CN110343087A - Synthesis of isoindolinone derivatives and preparation method thereof - Google Patents
Synthesis of isoindolinone derivatives and preparation method thereof Download PDFInfo
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Abstract
The invention discloses formula (I), (II) two class isoindolinone derivatives and its synthetic method, using aromatic amides class compound and alpha-carbonyl diazonium compound as raw material, under the action of catalyst, function dough is carried out by the adjusting of oxidant come the different loci to alpha-carbonyl diazonium compound, synthesis obtains formula (I), (II) two class isoindolinone derivatives.Preparation method of the present invention has many advantages, such as that catalyst low toxicity is cheap, is not necessarily to ligand control, raw material is simple and easy to get, universality is good, post-processing is easy, yield is good, environmentally friendly.
Description
Technical field
The invention belongs to organic compound synthesis and transition metal-catalyzed technical field, the c h bond for being related to cobalt catalysis is living
Change and the method for synthesizing isoindolinone derivatives is inserted into metal carbene migration.
Background technique
Isoindoline ketone compound as a kind of important nitrogen-containing heterocycle compound, widely exist in natural products and
In pharmaceutical activity molecule.Based on these, there are many explorations for the synthetic method of isoindoline ketone compound.Tradition is closed
Aza-Nazarov cyclization method is generally included at the method for isoindoline ketone compound, such as: document (1) Sai, K.K.S.；
O'Connor,M.J.；The cyclisation of Klumpp, D.A.Tetrahedron Lett.2011,52,2195-2198. aniline lithium salts is anti-
It answers, such as: document (2) Clayden, J.；Menet, C.J.Tetrahedron Lett.2003,44,3059-3062. and cloth
The special acid catalyzed Friedel-Crafts reaction of Lanace, such as: document (3) Enders, D.；Narine,A.A.；Toulgoat,
F.；Bisschops, T.Angew.Chem.Int.Ed.2008,47,5661-5665. are in addition to this, living by metal catalytic C-H
Being combined to various isoindoline ketone compounds is then that one kind is direct, easily, the method with Atom economy.
A kind of catalyst of the metallic cobalt as cheap low toxicity has very big grind in transition metal-catalyzed C-H activation
Study carefully space.Based on the shortcoming of existing synthesis, such as reaction raw materials are not easy to obtain, catalyst is expensive and functional group is simultaneous
Capacitive is relatively narrow etc..Therefore, it is still necessary to the iso-indoles quinolines that development is more economical, simplicity and reaction condition are mild
Synthetic method.
Summary of the invention
The object of the present invention is to provide two class iso-indoles quinoline ketone derivatives and its synthetic methods, have developed two kinds of cobalts and have urged
The synthetic method of inexpensive, the environment amenable isoindoline ketones derivant of change.
Two kinds of isoindoline ketones derivants proposed by the present invention are also many natural as organic synthesis intermediate
Essential building blocks in product and drug, and there is stronger bioactivity mostly, there is great valence in terms of pharmaceutical synthesis
Value.
Two kinds of isoindoline ketones derivants proposed by the present invention, structure such as formula (I), shown in (II):
Wherein,
R1For hydrogen, halogen, trifluoromethyl, C1-C10 alkyl, C1-C10 alkoxy, N, N dimethyl；
R2Phenyl, the C1-C10 alkoxy replaced for phenyl, electrophilic or electron donating group, the electron-withdrawing group are halogen
Element, electron donating group are C1-C10 alkyl, C1-C10 alkoxy；
Preferably,
R1For hydrogen, fluorine, chlorine, C1-C5 alkyl, trifluoromethyl, C1-C5 alkoxy, N, N dimethyl；
R2Phenyl, the C1-C5 alkoxy replaced for phenyl, electrophilic or electron donating group, the electron-withdrawing group are chlorine,
Electron donating group is C1-C5 alkyl, C1-C5 alkoxy；
It is further preferred that
R1For hydrogen, chlorine, methyl, trifluoromethyl, methoxyl group；
R2For phenyl.
The present invention also provides the synthetic methods of isoindoline ketones derivant shown in formula (I), with aromatic amides class
Closing object and alpha-carbonyl diazonium compound is raw material, and under the action of catalyst, oxidant, synthesis obtains different as shown in formula (I)
Indoline ketone derivative, shown in reaction process such as formula (III):
Wherein, R1、R2It is defined as above formula (I) and formula (II).
The specific steps of the reaction are as follows: in a solvent, be with aromatic amides class compound and alpha-carbonyl diazonium compound
Raw material, firstly, activating C (sp under the action of catalyst2)-H key；Then, under oxidant effect, α-diazonium compound is converted into
Ketenes intermediate selectively inserts the C-M of formation, and synthesis obtains the isoindoline as shown in formula (I) after reduction is eliminated
Ketones derivant.
Wherein, the catalyst includes CoBr2、Co(OAc)2、Co(acac)2Deng one of or it is a variety of；Preferably, it is
Co(OAc)2。
Wherein, the oxidant includes AgOAc, Ag2CO3、AgOTf、AgSbF6、K2S2O8, in TEMPO, TBHP etc. one
Kind is a variety of；It preferably, is AgOAc and TEMPO.
Wherein, the aromatic amides class compound, alpha-carbonyl diazonium compound, catalyst, the molar ratio of oxidant are preferred
For 1.0:2.0:0.1:3.5.
Wherein, the solvent is one of 1,2- dichloroethanes, toluene, tetrahydrofuran etc. or a variety of；It preferably, is 1,
2- dichloroethanes.
Wherein, the volumetric usage of the solvent is 1.0mL-2.0mL；It preferably, is 1.0mL.
Wherein, the temperature of the reaction is 100 DEG C -140 DEG C；It preferably, is 130 DEG C.
Wherein, the time of the reaction is 12-24 hours.
Wherein, the yield of the preparation method is 76-93%.
It is different from the synthetic method of traditional complexity, that the present invention develops is the hydrocarbon activation official promoted by transition metals cobalt
The method of energy dough, prepares isoindoline ketones derivant in the method for Atom economy.Prior synthesizing method is compared, gold is passed through
Belong to the advantage that the method for catalysis has step few, easy to operate, is catalyzed by transition metals cobalt compared with precious metal catalyst function dough
Advantage be that cheap low toxicity, universality is wider.
The present invention also provides the synthetic methods of isoindoline ketones derivant shown in formula (II), with aromatic amides class
Closing object and alpha-carbonyl diazonium compound is raw material, under conditions of changing catalyst, oxidant, the position different to diazonium compound
Point carries out functional group, and synthesis obtains the isoindoline ketones derivant as shown in formula (II), reaction process such as formula (IV) institute
Show:
Wherein, R1、R2It is defined as above formula (I) and formula (II).
The specific steps of the reaction are as follows: in a solvent, be with aromatic amides class compound and alpha-carbonyl diazonium compound
Raw material activates C (sp under the action of catalyst2)-H key, while under the action of catalyst, alpha-carbonyl diazonium compound generates metal
Cabbeen intermediate carries out migration insertion to the C-M of formation, and synthesis obtains the isoindolinone as shown in formula (II) after reduction is eliminated
Analog derivative.
Wherein, the catalyst includes CoBr2、Co(OAc)2、Co(acac)2Deng one of or it is a variety of；Preferably, it is
Co(acac)2。
Wherein, the oxidant include DTBP, TBHP, etc. one of or it is a variety of；It preferably, is TBHP.
Wherein, the aromatic amides class compound, alpha-carbonyl diazonium compound, catalyst, the molar ratio of oxidant are preferred
For 1.0:2.0:0.1:2.0.
Wherein, the solvent is one of 1,2- dichloroethanes, toluene, tetrahydrofuran etc. or a variety of；It preferably, is 1,
2- dichloroethanes.
Wherein, the volumetric usage of the solvent is 1.0mL-2.0mL；It preferably, is 1.0mL.
Wherein, the temperature of the reaction is 30 DEG C -130 DEG C；It preferably, is 30 DEG C.
Wherein, the time of the reaction is 6-12 hours.
Wherein, the yield of the preparation method is 73-95%.
Optimal conditions before relatively, by adjusting oxidant, what reduction reaction temperature can be selective obtains another kind of
Isoindoline ketones derivant.
The beneficial effects of the present invention are: preparation method of the present invention is cheap with catalyst low toxicity, controls without ligand, original
Expect the advantages that simple and easy to get, universality is good, post-processing is easy, yield is good, environmentally friendly, and the tune for passing through response parameter
Section, regioselectivity obtain two class isoindoline ketones derivants.
Specific embodiment
In conjunction with following specific embodiments, the present invention is described in further detail, and of the invention protects content not limit to
In following embodiment.Without departing from the spirit and scope of the invention, those skilled in the art it is conceivable that variation and excellent
Point is all included in the present invention, and using appended claims as protection scope.Implement process of the invention, condition,
Reagent, experimental method etc. are among the general principles and common general knowledge in the art, this hair in addition to what is specifically mentioned below
It is bright that there are no special restrictions to content.
The synthesis of embodiment 1:IA
Amide, alpha-carbonyl diazonium compound, solvent, catalyst, oxidant, additive are selected respectively to 8- aminoquinoline benzene
Formamide, 2- diazonium -1- carbonyl propiophenone, 1,2- dichloroethanes, cobalt acetate, TEMPO, silver acetate, spy's acid, the dosage of raw material
Respectively 8- aminoquinoline benzamide 0.1mmol, 2- diazonium -1- carbonyl propiophenone 0.2mmol, solvent 1ml, cobalt acetate
10mol%, TEMPO 50mol%, silver acetate 0.3mmol, spy acid 0.1mmol are reacted 12 hours at 130 DEG C, are then cooled down
To room temperature, filtering, column chromatographs to obtain target product formula (IA), yellow solid, separation yield 93%.mp 168-170℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3) δ 8.88 (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 spec data: HRMS (ESI) calcd for C25H19N2O2[M+H]+:379.1441,found
379.1449.
The synthesis of embodiment 2:IB
Amide, alpha-carbonyl diazonium compound, solvent, catalyst, oxidant, additive are selected respectively to 8- aminoquinoline pair
Methyl benzamide, 2- diazonium -1- carbonyl propiophenone, 1,2- dichloroethanes, cobalt acetate, TEMPO, silver acetate, spy's acid, raw material
Dosage be respectively 8- aminoquinoline benzamide 0.1mmol, 2- diazonium -1- carbonyl propiophenone 0.2mmol, solvent 1ml, cobalt acetate
10mol%, TEMPO 50mol%, silver acetate 0.3mmol, spy acid 0.1mmol are reacted 12 hours at 130 DEG C, are then cooled down
To room temperature, filtering, column chromatographs to obtain target product formula (IB), yellow solid, separation yield 82%.mp 156-158℃.
Nuclear magnetic data:1HNMR(400MHz,CDCl3) δ 8.86 (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 spec data: HRMS (ESI) calcd for C26H20N2NaO2[M+Na]+:415.1417,
found415.1416.
The synthesis of embodiment 3:IC
Amide, alpha-carbonyl diazonium compound, solvent, catalyst, oxidant, additive are selected respectively to 8- aminoquinoline pair
Methoxy benzamide, 2- diazonium -1- carbonyl propiophenone, 1,2- dichloroethanes, cobalt acetate, TEMPO, silver acetate, spy's acid, it is former
The dosage of material is respectively 8- aminoquinoline benzamide 0.1mmol, 2- diazonium -1- carbonyl propiophenone 0.2mmol, solvent 1ml, acetic acid
Cobalt 10mol%, TEMPO 50mol%, silver acetate 0.3mmol, spy acid 0.1mmol react 24 hours at 130 DEG C, then cold
But it to room temperature, filters, column chromatographs to obtain target product formula (IC), yellow solid, separation yield 85%.mp 83-85℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3) δ 8.88 (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 spec data: HRMS (ESI) calcd for C26H20N2NaO3[M+Na]+:431.1366,
found431.1372.
The synthesis of embodiment 4:ID
Amide, alpha-carbonyl diazonium compound, solvent, catalyst, oxidant, additive are selected respectively to 8- aminoquinoline pair
Trifluoromethyl benzamide, 2- diazonium -1- carbonyl propiophenone, 1,2- dichloroethanes, cobalt acetate, TEMPO, silver acetate, spy's acid,
The dosage of raw material is respectively 8- aminoquinoline benzamide 0.1mmol, 2- diazonium -1- carbonyl propiophenone 0.2mmol, solvent 1ml, second
Sour cobalt 10mol%, TEMPO 50mol%, silver acetate 0.3mmol, spy acid 0.1mmol, 130 DEG C react 20 hours, then
It is cooled to room temperature, filters, column chromatographs to obtain target product formula (ID), white solid, separation yield 76%.mp 210-212℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3) δ 8.87 (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 spec data: HRMS (ESI) calcd for C26H17F3N2NaO2[M+Na]+:469.1134,
found469.1138.
The synthesis of embodiment 5:IE
Amide, alpha-carbonyl diazonium compound, solvent, catalyst, oxidant, additive are selected respectively to 8- aminoquinoline pair
Chlorobenzamide, 2- diazonium -1- carbonyl propiophenone, 1,2- dichloroethanes, cobalt acetate, TEMPO, silver acetate, spy's acid, raw material
Dosage is respectively 8- aminoquinoline benzamide 0.1mmol, 2- diazonium -1- carbonyl propiophenone 0.2mmol, solvent 1ml, cobalt acetate
10mol%, TEMPO 50mol%, silver acetate 0.3mmol, spy acid 0.1mmol are reacted 12 hours at 130 DEG C, are then cooled down
To room temperature, filtering, column chromatographs to obtain target product formula (IE), white solid, separation yield 80%.mp 143-145℃.
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 spec data: HRMS (ESI) calcd for C25H17ClN2NaO2[M+Na]+:435.0871,
found435.0881.
The synthesis of embodiment 6:IIA
Amide, alpha-carbonyl diazonium compound, solvent, catalyst, oxidant select respectively to 8- aminoquinoline benzamide,
2- diazonium -1- carbonyl propiophenone, 1,2- dichloroethanes, acetylacetone cobalt, TBHP, the dosage of raw material are respectively 8- aminoquinoline benzene
Amide 0.1mmol, 2- diazonium -1- carbonyl propiophenone 0.2mmol, solvent 1ml, acetylacetone cobalt 10mol%, TBHP
0.3mmol, it reacts 6 hours, then filters, column chromatographs to obtain target product formula (IIA), yellow solid, separation yield at 30 DEG C
91%.mp 105-107℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3) δ 8.64 (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 spec data: HRMS (ESI) calcd for C25H19N2O2[M+H]+:379.1441,found
379.1445.
The synthesis of embodiment 7:IIB
Amide, alpha-carbonyl diazonium compound, solvent, catalyst, oxidant are selected respectively to 8- aminoquinoline to methylbenzene
Formamide, 2- diazonium -1- carbonyl propiophenone, 1,2- dichloroethanes, acetylacetone cobalt, TBHP, the dosage of raw material is respectively 8- ammonia
Base quinoline benzamide 0.1mmol, 2- diazonium -1- carbonyl propiophenone 0.2mmol, solvent 1ml, acetylacetone cobalt 10mol%, TBHP
0.3mmol, it reacts 10 hours, then filters, column chromatographs to obtain target product formula (IIB), brown solid, separation yield at 30 DEG C
95%.mp 205-207℃.
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 spec data: HRMS (ESI) calcd for C26H21N2O2[M+H]+:393.1598,found
393.1604.
The synthesis of embodiment 8:IIC
Amide, alpha-carbonyl diazonium compound, solvent, catalyst, oxidant are selected respectively to 8- aminoquinoline to methoxyl group
Benzamide, 2- diazonium -1- carbonyl propiophenone, 1,2- dichloroethanes, acetylacetone cobalt, TBHP, the dosage of raw material is respectively 8-
Aminoquinoline benzamide 0.1mmol, 2- diazonium -1- carbonyl propiophenone 0.2mmol, solvent 1ml, acetylacetone cobalt 10mol%,
TBHP 0.3mmol, it reacts 12 hours at 30 DEG C, then filters, column chromatographs to obtain target product formula (IIC), brown solid, separation
Yield 90%.mp 221-223℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3) δ 8.61 (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 spec data: HRMS (ESI) calcd for C26H21N2O3[M+H]+:409.1547,found
409.1549.
The synthesis of embodiment 9:IID
Amide, alpha-carbonyl diazonium compound, solvent, catalyst, oxidant are selected respectively to 8- aminoquinoline to fluoroform
Yl-benzamide, 2- diazonium -1- carbonyl propiophenone, 1,2- dichloroethanes, acetylacetone cobalt, TBHP, the dosage of raw material are respectively
8- aminoquinoline benzamide 0.1mmol, 2- diazonium -1- carbonyl propiophenone 0.2mmol, solvent 1ml, acetylacetone cobalt 10mol%,
TBHP 0.3mmol, it reacts 12 hours at 30 DEG C, then filters, column chromatographs to obtain target product formula (IID), brown solid, separation
Yield 73%.mp 135-137℃.
Nuclear magnetic data:1HNMR(400MHz,CDCl3) δ 8.64 (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):δ
195.2,168.7,148.6,147.8,142.8,136.9,136.7,135.2,134.8,134.7,133.7,132.1,
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 spec data: HRMS (ESI) calcd for C26H18F3N2O2[M+H]+:447.1315,
found447.1321.
The synthesis of embodiment 10:IIE
Amide, alpha-carbonyl diazonium compound, solvent, catalyst, oxidant are selected respectively to 8- aminoquinoline to fluorobenzene first
Amide, 2- diazonium -1- carbonyl propiophenone, 1,2- dichloroethanes, acetylacetone cobalt, TBHP, the dosage of raw material is respectively 8- amino
Quinoline benzamide 0.1mmol, 2- diazonium -1- carbonyl propiophenone 0.2mmol, solvent 1ml, acetylacetone cobalt 10mol%,
TBHP0.3mmol, it reacts 6 hours at 30 DEG C, then filters, column chromatographs to obtain target product formula (IIE), yellow solid, and separation is received
Rate 83%.mp 148-150℃.
Nuclear magnetic data:1H NMR(400MHz,CDCl3) δ 8.62 (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 spec data: HRMS (ESI) calcd for C25H18FN2O2[M+H]+:397.1347,found
397.1353.
For above-described embodiment only for illustrating technical concepts and features of the invention, its object is to allow those skilled in the art
It cans understand the content of the present invention and implement it accordingly, it is not intended to limit the scope of the present invention.It is all according to the present invention
Equivalent change or modification made by the essence of content, all covers in the scope of the present invention.
Claims (11)
1. liang class isoindolinone derivatives, which is characterized in that its structure such as formula (I), shown in (II):
Wherein, R1For hydrogen, halogen, trifluoromethyl, C1-C10 alkyl, C1-C10 alkoxy, N, N dimethyl；
R2For phenyl, the phenyl of electrophilic or electron donating group substituent group, C1-C10 alkoxy, the electron-withdrawing group is halogen,
Electron donating group is C1-C10 alkyl, C1-C10 alkoxy.
2. a kind of synthetic method of the isoindoline ketones derivant as shown in formula (I), which is characterized in that with aromatic amides class
Closing object and alpha-carbonyl diazonium compound is raw material, and under the action of catalyst, oxidant, synthesis obtains different as shown in formula (I)
Indoline ketone derivative, shown in reaction process such as formula (III):
Wherein, R1、R2Definition with claim 1.
3. synthetic method as claimed in claim 2, which is characterized in that the specific steps are that: in a solvent, with aromatic amides class
Compound and alpha-carbonyl diazonium compound are raw material, and the first step activates C (sp under the action of catalyst2)-H key；Second step,
Under oxidant effect, α-diazonium compound is converted into ketenes intermediate, selectively inserts to the C-M of formation, and reduction is eliminated
Synthesis obtains the isoindoline ketones derivant as shown in formula (I) afterwards.
4. synthetic method as claimed in claim 2 or claim 3, which is characterized in that the catalyst includes CoBr2、Co(OAc)2、Co
(acac)2One of or it is a variety of；The oxidant includes AgOAc, Ag2CO3、AgOTf、AgSbF6、K2S2O8、TEMPO、TBHP
One of or it is a variety of；The aromatic amides class compound, alpha-carbonyl diazonium compound, catalyst, oxidant molar ratio be
1.0:2.0:0.1:3.5.
5. synthetic method as claimed in claim 3, which is characterized in that the solvent is 1,2- dichloroethanes, toluene, tetrahydro furan
It one of mutters or a variety of；The volumetric usage of the solvent is 1.0-2.0mL.
6. synthetic method as claimed in claim 2, which is characterized in that the temperature of the reaction is 100-140 DEG C；The reaction
Time be 12-24 hours.
7. a kind of synthetic method of the isoindoline ketones derivant as shown in formula (II), which is characterized in that with aromatic amides class
Compound and alpha-carbonyl diazonium compound are raw material, different to diazonium compound under conditions of changing catalyst, oxidant
Site carries out function dough, and synthesis obtains the isoindoline ketones derivant as shown in formula (II), reaction process such as formula (IV)
It is shown:
Wherein, R1、R2Definition with claim 1.
8. synthetic method as claimed in claim 7, which is characterized in that the specific steps are that: in a solvent, with aromatic amides class
Compound and alpha-carbonyl diazonium compound are raw material, activate C (sp under the action of catalyst2)-H key, while in catalyst action
Under, alpha-carbonyl diazonium compound generates metal carbene intermediate, carries out migration insertion to the C-M of formation, reduction synthesizes after eliminating
Obtain the isoindoline ketones derivant as shown in formula (II).
9. synthetic method as claimed in claim 7 or 8, which is characterized in that the catalyst includes CoBr2、Co(OAc)2、Co
(acac)2One of or it is a variety of；Oxidant includes one of DTBP, TBHP or a variety of；The aromatic amides class compound,
Alpha-carbonyl diazonium compound, catalyst, oxidant molar ratio be 1.0:2.0:0.1:2.0.
10. synthetic method as claimed in claim 8, which is characterized in that the solvent be one of 1,2- dichloroethanes or
It is a variety of；The volumetric usage of the solvent is 1.0-2.0mL.
11. synthetic method as claimed in claim 7, which is characterized in that the temperature of the reaction is 30-130 DEG C；The reaction
Time be 6-12 hours.
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| CN112961086A (en) * | 2021-02-05 | 2021-06-15 | 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 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112961086A (en) * | 2021-02-05 | 2021-06-15 | 齐鲁工业大学 | 2-methylene-1-indanone derivative and synthesis method thereof |
| 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 |
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