- Access to 2-Arylquinazolin-4(3H)-ones through Intramolecular Oxidative C(sp3)?H/N?H Cross-Coupling Mediated by I2/DMSO
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A novel approach for the synthesis of 2-arylquinazolin-4(3H)-ones was developed. A series of title compounds were obtained with good functional group tolerance and good yields by I2/DMSO-mediated intramolecular oxidative cross-coupling of 2-(benzylamino)benzamides to form C=N double bonds. This method was applicable for gram-scale synthesis. A proposed reaction pathway based on some control experiments was also provided.
- Wen, Simiaomiao,Du, Yifan,Liu, Yiwen,Cui, Xiaofeng,Liu, Qixing,Zhou, Haifeng
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- N^N^O hydrazone capped pincer type palladium complex catalysed construction of quinazolinones from alcohols
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New Pincer type Pd(II) complex [Pd(NNO)(PPh3)] (1) prompted synthesis of quinazolinones via dehydrogenative coupling of readily accessible alcohols, and o-aminobenzamide is described. A diverse range of quinazolinones has been synthesized efficiently with good to excellent yields employing low catalyst loading (0.5 mol%) under the aerobic condition without any additives/oxidants. A plausible mechanism for the construction of quinazolinones has been proposed via cyclic aminal intermediate. Large-scale synthesis attests to the productiveness of the current strategy.
- Anandaraj, Pennamuthiriyan,Kamatchi, Thangavel Sathiya,Ramesh, Rengan
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- Catalyst-free synthesis of quinazolinones by oxidative cyclization under visible light in the absence of additives
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A general metal-free oxidative cyclization route was developed to synthesize quinazolinones under visible light. A series of substituted 2-aminobenzamides were reacted with aldehydes or ketones to produce the desired quinazolinones in good yields. Most importantly, the reaction did not require excess oxidant or high temperatures.
- Yang, Jiangnan,Xie, Zongbo,Chen, Zhongsheng,Jin, Liang,Li, Qian,Le, Zhanggao
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p. 1496 - 1501
(2021/05/03)
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- Metal-free catalyst for the visible-light-induced photocatalytic synthesis of quinazolinones
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In the present work, we have developed a novel and environmentally friendly method for the synthesis of quinazolinones using fluorescein as a photocatalyst via a condensation reaction of o-aminobenzamides and aldehydes under visible light irradiation. In this protocol, neither toxic oxidants nor transition-metal catalysts were needed, and a series of quinazolinones could be obtained in high efficiencies. In addition, this reaction can be extended to gram levels and has a large potential of wide application in future industrialization.
- Wang, Rongzhou,Liu, Shiyuan,Li, Longfei,Song, Ao,Yu, Shengsheng,Zhuo, Shuping,Xing, Ling-Bao
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- A magnetically retrievable copper ionic liquid nanocatalyst for cyclooxidative synthesis of 2-phenylquinazolin-4(3: H)-ones
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In the present work, we report the design and fabrication of a copper-containing ionic liquid supported magnetic nanocatalyst via a convenient and straightforward synthetic approach for the formation of 2-phenylquinazolin-4(3H)-ones using o-aminobenzamide and benzaldehydes as the reaction partners. The successful formation and properties of the as-prepared catalyst have been thoroughly investigated using diverse physico-chemical techniques including FT-IR, XRD, FE-SEM, TEM, ICP, VSM, BET and TGA. Using this nanocatalytic system, a variety of 2-phenylquinazolin-4(3H)-ones are synthesized in excellent yields with operational ease and short reaction times in an environmentally preferable solvent under open air and without using any external oxidizing agent. Besides, the catalyst possessed facile magnetic recoverability and remarkable reusability for six consecutive runs without any appreciable decrease in the catalytic efficiency.
- Gupta, Radhika,Arora, Gunjan,Yadav, Priya,Dixit, Ranjana,Srivastava, Anju,Sharma, Rakesh Kumar
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p. 890 - 898
(2021/02/03)
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- Method for synthesizing quinazolinone compound through visible light induction
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The method is mild in reaction condition, simple and convenient in post-treatment operation, free of additional additives, high I in reaction efficiency, wide II in substrate adaptability, high in product purity, green and environment-friendly, and the method has III the advantages of mild reaction conditions, no need of additional additives, high reaction efficiency, wide substrate adaptability.
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Paragraph 0041-0046
(2021/11/27)
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- Discovery of Novel Dual-Target Inhibitor of Bromodomain-Containing Protein 4/Casein Kinase 2 Inducing Apoptosis and Autophagy-Associated Cell Death for Triple-Negative Breast Cancer Therapy
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Bromodomain-containing protein 4 (BRD4) is an attractive epigenetic target in human cancers. Inhibiting the phosphorylation of BRD4 by casein kinase 2 (CK2) is a potential strategy to overcome drug resistance in cancer therapy. The present study describes the synthesis of multiple BRD4–CK2 dual inhibitors based on rational drug design, structure–activity relationship, and in vitro and in vivo evaluations, and 44e was identified to possess potent and balanced activities against BRD4 (IC50 = 180 nM) and CK2 (IC50 = 230 nM). In vitro experiments show that 44e could inhibit the proliferation and induce apoptosis and autophagy-associated cell death of MDA-MB-231 and MDA-MB-468 cells. In two in vivo xenograft mouse models, 44e displays potent anticancer activity without obvious toxicities. Taken together, we successfully synthesized the first highly effective BRD4–CK2 dual inhibitor, which is expected to be an attractive therapeutic strategy for triple-negative breast cancer (TNBC).
- Chen, Juncheng,Chiang, Cheng-Ming,He, Gu,Liu, Bo,Liu, Jie,Ouyang, Liang,Tang, Pan,Wang, Guan,Yang, Chengcan,Ye, Tinghong,Zhang, Jifa,Zhang, Jin,Zou, Ling
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p. 18025 - 18053
(2022/01/03)
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- Design, synthesis, characterization, enzymatic inhibition evaluations, and docking study of novel quinazolinone derivatives
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In this study, novel quinazolinone derivatives 7a-n were synthesized and evaluated against metabolic enzymes including α-glycosidase, acetylcholinesterase, butyrylcholinesterase, human carbonic anhydrase I, and II. These compounds exhibited high inhibitory activities in comparison to used standard inhibitors with Ki values in the range of 19.28–135.88 nM for α-glycosidase (Ki value for standard inhibitor = 187.71 nM), 0.68–23.01 nM for acetylcholinesterase (Ki value for standard inhibitor = 53.31 nM), 1.01–29.56 nM for butyrylcholinesterase (Ki value for standard inhibitor = 58.16 nM), 10.25–126.05 nM for human carbonic anhydrase I (Ki value for standard inhibitor = 248.18 nM), and 13.46–178.35 nM for human carbonic anhydrase II (Ki value for standard inhibitor = 323.72). Furthermore, the most potent compounds against each enzyme were selected in order to evaluate interaction modes of these compounds in the active site of the target enzyme. Cytotoxicity assay of the title compounds 7a-n against cancer cell lines MCF-7 and LNCaP demonstrated that these compounds do not show significant cytotoxic effects.
- Pedrood, Keyvan,Sherafati, Maedeh,Mohammadi-Khanaposhtani, Maryam,Asgari, Mohammad Sadegh,Hosseini, Samanesadat,Rastegar, Hossein,Larijani, Bagher,Mahdavi, Mohammad,Taslimi, Parham,Erden, Yavuz,Günay, Sevilay,Gul?in, ?lhami
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- Ruthenium(II)-catalyzed C?C/C?N coupling of 2-arylquinazolinones with vinylene carbonate: Access to fused quinazolinones
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In this work, ruthenium(II)-catalyzed C?C/C?N annulation of 2-arylquinazolinones with vinylene carbonate is reported to synthesize fused quinazolinones. This catalytic system tolerates a wide range of substrates with excellent functional-group compatibility. In this transformation, the vinylene carbonate acts as an ethynol surrogate without any external oxidant involved. Furthermore, preliminary mechanistic studies were conducted, and a plausible catalytic cycle was also proposed.
- Wang, Zhao-Hui,Wang, He,Wang, Hua,Li, Lei,Zhou, Ming-Dong
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supporting information
p. 995 - 999
(2021/03/03)
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- Synthesis of Difluoromethyl-Substituted Quinazolines through Selective Difluoromethylation
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A highly selective difluoromethylation of quinazolines has been achieved by using commercially available ethyl bromodifluoroacetate as difluorocarbene precursor, providing the corresponding difluoromethyl substituted quinazoline derivatives with up to 83% yield.
- Peng, Jing,Hu, Ludan,Chen, Mu-Wang,Deng, Zhihong,Peng, Yiyuan
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p. 2286 - 2292
(2021/03/04)
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- Method for photocatalytic synthesis of quinazolinone
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The invention discloses a method for photocatalytic synthesis of quinazolinone. Anthranilamide and aldehyde are used as raw materials, fluorescein is used as a photocatalyst, p-toluene sulfonic acid is used as an auxiliary catalyst, and the quinazolinone is obtained through photocatalytic reaction under the irradiation of visible light. The non-metal catalyst is used, so that the reaction cost is reduced; the reaction conditions are mild, and the reaction can be completed at room temperature; and the method is simple to operate, short in reaction time, simple in post-treatment, high in product yield and more environment-friendly. The method not only has high academic value, but also has a certain industrialization prospect.
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Paragraph 0028-0029
(2021/07/31)
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- Three-Component Couplings among Heteroarenes, Difluorocyclopropenes, and Water via C-H Activation
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Three-component couplings have been realized for efficiently constructing various nitrogen-containing skeletons via C-H activation, where difluorocyclopropenes have been first identified as coupling partners. Many substrates including sp2 and sp3 C-H substrates were well tolerated, furnishing the corresponding products in good yields. Furthermore, a catalyst-dependent reaction was also developed, enabling divergent construction of two different frameworks. The application value of these reactions was demonstrated in gram-scale experiments with as little as 1 mol % catalyst.
- Liu, Xuexin,Chen, Jian,Yang, Chunyan,Wu, Zhouping,Li, Zhiyang,Shi, Yuesen,Huang, Tianle,Yang, Zhongzhen,Wu, Yong
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supporting information
p. 6831 - 6835
(2021/09/08)
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- Antioxidant and ros inhibitory activities of heterocyclic 2-aryl-4(3h)-quinazolinone derivatives
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Background: Antioxidants are small molecules that prevent or delay the process of oxidations caused by highly reactive free radicals. These molecules are known for their ability to protect various cellular architecture and other biomolecules from oxidative stress and free radicals. Thus, antioxidants play a key role in the prevention of oxidative damages caused by highly reactive free radicals. Methods: In the present study, a series of previously synthesized heterocyclic 2-aryl-4(3H)-quinazolinone derivatives 1-25 were screened for antioxidant activity by employing in vitro DPPH and superoxide anion radical scavenging activities. ROS inhibitory activities were also evaluated by serum-opsonized zymosan activated whole blood phagocytes and isolated neutrophils. Cytotoxicity studies were carried out by employing an MTT assay against the 3T3 cell line. Results: Most of the 2-aryl-4(3H)-quinazolinone derivatives showed potent antioxidant activities in superoxide anion radical scavenging assay with IC50 value ranging between 0.57 μM-48.93 μM, as compared to positive control quercetin dihydrate (IC50 = 94.1 ± 1.1 μM ). Compounds 5, 6, and 14 showed excellent activity in DPPH assay. Compounds 5-8, 12-15, 17, and 20 showed promising activities in the ROS inhibition assay. All compounds were found to be non-cytotoxic against the 3T3 cell line. Structure antioxidant activity has been established. Conclusion: It can be concluded that most of the heterocyclic 2-aryl-4(3H)-quinazolinone derivatives 1-25 are identified as promising antioxidant agents that are capable of fighting against free radicals and oxidative stress. Thus, they can serve as a lead towards treating oxidative stress and related pathologies.
- Choudhary, Muhammad Iqbal,Khan, Khalid Mohammed,Perveen, Shahida,Saad, Syed Muhammad
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p. 806 - 815
(2021/11/17)
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- Pd/C Catalyzed Cascade Synthesis of 2-Arylquinazolinones from 2-Iodoacetanilides Employing Ammonia and CO Precursors
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An efficient and straightforward approach has been demonstrated for 2-aryl quinazolinones synthesis from 2-iodoacetanilides using ammonium carbamate/ammonium carbonate and oxalic acid under heterogeneous Pd/C catalyzed conditions. Herein, we have carried
- Shaifali,Mehara, Pushkar,Kumar, Ashish,Das, Pralay
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p. 2459 - 2464
(2021/03/31)
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- Zinc Stabilized Azo-anion Radical in Dehydrogenative Synthesis of N-Heterocycles. An Exclusively Ligand Centered Redox Controlled Approach
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Herein we report an exclusively ligand-centered redox controlled approach for the dehydrogenation of a variety of N-heterocycles using a Zn(II)-stabilized azo-anion radical complex as the catalyst. A simple, easy-to-prepare, and bench-stable Zn(II)-complex (1b) featuring the tridentate arylazo pincer, 2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline, in the presence of zinc-dust, undergoes reduction to form the azo-anion radical species [1b]- which efficiently dehydrogenates various saturated N-heterocycles such as 1,2,3,4-tetrahydro-2-methylquinoline, 1,2,3,4-tetrahydro-isoquinoline, indoline, 2-phenyl-2,3-dihydro-1H-benzoimidazole, 2,3-dihydro-2-phenylquinazolin-4(1H)-one, and 1,2,3,4-tetrahydro-2-phenylquinazolines, among others, under air. The catalyst has further been found to be compatible with the cascade synthesis of these N-heterocycles via dehydrogenative coupling of alcohols with other suitable coupling partners under air. Mechanistic investigation reveals that the dehydrogenation reactions proceed via a one-electron hydrogen atom transfer (HAT) pathway where the zinc-stabilized azo-anion radical ligand abstracts the hydrogen atom from the organic substrate(s), and the whole catalytic cycle proceeds via the exclusive involvement of the ligand-centered redox events where the zinc acts only as the template.
- Das, Siuli,Mondal, Rakesh,Chakraborty, Gargi,Guin, Amit Kumar,Das, Abhishek,Paul, Nanda D.
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p. 7498 - 7512
(2021/06/30)
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- Regioselective Synthesis of 2° Amides Using Visible-Light-Induced Photoredox-Catalyzed Nonaqueous Oxidative C-N Cleavage of N, N-Dibenzylanilines
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A visible-light-driven photoredox-catalyzed nonaqueous oxidative C-N cleavage of N,N-dibenzylanilines to 2° amides is reported. Further, we have applied this protocol on 2-(dibenzylamino)benzamide to afford quinazolinones with (NH4)2S2O8 as an additive. Mechanistic studies imply that the reaction might undergo in situ generation of α-amino radical to imine by C-N bond cleavage followed by the addition of superoxide ion to form amides.
- Neerathilingam, Nalladhambi,Bhargava Reddy, Mandapati,Anandhan, Ramasamy
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supporting information
p. 15117 - 15127
(2021/10/25)
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- An efficient transition-metal-free route to quinazolin-4(3H)-onesvia2-aminobenzamides and thiols
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An efficient approach to quinazolin-4(3H)-ones was developed by a one-pot intermolecular annulation reaction ofo-amino benzamides and thiols. This method has the features of good functional group tolerance, being transition metal and external oxidant free, and easy operation. Varieties of 2-aryl (heteroaryl) quinazolin-4(3H)-one, 2-phenyl-pyrido[2,3-d]pyrimidin-4(3H)-one and 3-phenyl-2H-1,2,4-benzo thiadiazine-1,1-dioxide derivatives were obtained with a yield of up to 98%. The control experiment revealed that the thiol substrate could promote the dehydroaromatization step.
- Dong, Yibo,Wu, Yangjie,Yan, Congcong,Yang, Jinchen,Zhang, Jinli
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supporting information
p. 15344 - 15349
(2021/09/07)
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- Direct Use of Benzylic Alcohols for Multicomponent Synthesis of 2-Aryl Quinazolinones Utilizing the π-Benzylpalladium(II) System in Water
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We demonstrate the direct use of benzylic alcohols for a multicomponent reaction of readily available isatoic anhydrides with amines in water, which is a synthetic route for the direct construction of a series of 2-aryl quinazolinones. This one-pot synthetic method involves the dehydrative N-benzylation of in situ generated anthranilamides followed by an amide-directed benzylic C?H amination process utilizing the π-benzylPd(II) system. Comparison of independent rate measurements using benzyl alcohol and its deuterated form gave a kinetic isotope effect of 3.5. Therefore, the benzylic C?H bond is cleaved in the rate-determining step. We successfully carried out a gram-scale reaction in 85% yield with simplified product isolation. (Figure presented.).
- Hikawa, Hidemasa,Nakayama, Taku,Takahashi, Makiko,Kikkawa, Shoko,Azumaya, Isao
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supporting information
p. 4075 - 4084
(2021/07/26)
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- Palladium-catalyzed one-pot synthesis of 2-substituted quinazolin-4(3H)-ones fromo-nitrobenzamide and alcohols
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Palladium-catalyzed 2-substituted quinazolin-4(3H)-one formation from readily availableo-nitrobenzamides and alcohols using hydrogen transfer is described. Various quinazolin-4(3H)-ones were obtained in good to high yields. The cascade reaction including
- Wang, Ke,Chen, Hao,Dai, Xinyan,Huang, Xupeng,Feng, Zhiqiang
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p. 13119 - 13123
(2021/04/22)
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- Improved, gram-scale synthesis of sildenafil in water using arylacetic acid as the acyl source in the pyrazolo[4,3-d]pyrimidin-7-one ring formation
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An improved, gram-scale synthesis of the blockbuster drug sildenafil, used for the treatment of male erectile dysfunction, has been developed. Unlike the previous literature, the current method demonstrates the use of arylacetic acid as an acyl source, a cheap oxidant K2S2O8, and water as the reaction medium in the key step of pyrrazolo[4,3-d]pyrimidin-7-one ring formation. As well as being a green and benign approach, the current method reduces the cost by half compared to our previous strategy. In addition, the general relevance of the method has been demonstrated in the synthesis of a variety of quinazolinone and benzothiazole derivatives with excellent functional group tolerance.
- Laha, Joydev K.,Gulati, Upma,Saima,Gupta, Anjali,Indurthi, Harish Kumar
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supporting information
p. 2643 - 2648
(2021/02/16)
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- Method for synthesizing 2 -phenylquinazolone compound by taking styrene compound as raw material
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The invention discloses a method for synthesizing a 2-phenyl quinazolinone compound. The method comprises the steps of adopting a styrene compound and 2-aminobenzamide as reaction raw materials; underthe combined action of a palladium catalyst, a ligand and oxygen, reacting to obtain the 2-phenyl quinazolinone compound, wherein the reaction temperature is 80 DEG C to 110 DEG C, a reaction formulais as shown in the below figure, and R is hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, nitro or methoxyl. The method provided by the invention has the beneficial effects that the raw material styrene compound is cheap and easy to get, so that the method is more economical; a preparation method is simple and convenient to operate, and the obtained product is easy to post-process, so that the method is suitable for large-scale industrial production; no high temperature and high pressure is needed, and a reaction condition is mild; the method is short in reaction time, high efficient to react, high in yield, and higher in reaction efficiency after reaction amplification.
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Paragraph 0047-0056
(2021/03/03)
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- Photocatalyst-free visible-light-promoted quinazolinone synthesis at room temperature utilizing aldehydes generatedin situ viaC=C bond cleavage
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This is the first report on a facile tandem route for synthesizing quinazolinones at room temperature from various aminobenzamides andin situ-generated aldehydes. The latter was formedviaC=C bond cleavage, and the overall reaction proceeded using molecular oxygen as a clean oxidant in the absence of a photocatalyst. Visible light, which was indispensable for the entire course of the reaction, played multiple roles. It initially cleaved styrene to an aldehyde, then facilitated its cyclization with ano-substituted aniline, and finally promoted the dehydrogenation of the cyclized intermediate. The previous step provided the feedstock for the next step in the reaction, thereby preventing volatilization, oxidation, and polymerization of the aldehyde. Thus, the overall process is simple, environmentally benign, and economically feasible.
- Xie, Zongbo,Lan, Jin,Yan, Liyuan,Chen, Xuehua,Li, Qian,Meng, Jia,Le, Zhanggao
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p. 2436 - 2441
(2021/04/02)
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- α-Keto Acids as Triggers and Partners for the Synthesis of Quinazolinones, Quinoxalinones, Benzooxazinones, and Benzothiazoles in Water
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A general and efficient method for the synthesis of quinazolinones, quinoxalinones, benzooxazinones, and benzothiazoles from the reactions of α-keto acids with 2-aminobenzamides, benzene-1,2-diamines, 2-aminophenols, and 2-aminobenzenethiols, respectively, is described. The reactions were conducted under catalyst-free conditions, using water as the sole solvent with no additive required, and successfully applied to the synthesis of sildenafil. More importantly, these reactions can be conducted on a mass scale, and the products can be easily purified through filtration and washing with ethanol (or crystallized).
- Huang, Jian,Chen, Wei,Liang, Jiazhi,Yang, Qin,Fan, Yan,Chen, Mu-Wang,Peng, Yiyuan
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p. 14866 - 14882
(2021/10/25)
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- Method for preparing 2 -phenyl quinazolinone compound
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The invention relates to a preparation method of 2 -phenyl quinazolinone compounds, in particular to II. To the method, 2 - (benzylamino) benzamide compound (I) is used as a raw material for reaction of the experiment model, a simple substance iodine cata
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Paragraph 0045-0047
(2021/10/30)
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- Aerobic primary and secondary amine oxidation cascade by a copper amine oxidase inspired catalyst
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Herein, we report a bioinspired catalytic system for the one-pot cascade oxidation of a native primary amine and anin situgenerated non-native secondary amine. The catalyst consists of ano-quinone cofactor phd (1,10-phenanthroline-5,6-dione) and a copper ion and operates under ambient air conditions. Quinazolin-4(3H)-ones, which are common pharmacophores present in numerous pharmaceuticals and bioactive compounds, were synthesized in high yields. A detailed kinetic and mechanistic study elucidates the role of the catalyst in the multi-step oxidative cascade reaction.
- Thorve, Pradip Ramdas,Maji, Biplab
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p. 1116 - 1124
(2021/02/26)
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- Iron catalyzed metal-ligand cooperative approaches towards sustainable synthesis of quinolines and quinazolin-4(3H)-ones
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Herein we report simple, efficient, and economically affordable metal-ligand cooperative strategies for synthesizing quinolines and quinazolin-4(3H)-ones via dehydrogenative functionalization of alcohols. Various polysubstituted quinolines and quinazolin-4(3H)-ones were prepared in good yields via dehydrogenative coupling of readily available alcohols with ketones and 2-aminobenzamides, respectively under air using a well-defined Fe(II)-catalyst, ([FeL1Cl2] (1)) bearing a redox-active azo-aromatic pincer 2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline) (L1). Control experiments and mechanistic investigation disclose that the one-electron reduced mono-anionic species [1]? bearing an iron-stabilized azo-anion radical ligand catalyzes these reactions. Both iron and the redox-active arylazo ligand participate synergistically during the different steps of these catalytic reactions.
- Mondal, Rakesh,Chakraborty, Gargi,Guin, Amit Kumar,Pal, Subhasree,Paul, Nanda D.
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- Electro-oxidative cyclization: Access to quinazolinones: Via K2S2O8without transition metal catalyst and base
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A K2S2O8-promoted oxidative tandem cyclization of primary alcohols with 2-aminobenzamides to synthesize quinazolinones was successfully achieved under undivided electrolytic conditions without a transition metal and base. The key feature of this protocol is the utilization of K2S2O8 as an inexpensive and easy-to-handle radical surrogate that can effectively promote the reaction via a simple procedure, leading to the formation of nitrogen heterocycles via direct oxidative cyclization at room temperature in a one-pot procedure under constant current. Owing to the use of continuous-flow electrochemical setups, this green, mild and practical electrosynthesis features high efficiency and excellent functional group tolerance and is easy to scale up.
- Hou, Huiqing,Hu, Yongzhi,Ke, Fang,Sun, Weiming,Wu, Xianghua,Yu, Ling,Zhou, Sunying
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p. 31650 - 31655
(2021/11/30)
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- Visible light induced tandem reactions: An efficient one pot strategy for constructing quinazolinones using in-situ formed aldehydes under photocatalyst-free and room-temperature conditions
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A facile tandem route has been developed for constructing quinazolinones from various aminobenzamides and in-situ generated aldehydes. Visible light was found to play a dual role: first oxidizes the alcohol to the aldehyde and then facilitates its cyclization with o-substituted aniline. Furthermore, alcohols are perfect alternatives to aldehydes because they are greener, more available, more economical, more stable, and less toxic than aldehydes. The first reaction step continuously provides material for the second step, which effectively reduces loss through volatilization, oxidation, and polymerization of the aldehyde, while avoiding its toxicity. A variety of quinazolinones can be prepared in the presence of visible light without any additional photocatalyst. The developed synthesis protocol proceeds with the merits of mild conditions, broad substrate scope, operational simplicity, and high atom efficiency, with an eco-energy source under metal-free, photocatalyst-free, and ambient conditions.
- Xie, Zongbo,Lan, Jin,Zhu, Haibo,Lei, Gaoyi,Jiang, Guofang,Le, Zhanggao
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supporting information
p. 1427 - 1431
(2020/11/02)
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- Palladium(II) N^O Chelating Complexes Catalyzed One-Pot Approach for Synthesis of Quinazolin-4(3 H)-ones via Acceptorless Dehydrogenative Coupling of Benzyl Alcohols and 2-Aminobenzamide
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A convenient protocol for the one-pot synthesis of quinazolin-4(3H)-ones using palladium(II) complexes via dehydrogenative coupling of readily available benzyl alcohols and 2-aminobenzamide has been described. New structurally related Pd(II) N^O chelating complexes of general configuration [Pd(L)Cl(PPh3)] (where L = dimethylamino benzoylhydrazone ligands) have been designed and synthesized. The formation of the complexes has been recognized by analytical and spectral methods (FT-IR, NMR, HR-MS). The presence of a square-planar geometry around the palladium(II) ion was confirmed by single crystal X-ray diffraction study. A wide range of substituted quinazolinones have been successfully achieved from a diverse range of benzyl alcohols in good to excellent yields using 1.0 mol % of catalyst loading under aerobic conditions. Furthermore, control experiments reveal that the dehydrogenative coupling reaction involves initially the formation of an aldehyde intermediate and subsequent formation of a cyclic aminal intermediate.
- Balaji, Sundarraman,Balamurugan, Gunasekaran,Ramesh, Rengan,Semeril, David
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p. 725 - 734
(2021/04/06)
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- Br?nsted acid catalyzed synthesis of 2‐aryl‐quinazolinones via cyclization of 2‐aminobenzamide with benzonitriles in PEG
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A simple and efficient Br?nsted acid catalyzed synthesis of 2‐aryl‐quinazolinones via cyclization of 2‐aminobenzamides with benzonitrile in PEG under metal and ligand‐free condition. All substituted benzonitriles were also well participated with the formation of the corresponding products in moderate to good yields.
- Botsa, Sathish Mohan,Karasala, Bharat Kumar,Matcha, Sowbhagya Lakshmi,Vidavalur, Siddaiah
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- Preparation method of quinazolinone derivative
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The invention discloses a preparation method of a quinazolinone derivative, wherein the preparation method comprises the following steps: dissolving an anthranilonitrile compound represented by a formula I and an aldehyde represented by a formula II in a
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Paragraph 0027-0030
(2021/04/14)
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- Electrochemically induced synthesis of quinazolinonesviacathode hydration ofo-aminobenzonitriles in aqueous solutions
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An efficient and practical electrochemically catalyzed transition metal-free process for the synthesis of substituted quinazolinones from simple and readily availableo-aminobenzonitriles and aldehydes in water has been accomplished. I2/base and water play an unprecedented and vital role in the reaction. By electrochemically catalysed hydrolysis ofo-aminobenzonitriles, the synthesis of quinazolinones with benzaldehyde was first proposed. The synthetic utility of this method was demonstrated by gram-scale operation, as well as the preparation of bioactiveN-(2,5-dichlorophenyl)-6-(2,2,2-trifluoroethoxy) pteridin-4-amine, which enables straightforward, practical and environmentally benign quinazolinone formation.
- Yang, Li,Hou, Huiqing,Li, Lan,Wang, Jin,Zhou, Sunying,Wu, Mei,Ke, Fang
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supporting information
p. 998 - 1003
(2021/02/16)
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- Linear-Organic-Polymer-Supported Iridium Complex as a Recyclable Auto-Tandem Catalyst for the Synthesis of Quinazolinones via Selective Hydration/Acceptorless Dehydrogenative Coupling from o-Aminobenzonitriles
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A linear-organic-polymer-supported iridium complex Cp*Ir@P4VP, which is designed and synthesized by the coordinative immobilization of [Cp*IrCl2]2 on poly(4-vinylpyridine), was proven to be an efficient heterogeneous autotandem catalyst for synthesizing quinazolinones via selective hydration/acceptorless dehydrogenative coupling from o-aminobenzonitriles. Furthermore, the synthesized catalyst was recycled five times without an obvious decrease in the catalytic activity.
- Hao, Shushu,Yang, Jiazhi,Liu, Peng,Xu, Jing,Yang, Chenchen,Li, Feng
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supporting information
p. 2553 - 2558
(2021/04/13)
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- An Efficient Synthesis of 2-Substituted Quinazolin-4(3H)-ones by Using Recyclable Wang Resin Supported Sulfonic Acid Catalyst
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An efficient synthesis of 2-substituted Quinazolin-4(3H)-ones has been developed from isatoic anhydride with various amidoximes by using a recyclable polymer-supported sulphonic acid catalyst. Excellent functional group compatibility and high yields are the important features of this protocol.
- Kalyani,Kallam, Srinivasa Reddy
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p. 790 - 796
(2022/03/01)
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- Method for photocatalytic synthesis of quinazolinone compound in aqueous phase (by machine translation)
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The method comprises the following steps: taking the compound of the formula (I) and the compound of the formula (II) as a solvent, adding a photocatalyst and a phase transfer catalyst to obtain the quinazolinone compound (III) under the condition of alkali and visible light. Compared with the prior art, the method not only can be applied to a large amount of functional groups, has high yield, few byproducts, and is simple and safe to operate, low in cost and environment-friendly. Wherein R is hydrogen or R1 Is H, C1 - C4 alkoxy, halogen or nitro; R2 Is H, substituted or unsubstituted phenyl, 2 - pyridyl or 2 - thienyl; the substituted phenyl is phenyl substituted by amino, nitro, C1 - C4 alkyl or C1 - C4 alkoxy. (by machine translation)
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Paragraph 0030; 0031; 0032; 0033; 0034; 0035
(2020/11/22)
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- Method for synthesizing quinazolinone compound by photo-catalyzing alcohol oxidation in water phase
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The invention discloses a method for synthesizing a quinazolinone compound by photo-catalyzing alcohol oxidation in a water phase, which comprises the following steps: by taking a compound shown as aformula (I) and a compound shown as a formula (II) as raw materials and water as a solvent, adding a visible light catalyst, and reacting under the conditions of alkali and visible light to obtain a quinazolinone compound (III). The method for preparing the quinazolinone compound is environmentally friendly, easy and convenient to operate, safe, cheap and efficient. Compared with the prior art, the method is applicable to a large number of functional groups, high in yield, few in byproducts, simple and safe to operate, low in cost and environment-friendly; wherein R1 is H, C1-C4 alkoxy, halogen or nitro; and R2 is H, substituted or unsubstituted phenyl, 2-pyridyl, 2-thienyl or 5-methylfuryl.
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Paragraph 0028-0031; 0040-0041
(2020/10/29)
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- Synthesis and in silico studies of quinazolinone derivatives as PARP-1 inhibitors
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Background: Cancer is a leading cause of deaths worldwide, accounting for 9.6 million deaths in 2018. According to the WHO, the most common causes of cancer deaths are lung, colorec-tal, stomach liver and breast cancer. Introduction: PARP-1 has a crucial role in cell proliferation, survival and death due to its role in the regula-tion of multiple biological processes. Quinazolinone and its derivatives represent a large class of biologically active compounds that exhibit a broad spectrum of biological activities such as anti-HIV, anticancer, antifun-gal, antibacterial, anticonvulsant, anti-inflammatory, antidepressant, antimalarial, antioxidant and anti-leishmanial activities. Methods: In this study, we have synthesized quinazolinone derivatives by reaction of 2-aminobenzamide and substituted benzaldehydes. The synthesized compounds were also screened in silico for their PARP-1 binding affinities by molecular docking studies using Schrodinger 2016 software. In silico ADME studies were also performed for the synthesized compounds by using QikProp tool of Schrodinger software. Results: Results of in silico studies indicated that quinazolinone derivatives exhibited a good affinity towards the active site of PARP-1. Out of all synthesized compounds, SVA-11 exhibited a maxi-mum dock score (-10.421). Results of ADME studies indicated the suitability of synthesized compounds as drug candidates. Conclusion: The synthesized compounds showed better docking scores than reference drug valipa-rib. Furthermore, they exhibited favorable ADME profile. Therefore, they may serve as lead compounds in the discovery of PARP-1 inhibitors.
- Verma, Sonia,Pathania, Akashdeep Singh,Baranwal, Somesh,Kumar, Pradeep
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p. 1552 - 1565
(2020/10/29)
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- Aerobic oxidative synthesis of quinazolinones and benzothiazoles in the presence of laccase/DDQ as a bioinspired cooperative catalytic system under mild conditions
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The current study applied laccase/DDQ as a bioinspired cooperative catalytic system for the synthesis of quinazolinones (80-95% yield) and benzothiazoles (65-98% yield) using air or O2 as ideal oxidants in aqueous media at ambient temperature. The aerobic oxidative cyclization reactions occur in two steps: (i) chemical cyclization; (ii) chemoenzymatic oxidation. These methods are more environment-friendly, efficient, simple and practical than other reported methods due to the use of O2 as an oxidant, laccase as an eco-friendly biocatalyst, aqueous media as the solvent and free from any toxic transition metal and halide catalysts. Therefore, these methods can be applied in pharmaceutical and other sensitive synthetic procedures.
- Abdelrasoul, Amira,Ghorashi, Nadia,Moradi, Reza,Rostami, Amin,Shokri, Zahra
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p. 14254 - 14261
(2020/04/23)
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- Rhodium-catalyzed [4+1] annulation of sulfoxonium ylides: Sequential ortho-C[sbnd]H functionalization/carbonyl α-amination toward polycyclic quinazolinones
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A rhodium-catalyzed [4+1] annulation between 2-aryl quinazolin-4(3H)-ones and sulfoxonium ylides was developed, leading to 12-aroyl isoindolo[1,2-b]quinazolin-10(12H)-ones in moderate to good yields. This reaction proceeds with sequential ortho-C[sbnd]H functionalization of 2-aryl quinazolin-4(3H)-ones and an intramolecular rhodium-catalyzed α-amination of carbonyl to furnish the cyclization. This procedure was applied to access some 13-aroyl luotonin A derivatives whereby the direct construction of ring c.
- Wang, Chang,Qian, Peng-Cheng,Chen, Fan,Cheng, Jiang
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supporting information
(2020/10/05)
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- Design and synthesis of a versatile cooperative catalytic aerobic oxidation system with co-immobilization of palladium nanoparticles and laccase into the cavities of MCF
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We have designed a versatile reusable cooperative catalyst oxidation system, consisting of palladium nanoparticles and laccase with unprecedented reactivity. This biohybrid catalyst was synthesized by the stepwise immobilization of laccase as an enzyme and Pd as a nanometallic component into the same cavity of siliceous mesocellular foams (MCF). MCF and nanobiohybrid catalyst were characterized by BET, SAXS, SEM, EDX elemental mapping, ICP-OES, TEM, TGA, FT-IR, and XPS techniques and the stepwise immobilization of laccase enzyme and Pd onto MCF was evaluated through several compelling electrochemical studies. The present catalytic system exhibits high activity toward (i) aerobic oxidation of alcohols to the corresponding carbonyl compounds, (ii) aerobic oxidation of cyclohexanol and cyclohexanone to phenol and (iii) aerobic dehydrogenation of important N-heteocyclic compounds (tetrahydro quinazolines, quinazolonones, pyrazolines and 1,4-diydropyridines) in the presence of catalytic amount of hydroquinone (HQ) as mediator in phosphate buffer (0.1 M, pH 4.5, 4 mL)/THF (4%, 1 mL) as solvent under mild conditions. The immobilization of both oxygen-activating catalyst (laccase) and oxidizing catalyst (Pd) onto the same support makes the present catalyst system superior to other currently available heterogeneous palladium based catalytic aerobic oxidation systems.
- Moradi, Sirvan,Shokri, Zahra,Ghorashi, Nadya,Navaee, Aso,Rostami, Amin
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p. 305 - 319
(2020/01/21)
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- A novel magnetically separable laccase-mediator catalyst system for the aerobic oxidation of alcohols and 2-substituted-2,3-dihydroquinazolin-4(1H)-ones under mild conditions
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In this study, a magnetically reusable artificial metalloenzyme has been constructed by co-immobilization of palladium nanoparticles as a strong oxidizing catalyst and laccase as an oxygen-activating enzyme into the cavities of magnetic mesocellular foams
- Shokri, Zahra,Azimi, Nahid,Moradi, Sirvan,Rostami, Amin
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- A Metal- and Ligand-Free Synthesis of Quinazolin-4(3H)-ones via a Bu4NI/TBHP-Mediated Oxidative Cleavage of the Olefinic C=C Bond
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Abstract: A metal and ligand-free protocol has been developed for the synthesis of quinazolin-4(3H)-ones in moderate to good yields from o-aminobenzamide and alkenes via a Bu4NI/TBHP-mediated oxidative cleavage of the C=C bond in alkenes.
- Gollamudi, P.,Inkollu, B.,Karasala, B. K.,Vidavalur, S.
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p. 1446 - 1454
(2020/10/02)
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- Imidazolium chloride as an additive for synthesis of 4(3H)-quinazolinones using anthranilamides and DMF derivatives
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Imidazolium chloride as an environmentally benign additive efficiently facilitates construction of 4(3H)-quinazolinones using anthranilamides and DMF derivatives. A series of 4(3H)-quinazolinones were prepared in moderate to excellent yields without conventional oxidants, metal catalysts and corrosive acids or other additives.
- Dai, Zeshu,Li, Dan,Li, Zhiyao,Liu, Heng,Luo, Wen,Shang, Suqin,Tian, Qingqiang,Wang, Shuqi,Wang, Xuetong,Wang, Yin,Wu, Huili,Xiao, Xin,Yuan, Jianyong,Zhou, Shangjun
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- Electrochemical Synthesis of Quinazolinones by the Metal-Free and Acceptor-Free Dehydrogenation of 2-Aminobenzamides
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An efficient approach has been developed for the construction of quinazolin-4(3 H)-ones by the selective anodic dehydrogenative oxidation/cyclization of benzylic chlorides and 2-aminobenzamides. The method features acceptor-free and metal-free dehydrogenation of amines to imines; a subsequent intermolecular addition provides the products in moderate to good yields.
- Yao, Yan,Meng, Xiu-Jin,Teng, Qing-Hu,Chen, Yan-Yan
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supporting information
p. 1795 - 1799
(2020/09/07)
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- Site-Selective C–H Amidation of 2-Aryl Quinazolinones Using Nitrene Surrogates
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The site-selective modifications of quinazolinones constitute a pivotal topic in drug discovery and material science. Herein, we describe the rhodium(III)-catalyzed C–H amidation of 2-aryl quinazolin-4(3H)-ones with a range of nitrene surrogates including dioxazolones, organic azides, and N-methoxyamides. Complete site-selectivity and functional group tolerance are observed. Notably, the large-scale reaction and late-stage functionalization highlight the synthetic potential of the developed protocol. Combined mechanistic investigations elucidate a plausible reaction mechanism of this process.
- Kim, Saegun,Jeoung, Daeun,Kim, Kunyoung,Lee, Seok Beom,Lee, Suk Hun,Park, Min Seo,Ghosh, Prithwish,Mishra, Neeraj Kumar,Hong, Suckchang,Kim, In Su
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supporting information
p. 7134 - 7143
(2020/10/02)
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- Nanoporous Cu doped ZnS nanoparticles an efficient photo catalyst for the chemoselective synthesis of 2-substituted azoles via C-N arylation/ CSp3– H oxidation/ cyclization/dehydration sequence in visible light
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ZnS and Cu:ZnS nanoparticles were prepared by aqueous chemical method and characterized by several analytical tools. Nanoparticles have an average size of about ~ 18 nm and possess highly open mesopores, moderate surface area, and uniform morphology. UV–vis spectra designate that doping of Cu shifted the optical response of the ZnS nanoparticles in to a visible region. These Cu:ZnS nanoparticles were employed as a photocatalyst for chemoselective synthesis of 2-substituted azoles by the reaction of benzyl bromides and 1,2-Diaminobenzene or 2-Mercaptoaniline in visible light. Analogous experiments confirmed that the reaction were proceeds through one pot C–N arylation/ CSp3– H oxidation/ cyclization/dehydration sequence. The enhanced catalytic activity by doping could be attributed to the presence of trapping level generated by copper doping which augments the relaxation time of electron and holes so that they are easily available for the reaction. The method was also applicable for the synthesis of quinazolin-4(3H)-ones.
- Dandia, Anshu,Bansal, Sarika,Sharma, Ruchi,Kumar Mahawar, Dinesh,Rathore, Kuldeep S.,Lal Meena, Mohan,Parewa, Vijay
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- Ortho -Naphthoquinone-catalyzed aerobic oxidation of amines to fused pyrimidin-4(3 H)-ones: A convergent synthetic route to bouchardatine and sildenafil
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A facile access to fused pyrimidin-4(3H)-one derivatives has been established by using the metal-free ortho-naphthoquinone-catalyzed aerobic cross-coupling reactions of amines. The utilization of two readily available amines allowed a direct coupling strategy to quinazolinone natural product, bouchardatine, as well as sildenafil (Viagra) in a highly convergent manner. This journal is
- Kim, Hun Young,Kim, Kyeongha,Oh, Kyungsoo
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p. 31101 - 31105
(2020/09/23)
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- Effect of Fe(iii)-based MOFs on the catalytic efficiency of the tandem cyclooxidative reaction between 2-aminobenzamide and alcohols
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The catalytic properties of metal-organic frameworks (MOFs) containing triangular Fe(iii) clusters in the promotion of organic syntheses and photocatalysis applications have been receiving substantial attention for decades. These clusters are appealing due to the strong Lewis acidity afforded by coordinatively unsaturated sites upon the removal of solvent from the framework. In this paper, triangular Fe(iii) cluster-based MOFs were shown to be highly efficient heterogeneous catalysts for the solvent-free one-pot condensation of 2-aminobenzamide and alcohols to form quinazolin-4-ones under microwave irradiation. The Fe-MOF catalysts ranging from microporous to mesoporous structures with a variety of geometrical pore structures were investigated. Because of the open accessible spaces for reactants and high density of active sites, MOF-907, built from trimer Fe clusters and a mixture of two linkers, was more effective than other Fe(iii)-MOFs. The catalyst can be used for a broad substrate scope and recycled several times without a significant drop-off in its activity.
- Dang, Minh-Huy Dinh,Nguyen, Trang Thi Minh,Nguyen, Linh Ho Thuy,Nguyen, Trang Thi Thu,Phan, Thang Bach,Tran, Phuong Hoang,Doan, Tan Le Hoang
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supporting information
p. 14529 - 14535
(2020/10/02)
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- Cobalt complexes of redox noninnocent azo-aromatic pincers. Isolation, characterization, and application as catalysts for the synthesis of quinazolin-4(3: H)-ones
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Herein we report the synthesis, characterization and catalytic application of three new cobalt(ii)-complexes of redox noninnocent arylazo ligands, 2-(phenylazo)-1,10-phenanthroline (L1a), 2-(4-chlorophenylazo)-1,10-phenanthroline (L1b) and 2,9-bis(phenyldiazo)-1,10-phenanthroline (L2) respectively. The reaction of L1a with CoIICl2·6H2O produced a μ-dichloro bridged binuclear cobalt(ii)-complex [CoII2(L1a)2Cl2] (1a) while the same reaction when carried out with 2-(4-chlorophenyl)azo-1,10-phenanthroline (L1b) and 2,9-bis(phenyldiazo)-1,10-phenanthroline (L2) ligands produced two new mononuclear five-coordinate cobalt(ii)-complexes 1b and 2 respectively. In complex 1a and 1b, the ligands L1a and L1b are coordinated to the cobalt(ii)-center in a tridentate mode utilizing all of its nitrogen donor sites while in complex 2 one of the azo-donor sites of the ligand L2 remain pendant. All these complexes were characterized using available spectroscopic techniques and DFT studies. We further explored the potential of these complexes as catalysts for the synthesis of pharmaceutically important organic compounds via the functionalization of alcohols. A variety of substituted quinazolin-4(3H)-ones were synthesized under aerobic conditions via the coupling of alcohols and 2-aminobenzamide using 1b as the catalyst. Mechanistic investigations revealed that both cobalt and the arylazo scaffold act synergistically during catalysis. This journal is
- Das, Siuli,Mandal, Sutanuva,Mondal, Rakesh,Paul, Nanda D.,Sinha, Suman
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supporting information
p. 8448 - 8459
(2020/07/10)
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- C2-substituted quinazolinone derivatives exhibit A1 and/or A2A adenosine receptor affinities in the low micromolar range
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Antagonists of the adenosine receptors (A1 and A2A subtypes) are widely researched as potential drug candidates for their role in Parkinson's disease-related cognitive deficits (A1 subtype), motor dysfunction (A2A subtype) and to exhibit neuroprotective properties (A2A subtype). Previously the benzo-α-pyrone based derivative, 3-phenyl-1H-2-benzopyran-1-one, was found to display both A1 and A2A adenosine receptor affinity in the low micromolar range. Prompted by this, the α-pyrone core was structurally modified to explore related benzoxazinone and quinazolinone homologues previously unknown as adenosine receptor antagonists. Overall, the C2-substituted quinazolinone analogues displayed superior A1 and A2A adenosine receptor affinity over their C2-substituted benzoxazinone homologues. The benzoxazinones were devoid of A2A adenosine receptor binding, with only two compounds displaying A1 adenosine receptor affinity. In turn, the quinazolinones displayed varying degrees of affinity (low micromolar range) towards the A1 and A2A adenosine receptor subtypes. The highest A1 adenosine receptor affinity and selectivity were favoured by methyl para-substitution of phenyl ring B (A1Ki = 2.50 μM). On the other hand, 3,4-dimethoxy substitution of phenyl ring B afforded the best A2A adenosine receptor binding (A2AKi = 2.81 μM) among the quinazolinones investigated. In conclusion, the quinazolinones are ideal lead compounds for further structural optimization to gain improved adenosine receptor affinity, which may find therapeutic relevance in Parkinson's disease-associated cognitive deficits and motor dysfunctions as well as exerting neuroprotective properties.
- Pieterse, Lianie,Terre'Blanche, Gisella,van der Walt, Mietha M.
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supporting information
(2020/06/08)
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