CN116332823B - Preparation method of isoindole-diketone derivative - Google Patents
Preparation method of isoindole-diketone derivative Download PDFInfo
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- CN116332823B CN116332823B CN202210776361.XA CN202210776361A CN116332823B CN 116332823 B CN116332823 B CN 116332823B CN 202210776361 A CN202210776361 A CN 202210776361A CN 116332823 B CN116332823 B CN 116332823B
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- isoindole
- acetophenone
- maleimide
- lewis acid
- iodine reagent
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- 238000002360 preparation method Methods 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 28
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000002841 Lewis acid Substances 0.000 claims abstract description 13
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 13
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 13
- 239000011630 iodine Substances 0.000 claims abstract description 13
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 13
- -1 acetophenone compound Chemical class 0.000 claims abstract description 11
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 8
- 150000003923 2,5-pyrrolediones Chemical class 0.000 claims abstract description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000001301 oxygen Substances 0.000 claims abstract description 7
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 7
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims abstract description 7
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 claims abstract description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000007306 functionalization reaction Methods 0.000 claims abstract description 4
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims abstract description 3
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 150000008062 acetophenones Chemical class 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 238000007115 1,4-cycloaddition reaction Methods 0.000 claims description 2
- 239000007789 gas Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 7
- 239000000463 material Substances 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 238000005580 one pot reaction Methods 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000007858 starting material Substances 0.000 abstract description 3
- 238000005899 aromatization reaction Methods 0.000 abstract 1
- 238000006352 cycloaddition reaction Methods 0.000 abstract 1
- 238000006356 dehydrogenation reaction Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000008204 material by function Substances 0.000 abstract 1
- 239000012046 mixed solvent Substances 0.000 abstract 1
- 239000000575 pesticide Substances 0.000 abstract 1
- 239000000758 substrate Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- 239000000047 product Substances 0.000 description 19
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- 238000001308 synthesis method Methods 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- IMOZEMNVLZVGJZ-QGZVFWFLSA-N apremilast Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CS(C)(=O)=O)N2C(C3=C(NC(C)=O)C=CC=C3C2=O)=O)=C1 IMOZEMNVLZVGJZ-QGZVFWFLSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 230000000055 hyoplipidemic effect Effects 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229940078552 o-xylene Drugs 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229940011530 otezla Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- UVSMNLNDYGZFPF-UHFFFAOYSA-N pomalidomide Chemical compound O=C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O UVSMNLNDYGZFPF-UHFFFAOYSA-N 0.000 description 1
- 229940008606 pomalyst Drugs 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229940034915 thalomid Drugs 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention mainly relates to an isoindole-diketone derivative prepared by utilizing an iodine reagent and Lewis acid to cooperatively promote cycloaddition, dehydrogenation and aromatization of two molecules of acetophenone and one molecule of maleimide. Under the action of an iodine reagent and Lewis acid, p-xylene and chlorobenzene are used as mixed solvents in an oxygen atmosphere, so that the technical scheme of generating isoindole-diketone by using an acetophenone compound and maleimide compound in a one-pot method is realized; the reaction system uses acetophenone and maleimide compounds which are easy to obtain as starting materials, the reaction has the characteristics of simple system, wide material sources, wide substrate applicability, good atomic economy, high yield and the like, and simultaneously, the system relates to the functionalization of a plurality of C (sp 3)-H/C(sp2) -H, realizes the formation of a plurality of C-C bonds and C-O bonds, and obtains the isoindole-dione and the derivative synthesized with high selectivity. The method for synthesizing the isoindole-diketone derivative can be used in a plurality of industrial production fields such as medicines, pesticides, organic functional materials and the like; is especially suitable for the high-efficiency selective synthesis of functional material molecules with luminous performance by a one-pot method.
Description
Technical Field
The invention relates to an isoindole-diketone compound and a synthesis method thereof, belonging to the field of organic synthesis.
Background
Isoindole-diketone derivatives are important organic compounds which are widely applied to drug molecules and natural products, and have a unique skeleton structure, so that the isoindole-diketone derivatives have strong luminous performance, and are also often applied to the field of photoelectric materials. For example: they have immunomodulating, anti-inflammatory, fungicidal, analgesic, antibacterial, antitumor, anxiolytic, anticonvulsant, antihistamine, hypolipidemic, herbicidal and insecticidal activities, and some commercial drugs containing isoindole-1, 3-dione backbones are useful for treating rheumatoid arthritis (Thalomid), multiple myeloma (Pomalyst), psoriasis (Otezla), and the like. In addition, isoindole-dione derivatives are widely used for the synthesis of valuable catalyst materials, dyes, polymers and fluorescent probes. The processes for the synthesis of such compounds to date have complex synthesis steps, require expensive transition metal catalysis and have poor atom economy, while often requiring prior functionalization of the starting materials.
Disclosure of Invention
Accordingly, it is an object of the present invention to provide a synthesis of isoindole-dione compounds and derivatives thereof.
The invention also aims to provide a synthesis method of the isoindole-diketone compound and the derivative thereof, which has the advantages of simple reaction conditions, convenient operation and high yield.
Thus, the isoindole-dione compound and the derivative thereof have the general formula I:
Wherein:
R is selected from various groups of linear alkyl, cycloalkyl, benzyl, naphthalene and aryl;
r1 is selected from various groups including alkyl, ester, halogen, trifluoromethyl and aryl;
The method 1 is characterized in that an iodine reagent and Lewis acid are used for promoting acetophenone and maleimide to undergo [4+2] cycloaddition and dehydroaromatization, and a plurality of C (sp 3)-H/C(sp2) -H functionalization is involved, so that a plurality of C-C bonds and C-O bonds are formed, and the method for synthesizing the isoindole-dione derivative with high selectivity is obtained; the preparation method is characterized in that acetophenone compounds and maleimide compounds are heated and stirred at 140 ℃ in the atmosphere of iodine reagent, lewis acid, solvent and oxygen.
The method according to method 1, wherein the acetophenone compound has the general formula of formula ii:
Wherein:
R 1 is selected from various groups including alkyl, ester, halogen, trifluoromethyl and aryl;
The method according to method 1, wherein the maleimide compound has the general formula iii:
Wherein:
r is selected from various groups of linear alkyl, cycloalkyl, benzyl, naphthalene and aryl.
The method of method 1, wherein the iodine reagent is: KI. One of NH 4I、ICl、IBr、NIS、I2O5、I2.
The method of method 1, wherein the Lewis acid is one of ：FeCl3、ZnCl2、CuBr2、Mg(OTf)2、Mn(OTf)2、BF3.Et2O.
The method according to the method 1, wherein the organic solvent is selected from one of tetrahydrofuran, toluene, acetonitrile, chlorobenzene, dimethyl sulfoxide, paraxylene and o-xylene, and the amount of the solvent is as follows: 0-1.5mL.
The method according to the method 1, wherein the molar ratio of the acetophenone compound to the maleimide compound to the iodine reagent to the Lewis acid is 1.0:0.5-1.5:0.5-1.5:0.5-1.0; the reaction temperature is 130-150 ℃, and the gas atmosphere of the reaction container is as follows: an oxygen atmosphere; the reaction time is 12-36h.
The technical scheme of the invention has the following advantages:
(I) According to the invention, under the synergistic promotion of an iodine reagent and Lewis acid, the technical scheme that acetophenone compounds and maleimide compounds are converted into isoindole-diketone compounds and derivatives thereof is realized in an oxygen atmosphere, a target product is directly and selectively synthesized by adopting a one-pot method in the reaction, the yield is moderately high, the great wasting dilemma of people, wealth and things caused by the existing multi-step synthesis method is overcome, and a large amount of development time and production period are saved; the reaction (II) is completed without transition metal, so that the use of expensive metal is avoided, meanwhile, the cheap and easily available acetophenone is used as the starting material, the synthesis method is simpler, the added value of the product is obviously increased, the availability is high, and the method has foreseeable market commercialization prospect; (III) under the promotion of iodine reagent and Lewis acid, the technical scheme of converting acetophenone compounds and maleimide compounds into isoindole-diketone compounds and derivatives thereof is realized in an oxygen atmosphere, and the method has the advantages of scientific and reasonable process, easy operation, few reaction steps and less required equipment. The isoindole-diketone compound derivative and the synthesis method thereof can be used in a plurality of fields such as dye, medicine, material and the like; is particularly suitable for researching and developing the high-efficiency and selective synthesis of the isoindole-diketone compound by a one-pot method.
Drawings
To demonstrate the products of the present invention, the present invention provides the nuclear magnetic hydrogen spectrogram and the nuclear magnetic carbon spectrogram of some examples.
FIGS. 1a and 1b show nuclear magnetic patterns of the product of example 1.
FIGS. 2a and 2b show nuclear magnetic patterns of the product of example 12.
Wherein a is a hydrogen spectrogram and b is a carbon spectrogram.
Detailed Description
The present invention will now be described in further detail in connection with the following formulas. The basic structure of the present invention is only schematically illustrated, and therefore it shows only the constitution related to the present invention:
Examples 1 to 20
The method comprises the following steps:
⑴ Adding acetophenone compounds, maleimide compounds, iodine reagents, lewis acid and organic solvents into a reaction container;
⑵ After the reactants are stirred uniformly, oxygen is filled in, and the mixture is put into a condition of 140 ℃ for reaction;
⑶ Purifying after the reaction is complete to obtain a product;
Acetophenone compounds, maleimide compounds, reaction conditions, reaction products and yields are shown in table 1:
table 1: the reactants and reaction conditions in examples 1-20
The nuclear magnetic data of the products of some examples are:
The nuclear magnetic data of the product of example 1 are as follows:
1H NMR(400MHz,CDCl3)δ8.51(s,1H),7.67(d,J＝7.0Hz,2H),7.64(s,1H),7.59(dd,J＝7.9,1.7Hz,2H),7.51-7.40(m,6H),3.15(s,3H).13C NMR(100MHz,CDCl3)δ171.0,167.3,151.8,138.9,136.0,135.9,135.1,133.9,129.3,129.2,128.6,128.6,128.5,128.2,125.6,115.7,23.8.
The nuclear magnetic data of the product of example 2 are as follows:
1H NMR(400MHz,CDCl3)δ8.48(s,1H),7.61(s,1H),7.57(d,J＝8.2Hz,2H),7.48(d,J＝8.2Hz,2H),7.31-7.25(m,4H),3.14(s,3H),2.42(s,6H).13C NMR(100MHz,CDCl3)δ171.1,167.4,151.7,138.6,138.6,138.5,136.1,134.0,133.1,132.3,129.3,129.1,129.0,128.96,125.1,115.6,23.8,21.4,21.4.
the nuclear magnetic data of the product of example 5 are as follows:
1H NMR(400MHz,CDCl3)δ8.60(s,1H),7.79(d,J＝8.3Hz,2H),7.76-7.68(m,7H),7.67(m,4H),7.52-7.44(m,4H),7.43-7.35(m,4H),3.18(s,3H).13C NMR(100MHz,CDCl3)δ171.0,167.4,151.9,141.5,141.4,140.6,140.5,138.7,135.7,134.8,134.0,133.5,129.7,129.6,129.0,128.9,128.87,127.8,127.6,127.3,127.2,127.17,126.7,125.5,115.8,23.8.
the nuclear magnetic data of the product of example 8 are as follows:
1H NMR(400MHz,CDCl3)δ8.52(s,1H),7.60(d,J＝8.6Hz,2H),7.55(s,1H),7.51(d,J＝8.5Hz,2H),7.47-7.41(m,4H),3.15(s,3H).13C NMR(100MHz,CDCl3)δ170.8,167.1,151.9,138.3,134.9,134.89,134.8,134.1,133.3,132.6,130.6,130.5,128.8,128.5,125.9,115.9,23.9.
the nuclear magnetic data of the product of example 10 are as follows:
1H NMR(400MHz,CDCl3)δ8.57(s,1H),8.14(dd,J＝8.2,3.8Hz,4H),7.75(d,J＝8.1Hz,2H),7.68-7.61(m,3H),3.95(s,6H),3.16(s,3H).13C NMR(100MHz,CDCl3)δ170.7,166.9,166.7,166.66,152.2,140.2,139.4,138.6,135.0,132.6,130.2,130.2,129.8,129.5,129.49,129.3,129.2,126.6,116.0,52.3,52.25,23.9.
the nuclear magnetic data of the product of example 11 are as follows:
1H NMR(400MHz,CDCl3)δ8.48(s,1H),7.61(s,1H),7.47(d,J＝6.6Hz,1H),7.46(s,1H),7.41-7.35(m,4H),7.26(s,1H),7.25(d,J＝8.0Hz,1H),3.15(s,3H),2.43(s,6H).13C NMR(100MHz,CDCl3)δ171.0,167.3,151.8,138.9,138.2,137.9,136.2,135.9,135.1,134.0,129.9,129.8,129.4,129.2,128.4,128.1,126.4,126.3,125.5,115.6,23.8,21.5,21.51.
The nuclear magnetic data of the product of example 13 are as follows:
1H NMR(400MHz,CDCl3)δ8.53(s,1H),7.80(s,1H),7.70(s,1H),7.63-7.55(m,4H),7.51(d,J＝7.7Hz,1H),7.34(q,J＝7.6Hz,2H),3.16(s,3H).13C NMR(100MHz,CDCl3)δ170.7,166.9,151.96,138.45,137.60,136.85,134.5,132.0,131.7,131.6,130.1 129.7,128.1,127.8,126.3,122.64,122.31,115.9,23.91..
The nuclear magnetic data of the product of example 16 are as follows:
1H NMR(400MHz,CDCl3)δ8.70(s,1H),7.68(d,J＝7.4Hz,2H),7.63(s,1H),7.60(d,J＝7.4Hz,2H),7.53-7.41(m,6H),4.14-4.03(m,1H),2.20(q,J＝15.3,13.4Hz,2H),1.82(dd,J＝42.5,11.1Hz,4H),1.42-1.18(m,4H).13CNMR(100MHz,CDCl3)δ171.4,167.2,152.0,138.8,136.0,135.9,135.3,133.6,129.3,129.2,129.17,128.6,128.4,128.2,125.4,115.5,51.0,30.0,26.1,25.2.
the nuclear magnetic data of the product of example 17 are as follows:
1H NMR(400MHz,CDCl3)δ8.72(s,1H),7.73(s,1H),7.71(d,J＝8.4Hz,2H),7.63(dd,J＝7.7,1.9Hz,2H),7.53-7.40(m,11H).13C NMR(100MHz,CDCl3)δ170.1,166.1,152.4,139.5,136.5,135.8,135.1,134.4,131.2,129.4,129.2,129.1,128.9,128.6,128.3,128.2,126.4,124.9,115.2.
The nuclear magnetic data of the product of example 18 are as follows:
1H NMR(400MHz,CDCl3)δ8.53(s,1H),7.66(d,J＝7.2Hz,2H),7.64(s,1H),7.59(d,J＝6.8Hz,2H),7.51-7.43(m,8H),7.37-7.28(m,3H),4.82(s,2H).13C NMR(100MHz,CDCl3)δ170.7,166.8,152.0,139.1,136.2,136.16,135.9,135.1,134.0,129.3,129.2,128.8,128.7,128.6,128.3,128.2,128.0,127.4,125.4,115.6,41.6.
the nuclear magnetic data of the product of example 19 are as follows:
1H NMR(400MHz,CDCl3)δ8.71(s,1H),7.71(d,J＝7.7Hz,3H),7.62(d,J＝7.0Hz,2H),7.50-7.43(m,6H),7.33-7.28(m,4H),2.40(s,3H).13C NMR(100MHz,CDCl3)δ170.2,166.2,152.4,139.4,138.3,136.4,135.8,135.1,134.3,129.8,129.4,129.2,128.7,128.6,128.5,128.2,126.3,125.0,115.3,21.2.
the nuclear magnetic data of the product of example 20 are as follows:
1H NMR(400MHz,CDCl3)δ8.65(s,1H),7.72(s,1H),7.70(d,J＝6.8Hz,1H),7.61(dd,J＝7.7,1.8Hz,2H),7.53-7.40(m,9H).13C NMR(100MHz,CDCl3)δ169.7,165.8,152.5,139.6,136.7,135.7,135.0,134.6,133.9,129.8,129.3,129.2,128.8,128.7,128.6,128.3,127.5,124.7,115.1.
With the above-described preferred embodiments according to the present invention as an illustration, the above-described descriptions can be used by persons skilled in the relevant art to make various changes and modifications without departing from the scope of the technical idea of the present invention. The technical scope of the present invention is not limited to the description, but must be determined according to the scope of claims.
Claims (2)
1. A method for synthesizing isoindole-dione derivatives with high selectivity by utilizing the synergy of an iodine reagent and a Lewis acid to promote acetophenone and maleimide to undergo [4+2] cycloaddition, dehydroaromatization and multiple C (sp 3)-H/C(sp2) -H functionalization and realize the formation of multiple C-C bonds and C-O bonds is characterized in that the method is obtained by heating and stirring two components of acetophenone compounds and maleimide compounds at 140 ℃ under the reaction conditions of the iodine reagent, the Lewis acid and an organic solvent,
The isoindole-dione derivative has a general formula I:
Wherein:
R is selected from linear alkyl, cycloalkyl, benzyl, aryl;
R 1 is selected from alkyl, ester, halogen, trifluoromethyl, aryl,
The general formula of the acetophenone compound is shown as formula II:
Wherein:
R 1 is selected from alkyl, ester, halogen, trifluoromethyl, aryl,
The general formula of the maleimide compound is shown in the formula III:
Wherein:
R is selected from the group consisting of straight chain alkyl, cycloalkyl, benzyl, aryl,
The iodine reagent is as follows: i 2 is provided, which is a part of the main body,
The Lewis acid is: BF 3 .Et2 O, the total number of which is,
The molar ratio of the acetophenone compound to the maleimide compound to the iodine reagent to the Lewis acid is 1.0:0.5-1.5:0.5-1.5:0.5-1.0; the gas atmosphere of the reaction vessel was: an oxygen atmosphere; the reaction time is 12-36 hours.
2. The method according to claim 1, wherein the organic solvent is selected from one of tetrahydrofuran, toluene, acetonitrile, chlorobenzene, dimethyl sulfoxide, para-xylene, ortho-xylene.
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