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2019 Volume 39 Issue 2
2019, 39(2): 287-300
doi: 10.6023/cjoc201807016
Abstract:
Thiocyanates (RSCN) are important synthetic intermediates, which have been widely used for the synthesis of pesticides, medicines and materials. In recent years, great advances in the synthesis and transformations of this class of compounds have been made, and many synthetic applications of those compounds have been emerged. In this review, the synthetic methods and transformations of thiocyanates are introduced systematically, which may provide assistance for the studies of thiocyanates in this area.
Thiocyanates (RSCN) are important synthetic intermediates, which have been widely used for the synthesis of pesticides, medicines and materials. In recent years, great advances in the synthesis and transformations of this class of compounds have been made, and many synthetic applications of those compounds have been emerged. In this review, the synthetic methods and transformations of thiocyanates are introduced systematically, which may provide assistance for the studies of thiocyanates in this area.
2019, 39(2): 301-317
doi: 10.6023/cjoc201807028
Abstract:
With the especial reactivity, selectivity, availability and stability, the allenamides have got more and more attention, and the reports on allenamides cyclization grow rapidly. This review gives an up-to-date overview of transition-metal-catalyzed allenamides cyclization, which are sorted by metal catalysts in eight categories of Pd, Ru, Rh, Au, Co, Ag, Pt and Ni. For most of these transformations, the plausible mechanisms are demonstrated in details. Clarification of these issues is the key point for understanding the transition-metal-catalyzed allenamides cyclization and developing new high performance methodologies for chemists.
With the especial reactivity, selectivity, availability and stability, the allenamides have got more and more attention, and the reports on allenamides cyclization grow rapidly. This review gives an up-to-date overview of transition-metal-catalyzed allenamides cyclization, which are sorted by metal catalysts in eight categories of Pd, Ru, Rh, Au, Co, Ag, Pt and Ni. For most of these transformations, the plausible mechanisms are demonstrated in details. Clarification of these issues is the key point for understanding the transition-metal-catalyzed allenamides cyclization and developing new high performance methodologies for chemists.
2019, 39(2): 318-327
doi: 10.6023/cjoc201807002
Abstract:
Aromatic nitro compounds are of great importance as chemical raw materials and organic synthesis intermediates. Traditional electrophilic nitration is difficult to achieve regioselective nitrification. In recent years, transition-metal-catalyzed C-H bond activation has developed rapidly. Most functional groups can be introduced into specific sites of aromatics through the chelation of transition metals with directing groups. Directing-group assisted C-H nitration, which is catalyzed by palladium, rhodium, ruthenium and other transition-metal, has made important progress due to its less byproducts, good regioselectivity and environmental protection. According to different transition metal catalysts, the research progress on transition-metal-catalyzed directing-group assisted C-H nitration is summarized, and the limitations of the research field and prospects for future develop-ment are presented.
Aromatic nitro compounds are of great importance as chemical raw materials and organic synthesis intermediates. Traditional electrophilic nitration is difficult to achieve regioselective nitrification. In recent years, transition-metal-catalyzed C-H bond activation has developed rapidly. Most functional groups can be introduced into specific sites of aromatics through the chelation of transition metals with directing groups. Directing-group assisted C-H nitration, which is catalyzed by palladium, rhodium, ruthenium and other transition-metal, has made important progress due to its less byproducts, good regioselectivity and environmental protection. According to different transition metal catalysts, the research progress on transition-metal-catalyzed directing-group assisted C-H nitration is summarized, and the limitations of the research field and prospects for future develop-ment are presented.
2019, 39(2): 328-338
doi: 10.6023/cjoc201806003
Abstract:
Diketopiperazines (DKPs) are derivatives of cyclodipeptides resulted from the condensation of two α-amino acids. The conformationally constrained six-membered ring makes DKP an attractive pharmacophore in medicinal chemistry, exhibiting a wide range of bioactivities. Recently, there has been increased interests in synthesizing DKPs and biosynthesis is an effective pathway to broaden their structural diversity. Different from non-ribosomal peptide synthetases (NRPSs)-dependent pathways, cyclodipeptide synthases (CDPSs) use aminoacyl-tRNAs (aa-tRNAs) as substrates and the resulting cyclodipeptides are further modified by associated tailoring enzymes to yield the final products. To date, six CDPS-dependent pathways for synthesizing DKPs compounds have been reported. A brief overview of recent progresses on CDPS-dependent DKPs biosynthetic pathway is provided.
Diketopiperazines (DKPs) are derivatives of cyclodipeptides resulted from the condensation of two α-amino acids. The conformationally constrained six-membered ring makes DKP an attractive pharmacophore in medicinal chemistry, exhibiting a wide range of bioactivities. Recently, there has been increased interests in synthesizing DKPs and biosynthesis is an effective pathway to broaden their structural diversity. Different from non-ribosomal peptide synthetases (NRPSs)-dependent pathways, cyclodipeptide synthases (CDPSs) use aminoacyl-tRNAs (aa-tRNAs) as substrates and the resulting cyclodipeptides are further modified by associated tailoring enzymes to yield the final products. To date, six CDPS-dependent pathways for synthesizing DKPs compounds have been reported. A brief overview of recent progresses on CDPS-dependent DKPs biosynthetic pathway is provided.
2019, 39(2): 339-349
doi: 10.6023/cjoc201806012
Abstract:
Biocatalysis is a basic method of asymmetric catalysis for preparing chiral Active Pharmaceutical Ingredients, which owns several "green merits":chemo-, regio-and high enantioselectivity. As the development of DNA seqencing, DNA synthesis and protein engineering, suitable enzymes can be efficiently developed for basic researches and industrial applications. Biocatalysis has been keeping as a hot spot in asymmetric synthesis recently. Carbonyl reductases have been widely used for stereoselectively transforming ketones to chiral second alcohols with only one stereocenter. When combining with Dynamic Kinetic Resolution (DKR), the bioreaction with carbonyl reductases can efficiently construct chiral alcohols with two stereocenters in one step. This review highlights the method of its mechanism and nearly twenty examples from research papers and patents for one decade. We attempt to analyze and conclude the characteristics of this method based on chemical structures and enzymes. At last, a practical and developing research method is recommended in three steps:screening-racemization-balance in sequence. It is hoped to be useful for future basic researches and industrial applications.
Biocatalysis is a basic method of asymmetric catalysis for preparing chiral Active Pharmaceutical Ingredients, which owns several "green merits":chemo-, regio-and high enantioselectivity. As the development of DNA seqencing, DNA synthesis and protein engineering, suitable enzymes can be efficiently developed for basic researches and industrial applications. Biocatalysis has been keeping as a hot spot in asymmetric synthesis recently. Carbonyl reductases have been widely used for stereoselectively transforming ketones to chiral second alcohols with only one stereocenter. When combining with Dynamic Kinetic Resolution (DKR), the bioreaction with carbonyl reductases can efficiently construct chiral alcohols with two stereocenters in one step. This review highlights the method of its mechanism and nearly twenty examples from research papers and patents for one decade. We attempt to analyze and conclude the characteristics of this method based on chemical structures and enzymes. At last, a practical and developing research method is recommended in three steps:screening-racemization-balance in sequence. It is hoped to be useful for future basic researches and industrial applications.
2019, 39(2): 350-362
doi: 10.6023/cjoc201806038
Abstract:
The cross-coupling of two electrophiles has emerged as an important and attractive method for carbon-carbon bond formation. This synthetic protocol avoids preparation of organometallic nucleophilic reagents and exhibits excellent functional group tolerance. Recently, breakthrough progress has been developed to the cross-electrophile coupling of C(sp2)-X/C(sp3)-X. The recent progress in the research of Ni-catalyzed electrophilic coupling for the construction of C(sp2)-C(sp2) and C(sp2)-C(sp3) is reviewed.
The cross-coupling of two electrophiles has emerged as an important and attractive method for carbon-carbon bond formation. This synthetic protocol avoids preparation of organometallic nucleophilic reagents and exhibits excellent functional group tolerance. Recently, breakthrough progress has been developed to the cross-electrophile coupling of C(sp2)-X/C(sp3)-X. The recent progress in the research of Ni-catalyzed electrophilic coupling for the construction of C(sp2)-C(sp2) and C(sp2)-C(sp3) is reviewed.
2019, 39(2): 363-376
doi: 10.6023/cjoc201806021
Abstract:
Cinnolines are "privileged scaffold" in new material and drug research, and development for their extensive biological activities such as anticancer, antibacterial, antiviral, anti-inflammatory, and sedative activities and good electron-accepting ability. As a result, the development of new synthetic routes to this important structure has been actively investigated in recent years. Especially, the C-H functionalization strategy has promoted the development of new methods greatly. The recent advances of the synthetic methods to cinnolines based on different synthetic strategies and raw materials are reviewed.
Cinnolines are "privileged scaffold" in new material and drug research, and development for their extensive biological activities such as anticancer, antibacterial, antiviral, anti-inflammatory, and sedative activities and good electron-accepting ability. As a result, the development of new synthetic routes to this important structure has been actively investigated in recent years. Especially, the C-H functionalization strategy has promoted the development of new methods greatly. The recent advances of the synthetic methods to cinnolines based on different synthetic strategies and raw materials are reviewed.
2019, 39(2): 377-389
doi: 10.6023/cjoc201806031
Abstract:
Under the catalysis of Cu(OTf)2, a hydroxy ylide trapping based multi-component reaction using water, diazoacetates, aromatic aldehydes and aromatic amines was successfully carried out to construct α-hydroxy-β-amino acid ester skeleton in one step. The taxol oxazolidine-type side chains were efficiently synthesized after further chemical transformations. Moreover, 14 taxane derivatives were synthesized through esterification of obtained side chains and 7-O-(triethylsilyl) baccatin Ⅲ or 7, 10-dimethoxy-10-beacetyl baccatin Ⅲ, and several novel compounds with excellent activity were discovered in the test of anti-tumor activity. In this paper, combining the methodology and application of multi-component reaction, a highly efficient method for synthesizing paclitaxel side chain derivatives was developed, which was applied into the semi-synthesis of paclitaxel analogues. This research provided a new approach to the study of structure-activity relationship and had potential application value.
Under the catalysis of Cu(OTf)2, a hydroxy ylide trapping based multi-component reaction using water, diazoacetates, aromatic aldehydes and aromatic amines was successfully carried out to construct α-hydroxy-β-amino acid ester skeleton in one step. The taxol oxazolidine-type side chains were efficiently synthesized after further chemical transformations. Moreover, 14 taxane derivatives were synthesized through esterification of obtained side chains and 7-O-(triethylsilyl) baccatin Ⅲ or 7, 10-dimethoxy-10-beacetyl baccatin Ⅲ, and several novel compounds with excellent activity were discovered in the test of anti-tumor activity. In this paper, combining the methodology and application of multi-component reaction, a highly efficient method for synthesizing paclitaxel side chain derivatives was developed, which was applied into the semi-synthesis of paclitaxel analogues. This research provided a new approach to the study of structure-activity relationship and had potential application value.
2019, 39(2): 406-411
doi: 10.6023/cjoc201804043
Abstract:
A colorimetric and fluorescent turn-off chemosensor for fluoride based on novel naphthalene-fused boron dipyrromethene (BODIPY) 5 was designed and synthesized. In various anions, only upon addition of fluoride, the UV-Vis absorption peak of probe 5 red-shifted 100 nm, reaching the near infrared (NIR) region. Thus, it can be used as naked-eye detector for fluoride ion. In the fluorescence test, upon addition of fluoride, the fluorescence of probe 5 quenched significantly. Confocal fluorescence microscopy experiments demonstrate that 5 can be used for monitoring fluoride in living cells.
A colorimetric and fluorescent turn-off chemosensor for fluoride based on novel naphthalene-fused boron dipyrromethene (BODIPY) 5 was designed and synthesized. In various anions, only upon addition of fluoride, the UV-Vis absorption peak of probe 5 red-shifted 100 nm, reaching the near infrared (NIR) region. Thus, it can be used as naked-eye detector for fluoride ion. In the fluorescence test, upon addition of fluoride, the fluorescence of probe 5 quenched significantly. Confocal fluorescence microscopy experiments demonstrate that 5 can be used for monitoring fluoride in living cells.
2019, 39(2): 412-418
doi: 10.6023/cjoc201807051
Abstract:
As the representative flavonoid and flavonoid glycoside of Chinese medicine Cirsium japonicum, pectolinarigenin and pectolinarin have important bioactivities. In this paper, the efficient semi-synthesis of pectolinarigenin had been achieved starting from commercially available scutellarin via a linear reaction sequence of 3 steps with the overall yield of 69.5%, wherein carboxyl esterification, selective hydroxy protecting, and glycosidic bond hydrolyzation were used. Afterwards, the chemical synthesis of pectolinarin had been accomplished by the glycosylation of pectolinarigenin and benzobromorutinose.
As the representative flavonoid and flavonoid glycoside of Chinese medicine Cirsium japonicum, pectolinarigenin and pectolinarin have important bioactivities. In this paper, the efficient semi-synthesis of pectolinarigenin had been achieved starting from commercially available scutellarin via a linear reaction sequence of 3 steps with the overall yield of 69.5%, wherein carboxyl esterification, selective hydroxy protecting, and glycosidic bond hydrolyzation were used. Afterwards, the chemical synthesis of pectolinarin had been accomplished by the glycosylation of pectolinarigenin and benzobromorutinose.
2019, 39(2): 419-426
doi: 10.6023/cjoc201807057
Abstract:
In order to develop more stable abscisic acid (ABA) analogs, a novel type of sulfonamide compounds was designed based on the similar synthesis strategy using pyrabactin and 2', 3'-benzo-iso-ABA (iso-PhABA) as precursors. Using 1-tetralone as raw material, 13 novel sulfonamides were synthesized by methylation, benzylic oxidation, hydrazone formation and sulfonamidation, and the reaction conditions of sulfonamidation were explored and optimized. The results of seed germination experiments showed that the target compounds exhibited different inhibition activities at a concentration of 50 μmol·L-1, and the inhibition rates of five compounds on Arabidopsis and lettuce seeds germination were greater than 50% and 40%, respectively. These results have important reference significance for the creation of new abscisic acid synthetic phytohormones.
In order to develop more stable abscisic acid (ABA) analogs, a novel type of sulfonamide compounds was designed based on the similar synthesis strategy using pyrabactin and 2', 3'-benzo-iso-ABA (iso-PhABA) as precursors. Using 1-tetralone as raw material, 13 novel sulfonamides were synthesized by methylation, benzylic oxidation, hydrazone formation and sulfonamidation, and the reaction conditions of sulfonamidation were explored and optimized. The results of seed germination experiments showed that the target compounds exhibited different inhibition activities at a concentration of 50 μmol·L-1, and the inhibition rates of five compounds on Arabidopsis and lettuce seeds germination were greater than 50% and 40%, respectively. These results have important reference significance for the creation of new abscisic acid synthetic phytohormones.
2019, 39(2): 427-433
doi: 10.6023/cjoc201807042
Abstract:
A new turn-off probe 6 was synthesized from bis(pyridin-2-ylmethyl)amine and truxene derivatives, and its structure was confirmed by 1H NMR and HRMS. The recognition behaviors of 6 to various metal ions were investigated and the results show that 6 exhibited good selectivity and high sensitivity to Cu2+ and Ni2+ with good anti-interference. The probe 6 presented apparent fluorescence quenching in DMF/H2O (V/V=8/2, pH=7.0) solution toward Cu2+ and Ni2+. HRMS analysis showed a 1:1 binding stoichiometry between 6 and Cu2+ or Ni2+. The detection limit for Cu2+ and Ni2+ was calculated to be 28 and 41 nmol/L, respectively. The detection limit of 6 for Cu2+ and Ni2+ was far lower than the maximum allowable level of World Health Organization (WHO) limit for drinking water.
A new turn-off probe 6 was synthesized from bis(pyridin-2-ylmethyl)amine and truxene derivatives, and its structure was confirmed by 1H NMR and HRMS. The recognition behaviors of 6 to various metal ions were investigated and the results show that 6 exhibited good selectivity and high sensitivity to Cu2+ and Ni2+ with good anti-interference. The probe 6 presented apparent fluorescence quenching in DMF/H2O (V/V=8/2, pH=7.0) solution toward Cu2+ and Ni2+. HRMS analysis showed a 1:1 binding stoichiometry between 6 and Cu2+ or Ni2+. The detection limit for Cu2+ and Ni2+ was calculated to be 28 and 41 nmol/L, respectively. The detection limit of 6 for Cu2+ and Ni2+ was far lower than the maximum allowable level of World Health Organization (WHO) limit for drinking water.
2019, 39(2): 434-442
doi: 10.6023/cjoc201807010
Abstract:
The N, N-dimethylformamide dialkyl acetal was used as the alkyl source to achieve different nitrogen alkylation reactions of N-H compounds. The reaction has the advantages of cheap raw materials, easy operation, mild reaction conditions, broad substrate scope and no metal participation. By studying the effects of solvents, temperature, reaction time, and the amount of N, N-dimethylformamide dialkyl acetal on the reaction, the optimal reaction conditions were obtained. The effect of different N, N-dimethylformamide dialkyl acetals on the alkylation ability of the substrate was investigated.
The N, N-dimethylformamide dialkyl acetal was used as the alkyl source to achieve different nitrogen alkylation reactions of N-H compounds. The reaction has the advantages of cheap raw materials, easy operation, mild reaction conditions, broad substrate scope and no metal participation. By studying the effects of solvents, temperature, reaction time, and the amount of N, N-dimethylformamide dialkyl acetal on the reaction, the optimal reaction conditions were obtained. The effect of different N, N-dimethylformamide dialkyl acetals on the alkylation ability of the substrate was investigated.
2019, 39(2): 449-455
doi: 10.6023/cjoc201807006
Abstract:
The novel host material containing indolocarbazole group, 10-phenyl-10-(4-(7-phenylindolo[2, 3-b]carbazol-5(7H)-yl)phenyl)anthracen-9(10H)-one (DphAn-5PhIdCz), was designed and synthesized. The structures were characterized by NMR and their photophysical properties such as ultraviolet-visible absorption wavelength, fluorescence emission wavelength, fluorescence quantum yield, and transient fluorescence lifetime were measured. The DphAn-5PhIdCz was found to exhibit the characteritics of bipolar and thermally activated delayed fluorescence. By using this material as host of green emitter, (ppy)2 Iracac, high-efficiency and low roll-off phosphorescent organic light-emitting diode (PhOLED) was fabricated with the maximum current efficiency of 56.12 cd·A-1, the maximum external quantum efficiency of 15.70% and the maximum power efficiency of 71.3 lm·W-1. These make DphAn-5PhIdCz a promising host for high performance PhOLED displays and lighting applications.
The novel host material containing indolocarbazole group, 10-phenyl-10-(4-(7-phenylindolo[2, 3-b]carbazol-5(7H)-yl)phenyl)anthracen-9(10H)-one (DphAn-5PhIdCz), was designed and synthesized. The structures were characterized by NMR and their photophysical properties such as ultraviolet-visible absorption wavelength, fluorescence emission wavelength, fluorescence quantum yield, and transient fluorescence lifetime were measured. The DphAn-5PhIdCz was found to exhibit the characteritics of bipolar and thermally activated delayed fluorescence. By using this material as host of green emitter, (ppy)2 Iracac, high-efficiency and low roll-off phosphorescent organic light-emitting diode (PhOLED) was fabricated with the maximum current efficiency of 56.12 cd·A-1, the maximum external quantum efficiency of 15.70% and the maximum power efficiency of 71.3 lm·W-1. These make DphAn-5PhIdCz a promising host for high performance PhOLED displays and lighting applications.
2019, 39(2): 456-462
doi: 10.6023/cjoc201807040
Abstract:
A concise and efficiently route for the synthesis of 3-substituted benzofurans via the intramolecular Heck reaction of bromoaryl 3-phenylallyl ethers has been developed. This simple and highly efficient palladium nanoparticles-catalyzed system showed good catalytic activity. The desired products were affored in good to high yields (45%~96%).
A concise and efficiently route for the synthesis of 3-substituted benzofurans via the intramolecular Heck reaction of bromoaryl 3-phenylallyl ethers has been developed. This simple and highly efficient palladium nanoparticles-catalyzed system showed good catalytic activity. The desired products were affored in good to high yields (45%~96%).
2019, 39(2): 469-474
doi: 10.6023/cjoc201807032
Abstract:
Nitroxyl (HNO), which is the one-electron reduced and further protonated form of nitric oxide, plays important biological functions. A lysosome-targeted dual-photon HNO fluorescent probe (Lyso-HNO), which contains 4-(2-amino-ethyl)morpholine as lysosomal-targetable groups, 1, 8-naphthalimide as two-photon fluorophore and triphenylphosphine as HNO reaction site, was synthesized and characterized. The recognition behaviors of Lyso-HNO to HNO were investigated. The results showed that Lyso-HNO exhibited good selectivity and sensitivity to HNO with fast response, . and the detection limit of Lyso-HNO to HNO was estimated to be 202 nmol·L-1. The probe can be applied to bioimaging exogenous lysosomal HNO by two-photon fluorescence confocal microscopy.
Nitroxyl (HNO), which is the one-electron reduced and further protonated form of nitric oxide, plays important biological functions. A lysosome-targeted dual-photon HNO fluorescent probe (Lyso-HNO), which contains 4-(2-amino-ethyl)morpholine as lysosomal-targetable groups, 1, 8-naphthalimide as two-photon fluorophore and triphenylphosphine as HNO reaction site, was synthesized and characterized. The recognition behaviors of Lyso-HNO to HNO were investigated. The results showed that Lyso-HNO exhibited good selectivity and sensitivity to HNO with fast response, . and the detection limit of Lyso-HNO to HNO was estimated to be 202 nmol·L-1. The probe can be applied to bioimaging exogenous lysosomal HNO by two-photon fluorescence confocal microscopy.
2019, 39(2): 475-481
doi: 10.6023/cjoc201808013
Abstract:
Allylic amines moiety exists extensively in natural products, medicines and functional materials. In addition, they are also a kind of versatile building blocks for organic synthesis. Using CH3CN as solvent, the palladium catalyzed allyl amination of cinnamyl carbonate and acylhydrazone compounds was realized under argon. The linear product was formed selectively and the up to 99% yield was obtained. The reaction has features of base free, mild reaction condition, simple operation and broad substrate scope.
Allylic amines moiety exists extensively in natural products, medicines and functional materials. In addition, they are also a kind of versatile building blocks for organic synthesis. Using CH3CN as solvent, the palladium catalyzed allyl amination of cinnamyl carbonate and acylhydrazone compounds was realized under argon. The linear product was formed selectively and the up to 99% yield was obtained. The reaction has features of base free, mild reaction condition, simple operation and broad substrate scope.
2019, 39(2): 491-499
doi: 10.6023/cjoc201806042
Abstract:
A series of novel acylhydrazone derivatives 6 containing carbazole moity were synthesized by carbazole and 4-cyanobenzyl chloride as starting materials via multi-step reactions. Their structures were characterized by IR, 1H NMR, 13C NMR spectra and elemental analysis. All synthesized target compounds were evaluated for the inhibitory activities against Cdc25B and PTP1B. The results show that the target compounds display significant inhibitory activities against Cdc25B/PTP1B. Among them, compound 4-((carbazol-9-yl)methyl)-N'-(2-hydroxy-1-naphthalenylmethylene)benzoyl hydrazide (6g) had the highest inhibitory activities against Cdc25B and PTP1B with IC50 values of (2.16±0.38) and (1.06±0.23) μg/mL, respectively. The molecular docking results indicated that the hydrogen bond and hydrophobic interaction formed between compound 6g and Cdc25B/PTP1B enzyme.
A series of novel acylhydrazone derivatives 6 containing carbazole moity were synthesized by carbazole and 4-cyanobenzyl chloride as starting materials via multi-step reactions. Their structures were characterized by IR, 1H NMR, 13C NMR spectra and elemental analysis. All synthesized target compounds were evaluated for the inhibitory activities against Cdc25B and PTP1B. The results show that the target compounds display significant inhibitory activities against Cdc25B/PTP1B. Among them, compound 4-((carbazol-9-yl)methyl)-N'-(2-hydroxy-1-naphthalenylmethylene)benzoyl hydrazide (6g) had the highest inhibitory activities against Cdc25B and PTP1B with IC50 values of (2.16±0.38) and (1.06±0.23) μg/mL, respectively. The molecular docking results indicated that the hydrogen bond and hydrophobic interaction formed between compound 6g and Cdc25B/PTP1B enzyme.
2019, 39(2): 500-506
doi: 10.6023/cjoc201805014
Abstract:
The non-controlled redox-active metal ions, especially copper, in the brain of patients with Alzheimer disease (AD) should be considered at the origin of the intense oxidative damage in AD brain. In this paper, we designed and synthesized new compounds based on 8-aminoquinoline motif with a lateral chain at the C2 position of the aromatic ring. The affinities for Cu(Ⅱ) and Zn(Ⅱ) of these ligands are reported in the present article. Among these chelators, TDMQ29 is specific for copper chelation with log Kapp[CuⅡ-TDMQ29] to be 15.7 and log Kapp[ZnⅡ-TDMQ29] to be 5.8. Such metal ligands can be consi-dered as potential ligands, which are able to regulate the homeostasis of copper in brains.
The non-controlled redox-active metal ions, especially copper, in the brain of patients with Alzheimer disease (AD) should be considered at the origin of the intense oxidative damage in AD brain. In this paper, we designed and synthesized new compounds based on 8-aminoquinoline motif with a lateral chain at the C2 position of the aromatic ring. The affinities for Cu(Ⅱ) and Zn(Ⅱ) of these ligands are reported in the present article. Among these chelators, TDMQ29 is specific for copper chelation with log Kapp[CuⅡ-TDMQ29] to be 15.7 and log Kapp[ZnⅡ-TDMQ29] to be 5.8. Such metal ligands can be consi-dered as potential ligands, which are able to regulate the homeostasis of copper in brains.
2019, 39(2): 507-514
doi: 10.6023/cjoc201806045
Abstract:
Nocardiopsis dassonvillei OUCMDZ-4534 was isolated and identified from the sponge, Dysidea avara, from Xisha Islands of China. Compounds 1~12 were isolated from the fermenation broth of N. dassonvillei OUCMDZ-4534. By means of spectroscopic analysis, electronic circular dichroism (ECD) and 13C NMR calculations, their structures were identified as (3aS, 7aS)-3a-hydroxy-3a, 7a-dihydrobenzofuran-2(3H)-one (1a), (3aR, 7aR)-3a-hydroxy-3a, 7a-dihydrobenzofuran-2(3H)-one (1b), phenazine (2), 1-hydroxyphenazine (3), 1-methoxyphenazine (4), 1, 6-dihydroxyphenazine (5), 1-hydroxy-6-methoxy-phenazine (6), 1, 6-dihydroxy phenazin-5-oxide (7), dihydrogeodin (8), 2-acetamidophenol (9), 2-benzamidophenol (10), (E)-7-hydroxy cinnamic acid (11), and (E)-7-hydroxy-6-methoxycinnamic acid (12), respectively. This is the first time to resolve racemic-1 and identify the absolute structures of 1a and 1b. Compounds 1 and 9 displayed selective inhibition on A549 and K562 cell lines with the half maximal inhibitory concentration (IC50) of 0.47 and 0.46 μmol·L-1, respectively. Compounds 4~8 showed inhibitory activities against K562, A549 and MCF-7 cell lines with IC50 values ranging from 0.02 to 1.48 μmol·L-1. Compound 11 was cytotoxic to K562 while compound 12 was active against K562 and MCF-7 cell lines with the IC50 values of 1.14, 0.88 and 0.65 μmol·L-1, respectively. Compounds 7 and 8 showed antimicrobial activities against Aspergillus fumigatus and Pseudoalteromonas nigrifaciens with the minimum inhibitory concentration (MIC) of 25.00 and 2.00 μg·mL-1, respectively. Compounds 4~6 and 9 also exhibited inhibitions against the H1N1 virus with the IC50 values of 0.04, 0.16, 0.06 and 0.30 mmol·L-1, respectively.
Nocardiopsis dassonvillei OUCMDZ-4534 was isolated and identified from the sponge, Dysidea avara, from Xisha Islands of China. Compounds 1~12 were isolated from the fermenation broth of N. dassonvillei OUCMDZ-4534. By means of spectroscopic analysis, electronic circular dichroism (ECD) and 13C NMR calculations, their structures were identified as (3aS, 7aS)-3a-hydroxy-3a, 7a-dihydrobenzofuran-2(3H)-one (1a), (3aR, 7aR)-3a-hydroxy-3a, 7a-dihydrobenzofuran-2(3H)-one (1b), phenazine (2), 1-hydroxyphenazine (3), 1-methoxyphenazine (4), 1, 6-dihydroxyphenazine (5), 1-hydroxy-6-methoxy-phenazine (6), 1, 6-dihydroxy phenazin-5-oxide (7), dihydrogeodin (8), 2-acetamidophenol (9), 2-benzamidophenol (10), (E)-7-hydroxy cinnamic acid (11), and (E)-7-hydroxy-6-methoxycinnamic acid (12), respectively. This is the first time to resolve racemic-1 and identify the absolute structures of 1a and 1b. Compounds 1 and 9 displayed selective inhibition on A549 and K562 cell lines with the half maximal inhibitory concentration (IC50) of 0.47 and 0.46 μmol·L-1, respectively. Compounds 4~8 showed inhibitory activities against K562, A549 and MCF-7 cell lines with IC50 values ranging from 0.02 to 1.48 μmol·L-1. Compound 11 was cytotoxic to K562 while compound 12 was active against K562 and MCF-7 cell lines with the IC50 values of 1.14, 0.88 and 0.65 μmol·L-1, respectively. Compounds 7 and 8 showed antimicrobial activities against Aspergillus fumigatus and Pseudoalteromonas nigrifaciens with the minimum inhibitory concentration (MIC) of 25.00 and 2.00 μg·mL-1, respectively. Compounds 4~6 and 9 also exhibited inhibitions against the H1N1 virus with the IC50 values of 0.04, 0.16, 0.06 and 0.30 mmol·L-1, respectively.
2019, 39(2): 390-396
doi: 10.6023/cjoc201808044
Abstract:
Synthesis of azidosphingosine has been described from D-galactose and L-arabinose with an overall yields of 27% an 20%, respectively. Our strategy features olefin cross-metathesis reaction, radical-induced isomerization, appel reaction, and azido replacement.
Synthesis of azidosphingosine has been described from D-galactose and L-arabinose with an overall yields of 27% an 20%, respectively. Our strategy features olefin cross-metathesis reaction, radical-induced isomerization, appel reaction, and azido replacement.
2019, 39(2): 397-405
doi: 10.6023/cjoc201807009
Abstract:
Rice sheath blight disease, one of three most important diseases in rice, can lead to crop production loss seriously. However, the application of fungicides is an effective way to prevent rice from diseases. After being used for a period of time, the plant pathogenic fungi may develop resistance to chemical fungicide, so it is necessary to discover compounds with novel structures and further to address the problem of fungicide resistance. By employing the intermediate derivatisation method (IDM), twenty-five new phenylpyrazoloxyl propionic acid derivatives were designed and synthesized. The biological activities of title compounds were tested against Rhizoctonia solani and their structure-activity relationships (SAR) were discussed as well. The preliminary bioassay results displayed that some compounds exhibited an excellent fungicidal activity against Rhizoctonia solani, especially 2-((1-(4-chlorophenyl)-1H-pyrazol-3-yl)oxy)-N-(4-nitrophenyl)propanamide (17) (EC50=1.05 mg/L) and 2-((1-(4-chlorophenyl)-1H-pyrazol-3-yl)oxy)-N-(pyridin-2-yl)propanamide (22) (EC50=1.02 mg/L) showing a com-parable activity to the commercial contrast tebuconazole (EC50=1.02 mg/L), and 2-((1-(4-chlorophenyl)-1H-pyrazol-3-yl)-oxy)-N-(3, 4-dichlorophenyl)propanamide (20) (EC50=0.95 mg/L) is a little more active than tebuconazole (EC50=1.02 mg/L).
Rice sheath blight disease, one of three most important diseases in rice, can lead to crop production loss seriously. However, the application of fungicides is an effective way to prevent rice from diseases. After being used for a period of time, the plant pathogenic fungi may develop resistance to chemical fungicide, so it is necessary to discover compounds with novel structures and further to address the problem of fungicide resistance. By employing the intermediate derivatisation method (IDM), twenty-five new phenylpyrazoloxyl propionic acid derivatives were designed and synthesized. The biological activities of title compounds were tested against Rhizoctonia solani and their structure-activity relationships (SAR) were discussed as well. The preliminary bioassay results displayed that some compounds exhibited an excellent fungicidal activity against Rhizoctonia solani, especially 2-((1-(4-chlorophenyl)-1H-pyrazol-3-yl)oxy)-N-(4-nitrophenyl)propanamide (17) (EC50=1.05 mg/L) and 2-((1-(4-chlorophenyl)-1H-pyrazol-3-yl)oxy)-N-(pyridin-2-yl)propanamide (22) (EC50=1.02 mg/L) showing a com-parable activity to the commercial contrast tebuconazole (EC50=1.02 mg/L), and 2-((1-(4-chlorophenyl)-1H-pyrazol-3-yl)-oxy)-N-(3, 4-dichlorophenyl)propanamide (20) (EC50=0.95 mg/L) is a little more active than tebuconazole (EC50=1.02 mg/L).
2019, 39(2): 482-490
doi: 10.6023/cjoc201807050
Abstract:
A catalyst system combined of PdCl2 with 1, 3-bis(diphenylphosphion)propane (dppp), which was simple and from commercially available materials, was reported for the highly efficient arylation of benzoxazoles at C-2 position with aryl bromides. This catalytic system could tolerate a great number of functional groups in benzoxazole and bromobenzene. With a low PdCl2 loading of 0.01 mol%, aryl bromides could be completely converted into the desired products for 24 h. If the loading of catalyst was up to 0.10 mol%, most of substrates could give more than 90% yields in 6 h. The exploration of the reaction mechanism discovered that Pd nanoparticles were formed during this reaction. The morphology and composition analysis of the Pd nanoparticles with transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) indicated that dppp played a key role to block the aggregation of palladium particles. In addition, the ring-opening pathway of benzoxazoles in the reaction process was proved by control experiments. Hot filtration experimental and high resolution mass spectrum (HRMS) analysis of filtrate suggested that the real active species were Pd(0)-Pd(Ⅱ)/dppp complexes.
A catalyst system combined of PdCl2 with 1, 3-bis(diphenylphosphion)propane (dppp), which was simple and from commercially available materials, was reported for the highly efficient arylation of benzoxazoles at C-2 position with aryl bromides. This catalytic system could tolerate a great number of functional groups in benzoxazole and bromobenzene. With a low PdCl2 loading of 0.01 mol%, aryl bromides could be completely converted into the desired products for 24 h. If the loading of catalyst was up to 0.10 mol%, most of substrates could give more than 90% yields in 6 h. The exploration of the reaction mechanism discovered that Pd nanoparticles were formed during this reaction. The morphology and composition analysis of the Pd nanoparticles with transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) indicated that dppp played a key role to block the aggregation of palladium particles. In addition, the ring-opening pathway of benzoxazoles in the reaction process was proved by control experiments. Hot filtration experimental and high resolution mass spectrum (HRMS) analysis of filtrate suggested that the real active species were Pd(0)-Pd(Ⅱ)/dppp complexes.
2019, 39(2): 443-448
doi: 10.6023/cjoc201807008
Abstract:
Using L-phenylalaninol as chiral precursor, a series of multi-aryl substituted imidazole amino alcohol derivatives containing appended chiral functionalities were synthesized through a "four component-one pot procedure" from the condensation reaction of L-phenylalaninol, dibenzoyl (benzil), ammonium acetate and different heterocyclic aryl-aldehyde. X-ray crystal analysis confirmed that the chiral carbon retained the S configuration of L-phenylalaninol. The chiral ligands in combination with Cu(OAc)2·H2O catalyzed the enantioselective Henry reaction of nitromethane and aromatic aldehydes with moderate to high yields and excellent enantioselectivities (>99%) with S configuration. The easy availability of catalyst components, mild reaction conditions and high enantioselectivity make the system attractive for practical application.
Using L-phenylalaninol as chiral precursor, a series of multi-aryl substituted imidazole amino alcohol derivatives containing appended chiral functionalities were synthesized through a "four component-one pot procedure" from the condensation reaction of L-phenylalaninol, dibenzoyl (benzil), ammonium acetate and different heterocyclic aryl-aldehyde. X-ray crystal analysis confirmed that the chiral carbon retained the S configuration of L-phenylalaninol. The chiral ligands in combination with Cu(OAc)2·H2O catalyzed the enantioselective Henry reaction of nitromethane and aromatic aldehydes with moderate to high yields and excellent enantioselectivities (>99%) with S configuration. The easy availability of catalyst components, mild reaction conditions and high enantioselectivity make the system attractive for practical application.
2019, 39(2): 463-468
doi: 10.6023/cjoc201807033
Abstract:
A simple and practical route for construction of various sulfonamides from nitroarenes and sulfonyl chlorides with iron powder as the sole reductant in water (green solvent) under open-air conditions was developed. The protocol features low-cost, environmentally benign solvent, mild reaction conditions and wide broad substrate scope.
A simple and practical route for construction of various sulfonamides from nitroarenes and sulfonyl chlorides with iron powder as the sole reductant in water (green solvent) under open-air conditions was developed. The protocol features low-cost, environmentally benign solvent, mild reaction conditions and wide broad substrate scope.
2019, 39(2): 515-520
doi: 10.6023/cjoc201807025
Abstract:
An 2, 2'-azobis(2-methylpropionitrile) (AIBN) initiated tandem reaction of vinyl azides with isopropylxanthic disulfide to construct C-S/C-N bonds was disclosed. A range of functionalized 6-sulfanylmethyl phenanthridines could be easily accessed in 50%~84% yields with a good regioselectivity. The mechanism study indicates a free radical pathway in this reaction.
An 2, 2'-azobis(2-methylpropionitrile) (AIBN) initiated tandem reaction of vinyl azides with isopropylxanthic disulfide to construct C-S/C-N bonds was disclosed. A range of functionalized 6-sulfanylmethyl phenanthridines could be easily accessed in 50%~84% yields with a good regioselectivity. The mechanism study indicates a free radical pathway in this reaction.
2019, 39(2): 532-537
doi: 10.6023/cjoc201807024
Abstract:
Reaction of 2-(1-hydroxy-1-arylalkyl)phenols with anhydride and NEt3 was reported, providing a practical way to the synthesis of ortho-acyloxy diarylalkenes, which is an important motif in many bioactive compounds and starting materials in many organic synthesis. This reaction can be achieved in one pot reaction under mild conditions in good yields.
Reaction of 2-(1-hydroxy-1-arylalkyl)phenols with anhydride and NEt3 was reported, providing a practical way to the synthesis of ortho-acyloxy diarylalkenes, which is an important motif in many bioactive compounds and starting materials in many organic synthesis. This reaction can be achieved in one pot reaction under mild conditions in good yields.
2019, 39(2): 521-526
doi: 10.6023/cjoc201805052
Abstract:
A novel poly(ethylene glycol) grafted 4-dimethylaminopyridine functionalized ionic liquid ([DMAP-PEG1000-DIL] [BF4]) was prepared and characterized by 1H NMR, 13C NMR, FT-IR and ESI-MS. In the presence of[DMAP-PEG1000-DIL] [BF4], various substituted aromatic aldehyde could react with malononitrile (or ethyl cyanoacetate) and phthalhydrazide in water to obtain a series of pyrazolo[1, 2-b]phthalazine-5, 10-dione derivatives with 85%~96% yields. The mild reaction conditions, high stable and recyclable ionic liquids, environmental friendliness are advantages of this methodology.
A novel poly(ethylene glycol) grafted 4-dimethylaminopyridine functionalized ionic liquid ([DMAP-PEG1000-DIL] [BF4]) was prepared and characterized by 1H NMR, 13C NMR, FT-IR and ESI-MS. In the presence of[DMAP-PEG1000-DIL] [BF4], various substituted aromatic aldehyde could react with malononitrile (or ethyl cyanoacetate) and phthalhydrazide in water to obtain a series of pyrazolo[1, 2-b]phthalazine-5, 10-dione derivatives with 85%~96% yields. The mild reaction conditions, high stable and recyclable ionic liquids, environmental friendliness are advantages of this methodology.
2019, 39(2): 527-531
doi: 10.6023/cjoc201807058
Abstract:
An effective visible-light mediated Ru-catalyzed protocol for accessing 6H-benzo[c]chromenes from benzyloxybenzenediazonium salt via a sequence of dediazoniation, intramolecular radical cyclization and aromaticzation has been developed. The protocol features mild conditions, simple operation and high efficiency, providing a new approach for synthesizing 6H-benzo[c]chromenes.
An effective visible-light mediated Ru-catalyzed protocol for accessing 6H-benzo[c]chromenes from benzyloxybenzenediazonium salt via a sequence of dediazoniation, intramolecular radical cyclization and aromaticzation has been developed. The protocol features mild conditions, simple operation and high efficiency, providing a new approach for synthesizing 6H-benzo[c]chromenes.
2019, 39(2): 538-543
doi: 10.6023/cjoc201808023
Abstract:
A simple and economic method for synthesizing quinazolinones from substituted 2-halobenzoic acids and amidines was developed by nickel-catalysis in wet polyethylene glycol 200 (PEG 200) as an eco-friendly medium. The present methodology is operationally simple, non-toxic and non-irritative, and varieties of quinazolinone derivatives were obtained in high yields of up to 94%.
A simple and economic method for synthesizing quinazolinones from substituted 2-halobenzoic acids and amidines was developed by nickel-catalysis in wet polyethylene glycol 200 (PEG 200) as an eco-friendly medium. The present methodology is operationally simple, non-toxic and non-irritative, and varieties of quinazolinone derivatives were obtained in high yields of up to 94%.
2019, 39(2): 544-549
doi: 10.6023/cjoc201807031
Abstract:
Shorter reaction times, higher product yields and enhanced selectivity are some of the outstanding advantages over conventional methods that the microwave-assisted organic synthesis possesses, which makes this methods develop into a significant mainstream both in industrial usages and academic researches. Microwave-assisted organic synthesis as a new protocol for green chemistry showcases the application of microwave heating in a number of areas of preparative chemistry as well as in the biosciences. Many name reactions can be performed by microwave-assisted, including the Diels-Alder reaction, the Witting reaction, the Heck reaction and the Mannich reaction. Meanwhile, α-diazoester was already a mature science 20 years ago, some areas that continue to attract the most attention are preparation of diazoester substrates, such as the Wolff rearrangement, C-H insertion, N-H insertion, Si-H insertion and so on. Therefore, it is necessary to develop a green and efficient method for the preparation of α-diazoester. Herein a new method of microwave-assisted synthesis of α-diazoesters compounds from 2-phenylacetates and tosyl azide in 30 min is described. The protocol provides a quick, efficient and green approach to various α-diazoesters compounds with up to 90% isolated yields and a broad range of functional groups.
Shorter reaction times, higher product yields and enhanced selectivity are some of the outstanding advantages over conventional methods that the microwave-assisted organic synthesis possesses, which makes this methods develop into a significant mainstream both in industrial usages and academic researches. Microwave-assisted organic synthesis as a new protocol for green chemistry showcases the application of microwave heating in a number of areas of preparative chemistry as well as in the biosciences. Many name reactions can be performed by microwave-assisted, including the Diels-Alder reaction, the Witting reaction, the Heck reaction and the Mannich reaction. Meanwhile, α-diazoester was already a mature science 20 years ago, some areas that continue to attract the most attention are preparation of diazoester substrates, such as the Wolff rearrangement, C-H insertion, N-H insertion, Si-H insertion and so on. Therefore, it is necessary to develop a green and efficient method for the preparation of α-diazoester. Herein a new method of microwave-assisted synthesis of α-diazoesters compounds from 2-phenylacetates and tosyl azide in 30 min is described. The protocol provides a quick, efficient and green approach to various α-diazoesters compounds with up to 90% isolated yields and a broad range of functional groups.
2019, 39(2): 550-554
doi: 10.6023/cjoc201808002
Abstract:
Aerogel is a kind of gel materials, of which the fluid phase is gas. Aerogel has the characteristics of low density and high porosity, and has a wide application prospects. In this work, a rapid solvents exchange method was developed, and using in-situ secondary extraction, rapid solvents exchange in aerogel preparation was achieved through the miscibility and immiscibility of ethanol-dichloromethane-water. Combined with hydrophobic treatment and vacuum drying, hydrophobic silica aerogel was obtained. The aerogel had a low density and a contact angle with water of 155.8°. The aerogel can load various organic fluorescent probe dyes, which can effectively avoid the fluorescence quenching caused by the aggregation of the probe molecules, which it will expand the practical application range of the organic fluorescent probes in wider fields.
Aerogel is a kind of gel materials, of which the fluid phase is gas. Aerogel has the characteristics of low density and high porosity, and has a wide application prospects. In this work, a rapid solvents exchange method was developed, and using in-situ secondary extraction, rapid solvents exchange in aerogel preparation was achieved through the miscibility and immiscibility of ethanol-dichloromethane-water. Combined with hydrophobic treatment and vacuum drying, hydrophobic silica aerogel was obtained. The aerogel had a low density and a contact angle with water of 155.8°. The aerogel can load various organic fluorescent probe dyes, which can effectively avoid the fluorescence quenching caused by the aggregation of the probe molecules, which it will expand the practical application range of the organic fluorescent probes in wider fields.
2019, 39(2): 555-560
doi: 10.6023/cjoc201807017
Abstract:
o-Quinone derivatives are not only a variety of active and important intermediate, but also widely used in the synthesis of natural products and medicinal chemistry. In the present study, the Sc(OTf)3 catalyzed oxo-Michael addition to o-quinone methides by alcohols was developed. The products were obtained in moderate to good yields (76%~97%) under mild conditions. Furthermore, the reaction could be scaled up to multigram scale.
o-Quinone derivatives are not only a variety of active and important intermediate, but also widely used in the synthesis of natural products and medicinal chemistry. In the present study, the Sc(OTf)3 catalyzed oxo-Michael addition to o-quinone methides by alcohols was developed. The products were obtained in moderate to good yields (76%~97%) under mild conditions. Furthermore, the reaction could be scaled up to multigram scale.
2019, 39(2): 561-565
doi: 10.6023/cjoc201807041
Abstract:
As the active component of precious Chinese medicine Aquilaria sinensis, 7, 4'-dimethylapigenin-5-O-glycoside showed inhibitory activity for nitric oxide (NO) production by activated RAW 264.7 cells. Because of the strong intramolecular H-bond, the 5-O-glucosidic linkage in flavonoids could not be efficiently constructed via conventional glycosylation method. In this paper, the efficient chemical synthesis of 7, 4'-dimethylapigenin-5-O-glycoside has been achieved for the first time starting from commercially available naringenin and D-glucose via a linear reaction sequence of 6 steps with the overall yield of 36.0%, wherein selective hydroxy protecting, reduction with sodium borohydride, glycosylation under phase transfer catalytic condition, oxidation with 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) and other reactions were used. This work definitely laid the foundation for the further pharmacological study of this natural compound.
As the active component of precious Chinese medicine Aquilaria sinensis, 7, 4'-dimethylapigenin-5-O-glycoside showed inhibitory activity for nitric oxide (NO) production by activated RAW 264.7 cells. Because of the strong intramolecular H-bond, the 5-O-glucosidic linkage in flavonoids could not be efficiently constructed via conventional glycosylation method. In this paper, the efficient chemical synthesis of 7, 4'-dimethylapigenin-5-O-glycoside has been achieved for the first time starting from commercially available naringenin and D-glucose via a linear reaction sequence of 6 steps with the overall yield of 36.0%, wherein selective hydroxy protecting, reduction with sodium borohydride, glycosylation under phase transfer catalytic condition, oxidation with 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) and other reactions were used. This work definitely laid the foundation for the further pharmacological study of this natural compound.
2019, 39(2): 566-570
doi: 10.6023/cjoc201805024
Abstract:
An facile, effective, copper-catalyzed one-pot approach to 2-benzyl-3, 4-dihydroquinolin-1-ones has been successfully developed. The compounds were achieved by the reaction of tetrahydroisoquinoline, benzyl azide and benzaldehyde in one-pot fashion via nucleophilic addition reaction followed by oxidation. The desired products were afforded in the high yield of 50%~70%. Moreover, The effects of different catalyst, additives, reaction temperature and proportion of substrates on the reaction were also investigated. The results showed that the optimizing conditions of reaction were CuCl2 as catalyst, CH3COOH as additive and toluene as solvent. A series of 2-benzyl-3, 4-dihydro-2H-isoquinolin-1-ones can be efficiently obtained under the optimizing conditions.
An facile, effective, copper-catalyzed one-pot approach to 2-benzyl-3, 4-dihydroquinolin-1-ones has been successfully developed. The compounds were achieved by the reaction of tetrahydroisoquinoline, benzyl azide and benzaldehyde in one-pot fashion via nucleophilic addition reaction followed by oxidation. The desired products were afforded in the high yield of 50%~70%. Moreover, The effects of different catalyst, additives, reaction temperature and proportion of substrates on the reaction were also investigated. The results showed that the optimizing conditions of reaction were CuCl2 as catalyst, CH3COOH as additive and toluene as solvent. A series of 2-benzyl-3, 4-dihydro-2H-isoquinolin-1-ones can be efficiently obtained under the optimizing conditions.
