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2018 Volume 38 Issue 6
2018, 38(6): 1275-1291
doi: 10.6023/cjoc201712029
Abstract:
Diazo compounds are versatile building blocks in organic synthesis. They are served as 1, 3-dipoles, nucleophiles and carbene precursors in the construction of various organic molecules. However, the utility of diazo compounds is significantly limited by toxicity, instability and explosive potential. The application of continuous flow technology in this field could ensure the safety of these reactions. It also provides the possibility to utilize diazo compounds in a large scale. Categorized by the types of diazo compounds, the application of continuous flow technology in transformations of diazo compounds is systematically reviewed in this paper.
Diazo compounds are versatile building blocks in organic synthesis. They are served as 1, 3-dipoles, nucleophiles and carbene precursors in the construction of various organic molecules. However, the utility of diazo compounds is significantly limited by toxicity, instability and explosive potential. The application of continuous flow technology in this field could ensure the safety of these reactions. It also provides the possibility to utilize diazo compounds in a large scale. Categorized by the types of diazo compounds, the application of continuous flow technology in transformations of diazo compounds is systematically reviewed in this paper.
2018, 38(6): 1292-1318
doi: 10.6023/cjoc201801003
Abstract:
Frustrated Lewis pairs (FLPs) chemistry has grown rapidly during the last decade and provided a new strategy for the activation of a variety of small molecules, such as hydrogen, olefins, alkynes, carbon dioxide, tetrahydrofuran and hydrosilane etc. The activations of these molecules have probided a new method in the utility of main group element. The structure and reactivity of FLPs are reviewed and the recent progress in activation of small molecules promoted by frustrated Lewis pairs is introduced.
Frustrated Lewis pairs (FLPs) chemistry has grown rapidly during the last decade and provided a new strategy for the activation of a variety of small molecules, such as hydrogen, olefins, alkynes, carbon dioxide, tetrahydrofuran and hydrosilane etc. The activations of these molecules have probided a new method in the utility of main group element. The structure and reactivity of FLPs are reviewed and the recent progress in activation of small molecules promoted by frustrated Lewis pairs is introduced.
2018, 38(6): 1319-1326
doi: 10.6023/cjoc201802001
Abstract:
Pyrrolidines and pyrrolines, as important building blocks, are widely applied in the fields of medicine, agriculture and materials. Many synthetic methods for the preparation of pyrrolidines and pyrrolines have been reported over the past few years. Recently, following the rapid development of organometallic chemistry, the metal-catalyzed functionalization of unsaturated hydrocarbons has gradually become the research focus of organic synthesis methodology, due to the high efficiency and diversity of functionalization. Therefore the constructions of pyrrolidines and pyrrolines using metal-catalyzed unsaturated hydrocarbon functionalization are important and very useful. The development of metal-catalyzed functionalizations of different types of unsaturated hydrocarbons for the synthesis of pyrrolidines and pyrrolines is summarized.
Pyrrolidines and pyrrolines, as important building blocks, are widely applied in the fields of medicine, agriculture and materials. Many synthetic methods for the preparation of pyrrolidines and pyrrolines have been reported over the past few years. Recently, following the rapid development of organometallic chemistry, the metal-catalyzed functionalization of unsaturated hydrocarbons has gradually become the research focus of organic synthesis methodology, due to the high efficiency and diversity of functionalization. Therefore the constructions of pyrrolidines and pyrrolines using metal-catalyzed unsaturated hydrocarbon functionalization are important and very useful. The development of metal-catalyzed functionalizations of different types of unsaturated hydrocarbons for the synthesis of pyrrolidines and pyrrolines is summarized.
2018, 38(6): 1327-1340
doi: 10.6023/cjoc201712044
Abstract:
o-Carboranes, as well as its derivative o-carborynes, can react with a variety of unsaturated compounds through cycloadditions and transform into various functionalized carboranes which have potential applications in many an area such as boron neutron capture therapy, catalytic systhesis and drug design. Recently, people have made remarkable achievements in the functionalization of o-carboranes and o-carborynes, especially in aspects of reaction condition optimization, selectivity controlling and reaction mechanism exploration. The most recent experimental achievements in the area of cycloaddition between o-carboranes and unsaturated compounds, alkenes, polycyclic or heterocyclic aromatics, in the past ten years are summarized. The reaction mechanisms and corresponding computational findings of o-carboryne-involved [2+2+2], [2+2+1], [2+2], [3+2], [4+2] and[5+2] cycloadditions are summarized and emphasized. Moreover, the prospects of future development in this area are discussed in the end.
o-Carboranes, as well as its derivative o-carborynes, can react with a variety of unsaturated compounds through cycloadditions and transform into various functionalized carboranes which have potential applications in many an area such as boron neutron capture therapy, catalytic systhesis and drug design. Recently, people have made remarkable achievements in the functionalization of o-carboranes and o-carborynes, especially in aspects of reaction condition optimization, selectivity controlling and reaction mechanism exploration. The most recent experimental achievements in the area of cycloaddition between o-carboranes and unsaturated compounds, alkenes, polycyclic or heterocyclic aromatics, in the past ten years are summarized. The reaction mechanisms and corresponding computational findings of o-carboryne-involved [2+2+2], [2+2+1], [2+2], [3+2], [4+2] and[5+2] cycloadditions are summarized and emphasized. Moreover, the prospects of future development in this area are discussed in the end.
Transition-Metal-Catalyzed Guanylation Reaction of Amines with Carbodiimides Constructing Guanidines
2018, 38(6): 1341-1349
doi: 10.6023/cjoc201801037
Abstract:
Guanidine derivatives are an important class of nitrogen-containing organic compounds, which are widely used in various pharmaceuticals, agrochemicals, sweeteners, explosives, and so on. Although classical methods for the synthesis of guanidines are established, there are still many fatal shortcomings which need to be resolved. In recent years, it has been gradually turned to the direct catalytic guanylation reaction of amines with carbodiimides. In this paper, the recent progress in transition-metal-catalyzed guanylation reaction of amines with carbodiimides to construct acyclic or cyclic guanidines based on the catalytic reaction mechanism, reaction system, the scope of substrates, etc. is reviewed.
Guanidine derivatives are an important class of nitrogen-containing organic compounds, which are widely used in various pharmaceuticals, agrochemicals, sweeteners, explosives, and so on. Although classical methods for the synthesis of guanidines are established, there are still many fatal shortcomings which need to be resolved. In recent years, it has been gradually turned to the direct catalytic guanylation reaction of amines with carbodiimides. In this paper, the recent progress in transition-metal-catalyzed guanylation reaction of amines with carbodiimides to construct acyclic or cyclic guanidines based on the catalytic reaction mechanism, reaction system, the scope of substrates, etc. is reviewed.
2018, 38(6): 1350-1363
doi: 10.6023/cjoc201801017
Abstract:
Imines are a class of active intermediates and have good antibacterial activity, therefore, they have received the extensive concern of scientists. Since the preparation method of imines by oxidative coupling of amines has the advantages of high atom economy and environmental friendliness, it has become a research hotspot. The recent progress in oxidative coupling of amines to imines is summarized from two aspects:catalyst and catalytic mechanism in this article. We introduced all kinds of catalytic systems in detail such as noble metal, non-noble metal, photocatalysis, biomimetic catalysis, poly aniline, graphite oxide, and azobisisobutyronitrile (AIBN). The catalytic performance, advantages and drawbacks and applicability of which are highlighted. And the catalytic mechanisms of the main catalytic systems are also discussed. It should be pointed out that these catalytic systems for oxidative coupling of amines to imines showed varying degrees of success as well as limitations like high cost of catalyst, harsh reaction condition, use of oxidant, alkaline additives and/or toxic organic solvents. Finally, based on the existential problems for oxidative coupling of amines to imines, the research directions in this field are predicted.
Imines are a class of active intermediates and have good antibacterial activity, therefore, they have received the extensive concern of scientists. Since the preparation method of imines by oxidative coupling of amines has the advantages of high atom economy and environmental friendliness, it has become a research hotspot. The recent progress in oxidative coupling of amines to imines is summarized from two aspects:catalyst and catalytic mechanism in this article. We introduced all kinds of catalytic systems in detail such as noble metal, non-noble metal, photocatalysis, biomimetic catalysis, poly aniline, graphite oxide, and azobisisobutyronitrile (AIBN). The catalytic performance, advantages and drawbacks and applicability of which are highlighted. And the catalytic mechanisms of the main catalytic systems are also discussed. It should be pointed out that these catalytic systems for oxidative coupling of amines to imines showed varying degrees of success as well as limitations like high cost of catalyst, harsh reaction condition, use of oxidant, alkaline additives and/or toxic organic solvents. Finally, based on the existential problems for oxidative coupling of amines to imines, the research directions in this field are predicted.
2018, 38(6): 1364-1376
doi: 10.6023/cjoc201712031
Abstract:
Fluorescent imaging technology has received great attention owing to their advantageous features in high sensitivity, relatively simple operations and real-time living cells, tissue and in vivo imaging. Compared with one-photon confocal imaging, two-photon confocal imaging offers considerable advantages such as high resolution, deep-tissue depth, lower tissue auto-fluorescence and so on. As typical D-π-A two-photon dyes, 1, 8-naphthalimide dyes have wide application in two-photon imaging for enzyme, reactive carbon species, reactive oxygen species, reactive nitrogen species, biothiols and ions due to their advantages such as high photostability, large Stokes/anti-Stokes shifts. According to the mechanisms of intramolecular charge transfer, photoinduced electron transfer and fluorescence resonance energy transfer, etc., the application in two-photon imaging of 1, 8-naphthalimide dyes is summarized and emphasized.
Fluorescent imaging technology has received great attention owing to their advantageous features in high sensitivity, relatively simple operations and real-time living cells, tissue and in vivo imaging. Compared with one-photon confocal imaging, two-photon confocal imaging offers considerable advantages such as high resolution, deep-tissue depth, lower tissue auto-fluorescence and so on. As typical D-π-A two-photon dyes, 1, 8-naphthalimide dyes have wide application in two-photon imaging for enzyme, reactive carbon species, reactive oxygen species, reactive nitrogen species, biothiols and ions due to their advantages such as high photostability, large Stokes/anti-Stokes shifts. According to the mechanisms of intramolecular charge transfer, photoinduced electron transfer and fluorescence resonance energy transfer, etc., the application in two-photon imaging of 1, 8-naphthalimide dyes is summarized and emphasized.
2018, 38(6): 1377-1393
doi: 10.6023/cjoc201712034
Abstract:
Triplet-triplet annihilation (TTA) upconversion, a unique technique that converting low-energy photons into higher-energy photons, has attracted much attention owing to its potential applications in various fields, such as solar cells, bioimaging, photocatalysis and photoelectric device. TTA upconversion has several advantages over other upconversion methods, such as allowing for the use of low excitation power density, readily tunable excitation/emission wavelength and high upconversion quantum yield. Both triplet-triplet energy transfer (TTET) and TTA processes in TTA upconversion follow the Dexter energy transfer mechanism. The components involved have to diffuse in the media and collide within the lifetime of their excited states to complete the energy transfer. Thus, most efficient TTA-based upconversion has been achieved with donor-acceptor pairs that are molecularly dissolved in deaerated organic solvents, which however significantly limited their practical applications. In recent years, more and more efforts have beendevoted to explore high-efficient TTA upconversion under aerated conditions by employing specific solid materials or viscous liquids as matrices to block oxygen. The recent advance of research of TTA upconversion in aggregated systems is summarized, including rubbery polymers, gels, molecular crystals, nanoparticles and supramolecular self-assemblies.
Triplet-triplet annihilation (TTA) upconversion, a unique technique that converting low-energy photons into higher-energy photons, has attracted much attention owing to its potential applications in various fields, such as solar cells, bioimaging, photocatalysis and photoelectric device. TTA upconversion has several advantages over other upconversion methods, such as allowing for the use of low excitation power density, readily tunable excitation/emission wavelength and high upconversion quantum yield. Both triplet-triplet energy transfer (TTET) and TTA processes in TTA upconversion follow the Dexter energy transfer mechanism. The components involved have to diffuse in the media and collide within the lifetime of their excited states to complete the energy transfer. Thus, most efficient TTA-based upconversion has been achieved with donor-acceptor pairs that are molecularly dissolved in deaerated organic solvents, which however significantly limited their practical applications. In recent years, more and more efforts have beendevoted to explore high-efficient TTA upconversion under aerated conditions by employing specific solid materials or viscous liquids as matrices to block oxygen. The recent advance of research of TTA upconversion in aggregated systems is summarized, including rubbery polymers, gels, molecular crystals, nanoparticles and supramolecular self-assemblies.
2018, 38(6): 1394-1400
doi: 10.6023/cjoc201711018
Abstract:
A turn-on supramolecular fluorescent probe between cucurbit[8]uril (Q[8]) and pyronine Y (PyY) (designated 2PyY@Q[8]) showed a remarkable fluorescence “turn-on” response to lapatinib ditosylate (LD). The 2PyY@Q[8] fluorescent probe can be used to detect lapatinib ditosylate with high sensitivity and selectivity with a detection limit of ca. 10-8 mol/L. A good linear relationship of emission intensity for lapatinib ditosylate at concentrations of 10×10-8～250×10-8 mol/L was observed. The cell imaging study showed that the 2PyY@Q[8] complex could be used to image lapatinib in prostate cancer (PC3) cells, which may help to elucidate relevant biological processes at the molecular level.
A turn-on supramolecular fluorescent probe between cucurbit[8]uril (Q[8]) and pyronine Y (PyY) (designated 2PyY@Q[8]) showed a remarkable fluorescence “turn-on” response to lapatinib ditosylate (LD). The 2PyY@Q[8] fluorescent probe can be used to detect lapatinib ditosylate with high sensitivity and selectivity with a detection limit of ca. 10-8 mol/L. A good linear relationship of emission intensity for lapatinib ditosylate at concentrations of 10×10-8～250×10-8 mol/L was observed. The cell imaging study showed that the 2PyY@Q[8] complex could be used to image lapatinib in prostate cancer (PC3) cells, which may help to elucidate relevant biological processes at the molecular level.
2018, 38(6): 1414-1421
doi: 10.6023/cjoc201802005
Abstract:
17 novel sorafenib derivatives possessing diphenylamine and thiourea structures were designed and synthesized using 2-picolinic acid and substituted anilines as raw materials. The structures of the target compounds were all characterized by NMR and HRMS. In addition, the in vitro antiproliferation activity of the target compounds was studied in human colon cancer cell HCT116, human breast cancer cell line MDA-MB-231, human prostate cancer cell line PC-3 and mouse melanoma cell line B16BL6. The results showed that 1-(4-chloro-3-trifluoromethylphenyl)-3-(4-(2-(isopropylcarbamoyl)pyridine-4-amino)phenyl)thiourea (9g) had better inhibitory activity against four cell lines than the positive drug sorafenib, and 1-(3-trifluoromethyl-4-chlorophenyl)-3-{4-[2-(methylcarbamoyl)pyridine-4-amino]phenyl}thiourea (9b) and 1-(3-trifluoro-methyl-4-fluorophenyl)-3-{4-[2-(isopropylcarbamoyl)pyridine-4-amino]phenyl}thiourea (9j) had better inhibitory activity against MDA-MB-231, PC-3 and B16BL6 cell lines. The molecular docking of the active small molecule 9j was further studied, and its binding mode with the active site of the 3-D crystal structure (5HI2) of B-Raf receptor was discussed, which provided a useful reference for the design and synthesis of novel sorafenib derivatives in the future.
17 novel sorafenib derivatives possessing diphenylamine and thiourea structures were designed and synthesized using 2-picolinic acid and substituted anilines as raw materials. The structures of the target compounds were all characterized by NMR and HRMS. In addition, the in vitro antiproliferation activity of the target compounds was studied in human colon cancer cell HCT116, human breast cancer cell line MDA-MB-231, human prostate cancer cell line PC-3 and mouse melanoma cell line B16BL6. The results showed that 1-(4-chloro-3-trifluoromethylphenyl)-3-(4-(2-(isopropylcarbamoyl)pyridine-4-amino)phenyl)thiourea (9g) had better inhibitory activity against four cell lines than the positive drug sorafenib, and 1-(3-trifluoromethyl-4-chlorophenyl)-3-{4-[2-(methylcarbamoyl)pyridine-4-amino]phenyl}thiourea (9b) and 1-(3-trifluoro-methyl-4-fluorophenyl)-3-{4-[2-(isopropylcarbamoyl)pyridine-4-amino]phenyl}thiourea (9j) had better inhibitory activity against MDA-MB-231, PC-3 and B16BL6 cell lines. The molecular docking of the active small molecule 9j was further studied, and its binding mode with the active site of the 3-D crystal structure (5HI2) of B-Raf receptor was discussed, which provided a useful reference for the design and synthesis of novel sorafenib derivatives in the future.
2018, 38(6): 1437-1446
doi: 10.6023/cjoc201712005
Abstract:
Highly diastereoselective Michael addition reactions of chiral Ni(Ⅱ)-complex of glycine with α, β-unsaturated ketones in the presence of 1, 8-diazabicyclo[5.4.0]undec-7-ene (DBU) and MeOH at ambient temperature were achieved. The operationally convenient procedure for preparation of the target products renders that this method is an attractive strategy for practical synthesis of 3, 5-disubstituted prolines.
Highly diastereoselective Michael addition reactions of chiral Ni(Ⅱ)-complex of glycine with α, β-unsaturated ketones in the presence of 1, 8-diazabicyclo[5.4.0]undec-7-ene (DBU) and MeOH at ambient temperature were achieved. The operationally convenient procedure for preparation of the target products renders that this method is an attractive strategy for practical synthesis of 3, 5-disubstituted prolines.
2018, 38(6): 1447-1453
doi: 10.6023/cjoc201712030
Abstract:
A series of 2-morpholino-1-propyl-1H-indole-3-substituted acylhydrazone derivatives were designed and synthesized from oxindole. All the compounds were characterized by 1H NMR, 13C NMR and HRMS spectra, and their antibacterial activities were evaluated via turbidimeter test in vitro. The preliminary bioassay results indicated that all of the title compounds exhibited certain antibacterial activities in vitro against Xanthomonas axonopodis pv. Citri (X. citri), Ralstonia.solanacearum (R. solanacearum) and Xanthomonas oryzae pv. Oryzae (X. oryzae). These title compounds 2-cyano-N'-((2-morpholino-1-propyl-1H-indol-3-yl)methylene)acetohydrazide (12a), 4-chloro-N'-((2-morpholino-1-propyl-1H-indol-3-ylmethylene)ben-zohydrazide (12c), 4-fluoro-N'-((2-morpholino-1-propyl-1H-indol-3-yl)methylene)benzohydrazide (12f), N'-((2-morpholino-1-propyl-1H-indol-3-yl)methylene)-4-nitrobenzohydrazide (12k) and N'-((2-morpholino-1-propyl-1H-indol-3-yl)methylene) isonicotinohydrazide (12m) displayed good antibacterial activities. The concentration of 50% inhibition rate (EC50) of 12a, 12c, 12f, 12k and 12m against X. oryzae were 73.79, 61.94, 59.70, 36.72 and 82.79 μg/mL respectively, which was significantly superior to the control bismerthiazol and thiodiazole-copper (92.46 μg/mL and 120.22 μg/mL).
A series of 2-morpholino-1-propyl-1H-indole-3-substituted acylhydrazone derivatives were designed and synthesized from oxindole. All the compounds were characterized by 1H NMR, 13C NMR and HRMS spectra, and their antibacterial activities were evaluated via turbidimeter test in vitro. The preliminary bioassay results indicated that all of the title compounds exhibited certain antibacterial activities in vitro against Xanthomonas axonopodis pv. Citri (X. citri), Ralstonia.solanacearum (R. solanacearum) and Xanthomonas oryzae pv. Oryzae (X. oryzae). These title compounds 2-cyano-N'-((2-morpholino-1-propyl-1H-indol-3-yl)methylene)acetohydrazide (12a), 4-chloro-N'-((2-morpholino-1-propyl-1H-indol-3-ylmethylene)ben-zohydrazide (12c), 4-fluoro-N'-((2-morpholino-1-propyl-1H-indol-3-yl)methylene)benzohydrazide (12f), N'-((2-morpholino-1-propyl-1H-indol-3-yl)methylene)-4-nitrobenzohydrazide (12k) and N'-((2-morpholino-1-propyl-1H-indol-3-yl)methylene) isonicotinohydrazide (12m) displayed good antibacterial activities. The concentration of 50% inhibition rate (EC50) of 12a, 12c, 12f, 12k and 12m against X. oryzae were 73.79, 61.94, 59.70, 36.72 and 82.79 μg/mL respectively, which was significantly superior to the control bismerthiazol and thiodiazole-copper (92.46 μg/mL and 120.22 μg/mL).
2018, 38(6): 1454-1461
doi: 10.6023/cjoc201712042
Abstract:
The α-chlorination of α-substituted-α-cyano ketone compounds and 1, 3-dicabonyl compounds is described. Using 0.34 equiv. trichloroisocyanuric acid as chlorine source, the chlorination can efficiently access at room temperature in a mild condition without additional oxidant or base. The chloride products can be obtained in a higher yield.
The α-chlorination of α-substituted-α-cyano ketone compounds and 1, 3-dicabonyl compounds is described. Using 0.34 equiv. trichloroisocyanuric acid as chlorine source, the chlorination can efficiently access at room temperature in a mild condition without additional oxidant or base. The chloride products can be obtained in a higher yield.
2018, 38(6): 1477-1483
doi: 10.6023/cjoc201801020
Abstract:
The interaction of a pair of amino acid enantiomers, L-3-(2-naphthyl)-alanine (L-NA) and D-3-(2-naphthyl)-alanine (D-NA), with cucurbit[7]uril (Q[7]) and inverted cucurbit[7]uril (iQ[7]) was investigated, respectively, by using NMR spectroscopy, electronic absorption spectroscopy, fluorescence spectroscopies, isothermal titration calorimetry (ITC) experiments and MALDI-TOF mass spectrometry. Furthermore, the similarities and differences of the self-assembly patterns between the two kinds of cucurbituril with different cavity sizes and this pair of amino acid enantiomers were also researched. The results obtained from the experiment revealed that the naphthyl groups of amino acids were all entrapped in the cavity of the Q[n]s, whereas the other section of amino acids remained outside the portal and thus resulted in a more stable supramolecular self-assembly at a 1:1 ratio. Meanwhile, we found that the two different kinds of cucurbit[7]urils showed a slightly different selectivity for the L/D-NA chiral enantiomer.
The interaction of a pair of amino acid enantiomers, L-3-(2-naphthyl)-alanine (L-NA) and D-3-(2-naphthyl)-alanine (D-NA), with cucurbit[7]uril (Q[7]) and inverted cucurbit[7]uril (iQ[7]) was investigated, respectively, by using NMR spectroscopy, electronic absorption spectroscopy, fluorescence spectroscopies, isothermal titration calorimetry (ITC) experiments and MALDI-TOF mass spectrometry. Furthermore, the similarities and differences of the self-assembly patterns between the two kinds of cucurbituril with different cavity sizes and this pair of amino acid enantiomers were also researched. The results obtained from the experiment revealed that the naphthyl groups of amino acids were all entrapped in the cavity of the Q[n]s, whereas the other section of amino acids remained outside the portal and thus resulted in a more stable supramolecular self-assembly at a 1:1 ratio. Meanwhile, we found that the two different kinds of cucurbit[7]urils showed a slightly different selectivity for the L/D-NA chiral enantiomer.
2018, 38(6): 1484-1492
doi: 10.6023/cjoc201710005
Abstract:
Using a testosterone as a raw material, a steroidal skelecton with A-homo-lactam was constructed. Then, some new aza-A-homocholesteryl-lactam thiazole derivatives were synthesized by modifying of the 17-hydroxyl and introducing of various heterocycles, and their structures were determined by IR, NMR and HRMS. The antiproliferative activity of the compounds against different carcinoma cells was assayed. The results show that some compounds display a distinct antiproliferative activity against tested cancer cells and are almost inactive to HEK293T cells.
Using a testosterone as a raw material, a steroidal skelecton with A-homo-lactam was constructed. Then, some new aza-A-homocholesteryl-lactam thiazole derivatives were synthesized by modifying of the 17-hydroxyl and introducing of various heterocycles, and their structures were determined by IR, NMR and HRMS. The antiproliferative activity of the compounds against different carcinoma cells was assayed. The results show that some compounds display a distinct antiproliferative activity against tested cancer cells and are almost inactive to HEK293T cells.
2018, 38(6): 1500-1506
doi: 10.6023/cjoc201710011
Abstract:
Sixteen bridging ligand compounds of azo with 1, 3, 5-substitued triazole had been synthesized from 1, 3, 5-trisub-stituted-1, 2, 4-triazoles by the oxidative coupling reaction using potassium permanganate or sodium dichloroisocyamirate as the oxidant. The structures of the target compounds were determined by 1H NMR, 13C NMR, IR, MS, HRMS and X-ray diffraction. They were tested for in vitro fungicidal activities by the mycelium growth rate method. The results indicated that most of the title compounds had a certain inhibitory activity at the concentration of 50 μg/mL. Especially, the inhibition rate of 1, 2-bis(1-butyl-3-(2-chlorophenyl)-1H-1, 2, 4-triazol-5-yl)diazene (3h) and 1, 2-bis(3-(4-chlorophenyl)-1-propyl-1H-1, 2, 4-triazol-5-yl)diazene (3k) were close to that of triadimefon when against Pythium aphanidermatum, while the inhibition rate of 1, 2-bis(3-(2-chlorophenyl)-1-propyl-1H-1, 2, 4-triazol-5-yl)diazene (3g) was higher than that of riadimefon. The reactions of these compounds were simple and mild, which was of reference significance to the creation and synthesis of new pesticides.
Sixteen bridging ligand compounds of azo with 1, 3, 5-substitued triazole had been synthesized from 1, 3, 5-trisub-stituted-1, 2, 4-triazoles by the oxidative coupling reaction using potassium permanganate or sodium dichloroisocyamirate as the oxidant. The structures of the target compounds were determined by 1H NMR, 13C NMR, IR, MS, HRMS and X-ray diffraction. They were tested for in vitro fungicidal activities by the mycelium growth rate method. The results indicated that most of the title compounds had a certain inhibitory activity at the concentration of 50 μg/mL. Especially, the inhibition rate of 1, 2-bis(1-butyl-3-(2-chlorophenyl)-1H-1, 2, 4-triazol-5-yl)diazene (3h) and 1, 2-bis(3-(4-chlorophenyl)-1-propyl-1H-1, 2, 4-triazol-5-yl)diazene (3k) were close to that of triadimefon when against Pythium aphanidermatum, while the inhibition rate of 1, 2-bis(3-(2-chlorophenyl)-1-propyl-1H-1, 2, 4-triazol-5-yl)diazene (3g) was higher than that of riadimefon. The reactions of these compounds were simple and mild, which was of reference significance to the creation and synthesis of new pesticides.
2018, 38(6): 1516-1524
doi: 10.6023/cjoc201712018
Abstract:
In order to study the structure-activity relationships of dinaphthofuran derivatives, two series of dinaphtho[2, 1-b:1', 2'-d]furan derivatives were synthesized. The structures of all compounds were identified by 1H NMR, 13C NMR, HRMS and IR spectra. The in vitro antitumor activity of the synthesized derivatives was tested by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Most of them exhibited strong inhibitory activity on human hepatocellular carcinoma cell lines (HepG2 and SMMC-7721 cells), uterine cervix cancer Hela cells and acute promyelocytic leukemia NB4 cells. Compound 13k exhibited significant inhibitory activity against SMMC-7721 cells with IC50 vaue of 0.57 μmol·L-1, much lower than 20.21 μmol·L-1 of the positive control 5-Fu.
In order to study the structure-activity relationships of dinaphthofuran derivatives, two series of dinaphtho[2, 1-b:1', 2'-d]furan derivatives were synthesized. The structures of all compounds were identified by 1H NMR, 13C NMR, HRMS and IR spectra. The in vitro antitumor activity of the synthesized derivatives was tested by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Most of them exhibited strong inhibitory activity on human hepatocellular carcinoma cell lines (HepG2 and SMMC-7721 cells), uterine cervix cancer Hela cells and acute promyelocytic leukemia NB4 cells. Compound 13k exhibited significant inhibitory activity against SMMC-7721 cells with IC50 vaue of 0.57 μmol·L-1, much lower than 20.21 μmol·L-1 of the positive control 5-Fu.
2018, 38(6): 1401-1413
doi: 10.6023/cjoc201712009
Abstract:
A series of hexahydroquinazolin-2-amine-based derivatives have been designed and synthesized from renewable isolongifolanone. Their solid states exhibited an enhanced emission and a dark green to bright yellow color range. In addition to good thermal stability, their solid-state fluorescence is not readily restricted by multiple conventional factors such as long term UV irradiation, increasing operated pressure and elevated heating temperature. In contrast to the derivatives which undergo serious aggregation-caused quenching (ACQ), the dimethylamino-substituted derivative 1-6, 6, 10, 10-tetramethyl-4-(4'-(N, N-dimethylamino)phenyl)-5, 7, 8, 9, 10, 10a-hexahydro-6H-6a, 9-methanobenzo[h]quinazolin-2-imino)methyl)naphthalen-2-ol (3e) demonstrate obvious aggregation-induced emission (AIE) characteristics. Moreover, these fluorescent derivatives were also used for specific and sensitive sensing of Zn2+ ion in aqueous solutions. Then, their photophysical mechanisms were obtained by the density functional theory calculations. These probes were successfully applied to image Zn2+ ion in pollen grains of Althaea rosea.
A series of hexahydroquinazolin-2-amine-based derivatives have been designed and synthesized from renewable isolongifolanone. Their solid states exhibited an enhanced emission and a dark green to bright yellow color range. In addition to good thermal stability, their solid-state fluorescence is not readily restricted by multiple conventional factors such as long term UV irradiation, increasing operated pressure and elevated heating temperature. In contrast to the derivatives which undergo serious aggregation-caused quenching (ACQ), the dimethylamino-substituted derivative 1-6, 6, 10, 10-tetramethyl-4-(4'-(N, N-dimethylamino)phenyl)-5, 7, 8, 9, 10, 10a-hexahydro-6H-6a, 9-methanobenzo[h]quinazolin-2-imino)methyl)naphthalen-2-ol (3e) demonstrate obvious aggregation-induced emission (AIE) characteristics. Moreover, these fluorescent derivatives were also used for specific and sensitive sensing of Zn2+ ion in aqueous solutions. Then, their photophysical mechanisms were obtained by the density functional theory calculations. These probes were successfully applied to image Zn2+ ion in pollen grains of Althaea rosea.
2018, 38(6): 1507-1515
doi: 10.6023/cjoc201712002
Abstract:
1, 5-Bromotrichloromethylation of α-cyclopropylstyrenes via a radical chain pathway was achieved with Ir[dF(CF3)ppy]2(dtbbpy)PF6 as a photoinitiator under visible-light irradiation to give trisubstituted styrenes with Z/E ratio of 30:70. When the reaction mixture was further irradiated, the Z/E ratio could be reversed and increased to 99:1, probably via an energy-transfer pathway involving the Ir photocatalyst. This visible-light-induced catalytic isomerization protocol could also be applied to trisubstituted styrenes to obtain products with Z/E ratios up to 99:1.
1, 5-Bromotrichloromethylation of α-cyclopropylstyrenes via a radical chain pathway was achieved with Ir[dF(CF3)ppy]2(dtbbpy)PF6 as a photoinitiator under visible-light irradiation to give trisubstituted styrenes with Z/E ratio of 30:70. When the reaction mixture was further irradiated, the Z/E ratio could be reversed and increased to 99:1, probably via an energy-transfer pathway involving the Ir photocatalyst. This visible-light-induced catalytic isomerization protocol could also be applied to trisubstituted styrenes to obtain products with Z/E ratios up to 99:1.
2018, 38(6): 1422-1430
doi: 10.6023/cjoc201801009
Abstract:
25 kinds of 6, 7-dihydro-5H-cyclopenta[4, 5]thieno[2, 3-d]pyrimidin-4-amines were synthesized. Under microwave irradiation conditions, cyclopentanone, malononitrile and elemental sulfur reacted in ethanol to form 2-amino-5, 6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (1). Compound 1 reacted with N, N-dimethylformamide dimethyl acetal to give N-(3-cyano-5, 6-dihydro-4H-cyclopenta[b]-thien-2-yl)-N, N-dimethylmethanimidamide (2) under microwave irradiation conditions. Treatment of the compound 2 with aromatic amine under microwave irradiation yielded the corresponding compounds 6, 7-dihydro-5H-cyclopenta[4, 5]thieno[2, 3-d]pyrimidin-4-amine with good yields. The structures of the 25 target compounds were confirmed by melting point, NMR, IR and HRMS techniques.
25 kinds of 6, 7-dihydro-5H-cyclopenta[4, 5]thieno[2, 3-d]pyrimidin-4-amines were synthesized. Under microwave irradiation conditions, cyclopentanone, malononitrile and elemental sulfur reacted in ethanol to form 2-amino-5, 6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (1). Compound 1 reacted with N, N-dimethylformamide dimethyl acetal to give N-(3-cyano-5, 6-dihydro-4H-cyclopenta[b]-thien-2-yl)-N, N-dimethylmethanimidamide (2) under microwave irradiation conditions. Treatment of the compound 2 with aromatic amine under microwave irradiation yielded the corresponding compounds 6, 7-dihydro-5H-cyclopenta[4, 5]thieno[2, 3-d]pyrimidin-4-amine with good yields. The structures of the 25 target compounds were confirmed by melting point, NMR, IR and HRMS techniques.
2018, 38(6): 1431-1436
doi: 10.6023/cjoc201801034
Abstract:
A practical amidation reaction for the synthesis of primary amides is presented, in which the simple NH4Cl was identified as a practical and convenient amine source. A series of aromatic and aliphatic acid chlorides were successfully compatible with this protocol, affording the corresponding amides in good to excellent yields, which provides a rapid and reliable approach to amides from simple starting materials. Introducing the appropriate N-methyl pyrrolidone (NMP) into the system as solvent and acid-binding reagent plays a key role to avoid the use of stoichiometric amounts of base.
A practical amidation reaction for the synthesis of primary amides is presented, in which the simple NH4Cl was identified as a practical and convenient amine source. A series of aromatic and aliphatic acid chlorides were successfully compatible with this protocol, affording the corresponding amides in good to excellent yields, which provides a rapid and reliable approach to amides from simple starting materials. Introducing the appropriate N-methyl pyrrolidone (NMP) into the system as solvent and acid-binding reagent plays a key role to avoid the use of stoichiometric amounts of base.
2018, 38(6): 1462-1468
doi: 10.6023/cjoc201712011
Abstract:
Two fluorescent compounds, 7-hydroxy-6-oxo-6H-benzo[c]chromene-8-carboxylic acid (3a) and 2, 3-benzo[f]-7-hydroxy-6-oxo-6H-benzo[c]chromene-8-carboxylic acid (3b) have been synthesized and characterized by the method of X-ray single crystal diffraction. 3a and 3b show high fluorescence quantum efficiency in both ethanol solution and solid state. In the crystal-state, dimerization of carboxylic group and intermolecular interaction lead to 3a owned a high fluorescence quantum efficiency (ФF=0.32). The dimers existing in 3a crystal lattice, are composed of carboxylic acid groups and have strong intermolecular interactions (bond lengths are 0.1870 nm, bond angles are 166.8°). All the atoms in dimer are nearly coplanar, showing extremely strong plane rigidity. The dimers are connected by C-H…O intermolecular hydrogen bonds, and the edge-to-face stackings exist in neighbor dimers.
Two fluorescent compounds, 7-hydroxy-6-oxo-6H-benzo[c]chromene-8-carboxylic acid (3a) and 2, 3-benzo[f]-7-hydroxy-6-oxo-6H-benzo[c]chromene-8-carboxylic acid (3b) have been synthesized and characterized by the method of X-ray single crystal diffraction. 3a and 3b show high fluorescence quantum efficiency in both ethanol solution and solid state. In the crystal-state, dimerization of carboxylic group and intermolecular interaction lead to 3a owned a high fluorescence quantum efficiency (ФF=0.32). The dimers existing in 3a crystal lattice, are composed of carboxylic acid groups and have strong intermolecular interactions (bond lengths are 0.1870 nm, bond angles are 166.8°). All the atoms in dimer are nearly coplanar, showing extremely strong plane rigidity. The dimers are connected by C-H…O intermolecular hydrogen bonds, and the edge-to-face stackings exist in neighbor dimers.
2018, 38(6): 1469-1476
doi: 10.6023/cjoc201712036
Abstract:
A Lewis acid-catalyzed[3+2] cycloaddition of trifluoromethylated N-acylhydrazones with alkenes was explored, and a series of CF3-substituted pryazolidines were obtained in high yields (up to 91%). The reaction features the use of cheap and readily available trifluoromethylated N-acylhydrazones as trifluoromethyl building blocks, mild reaction conditions and easy operation. Furthermore, the cycloadducts can be transformed into trifluoromethylated pyrazolines in excellent yields.
A Lewis acid-catalyzed[3+2] cycloaddition of trifluoromethylated N-acylhydrazones with alkenes was explored, and a series of CF3-substituted pryazolidines were obtained in high yields (up to 91%). The reaction features the use of cheap and readily available trifluoromethylated N-acylhydrazones as trifluoromethyl building blocks, mild reaction conditions and easy operation. Furthermore, the cycloadducts can be transformed into trifluoromethylated pyrazolines in excellent yields.
2018, 38(6): 1525-1529
doi: 10.6023/cjoc201712020
Abstract:
Benzylic C-H fluorination has emerged as a valuable tool for the introduction of fluorine. However, the powerfulness of benzylic C-H fluorination has not been tested in any multi-step synthesis. α, β-Difluoro-γ-amino acids are useful entities for biological application owing to the so-called fluorine conformational effect. In this work, benzylic C-H fluorination has been successfully utilized as the key step for the formal synthesis of syn-α, β-difluoro-γ-amino acid 1, a very challenging but useful target. The approach developed in this work could be viewed as more practical compared to the previous one, because:(1) no corrosive and toxic nucleophilic fluorinating reagents are used, (2) the overall yield is 18% (the previous approach is about 5%), and (3) the key benzylic C-H reaction developed by Chen and co-workers was scaled up to one gram without decreasing its original efficiency. A striking fluorine effect was observed:a carbon with one fluorine atom on the adjacent carbon is much less reactive than an ordinary carbon for the benzylic C-H fluorination.
Benzylic C-H fluorination has emerged as a valuable tool for the introduction of fluorine. However, the powerfulness of benzylic C-H fluorination has not been tested in any multi-step synthesis. α, β-Difluoro-γ-amino acids are useful entities for biological application owing to the so-called fluorine conformational effect. In this work, benzylic C-H fluorination has been successfully utilized as the key step for the formal synthesis of syn-α, β-difluoro-γ-amino acid 1, a very challenging but useful target. The approach developed in this work could be viewed as more practical compared to the previous one, because:(1) no corrosive and toxic nucleophilic fluorinating reagents are used, (2) the overall yield is 18% (the previous approach is about 5%), and (3) the key benzylic C-H reaction developed by Chen and co-workers was scaled up to one gram without decreasing its original efficiency. A striking fluorine effect was observed:a carbon with one fluorine atom on the adjacent carbon is much less reactive than an ordinary carbon for the benzylic C-H fluorination.
2018, 38(6): 1530-1537
doi: 10.6023/cjoc201712045
Abstract:
Employing molecular iodine as the sole oxidant, a new and transition metal-free diamination reaction of α, β-unsaturated ketones with 2-aminopyridines has been developed. It can not only produce 3-acyl imidazo[1, 2-a]pyridines but can also generate novel 2-acyl derivatives regioselectively by changing the solvent and substituents in the 2-aminopyridine substrates.
Employing molecular iodine as the sole oxidant, a new and transition metal-free diamination reaction of α, β-unsaturated ketones with 2-aminopyridines has been developed. It can not only produce 3-acyl imidazo[1, 2-a]pyridines but can also generate novel 2-acyl derivatives regioselectively by changing the solvent and substituents in the 2-aminopyridine substrates.
2018, 38(6): 1493-1499
doi: 10.6023/cjoc201710009
Abstract:
A metal-free synthetic protocol for N-vinylazoles has been developed. Twenty-two structurally diversed N-vinylazoles including 15 new compounds are obtained with good to high yield at near room temperature, and all of products consist trans-alkene moieties with high stereoselectivity.
A metal-free synthetic protocol for N-vinylazoles has been developed. Twenty-two structurally diversed N-vinylazoles including 15 new compounds are obtained with good to high yield at near room temperature, and all of products consist trans-alkene moieties with high stereoselectivity.
2018, 38(6): 1538-1543
doi: 10.6023/cjoc201802019
Abstract:
1, 3-Diyne compounds are important inter mediates in organic synthesis, which are widely used in pharmaceutical chemistry, organic synthesis and materials science. A highly efficient for the synthesis of 1, 3-diyne via cross-coupling of alkynyl bromides with alkynyl aluminium reagents catalyzed by nickel has been developed. The coupling reaction of alkynyl bromides with alkynyl aluminium reagents mediated by Ni(acac)2 (5 mol%)/1, 2-bis(diphenylphosphino)ethane nickel(Ⅱ) chloride (DPPE) (10 mol%)in 1, 2-dimethoxyethane afforded the corresponding coupling products 1, 3-diyne in good to excellent yields(up to 90%) at room temperature for 5 h. The coupling reaction of alkynyl aluminum with different substituents and alkynyl bromine with various substituents can afforded the coupling products in good yields. Importantly, the α-ethynylnaphthalene and 2-ethynylthiophene were also suitable for the reaction. This process is simple and easily performed, which provides an efficient method for the synthesis of 1, 3-diynes derivatives.
1, 3-Diyne compounds are important inter mediates in organic synthesis, which are widely used in pharmaceutical chemistry, organic synthesis and materials science. A highly efficient for the synthesis of 1, 3-diyne via cross-coupling of alkynyl bromides with alkynyl aluminium reagents catalyzed by nickel has been developed. The coupling reaction of alkynyl bromides with alkynyl aluminium reagents mediated by Ni(acac)2 (5 mol%)/1, 2-bis(diphenylphosphino)ethane nickel(Ⅱ) chloride (DPPE) (10 mol%)in 1, 2-dimethoxyethane afforded the corresponding coupling products 1, 3-diyne in good to excellent yields(up to 90%) at room temperature for 5 h. The coupling reaction of alkynyl aluminum with different substituents and alkynyl bromine with various substituents can afforded the coupling products in good yields. Importantly, the α-ethynylnaphthalene and 2-ethynylthiophene were also suitable for the reaction. This process is simple and easily performed, which provides an efficient method for the synthesis of 1, 3-diynes derivatives.
2018, 38(6): 1544-1548
doi: 10.6023/cjoc201801004
Abstract:
Tritertbutylphosphinimine phenoxy titanium complexes (t-Bu3)PNTi(OAr)Cl2 [Ar=C6H5(4a), 2, 6-Me2C6H3 (4b), 2, 6-i-Pr2C6H3 (4c) and 2, 6-t-Bu2C6H3 (4d)] were synthesized via the reaction of corresponding substituted phenol lithium salts with tritertbutylphosphinimine trichloride titanium (3). The compounds were characterized by means of 1H NMR, 13C NMR, 31P NMR spectroscopic and elemental analyses, and the molecular structures of 3, 4b and 4d were further confirmed by single-crystal X-ray diffraction analysis. When activated with methylaluminoxane (MAO), 4a~4d displayed not only high catalytic activities, but also increasing performances on ethylene polymerization with increasing the sterical hindrance of substituents. Furthermore, 4c depicted a good thermal stability, with which the polyethylene products of different molecular weights and molecular weight distributions can be obtained by tuning the polymerization conditions.
Tritertbutylphosphinimine phenoxy titanium complexes (t-Bu3)PNTi(OAr)Cl2 [Ar=C6H5(4a), 2, 6-Me2C6H3 (4b), 2, 6-i-Pr2C6H3 (4c) and 2, 6-t-Bu2C6H3 (4d)] were synthesized via the reaction of corresponding substituted phenol lithium salts with tritertbutylphosphinimine trichloride titanium (3). The compounds were characterized by means of 1H NMR, 13C NMR, 31P NMR spectroscopic and elemental analyses, and the molecular structures of 3, 4b and 4d were further confirmed by single-crystal X-ray diffraction analysis. When activated with methylaluminoxane (MAO), 4a~4d displayed not only high catalytic activities, but also increasing performances on ethylene polymerization with increasing the sterical hindrance of substituents. Furthermore, 4c depicted a good thermal stability, with which the polyethylene products of different molecular weights and molecular weight distributions can be obtained by tuning the polymerization conditions.
2018, 38(6): 1556-1561
doi: 10.6023/cjoc201712038
Abstract:
A high efficient method for the synthesis of 1, 3-diynes derivatives which employed terminal alkynes as the substrates and copper(I) oxide as the catalyst was developed. This method possessed the character of base-free and mild reaction conditions. The reaction mechanism was also studied. Furthermore, this reaction could be magnified to gram scale and the catalyst of copper(I) oxide could be recycled.
A high efficient method for the synthesis of 1, 3-diynes derivatives which employed terminal alkynes as the substrates and copper(I) oxide as the catalyst was developed. This method possessed the character of base-free and mild reaction conditions. The reaction mechanism was also studied. Furthermore, this reaction could be magnified to gram scale and the catalyst of copper(I) oxide could be recycled.
2018, 38(6): 1562-1565
doi: 10.6023/cjoc201712006
Abstract:
Two new[named turmerones E (1) and F (2), resp.] and one major known[i.e., (+)-(S)-ar-turmerone] bisabolane-type sesquiterpenoids were isolated from the 95% EtOH extract of the rhizome of Curcuma longa. The structures were determined by spectroscopic data (IR, UV, 1D/2D NMR, ECD, HRESIMS) and/or comparing with those reported physicochemical data in related literature.
Two new[named turmerones E (1) and F (2), resp.] and one major known[i.e., (+)-(S)-ar-turmerone] bisabolane-type sesquiterpenoids were isolated from the 95% EtOH extract of the rhizome of Curcuma longa. The structures were determined by spectroscopic data (IR, UV, 1D/2D NMR, ECD, HRESIMS) and/or comparing with those reported physicochemical data in related literature.
2018, 38(6): 1549-1555
doi: 10.6023/cjoc201801023
Abstract:
Berberine, honokiol, quercetin are the lead compounds with outstanding anti-tumor activities. Three novel products were synthesized from honokiol, quercetin and berberine. The structures of the products were firstly confirmed by 1H NMR, 13C NMR, 2D NMR, HRMS, IR and UV. All products were evaluated for their anti-tumor activities against HepG2 cell in vitro and the results showed that the inhibitory effects of two compounds on HepG2 cell were far superior to honokiol and berberine hydrochloride, and the anti-tumor activities were similar to the reference drug cisplatin. It means that compounds 1 and 2 are expected to be the potential anti-tumor drugs.
Berberine, honokiol, quercetin are the lead compounds with outstanding anti-tumor activities. Three novel products were synthesized from honokiol, quercetin and berberine. The structures of the products were firstly confirmed by 1H NMR, 13C NMR, 2D NMR, HRMS, IR and UV. All products were evaluated for their anti-tumor activities against HepG2 cell in vitro and the results showed that the inhibitory effects of two compounds on HepG2 cell were far superior to honokiol and berberine hydrochloride, and the anti-tumor activities were similar to the reference drug cisplatin. It means that compounds 1 and 2 are expected to be the potential anti-tumor drugs.
