CN117305866A - Synthesis method of N-benzyl diaryl sulfoxide imine compound - Google Patents
Synthesis method of N-benzyl diaryl sulfoxide imine compound Download PDFInfo
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- CN117305866A CN117305866A CN202311345463.7A CN202311345463A CN117305866A CN 117305866 A CN117305866 A CN 117305866A CN 202311345463 A CN202311345463 A CN 202311345463A CN 117305866 A CN117305866 A CN 117305866A
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- benzyl
- sulfoxide imine
- diaryl sulfoxide
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- 238000001308 synthesis method Methods 0.000 title claims description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- -1 alkyl arene Chemical class 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 18
- 239000003054 catalyst Substances 0.000 claims abstract description 13
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 11
- LJUQGASMPRMWIW-UHFFFAOYSA-N 5,6-dimethylbenzimidazole Chemical compound C1=C(C)C(C)=CC2=C1NC=N2 LJUQGASMPRMWIW-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 239000003960 organic solvent Substances 0.000 claims description 7
- 239000003513 alkali Substances 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 4
- 239000007772 electrode material Substances 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 2
- 229940126214 compound 3 Drugs 0.000 claims description 2
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 2
- 239000003792 electrolyte Substances 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000005059 halophenyl group Chemical group 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 11
- 239000001257 hydrogen Substances 0.000 abstract description 11
- 229910052799 carbon Inorganic materials 0.000 abstract description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 8
- 239000007800 oxidant agent Substances 0.000 abstract description 8
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 229910052723 transition metal Inorganic materials 0.000 abstract description 6
- 150000003624 transition metals Chemical class 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 230000001590 oxidative effect Effects 0.000 abstract description 5
- 125000001743 benzylic group Chemical group 0.000 abstract description 3
- 230000005518 electrochemistry Effects 0.000 abstract description 3
- 238000006880 cross-coupling reaction Methods 0.000 abstract description 2
- 230000003647 oxidation Effects 0.000 abstract description 2
- 238000007254 oxidation reaction Methods 0.000 abstract description 2
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- 125000005555 sulfoximide group Chemical group 0.000 description 12
- 239000000758 substrate Substances 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 8
- RRXSYZFVDIRTFB-UHFFFAOYSA-N C[CH]C1=CC=C(OC)C=C1 Chemical group C[CH]C1=CC=C(OC)C=C1 RRXSYZFVDIRTFB-UHFFFAOYSA-N 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 238000006356 dehydrogenation reaction Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- WLWNRAWQDZRXMB-YLFCFFPRSA-N (2r,3r,4r,5s)-n,3,4,5-tetrahydroxy-1-(4-phenoxyphenyl)sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1S(=O)(=O)C(C=C1)=CC=C1OC1=CC=CC=C1 WLWNRAWQDZRXMB-YLFCFFPRSA-N 0.000 description 2
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical group O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- HDNRAPAFJLXKBV-UHFFFAOYSA-N 1-ethyl-4-methoxybenzene Chemical compound CCC1=CC=C(OC)C=C1 HDNRAPAFJLXKBV-UHFFFAOYSA-N 0.000 description 2
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 2
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 2
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- 239000011941 photocatalyst Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- UELYDGOOJPRWGF-SRQXXRKNSA-N (2r,3r)-3-[2-[4-(cyclopropylsulfonimidoyl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxybutan-2-ol Chemical compound C1=C(C(F)(F)F)C(O[C@H](C)[C@H](O)C)=NC(NC=2C=CC(=CC=2)[S@](=N)(=O)C2CC2)=N1 UELYDGOOJPRWGF-SRQXXRKNSA-N 0.000 description 1
- FAFIKYMDDCNLAH-UHFFFAOYSA-N BrN=[SH2]=O Chemical compound BrN=[SH2]=O FAFIKYMDDCNLAH-UHFFFAOYSA-N 0.000 description 1
- HVNQUZHHKOBDFX-UHFFFAOYSA-N C(C1=CC=CC=C1)N=[SH2]=O Chemical compound C(C1=CC=CC=C1)N=[SH2]=O HVNQUZHHKOBDFX-UHFFFAOYSA-N 0.000 description 1
- IVAXVDOVHLUHNX-UHFFFAOYSA-N CC1=CC2=C(N=CN2)C=C1C.CC1=CC2=C(N=CN2)C=C1C Chemical compound CC1=CC2=C(N=CN2)C=C1C.CC1=CC2=C(N=CN2)C=C1C IVAXVDOVHLUHNX-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 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 description 1
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- PDCKRJPYJMCOFO-UHFFFAOYSA-N azanediyl (triplet) Chemical group [NH] PDCKRJPYJMCOFO-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001723 carbon free-radicals Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- 239000012969 di-tertiary-butyl peroxide Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- HHDPJRSXPOGIOP-UHFFFAOYSA-L manganese(2+);dibromide;tetrahydrate Chemical compound O.O.O.O.[Mn+2].[Br-].[Br-] HHDPJRSXPOGIOP-UHFFFAOYSA-L 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- HSOWGTFAGFRXKH-UHFFFAOYSA-N n,n-diethyl-2-[[oxo(diphenyl)-$l^{6}-sulfanylidene]amino]ethanamine Chemical compound C=1C=CC=CC=1S(=O)(=NCCN(CC)CC)C1=CC=CC=C1 HSOWGTFAGFRXKH-UHFFFAOYSA-N 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229950002433 roniciclib Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical group [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229950008871 suloxifen Drugs 0.000 description 1
- 238000010490 three component reaction Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/07—Oxygen containing compounds
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/09—Nitrogen containing compounds
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/20—Processes
Abstract
The invention discloses a method for synthesizing an N-benzyl diaryl sulfoxide imine compound, belonging to the technical field of organic chemistry. With N-H diaryl sulfoximine 1 and a benzylic carbon (sp 3 ) The hydrogen bond alkyl arene 2 is used as a raw material, and N-H/C-H cross coupling is performed under the catalysis of electrochemical anodic oxidation and 5,6-dimethyl benzoimidazole, so that the rapid synthesis of the N-benzyl diaryl sulfoxide imine compound is realized. The invention adopts electrochemistry to directly couple N-H/C-H, has high atom/step economy, simultaneously the reaction does not need transition metal catalyst and oxidant, is environment-friendly, has mild reaction conditions, and provides a new way for synthesizing N-benzyl diaryl sulfoxide imine series products.
Description
Technical Field
The invention relates to a method for synthesizing N-benzyl diaryl sulfoxide imine, belonging to the technical field of organic chemistry.
Background
Sulfoximine derivatives, which are widely used in the medical field, such as the bronchodilator Shu Luoxi, suloxifen and Roniciclib, are potent pan-CDK inhibitors and novel oral cytotoxic agents, which have been studied for the treatment of small cell lung cancer. In addition to the pharmaceutical field, many sulfoximines are used as chiral ligands in the field of organic synthesis, which has important applications in asymmetric synthesis.
In 2018, literature reported the use of high iodides containing sulfoximine structures with benzyl positions under photocatalysisSp of carbon 3 Hydrogen bonding to give N-benzyl sulfoximine, however, the economy of the reaction atoms is very poor and noble metal Ru is used as photocatalyst. N-H sulfoximine is used as a substrate and contains benzylic carbon sp 3 The hydrogen bond substrate is subjected to N-H/C-H cross dehydrogenation coupling reaction, so that the synthesis of the N-benzyl sulfoxide imine has high atom and step economy. The traditional N-H/C-H cross-dehydrogenation coupling reactions of this type use the transition metal FeBr 3 As a catalyst and a large amount of peroxide DTBP as an oxidizing agent was added. In 2022, a photocatalytic N-H/C-H cross dehydrogenation coupling reaction is reported, however, the reaction still uses noble metal Ru as a photocatalyst, and an equivalent brominating reagent NBS needs to be added to convert N-H sulfoximine into N-Br sulfoximine, which is not a direct N-H/C-H cross dehydrogenation coupling reaction.
The electrochemical organic synthesis has the incomparable advantage of the traditional method, can directly carry out oxidation reduction by utilizing the electrode, does not need the use of an oxidant and a reducing agent, is a green synthesis method, and becomes a new hot spot in the field of organic synthesis in recent years. However, very few examples of direct N-H functionalization reactions using electrochemistry to effect N-H sulfoximines are available. In 2021, the literature reports the electrochemically participated nickel-catalyzed N-H arylation of N-H sulfoximines with aryl halides, which is however still a transition metal-catalyzed cross-coupling reaction. In 2022, the literature reports the three-component reaction of electrochemically involved N-H sulfoximines with aryl olefins and alcohols. The two reactions are obtained by N-phenyl sulfoxide imine and N-phenethyl sulfoxide imine, and N-benzyl sulfoxide imine can not be obtained. For N-H sulfoximine and benzyl-containing carbon sp under electrochemistry 3 The hydrogen bond substrate N-H/C-H cross-dehydrogenation coupling reaction only reported in 2021 literature for N-H sulfoxide imines with diarylmethanes. However, the reaction substrate is severely limited and is only applicable to diarylmethanes containing two aryl groups, and is not applicable to common compounds containing 1 aryl group.
By adopting a green electrochemical synthesis method, the N-H sulfoxide imine and the benzyl position C (sp) of the common compound containing 1 aryl group with wider substrate range 3 ) N-H/C-H cross-deprotection of the-H bondThe hydrogen coupling reaction has very high atom economy and step economy, and is a method for preparing the N-benzyl diaryl sulfoxide imine rapidly and efficiently. However, no relevant literature has been reported so far, and thus it is still necessary to explore a method for constructing N-benzyldiaryl sulfoximine and the like under mild conditions without a transition metal catalyst and without an oxidizing agent.
Disclosure of Invention
To overcome the problems of N-H sulfoximine and benzylic carbon (sp 3 ) The present invention has the defect of N-H/C-H coupling reaction by hydrogen bond, and in the present invention, both anode and cathode are carbon electrodes, and under the participation of anode and catalyst 5,6-dimethyl benzoimidazole, benzyl carbon (sp 3 ) Hydrogen bonds are oxidized to carbon radicals, which in turn are oxidized by the anode to carbonium ions. And reducing hexafluoroisopropanol serving as an additive into hydrogen at a cathode, taking hexafluoroisopropanol anions as alkali, capturing H on N-H sulfoxide imine N to generate benzyl N anions, and reacting with carbocation to obtain N-benzyl diaryl sulfoxide imine. The invention does not need transition metal catalyst and oxidant, has wide substrate application range, has good reaction effect on common compounds containing 1 aryl group with more general applicability, has mild reaction condition and is carried out at room temperature, thereby providing a new way for synthesizing N-benzyl diaryl sulfoxide imine series products.
The invention discloses a synthesis method of N-benzyl diaryl sulfoxide imine, which comprises the following operations: N-H diaryl sulfoxide imine 1 and alkyl aromatic hydrocarbon 2 are used as raw materials, tetrabutylammonium tetrafluoroborate is used as electrolyte in the presence of a catalyst and alkali, and N-benzyl diaryl sulfoxide imine compound 3 is obtained through constant current reaction in an organic solvent; the reaction equation is as follows:
wherein: ar (Ar) 1 And Ar is a group 2 Each independently selected from phenyl, C1-C4 alkylphenyl, C1-C4 alkoxyphenyl, halophenyl, cyanophenyl, or thienyl; r is R 1 Selected from methoxy or ethoxy; r is R 2 Is C1-C4 alkyl, acetoxyalkyl orC1-C4 alkoxycarbonyl.
Further, in the above-mentioned technical scheme, the electrode material is selected from the group consisting of Pt (+)/Pt (-), C (+)/C (-), C (+)/Pt (-), pt (+)/C (-), GF (+)/C (-), ni (+)/C (-), and preferably C (+)/C (-) during the constant current reaction.
Further, in the above technical scheme, the catalyst is selected from Benzoquinone (BQ), 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ), potassium iodide (KI), manganese bromide tetrahydrate (Mn Br) 2 ·4H 2 O), N-iodosuccinimide (NIS), 10-phenyl-10H-phenothiazine (10-phenyl-10H-phenothiazine), 5, 6-dimethylbenzimidazole (5, 6-dimethylbenz imidazole), N-hydroxyphthalimide (NHPI), preferably 5, 6-dimethylbenzimidazole.
Further, in the above technical scheme, the base is selected from t-BuONa or K 2 CO 3 Preferably K 2 CO 3 。
Further, in the above technical scheme, the organic solvent is selected from DCE and CH 3 CN or DCE/HFIP.
Further, in the above technical scheme, the molar ratio of the N-H diaryl sulfoxide imine 1 to the alkyl aromatic hydrocarbon 2 is 1:2-3, preferably 1:3.
further, in the above technical scheme, the reaction temperature is selected from 20-70 ℃, preferably room temperature.
Based on the above results and the reports in the prior art, taking diphenyl sulfoxide imine 1a and 4-ethyl anisole 2a as examples, the reaction product 3a is presumed to have the following reaction mechanism:
on the anode, the catalyst 5,6-dimethyl benzoimidazole is stripped of H on N by the alkali hexafluoroisopropanol anion, and then anodized to a free radical compound A. After oxidation of starting material 2a to benzyl radical intermediate B, the reaction proceeds again with 5, 6-dimethylbenzimidazole. The benzyl radical intermediate B may be directly anodically oxidized to the benzyl carbocation intermediate C. At the cathode, hexafluoroisopropanol can be reduced to hydrogen and hexafluoroisopropanol anions. The hexafluoroisopropanol is used as alkali to remove H on N of a reactant sulfoximine 1a, and the intermediate D of N negative ions at the 1a benzyl position is combined with the intermediate C of carbobenzyl positive ions to obtain a target product 3a.
The invention has the beneficial effects that:
1. the N-H diaryl sulfoxide imine and alkyl arene containing carbon and hydrogen bonds are used as raw materials, under the electrochemical conditions of no transition metal oxidant and no oxidant, the N-H/C-H cross dehydrogenation coupling reaction is realized, the reaction does not need to prepare a pre-functionalized substrate, the method has very high atom and step economy, the byproduct is only hydrogen, the reaction condition is mild, the reaction can be carried out at room temperature, the reaction time is only 2 hours, and the efficient green synthesis of the N-benzyl diaryl sulfoxide imine is realized.
2. Overcomes the defects of the traditional N-benzyl sulfoxide imine synthesis method, such as the use of transition metal and a large amount of oxidizing agents. The electrochemical N-benzyl sulfoxide imine synthesis substrate is severely limited, and is only applicable to diaryl methane compounds containing two aryl groups, but not applicable to common compounds containing 1 aryl group. The invention has good reaction effect on the common compound with more general applicability and 1 aryl, and provides a brand new synthesis strategy for synthesizing N-benzyl diaryl sulfoxide imine series products.
Detailed Description
Example 1
Optimization of reaction conditions
Into a 10mL diaphragm-free electrolytic cell, solid compound 1a (0.3 mmol) and n-Bu were added in this order 4 NBF 4 (0.3 mmol), base and catalyst, followed by liquid compound 2a and organic solvent (5 mL). The bottle mouth is plugged by a rubber plug inserted into the electrode. And 8mA constant current is supplied for reaction for 2 hours. The solvent is removed by a rotary evaporator, and the target product is obtained by column chromatography separation. The optimized reaction results were as follows:
in the reaction condition screening process, the influence of electrode materials (1-6), catalysts (7-14), bases (15-19), organic solvents (20-25), the molar ratio of 1a to 2a (26), the reaction temperature (27) and the like is examined. The optimal reaction conditions were finally determined: the electrode material is C (+)/C (-), the catalyst is 5,6-dimethyl benzoimidazole, and the alkali is K 2 CO 3 The organic solvent is DCE/HFIP (10/1), the molar ratio of the raw material 1a/2a is 1/3, and the reaction temperature is room temperature.
Example 2:
in a diaphragm-free electrolytic cell, compound 1a (0.3 mmol), 5, 6-dimethylbenzimidazole (20 mol%), n-Bu were added in this order 4 NBF 4 (0.3mmol)、K 2 CO 3 (0.3 mmol) and 2a (0.9 mmol), 1, 2-dichloroethane (5 mL) and hexafluoroisopropanol (0.5 mL) were added. Two carbon rods (with the diameter of 6 mm) are inserted after the rubber plug is punched, then the rubber plug is plugged into the bottle mouth, the two carbon rods are connected with a power supply, and 8mA constant current is introduced. After 2 hours of reaction at room temperature, the solvent was removed by rotary evaporator and petroleum ether: ethyl acetate = 5: column chromatography with eluent 1 gave 80.3mg of product 3a as pale yellow liquid in 76% yield. 1 H NMR(600MHz,CDCl 3 )δ8.05-8.03(m,2H),7.84-7.82(m,2H),7.52-7.44(m,4H),7.39-7.37(m,2H),7.34-7.32(m,2H),6.86-6.84(m,2H),4.36(q,J＝6.6Hz,1H),3.80(s,3H),1.54(d,J＝6.6Hz,3H). 13 CNMR(151MHz,CDCl 3 )δ158.2,141.6,141.0,140.0,132.4,132.3,129.1,129.0,128.6,127.3,113.6,55.4,53.8,28.3.
Example 3:
according to the reaction conditions of example 2, only the structures of substrates 1 and 2 were changed, and the reaction results were as follows:
N-[1-(4-methoxyphenyl)ethyl]-1-(4-methylphenyl)-1-oxo-1-phenyl-λ 6 -sul fanimine(3b):Pale yellow oil；57.8mg,53％yield； 1 H NMR(600MHz,CDCl 3 )δ8.02(d,J＝7.2Hz,2H),7.91(d,J＝8.2Hz,2H),7.81(d,J＝7.5Hz,2H),7.70(d,J＝8.2Hz,2H),7.49-7.42(m,4H),7.38-7.31(m,6H),7.26-7.24(m,2H),7.17(d,J＝8.1Hz,2H),6.86-6.83(m,4H),4.37-7.33(m,2H),3.80(s,3H),3.79(s,3H),2.37(s,3H),2.34(s,3H),1.53(d,J＝6.6Hz,6H). 13 C NMR(151MHz,CDCl 3 )δ158.2,143.2,143.1,141.9,141.3,140.1,140.0,138.6,137.8,132.3,132.2,129.8,129.8,129.1,129.1,128.9,128.6,128.4,127.3,113.6,55.4,53.7,53.7,28.4,28.3,21.6,21.5.
1-(4-chlorophenyl)-N-[1-(4-methoxyphenyl)ethyl]-1-oxo-1-phenyl-λ 6 -sulfanimine(3c):Pale yellow oil；80.9mg,70％yield； 1 H NMR(600MHz,CDCl 3 )δ8.03-8.01(m,2H),7.97-7.95(m,2H),7.82-7.80(m,2H),7.74-7.71(m,2H),7.53-7.46(m,4H),7.44-7.38(m,4H),7.34-7.29(m,6H),6.86-6.83(m,4H),4.38-4.34(m,2H),3.80(s,3H),3.80(s,3H),1.54-1.53(m,6H). 13 C NMR(151MHz,CDCl 3 )δ158.3,158.3,141.3,140.6,140.3,139.7,139.6,139.1,138.9,132.7,132.6,130.5,130.0,129.4,129.4,129.3,129.0,128.5,127.3,113.7,113.7,55.4,53.8,53.7,28.3,28.2.
1-(4-methoxyphenyl)-N-[1-(4-methoxyphenyl)ethyl]-1-oxo-1-phenyl-λ 6 -sulfanimine(3d):Pale yellow oil；78.3mg,68％yield； 1 H NMR(600MHz,CDCl 3 )δ8.03-8.01(m,2H),7.98-7.95(m,2H),7.81-7.94(m,2H),7.76-7.74(m,2H),7.49-7.41(m,4H),7.38-7.31(m,6H),6.95-6.92(m,2H),6.87-6.83(m,6H),4.38-4.32(m,2H),3.81(s,3H),3.80(s,3H),3.79(s,3H),3.79(s,3H),1.54(d,J＝2.8Hz,3H),1.53(d,J＝2.8Hz,3H). 13 C NMR(151MHz,CDCl 3 )δ162.9,162.8,158.2,142.2,141.5,140.1,140.0,133.0,132.2,132.0,131.1,130.7,129.0,128.7,128.2,127.3,127.3,114.4,114.4,113.6,113.6,55.7,55.6,55.3,53.7,53.7,28.4,28.3.
1-(4-bromophenyl)-N-[1-(4-methoxyphenyl)ethyl]-1-(4-methylphenyl)-1-oxo-λ 6 -sulfanimine(3e):Pale yellow oil；77.2mg,58％yield； 1 H NMR(600MHz,CDCl 3 )δ7.90-7.86(m,4H),7.69-7.68(m,2H),7.65-7.62(m,2H),7.59-7.56(m,2H),7.49-7.47(m,2H),7.33-7.26(m,6H),7.19(d,J＝8.1Hz,2H),6.86-6.82(m,4H),4.34(q,J＝6.6Hz,2H),3.80(s,3H),3.80(s,3H),2.38(s,3H),2.35(s,3H),1.53(d,J＝6.7Hz,3H),1.52(d,J＝6.8Hz,3H). 13 C NMR(151MHz,CDCl 3 )δ158.3,158.3,143.5,143.5,141.2,140.6,139.8,139.7,138.2,137.4,132.3,132.3,130.5,130.0,130.0,129.9,129.1,128.5,127.4,127.3,127.3,113.7,55.4,53.8,53.7,28.3,21.6,21.6.
4-[(4-chlorophenyl){[1-(4-methoxyphenyl)ethyl]azanylidene}(oxo)-λ 6 -sulfanyl]benzene-1-carbonitrile(3f):Pale yellow oil；65.3mg,53％yield； 1 H NMR(600MHz,CDCl 3 )δ8.11-8.10(m,2H),7.96-7.94(m,2H),7.85-7.84(m,2H),7.76-7.75(m,2H),7.72-7.70(m,2H),7.64-7.63(m,2H),7.47-7.45(m,2H),7.38-7.36(m,2H),7.28-7.25(m,2H),7.24-7.22(m,2H),6.85-6.79(m,4H),4.38-4.33(m,2H),3.80(s,3H),3.79(s,3H),1.54-1.51(m,6H). 13 C NMR(151MHz,CDCl 3 )δ158.5,146.0,145.8,140.0,139.8,139.0,138.9,138.9,138.5,133.0,132.9,130.7,130.1,129.7,129.7,129.5,129.1,127.3,117.5,116.3,116.1,113.8,113.8,55.4,53.9,53.8,28.1,28.0..
1-(4-chlorophenyl)-1-(4-methoxyphenyl)-N-[1-(4-methoxyphenyl)ethyl]-1-oxo-λ 6 -sulfanimine(3g):Pale yellow oil；79.6mg,64％yield； 1 H NMR(600MHz,CDCl 3 )δ7.95-7.92(m,4H),7.73-7.69(m,4H),7.42-7.40(m,2H),7.33-7.29(m,6H),6.95-6.93(m,2H),6.87-6.83(m,6H),4.36-4.31(m,2H),3.82(s,3H),3.81-3.79(m,9H),1.53(d,J＝6.8Hz,3H),1.51(d,J＝6.8Hz,3H). 13 C NMR(151MHz,CDCl 3 )δ163.1,163.0,158.3,140.9,140.2,139.9,139.8,138.7,138.6,132.6,131.8,131.1,130.6,130.2,129.8,129.3,129.3,127.3,127.3,114.5,114.5,113.7,55.7,55.7,55.4,53.7,53.7,28.3,28.3.
N-[1-(4-methoxyphenyl)ethyl]-1-oxo-1-phenyl-1-(thiophen-2-yl)-λ 6 -sulfanimine(3h):Pale yellow oil；81.1mg,76％yield； 1 H NMR(600MHz,CDCl 3 )δ8.12-8.10(m,2H),7.95-7.94(m,2H),7.59-7.58(m,2H),7.53-7.47(m,5H),7.43-7.41(m,2H),7.38-7.33(m,4H),7.31(dd,J＝3.7,1.2Hz,1H),7.04(dd,J＝4.9,3.9Hz,1H),6.94(dd,J＝4.9,3.8Hz,1H),6.89-6.83(m,4H),4.57(q,J＝6.6Hz,1H),4.44(q,J＝6.6Hz,1H),3.81(s,3H),3.79(s,3H),1.57(d,J＝6.6Hz,3H),1.55(d,J＝6.6Hz,3H). 13 C NMR(151MHz,CDCl 3 )δ158.2,158.2,143.7,143.0,142.2,141.4,139.8,139.5,133.7,133.5,133.3,132.6,132.5,129.1,128.5,128.0,128.0,127.9,127.3,113.6,113.6,55.3,55.3,53.9,53.9,28.4,28.0.
N-[1-(4-ethoxyphenyl)ethyl]-1-oxo-1,1-diphenyl-λ 6 -sulfanimine(3i):Paleyellow oil；70.5mg,64％yield； 1 H NMR(600MHz,CDCl 3 )δ8.04(d,J＝7.5Hz,2H),7.83(d,J＝7.8Hz,2H),7.51-7.43(m,4H),7.38(t,J＝7.7Hz,2H),7.31(d,J＝8.5Hz,2H),6.84(d,J＝8.4Hz,2H),4.36(q,J＝6.5Hz,1H),4.03(q,J＝7.0Hz,2H),1.54(d,J＝6.6Hz,3H),1.41(t,J＝7.0Hz,3H). 13 C NMR(151MHz,CDCl 3 )δ157.6,141.6,141.0,139.8,132.4,132.3,129.1,129.0,128.5,127.3,114.2,63.5,53.7,28.3,15.1.
N-[1-(4-methoxyphenyl)propyl]-1-oxo-1,1-diphenyl-λ 6 -sulfanimine(3j):Pale yellow oil；78.9mg,72％yield； 1 H NMR(600MHz,CDCl 3 )δ8.02-8.00(m,2H),7.77(dd,J＝8.2,0.9Hz,2H),7.50-7.41(m,4H),7.34(t,J＝7.8Hz,2H),7.23-7.21(m,2H),6.82(d,J＝8.6Hz,2H),4.03(t,J＝6.7Hz,1H),3.80(s,3H),1.94-1.87(m,1H),1.84-1.77(m,1H),0.89(t,J＝7.3Hz,3H). 13 C NMR(151MHz,CDCl 3 )δ158.2,141.5,141.1,138.6,132.4,132.3,129.1,129.1,129.0,128.6,127.9,113.5,60.1,55.3,34.5,11.1.
3-(4-methoxyphenyl)-3-[(oxodiphenyl-λ 6 -sulfanylidene)amino]propyl ace tate(3k):Pale yellow oil；76.1mg,60％yield； 1 H NMR(600MHz,CDCl 3 )δ7.96(d,J＝7.6Hz,2H),7.78(d,J＝7.7Hz,2H),7.49-7.42(m,4H),7.35(t,J＝7.5Hz,2H),7.23(d,J＝8.4Hz,2H),6.81(d,J＝8.4Hz,2H),4.31-4.24(m,2H),4.12-4.08(m,1H),3.78(s,3H),2.21-2.15(m,1H),2.10-2.04(m,1H),1.95(s,3H). 13 CNMR(151MHz,CDCl 3 )δ171.2,158.4,141.1,140.9,137.8,132.4,132.4,129.1,129.0,128.9,128.5,127.7,113.7,62.3,55.3,55.1,39.9,21.1.
methyl 2-(4-methoxyphenyl)-2-[(oxodiphenyl-λ 6 -sulfanylidene)amino]ac etate(3l):Pale yellow oil；65.8mg,55％yield； 1 H NMR(600MHz,CDCl 3 )δ8.01(d,J＝7.4Hz,2H),7.91(d,J＝7.6Hz,2H),7.53-7.40(m,8H),6.85(d,J＝8.6Hz,2H),4.89(s,1H),3.78(s,3H),3.64(s,3H). 13 CNMR(151MHz,CDCl 3 )δ173.3,159.2,140.6,140.3,132.8,132.7,132.2,129.2,129.2,128.8,128.7,128.5,113.9,60.2,55.3,52.4.
the foregoing embodiments illustrate the basic principles, principal features and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the above-described embodiments, and that the above-described embodiments and descriptions are merely illustrative of the principles of the present invention, and various changes and modifications may be made without departing from the scope of the principles of the invention, which are defined in the appended claims.
Claims (7)
1. The synthesis method of the N-benzyl diaryl sulfoxide imine compound is characterized by comprising the following operations: N-H diaryl sulfoxide imine 1 and alkyl aromatic hydrocarbon 2 are used as raw materials, tetrabutylammonium tetrafluoroborate is used as electrolyte in the presence of a catalyst and alkali, and N-benzyl diaryl sulfoxide imine compound 3 is obtained through constant current reaction in an organic solvent; the reaction equation is expressed as follows:
wherein: ar (Ar) 1 And Ar is a group 2 Each independently selected from phenyl, C1-C4 alkylphenyl, C1-C4 alkoxyphenyl, halophenyl, cyanophenyl, or thienyl; r is R 1 Selected from methoxy or ethoxy; r is R 2 Is C1-C4 alkyl, acetoxyalkyl or C1-C4 alkoxycarbonyl.
2. The method for synthesizing the N-benzyl diaryl sulfoxide imine compound according to claim 1, wherein the method is characterized in that: in the constant current reaction, the electrode material is selected from Pt (+)/Pt (-), C (+)/C (-), C (+)/Pt (-), pt (+)/C (-), GF (+)/C (-), and Ni (+)/C (-).
3. The method for synthesizing the N-benzyl diaryl sulfoxide imine compound according to claim 1, wherein the method is characterized in that: the catalyst is 5,6-dimethyl benzoimidazole.
4. The method for synthesizing the N-benzyl diaryl sulfoxide imine compound according to claim 1, wherein the method is characterized in that: the base is selected from t-Buona or K 2 CO 3 。
5. The method for synthesizing the N-benzyl diaryl sulfoxide imine compound according to claim 1, wherein the method is characterized in that: the organic solvent is selected from DCE, CH 3 CN or DCE/HFIP.
6. The method for synthesizing the N-benzyl diaryl sulfoxide imine compound according to claim 1, wherein the method is characterized in that: the molar ratio of the N-H diaryl sulfoxide imine 1 to the alkyl aromatic hydrocarbon 2 is 1:2-3.
7. The method for synthesizing an N-benzyldiaryl sulfoximine compound according to claim 1, wherein: the reaction temperature is selected from 20-70 ℃.
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