MHz,CDCl 3 )δ7.09(m,J＝8.4,2.9Hz,3H),7.04–6.94(m,2H),6.90–6.83(m,2H),3.94(s,2H),3.83(s,3H),2.34(s,3H),2.25(s,3H). 13 C NMR(101MHz,CDCl 3 )δ157.79,139.11,135.34,133.36,132.58,130.60,130.16,129.63,126.99,113.78,55.25,38.53,21.01,19.18.MS(70eV):m/z(％):226(M + ,64.37)。
this result further confirmed the molecular structure of the product as described above for molecular structure I1.
Example 2
This example provides 4- (4-methoxybenzyl) -1, 1' -biphenyl and a method for preparing the same. The structural formula of the 4- (4-methoxybenzyl) -1, 1' -biphenyl is shown as the following molecular structural formula I2:
the preparation method refers to the preparation method of 1- (4-methoxybenzyl) -2, 4-dimethylbenzene in example 1, except that 4-chloromethyl-1, 1' -biphenyl (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, the filtrate is dried by spinning and separated by column chromatography to obtain the target product, white solid and 74% yield.
The product I2 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(400MHz,CDCl 3 )δ7.65–7.60(m,2H),7.60–7.55(m,2H),7.51–7.44(m,2H),7.41–7.35(m,1H),7.33–7.29(m,2H),7.23–7.17(m,2H),6.95–6.88(m,2H),4.02(s,2H),3.84(s,3H). 13 C NMR(101MHz,CDCl 3 )δ158.04,141.04,140.74,138.96,133.14,129.91,129.21,128.73,127.21,127.07,127.02,113.95,55.28,40.70.MS(70eV):m/z(％):274(M + ,100)。
this result further confirmed the molecular structure of the product as described above for molecular structure I2.
Example 3
This example provides 1-bromo-4- (4-methoxybenzyl) benzene and a process for its preparation. The structural formula of the 1-bromo-4- (4-methoxybenzyl) benzene is shown as the following molecular structural formula I3:
the preparation method refers to the preparation method of 1- (4-methoxybenzyl) -2, 4-dimethylbenzene in example 1, except that 1-bromo-4- (chloromethyl) benzene (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, the filtrate is dried by spinning and separated by column chromatography to obtain the target product, colorless liquid and 80% yield.
The product I3 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(400MHz,CDCl 3 )δ7.48–7.42(m,2H),7.17–7.06(m,4H),6.94–6.87(m,2H),3.92(s,2H),3.84(s,3H). 13 C NMR(101MHz,CDCl 3 )δ158.14,140.63,132.57,131.51,130.59,129.86,119.86,114.01,55.29,40.44.MS(70eV):m/z(％):278(M + ,62.53),276(M + ,66.90).
this result further confirmed the molecular structure of the product as described above for molecular structure I3.
Example 4
This example provides 1-iodo-4- (4-methoxybenzyl) benzene and a method for its preparation. The structural formula of the 1-iodine-4- (4-methoxybenzyl) benzene is shown as the following molecular structural formula I4:
the preparation method refers to the preparation method of 1- (4-methoxybenzyl) -2, 4-dimethylbenzene in example 1, except that 1-iodo-4- (chloromethyl) benzene (0.5mmol) is used instead of 2- (chloromethyl) -1, 4-dimethylbenzene, and the filtrate is dried by spinning and separated by column chromatography to obtain the target product, white solid and 57% yield.
The product I4 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(400MHz,CDCl 3 )δ7.66–7.59(m,2H),7.14–7.08(m,2H),6.99–6.93(m,2H),6.91–6.83(m,2H),3.89(s,2H),3.82(s,3H). 13 C NMR(101MHz,CDCl 3 )δ158.12,141.28,137.46,132.49,130.90,129.82,113.99,91.18,55.27,40.52.MS(70eV):m/z(％):324(M + ,100).
this result further confirmed the molecular structure of the product as described above for molecular structure I4.
Example 5
This example provides 1-bromo-3- (4-methoxybenzyl) benzene and a method for its preparation. The structural formula of the 1-bromo-3- (4-methoxybenzyl) benzene is shown as the following molecular structural formula I5:
the preparation method refers to the preparation method of 1- (4-methoxybenzyl) -2, 4-dimethylbenzene in example 1, except that 1-bromo-3- (chloromethyl) benzene (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, the filtrate is dried by spinning and separated by column chromatography to obtain the target product, colorless liquid and 60% yield.
The product I5 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(400MHz,CDCl 3 )δ7.37(m,2H),7.21–7.10(m,4H),6.93–6.86(m,2H),3.93(s,2H),3.83(s,3H). 13 C NMR(101MHz,CDCl 3 )δ158.17,143.97,132.27,131.80,129.98,129.89,129.14,127.46,122.55,114.02,55.27,40.66.MS(70eV):m/z(％):276(M + ,77.03),278(M + ,59.70).
this result further confirmed the molecular structure of the product as described above for molecular structure I5.
Example 6
This example provides 1-iodo-3- (4-methoxybenzyl) benzene and a method for its preparation. The structural formula of the 1-iodine-3- (4-methoxybenzyl) benzene is shown as the following molecular structural formula I6:
the preparation method is as follows 1- (4-methoxybenzyl) -2, 4-dimethylbenzene preparation method in example 1, except that 1-iodo-3- (chloromethyl) benzene (0.5mmol) is used instead of 2- (chloromethyl) -1, 4-dimethylbenzene, filtrate is dried by spinning, and column chromatography separation is carried out to obtain the target product, white solid, yield 65%.
The product I6 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(400MHz,CDCl 3 )δ7.58(m,2H),7.18(d,J＝7.8Hz,1H),7.16–7.09(m,2H),7.05(t,J＝7.7Hz,1H),6.93–6.85(m,2H),3.91(s,2H),3.83(s,3H). 13 C NMR(101MHz,CDCl 3 )δ158.17,144.06,137.76,135.13,132.30,130.19,129.90,128.12,114.04,94.65,55.29,40.58.MS(70eV):m/z(％):324(M + ,100).
this result further confirmed the molecular structure of the product as described above for molecular structure I6.
Example 7
This example provides 4- (4-methoxybenzyl) benzonitrile and a preparation method thereof. The structural formula of 4- (4-methoxybenzyl) benzonitrile is shown in the following molecular structural formula I7:
the preparation method refers to the preparation method of 1- (4-methoxybenzyl) -2, 4-dimethylbenzene in example 1, except that 4- (chloromethyl) benzonitrile (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, 0.1mmol of potassium bromide is added, the filtrate is dried in a rotary manner, and the target product is obtained by column chromatography separation, colorless liquid and 68% yield.
The prepared product I7 was subjected to characterization data analysis, and the results were: 1 H NMR(400MHz,CDCl 3 )δ7.62–7.55(m,2H),7.29(d,J＝8.4Hz,2H),7.15–7.06(m,2H),6.92–6.83(m,2H),3.99(s,2H),3.81(s,3H). 13 C NMR(101MHz,CDCl 3 )δ158.34,147.23,132.26,131.38,129.94,129.50,119.03,114.14,109.90,55.27,41.09.MS(70eV):m/z(％):223(M + ,100).
this result further confirmed the molecular structure of the product as described above for molecular structure I7.
Example 8
This example provides ethyl-4- (4-methoxybenzyl) benzoate and a method for preparing the same. The structural formula of ethyl-4- (4-methoxybenzyl) benzoate is shown in the following molecular structural formula I8:
the preparation method was carried out according to the preparation method of 1- (4-methoxybenzyl) -2, 4-dimethylbenzene in example 1, except that ethyl-4- (chloromethyl) benzoate (0.5mmol) was used instead of 2- (chloromethyl) -1, 4-dimethylbenzene, and 0.1mmol of potassium bromide was added, and the filtrate was dried by spinning and separated by column chromatography to obtain the objective product as a white solid in a yield of 72%.
The prepared product I8 was subjected to characterization data analysis, and the results were: 1 H NMR(400MHz,CDCl 3 )δ8.05–7.97(m,2H),7.32–7.23(m,2H),7.18–7.09(m,2H),6.92–6.83(m,2H),4.40(q,J＝7.1Hz,2H),4.00(s,2H),3.81(s,3H),1.42(t,J＝7.1Hz,3H). 13 CNMR(101MHz,CDCl 3 )δ166.59,158.16,146.92,132.28,129.90,129.77,128.80,128.35,114.00,60.82,55.23,41.03,14.37.MS(70eV):m/z(％):270(M + ,100).
this result further confirmed the molecular structure of the product as described above for molecular structure I8.
Example 9
This example provides 1,2,3,4, 5-pentafluorophenyl-6- (4-methoxybenzyl) benzene and a process for its preparation. The structural formula of 1,2,3,4, 5-pentafluorophenyl-6- (4-methoxybenzyl) benzene is shown in molecular structural formula I9:
the preparation method was carried out according to the preparation method of 1- (4-methoxybenzyl) -2, 4-dimethylbenzene in example 1, except that 1,2,3,4, 5-pentafluorophenyl-6- (chloromethyl) benzene (0.5mmol) was used instead of 2- (chloromethyl) -1, 4-dimethylbenzene, and 0.1mmol of potassium bromide was added, and the filtrate was spin-dried and separated by column chromatography to obtain the objective product in the form of a white solid with a yield of 37%.
The product I9 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(400MHz,CDCl 3 )δ7.20(d,J＝8.3Hz,2H),6.89–6.82(m,2H),3.99(s,2H),3.81(s,3H). 13 C NMR(101MHz,CDCl 3 )δ158.56,144.89(dm,J＝247Hz),140.04(dm,J＝247Hz),137.41(dm,J＝229Hz),129.52,129.38,114.87(t,J＝19Hz),114.15,55.21,27.29(d,J＝3Hz).MS(70eV):m/z(％):288(M + ,100).
this result further confirmed the molecular structure of the product as described above for molecular structure I9.
Example 10
This example provides a (4- (4-methoxybenzyl) phenyl) (methyl) sulfide and a method for preparing the same. The structural formula of the (4- (4-methoxybenzyl) phenyl) (methyl) thioether is shown in the following molecular structural formula I10:
the preparation method is as follows 1- (4-methoxybenzyl) -2, 4-dimethylbenzene preparation method in example 1, except that (4- (4-chloromethyl) phenyl) (methyl) thioether (0.5mmol) is adopted to replace 2- (chloromethyl) -1, 4-dimethylbenzene, filtrate is dried by spinning, and column chromatography separation is carried out to obtain the target product, white solid and yield is 40%.
The product I10 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(400MHz,CDCl 3 )δ7.27–7.22(m,2H),7.17–7.11(m,4H),6.91–6.86(m,2H),3.93(s,2H),3.83(s,3H),2.50(s,3H). 13 C NMR(101MHz,CDCl 3 )158.01,138.72,135.62,133.12,129.82,129.36,127.14,113.91,55.27,40.49,16.26.MS(70eV):m/z(％):244(M + ,100).
this result further confirmed the molecular structure of the product as described above for molecular structure I10.
Example 11
This example provides 1-methoxy-4- (4- (three methoxy) phenyl) benzene and a method for its preparation. The structural formula of the 1-methoxy-4- (4- (three-methoxy) phenyl) benzene is shown as the following molecular structural formula I11:
the preparation method refers to the preparation method of 1- (4-methoxybenzyl) -2, 4-dimethylbenzene in example 1, except that 1- (chloromethyl) -4- (three-methoxy) benzene (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, the filtrate is dried by spinning and separated by column chromatography to obtain the target product, colorless liquid and the yield is 70%.
The product I11 thus prepared was subjected to characterization data analysis, which resulted inThe fruit is as follows: 1 H NMR(400MHz,CDCl 3 )δ7.25–7.20(m,2H),7.19–7.11(m,4H),6.93–6.87(m,2H),3.97(s,2H),3.83(s,3H). 13 C NMR(101MHz,CDCl 3 )δ158.17,147.53(q,J＝2Hz),140.37,132.53,129.98,129.85,120.98,120.52(q,J＝258Hz),114.01,55.23,40.30.MS(70eV):m/z(％):282(M + ,100).
this result further confirmed the molecular structure of the product as described above for molecular structure I11.
Example 12
This example provides 4-benzyl-N, N-dimethylaniline and a method for its preparation. The structural formula of the 4-benzyl-N, N-dimethylaniline is shown as the following molecular structural formula I12:
the preparation method is as follows 1- (4-methoxybenzyl) -2, 4-dimethylbenzene preparation method in example 1, except that benzyl chloride (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, and (4- (diphenylamino) phenyl) boronic acid (0.75mmol) is used to replace 4-methoxybenzeneboronic acid, the filtrate is dried by spinning, and column chromatography separation is carried out to obtain the target product, white solid and yield 81%.
The prepared product I12 was subjected to characterization data analysis, and the results were: 1 H NMR(400MHz,CDCl 3 )δ7.44–7.35(m,2H),7.35–7.25(m,7H),7.16(d,J＝8.6Hz,6H),7.13–7.03(m,4H),4.02(s,2H). 13 C NMR(101MHz,CDCl 3 )δ147.96,145.90,141.28,135.72,129.74,129.22,129.00,128.53,126.13,124.56,123.97,122.51,41.42.MS(70eV):m/z(％):335(M + ,100).
this result further confirmed the molecular structure of the product as described above for molecular structure I12.
Example 13
The embodiment provides a 9-benzyl phenanthroline and a preparation method thereof. The structural formula of the 9-benzylphenanthroline is shown as a molecular structural formula I13:
the preparation method refers to the preparation method of 1- (4-methoxybenzyl) -2, 4-dimethylbenzene in example 1, except that benzyl chloride (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, phenanthroline-9-boronic acid (0.75mmol) is used to replace 4-methoxybenzeneboronic acid, filtrate is dried by spinning, and column chromatography separation is performed to obtain a target product, a white solid and a yield of 84%.
The product I13 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(400MHz,CDCl 3 )δ8.76(dd,J＝23.7,8.2Hz,2H),8.09(d,J＝8.1Hz,1H),7.87(d,J＝7.4Hz,1H),7.73–7.57(m,5H),7.39–7.21(m,5H),4.55(s,2H). 13 C NMR(101MHz,CDCl 3 )δ140.29,134.79,131.83,131.40,130.84,129.96,128.82,128.53,128.48,128.30,127.96,126.68,126.65,126.28,126.19,125.06,123.14,122.51,39.64.MS(70eV):m/z(％):268(M + ,100).
this result further confirmed the molecular structure of the product as described above for molecular structure I13.
Example 14
This example provides a 1-benzyl-4-phenoxybenzene and a method for its preparation. The structural formula of the 1-benzyl-4-phenoxybenzene is shown as the following molecular structural formula I14:
the preparation method was carried out according to the preparation method of 1- (4-methoxybenzyl) -2, 4-dimethylbenzene in example 1, except that benzyl chloride (0.5mmol) was used instead of 2- (chloromethyl) -1, 4-dimethylbenzene and (4-phenoxyphenyl) boronic acid (0.75mmol) was used instead of 4-methoxybenzeneboronic acid, and the filtrate was dried by spinning and separated by column chromatography to obtain the objective product as a white solid with a yield of 52%.
The prepared product I14 was subjected to characterization data analysis, and the results were: 1 H NMR(400MHz,CDCl 3 )δ7.38–7.30(m,4H),7.28–7.21(m,3H),7.21–7.16(m,2H),7.15–7.08(m,1H),7.06–7.00(m,2H),7.00–6.94(m,2H),4.00(s,2H). 13 C NMR(101MHz,CDCl 3 )δ157.47,155.38,141.15,136.09,130.12,129.66,128.87,128.49,126.11,123.00,119.03,118.61,41.20.MS(70eV):m/z(％):260(M + ,79.81).
this result further confirmed the molecular structure of the product as described above for molecular structure I14.
Example 15
This example provides a mono (4-benzylphenoxy) (tert-butyl) dimethylsilane and a process for its preparation. (4-Benzylphenoxy) (tert-butyl) dimethylsilane of the formula I15:
the preparation method refers to the preparation method of 1- (4-methoxybenzyl) -2, 4-dimethylbenzene in example 1, except that benzyl chloride (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, and (4- ((tert-butyl dimethylsilyl) oxy) phenyl) boric acid (0.75mmol) is used to replace 4-methoxybenzeneboronic acid, and the filtrate is dried by spinning and separated by column chromatography to obtain the target product, colorless liquid and yield of 72%.
The prepared product I15 was subjected to characterization data analysis, and the results were: 1 H NMR(400MHz,CDCl 3 )δ7.32(m,2H),7.26–7.19(m,3H),7.10–7.04(m,2H),6.83–6.77(m,2H),3.96(s,2H),1.02(s,9H),0.23(s,6H). 13 C NMR(101MHz,CDCl 3 )δ153.88,141.57,133.76,129.82,128.85,128.38,125.94,119.95,41.12,25.70,18.19,-4.41.MS(70eV):m/z(％):298(M + ,28.77).
this result further confirmed the molecular structure of the product as described above for molecular structure I15.
Example 16
This example provides a 1-benzyl-3, 5-dimethoxybenzene and its preparation. The structural formula of the 1-benzyl-3, 5-dimethoxybenzene is shown as the following molecular structural formula I16:
the preparation method is as follows 1- (4-methoxybenzyl) -2, 4-dimethylbenzene preparation method in example 1, except that benzyl chloride (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, and (3, 5-dimethoxyphenyl) boronic acid (0.75mmol) is used to replace 4-methoxybenzeneboronic acid, the filtrate is dried by spinning, and column chromatography separation is carried out to obtain the target product, colorless liquid and yield is 58%.
The prepared product I16 was subjected to characterization data analysis, and the results were: 1 H NMR(400MHz,CDCl 3 )δ7.33–7.26(m,2H),7.26–7.17(m,3H),7.00(d,J＝8.2Hz,1H),6.51(d,J＝2.4Hz,1H),6.45(dd,J＝8.2,2.4Hz,1H),3.94(s,2H),3.82(s,6H). 13 C NMR(101MHz,CDCl 3 )δ159.40,158.21,141.46,130.53,128.81,128.20,125.65,122.13,103.96,98.58,55.36,55.34,35.22.MS(70eV):m/z(％):228(M + ,100).
this result further confirmed the molecular structure of the product as described above for molecular structure I16.
Example 17
This example provides a 1-benzyl-2-chloro-4-methoxybenzene and its preparation. The structural formula of the 1-benzyl-2-chloro-4-methoxybenzene is shown as the following molecular structural formula I17:
the preparation method is as follows 1- (4-methoxybenzyl) -2, 4-dimethylbenzene preparation method in example 1, except that benzyl chloride (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, and (2-chloro-4-methoxyphenyl) boric acid (0.75mmol) is used to replace 4-methoxybenzeneboronic acid, the filtrate is dried by spinning, and column chromatography separation is carried out to obtain the target product, colorless liquid and yield is 52%.
The product I17 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(400MHz,CDCl 3 )δ7.36–7.29(m,2H),7.26–7.18(m,3H),7.09(d,J＝8.5Hz,1H),6.97(d,J＝2.6Hz,1H),6.78(dd,J＝8.5,2.7Hz,1H),4.07(s,2H),3.81(s,3H). 13 C NMR(101MHz,CDCl 3 )δ158.64,140.05,134.57,131.47,130.67,128.80,128.43,126.13,114.76,113.03,55.50,38.37.MS(70eV):m/z(％):232(M + ,82.15).
this result further confirmed the molecular structure of the product as described above for molecular structure I17.
Example 18
This example provides a 5-benzyl-1-p-toluenesulfonyl indoline and its preparation method. The structural formula of the 5-benzyl-1-p-toluenesulfonyl indoline is shown as the following molecular structural formula I18:
the preparation method refers to the preparation method of 1- (4-methoxybenzyl) -2, 4-dimethylbenzene in example 1, except that benzyl chloride (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, and (1-p-toluenesulfonyl indoline-5-) boric acid (0.75mmol) is used to replace 4-methoxybenzeneboronic acid, and the filtrate is dried by spinning and separated by column chromatography to obtain the target product, white solid and yield 45%.
The prepared product I18 was subjected to characterization data analysis, and the results were: 1 H NMR(500MHz,CDCl 3 )δ7.67(d,J＝8.2Hz,2H),7.55(d,J＝8.2Hz,1H),7.31–7.26(m,2H),7.23–7.19(m,3H),7.16(d,J＝7.3Hz,2H),7.04(d,J＝8.2Hz,1H),6.88(s,1H),3.93–3.85(m,4H),2.82(t,J＝8.3Hz,2H),2.38(s,3H). 13 C NMR(126MHz,CDCl 3 )δ143.91,141.14,140.32,136.80,134.27,132.19,129.60,128.84,128.47,128.27,127.36,126.12,125.56,114.96,50.11,41.39,27.90,21.50.HRMS(ESI-TOF)[M+Na] + calculated for[C 22 H 21 NNaO 2 S] + 386.1185,found 386.1186.
this result further confirmed the molecular structure of the product as described above for molecular structure I18.
Example 19
This example provides a 1, 6-dibenzyl-3, 4-dihydroquinolin-2 (1H) -one and a process for its preparation. The structural formula of 1, 6-dibenzyl-3, 4-dihydroquinoline-2 (1H) -ketone is shown as the following molecular structural formula I19:
the preparation method is as follows 1- (4-methoxybenzyl) -2, 4-dimethylbenzene preparation method in example 1, except that benzyl chloride (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, (1-benzyl-2-oxo-1, 2,3, 4-tetrahydroquinoline-6-) boric acid (0.75mmol) is used to replace 4-methoxybenzeneboronic acid, the filtrate is dried by spinning, and column chromatography separation is carried out to obtain the target product, white solid, yield is 57%.
The product I19 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(500MHz,CDCl 3 )δ7.32–7.27(m,4H),7.25–7.17(m,6H),7.00(s,1H),6.93(dd,J＝8.3,1.8Hz,1H),6.80(d,J＝8.3Hz,1H),5.17(s,2H),3.90(s,2H),2.95–2.92(m,2H),2.79–2.76(m,2H). 13 C NMR(126MHz,CDCl 3 )δ170.40,140.90,138.15,137.18,135.85,128.87,128.71,128.52,128.30,127.70,127.03,126.45,126.19,115.61,46.22,41.14,31.93,25.64.HRMS(ESI-TOF)[M+H] + calculated for[C 23 H 22 NO] + 328.1696,found 328.1695.
this result further confirmed the molecular structure of the product as described above for molecular structure I19.
Example 20
This example provides a 5- (p-methylphenyl) -3- (trifluoromethyl) -1- (4- (3,4, 5-trimethoxybenzyl) phenyl) -1H-pyrazole and process for its preparation. The structural formula of 5- (p-methylphenyl) -3- (trifluoromethyl) -1- (4- (3,4, 5-trimethoxybenzyl) phenyl) -1H-pyrazole is shown in the following molecular structural formula I20:
the preparation method is as follows 1- (4-methoxybenzyl) -2, 4-dimethylbenzene preparation method in example 1, except that 1- (4- (chloromethyl) phenyl) -5- (p-methylphenyl) -3- (trifluoromethyl) -1H-pyrazole (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene and (3,4, 5-trimethoxyphenyl) boric acid (0.75mmol) is used to replace 4-methoxybenzeneboronic acid, filtrate is dried by spinning, and column chromatography separation is carried out to obtain the target product, white solid and yield of 52%.
The product I20 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(500MHz,CDCl 3 )δ7.20(q,J＝8.4Hz,4H),7.10(s,4H),6.79(d,J＝8.5Hz,1H),6.70(s,1H),6.61(d,J＝8.5Hz,1H),3.93(s,2H),3.87(s,3H),3.85(s,3H),3.69(s,3H),2.35(s,3H). 13 C NMR(126MHz,CDCl 3 )δ152.71,151.94,144.74,142.99(q,J＝38Hz),142.59,142.19,138.95,137.34,129.39,129.27,128.66,126.60,126.46,125.42,124.48,121.40(q,J＝269Hz)107.30,105.09,60.67,60.60,56.06,35.63,21.21.HRMS(ESI-TOF)[M+H] + calculated for[C 27 H 26 F 3 N 2 O 3 ] + 483.1890,found 483.1892.
this result further confirmed the molecular structure of the product as described above for molecular structure I20.
Example 21
This example provides a 2- (4- (benzyloxy) phenyl) -1- (4-chlorobenzyl) -3-methyl-5- (4- (trifluoromethoxy) benzyl) -1H-indole and its preparation. The structural formula of 2- (4- (benzyloxy) phenyl) -1- (4-chlorobenzyl) -3-methyl-5- (4- (trifluoromethoxy) benzyl) -1H-indole is shown in molecular structural formula I21 below:
the preparation method is as follows 1- (4-methoxybenzyl) -2, 4-dimethylbenzene preparation method in example 1, except that 1- (chloromethyl) -4- (trifluoromethoxy) benzene (0.5mmol) is used instead of 2- (chloromethyl) -1, 4-dimethylbenzene, (2- (4- (benzyloxy) phenyl) -1- (4-chlorobenzyl) -3-methyl-1H indole-5-) boronic acid (0.75mmol) is used instead of 4-methoxybenzeneboronic acid, filtrate is dried by spinning, and column chromatography separation is carried out, thus obtaining the target product, white solid and 76% yield.
The product I21 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(500MHz,CDCl 3 )δ7.50–7.40(m,5H),7.39–7.33(m,1H),7.26(d,J＝8.3Hz,2H),7.23–7.17(m,4H),7.13(d,J＝7.9Hz,2H),7.07(d,J＝8.3Hz,1H),7.05–7.00(m,2H),6.98(dd,J＝8.4,1.6Hz,1H),6.87(d,J＝8.5Hz,2H),5.15(s,2H),5.11(s,2H),4.11(s,2H),2.27(s,3H). 13 C NMR(126MHz,CDCl 3 )δ158.74,147.48(d,J＝3Hz),141.17,137.95,137.08,136.83,135.48,132.84,131.68,131.58,130.02,129.20,128.73,128.63,128.07,127.51,127.48,124.38,123.20,120.84,120.57(q,J＝257Hz)118.85,114.89,110.00,109.00,70.16,47.00,41.47,9.38.HRMS(ESI-TOF)[M+H] + calculated for[C 37 H 30 ClF 3 NO 2 ] + 612.1912,found 612.1917.
this result further confirmed the molecular structure of the product as described above for molecular structure I21.
Example 22
This example provides a 4- (4- (((3R,5S,8R,9S,10S,13S,14S) -10, 13-dimethyl-17-oxohexadecahydro-1H-cyclopenta [ a ] phenanthrene-3-) oxy) benzyl) benzoic acid ethyl ester and a process for its preparation. The structural formula of ethyl 4- (4- (((3R,5S,8R,9S,10S,13S,14S) -10, 13-dimethyl-17-oxohexadecahydro-1H-cyclopenta [ a ] phenanthrene-3-) oxy) benzyl) benzoate is shown in the following molecular structural formula I22:
the preparation method is as follows 1- (4-methoxybenzyl) -2, 4-dimethylbenzene preparation method in example 1, except that 4- (chloromethyl) -benzoic acid ethyl ester (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, and (4- (4- (((3R,5S,8R,9S,10S,13S,14S) -10, 13-dimethyl-17-oxohexadecahydro-1H-cyclopenta [ a ] phenanthrene-3-) oxy) benzyl) phenyl) boronic acid (0.75mmol) is used to replace 4-methoxybenzeneboronic acid, and the filtrate is dried by spinning and separated by column chromatography to obtain the target product, white solid, yield 65%.
The product I21 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(500MHz,CDCl 3 )δ7.96(d,J＝8.4Hz,2H),7.25(d,J＝8.0Hz,2H),7.06(d,J＝8.5Hz,2H),6.83(d,J＝8.5Hz,2H),4.49(t,J＝2.8Hz,1H),4.36(q,J＝7.1Hz,2H),3.96(s,2H),2.44(dd,J＝19.2,8.7Hz,1H),2.07(dt,J＝18.9,9.1Hz,1H),2.00–1.86(m,2H),1.82–1.77(m,2H),1.70–1.43(m,8H),1.41–1.37(m,4H),1.34–1.17(m,5H),1.03(qd,J＝12.4,5.0Hz,1H),0.87–0.85(m,7H). 13 C NMR(126MHz,CDCl 3 )δ221.13,166.58,156.32,146.89,132.06,129.85,129.74,128.81,128.43,116.28,72.12,60.76,54.39,51.58,47.82,41.10,39.64,36.01,35.85,35.14,32.77,32.68,31.64,30.83,28.19,25.65,21.77,20.12,14.34,13.85,11.44.HRMS(ESI-TOF)[M+Na] + calculated for[C 35 H 44 NaO 4 ] + 551.3132,found 551.3131.
this result further confirmed the molecular structure of the product as described above for molecular structure I22.
Example 23
This example provides a structural formula of ethyl 2- (4- (4-chlorobenzyl) phenoxy) -2-methylbutyrate (benzclofibrate) shown by the following molecular formula I23:
the preparation method is as follows 1- (4-methoxybenzyl) -2, 4-dimethylbenzene preparation method in example 1, except that 1-chloro-4- (chloromethyl) benzene (0.5mmol) is used to replace 2- (chloromethyl) -1, 4-dimethylbenzene, (4- ((1-ethoxy-2-methyl-1-oxobutane-2-) oxy) phenyl) boronic acid (0.75mmol) is used to replace 4-methoxybenzeneboronic acid, the filtrate is dried by spinning, and column chromatography separation is performed to obtain the target product, colorless liquid and yield of 51%.
The product I21 prepared was subjected to characterization data analysis, which resulted in: 1 H NMR(400MHz,CDCl 3 )δ7.28–7.23(m,2H),7.16–7.08(m,2H),7.07–6.98(m,2H),6.87–6.77(m,2H),4.26(qd,J＝7.1,0.9Hz,2H),3.89(s,2H),1.99(dtt,J＝21.4,13.7,7.5Hz,2H),1.51(s,3H),1.28(t,J＝7.1Hz,3H),1.00(t,J＝7.5Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ174.00,153.89,139.80,134.05,131.79,130.18,129.44,128.48,119.34,81.93,61.21,40.37,32.56,20.75,14.15,7.85.MS(70eV):m/z(％):346(M + ,12.58),348(M + ,4.61).
this result further confirmed the molecular structure of the product as described above for molecular structure I23.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (4)
1. A preparation method of diarylmethane compounds comprises the following steps:
provided are a sulfonic acid ester compound A and a boric acid B of benzyl halogenated hydrocarbon or benzyl alcohol respectively represented by the following structural formula:
adding the sulfonic ester compound A of benzyl halogenated hydrocarbon or benzyl alcohol and the boric acid B into a reaction system containing an organic small molecular catalyst, an alkali reagent and a solvent to react at the temperature of 20-140 ℃ to obtain the diarylmethane compound shown as the following structural general formula (I):
wherein, the compound A, B and the R in the structural formula of the (I) 1 Are all C 1 -C 20 Alkyl radical, C 1 -C 20 Heteroalkyl group, C 3 -C 20 Cycloalkyl radical, C 3 -C 20 Heterocycloalkyl radical, C 2 -C 20 Alkenyl radical, C 2 -C 20 Heteroalkenyl radical, C 3 -C 20 Cycloalkenyl radical, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl group, C 3 -C 20 Any one of a heterocyclic alkynyl group and a hydrogen atom substituent group;
the R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is C 1 -C 20 Alkyl radical, C 1 -C 20 Heteroalkyl group, C 3 -C 20 Cycloalkyl, C 3 -C 20 Heterocycloalkyl radical, C 2 -C 20 Alkenyl radical, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl radical, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl, C 3 -C 20 Any one of heterocyclic alkynyl, nitro, cyano, halogen and hydrogen atom substituent;
wherein, X is a halogen atom or a sulfonyloxy group;
the organic micromolecule catalyst is a heterocyclic compound with the following molecular structure general formula C:
y in the structural general formula C is a sulfur atom or an oxygen atom; in the structural general formula C, R 12 、R 13 、R 14 、R 15 Are identical or different and are C 1 -C 20 Alkyl radical, C 1 -C 20 Heteroalkyl group, C 3 -C 20 Cycloalkyl radical, C 3 -C 20 Heterocycloalkyl radical, C 2 -C 20 Alkenyl radical, C 2 -C 20 Heteroalkenyl, C 3 -C 20 Cycloalkenyl radical, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl, C 3 -C 20 Any one of heterocyclic alkynyl, amino, nitro, cyano, halogen and hydrogen atom substituent;
the mol ratio of the organic small molecular catalyst to the alkali reagent to the compound A to the compound B is (0.1-20) to (1-200): (1-100):(1-200).
2. The production method according to claim 1, characterized in that:
the alkali reagent is at least one of lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, potassium pyrophosphate, triethylamine, diisopropylethylamine, sodium methoxide, sodium ethoxide and sodium ethylmercaptide.
3. The production method according to claim 1, characterized in that: r is 1 Is C 1 -C 20 Alkyl radical, C 1 -C 20 Heteroalkyl group, C 3 -C 20 Cycloalkyl radical, C 3 -C 20 Cycloalkenyl radical, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Any one of heteroalkynyl groups and hydrogen atom substituents;
the R is 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 And R 11 Is C 1 -C 20 Alkyl radical, C 1 -C 20 Heteroalkyl group, C 3 -C 20 Cycloalkyl radical, C 3 -C 20 Heterocycloalkyl radical, C 2 -C 20 Alkenyl radical, C 2 -C 20 Heteroalkenyl radical, C 3 -C 20 Cycloalkenyl radical, C 3 -C 20 Heterocycloalkenyl, C 2 -C 20 Alkynyl, C 2 -C 20 Heteroalkynyl, C 3 -C 20 Cycloalkynyl group, C 3 -C 20 Any one of heterocyclic alkynyl, amino, nitro, cyano, halogen and hydrogen atom substituent.
4. The production method according to claim 1, characterized in that: the R is 1 Is C 1 -C 5 Alkyl radical, C 3 -C 20 Any of cycloalkyl groups and hydrogen atom substituents;
R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 and R 11 Is C 1 -C 6 Alkyl, aryl, heteroaryl, and heteroaryl,C 1 -C 10 Heteroalkyl group, C 3 -C 8 Cycloalkyl radical, C 3 -C 8 Heterocycloalkyl radical, C 2 -C 6 Any one of alkynyl, nitro, cyano, halogen and hydrogen atom substituent.
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| CN110015952A (en) | 2019-07-16 |
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