CN115807233A - Method for electrochemically synthesizing substituted indole from gamma-hydroxylamine - Google Patents
Method for electrochemically synthesizing substituted indole from gamma-hydroxylamine Download PDFInfo
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- CN115807233A CN115807233A CN202211590203.1A CN202211590203A CN115807233A CN 115807233 A CN115807233 A CN 115807233A CN 202211590203 A CN202211590203 A CN 202211590203A CN 115807233 A CN115807233 A CN 115807233A
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- tetrabutylammonium
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- 238000000034 method Methods 0.000 title claims abstract description 25
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 150000002475 indoles Chemical class 0.000 title claims abstract description 22
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title claims abstract description 20
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 19
- 239000012456 homogeneous solution Substances 0.000 claims abstract description 31
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- 230000035484 reaction time Effects 0.000 claims abstract description 10
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- 238000003487 electrochemical reaction Methods 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 49
- -1 tetrabutylammonium hexafluorophosphate Chemical compound 0.000 claims description 40
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 8
- 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 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 238000004440 column chromatography Methods 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 4
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 claims description 4
- 229910001486 lithium perchlorate Inorganic materials 0.000 claims description 4
- 239000003208 petroleum Substances 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 claims description 4
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical class C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 238000010898 silica gel chromatography Methods 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 230000005518 electrochemistry Effects 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- MCZDHTKJGDCTAE-UHFFFAOYSA-M tetrabutylazanium;acetate Chemical compound CC([O-])=O.CCCC[N+](CCCC)(CCCC)CCCC MCZDHTKJGDCTAE-UHFFFAOYSA-M 0.000 claims description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 7
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 36
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 35
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- 238000001228 spectrum Methods 0.000 description 35
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 24
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- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 16
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
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- 238000010276 construction Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
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- 229920006362 Teflon® Polymers 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
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- 125000005843 halogen group Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
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- 238000011068 loading method Methods 0.000 description 1
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- FTKFWBRBQCQSHY-UHFFFAOYSA-N n-(3-formyl-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)benzamide Chemical compound S1C=2CCCCC=2C(C=O)=C1NC(=O)C1=CC=CC=C1 FTKFWBRBQCQSHY-UHFFFAOYSA-N 0.000 description 1
- QRXZFQZJQMAMGW-FMIVXFBMSA-N n-[4-[(e)-3-(2-chlorophenyl)prop-2-enoyl]phenyl]thiophene-2-carboxamide Chemical compound ClC1=CC=CC=C1\C=C\C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=CS1 QRXZFQZJQMAMGW-FMIVXFBMSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
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- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
Abstract
The invention discloses a method for electrochemically synthesizing substituted indole by gamma-hydroxylamine, which is characterized in that homogeneous solution obtained by mixing a substrate, an organic additive, an electrolyte and a solvent is added into an electrochemical reaction device with a cathode and an anode, and the substituted indole is synthesized by an electrocatalysis one-step method. By combining the technology of synthesizing substituted indole by gamma-hydroxylamine and organic electrocatalysis, the oxidation-reduction reaction is realized by using clean electric energy, and the use of oxidation or reduction reagents is avoided. This electrochemical indole synthesis strategy has excellent functional group, water and air tolerance. Compared with the prior art, the synthesis method is efficient and economical, the product has no metal residue, the reaction time is short, the raw materials are simple and easy to obtain, and the yield is high; the application of the composite material in the field of biomedical materials is more competitive.
Description
Technical Field
The invention belongs to the field of medicinal chemistry and fine chemistry synthesis, and particularly relates to a method for electrochemically synthesizing substituted indole from gamma-hydroxylamine.
Background
The basic skeleton of the indole compounds is a benzopyrrole ring, and the compounds are widely present in active organisms, natural products and drug molecular structures. The compound with indole as basic parent nucleus structure has various pharmacological activities of tumor resistance, inflammation resistance, bacteria resistance and the like, so that the synthesis, development and application of the compound are methodology research which is very important, and the compound has wide development prospect.
It was found by earlier search that N radicals have not gained much attention in synthetic chemistry compared to C radicals, probably because of their higher reactivity and lack of efficient preparation methods. In most cases, the N radical is generated by cleavage of a reactive N-X bond, where X can be a halogen atom or a N, O, S group. At the same time, most of the R1R2N-X type precursors of N radicals are less stable and require in situ synthesis, and it is therefore very important to develop new, stable, easy to prepare, cheap and efficient N-radical precursors.
The most important and difficult link in the synthesis of nitrogen-containing compounds is the construction of carbon-nitrogen bonds. The construction reaction of carbon-nitrogen bond is a very important reaction in organic chemistry, but many organic reactions also cause certain environmental pollution problems while constructing carbon-nitrogen bond. With the increase of the call of 'green chemistry', chemists increasingly prefer to carry out organic reaction under the green and pollution-free conditions, and synthesize a new compound through carbon-nitrogen bond construction reaction induced under electrochemical catalysis, so that the new compound has certain biological activity and pharmaceutical activity, or carry out functional modification and modification on the existing compound, so that the new compound can be widely applied to the production of chemical industry and fine chemicals. The green chemistry goal can be well achieved.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to solve the technical problem of the prior art and provides a method for electrochemically synthesizing substituted indole from gamma-hydroxylamine so as to solve the problems of low reaction efficiency and large metal residue in the prior art.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a method for synthesizing substituted indole by gamma-hydroxylamine electrochemistry is characterized in that homogeneous solution obtained by mixing a substrate 1, an organic additive, an electrolyte and a solvent is added into an electrochemical reaction device with a cathode and an anode, and substituted indole 2 is synthesized by an electrocatalysis one-step method;
the reaction equation is as follows:
wherein R1 is selected from any one of electron-donating group hydrogen, alkyl with 1-4C, phenyl or substituted phenyl;
r2 is selected from any one of electron-donating group hydrogen, alkyl with 1-4C, phenyl or substituted phenyl;
r is selected from any one of alkyl, phenyl or substituted phenyl of 1-4C.
Specifically, the organic additive is selected from one or the combination of more than two of trifluoroacetic acid, methanesulfonic acid, acetic acid and p-toluenesulfonic acid; preferably acetic acid and/or p-toluenesulfonic acid; further preferred is p-toluenesulfonic acid.
Specifically, the electrolyte is any one or a combination of more than two of tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium acetate, tetrabutylammonium iodide and lithium perchlorate; preferably one or the combination of more than two of tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate and lithium perchlorate; further preferably tetrabutylammonium hexafluorophosphate and/or tetrabutylammonium tetrafluoroborate; still more preferred is tetrabutylammonium tetrafluoroborate.
Specifically, the solvent is selected from any one or the combination of more than two of dichloroethane, N-dimethylformamide, dimethyl sulfoxide, trifluoroethanol, acetonitrile, hexafluoroisopropanol, trichloroethylene, N-dimethylaniline and tetrahydrofuran; preferably one or the combination of more than two of dimethyl sulfoxide, trifluoroethanol, acetonitrile, hexafluoroisopropanol, trichloroethylene, N-dimethylaniline and tetrahydrofuran; more preferably, it is any one or a combination of two or more of trifluoroethanol, acetonitrile and hexafluoroisopropanol; more preferably, the mixed solution of trifluoroethanol and acetonitrile in a volume ratio of 3.5.
Specifically, the molar ratio of the substrate 1 to the organic additive is 1:1-3; preferably 1:1 to 2, more preferably 1:1 to 1.8, and still more preferably 1.5.
Specifically, the molar ratio of the substrate 1 to the electrolyte is 1; preferably 1.5 to 1.5, more preferably 1:1 to 1.5, and still more preferably 1:1.
Specifically, the concentration of the substrate 1 in the homogeneous solution is 0.02 to 0.08mmol/mL, preferably 0.02 to 0.06mmol/mL, more preferably 0.02 to 0.04mmol/mL, and still more preferably 0.03mmol/mL.
Specifically, the concentration of the organic additive in the homogeneous solution is 0.03-0.12 mmol/mL, preferably 0.03-0.1 mmol/mL, more preferably 0.03-0.06 mmol/mL, and even more preferably 0.045mmol/mL.
Specifically, the concentration of the electrolyte in the homogeneous solution is 0.02 to 0.08mmol/mL, preferably 0.03 to 0.05mmol/mL, more preferably 0.03 to 0.04mmol/mL, and still more preferably 0.03mmol/mL.
Specifically, the current intensity introduced by the electrocatalysis reaction is 5-20 mA; preferably 5 to 15mA; further preferably 8mA.
Specifically, the electrocatalytic reaction time is 90-180 min, preferably 90-160 min, and more preferably 120min; the reaction temperature is 50 to 80 ℃, preferably 50 to 70 ℃, and more preferably 70 ℃.
Further, the method also comprises the following purification steps: extracting the reaction liquid obtained after the reaction is finished to obtain an organic phase, concentrating, and carrying out column chromatography to obtain a substituted indole compound;
the extraction is to extract the reaction solution by ethyl acetate and saturated sodium chloride aqueous solution;
the column chromatography adopts silica gel column chromatography;
the eluent for column chromatography is a mixed solvent of petroleum ether and ethyl acetate according to the volume ratio of 1.
Has the advantages that:
the invention combines the technology of synthesizing substituted indole by gamma-hydroxylamine and the organic electro-catalysis technology, realizes the oxidation-reduction reaction by using clean electric energy, and avoids using oxidation or reduction reagents. This electrochemical indole synthesis strategy has excellent functional group, water and air tolerance. Compared with the prior art, the synthesis method is efficient and economical, and the product has no metal residue and high yield; the application of the composite material in the field of biomedical materials is more competitive.
Drawings
The foregoing and/or other advantages of the invention will become further apparent from the following detailed description of the invention when taken in conjunction with the accompanying drawings.
FIG. 1 is a reaction equation for synthesizing substituted indole compounds according to the present invention.
FIG. 2 is a schematic diagram of a reaction apparatus for synthesizing a substituted indole compound according to the present invention.
FIG. 3 is a NMR spectrum of product 2a of example 1.
FIG. 4 is a NMR carbon spectrum of product 2a of example 1.
FIG. 5 is a NMR spectrum of product 2b of example 2.
FIG. 6 is a NMR carbon spectrum of product 2b of example 2.
FIG. 7 is a NMR spectrum of product 2c of example 3.
FIG. 8 is a NMR carbon spectrum of product 2c of example 3.
FIG. 9 is a NMR spectrum of product 2d of example 4.
FIG. 10 is a NMR carbon spectrum of product 2d of example 4.
FIG. 11 is a NMR spectrum of product 2e of example 5.
FIG. 12 is a NMR carbon spectrum of product 2e of example 5.
FIG. 13 is a NMR spectrum of product 2f of example 6.
FIG. 14 is a NMR carbon spectrum of product 2f of example 6.
FIG. 15 is the NMR chart of 2g of the product of example 7.
FIG. 16 is a NMR carbon spectrum of 2g of the product of example 7.
FIG. 17 is a NMR spectrum of product 2h of example 8.
FIG. 18 is the NMR carbon spectrum of product 2h from example 8.
FIG. 19 is a NMR spectrum of product 2i in example 9.
FIG. 20 is a NMR carbon spectrum of product 2i of example 9.
FIG. 21 is a NMR spectrum of product 2j of example 10.
FIG. 22 is a NMR carbon spectrum of product 2j of example 10.
FIG. 23 is a NMR spectrum of product 2k in example 11.
FIG. 24 is a NMR carbon spectrum of product 2k of example 11.
FIG. 25 is a NMR fluorine spectrum of product 2k of example 11.
FIG. 26 is a NMR spectrum of 2m, a product of example 12.
FIG. 27 is a NMR carbon spectrum of product 2m in example 12.
FIG. 28 is the NMR fluorine spectrum of 2m product of example 12.
Detailed Description
The invention will be better understood from the following examples.
The invention provides a method for electrochemically synthesizing substituted indole by gamma-hydroxylamine, which is characterized in that a homogeneous solution obtained by mixing a substrate 1, an organic additive, an electrolyte and a solvent is added into an electrochemical reaction device with a cathode and an anode, and substituted indole 2 is synthesized by an electrocatalysis one-step method. The reaction equation is shown in FIG. 1, and the reaction apparatus is shown in FIG. 2. The present invention provides specific embodiments of the 12 substituted indoles of table 1 below.
TABLE 1
Example 1
Dissolving N- (2- (1-hydroxy-1-phenylethyl) phenyl) ethanesulfonamide (91.5mg, 0.3mmol,1 equivalent), p-toluenesulfonic acid (77.5mg, 0.45mmol,1.5 equivalent), tetrabutylammonium tetrafluoroborate (987.8mg, 0.3mmol,1 equivalent) in solvent ACN/TCE (6.5 + 3.5) mL at 70 ℃ to obtain a homogeneous solution, adding the homogeneous solution into a 10mL three-necked round-bottomed flask equipped with a carbon cloth (40mm x 20mm) anode and a platinum sheet (20 mm x 0.1 mm) cathode, controlling the current to be 8mA, and controlling the reaction time to be 120min; after completion of the reaction, the product was identified by TLC. The solvent was removed in vacuo. The product was separated with petroleum ether and ethyl acetate 10 eluent and dried in vacuo for 4h. The product 2a obtained had a conversion of 70%.
The nmr hydrogen spectrum of product 2a is shown in fig. 3, and the nmr carbon spectrum is shown in fig. 4:
1H NMR(400MHz,DMSO-d6)δ7.96-7.90(m,2H),7.84(s,1H),7.76-7.71(m,2H),7.54-7.48(m,2H),7.48-7.43(m,1H),7.42-7.37(m,2H),3.67(q,J=7.3Hz,2H),1.11(t,J=7.3Hz,3H);13C NMR(101MHz,DMSO-d6)δ135.41,132.59,129.02,127.96,127.63,127.44,124.91,124.03,123.62,121.46,120.31,113.33,48.33,7.81;HRMS(EI-TOF)Calcd for C16H15NO2S[M]+:285.0800;found:285.0823.
example 2
Dissolving N- (2- (1-hydroxy-1-phenylethyl) phenyl) benzenesulfonamide (105.9mg, 0.3mmol,1 equivalent), p-toluenesulfonic acid (77.5mg, 0.45mmol,1.5 equivalent) and tetrabutylammonium tetrafluoroborate (987.8mg, 0.3mmol, equivalent) in solvent ACN/TCE (6.5 + 3.5) mL at 70 ℃ to obtain a homogeneous solution, adding the homogeneous solution into a 10mL three-neck round-bottom flask provided with a carbon cloth (40mm x 20mm) anode and a platinum sheet (20 mm x 0.1 mm) cathode, controlling the current to be 8mA, and controlling the reaction time to be 120min; after completion of the reaction, the product was identified by TLC. The solvent was removed in vacuo. The purification procedure was the same as in example 1, and the conversion of the product 2b obtained was 73%.
The nmr hydrogen spectrum of product 2b is shown in fig. 5, and the nmr carbon spectrum is shown in fig. 6:
1H NMR(400MHz,DMSO-d6)δ8.15-8.14(m,2H),8.12-8.12(m,2H),7.88(d,J=7.9Hz,1H),7.78-7.73(m,3H),7.67-7.63(m,2H),7.56-7.53(m,2H),7.49-7.37(m,3H);13C NMR(101MHz,DMSO-d6)δ136.91,134.81,134.74,132.29,129.89,129.01,128.47,127.69,127.63,126.88,125.19,124.04,123.63,123.15,120.44,113.52;HRMS(EI-TOF)Calcd for C20H15NO2S[M]+:333.0818;found:333.0828.
example 3
4-chloro-N- (2- (1-hydroxy-1-phenylethyl) phenyl) benzenesulfonamide (116.1mg, 0.3mmol,1 equiv.), p-toluenesulfonic acid (77.5mg, 0.45mmol,1.5 equiv.), tetrabutylammonium tetrafluoroborate (987.8mg, 0.3mmol,1 equiv.) were dissolved in a solvent ACN/TCE (6.5 + 3.5) mL at 70 ℃ to obtain a homogeneous solution, which was charged into a 10mL three-necked round-bottomed flask equipped with a carbon cloth (40mm. Times.20mm) anode and a platinum sheet (20 mm. Times.20 mm. Times.0.1 mm) cathode, with a current controlled at 8mA, for a reaction time of 120min; after completion of the reaction, the product was identified by TLC. The solvent was removed in vacuo. The purification procedure was the same as in example 1, and the product 2c obtained had a conversion of 75%.
The nmr hydrogen spectrum of product 2c is shown in fig. 7, and the nmr carbon spectrum is shown in fig. 8:
1H NMR(400MHz,DMSO-d6)δ8.12-8.07(m,3H),8.03(dt,J=8.3,1.2Hz,1H),7.84(dt,J=7.8,1.1Hz,1H),7.74-7.70(m,2H),7.69-7.65(m,2H),7.53-7.47(m,2H),7.46-7.32(m,3H);13C NMR(101MHz,DMSO-d6)δ139.91,135.61,134.78,132.21,130.11,129.04,128.87,128.58,127.75,125.38,124.26,123.61,123.53,120.55,113.54;HRMS(EI-TOF)Calcd for C20H14ClNO2S[M]+:367.0428;found:367.0442.
example 4
Dissolving N- (2- (1-hydroxy-1-phenylpropyl) phenyl) -4-methylbenzenesulfonamide (114.3mg, 0.3mmol,1 equiv.), p-toluenesulfonic acid (77.5mg, 0.45mmol,1.5 equiv.), tetrabutylammonium tetrafluoroborate (987.8mg, 0.3mmol,1 equiv.) in a solvent ACN/TCE (6.5 + 3.5) mL at 70 ℃ to obtain a homogeneous solution, adding the homogeneous solution into a 10mL three-necked round bottom flask equipped with a carbon cloth (40mm. Times.20mm) anode and a platinum sheet (20 mm. Times.20 mm. Times.0.1 mm) cathode, controlling the current to be 8mA, and reacting for 120min; after completion of the reaction, the product was identified by TLC. The solvent was removed in vacuo. The purification procedure was the same as in example 1, and the conversion of the product 2d was 77%.
The nmr hydrogen spectrum of product 2d is shown in fig. 9, and the nmr carbon spectrum is shown in fig. 10:
1H NMR(400MHz,DMSO-d6)δ8.18(d,J=8.2Hz,1H),7.86(d,J=8.4Hz,2H),7.55(t,J=7.4Hz,2H),7.49-7.35(m,7H),7.28(t,J=8.0Hz 1H),2.64(s,3H),2.35(s,3H);13C NMR(101MHz,DMSO-d6)δ145.41,135.31,134.99,133.02,132.20,130.38,129.82,129.21,128.81,127.58,126.40,124.49,123.92,121.90,118.96,114.18,21.03,13.40;HRMS(EI-TOF)Calcd for C22H19NO2S[M]+:361.1131;found:361.1139.
example 5
Dissolving N- (2- (1-hydroxy-1,2-diphenylethyl) phenyl) -4-methylbenzenesulfonamide (132.9mg, 0.3mmol,1 equivalent), p-toluenesulfonic acid (77.5mg, 0.45mmol,1.5 equivalent) and tetrabutylammonium tetrafluoroborate (987.8mg, 0.3mmol,1 equivalent) in solvent ACN/TCE (6.5 + 3.5) mL at 70 ℃ to obtain a homogeneous solution, adding the homogeneous solution into a 10mL three-necked flask equipped with a carbon cloth (40mm x 20mm) anode and a platinum sheet (20 mm x 0.1 mm) cathode, controlling the current to be 8mA, and reacting for 120min round bottom; after completion of the reaction, the product was identified by TLC. The solvent was removed in vacuo. The purification procedure was the same as in example 1, and the product 2e was obtained with a 73% conversion.
The nmr hydrogen spectrum of product 2e is shown in fig. 11, and the nmr carbon spectrum is shown in fig. 12:
1H NMR(400MHz,DMSO-d6)δ8.30(d,J=8.4Hz,1H),7.54-7.41(m,5H),7.41-7.26(m,10H),7.15(dd,J=7.9,1.6Hz,2H),2.34(s,3H);13C NMR(101MHz,DMSO-d6)δ145.29,136.58,136.13,134.28,131.89,131.70,130.66,129.97,129.73,129.64,128.67,128.42,127.44,127.31,126.49,125.50,124.59,124.12,119.80,115.55,21.06;HRMS(EI-TOF)Calcd for C27H21NO2S[M]+:423.1288;found:423.1304.
example 6
Dissolving N- (2- (2-hydroxybut-2-yl) phenyl) -4-methylbenzenesulfonamide (95.7mg, 0.3mmol,1 equiv.), p-toluenesulfonic acid (77.5mg, 0.45mmol,1.5 equiv.), tetrabutylammonium tetrafluoroborate (987.8mg, 0.3mmol,1 equiv.) in a solvent ACN/TCE (6.5 + 3.5) mL at 70 ℃ to obtain a homogeneous solution, adding the homogeneous solution to a 10mL three-necked round bottom flask equipped with a carbon cloth (40mm. Times.20mm) anode and a platinum sheet (20 mm. Times.20 mm. Times.0.1 mm) cathode, controlling the current to be 8mA, and reacting for 120min; after completion of the reaction, the product was identified by TLC. The solvent was removed in vacuo. The purification procedure was the same as in example 1, and the product 2f was obtained with a 79% conversion.
The nmr hydrogen spectrum of the product 2f is shown in fig. 13, and the nmr carbon spectrum is shown in fig. 14.
1 H NMR(400MHz,DMSO-d 6 )δ7.99(d,J=8.2Hz,1H),7.60(d,J=8.4Hz,2H),7.34(d,J=7.7Hz,1H),7.27-7.19(m,3H),7.17-7.13(m,1H),2.43(s,3H),2.17(s,3H),2.01(s,3H); 13 C NMR(101MHz,DMSO-d 6 )δ145.06,135.37,135.07,132.10,130.86,130.19,126.12,124.10,123.45,118.66,116.00,113.99,20.96,12.52,8.53;HRMS(EI-TOF)Calcd for C 17 H 17 NO 2 S[M] + :299.0975;found:299.0977.
Example 7
Dissolving N- (2- (1-hydroxy-1-phenyl-2- (p-tolyl) ethyl) phenyl) -4-methylbenzenesulfonamide (137.1mg, 0.3mmol,1 equiv.), p-toluenesulfonic acid (77.5mg, 0.45mmol,1.5 equiv.), tetrabutylammonium tetrafluoroborate (987.8mg, 0.3mmol,1 equiv.) in solvent ACN/TCE (6.5 + 3.5) mL at 70 ℃ to obtain a homogeneous solution, adding the homogeneous solution to a 10mL three-necked flask equipped with a carbon cloth (40mm. Times.20mm) anode and a platinum sheet (20 mm. Times.20 mm. Times.0.1 mm) cathode, controlling the current to be 8mA, and the reaction time to be 120min round bottom; after completion of the reaction, the product was identified by TLC. The solvent was removed in vacuo. The purification procedure was the same as in example 1, and 2g of the product was obtained with a 75% conversion.
The NMR spectrum of the product 2g is shown in FIG. 15, and the NMR spectrum is shown in FIG. 16:
1H NMR(400MHz,DMSO-d6)δ8.29(d,J=8.4Hz,1H),7.52-7.40(m,4H),7.39-7.27(m,6H),7.25-7.11(m,6H),2.38(s,3H),2.33(s,3H);13C NMR(101MHz,DMSO-d6)δ145.22,137.99,136.73,136.11,134.27,132.01,131.55,129.92,129.83,129.63,128.42,128.07,127.67,127.25,126.47,125.37,124.55,123.97,119.70,115.58,21.06,20.99;HRMS(EI-TOF)Calcd for C28H23NO2S[M]+:437.1444;found:437.1423.
example 8
Dissolving N- (2- (1-hydroxy-1- (4-methoxyphenyl) ethyl) phenyl) -4-methylbenzenesulfonamide (119.1mg, 0.3mmol,1 equivalent), p-toluenesulfonic acid (77.5mg, 0.45mmol,1.5 equivalent), tetrabutylammonium tetrafluoroborate (987.8mg, 0.3mmol,1 equivalent) in solvent ACN/TCE (6.5 + 3.5) mL at 70 ℃ to obtain a homogeneous solution, adding the homogeneous solution into a 10mL three-necked round bottom flask equipped with a carbon cloth (40mm x 20mm) anode and a platinum sheet (20 mm x 0.1 mm) cathode, controlling the current to be 8mA, and reacting for 120min; after completion of the reaction, the product was identified by TLC. The solvent was removed in vacuo. The purification procedure was as in example 1, and the 2h conversion of the product was 77%.
The nmr hydrogen spectrum of product 2h is shown in fig. 17, and the nmr carbon spectrum is shown in fig. 18:
1H NMR(400MHz,DMSO-d6)δ8.06(d,J=8.3Hz,1H),8.02(s,1H),7.98(d,J=8.4Hz,2H),7.83(d,J=7.9Hz,1H),7.71-7.67(m,2H),7.49-7.40(m,3H),7.37(t,J=7.5Hz,1H),7.12-7.08(m,2H),3.86(s,3H),2.35(s,3H);13C NMR(101MHz,DMSO-d6)δ158.85,145.53,134.80,134.05,130.26,128.89,128.69,126.87,125.01,124.63,123.85,122.83,122.77,120.38,114.45,113.51,55.21,21.01;HRMS(EI-TOF)Calcd for C22H19NO3S[M]+:377.1080;found:377.1083.
example 9
Dissolving N- (2- (1-hydroxy-1-phenylethyl) phenyl) - [1,1' -biphenyl ] -4-sulfonamide (128.7mg, 0.3mmol,1 equivalent), p-toluenesulfonic acid (77.5mg, 0.45mmol,1.5 equivalent), tetrabutylammonium tetrafluoroborate (987.8mg, 0.3mmol,1 equivalent) in solvent ACN/TCE (6.5 + 3.5) mL at 70 ℃ to obtain a homogeneous solution, adding the homogeneous solution into a 10mL three-necked flask equipped with a carbon cloth (40mm x 20mm) anode and a platinum sheet (20 mm x 0.1 mm) cathode, controlling the current to be 8mA, and controlling the reaction time to be 120min; after completion of the reaction, the product was identified by TLC. The solvent was removed in vacuo. The purification procedure was the same as in example 1, and the conversion of the product 2i was 73%.
The nmr hydrogen spectrum of product 2i is shown in fig. 19, and the nmr carbon spectrum is shown in fig. 20:
1H NMR(400MHz,DMSO-d6)δ8.21-8.20(m,2H),8.19-8.19(m,1H),8.14(d,J=8.3Hz,1H),7.93-7.89(m,3H),7.80-7.78(m,2H),7.73-7.70(m,2H),7.61-7.39(m,8H);13C NMR(101MHz,DMSO-d6)δ146.07,137.82,135.55,134.81,132.30,129.10,128.99,128.91,127.99,127.69,127.68,127.62,127.58,127.22,125.23,124.05,123.65,123.14,120.46,113.53;HRMS(EI-TOF)Calcd for C26H19NO2S[M]+:409.1131;found:409.1138.
example 10
Dissolving 4-bromo-N- (2- (1-hydroxy-1-phenylethyl) phenyl) benzenesulfonamide (129.3mg, 0.3mmol,1 equiv.), p-toluenesulfonic acid (77.5mg, 0.45mmol,1.5 equiv.), tetrabutylammonium tetrafluoroborate (987.8mg, 0.3mmol,1 equiv.) in solvent ACN/TCE (6.5 + 3.5) mL at 70 ℃ to obtain a homogeneous solution, adding the homogeneous solution into a 10mL three-necked round bottom flask equipped with a carbon cloth (40mm x 20mm) anode and a platinum sheet (20 mm x 0.1 mm) cathode, controlling the current to be 8mA, and controlling the reaction time to be 120min; after completion of the reaction, the product was identified by TLC. The solvent was removed in vacuo. The purification procedure was the same as in example 1, and the product 2j was obtained with a conversion of 78%.
The nmr hydrogen spectrum of product 2j is shown in fig. 21, and the nmr carbon spectrum is shown in fig. 22:
1H NMR(400MHz,DMSO-d6)δ8.09(s,1H),8.03-7.99(m,3H),7.85-7.81(m,3H),7.74-7.72(m,2H),7.52-7.34(m,5H);13C NMR(101MHz,DMSO-d6)δ136.01,134.79,133.08,132.23,129.12,129.08,128.88,128.60,127.78,125.42,124.30,123.63,123.57,120.59,113.56;HRMS(EI-TOF)Calcd for C20H14BrNO2S[M]+:410.9923;found:410.9931.
example 11
Dissolving N- (2- (1-hydroxy-1-phenylethyl) phenyl) -4- (trifluoromethyl) benzenesulfonamide (126.3mg, 0.3mmol,1 equiv.), p-toluenesulfonic acid (77.5mg, 0.45mmol,1.5 equiv.), tetrabutylammonium tetrafluoroborate (987.8mg, 0.3mmol,1 equiv.) in solvent ACN/TCE (6.5 mg, 3.5 equiv.) mL at 70 ℃ to obtain a homogeneous solution, adding the homogeneous solution into a 10mL three-necked round-bottomed flask equipped with a carbon cloth (40mm. Times.20mm) anode and a platinum sheet (20 mm. Times.20 mm. Times.0.1 mm) cathode, controlling the current to be 8mA, and reacting for 120min; after completion of the reaction, the product was identified by TLC. The solvent was removed in vacuo. The purification procedure was the same as in example 1, and the 2k conversion of the product was 76%.
The nmr hydrogen spectrum, nmr carbon spectrum, and nmr fluorine spectrum of the product 2k are shown in fig. 23, 24, and 25, respectively.
1 H NMR(400MHz,DMSO-d 6 )δ8.33-8.28(m,2H),8.15(s,1H),8.05(dt,J=8.4,1.0Hz,1H),7.98(dt,J=8.3,0.9Hz,2H),7.84(dt,J=7.9,1.1Hz,1H),7.76-7.70(m,2H),7.52-7.46(m,2H),7.46-7.33(m,3H); 13 C NMR(101MHz,DMSO-d 6 )δ140.53,134.75,134.19,133.87,132.07,129.00,128.60,127.97,127.77,127.75,127.14(q,J=3.7Hz),125.47,124.37,123.80,123.55,121.67,120.60,113.48; 19 F NMR(376MHz,DMSO-d 6 )δ-61.96;HRMS(EI-TOF)Calcd for C 21 H 14 F 3 NO 2 S[M] + :401.0692;found:401.0705.
Example 12
Dissolving N- (2- (1-hydroxy-1-phenylethyl) phenyl) -2- (trifluoromethyl) benzenesulfonamide (126.3mg, 0.3mmol,1 equiv.), p-toluenesulfonic acid (77.5mg, 0.45mmol,1.5 equiv.), tetrabutylammonium tetrafluoroborate (987.8mg, 0.3mmol,1 equiv.) in solvent ACN/TCE (6.5 mg, 3.5 equiv.) mL at 70 ℃ to obtain a homogeneous solution, adding the homogeneous solution into a 10mL three-necked round-bottomed flask equipped with a carbon cloth (40mm. Times.20mm) anode and a platinum sheet (20 mm. Times.20 mm. Times.0.1 mm) cathode, controlling the current to be 8mA, and controlling the reaction time to be 120min; after completion of the reaction, the product was identified by TLC. The solvent was removed in vacuo. The purification procedure was the same as in example 1, and the 2m conversion of the product was 72%.
The hydrogen nuclear magnetic resonance spectrum, the carbon nuclear magnetic resonance spectrum, and the fluorine nuclear magnetic resonance spectrum of the product 2m are shown in fig. 26, 27, and 28, respectively.
1 H NMR(400MHz,DMSO-d 6 )δ8.10(dd,J=7.8,1.4Hz,1H),8.05(s,1H),7.95-7.90(m,2H),7.86(td,J=7.9,1.5Hz,1H),7.82-7.79(m,1H),7.78-7.74(m,2H),7.70(dd,J=8.0,1.2Hz,1H),7.55-7.49(m,2H),7.45-7.36(m,3H); 13 C NMR(101MHz,DMSO-d 6 )δ136.42,135.12,135.07,134.25,132.06,129.84,129.24(d,J=6.1Hz),129.04,128.90,128.23,128.16,127.81,127.77,127.68,126.29(d,J=5.9Hz),125.99,125.43,124.30,124.03,123.82,122.67,121.10,120.72,113.33; 19 F NMR(376MHz,DMSO-d 6 )δ-55.98;HRMS(EI-TOF)Calcd for C 21 H 14 F 3 NO 2 S[M] + :401.0692;found:401.0707.
Comparative example 1
2-alkenylaniline (0.076 g, 0.20 mmol) and iodine (III) reagent (0.140 g,0.4 mmol) were charged to a polytetrafluoroethylene-sealed reaction flask under air. MeCN (2.5 ml) was added to the mixture. The reaction vessel was sealed with a teflon lid. The reaction mixture was stirred vigorously at 100 ℃ for 15 minutes. Complete disappearance of substrate was monitored by TLC. The solvent was removed under reduced pressure. The crude product was purified by dry loading with silica using an eluent (1: 30 ethyl acetate: petroleum ether) to give 3- (4-methoxyphenyl) -1-tosyl-1H-indole with a conversion of 51%. Due to the use of the metal catalyst, the metal residue is large, the reaction is carried out at high temperature, the operation is dangerous, and the yield is low.
Comparative example 2
FeCl is added 3 ·6H 2 O (5-25 mol%) and DDQ (0.1-0.2mmol, 2 equivalents) Adding 4-methyl-N- [2- [ (1E) -2- (4-methylphenyl) ethenyl into a pressure pipe]Phenyl radical]ClCH of benzenesulfonamide (0.05-0.1 mmol,1 equivalent) 2 CH 2 Cl (1-2mL, 0.05M) solution. The resulting mixture was stirred at 80 ℃ for 30 minutes under an Ar atmosphere. After completion of the reaction, the reaction mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate: n-hexane = 1: 5) to give 3- (4-methylphenyl) -1- [ (4-methylphenyl) sulfonyl group]-1H-indole, conversion 57%. Due to the use of the metal catalyst, metal residues are large and the yield is low.
The present invention provides a method and a concept for electrochemical synthesis of substituted indole from gamma-hydroxylamine, and a method and a way for implementing the technical scheme are many, and the above description is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, a plurality of modifications and embellishments can be made without departing from the principle of the present invention, and these modifications and embellishments should also be regarded as the protection scope of the present invention. All the components not specified in the present embodiment can be realized by the prior art.
Claims (10)
1. A method for synthesizing substituted indole by gamma-hydroxylamine electrochemistry is characterized in that homogeneous solution obtained by mixing a substrate 1, an organic additive, an electrolyte and a solvent is added into an electrochemical reaction device with a cathode and an anode, and substituted indole 2 is synthesized by an electrocatalysis one-step method;
the reaction equation is as follows:
wherein R1 is selected from any one of electron-donating group hydrogen, alkyl with 1-4C, phenyl or substituted phenyl;
r2 is selected from any one of electron-donating group hydrogen, alkyl with 1-4C, phenyl or substituted phenyl;
r is selected from any one of alkyl, phenyl or substituted phenyl with 1-4C.
2. The method of claim 1, wherein the organic additive is selected from the group consisting of trifluoroacetic acid, methanesulfonic acid, acetic acid, p-toluenesulfonic acid, and combinations of two or more thereof; preferably acetic acid and/or p-toluenesulfonic acid; further preferred is p-toluenesulfonic acid.
3. The method for electrochemically synthesizing substituted indoles from γ -hydroxylamine as claimed in claim 1, wherein the electrolyte is one or a combination of two or more of tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium acetate, tetrabutylammonium iodide and lithium perchlorate; preferably one or the combination of more than two of tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate and lithium perchlorate; further preferably tetrabutylammonium hexafluorophosphate and/or tetrabutylammonium tetrafluoroborate; still more preferably tetrabutylammonium tetrafluoroborate.
4. The method of claim 1, wherein the solvent is selected from the group consisting of dichloroethane, N-dimethylformamide, dimethylsulfoxide, trifluoroethanol, acetonitrile, hexafluoroisopropanol, trichloroethylene, N-dimethylaniline and tetrahydrofuran; preferably one or the combination of more than two of dimethyl sulfoxide, trifluoroethanol, acetonitrile, hexafluoroisopropanol, trichloroethylene, N-dimethylaniline and tetrahydrofuran; more preferably, it is any one or a combination of two or more of trifluoroethanol, acetonitrile and hexafluoroisopropanol; more preferably, the mixed solution of trifluoroethanol and acetonitrile in a volume ratio of 3.5.
5. The method for electrochemically synthesizing substituted indoles from γ -hydroxylamine as in claim 1 wherein the molar ratio of substrate 1 to organic additive is 1:1-3; preferably 1:1 to 2, more preferably 1:1 to 1.8, and still more preferably 1.
6. The method for electrochemically synthesizing substituted indoles from γ -hydroxylamine as claimed in claim 1, wherein the molar ratio of substrate 1 to electrolyte is 1; preferably 1.5 to 1.5, more preferably 1:1 to 1.5, and still more preferably 1:1.
7. The method for electrochemically synthesizing substituted indole from γ -hydroxylamine according to claim 1, wherein the concentration of the substrate 1 in the homogeneous solution is 0.02 to 0.08mmol/mL, preferably 0.02 to 0.06mmol/mL, more preferably 0.02 to 0.04mmol/mL, and still more preferably 0.03mmol/mL.
8. The method for electrochemically synthesizing substituted indoles from γ -hydroxylamine as claimed in claim 1, wherein the electrocatalytic reaction is conducted at a current intensity of 5-20 mA; preferably 5 to 15mA; further preferably 8mA.
9. The method for electrochemically synthesizing substituted indoles from γ -hydroxylamine as claimed in claim 1, wherein the electrocatalytic reaction time is 90-180 min, preferably 90-160 min, and more preferably 120min; the reaction temperature is 50 to 80 ℃, preferably 50 to 70 ℃, and more preferably 70 ℃.
10. The method for electrochemically synthesizing substituted indole from gamma-hydroxylamine according to claim 1, wherein the reaction solution obtained after the reaction is finished is extracted to obtain an organic phase, and the organic phase is concentrated and subjected to column chromatography to obtain a substituted indole compound;
the extraction is to extract the reaction solution by ethyl acetate and saturated sodium chloride aqueous solution;
the column chromatography adopts silica gel column chromatography;
the eluent for column chromatography is a mixed solvent of petroleum ether and ethyl acetate according to the volume ratio of 1.
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