CN110724173B - Sulfonic acid catalysis-based method for directionally transferring hydroxy-m-benzoyl - Google Patents
Sulfonic acid catalysis-based method for directionally transferring hydroxy-m-benzoyl Download PDFInfo
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- CN110724173B CN110724173B CN201911105753.8A CN201911105753A CN110724173B CN 110724173 B CN110724173 B CN 110724173B CN 201911105753 A CN201911105753 A CN 201911105753A CN 110724173 B CN110724173 B CN 110724173B
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- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 title claims abstract description 52
- 238000000034 method Methods 0.000 title claims abstract description 52
- 238000007171 acid catalysis Methods 0.000 title abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 54
- 238000013508 migration Methods 0.000 claims abstract description 30
- 239000000758 substrate Substances 0.000 claims abstract description 17
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 12
- -1 benzoyl compound Chemical class 0.000 claims description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 28
- 230000005012 migration Effects 0.000 claims description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 239000012445 acidic reagent Substances 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 230000009471 action Effects 0.000 claims description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 6
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 125000005489 p-toluenesulfonic acid group Chemical group 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 34
- 125000002252 acyl group Chemical group 0.000 abstract description 29
- 125000000524 functional group Chemical group 0.000 abstract description 17
- 238000006555 catalytic reaction Methods 0.000 abstract description 14
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 150000002905 orthoesters Chemical class 0.000 abstract description 4
- 238000012546 transfer Methods 0.000 abstract description 2
- 125000002092 orthoester group Chemical group 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- 238000006276 transfer reaction Methods 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 13
- 150000001720 carbohydrates Chemical class 0.000 description 12
- 239000012043 crude product Substances 0.000 description 11
- 230000003472 neutralizing effect Effects 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- SPXOTSHWBDUUMT-UHFFFAOYSA-N 138-42-1 Chemical compound OS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-N 0.000 description 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- SBMYBOVJMOVVQW-UHFFFAOYSA-N 2-[3-[[4-(2,2-difluoroethyl)piperazin-1-yl]methyl]-4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound FC(CN1CCN(CC1)CC1=NN(C=C1C=1C=NC(=NC=1)NC1CC2=CC=CC=C2C1)CC(=O)N1CC2=C(CC1)NN=N2)F SBMYBOVJMOVVQW-UHFFFAOYSA-N 0.000 description 1
- FARHYDJOXLCMRP-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]pyrazol-3-yl]oxyacetic acid Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(N1CC2=C(CC1)NN=N2)=O)OCC(=O)O FARHYDJOXLCMRP-UHFFFAOYSA-N 0.000 description 1
- XXZCIYUJYUESMD-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(morpholin-4-ylmethyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCOCC1 XXZCIYUJYUESMD-UHFFFAOYSA-N 0.000 description 1
- WWSJZGAPAVMETJ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-ethoxypyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OCC WWSJZGAPAVMETJ-UHFFFAOYSA-N 0.000 description 1
- FYELSNVLZVIGTI-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-5-ethylpyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1CC)CC(=O)N1CC2=C(CC1)NN=N2 FYELSNVLZVIGTI-UHFFFAOYSA-N 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000003855 acyl compounds Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007646 directional migration Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 238000007146 photocatalysis Methods 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000006049 ring expansion reaction Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- CITILBVTAYEWKR-UHFFFAOYSA-L zinc trifluoromethanesulfonate Substances [Zn+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F CITILBVTAYEWKR-UHFFFAOYSA-L 0.000 description 1
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- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/14—Acyclic radicals, not substituted by cyclic structures attached to a sulfur, selenium or tellurium atom of a saccharide radical
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- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/12—Formation or introduction of functional groups containing oxygen of carboxylic acid ester groups
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/02—Preparation of carboxylic acid esters by interreacting ester groups, i.e. transesterification
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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- C07C67/03—Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
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- C07C67/24—Preparation of carboxylic acid esters by reacting carboxylic acids or derivatives thereof with a carbon-to-oxygen ether bond, e.g. acetal, tetrahydrofuran
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- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
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Abstract
The invention discloses a sulfonic acid catalysis-based method for directionally transferring an inter-hydroxyl benzoyl group, which relates to the technical field of chemical synthesis, in particular to a method for transferring an acyl group by an ortho ester intermediate through high regioselectivity under the catalysis condition of the benzoyl group in sulfonic acid, wherein the transfer characteristic is as follows: two hydroxyl groups sterically capable of forming a 5-or 6-membered orthoester ring, the benzoyl group can migrate from a secondary or tertiary hydroxyl group to a primary hydroxyl group and from an ortho-position secondary hydroxyl group to a neutral-position secondary hydroxyl group. The invention uses sulfonic acid to promote the acyl functional group in the substrate to carry out 1, 2-or 1, 3-migration reaction, and the whole synthesis reaction has mild condition, simple operation and atom economy.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a sulfonic acid catalysis-based method for directionally transferring a benzoyl group between hydroxyls.
Background
The selection and use of protecting groups is of paramount importance in the total synthesis of natural products, in particular in carbohydrates. Benzoyl is used as a cheap, stable and simple-to-mount protecting group, is often used for protecting and selectively deprotecting hydroxyl, amino, sulfydryl and other groups, and is widely used in organic synthesis.
Acyl migration is an important class of functional group transformation reactions in organic synthesis. Acyl functional groups can be introduced into designated positions through intramolecular acyl rearrangement reaction, so that the synthesis method of the acyl compounds can be greatly expanded. The reaction mechanism is divided into two inducing ways, namely free radicals and negative ions, wherein the former way generally utilizes alkyl free radicals generated in the reaction to make acyl migrate so as to complete ring expansion reaction, and the latter way utilizes the intermediate negative ions to firstly carry out nucleophilic addition on carbonyl and then induces acyl rearrangement by oxygen negative ions. According to the difference in migration position, the acyl group migration reaction is largely divided into 1, 2-acyl group migration, 1, 3-acyl group migration, 1, 4-acyl group migration and 1, 5-acyl group migration, of which 1, 2-acyl group migration reaction is most widely studied.
As early as 1979, agBF4 was reported to catalyze the rearrangement of a-hydroxy-b-chlorocarbonyl compounds to b-phenylacetaldehyde derivatives. In this reaction, the phenylacetyl group migrates from the a-position to the b-position of the hydroxyl group, i.e., a 1, 2-acyl group transfer reaction occurs. In addition, under the action of Lewis acid zinc trifluoromethanesulfonate, the b-lactone co-migrates with 1, 2-acyl and d-lactone in the molecule to precisely synthesize the spiro bridgehead g-butyrolactone compound. Photocatalysis may also effect acyl transfer reactions.
Until now, reports on acyl migration have focused mainly on the migration from the oxygen of the phenolic hydroxyl group to the adjacent carbon. There are only a few reports of the phenomenon of acyl migration between hydroxyl groups, and there is no report of any directional migration of acyl groups between hydroxyl groups.
Disclosure of Invention
The invention aims to: aiming at the defects in the prior art, the invention provides a sulfonic acid catalysis-based method for directionally transferring the m-hydroxybenzoyl group, provides a new reliable technical route and a new synthesis strategy, and has wide application prospect in the technical field of organic chemistry.
The technical scheme adopted by the invention is as follows:
a sulfonic acid catalyzed oriented migration method of hydroxyl-m-benzoyl, which comprises the following steps:
and (2) carrying out benzoyl migration reaction on the benzoyl compound I or III in the organic solvent A under the action of a sulfonic acid reagent to obtain a compound II or IV:
R 1 is C1-C6 alkyl, C5-C6 cyclane, phenyl, C1-C6 substituted phenyl, benzyl, naphthyl, heterocycle containing N, O, amino acid side chain or forms a ring with R3;
R 2 hydrogen, triphenylmethyl, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl or tetrahydropyranyl ether;
R 3 is hydrogen or forms a ring with R1;
wherein R is 1 And R 3 In ring formation, R 1 The hydroxy group on the carbon being a vicinal hydroxy group, R 3 The hydroxyl group on the carbon is an ortho-hydroxyl group.
The present invention has found that when a benzoate and a sterically close hydroxyl group are present in a compound, the sulfonic acid reagent catalyzes the formation of a 5-or 6-membered cyclic orthoester intermediate from the benzoyl group and the adjacent hydroxyl group, and the orthoester is hydrolyzed under acidic conditions to complete the acyl group transfer.
According to the invention, the direction of acyl migration has stronger selectivity, such as migration from a secondary hydroxyl to a primary hydroxyl, and migration from a flat-position secondary hydroxyl to an upright-position secondary hydroxyl. Thus, the present invention utilizes sulfonic acid to promote 1, 2-or 1, 3-migration of acyl functional groups in a substrate.
Further, the method specifically comprises the following steps: dissolving benzoyl compound I or III in organic solvent A, adding sulfonic acid reagent, reacting for 1-12h, washing the obtained reaction solution, drying, filtering, removing solvent under reduced pressure, and purifying to obtain compound II and compound IV; the concentration of the reaction substrate is 0.01-0.1mol/L.
Further, the reaction solution is washed by saturated sodium bicarbonate solution and saturated brine in sequence, dried by anhydrous sodium sulfate, filtered, decompressed to remove the solvent, and purified by a chromatographic silica gel column separation or crystallization mode to obtain the compounds II and IV.
Furthermore, the mass ratio of the benzoyl compound I or III to the sulfonic acid reagent is 1.
Further, the reaction temperature is 0-30 ℃; the sulfonic acid reagent is p-toluenesulfonic acid, p-nitrobenzenesulfonic acid, methanesulfonic acid or trifluoromethanesulfonic acid; the organic solvent A is a mixed solvent of dichloromethane or 1, 2-dichloroethane and methanol or ethanol according to a volume ratio of 10-100.
Further, in benzoyl compound I or III, when R is 3 When it is hydrogen, R 1 Is C1-C6 alkyl, C5-C6 cyclane, phenyl, C1-C6 substituted phenyl, benzyl, naphthyl, heterocycle containing N, O or amino acid side chain; r 2 Is hydrogen, triphenylmethyl, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl or tetrahydropyranyl ether group.
Further, when benzoyl compound I or III, substituent R 3 And R 1 In ring formation, R 1 The hydroxy group on the carbon being a vicinal hydroxy group, R 3 The hydroxyl group on the carbon is an upright position hydroxyl group; r 2 Is hydrogen, triphenylmethyl, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl or tetrahydropyranyl ether.
Further, the reaction temperature is 25-30 ℃; the sulfonic acid reagent is p-toluenesulfonic acid or p-nitrobenzenesulfonic acid; the organic solvent A is a mixed solvent of dichloromethane and methanol according to a volume ratio of 50-100.
Further, in benzoyl compound I or III, when R is 3 When it is hydrogen, R 1 Is C1-C6 alkyl, C5-C6 cyclane, phenyl, C1-C6 substituted phenyl, benzyl or amino acid side chain; r 2 Hydrogen, triphenylmethyl or trimethylsilyl.
Further, in benzoyl compounds I and III, the substituent R 3 And R 1 When forming a ring, R 1 The hydroxy group on the carbon is a planar hydroxy group, R 3 The hydroxyl group on the carbon is an upright position hydroxyl group; r 2 Hydrogen, triphenylmethyl or trimethylsilyl.
In summary, due to the adoption of the technical scheme, the invention has the beneficial effects that:
1. in the invention, under the catalysis condition of sulfonic acid, the benzoyl group can complete the migration of acyl group through the high regioselectivity of the ortho ester intermediate, and the migration is characterized in that: two hydroxyl groups sterically capable of forming a 5-or 6-membered orthoester ring, the benzoyl group being capable of migrating from a secondary or tertiary hydroxyl group to a primary hydroxyl group and from an upright secondary hydroxyl group to a flat secondary hydroxyl group;
2. the invention uses sulfonic acid to promote acyl functional groups in the substrate to generate 1, 2-or 1, 3-migration reaction, the whole synthesis reaction condition is mild, the operation is simple, and the atom is economic;
3. the invention provides a new reliable technical route and a synthesis strategy, and has wide application prospect in the technical field of organic chemistry.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and those skilled in the art can also obtain other related drawings based on the drawings without inventive efforts.
FIG. 1 shows examples 1,4 and 7 1 H NMR；
FIG. 2 shows examples 1,4 and 7 13 C NMR；
FIG. 3 shows examples 2, 5 and 8 1 H NMR；
FIG. 4 shows examples 2, 5 and 8 13 C NMR；
FIG. 5 shows examples 3, 6 and 9 1 H NMR；
FIG. 6 shows examples 3, 6 and 9 13 C NMR；
FIG. 7 shows example 10 1 H NMR；
FIG. 8 shows example 10 13 C NMR；
FIG. 9 shows example 11 1 H NMR；
FIG. 10 shows example 11 13 C NMR；
FIG. 11 is a drawing showing a modified example of example 12 1 H NMR；
FIG. 12 is a drawing showing a structure of example 12 13 C NMR。
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention. The components of embodiments of the present invention generally described and illustrated in the figures herein may be arranged and designed in a wide variety of different configurations.
Thus, the following detailed description of the embodiments of the present invention, presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments of the present invention without making any creative effort, shall fall within the protection scope of the present invention.
It is noted that relational terms such as "first" and "second," and the like, may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrases "comprising a," "8230," "8230," or "comprising" does not exclude the presence of additional like elements in a process, method, article, or apparatus that comprises the element.
The features and properties of the present invention are described in further detail below with reference to examples.
The experimental procedures are not specifically described in the following examples, and are carried out in a conventional manner using reagents which are generally commercially available.
All examples are given 1 H-NMR or 13 The C-NMR nuclear magnetic resonance instrument (Brucker company) records that the chemical shift is expressed by ppm, the silica gel used for separation is 200-300 meshes, and the mixture ratio of the eluent is volume ratio.
Example 1
The embodiment provides a sulfonic acid catalysis-based method for directionally transferring a benzoyl group between hydroxyl groups, in particular to a method for performing 1, 2-transfer reaction on an acyl functional group of a non-sugar substrate under the catalysis condition of sulfonic acid, wherein the reaction formula is as follows:
the method comprises the following specific steps:
compound 1 (84mg, 0.17mmol) was treated with dry CH 2 Cl 2 MeOH (v: v =2:1,3.4 mL) was dissolved in a round-bottom flask, stirred at room temperature, then TsOH (32mg, 0.17mmol) was added, the reaction mixture was stirred at room temperature for 1h, and after completion of the reaction, et was used 3 Neutralizing the system to alkalescence by N, and concentrating under reduced pressure. The crude product was purified by flash column (6: 82.3 percent.
(c 1.0,CHCl 3 )； 1 H NMR(600MHz,CDCl 3 ):δ8.11(dd,J＝7.8,0.6Hz,2H),7.59-7.57(m,1H),7.47-7.44(m,4H),7.39-7.37(m,2H),7.34-7.31(m,1H),6.12(dd,J＝7.8,2.8Hz,1H),4.06(dd,J＝12,7.8Hz,1H),3.95(d,J＝12.6Hz,1H)； 13 C NMR(150MHz,CDCl 3 ):δ116.1,137.0,133.3,130.0,129.8,128.7,128.5,126.6,126.2,77.4,77.2,76.8,66.2。
Example 2
The embodiment provides a sulfonic acid catalysis-based method for directionally transferring a hydroxyl-m-benzoyl group, in particular to a method for performing 1, 2-transfer reaction on an acyl functional group of a saccharide substrate under the catalysis condition of sulfonic acid, wherein the reaction formula is as follows:
the method comprises the following specific steps:
compound 3 (51mg, 0.06mmol) was applied with dry CH 2 Cl 2 (6 mL) was dissolved in a round-bottom flask, stirred at room temperature, tsOH (12mg, 0.06mmol) was added, the reaction mixture was stirred at room temperature for 15min, meOH (5. Mu.L, 0.12 mmol) was added, the reaction was allowed to react at room temperature for 20h, and after completion of the reaction, et was added 3 Neutralizing the system to alkalescence by N, and concentrating under reduced pressure. The crude product was purified flash through a chromatography column (10.
(c 0.8,CHCl 3 )； 1 H NMR(600MHz,CDCl 3 ):δ8.12(dd,J＝7.8,0.6Hz,2H),8.04-8.02(m,4H),7.63-7.54(m,3H),7.50(t,J＝7.8Hz 2H),7.45-7.40(m,6H),7.10(d,J＝8.4Hz,2H),4.66(dd,J＝4.2,1.8Hz,1H),4.59-4.55(m,1H),4.53-4.78(m,2H),2.75(d,J＝6.4Hz,1H),2.31(s,3H)； 13 C NMR(150MHz,CDCl 3 ):δ116.5,166.0,165.3,138.3,133.7,133.6,133.1,133.0,129.9,129.8,129.7,129.4,128.9,128.8,128.6,128.4,92.0,83.1,81.8,78.2,77.2,77.0,76.8,68.9,66.1,21.2。
Example 3
The embodiment provides a sulfonic acid catalysis-based method for directionally transferring a hydroxyl-m-benzoyl group, in particular to a method for performing 1, 3-transfer reaction on an acyl functional group of a saccharide substrate under the catalysis condition of sulfonic acid, wherein the reaction formula is as follows:
the method comprises the following specific steps:
compound 5 (57mg, 0.07mmol) was reacted with dry CH 2 Cl 2 (7 mL) was dissolved in a round bottom flask and stirred at room temperature, then TsOH (13mg, 0.07mmol) was added, the reaction mixture was stirred at room temperature for 15min, meOH (6. Mu.L, 0.14 mmol) was added, the reaction was allowed to react at room temperature for 20h, and after completion the reaction was treated with Et 3 Neutralizing the system to alkalescence by N, and concentrating under vacuum and reduced pressure. The crude product was purified by flash column chromatography (4.
(c 0.7,CHCl 3 )； 1 H NMR(600MHz,CDCl 3 ):δ8.06(dd,J＝7.8,0.6Hz,2H),7.99-7.95(m,4H),7.62-7.59(m,1H),7.53-7.45(m,4H),7.40-7.35(m,6H),6.98(d,J＝7.8Hz,2H),5.78(t,J＝9.6Hz,1H),5.38(dd,J＝10.2,3Hz,1H),4.90(d,J＝10.2Hz,1H),4.69-4.62(m,2H),4.38(s,1H),4.12(t,J＝6.6Hz,1H),2.49(d,J＝4.8Hz,1H),2.29(s,3H)； 13 C NMR(150MHz,CDCl 3 ):δ166.4,165.8,165.3,138.3,113.5,133.3,133.2,129.129.8,129.8,129.7,129.5,129.0,128.7,128.5,128.5,128.4,87.1,77.2,77.0,76.8,76.2,75.3,68.0,67.7,63.2,21.2。
Example 4
The embodiment provides a sulfonic acid catalysis-based method for directionally transferring a hydroxyl-m-benzoyl group, in particular to a method for performing 1, 2-transfer reaction on an acyl functional group of a non-saccharide substrate under the catalysis condition of sulfonic acid, wherein the reaction formula is as follows:
the method comprises the following specific steps:
compound 7 (30mg, 0.12mmol) was reacted with dry CH 2 Cl 2 (12 mL) was dissolved in a round bottom flask, tsOH (11mg, 0.06mmol) was added, the reaction mixture was stirred at 30 ℃ for 15min, meOH (10. Mu.L, 0.24 mmol) was added, the reaction was allowed to react at 30 ℃ for 24h, and after completion the reaction was Et 3 N neutralizes the system to alkalescenceVacuum concentrating under reduced pressure. The crude product was purified by flash column (6: 85.1 percent.
Example 5
The embodiment provides a sulfonic acid catalysis-based method for directionally transferring a hydroxyl-m-benzoyl group, in particular to a method for performing 1, 2-transfer reaction on an acyl functional group of a saccharide substrate under the catalysis condition of sulfonic acid, wherein the reaction formula is as follows:
the method comprises the following specific steps:
compound 8 (31mg, 0.05mmol) was treated with dry CH 2 Cl 2 (5 mL) was dissolved in a round-bottom flask, tsOH (6 mg, 0.03mmol) was added, the reaction mixture was stirred at 30 ℃ for 15min, meOH (4. Mu.L, 0.10 mmol) was added, the reaction was allowed to react at 30 ℃ for 20h, and after completion of the reaction, et was added 3 Neutralizing the system to alkalescence by N, and concentrating under reduced pressure. The crude product was purified flash through a chromatography column (10.
Example 6
The embodiment provides a sulfonic acid catalysis-based method for directionally transferring a hydroxyl-m-benzoyl group, and particularly relates to a method for performing 1, 3-transfer reaction on an acyl functional group of a saccharide substrate under the catalysis condition of sulfonic acid, wherein the reaction formula is as follows:
the method comprises the following specific steps:
compound 9 (33mg, 0.07mmol) was applied with dry CH 2 Cl 2 (7 mL) was dissolved in a round-bottom flask, tsOH (8 mg, 0.04mmol) was added, the reaction mixture was stirred at 30 ℃ for 15min, meOH (6. Mu.L, 0.14 mmol) was added, the reaction was allowed to react at 30 ℃ for 24h, and after completion of the reaction, et was used 3 Neutralizing the system to alkalescence by N, and concentrating under reduced pressure. The crude was purified rapidly by chromatography column (4Product, light yellow syrupy compound 6 was obtained in 70.1% yield.
Example 7
The embodiment provides a sulfonic acid catalysis-based method for directionally transferring a hydroxyl-m-benzoyl group, in particular to a method for performing 1, 2-transfer reaction on an acyl functional group of a saccharide substrate under the catalysis condition of sulfonic acid, wherein the reaction formula is as follows:
the method comprises the following specific steps:
compound 10 (52mg, 0.17mmol) was applied to dry CH 2 Cl 2 (17 mL) was dissolved in a round bottom flask and then TsOH (64mg, 0.34mmol) was added and the reaction mixture stirred at 30 ℃ for 15min then MeOH (14. Mu.L, 0.34 mmol) was added and the reaction mixture stirred at 30 ℃ for 24h and after completion the reaction was Et 3 Neutralizing the system to alkalescence by N, and concentrating under vacuum and reduced pressure. The crude product was purified by flash column (6: 71.3 percent.
Example 8
The embodiment provides a sulfonic acid catalysis-based method for directionally transferring a hydroxyl-m-benzoyl group, in particular to a method for performing 1, 2-transfer reaction on an acyl functional group of a saccharide substrate under the catalysis condition of sulfonic acid, wherein the reaction formula is as follows:
the method comprises the following specific steps:
compound 11 (33mg, 0.06mmol) was treated with dry CH 2 Cl 2 (6 mL) was dissolved in a round bottom flask, tsOH (23mg, 0.12mmol) was added, the reaction mixture was stirred at 30 ℃ for 15min, meOH (5. Mu.L, 0.12 mmol) was added, the reaction was allowed to react at 30 ℃ for 24h, and after completion the reaction was Et 3 Neutralizing the system to alkalescence by N, and concentrating under vacuum and reduced pressure. The crude product was purified by flash column chromatography (10.6％。
Example 9
The embodiment provides a sulfonic acid catalysis-based method for directionally transferring a hydroxyl-m-benzoyl group, in particular to a method for performing 1, 3-transfer reaction on an acyl functional group of a saccharide substrate under the catalysis condition of sulfonic acid, wherein the reaction formula is as follows:
the method comprises the following specific steps:
compound 12 (47mg, 0.07mmol) was reacted with dry CH 2 Cl 2 (7 mL) was dissolved in a round bottom flask, tsOH (26mg, 0.14mmol) was added, the reaction mixture was stirred at 30 ℃ for 15min, meOH (6. Mu.L, 0.14 mmol) was added, the reaction was allowed to react at 30 ℃ for 24h, and after completion the reaction was treated with Et 3 Neutralizing the system to alkalescence by N, and concentrating under vacuum and reduced pressure. The crude product was purified by flash column chromatography (4.
Example 10
The embodiment provides a sulfonic acid catalysis-based method for directionally transferring a hydroxyl-m-benzoyl group, in particular to a method for performing 1, 2-transfer reaction on an acyl functional group of a non-saccharide substrate under the catalysis condition of sulfonic acid, wherein the reaction formula is as follows:
the method comprises the following specific steps:
compound 13 (52mg, 0.10mmol) was purified using dry CH2Cl 2 (10 mL) was dissolved in an in situ flask, tsOH (15mg, 0.05mmol) was added, the reaction mixture was stirred at 30 ℃ for 15min, meOH (8. Mu.L, 0.2 mmol) was added, the reaction was allowed to react at 30 ℃ for 24h, and after completion of the reaction, et was used 3 Neutralizing the system to alkalescence by N, and concentrating under reduced pressure. The crude product was purified by flash column chromatography (6: 85.1 percent.
(c 0.25,CHCl 3 )； 1 H NMR(600MHz,CDCl 3 ):δ8.07(dd,J＝8.4,1.2Hz,2H),7.60(t,J＝7.2Hz,1H),7.47(t,J＝7.8Hz,1H),7.32-7.29(m,2H),7.00(t,J＝7.8Hz,1H),7.60(d,J＝7.8Hz,1H),4.58-4.52(m,2H),4.40(dd,J＝10.2,4.8Hz,1H),2.70(d,J＝4.8Hz,1H),1.58(s,2H)； 13 C NMR(150MHz,CDCl 3 ):δ166.8,158.3,133.3,133.3,129.7,129.6,129.5,129.4,128.5,121.4,114.6,114.6,77.2,77.0,76.8,68.8,68.8,68.7,65.9,31.5,29.7。
Example 11
The embodiment provides a sulfonic acid catalysis-based method for directionally transferring a hydroxyl-m-benzoyl group, in particular to a method for performing 1, 2-transfer reaction on an acyl functional group of a saccharide substrate under the catalysis condition of sulfonic acid, wherein the reaction formula is as follows:
the method comprises the following specific steps:
compound 15 (80mg, 0.11mmol) was applied over dry CH 2 Cl 2 (11 mL) was dissolved in an in situ flask, tsOH (17mg, 0.06mmol) was then added, the reaction mixture was stirred at 30 ℃ for 15min, meOH (9. Mu.L, 0.22 mmol) was added, the reaction was allowed to react at 30 ℃ for 24h, and after completion the reaction was Et 3 Neutralizing the system to alkalescence by N, and concentrating under reduced pressure. The crude product was purified by flash column chromatography (8: 90.7 percent.
(c0.6,CHCl 3 )； 1 H NMR(600MHz,CDCl 3 ):δ8.08-8.04(m,6H),7.61-7.54(m,3H),7.47-7.41(m,6H),5.65(dd,J＝4.8,0.6Hz 1H),5.52(d,J＝1.2Hz,1H),5.17(s,1H),4.64-4.60(m,1H),4.51-4.47(m,2H),4.39(dd,J＝5.4,2.4Hz,1H),3.44(s,3H)； 13 C NMR(150MHz,CDCl 3 ):δ166.5,166.2,165.4,133.6,133.1,130.0,129.9,129.8,129.7,129.1,129.0,128.6,128.5,128.4,128.3,107.0,83.0,81.6,78.2,77.2,77.0,76.8,69.0,66.2,55.1,29.7,22.7,14.6,14.6。
Example 12
The embodiment provides a sulfonic acid catalysis-based method for directionally transferring a hydroxyl-m-benzoyl group, in particular to a method for performing 1, 2-transfer reaction on an acyl functional group of a saccharide substrate under the catalysis condition of sulfonic acid, wherein the reaction formula is as follows:
the method comprises the following specific steps:
compound 17 (22mg, 0.03mmol) was applied with dry CH 2 Cl 2 (3 mL) was dissolved in a round bottom flask, tsOH (4 mg, 0.02mmol) was added, the reaction mixture was stirred at 30 ℃ for 15min, meOH (3. Mu.L, 0.06 mmol) was added, the reaction was allowed to react at 30 ℃ for 24h, and after completion the reaction was treated with Et 3 Neutralizing the system to alkalescence by N, and concentrating under reduced pressure. The crude product was purified by flash column chromatography (12: 63.7%,.
(c 0.5,CHCl 3 )； 1 H NMR(600MHz,CDCl 3 ):δ8.08-8.03(m,6H),7.61-7.54(m,3H),7.47-7.40(m,6H),5.64(d,J＝4.8Hz 1H),5.51(d,J＝0.6Hz,1H),5.26(s,1H),4.62(dd,J＝12,7.8Hz,1H),4.50-4.48(m,2H),4.37(dd,J＝4.8,2.4Hz,1H),2.73(d,J＝8.4Hz,1H), 13 C NMR(150MHz,CDCl 3 ):δ166.5,166.1,165.4,133.6,133.1,130.0,129.9,129.8,129.7,129.2,129.1,128.7,128.6,128.5,128.4,127.8,105.7,83.1,81.4,78.2,77.2,77.0,76.8,69.1,67.7,66.2,31.8,29.7,29.5,29.4,29.3,26.2,22.7,14.1。
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 (7)
1. A sulfonic acid catalyzed oriented migration method of a hydroxyl-m-benzoyl group is characterized by comprising the following steps:
under the action of a sulfonic acid reagent, benzoyl compound I is subjected to benzoyl migration reaction in an organic solvent A to prepare a compound II, wherein the sulfonic acid reagent is p-toluenesulfonic acid;
R 1 is phenyl;
R 2 hydrogen, triphenylmethyl, trimethylsilyl, triethylsilyl or tert-butyldimethylsilyl;
R 3 is hydrogen.
2. The sulfonic acid catalyzed oriented migration method of hydroxyisophthaloyl groups according to claim 1, further comprising: dissolving a benzoyl compound I in an organic solvent A, adding a sulfonic acid reagent, reacting for 1-12h, washing and drying the obtained reaction solution, filtering, decompressing to remove the solvent, and then purifying to obtain a compound II; the concentration of the reaction substrate is 0.01-0.1mol/L.
3. The sulfonic acid catalyzed oriented migration of hydroxybenzoyl groups based on claim 2, characterized in that: washing the reaction solution with saturated sodium bicarbonate solution and saturated sodium chloride solution in sequence, drying with anhydrous sodium sulfate, filtering, removing the solvent under reduced pressure, and purifying by a chromatographic silica gel column separation or crystallization way to obtain a compound II.
4. The sulfonic acid catalyzed oriented migration of hydroxybenzoyl groups based on claim 2, characterized in that: the mass ratio of the benzoyl compound I to the sulfonic acid reagent is 1.
5. The sulfonic acid catalyzed oriented migration of hydroxybenzoyl groups based on claim 4, characterized in that: the reaction temperature is 0-30 ℃; the organic solvent A is a mixed solvent of dichloromethane or 1, 2-dichloroethane and methanol or ethanol according to a volume ratio of 10-100.
6. The sulfonic acid catalyzed oriented migration of hydroxybenzoyl groups based on claim 5, characterized in that: the reaction temperature is 25-30 ℃; the organic solvent A is a mixed solvent of dichloromethane and methanol according to a volume ratio of 50-100.
7. The sulfonic acid catalyzed oriented migration of hydroxybenzoyl groups based on claim 6, characterized in that: in the benzoyl compound I, when R is 3 When it is hydrogen, R 1 Is phenyl; r 2 Is hydrogen, triphenylmethyl or trimethylsilyl.
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| Influence of Silyl Protections on the Anomeric Reactivity of Galactofuranosyl Thioglycosides and Application of the Silylated Thiogalactofuranosides to One-Pot Synthesis of Diverse β‑D‑Oligogalactofuranosides;Shuai Wang等;《J. Org. Chem.》;20141013;第79卷;10203−10217 * |
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