CN110343087B - Synthesis of isoindolinone derivatives and preparation method thereof - Google Patents
Synthesis of isoindolinone derivatives and preparation method thereof Download PDFInfo
- Publication number
- CN110343087B CN110343087B CN201910625351.4A CN201910625351A CN110343087B CN 110343087 B CN110343087 B CN 110343087B CN 201910625351 A CN201910625351 A CN 201910625351A CN 110343087 B CN110343087 B CN 110343087B
- Authority
- CN
- China
- Prior art keywords
- catalyst
- formula
- carbonyl
- oxidant
- solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses two types of isoindolinone derivatives shown in formulas (I) and (II) and a synthesis method thereof. The preparation method has the advantages of low toxicity and low price of the catalyst, no need of ligand control, simple and easily obtained raw materials, good universality, simple and convenient post-treatment, good yield, environmental friendliness and the like.
Description
Technical Field
The invention belongs to the technical field of organic compound synthesis and transition metal catalysis, and relates to a method for synthesizing isoindolinone derivatives through cobalt-catalyzed C-H bond activation and metal carbene migration insertion.
Background
Isoindolinone compounds are used as an important nitrogen-containing heterocyclic compound and widely exist in natural products and pharmaceutically active molecules. Based on these, many researches have been made on a method for synthesizing isoindolinone compounds. Conventional methods for synthesizing isoindolinones generally include the Aza-Nazarov cyclization method, for example: document (1) Sai, k.k.s.; o' Connor, m.j.; klumpp, d.a. tetrahedron lett.2011,52, 2195-: document (2) Clayden, j.; menet, C.J.tetrahedron Lett.2003,44, 3059-: document (3) Enders, d.; narine, a.a.; toulgoat, f.; in addition to Bisschops, t.angelw.chem.int.ed.2008, 47, 5661-.
Metallic cobalt has a great research space in transition metal catalyzed C-H activation as a cheap and low-toxicity catalyst. Based on the defects of the existing synthesis, such as the difficulty in obtaining reaction raw materials, the high price of the catalyst, the narrow compatibility of functional groups and the like. Therefore, there is still a need to develop a more economical, simple and mild synthesis method of isoindoline compounds.
Disclosure of Invention
The invention aims to provide two types of isoindole quinolinone derivatives and a synthesis method thereof, and develops two cobalt-catalyzed synthesis methods of the isoindole quinolinone derivatives with low cost and environmental friendliness.
The two isoindolinone derivatives provided by the invention are used as organic synthesis intermediates, are main structural units in a plurality of natural products and medicines, mostly have stronger biological activity, and have great value in the aspect of medicine synthesis.
The structures of two isoindolinone derivatives provided by the invention are shown as formulas (I) and (II):
wherein the content of the first and second substances,
R1hydrogen, halogen, trifluoromethyl, C1-C10 alkyl, C1-C10 alkoxy, N dimethyl;
R2is phenyl, phenyl substituted by electron withdrawing or donating groups, C1-C10 alkoxy, the electron withdrawing group is halogen, and the electron donating group is C1-C10 alkyl, C1-C10 alkoxy;
preferably, the first and second electrodes are formed of a metal,
R1hydrogen, fluorine, chlorine, C1-C5 alkyl, trifluoromethyl, C1-C5 alkoxy, N dimethyl;
R2is phenyl, phenyl substituted by electron withdrawing or donating groups, C1-C5 alkoxy, the electron withdrawing group is chlorine, and the electron donating group is C1-C5 alkyl, C1-C5 alkoxy;
it is further preferred that the first and second liquid crystal compositions,
R1hydrogen, chlorine, methyl, trifluoromethyl, methoxy;
R2is phenyl.
The invention also provides a synthesis method of the isoindolinone derivative shown in the formula (I), which comprises the following steps of taking the aromatic amide compound and the alpha-carbonyl diazo compound as raw materials, and synthesizing the isoindolinone derivative shown in the formula (I) under the action of a catalyst and an oxidant, wherein the reaction process is shown in the formula (III):
wherein R is1、R2The definitions of (A) and (B) are as above.
The reaction comprises the following specific steps: in a solvent, taking an aromatic amide compound and an alpha-carbonyl diazo compound as raw materials, firstly, activating C (sp) under the action of a catalyst2) -a H bond; then, under the action of an oxidant, converting the alpha-diazo compound into an ketene intermediate, selectively inserting the formed C-M, and synthesizing to obtain the isoindolinone derivative shown in the formula (I) after reduction elimination.
Wherein the catalystThe reagent comprises CoBr2、Co(OAc)2、Co(acac)2One or more of the following; preferably, it is Co (OAc)2。
Wherein the oxidant comprises AgOAc, Ag2CO3、AgOTf、AgSbF6、K2S2O8One or more of TEMPO, TBHP, etc.; preferably, AgOAc and TEMPO.
Wherein the molar ratio of the aromatic amide compound to the alpha-carbonyl diazo compound to the catalyst to the oxidant is preferably 1.0: 2.0: 0.1: 3.5.
wherein the solvent is one or more of 1, 2-dichloroethane, toluene, tetrahydrofuran, and the like; preferably, it is 1, 2-dichloroethane.
Wherein the volume dosage of the solvent is 1.0mL-2.0 mL; preferably, it is 1.0 mL.
Wherein the reaction temperature is 100-140 ℃; preferably 130 deg.c.
Wherein the reaction time is 12-24 hours.
Wherein the yield of the preparation method is 76-93%.
Different from the traditional complex synthetic method, the invention develops a method for preparing the isoindolinone derivatives by using a transition metal cobalt-promoted carbon-hydrogen activated functionalization method in an atom-economic method. Compared with the traditional synthesis method, the method using metal catalysis has the advantages of fewer steps and simplicity in operation, and the transition metal cobalt is used for catalyzing functionalization with noble metal catalysis, so that the method is cheap, low in toxicity and wide in universality.
The invention also provides a synthesis method of the isoindolinone derivative shown in the formula (II), which comprises the following steps of taking the aromatic amide compound and the alpha-carbonyl diazo compound as raw materials, functionalizing different sites of the diazo compound under the condition of changing a catalyst and an oxidant, and synthesizing to obtain the isoindolinone derivative shown in the formula (II), wherein the reaction process is shown in the formula (IV):
wherein R is1、R2The definitions of (A) and (B) are as above.
The reaction comprises the following specific steps: in a solvent, taking an aromatic amide compound and an alpha-carbonyl diazo compound as raw materials, and activating C (sp) under the action of a catalyst2) And (3) generating a metal carbene intermediate by using an alpha-carbonyl diazo compound under the action of a catalyst, carrying out migration insertion on the formed C-M, and synthesizing the isoindolinone derivative shown in the formula (II) after reduction elimination.
Wherein the catalyst comprises CoBr2、Co(OAc)2、Co(acac)2One or more of the following; preferably, it is Co (acac)2。
Wherein the oxidizing agent comprises one or more of DTBP, TBHP, and the like; preferably, it is TBHP.
Wherein the molar ratio of the aromatic amide compound to the alpha-carbonyl diazo compound to the catalyst to the oxidant is preferably 1.0: 2.0: 0.1: 2.0.
wherein the solvent is one or more of 1, 2-dichloroethane, toluene, tetrahydrofuran, and the like; preferably, it is 1, 2-dichloroethane.
Wherein the volume dosage of the solvent is 1.0mL-2.0 mL; preferably, it is 1.0 mL.
Wherein the reaction temperature is 30-130 ℃; preferably, it is 30 ℃.
Wherein the reaction time is 6-12 hours.
Wherein the yield of the preparation method is 73-95%.
Compared with the prior optimal conditions, the other isoindolinone derivatives can be selectively obtained by adjusting the oxidant and reducing the reaction temperature.
The invention has the beneficial effects that: the preparation method has the advantages of low toxicity and low price of the catalyst, no need of ligand control, simple and easily obtained raw materials, good universality, simple and convenient post-treatment, good yield, environmental friendliness and the like, and two types of isoindolinone derivatives can be obtained regioselectively by adjusting reaction parameters.
Detailed Description
The present invention will be described in further detail with reference to the following specific examples, but the present invention is not limited to the following examples. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected. The procedures, conditions, reagents, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited.
Example 1: synthesis of IA
Amide, alpha-carbonyl diazo compound, solvent, catalyst and oxidant, wherein the additive is respectively selected from 8-aminoquinoline benzamide, 2-diazo-1-carbonyl propiophenone, 1, 2-dichloroethane, cobalt acetate, TEMPO, silver acetate and pivalic acid, the dosage of the raw materials is respectively 0.1mmol of 8-aminoquinoline benzamide, 0.2mmol of 2-diazo-1-carbonyl propiophenone, 1ml of solvent, 10 mol% of cobalt acetate, 50 mol% of TEMPO, 0.3mmol of silver acetate and 0.1mmol of pivalic acid, the raw materials react at 130 ℃ for 12 hours, then the reaction product is cooled to room temperature, and the product is filtered and subjected to column chromatography to obtain the target product formula (IA) and yellow solid, and the separation yield is 93%. mp 168 and 170 ℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ8.88(d,J＝4.0Hz,1H),8.17(d,J＝8.4Hz,1H),8.01(d,J＝7.6Hz,1H),7.86-7.79(m,2H),7.65(d,J＝8.0Hz,2H),7.61-7.51(m,4H),7.47(t,J＝7.6Hz,1H),7.42-7.38(m,1H),7.35-7.29(m,2H),6.61-6.50(m,1H),3.46-3.35(dd,J＝4.8,17.2Hz,1H),3.30-3.21(dd,J＝8.4,17.2Hz,1H)；13C NMR(100MHz,CDCl3):δ197.8,168.6,150.6,146.6,144.9,136.5,136.5,133.8,133.5,132.2,132.1,130.4,129.5,128.6,128.5,128.3,128.0,126.4,124.4,123.2,121.7,59.5,41.9；
high resolution mass spectral data：HRMS(ESI)calcd for C25H19N2O2[M+H]+:379.1441,found 379.1449.
Example 2: synthesis of IB
Amide, alpha-carbonyl diazo compound, solvent, catalyst and oxidant, wherein the additive is respectively selected from 8-aminoquinoline p-methylbenzamide, 2-diazo-1-carbonyl propiophenone, 1, 2-dichloroethane, cobalt acetate, TEMPO, silver acetate and pivalic acid, the dosage of the raw materials is respectively 0.1mmol of 8-aminoquinoline benzamide, 0.2mmol of 2-diazo-1-carbonyl propiophenone, 1ml of solvent, 10 mol% of cobalt acetate, 50 mol% of TEMPO, 0.3mmol of silver acetate and 0.1mmol of pivalic acid, the raw materials react at 130 ℃ for 12 hours, then the reaction product is cooled to room temperature and filtered, the target product formula IB (IB) is obtained by column chromatography, yellow solid is obtained, and the separation yield is 82%. mp 156-.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ8.86(d,J＝2.8Hz,1H),8.16(d,J＝6.4Hz,1H),7.88(d,J＝7.6Hz,1H),7.84(d,J＝7.2Hz,1H),7.80(d,J＝8.4Hz,1H),7.66(d,J＝8.0Hz,2H),7.61-7.55(m,1H),7.50-7.44(m,1H),7.41-7.37(m,1H),7.37-7.35(m,1H),7.35-7.28(m,3H),6.53-6.50(dd,J＝4.4,8.0Hz,1H),3.42-3.36(dd,J＝4.8,17.2Hz,1H),3.28-3.22(dd,J＝8.4,17.2Hz,1H),2.45(s,3H)；13C NMR(100MHz,CDCl3):δ198.0,168.8,150.7,147.2,145.1,143.0,136.7,136.5,134.1,133.5,130.5,129.6,129.6,128.7,128.3,128.1,126.5,124.3,123.8,121.7,59.4,42.1,21.8；
high resolution mass spectral data: HRMS (ESI) calcd for C26H20N2NaO2[M+Na]+:415.1417,found 415.1416.
Example 3: synthesis of IC
Amide, alpha-carbonyl diazo compound, solvent, catalyst and oxidant, wherein the additive respectively selects p-8-aminoquinoline p-methoxybenzamide, 2-diazo-1-carbonyl propiophenone, 1, 2-dichloroethane, cobalt acetate, TEMPO, silver acetate and pivalic acid, the dosage of the raw materials respectively is 0.1mmol of 8-aminoquinoline benzamide, 0.2mmol of 2-diazo-1-carbonyl propiophenone, 1ml of solvent, 10 mol% of cobalt acetate, 50 mol% of TEMPO, 0.3mmol of silver acetate and 0.1mmol of pivalic acid, the raw materials react at 130 ℃ for 24 hours, then the reaction product is cooled to room temperature and filtered, the column chromatography is carried out to obtain the target product formula (IC) and yellow solid, and the separation yield is 85%. mp 83-85 ℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ8.88(d,J＝2.4Hz,1H),8.16(d,J＝6.8Hz,1H),7.91(d,J＝8.0Hz,1H),7.85(d,J＝7.2Hz,1H),7.80(d,J＝8.4Hz,1H),7.67(d,J＝7.6Hz,2H),7.58(t,J＝8.0Hz,1H),7.48(t,J＝7.2Hz,1H),7.42-7.38(m,1H),7.32(t,J＝7.6Hz,2H),7.12-6.92(m,2H),6.55-6.51(dd,J＝4.8,8.8Hz,1H),3.84(s,3H),3.41-3.36(dd,J＝4.4,16.8Hz,1H),3.37-3.21(dd,J＝8.4,17.2Hz,1H)；13C NMR(100MHz,CDCl3):δ198.0,168.5,163.5,150.7,149.1,145.1,136.7,136.5,134.1,133.6,130.5,129.7,128.7,128.2,128.1,126.5,125.9,124.8,121.7,115.3,108.0,59.3,55.5,42.2；
high resolution mass spectral data: HRMS (ESI) calcd for C26H20N2NaO3[M+Na]+:431.1366,found 431.1372.
Example 4: synthesis of ID
Amide, alpha-carbonyl diazo compound, solvent, catalyst and oxidant, wherein the additive respectively selects 8-aminoquinoline p-trifluoromethyl benzamide, 2-diazo-1-carbonyl propiophenone, 1, 2-dichloroethane, cobalt acetate, TEMPO, silver acetate and pivalic acid, the dosage of the raw materials respectively is 0.1mmol of 8-aminoquinoline benzamide, 0.2mmol of 2-diazo-1-carbonyl propiophenone, 1ml of solvent, 10 mol% of cobalt acetate, 50 mol% of TEMPO, 0.3mmol of silver acetate and 0.1mmol of pivalic acid, the raw materials react at 130 ℃ for 20 hours, then the reaction product is cooled to room temperature, filtered and subjected to column chromatography to obtain the target product formula (ID), a white solid and the separation yield is 76%. mp 210 and 212 ℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ8.87(d,J＝4.0Hz,1H),8.18(d,J＝8.0Hz,1H),8.12(d,J＝8.0Hz,1H),7.90(s,1H),7.87-7.83(m,2H),7.82-7.77(m,1H),7.67(d,J＝8.0Hz,2H),7.61(t,J＝8.0Hz,1H),7.49(t,J＝7.6Hz,1H),7.45-7.40(m,1H),7.33(t,J＝7.6Hz,2H),6.73-6.53(m,1H),3.55-3.43(dd,J＝4.4,17.6Hz,1H),3.33-3.22(dd,J＝8.4,17.6Hz,1H)；13C NMR(100MHz,CDCl3):δ197.4167.3,150.9,147.1,144.8,136.6,136.4,135.6,134.2,133.9,133.7,133.4,130.4,129.7,128.8,128.0,126.5,125.8,125.8,125.0,121.9,120.9,120.9,59.5,41.5；
high resolution mass spectral data: HRMS (ESI) calcd for C26H17F3N2NaO2[M+Na]+:469.1134,found 469.1138.
Example 5: synthesis of IE
Amide, alpha-carbonyl diazo compound, solvent, catalyst and oxidant, wherein the additive is selected from p-8-aminoquinoline p-chlorobenzamide, 2-diazo-1-carbonyl propiophenone, 1, 2-dichloroethane, cobalt acetate, TEMPO, silver acetate and pivalic acid, the dosage of the raw materials is respectively 0.1mmol of 8-aminoquinoline benzamide, 0.2mmol of 2-diazo-1-carbonyl propiophenone, 1ml of solvent, 10 mol% of cobalt acetate, 50 mol% of TEMPO, 0.3mmol of silver acetate and 0.1mmol of pivalic acid, the raw materials react at 130 ℃ for 12 hours, then the reaction product is cooled to room temperature and filtered, the target product formula (IE) is obtained by column chromatography, the white solid is obtained, and the separation yield is 80%. mp 143-.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)8.87(d,J＝4.4Hz,1H),8.18(d,J＝8.8Hz,1H),7.93(d,J＝8.0Hz,1H),7.84(t,J＝7.2Hz,2H),7.68(d,J＝7.6Hz,2H),7.63-7.57(m,2H),7.49(t,J＝8.0Hz,2H),7.44-7.39(m,1H),7.34(t,J＝7.6Hz,2H),6.57-6.54(dd,J＝4.4,8.8Hz,1H),3.44-3.39(dd,J＝4.4,17.6Hz,1H),3.28-3.22(dd,J＝8.8,17.6Hz,1H)；13C NMR(100MHz,CDCl3):δ197.5,167.7,150.8,148.4,144.9,138.6,136.6,136.4,133.7,133.6,130.8,130.4,129.7,129.2,128.8,128.6,128.1,126.5,125.7,124.0,121.9,59.1,41.7；
high resolution mass spectral data: HRMS (ESI) calcd for C25H17ClN2NaO2[M+Na]+:435.0871,found 435.0881.
Example 6: synthesis of IIA
The amide, the alpha-carbonyl diazo compound, the solvent, the catalyst and the oxidant are respectively selected from 8-aminoquinoline benzamide, 2-diazo-1-carbonyl propiophenone, 1, 2-dichloroethane, cobalt acetylacetonate and TBHP, the dosage of the raw materials is respectively 0.1mmol of 8-aminoquinoline benzamide, 0.2mmol of 2-diazo-1-carbonyl propiophenone, 1ml of the solvent, 10mol of cobalt acetylacetonate and 0.3mmol of TBHP, the raw materials react for 6 hours at 30 ℃, and then the mixture is filtered and subjected to column chromatography to obtain a target product, namely a formula (IIA) and a yellow solid, and the separation yield is 91%. mp 105-.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ8.64(d,J＝4.0Hz,1H),8.16(d,J＝8.4Hz,1H),8.02(d,J＝7.6Hz,1H),7.79(m,J＝8.0Hz,1H),7.70(d,J＝7.6Hz,1H),7.63-7.57(m,3H),7.54-7.50(m,2H),7.44(d,J＝7.2Hz,1H),7.38-7.35(m,1H),7.33-7.29(m,1H),7.22-7.16(m,2H),1.67(s,3H)；13C NMR(100MHz,CDCl3):δ196.2,170.2,148.6,147.3,143.1,137.1,136.5,134.2,133.2,131.8,131.5,129.3,129.3,129.1,128.4,128.2,127.7,126.7,125.1,122.5,121.8,76.2,21.8；
high resolution mass spectral data: HRMS (ESI) calcd for C25H19N2O2[M+H]+:379.1441,found 379.1445.
Example 7: synthesis of IIB
The amide, the alpha-carbonyl diazo compound, the solvent, the catalyst and the oxidant are respectively selected from 8-aminoquinoline p-methylbenzamide, 2-diazo-1-carbonyl propiophenone, 1, 2-dichloroethane, cobalt acetylacetonate and TBHP, the dosage of the raw materials is respectively 0.1mmol of 8-aminoquinoline benzamide, 0.2mmol of 2-diazo-1-carbonyl propiophenone, 1ml of the solvent, 10mol of cobalt acetylacetonate and 0.3mmol of TBHP, the raw materials react for 10 hours at 30 ℃, then the mixture is filtered and subjected to column chromatography to obtain a target product, namely a brown solid with a separation yield of 95 percent, and the formula (IIB) is a target product. mp 205-.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)8.63(d,J＝4.4Hz,1H),8.16(d,J＝6.8Hz,1H),7.91(d,J＝7.6Hz,1H),7.78(d,J＝8.4Hz,1H),7.68(d,J＝7.6Hz,1H),7.62(d,J＝8.0Hz,2H),7.51(t,J＝8.0Hz,1H),7.40-7.31(m,3H),7.27-7.19(m,3H),2.43(s,3H),1.64(s,3H)；13C NMR(100MHz,CDCl3):δ196.5,170.3,148.5,147.7,144.2,143.3,137.3,136.5,134.5,131.8,130.5,129.3,129.2,129.0,128.4,128.2,127.5,126.7,124.9,122.9,121.8,76.1,22.0,21.7；
high resolution mass spectral data: HRMS (ESI) calcd for C26H21N2O2[M+H]+:393.1598,found 393.1604.
Example 8: synthesis of IIC
The amide, the alpha-carbonyl diazo compound, the solvent, the catalyst and the oxidant are respectively selected from 8-aminoquinoline p-methoxybenzamide, 2-diazo-1-carbonyl propiophenone, 1, 2-dichloroethane, cobalt acetylacetonate and TBHP, the dosage of the raw materials is respectively 0.1mmol of 8-aminoquinoline benzamide, 0.2mmol of 2-diazo-1-carbonyl propiophenone, 1ml of the solvent, 10mol of cobalt acetylacetonate and 0.3mmol of TBHP, the raw materials react for 12 hours at 30 ℃, then the mixture is filtered and subjected to column chromatography to obtain a target product formula (IIC) and a brown solid, and the separation yield is 90%. mp 221-.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ8.61(s,1H),8.15(d,J＝8.4Hz,1H),7.92(d,J＝8.4Hz,1H),7.80-7.71(m,2H),7.65(d,J＝8.0Hz,2H),7.55-7.49(m,1H),7.39-7.31(m,2H),7.24-7.17(m,2H),7.03(d,J＝6.4Hz,1H),6.89(s,1H),3.84(s,3H),1.65(s,3H)；13C NMR(100MHz,CDCl3):δ196.3,170.0,164.2,149.8,148.3,143.1,137.3,136.5,134.5,131.8,129.3,129.2,128.4,128.1,127.3,126.7,126.6,124.1,121.8,116.4,106.6,76.0,55.7,22.1；
high resolution mass spectral data: HRMS (ESI) calcd for C26H21N2O3[M+H]+:409.1547,found 409.1549.
Example 9: synthesis of IID
The amide, the alpha-carbonyl diazo compound, the solvent, the catalyst and the oxidant are respectively selected from 8-aminoquinoline p-trifluoromethyl benzamide, 2-diazo-1-carbonyl propiophenone, 1, 2-dichloroethane, cobalt acetylacetonate and TBHP, the dosage of the raw materials is respectively 0.1mmol of 8-aminoquinoline benzamide, 0.2mmol of 2-diazo-1-carbonyl propiophenone, 1ml of the solvent, 10mol of cobalt acetylacetonate and 0.3mmol of TBHP, the raw materials react for 12 hours at 30 ℃, and then the mixture is filtered and subjected to column chromatography to obtain a target product of formula (IID) and a brown solid, and the separation yield is 73%. mp 135-.
Nuclear magnetic data:1HNMR(400MHz,CDCl3)δ8.64(d,J＝3.2Hz,1H),8.19(d,J＝8.0Hz,1H),8.11(d,J＝8.0Hz,1H),7.86-7.78(m,2H),7.75-7.70(m,2H),7.60-7.54(m,3H),7.42-7.38(m,1H),7.37-7.32(m,1H),7.23-7.17(m,2H),1.70(s,3H)；13C NMR(100MHz,CDCl3):δ195.2,168.7,148.6,147.8,142.8,136.9,136.7,135.2,134.8,134.7,133.7,132.1,129.3,129.2,128.6,128.2,128.0,126.8,126.6,126.6,125.7,125.0,122.3,122.1,119.8,119.8,76.4,21.7；
high resolution mass spectral data: HRMS (ESI) calcd for C26H18F3N2O2[M+H]+:447.1315,found 447.1321.
Example 10: synthesis of IIE
The amide, the alpha-carbonyl diazo compound, the solvent, the catalyst and the oxidant are respectively selected from 8-aminoquinoline p-fluorobenzamide, 2-diazo-1-carbonyl propiophenone, 1, 2-dichloroethane, cobalt acetylacetonate and TBHP, the dosage of the raw materials is respectively 0.1mmol of 8-aminoquinoline benzamide, 0.2mmol of 2-diazo-1-carbonyl propiophenone, 1ml of the solvent, 10mol of cobalt acetylacetonate and 0.3mmol of TBHP0.3mmol, the reaction is carried out for 6 hours at 30 ℃, then the filtration and the column chromatography are carried out to obtain the target product formula (IIE) and yellow solid, and the separation yield is 83%. mp 148 and 150 ℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3)δ8.62(d,J＝3.6Hz,1H),8.17(d,J＝8.4Hz,1H),8.02-7.96(m,1H),7.80(d,J＝8.4Hz,1H),7.75(d,J＝7.6Hz,1H),7.62(d,J＝8.0Hz,2H),7.57-7.52(m,1H),7.40-7.36(m,1H),7.36-7.31(m,1H),7.25-7.18(m,3H),7.12(d,J＝7.6Hz,1H),1.66(s,3H)；13C NMR(100MHz,CDCl3):δ195.4,169.1,167.5,164.9,150.0,149.9,148.4,142.9,137.0,136.6,134.0,132.0,129.3,129.2,128.5,128.1,127.6,127.3,127.2,126.8,121.9,117.3,117.1,110.0,109.8,75.9,21.8；
high resolution mass spectral data: HRMS (ESI) calcd for C25H18FN2O2[M+H]+:397.1347,found 397.1353.
The above embodiments are only for illustrating the technical concept and features of the present invention, and the purpose of the embodiments is to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present disclosure are covered by the scope of the present disclosure.
Claims (10)
1. A method for synthesizing isoindolinone derivatives shown in formula (I) is characterized in that aromatic amide compounds and alpha-carbonyl diazo compounds are used as raw materials, and the isoindolinone derivatives shown in formula (I) are synthesized under the action of a catalyst and an oxidant, wherein the reaction process is shown in formula (III):
wherein R is1Is hydrogen, halogen, trifluoromethyl, C1-C10 alkyl, C1-C10 alkoxy;
R2is phenyl;
the catalyst is Co (OAc)2(ii) a The oxidant is AgOAc and TEMPO.
2. The synthetic method according to claim 1, comprising the specific steps of: in a solvent, taking an aromatic amide compound and an alpha-carbonyl diazo compound as raw materials, firstly, activating C (sp) under the action of a catalyst2) -a H bond; and secondly, under the action of an oxidant, converting the alpha-diazo compound into an ketene intermediate, selectively inserting the formed C-M, and synthesizing the isoindolinone derivative shown in the formula (I) after reduction elimination.
3. The synthesis method according to claim 1 or 2, wherein the molar ratio of the aromatic amide compound, the α -carbonyl diazo compound, the catalyst and the oxidant is 1.0: 2.0: 0.1: 3.5.
4. the synthesis method of claim 2, wherein the solvent is one or more of 1, 2-dichloroethane, toluene, tetrahydrofuran; the volume dosage of the solvent is 1.0-2.0 mL.
5. The method of claim 1, wherein the reaction temperature is 100-140 ℃; the reaction time is 12-24 hours.
6. A method for synthesizing isoindolinone derivatives shown in formula (II) is characterized in that aromatic amide compounds and alpha-carbonyl diazo compounds are used as raw materials, different sites of the diazo compounds are functionalized under the condition of changing catalysts and oxidants, and the isoindolinone derivatives shown in formula (II) are synthesized, wherein the reaction process is shown in formula (IV):
wherein R is1Is hydrogen, halogen, trifluoromethyl, C1-C10 alkyl, C1-C10 alkoxy;
R2is phenyl;
the catalyst is Co (acac)2(ii) a The oxidant is TBHP.
7. The synthetic method according to claim 6, characterized in that it comprises the following steps: in a solvent, taking an aromatic amide compound and an alpha-carbonyl diazo compound as raw materials, and activating C (sp) under the action of a catalyst2) And (3) generating a metal carbene intermediate by using an alpha-carbonyl diazo compound under the action of an oxidant, carrying out migration insertion on the formed C-M, and synthesizing the isoindolinone derivative shown in the formula (II) after reduction elimination.
8. The synthesis method according to claim 6 or 7, wherein the molar ratio of the aromatic amide compound to the α -carbonyl diazo compound to the catalyst to the oxidant is 1.0: 2.0: 0.1: 2.0.
9. the method of synthesis according to claim 7, wherein the solvent is 1, 2-dichloroethane; the volume dosage of the solvent is 1.0-2.0 mL.
10. The method of synthesis according to claim 6, wherein the reaction temperature is between 30 ℃ and 130 ℃; the reaction time is 6-12 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910625351.4A CN110343087B (en) | 2019-07-11 | 2019-07-11 | Synthesis of isoindolinone derivatives and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910625351.4A CN110343087B (en) | 2019-07-11 | 2019-07-11 | Synthesis of isoindolinone derivatives and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110343087A CN110343087A (en) | 2019-10-18 |
| CN110343087B true CN110343087B (en) | 2022-02-11 |
Family
ID=68175058
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910625351.4A Active CN110343087B (en) | 2019-07-11 | 2019-07-11 | Synthesis of isoindolinone derivatives and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110343087B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112961086B (en) * | 2021-02-05 | 2022-10-21 | 齐鲁工业大学 | 2-methylene-1-indanone derivative and synthesis method thereof |
| CN114773293A (en) * | 2022-01-11 | 2022-07-22 | 华东师范大学 | Tetrahydroindenone-isoselenazole derivative and synthesis method and application thereof |
-
2019
- 2019-07-11 CN CN201910625351.4A patent/CN110343087B/en active Active
Non-Patent Citations (7)
| Title |
|---|
| Co(II)/Cu(II)-cocatalyzed oxidative C–H/N–H functionalization of benzamides with ketones: a facile route to isoindolin-1-ones;Xi Zhou 等;《Chemical Communications》;20190613;第55卷(第59期);第8604-8607页Scheme1及cheme2 * |
| Cobalt(II)-Catalyzed Oxidative C−H Alkenylations: Regio- and Site-Selective Access to Isoindolin-1-one;Wenbo Ma 等;《ACS Catalysis》;20150320;第5卷(第5期);第2283页Scheme2 * |
| Palladium-Catalyzed Regioselective Carbonylative Coupling/Amination of Aryl Iodides with Unactivated Alkenes: Efficient Synthesis of β‑Aminoketones;Jin-Bao Peng 等;《ACS Catalysis》;20190301;第9卷(第4期);第2980页表4 * |
| Rhodium-Catalyzed Alkylation of C−H Bonds in Aromatic Amides with α,β-Unsaturated Esters;Kaname Shibata 等;《Organic Letters》;20140916;第16卷(第19期);第5149页Scheme3 * |
| Ruthenium-catalyzed ortho-C–H bond alkylation of aromatic amides with a,b-unsaturated ketones via bidentate-chelation assistance;Guy Rouquet 等;《Chemical Science》;20130319;第4卷(第5期);全文 * |
| Wenbo Ma 等.Cobalt(II)-Catalyzed Oxidative C−H Alkenylations: Regio- and Site-Selective Access to Isoindolin-1-one.《ACS Catalysis》.2015,第5卷(第5期), * |
| Xi Zhou 等.Co(II)/Cu(II)-cocatalyzed oxidative C–H/N–H functionalization of benzamides with ketones: a facile route to isoindolin-1-ones.《Chemical Communications》.2019,第55卷(第59期), * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110343087A (en) | 2019-10-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Varala et al. | Bismuth triflate catalyzed one-pot synthesis of 3, 4-dihydropyrimidin-2 (1H)-ones: An improved protocol for the Biginelli reaction | |
| Filian et al. | Pd (0)‐guanidine@ MCM‐41: a very effective catalyst for rapid production of bis (pyrazolyl) methanes | |
| Enders et al. | Preparation and application of 1, 3, 4-triphenyl-4, 5-dihydro-1H-1, 2, 4-triazol-5-ylidene, a stable carbene | |
| CN110343087B (en) | Synthesis of isoindolinone derivatives and preparation method thereof | |
| Jin et al. | An efficient and convenient approach to the synthesis of benzopyrans by a three-component coupling of one-pot reaction | |
| Gupta et al. | Covalently anchored sulfonic acid on silica gel as an efficient and reusable heterogeneous catalyst for the one-pot synthesis of Hantzsch 1, 4-dihydropyridines under solvent-free conditions | |
| Yu et al. | Iron (III) chloride promoted desulfitative C–C coupling reaction of α-oxo ketene dithioacetals and indoles: highly selective synthesis of β, β-bisindolyl and β-indolyl α, β-unsaturated carbonyl compounds | |
| Xiao et al. | N-Heterocyclic carbene-palladium (II)-1-methylimidazole complex catalyzed α-arylation of ketones with aryl chlorides | |
| Shen et al. | Brønsted Acid Catalyzed C3-Alkylation of 2-Indolylmethanols with Azlactones via an Umpolung Strategy | |
| Yuan et al. | One-Pot synthesis of trifluoromethylated pyrazol-4-yl-pyrrole-2, 5-dione derivatives | |
| Belov et al. | Synthesis of 5-arylpyrrole-2-carboxylic acids as key intermediates for NBD series HIV-1 entry inhibitors | |
| Seki | Studies on the Cocatalyst in Ruthenium-Catalyzed C–H Arylation | |
| Chang et al. | MeONH2· HCl-Mediated α-Methylenation/Conjugate Addition of α-Sulfonyl o-Hydroxyacetophenones with Methyl Sulfoxides: Route to 3-Sulfonylchroman-4-ones | |
| Hong et al. | Copper-Catalyzed Carbene Insertion into the Sulfur–Sulfur Bond of RS–SCF2H/SCF3 under Mild Conditions | |
| CN110483387B (en) | Method for synthesizing nicotinamide amide derivative by one-pot method | |
| Wang et al. | Cascade Reactions to Substituted 1H-Pyrrole-3-carbonitriles via Ligand-Free Palladium (II)-Catalyzed C (sp)–C (sp2) Coupling | |
| Yavari et al. | A Synthesis of Novel Perinaphthenones from Acetylenic Esters and Acenaphthoquinone–Malononitrile Adduct in the Presence of Triphenylphosphine | |
| Hsu et al. | Mild and Efficient Copper-Catalyzed Synthesis of Trisubstituted Pyrroles | |
| Kaur et al. | Click chemistry approach to isoindole-1, 3-dione tethered 1, 2, 3-triazole derivatives | |
| Cibian et al. | Facile synthesis of hydroxyformamidines by the N-oxidation of their corresponding formamidines | |
| Khera et al. | Synthesis of functionalized 3, 4-diarylbenzophenones and 2, 4-diarylbenzophenones by site-selective suzuki and sonogashira cross-coupling reactions of bis (triflates) of 3, 4-and 2, 4-dihydroxybenzophenone | |
| Li et al. | Rh (III)‐Catalyzed Reaction of 2‐Aryl‐3‐acyl‐1H‐indoles with α‐Diazo Carbonyl Compounds: Synthesis of 5‐Carbonyl Substituted Benzo [a] carbazoles via [5+ 1] Annulation | |
| Shi et al. | Highly regioselective synthesis of substituted pyrroles utilizing low-valent titanium reagent | |
| Yadav et al. | An Efficient Protocol for Multicomponent Stereoselective Synthesis of 3-Amino-2 (1H)-pyridinones Using CeCl3˙ 7H2O/NaI as a Reaction Promoter | |
| CN113636972B (en) | Polysubstituted benzene compound and synthesis method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |