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2020 Volume 40 Issue 3
2020, 40(3): 551-562
doi: 10.6023/cjoc201911007
Abstract:
Polycyclic xanthone natural products are a family of polyketides which are characterized by highly oxygenated angular hexacyclic frameworks. In the last decade, there has been a noticeable increase in reports on both synthetic and pharmacological investigations of this class of natural molecules due to their unique chemical structures and biological activities. Most members of this class of molecules show strong activities towards Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, potent antifungal activity and antitumour activity. The synthetic studies of some members of this class of natural products is summarized.
Polycyclic xanthone natural products are a family of polyketides which are characterized by highly oxygenated angular hexacyclic frameworks. In the last decade, there has been a noticeable increase in reports on both synthetic and pharmacological investigations of this class of natural molecules due to their unique chemical structures and biological activities. Most members of this class of molecules show strong activities towards Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, potent antifungal activity and antitumour activity. The synthetic studies of some members of this class of natural products is summarized.
2020, 40(3): 563-574
doi: 10.6023/cjoc201910031
Abstract:
Over the last decades, the transition metal-catalyzed cross-coupling reactions have become powerful organic synthetic methods for forming carbon-carbon and carbon-heteroatom bonds. Very recently, the introduction of visible light into transition metal catalysis opened a new avenue for achieving novel, highly enabling cross-coupling reactions that otherwise were elusive. This type of reaction has received extensive attention due to its simple, mild conditions and no need of photocatalyst. Based on the classification of transition metals, the research progress of transition metal-catalyzed cross-coupling reactions directly promoted by visible light is reviewed.
Over the last decades, the transition metal-catalyzed cross-coupling reactions have become powerful organic synthetic methods for forming carbon-carbon and carbon-heteroatom bonds. Very recently, the introduction of visible light into transition metal catalysis opened a new avenue for achieving novel, highly enabling cross-coupling reactions that otherwise were elusive. This type of reaction has received extensive attention due to its simple, mild conditions and no need of photocatalyst. Based on the classification of transition metals, the research progress of transition metal-catalyzed cross-coupling reactions directly promoted by visible light is reviewed.
2020, 40(3): 575-588
doi: 10.6023/cjoc201910010
Abstract:
Enantiopure amines are important building blocks with a plethora of applications in the fields of medicine, agriculture and materials. Kinetic resolution (KR) of racemic amines is one of the most important methods for obtaining enantiopure amines. However, KR of amines is little investigated because of their high reactivity and coordinating ability in the corresponding KR of alcohols. Till now, major developments using non-enzymatic catalysts for KR of amines have been extensively achieved by catalytic acylation (or deacylation). Only recently the non-acylation KR of amines is improving. The relatively wide range of different catalytic asymmetric reactions have been employed as strategies for the efficient KR of amines. For some cases, the asymmetric reactions do not involve with nitrogen atoms of racemic substrates. This review aims to introduce the development of the non-acylation KR of amines for the synthesis of enantiopure amines.
Enantiopure amines are important building blocks with a plethora of applications in the fields of medicine, agriculture and materials. Kinetic resolution (KR) of racemic amines is one of the most important methods for obtaining enantiopure amines. However, KR of amines is little investigated because of their high reactivity and coordinating ability in the corresponding KR of alcohols. Till now, major developments using non-enzymatic catalysts for KR of amines have been extensively achieved by catalytic acylation (or deacylation). Only recently the non-acylation KR of amines is improving. The relatively wide range of different catalytic asymmetric reactions have been employed as strategies for the efficient KR of amines. For some cases, the asymmetric reactions do not involve with nitrogen atoms of racemic substrates. This review aims to introduce the development of the non-acylation KR of amines for the synthesis of enantiopure amines.
2020, 40(3): 589-597
doi: 10.6023/cjoc201909032
Abstract:
The C-N bond is widely found in medicinal molecules, natural products and functional materials. Therefore, it has great significance to develop simple and efficient methods for the construction of C-N bond. Recently, remarkable progress has been made in construction of C-N bond involving C(sp2)-H bond through transition-metal-free radical reactions. Due to the relatively mild reaction condition and high reactivity, it provides a novel approach to construct C-N bond. In this review, the recent developments in this area are summarized on the basis of different nitrogen sources.
The C-N bond is widely found in medicinal molecules, natural products and functional materials. Therefore, it has great significance to develop simple and efficient methods for the construction of C-N bond. Recently, remarkable progress has been made in construction of C-N bond involving C(sp2)-H bond through transition-metal-free radical reactions. Due to the relatively mild reaction condition and high reactivity, it provides a novel approach to construct C-N bond. In this review, the recent developments in this area are summarized on the basis of different nitrogen sources.
2020, 40(3): 598-613
doi: 10.6023/cjoc201909030
Abstract:
Alkyl carboxylic acids are among the most ubiquitous organic molecules found in nature. The reactions using abundant carboxylic acid and its derivatives as starting materials deserve widespread attention over the world. They are often easy to generate alkyl radical by photoredox catalysis under mild conditions for building various chemical bonds in organic chemistry. Based on the reaction modes, decarboxylation of alkylcarboxylic acids and their derivatives, the recent progress in decarboxylation of alkylcarboxylic acids and their derivatives under visible light is reviewed.
Alkyl carboxylic acids are among the most ubiquitous organic molecules found in nature. The reactions using abundant carboxylic acid and its derivatives as starting materials deserve widespread attention over the world. They are often easy to generate alkyl radical by photoredox catalysis under mild conditions for building various chemical bonds in organic chemistry. Based on the reaction modes, decarboxylation of alkylcarboxylic acids and their derivatives, the recent progress in decarboxylation of alkylcarboxylic acids and their derivatives under visible light is reviewed.
2020, 40(3): 614-624
doi: 10.6023/cjoc201909029
Abstract:
Because of the N-H group structure in the macrocyclic compound containing hydrogen bond Donors, it can provide additional intermolecular forces in the host-guest chemistry, and this character is widely used in the molecular recognition, self-assembly, supramolecular catalysis and other fields. The recent progress on the synthetic methods of macrocyclic compounds based on (thio) urea, amide and its molecular recognition in 2010~2019 are summarized. It is hoped that this review can be referred to synthesis and applications of this kind of macrocyclic compounds.
Because of the N-H group structure in the macrocyclic compound containing hydrogen bond Donors, it can provide additional intermolecular forces in the host-guest chemistry, and this character is widely used in the molecular recognition, self-assembly, supramolecular catalysis and other fields. The recent progress on the synthetic methods of macrocyclic compounds based on (thio) urea, amide and its molecular recognition in 2010~2019 are summarized. It is hoped that this review can be referred to synthesis and applications of this kind of macrocyclic compounds.
2020, 40(3): 625-644
doi: 10.6023/cjoc201909015
Abstract:
Ligands can regulate both the steric and electronic effects of the catalytic center in transition-metal-catalyzed C-H activation reactions, leading to the site-selective C-H functionalization of arenes. In recent years, ligand-promoted remote C-H functionalization of arenes has developed rapidly. The recent progress on ligand-promoted transition-metal-catalyzed remote meta-selective C-H bond functionalization of arenes is summarized, and the limitations of the research field and prospects for future development are presented.
Ligands can regulate both the steric and electronic effects of the catalytic center in transition-metal-catalyzed C-H activation reactions, leading to the site-selective C-H functionalization of arenes. In recent years, ligand-promoted remote C-H functionalization of arenes has developed rapidly. The recent progress on ligand-promoted transition-metal-catalyzed remote meta-selective C-H bond functionalization of arenes is summarized, and the limitations of the research field and prospects for future development are presented.
2020, 40(3): 645-650
doi: 10.6023/cjoc201912018
Abstract:
The C=C double bond cleavage of NH2-functionalized enaminones has been realized at room temperature to provide various N-sulfonyl amidines by reacting with sulfonyl azides. The reactions take place with good substrate tolerance in the presence of 1, 8-Diazabicyclo[5.4.0]undec-7-ene (DBU) without any metal or oxidant reagent. The 15N-labelling experiment on enaminone indicates that the sulfonyl azide component donates solely the sulfonamide fragment, and the reaction mechanism involving a key decomposition of the in situ generated 1, 2, 3-triazoline intermediate is convictively supported.
The C=C double bond cleavage of NH2-functionalized enaminones has been realized at room temperature to provide various N-sulfonyl amidines by reacting with sulfonyl azides. The reactions take place with good substrate tolerance in the presence of 1, 8-Diazabicyclo[5.4.0]undec-7-ene (DBU) without any metal or oxidant reagent. The 15N-labelling experiment on enaminone indicates that the sulfonyl azide component donates solely the sulfonamide fragment, and the reaction mechanism involving a key decomposition of the in situ generated 1, 2, 3-triazoline intermediate is convictively supported.
2020, 40(3): 651-662
doi: 10.6023/cjoc201911016
Abstract:
A nickel-catalyzed Negishi coupling of cyclobutanone oxime esters with aryl zinc reagents has been developed, in which nickel serves both as an initiator for imine radicals and a catalyst for the coupling of aryl zinc reagents with oxime esters. The protocol can avoid the use of poisonous cyanide and has broad substrate scope as well as good functional group compatibility. Therefore, this method provides an attractive strategy for the synthesis of valuable nitriles. Preliminary mechanistic studies indicate that a radical pathway is involved in the product formation.
A nickel-catalyzed Negishi coupling of cyclobutanone oxime esters with aryl zinc reagents has been developed, in which nickel serves both as an initiator for imine radicals and a catalyst for the coupling of aryl zinc reagents with oxime esters. The protocol can avoid the use of poisonous cyanide and has broad substrate scope as well as good functional group compatibility. Therefore, this method provides an attractive strategy for the synthesis of valuable nitriles. Preliminary mechanistic studies indicate that a radical pathway is involved in the product formation.
2020, 40(3): 688-693
doi: 10.6023/cjoc201909021
Abstract:
The Ru(Ⅱ)-catalyzed regioselective[4+1] cycloaddition of azobenzenes with ethyl glyoxalate through C-H bond activation has been developed. This method provides a facile approach to various 3-carboxylate indazoles in moderate to good yields. Meantime, the kinetic isotope effect was further investigated and the results indicated that the C-H bond-breaking was possibly not involved in the rate-limiting step of this transformation.
The Ru(Ⅱ)-catalyzed regioselective[4+1] cycloaddition of azobenzenes with ethyl glyoxalate through C-H bond activation has been developed. This method provides a facile approach to various 3-carboxylate indazoles in moderate to good yields. Meantime, the kinetic isotope effect was further investigated and the results indicated that the C-H bond-breaking was possibly not involved in the rate-limiting step of this transformation.
2020, 40(3): 694-703
doi: 10.6023/cjoc201909009
Abstract:
The catalyst-free domino reaction of ethyl 4-hydroxyalkyl-2-ynoate and N-heteroaryl-methyl-N-2, 2-difluoroethan-1-amine was developed, and used to synthesize 4-(N-(2, 2-difluoroethyl)(N-heteroarylmethyl)amino)-5, 5-disubstitutedfuran-2(5H)-one in methanol under the reflux condition with yields of 39%~83%. Their structures were characterized by 1H NMR, 13C NMR, and HR-ESI-MS data, further confirmed by the X-ray crystal diffraction of 3-chloro-4-((N-2, 2-difluoroethyl)(N-pyrimidin-5-ylmethyl)amino)-5, 5-spiro(4-methoxycyclohexyl)furan-2(5H)-one (8). The bioassay results showed that 4-((N-2, 2-difluoroethyl)(N-6-chloropyridin-3-ylmethyl)amino)-5, 5-dimethylfuran-2(5H)-one (3a) and 4-((N-2, 2-difluoroethyl)(N-6-fluoropyridin-3-ylmethyl)-amino)-5, 5-dimethylfuran-2(5H)-one (3c) exhibit 100% mortality against Myzus persicae at the concentration of 600 μg·mL-1, respectively.
The catalyst-free domino reaction of ethyl 4-hydroxyalkyl-2-ynoate and N-heteroaryl-methyl-N-2, 2-difluoroethan-1-amine was developed, and used to synthesize 4-(N-(2, 2-difluoroethyl)(N-heteroarylmethyl)amino)-5, 5-disubstitutedfuran-2(5H)-one in methanol under the reflux condition with yields of 39%~83%. Their structures were characterized by 1H NMR, 13C NMR, and HR-ESI-MS data, further confirmed by the X-ray crystal diffraction of 3-chloro-4-((N-2, 2-difluoroethyl)(N-pyrimidin-5-ylmethyl)amino)-5, 5-spiro(4-methoxycyclohexyl)furan-2(5H)-one (8). The bioassay results showed that 4-((N-2, 2-difluoroethyl)(N-6-chloropyridin-3-ylmethyl)amino)-5, 5-dimethylfuran-2(5H)-one (3a) and 4-((N-2, 2-difluoroethyl)(N-6-fluoropyridin-3-ylmethyl)-amino)-5, 5-dimethylfuran-2(5H)-one (3c) exhibit 100% mortality against Myzus persicae at the concentration of 600 μg·mL-1, respectively.
Cobalt-Catalyzed Bidentate-Assisted Regioselective C—H Alkoxylation of 1-Naphthylamide with Alcohols
2020, 40(3): 714-723
doi: 10.6023/cjoc201908040
Abstract:
The cobalt-catalyzed regioselective C-H alkoxylation of 1-naphthylamide with alcohols through a bidentate-chelation assistance has been developed. In this transformation, not only primary and secondary alcohols, but also aliphatic diols and oligoethylene glycols, which always be employed as O, O-donor ligands and reducing agents in transition metal catalyzed coupling reaction, were all tolerated under current reaction conditions. It is noteworthy that deuterium labeled 8-alkoxyl-1-N-(naphthalen-1-yl)picolinamide derivative was easily achieved under this catalytic system. In addition, control experiments suggested that picolinoyl was the key directing group, and furthermore, the C(8)-H alkoxylation reaction might proceed through a single-electron-transfer (SET) process.
The cobalt-catalyzed regioselective C-H alkoxylation of 1-naphthylamide with alcohols through a bidentate-chelation assistance has been developed. In this transformation, not only primary and secondary alcohols, but also aliphatic diols and oligoethylene glycols, which always be employed as O, O-donor ligands and reducing agents in transition metal catalyzed coupling reaction, were all tolerated under current reaction conditions. It is noteworthy that deuterium labeled 8-alkoxyl-1-N-(naphthalen-1-yl)picolinamide derivative was easily achieved under this catalytic system. In addition, control experiments suggested that picolinoyl was the key directing group, and furthermore, the C(8)-H alkoxylation reaction might proceed through a single-electron-transfer (SET) process.
2020, 40(3): 740-747
doi: 10.6023/cjoc201907040
Abstract:
A highly efficient and regioselective C-3-alkylation of 2-arylindoles with maleimides has been developed using Ag(I) as catalyst. 3-(2-Aryl-1H-indol-3-yl)pyrrolidine-2, 5-diones were afforded with high yields (up to 97%) under relatively mild reaction conditions. The method features operational simplicity and avoiding external oxidant.
A highly efficient and regioselective C-3-alkylation of 2-arylindoles with maleimides has been developed using Ag(I) as catalyst. 3-(2-Aryl-1H-indol-3-yl)pyrrolidine-2, 5-diones were afforded with high yields (up to 97%) under relatively mild reaction conditions. The method features operational simplicity and avoiding external oxidant.
2020, 40(3): 748-755
doi: 10.6023/cjoc201907032
Abstract:
Four D-A-D-A-D structured organic small molecules (OSMs) DOBT-8T, BT-8T, FBT-8T and FFBT-8T have been designed for organic solar cells, which contain tetrathiophene as the core donor unit, bithiophene as the termial donor unit, combining different electron-withdrawing fragments DOBT, BT, FBT and FFBT as acceptor unit, respectively. The designed four OSMs were analyzed using density functional theory (DFT) and time dependent-DFT (TDDFT) calculations at B3LYP/6-31G(d) level. The effects of structure modification of benzothiadiazole acceptor unit on modulating the electron-donating ability of OSMs were fully investigated. Results showed that the geometrical structure, the band-gap, HOMO/LUMO energy levels, orbital spatial distribution, energetic driving force, open-circuit voltage and NPA atomic charge of these OSMs can be systematically altered by varying the electron-withdrawing properties with different benzothiadiazole acceptor units. Compared to other OSMs, FBT-8T displayed the more narrowed Eg and relatively deeper HOMO level with FBT as acceptor. FFBT-8T exhibited the most deep-lying HOMO level of the four designed OSMs and suitable Eg value by using FFBT as acceptor. The power conversion efficiencies (PCEs) of ca. 4.7% and ca. 5.2% were achieved by the photovoltaic devices based on FBT-8T:PC61BM and FFBT-8T:PC61BM systems, respectively, predicting with Scharber models. On the basis of these results, FBT-8T and FFBT-8T as potential OSMs donor materials for high-efficiency organic bulk hetero-junction solar cell were proposed.
Four D-A-D-A-D structured organic small molecules (OSMs) DOBT-8T, BT-8T, FBT-8T and FFBT-8T have been designed for organic solar cells, which contain tetrathiophene as the core donor unit, bithiophene as the termial donor unit, combining different electron-withdrawing fragments DOBT, BT, FBT and FFBT as acceptor unit, respectively. The designed four OSMs were analyzed using density functional theory (DFT) and time dependent-DFT (TDDFT) calculations at B3LYP/6-31G(d) level. The effects of structure modification of benzothiadiazole acceptor unit on modulating the electron-donating ability of OSMs were fully investigated. Results showed that the geometrical structure, the band-gap, HOMO/LUMO energy levels, orbital spatial distribution, energetic driving force, open-circuit voltage and NPA atomic charge of these OSMs can be systematically altered by varying the electron-withdrawing properties with different benzothiadiazole acceptor units. Compared to other OSMs, FBT-8T displayed the more narrowed Eg and relatively deeper HOMO level with FBT as acceptor. FFBT-8T exhibited the most deep-lying HOMO level of the four designed OSMs and suitable Eg value by using FFBT as acceptor. The power conversion efficiencies (PCEs) of ca. 4.7% and ca. 5.2% were achieved by the photovoltaic devices based on FBT-8T:PC61BM and FFBT-8T:PC61BM systems, respectively, predicting with Scharber models. On the basis of these results, FBT-8T and FFBT-8T as potential OSMs donor materials for high-efficiency organic bulk hetero-junction solar cell were proposed.
2020, 40(3): 663-668
doi: 10.6023/cjoc201910022
Abstract:
The promotion of two sulfate or carboxylate-bearing acyclic cucurbiturils for the water-solubility of arenes and aromatic aldehydes is described. 1H NMR experiments reveals that sulfate-bearing acyclic cucurbituril (acCB-1) signficantly improves the water-solubility of a number of arenes and aldehydes. For 4, 4'-dimethylbiphenyl and biphenyl-4, 4'-dicarbaldehyde, the solubility can be improved to 8.9 and 11.2 mmol/L, respectively. 19F NMR experiments demonstrate that carboxylate-bearing acyclic cucurbituril can increase the water-solubilities of pentafluorotoluene and hexafluorobenzene to 5.6 and 3.0 mmol/L, respectively. It is also found that the water-solubilization of acCB-1 for aromatic aldehydes can promote their reaction with acylhydrazines to form hydrozone derivatives. By making use of this promotion, two hydrazone-based macrocycles can be formed from the coupling reactions of two aromatic dialdehdes and one diacylhydrazine in water.
The promotion of two sulfate or carboxylate-bearing acyclic cucurbiturils for the water-solubility of arenes and aromatic aldehydes is described. 1H NMR experiments reveals that sulfate-bearing acyclic cucurbituril (acCB-1) signficantly improves the water-solubility of a number of arenes and aldehydes. For 4, 4'-dimethylbiphenyl and biphenyl-4, 4'-dicarbaldehyde, the solubility can be improved to 8.9 and 11.2 mmol/L, respectively. 19F NMR experiments demonstrate that carboxylate-bearing acyclic cucurbituril can increase the water-solubilities of pentafluorotoluene and hexafluorobenzene to 5.6 and 3.0 mmol/L, respectively. It is also found that the water-solubilization of acCB-1 for aromatic aldehydes can promote their reaction with acylhydrazines to form hydrozone derivatives. By making use of this promotion, two hydrazone-based macrocycles can be formed from the coupling reactions of two aromatic dialdehdes and one diacylhydrazine in water.
2020, 40(3): 669-678
doi: 10.6023/cjoc201909042
Abstract:
A series of novel hybrid compounds between piperonyl and imidazolium salts were prepared from tryptophol by four steps of reduction, mesylation, coupling and salt formation. Their structures were confirmed by 1H NMR, 13C NMR, HRMS and X-ray crystallographic analysis. These compounds were evaluated in vitro against a panel of human tumor cell lines. The results showed that 1-((benzo[d] [1, 3]dioxol-5-ylmethyl)-3-(2-naphthylmethyl))-5, 6-dimethyl-1H-benzo[d]imidazol-3-ium bromide (30) exhibited remarkable inhibitory activity selectively against HL-60, SMMC-7721, A-549, MCF-7 and SW480 cell lines compared with DDP. In particular, the compound was more selective to HL-60 cell lines with IC50 values 7.2-fold lower than DDP. Further studies showed that compound 30 has the effect of inducing SMMC-7721 cell line arrest and cell apoptosis in cell cycle G0/G1.
A series of novel hybrid compounds between piperonyl and imidazolium salts were prepared from tryptophol by four steps of reduction, mesylation, coupling and salt formation. Their structures were confirmed by 1H NMR, 13C NMR, HRMS and X-ray crystallographic analysis. These compounds were evaluated in vitro against a panel of human tumor cell lines. The results showed that 1-((benzo[d] [1, 3]dioxol-5-ylmethyl)-3-(2-naphthylmethyl))-5, 6-dimethyl-1H-benzo[d]imidazol-3-ium bromide (30) exhibited remarkable inhibitory activity selectively against HL-60, SMMC-7721, A-549, MCF-7 and SW480 cell lines compared with DDP. In particular, the compound was more selective to HL-60 cell lines with IC50 values 7.2-fold lower than DDP. Further studies showed that compound 30 has the effect of inducing SMMC-7721 cell line arrest and cell apoptosis in cell cycle G0/G1.
2020, 40(3): 679-687
doi: 10.6023/cjoc201909036
Abstract:
Seven new monoterpenoid indole alkaloids, kopsiofficines A~G, together with twenty known alkaloids, were isolated from the stems of Kopsia officinalis. Their structures were elucidated on the basis of extensive spectroscopic methods. The anti-inflammatory activities of all alkaloids were evaluated on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells by the inhibiting the production of IL-1β, PGE2 and TNF-α. Among them, kopsiofficines A (1), kopsiofficines B (2), kopsiofficines D (4), kopsiofficines F (6), kopsiofficines G (7), 12-methoxykopsine (11), kopsinoline (15), (-)-N-methoxycarbonyl-11, 12-methylenedioxykopsinaline (16), kopsinine (18) and kopsinic acid (20) exhibited significant anti-inflammatory activity, which were comparable to that of dexamethasone. The results supposed that the acetonyl group at C-5 of monoterpenoid indole alkaloids play an important role in their anti-inflammatory activity.
Seven new monoterpenoid indole alkaloids, kopsiofficines A~G, together with twenty known alkaloids, were isolated from the stems of Kopsia officinalis. Their structures were elucidated on the basis of extensive spectroscopic methods. The anti-inflammatory activities of all alkaloids were evaluated on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells by the inhibiting the production of IL-1β, PGE2 and TNF-α. Among them, kopsiofficines A (1), kopsiofficines B (2), kopsiofficines D (4), kopsiofficines F (6), kopsiofficines G (7), 12-methoxykopsine (11), kopsinoline (15), (-)-N-methoxycarbonyl-11, 12-methylenedioxykopsinaline (16), kopsinine (18) and kopsinic acid (20) exhibited significant anti-inflammatory activity, which were comparable to that of dexamethasone. The results supposed that the acetonyl group at C-5 of monoterpenoid indole alkaloids play an important role in their anti-inflammatory activity.
2020, 40(3): 704-713
doi: 10.6023/cjoc201909002
Abstract:
A novel tandem metal relay catalytic system of Zn/Y has been successfully developed. By using this unprecedented Zn(OTf)2/Y(OTf)3 bimetallic relay catalytic system, a variety of oxazole α-hydroxy amides derivatives were obtained from easily available N-(propargyl)-arylamides and various 1-benzylindoline-2, 3-dione derivatives through intramolecular cycloisomerization/intermolecular Alder-ene reaction under mild conditions. The first step of the one-pot procedure is that Zn(OTf)2 acts as a π acid to activate the triple bond of N-(propargyl)-arylamides, and a subsequent intramolecular 5-exo-dig cyclization forms the oxazoline intermediate. Separately, Y(OTf)3 acts as Lewis acid, then oxazoline intermediate and 1-benzylindoline-2, 3-dione derivatives are transformed to the oxazole α-hydroxy amide derivatives in good to excellent yields in an intermolecular Alder-ene reaction. Control experiments in the optimization section disclose the fact that Zn(OTf)2 and Y(OTf)3 are both indispensable for this intramolecular cycloisomerization/intermolecular Alder-ene reaction. Generally, the synthetic reactions run under air atmosphere by heating all the substrates and reagents in one-pot at 100℃. The present method benefits from the distinctive features of simple reaction conditions, high atom economy and broad substrate tolerance. It is of great significance for the synthesis of oxazole derivatives.
A novel tandem metal relay catalytic system of Zn/Y has been successfully developed. By using this unprecedented Zn(OTf)2/Y(OTf)3 bimetallic relay catalytic system, a variety of oxazole α-hydroxy amides derivatives were obtained from easily available N-(propargyl)-arylamides and various 1-benzylindoline-2, 3-dione derivatives through intramolecular cycloisomerization/intermolecular Alder-ene reaction under mild conditions. The first step of the one-pot procedure is that Zn(OTf)2 acts as a π acid to activate the triple bond of N-(propargyl)-arylamides, and a subsequent intramolecular 5-exo-dig cyclization forms the oxazoline intermediate. Separately, Y(OTf)3 acts as Lewis acid, then oxazoline intermediate and 1-benzylindoline-2, 3-dione derivatives are transformed to the oxazole α-hydroxy amide derivatives in good to excellent yields in an intermolecular Alder-ene reaction. Control experiments in the optimization section disclose the fact that Zn(OTf)2 and Y(OTf)3 are both indispensable for this intramolecular cycloisomerization/intermolecular Alder-ene reaction. Generally, the synthetic reactions run under air atmosphere by heating all the substrates and reagents in one-pot at 100℃. The present method benefits from the distinctive features of simple reaction conditions, high atom economy and broad substrate tolerance. It is of great significance for the synthesis of oxazole derivatives.
2020, 40(3): 724-730
doi: 10.6023/cjoc201908036
Abstract:
Cu(Ⅱ)-promoted dimethylthiolation of C(sp2)-H bonds using DMSO as the methylthiolation source with the assistance of an 8-aminoquinoline directing group have been developed. A number of dimethylthiolated benzamides were efficiently synthesized using CuSO4·5H2O as a promoter in moderate to good yields. In addition, this reaction system features facile conditions and no other oxidant additive was required.
Cu(Ⅱ)-promoted dimethylthiolation of C(sp2)-H bonds using DMSO as the methylthiolation source with the assistance of an 8-aminoquinoline directing group have been developed. A number of dimethylthiolated benzamides were efficiently synthesized using CuSO4·5H2O as a promoter in moderate to good yields. In addition, this reaction system features facile conditions and no other oxidant additive was required.
2020, 40(3): 731-739
doi: 10.6023/cjoc201907052
Abstract:
In order to find new anti-tumor drugs, a series of novel 1, 3, 4-oxadiazole and 1, 3, 4-thiadiazole derivatives were designed and synthesized. The target compounds were evaluated for antitumor activity in vitro on four human cancer cell lines including B-16 (skin melanoma cells), PC-3 (human prostate cancer cells), U87 (human primary glioblastoma cells) and A549 (human non-small cell lung cancer cells). The results displayed that some of the compounds had good activities, especially, 5-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-N-(2-methoxyphenyl)-1, 3, 4-thiadiazole-2-carboxamide (8b) and 5-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-N-(4-methoxyphenyl)-1, 3, 4-thiadiazole-2-carboxamide (8c) showed high antitumor activities against four cancer cell lines, which was better than dasatinib. These compounds were further studied for their possible target of tumor suppression.
In order to find new anti-tumor drugs, a series of novel 1, 3, 4-oxadiazole and 1, 3, 4-thiadiazole derivatives were designed and synthesized. The target compounds were evaluated for antitumor activity in vitro on four human cancer cell lines including B-16 (skin melanoma cells), PC-3 (human prostate cancer cells), U87 (human primary glioblastoma cells) and A549 (human non-small cell lung cancer cells). The results displayed that some of the compounds had good activities, especially, 5-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-N-(2-methoxyphenyl)-1, 3, 4-thiadiazole-2-carboxamide (8b) and 5-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-N-(4-methoxyphenyl)-1, 3, 4-thiadiazole-2-carboxamide (8c) showed high antitumor activities against four cancer cell lines, which was better than dasatinib. These compounds were further studied for their possible target of tumor suppression.
2020, 40(3): 756-762
doi: 10.6023/cjoc201907030
Abstract:
The[3+2] cycloaddition of methylenedihydrobenzofurandiones and nitrilimines worked efficiently in CHCl3 at room temperature in the presence of Et3N, producing biologically interesting spirocyclic pyrazole derivatives in high yield (78%~94%) with excellent diastereoselectivity.
The[3+2] cycloaddition of methylenedihydrobenzofurandiones and nitrilimines worked efficiently in CHCl3 at room temperature in the presence of Et3N, producing biologically interesting spirocyclic pyrazole derivatives in high yield (78%~94%) with excellent diastereoselectivity.
2020, 40(3): 763-773
doi: 10.6023/cjoc201905030
Abstract:
Polymer 3 based on 1-(4-hexyloxy)-benzene and 2, 4, 6-triphenyl-1, 3, 5-triazine functionalized fluorene units was synthesized and characterized, whose optoelectronic properties were further compared with those of poly(9, 9-dihexyl-fluorene) (1) and poly(9, 9-di(1-(4-hexyloxy)-phenyl)-fluorene) (2). The 5% weight loss temperatures of polymers 1, 2 and 3 thin solid powders are 274, 318 and 401℃, and their glass transition temperatures in the same state are 91, 120 and 139℃, respectively. The maximum absorption and photoluminescent emission peaks of polymers 1, 2 and 3 in toluene solution are 380 and 435 nm, and their optical band gaps in toluene solution are 2.95, 2.95 and 2.91 eV. The triplet energy levels of polymers 1, 2 and 3 are 2.82, 2.81 and 2.97 eV, while their singlet energy levels are 3.14, 3.13 and 3.12 eV, which makes the singlet-triplet energy splitting gaps for polymers 1, 2 and 3 to be 0.32, 0.32 and 0.15 eV. The highest occupied molecular orbital energy levels of polymers 1, 2 and 3 are -5.72, -5.95 and -5.96 eV and the lowest unoccupied molecular orbital energy levels are -2.70, -2.39 and -2.34 eV. The introduction of 4-hexoxybenzene widened the energy band gaps of the polymers, while the electron deficient 2, 4, 6-triphenyl-1, 3, 5-triazine made the single-triplet energy splitting gaps of the polymers successively decreased, but it did not endow polymer 3 with thermally activated delayed fluorescence characteristic. With the introduction of rigid and electron deficient 2, 4, 6-triphenyl-1, 3, 5-triazine into the 9-carbon of the fluorene units in the polymer, the thermal stability, color purity and photostability of blue light emitting solid were improved in the turn of polymers 1, 2 and 3, which were further validated by the stable electroluminescent spectra of polymer 3. The wide-angle X-ray diffraction results of the polymers 1, 2 and 3 powders show that all polymers have excellent amorphous properties in nature. The phase diversity of polymer 3 powder locates between those of polymers 1 and 2, and the alkoxyl phenyl substituted group on the polymer 2 side chain is helpful to improve the diversity of ordered morphology in solid powder. The random copolymer 3 exhibits much better photoelectric properties than those of polymers 1 and 2.
Polymer 3 based on 1-(4-hexyloxy)-benzene and 2, 4, 6-triphenyl-1, 3, 5-triazine functionalized fluorene units was synthesized and characterized, whose optoelectronic properties were further compared with those of poly(9, 9-dihexyl-fluorene) (1) and poly(9, 9-di(1-(4-hexyloxy)-phenyl)-fluorene) (2). The 5% weight loss temperatures of polymers 1, 2 and 3 thin solid powders are 274, 318 and 401℃, and their glass transition temperatures in the same state are 91, 120 and 139℃, respectively. The maximum absorption and photoluminescent emission peaks of polymers 1, 2 and 3 in toluene solution are 380 and 435 nm, and their optical band gaps in toluene solution are 2.95, 2.95 and 2.91 eV. The triplet energy levels of polymers 1, 2 and 3 are 2.82, 2.81 and 2.97 eV, while their singlet energy levels are 3.14, 3.13 and 3.12 eV, which makes the singlet-triplet energy splitting gaps for polymers 1, 2 and 3 to be 0.32, 0.32 and 0.15 eV. The highest occupied molecular orbital energy levels of polymers 1, 2 and 3 are -5.72, -5.95 and -5.96 eV and the lowest unoccupied molecular orbital energy levels are -2.70, -2.39 and -2.34 eV. The introduction of 4-hexoxybenzene widened the energy band gaps of the polymers, while the electron deficient 2, 4, 6-triphenyl-1, 3, 5-triazine made the single-triplet energy splitting gaps of the polymers successively decreased, but it did not endow polymer 3 with thermally activated delayed fluorescence characteristic. With the introduction of rigid and electron deficient 2, 4, 6-triphenyl-1, 3, 5-triazine into the 9-carbon of the fluorene units in the polymer, the thermal stability, color purity and photostability of blue light emitting solid were improved in the turn of polymers 1, 2 and 3, which were further validated by the stable electroluminescent spectra of polymer 3. The wide-angle X-ray diffraction results of the polymers 1, 2 and 3 powders show that all polymers have excellent amorphous properties in nature. The phase diversity of polymer 3 powder locates between those of polymers 1 and 2, and the alkoxyl phenyl substituted group on the polymer 2 side chain is helpful to improve the diversity of ordered morphology in solid powder. The random copolymer 3 exhibits much better photoelectric properties than those of polymers 1 and 2.
2020, 40(3): 774-781
doi: 10.6023/cjoc201910013
Abstract:
In search of novel pyrazole oximes with good biological activities, twenty pyrazole oxime compounds were prepared by introducing an oxazole unit into pyrazole oxime based on the structure of fenpyroximate. The structures of the target compounds were confirmed by 1H NMR, 13C NMR and elemental analysis. Preliminary bioassay displayed that some target compounds had wonderful insecticidal activities against Oriental armyworm or Aphis medicaginis at the concentrations of 500 and 100 μg/mL. At the concentration of 100 μg/mL, 5-(3-fluorophenoxy)-1, 3-dimethyl-1H-pyrazole-4-formyl-O-((5-(4-chlo-rophenyl)oxazol-2-yl)methyl)oxime (9j), 5-(4-fluorophenoxy)-1, 3-dimethyl-1H-pyrazole-4-formyl-O-((5-(4-chlorophenyl)-oxazol-2-yl)methyl)oxime (9k), 5-(4-t-butylphenoxy)-1, 3-dimethyl-1H-pyrazole-4-formyl-O-((5-(4-chlorophenyl)oxazol-2-yl)methyl)oxime (9r) and 5-(4-methoxyphenoxy)-1, 3-dimethyl-1H-pyrazole-4-formyl-O-((5-(4-chlorophenyl)oxazol-2-yl)me-thyl)oxime (9s) showed 100% mortality rate against Oriental armyworm, and 5-(4-bromophenoxy)-1, 3-dimethyl-1H-pyra-zole-4-formyl-O-((5-(4-fluorophenyl)oxazol-2-yl)methyl)oxime (9g) and 9s exhibited 100% insecticidal property against Aphis medicaginis. Additionally, compound 9s possessed 70% insecticidal activity against Tetranychus cinnabarinus at 500 μg/mL.
In search of novel pyrazole oximes with good biological activities, twenty pyrazole oxime compounds were prepared by introducing an oxazole unit into pyrazole oxime based on the structure of fenpyroximate. The structures of the target compounds were confirmed by 1H NMR, 13C NMR and elemental analysis. Preliminary bioassay displayed that some target compounds had wonderful insecticidal activities against Oriental armyworm or Aphis medicaginis at the concentrations of 500 and 100 μg/mL. At the concentration of 100 μg/mL, 5-(3-fluorophenoxy)-1, 3-dimethyl-1H-pyrazole-4-formyl-O-((5-(4-chlo-rophenyl)oxazol-2-yl)methyl)oxime (9j), 5-(4-fluorophenoxy)-1, 3-dimethyl-1H-pyrazole-4-formyl-O-((5-(4-chlorophenyl)-oxazol-2-yl)methyl)oxime (9k), 5-(4-t-butylphenoxy)-1, 3-dimethyl-1H-pyrazole-4-formyl-O-((5-(4-chlorophenyl)oxazol-2-yl)methyl)oxime (9r) and 5-(4-methoxyphenoxy)-1, 3-dimethyl-1H-pyrazole-4-formyl-O-((5-(4-chlorophenyl)oxazol-2-yl)me-thyl)oxime (9s) showed 100% mortality rate against Oriental armyworm, and 5-(4-bromophenoxy)-1, 3-dimethyl-1H-pyra-zole-4-formyl-O-((5-(4-fluorophenyl)oxazol-2-yl)methyl)oxime (9g) and 9s exhibited 100% insecticidal property against Aphis medicaginis. Additionally, compound 9s possessed 70% insecticidal activity against Tetranychus cinnabarinus at 500 μg/mL.
2020, 40(3): 782-786
doi: 10.6023/cjoc201909023
Abstract:
In order to find pesticidal lead compounds with high activity, a series of novel diamide compounds were designed and synthesized by using metalaxyl as a leading compound, as well as the principle of active substructure combination. The structures of the target compounds were confirmed by 1H NMR, 13C NMR and HRMS. The preliminary bioassay showed that compound 5j showed an 85% inhibition rate against Pseudoperoniospora cubensis at 50 mg/L, most of the target compounds had good insecticidal activity against Oriental armyworm at 500 mg/L, and compounds 5b, 5f, 5g, 5h, 5i and 5l have a mortality rate of 100% against Oriental armyworm. At 250 mg/L, the mortality rate of compounds 5f, 5h and 5l against Oriental armyworm was 50%.
In order to find pesticidal lead compounds with high activity, a series of novel diamide compounds were designed and synthesized by using metalaxyl as a leading compound, as well as the principle of active substructure combination. The structures of the target compounds were confirmed by 1H NMR, 13C NMR and HRMS. The preliminary bioassay showed that compound 5j showed an 85% inhibition rate against Pseudoperoniospora cubensis at 50 mg/L, most of the target compounds had good insecticidal activity against Oriental armyworm at 500 mg/L, and compounds 5b, 5f, 5g, 5h, 5i and 5l have a mortality rate of 100% against Oriental armyworm. At 250 mg/L, the mortality rate of compounds 5f, 5h and 5l against Oriental armyworm was 50%.
2020, 40(3): 787-793
doi: 10.6023/cjoc201908024
Abstract:
A series of novel aromatic amide compounds with N-pyridylpyrazole and 1, 3, 4-oxadiazole heterocyclic motifs were successfully synthesized with N-pyridylpyrazole carboxylic acid and 2-amino-3-methylbenzoic acid as the starting materials, via multi-step reactions of nucleophilic addition, cyclization, acylation, etc. The preliminary bioassay tests indicated that most of these compounds have apparent insecticidal activities, among which compounds N-(2-(5-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-1, 3, 4-oxadiazol-2-yl)-4-chloro-6-methylphenyl)acetamide (8a) and N-(2-(5-(3-bromo-1-(3-chloro-pyridin-2-yl)-1H-pyrazol-5-yl)-1, 3, 4-oxadiazol-2-yl)-4-chloro-6-methylphenyl)-3-chloro-2, 2-dimethylpropanamide (8e) possessed a mortality rate of 70% towards Mythimna separata Walker at the concentration of 200 mg·L-1. Some of the compounds exhibited good fungicidal activities at 50 mg·L-1 against Sclerotinia sclerotiorum with the growth inhibitory rates of 54.5%~63.6%, which is more effective than the controls of triadimefon and chlorantraniliprole. Several compounds such as N-(2-(5-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-1, 3, 4-oxadiazol-2-yl)-4-chloro-6-methylphenyl)pivalamide (8f) and N-(2-(5-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-1, 3, 4-oxadiazol-2-yl)-4-chloro-6-methylphenyl)-4-fluoroben-zamide (8h) showed moderate fungicidal activity against Physalospora piricola. It is worth noting that compound 8e, which has favorable insecticidal and fungicidal activities towards Mythimna separata Walker and Sclerotinia sclerotiorum respectively, could be used as novel reference structure for new agrochemical innovations.
A series of novel aromatic amide compounds with N-pyridylpyrazole and 1, 3, 4-oxadiazole heterocyclic motifs were successfully synthesized with N-pyridylpyrazole carboxylic acid and 2-amino-3-methylbenzoic acid as the starting materials, via multi-step reactions of nucleophilic addition, cyclization, acylation, etc. The preliminary bioassay tests indicated that most of these compounds have apparent insecticidal activities, among which compounds N-(2-(5-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-1, 3, 4-oxadiazol-2-yl)-4-chloro-6-methylphenyl)acetamide (8a) and N-(2-(5-(3-bromo-1-(3-chloro-pyridin-2-yl)-1H-pyrazol-5-yl)-1, 3, 4-oxadiazol-2-yl)-4-chloro-6-methylphenyl)-3-chloro-2, 2-dimethylpropanamide (8e) possessed a mortality rate of 70% towards Mythimna separata Walker at the concentration of 200 mg·L-1. Some of the compounds exhibited good fungicidal activities at 50 mg·L-1 against Sclerotinia sclerotiorum with the growth inhibitory rates of 54.5%~63.6%, which is more effective than the controls of triadimefon and chlorantraniliprole. Several compounds such as N-(2-(5-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-1, 3, 4-oxadiazol-2-yl)-4-chloro-6-methylphenyl)pivalamide (8f) and N-(2-(5-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-1, 3, 4-oxadiazol-2-yl)-4-chloro-6-methylphenyl)-4-fluoroben-zamide (8h) showed moderate fungicidal activity against Physalospora piricola. It is worth noting that compound 8e, which has favorable insecticidal and fungicidal activities towards Mythimna separata Walker and Sclerotinia sclerotiorum respectively, could be used as novel reference structure for new agrochemical innovations.
2020, 40(3): 794-800
doi: 10.6023/cjoc201908012
Abstract:
In order to find more efficient and low toxicity antitumor drugs, a series of novel 1, 3-disubstituted pyridazinone derivatives were synthesized and evaluated for their antiproliferative activities against four human cancer cell lines (MCF-7, PC-3, SW-620 and HGC-27) in vitro. The results showed that most compounds had good antiproliferative activities, especially 2-(4-(4-bromophenyl)-1-oxo-tolylazine-2(1H)-yl)-N-(2-fluorophenyl)acetamide (5g) exhibited better antiproliferative activities with IC50 value of 6.01 μmol/L. In a nutshell, this work provided clues to discover antitumor agent based on the quinazoline scaffold.
In order to find more efficient and low toxicity antitumor drugs, a series of novel 1, 3-disubstituted pyridazinone derivatives were synthesized and evaluated for their antiproliferative activities against four human cancer cell lines (MCF-7, PC-3, SW-620 and HGC-27) in vitro. The results showed that most compounds had good antiproliferative activities, especially 2-(4-(4-bromophenyl)-1-oxo-tolylazine-2(1H)-yl)-N-(2-fluorophenyl)acetamide (5g) exhibited better antiproliferative activities with IC50 value of 6.01 μmol/L. In a nutshell, this work provided clues to discover antitumor agent based on the quinazoline scaffold.
2020, 40(3): 801-805
doi: 10.6023/cjoc201908010
Abstract:
Reaction of RE(CH2SiMe3)3(THF)2 with 1.5 equiv. of (C4H3NHCH2)2NCH3 (1) in toluene gave nitrogen-containing bridged dipyrrolyl dinuclear rare-earth metal complexes[η1:η1:η1-(C4H3NCH2)2NCH3]RE{m-η5:η1:η5:η1:η1-(C4H3NCH2)2N-CH3}RE[η1:η1:η1-(C4H3NCH2)2NCH3](THF)[RE=Y (2), Er (3), Yb (4)]. All complexes were fully characterized by spectroscopic methods and elemental analyses. The structures of complexes 2 and 4 were further determined by single-crystal X-ray diffraction. The catalytic properties of rare-earth metal complexes on the ring-opening polymerization of e-caprolactone have been studied.
Reaction of RE(CH2SiMe3)3(THF)2 with 1.5 equiv. of (C4H3NHCH2)2NCH3 (1) in toluene gave nitrogen-containing bridged dipyrrolyl dinuclear rare-earth metal complexes[η1:η1:η1-(C4H3NCH2)2NCH3]RE{m-η5:η1:η5:η1:η1-(C4H3NCH2)2N-CH3}RE[η1:η1:η1-(C4H3NCH2)2NCH3](THF)[RE=Y (2), Er (3), Yb (4)]. All complexes were fully characterized by spectroscopic methods and elemental analyses. The structures of complexes 2 and 4 were further determined by single-crystal X-ray diffraction. The catalytic properties of rare-earth metal complexes on the ring-opening polymerization of e-caprolactone have been studied.
2020, 40(3): 806-807
doi: 10.6023/cjoc202000011
Abstract:
2020, 40(3): 808-809
doi: 10.6023/cjoc202000012
Abstract:
2020, 40(3): 810-811
doi: 10.6023/cjoc202000013
Abstract:
2020, 40(3): 814-815
doi: 10.6023/cjoc202000015
Abstract:
