- Efficient One-Pot Synthesis of 3-Substituted Phthalides via Additive Arylation of Organozinc Intermediate
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In recent years, substitution at the third position on phthalides has been proven a valua-ble synthetic intermediate for developing active molecules. We reported a direct and efficient one-pot method for the synthesis of 3-aryl Phthalides performed by adding organo-zinc reagent on methyl-2-formylbenzoate; reagent formed in-situ by the reaction between diethylzinc and different aryl boronic acid derivatives without using any ligand. The possible mechanism involved a coordi-nated zinc carbonyl transition state, arylation, and followed by the intramolecular cyclization. The substituents groups in boronic having different electronic and steric properties played an important role in the reaction completion time and yield. The structure elucidation and confirmation of the synthesized compounds were done by using H-NMR analytical data. The method can be useful for synthesizing various scaffolds and intermediates in search of potentially active compounds.
- Hasan, Mohsin,Tonk, Rajiv Kumar,Yadav, Vivek
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p. 783 - 789
(2022/02/17)
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- Direct and selective synthesis of 3-arylphthalides via nickel-catalyzed aryl addition/intramolecular esterification
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Herein we report a nickel-catalyzed aryl addition/intramolecular esterification in a cascade fashion. Under the combination of commercially available nickel precursor and tridentate ligand, the one pot protocol offers a direct, simple and regioselective approach to access 3-aryl phthalide derivatives from two readily available substrates with good efficiency, broad scope as well as satisfactory functional group compatibility.
- Qiang, Qing,Liu, Feipeng,Rong, Zi-Qiang
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supporting information
(2021/05/10)
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- Metal-Free Aerobic Oxidative C–O Coupling of C(sp3)–H with Carboxylic Acids Catalyzed by DDQ and tert-Butyl Nitrite
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The formation of the C–O bond is one of the hot topics in the area of C(sp3)–H bond functionalization. A metal-free oxidative cross-coupling between benzylic C(sp3)–H bond and carboxylic acids has been developed. The reactions were performed with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as the catalyst, tert-butyl nitrite (TBN) as the co-catalyst, and molecular oxygen as the terminal oxidant. A variety of diarylmethanes could be successfully coupled with various carboxylic acids to obtain diarylmethanol esters in good to excellent yields. In addition, 2-benzylbenzoic acids could be converted into phthalides in moderate yields through an intramolecular oxidative cyclization.
- Pan, Decheng,Pan, Zilong,Hu, Zhiming,Li, Meichao,Hu, Xinquan,Jin, Liqun,Sun, Nan,Hu, Baoxiang,Shen, Zhenlu
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p. 5650 - 5655
(2019/08/20)
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- Rhenium-Catalyzed Phthalide Synthesis from Benzamides and Aldehydes via C-H Bond Activation
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The [4 + 1] annulation of benzamides and aldehydes for phthalide synthesis was achieved via rhenium-catalyzed C-H activation, which demonstrates an unprecedented reaction pattern distinct from those of other transition-metal catalyses. The reaction also features readily available starting materials, a wide scope for both electro-rich and electro-deficient substrates, and the elimination of homoannulation byproducts.
- Jia, Bing,Yang, Yunhui,Jin, Xiqing,Mao, Guoliang,Wang, Congyang
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p. 6259 - 6263
(2019/09/06)
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- Catalytic asymmetric synthesis of 3-aryl phthalides enabled by arylation-lactonization of 2-formylbenzoates
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The catalytic asymmetric synthesis of 3-aryl phthalides is reported through a sequential asymmetric arylation-lactonization reaction. The reaction is enabled by a boron-zinc exchange to generate reactive arylating agents, which react with 2-formylbenzoates in the presence of a chiral amino naphthol ligand. The enantiodetermining step is the arylation of the aldehyde, which then undergoes a lactonization event to yield the corresponding phthalides in good yields and enantioselectivities.
- Carlos, Andressa M. M.,Stieler, Rafael,Lüdtke, Diogo S.
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supporting information
p. 283 - 289
(2019/01/10)
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- Rhodium or palladium-catalyzed cascade aryl addition/intramolecular lactonization of phthalaldehydonitrile to access 3-aryl and 3-alkenyl phthalides
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A rhodium or palladium-catalyzed addition of boronic acids to phthalaldehydonitrile, followed by an intramolecular lactonization of cyano to access 3-substituted phthalides, is described. This procedure tolerates a series of functional groups, such as methoxy, fluoro, chloro, and vinyl groups. It is a novel procedure for the synthesis of 3-arylphthalides.
- Lv, Guanglei,Huang, Genping,Zhang, Guangyou,Pan, Changduo,Chen, Fan,Cheng, Jiang
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supporting information; experimental part
p. 4879 - 4886
(2011/07/29)
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- Rhodium or palladium-catalyzed cascade aryl addition/ intramolecular lactonization of phthalaldehyde with potassium organotrifluoroborates to access 3-arylphthalides
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An efficient rhodium-catalyzed lactonization of phthalaldehyde with potassium organotrifluoroborates to access 3-arylphthalides has been developed. Moreover, palladium is a also good catalyst for such transformation.
- Luo, Fang,Pan, Shen,Pan, Changduo,Qian, Pengcheng,Cheng, Jiang
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supporting information; experimental part
p. 320 - 324
(2011/04/23)
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- Rhodium-catalyzed cascade reaction: Aryl addition/intramolecular esterification to access 3-aryl and 3-alkenyl phthalides
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Chemical Equation Reprentation First one and then the other: A rhodiumcatalyzed addition of aryl and alkenyl boronic acids to phthalaldehyde and subsequent intramolecular esterification is described (see scheme; cod = l,5-cyclooctadiene, dppb = 1,4-bis(diphenylphosphino)butane). The method is facile and practical for accessing 3-aryl and 3-alkenyl phthalides in moderate to good yields. Several functional groups are tolerated under the reaction conditions.
- Ye, Zhishi,Lv, Guanglei,Wang, Wenhui,Zhang, Manli,Cheng, Jiang
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supporting information; experimental part
p. 3671 - 3674
(2010/08/04)
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- Palladium-catalyzed cascade aryl addition/intramolecular lactonization of phthalaldehyde to access 3-aryl- and alkenylphthalides
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A palladium-catalyzed addition of arylboronic acids to phthalaldehyde, followed by an intramolecular lactonization to access 3-substituted phthalides, is described. The procedure tolerates a series of functional groups, such as methoxyl, fluoro, chloro, and trifluoromethyl groups. It represents a procedure for the synthesis of 3-substituted phthalides.
- Ye, Zhishi,Qian, Pengcheng,Lv, Guanglei,Luo, Fang,Cheng, Jiang
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supporting information; experimental part
p. 6043 - 6045
(2010/11/18)
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- Cascade synthesis of racemic 3-arylphthalides
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Use of the modified reagent system of NaBH4-Amberlyst-15 (H +) for the reduction of o-aroylbenzoates 1a-f followed by simple trituration in aqueous HCl, results in the formation of 3-arylphthalide 3a-f in very short reaction time.
- Patil,Karnik
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p. 710 - 712
(2008/09/18)
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- Highly efficient cyclization of o-iodobenzoates with aldehydes catalyzed by cobalt bidentate phosphine complexes: A novel entry to chiral phthalides
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Methyl 2-iodobenzoates 1a-c undergo cyclization reactions with various aromatic aldehydes 2a-m (RC6CHO: R = H 2a, 4-CH3, 2b, 4tBu 2c, 4-OMe 2d, 3-OMe 2e, 4-C1 2f, 4-CF3 2g, 4-CN 2h, 4-Ph 2i; benzo [d][1,3]dioxole-5-carbaldehyde (2j), 1napthaldehyde (2k), benzofuran-2- carbaldehyde (21), and isonicotinaldehyde (2m)) in the presence of [CoI2(dppe)] (dppe = l,2-bis(diphenylphosphino)ethane) and Zn powder in dry THF at 75 °C for 24 h to give the corresponding phthalide derivatives 3a-m and 3q-t in good to excellent yields. Under similar reaction conditions, less reactive aliphatic aldehydes, heptanal (2n), butyraldehyde (2o), and 2-phenylacetaldehyde (2p) also underwent cyclization reactions with la to provide 3n-p, respectively, in fair to good yields. The catalytic reaction can be further extended to cinnamyl aldehyde (2q) with la to give the corresponding phthalide derivative 3u. This synthetic method is compatible with a variety of functional groups on the aryl ring of 2. The high efficiency of the cobalt catalyst containing a dppe (dppe = l,2-bis(diphenylphosphino)ethane) ligand encouraged us to investigate the asymmetric version of the present catalytic reaction by employing bidentate chiral ligands. Thus, aromatic aldehydes 2a-c, 2f, and 2 g undergo cyclization with 2-iodobenzoate (la) smoothly in the presence of [CoI2{(S,S)- dipamp}] ((S,S)-dipamp = (1S,2S)-(+)-bis[2-methoxyphenyl]phenylphosphino)ethane) and zinc powder in THF at 75 °C for 24 h, giving the corresponding (S)-phthalides 4a-e in 8189 % yields with 70-98 % ee. A possible mechanism for the present catalytic reaction is proposed.
- Chang, Hong-Tai,Jeganmohan, Masilamani,Cheng, Chien-Hong
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p. 4356 - 4363
(2008/02/05)
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- Efficient synthesis of isobenzofuran-1(3H)-ones (Phthalides) and selected biological evaluations
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The studies presented here deal with the convenient and efficient one-step conversion of o-alkylbenzoic acids into their corresponding isobenzofuran-1 (3H)-ones (phthalides) using NaBrO3/NaHSO3 in a two-phase system. A range of o-alkylbenzoic acids was used with the object of getting a variety of phthalide derivatives as multipurpose biologically active compounds. Seventeen phthalides have been synthesized and tested for cytotoxicity, antibacterial and antifungal activities. Some of these compounds showed promising cytotoxic effects against Artemia salina. Compounds 4j-4p were highly active against Gram-negative and Gram-positive bacteria among all tested compounds. In the fungicidal assay, the compounds showed a broad spectrum of activity against six fungi. All compounds were characterized via elemental analysis, UV, IR, mass and-NMR spectroscopy. ECV · Editio Cantor Verlag.
- Bayer, Ernst,Hayat, Safdar,Atta-Ur-Rahman,Choudhary, M. Iqbal,Khan, Khalid Mohammed,Shah, Syed Tasadaque Ali,Imran-Ul-Haq,Anwar, M. Usman,Voelter, Wolfgang
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p. 588 - 597
(2007/10/03)
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- Synthesis of phthalide derivatives using nickel-catalyzed cyclization of o-haloesters with aldehydes
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The reaction of o-bromobenzoate (1b) with benzaldehyde (2a) in the presence of [NiBr2(dppe)] (dppe = 1,2-bis(diphenylphosphino)ethane) and zinc powder in THF (24 hours, reflux temperature), afforded 3-phenyl-3H- isobenzofuran-1-one (3a) in an 86% yield. Similarly, o-iodobenzoate reacts with 2a to give 3a, but in a lower yield (50%). A series of substituted aromatic and aliphatic aldehydes (2b, 4-MeC6H4CHO; 2c, 4-MeOC 6H4CHO; 2d, 3-MeOC6H4-CHO 2e, 2-MeOC6H4-CHO; 2f, 4-CNC6H4CHO; 2g, 4-(Me)3-CC6H4CHO; 2h, 4-C6H 4C6H4CHO; 2i, 4-ClC6H 4CHO; 2j, 4-CF3C6H4CHO; 2k, CH 3(CH2)5CHO; 21, CH3(CH 2)2-CHO) also underwent cyclization with o-bromobenzoate (1b) producing the corresponding phthalide derivatives in moderate to excellent yields and with high chemoselectivity. Like 1b, methyl 2-bromo-4,5- dimethoxybenzoate (1c) reacts with tolualdehyde (2b) to give the corresponding substituted phthalide 3m in a 71% yield. The methodology can be further applied to the synthesis of six-membered lactones. The reaction of methyl 2-(2-bromophenyl)acetate (1d) with benzaldehyde under similar reaction conditions afforded six-membered lactone 3o in a 68% yield. A possible catalytic mechanism for this cyclization is also proposed.
- Rayabarapu, Dinesh Kumar,Chang, Hong-Tai,Cheng, Chien-Hong
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p. 2991 - 2996
(2007/10/03)
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- An alternative method for the synthesis of γ-lactones by using cesium fluoride-celite/acetonitrile combination
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A variety of 2-(1-bromoalkyl) benzoic acids 4 undergo intramolecular nucleophilic substitution reaction when treated with a CsF-Celite as solid base in acetonitrile under reflux condition to give the corresponding cyclized phthalides in moderate to very good yield. These 2-(1-bromoalkyl) benzoic acids 4 are formed by the α-bromination of 2-alkylbenzoic acids 3 using N-bromosuccinimide and a catalytic amount of α,α′ -azoisobutyronitrile in carbon tetrachloride under reflux.
- Khan, Khalid Mohammed,Hayat, Safdar,Zia-Ullah,Atta-ur-Rahman,Iqbal-Choudhary,Maharvi, Ghulam Murtaza,Bayert, Ernst
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p. 3435 - 3453
(2007/10/03)
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- Process for forming certain substituted phthalimidines
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The process of preparing a compound of the formula: STR1 wherein, Y and Z are each H, alkyl, halo, alkoxy, trifluoromethyl, hydroxy, alkanoyloxy, or alkanoylamino; X is F, Cl, Br, or NR1 R2 wherein R1 and R2 are
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- Intermediates for the synthesis of phthalimidines
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Compounds of the formula STR1 wherein, Y and Z are each H, alkyl, halo, alkoxy, trifluoromethyl, hydroxy, alkanoyloxy, or alkanoylamino; X is F, Cl Br or NR1 R2 in which R1 and R2 are each hydrogen, alkyl, alken
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- Substituted phthalide derivatives
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Method of preparing chlorthalidone, an antihypertensive agent, and derivatives using a novel 3-(4'-chloro-3'-chlorosulfonylphenyl)phthalide intermediate and derivatives, and method of preparing said novel intermediate, are disclosed.
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