- Hydrogen-bond-assisted transition-metal-free catalytic transformation of amides to esters
-
The amide C-N cleavage has drawn a broad interest in synthetic chemistry, biological process and pharmaceutical industry. Transition-metal, luxury ligand or excess base were always vital to the transformation. Here, we developed a transition-metal-free hydrogen-bond-assisted esterification of amides with only catalytic amount of base. The proposed crucial role of hydrogen bonding for assisting esterification was supported by control experiments, density functional theory (DFT) calculations and kinetic studies. Besides broad substrate scopes and excellent functional groups tolerance, this base-catalyzed protocol complements the conventional transition-metal-catalyzed esterification of amides and provides a new pathway to catalytic cleavage of amide C-N bonds for organic synthesis and pharmaceutical industry. [Figure not available: see fulltext.]
- Huang, Changyu,Li, Jinpeng,Wang, Jiaquan,Zheng, Qingshu,Li, Zhenhua,Tu, Tao
-
-
- Supramolecular Pd(II) complex of DPPF and dithiolate: An efficient catalyst for amino and phenoxycarbonylation using Co2(CO)8 as sustainable C1 source
-
Highly active, efficient and robust “dppf ligated tetranuclear palladium dithiolate complex” was synthesized and applied as a catalyst for chemical fixation of carbon monoxide for the synthesis value added chemicals such as tertiary amide and aromatic esters. The synthesized catalyst was characterized using different analytical techniques such as elemental analysis, 1H and 31P NMR spectroscopy. The use of Co2(CO)8 as a cheap, less toxic and low melting solid surrogate are additional advantages over the current protocol. The catalyst showed superior activity towards the Amino (10?3 mol % catalyst) and Phenoxycarbonylation (10-2 mol % catalyst) and high TON (104 to 103) and TOF (103 to 102 h-1). The Betol and Lintrin (active drug molecules) were synthesized under an optimized reaction condition. The scalability of the current protocol has been demonstrated up-to the gram level.
- Gaikwad, Vinayak V.,Mane, Pravin A.,Dey, Sandip,Patel, Divya,Bhanage, Bhalchandra M.
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-
- Palladium-Catalyzed Aerobic Oxidative Coupling of Amides with Arylboronic Acids by Cooperative Catalysis
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The first fluoride and palladium co-catalyzed conversion of amide to ester through an aerobic oxidative coupling pathway is reported. This new approach presents a practical process that employs easily available oxygen and commercially available arylboronic acids as coupling partners, uses a wide range of N- tosylamides, and proceeds under mild reaction conditions. This protocol demonstrates broad functional group tolerance, and provides an alternative option to synthesize esters from N-tosylamides which obtained by simply N-functionalization of secondary amides.
- Li, Yue,Wu, Hongxiang,Zeng, Zhuo
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supporting information
p. 4357 - 4361
(2019/07/09)
-
- Base-Promoted Amidation and Esterification of Imidazolium Salts via Acyl C-C bond Cleavage: Access to Aromatic Amides and Esters
-
Imidazolium salts have been effectively employed as suitable acyl transfer agents in amidation and esterification in organic synthesis. The weak acyl C(O)-C imidazolium bond was exploited to generate acyl electrophiles, which further react with amines and alcohols to afford amides and esters. The broad substrate scope of anilines and benzylic amines and base-promoted conditions are the benefits of this route. Interestingly, phenol, benzylic alcohols, and a biologically active alcohol can also be subjected to esterification under the optimized conditions.
- Karthik, Shanmugam,Muthuvel, Karthick,Gandhi, Thirumanavelan
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p. 738 - 751
(2019/01/24)
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- Oxime palladacycle in PEG as a highly efficient and recyclable catalytic system for phenoxycarbonylation of aryl iodides with phenols
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In this report, we have developed a sustainable protocol for the synthesis of aromatic esters by a carbonylative method using di-μ-chlorobis [5-hydroxy-2-[1-(hydroxyimino-?N) ethyl] phenyl-?C] palladium (II) dimer (1) catalyst in PEG-400 as a greener and recyclable solvent. The reaction is carried out at room temperature using CO in a balloon. Good to excellent yield of various esters can be synthesize using this protocol. Direct insertion of CO moiety leads to the high atom and step economy. Compared to previous protocol this phosphine free approach for the synthesis of aromatic esters provides high Turnover Number (TON) and Turnover Frequency (TOF). Developed approach has an alternative route for use of conventional palladium precursor with high conversion and selectivity. The catalyst system and product can easily be separated using diethyl ether as a solvent. The Pd/PEG-400 system could be reused up to a fifth consecutive cycle without any loss of its activity and selectivity.
- Gaikwad, Vinayak V.,Bhanage, Bhalchandra M.
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- Electrodimerization of N-Alkoxyamides for Zinc(II) Catalyzed Phenolic Ester Synthesis under Mild Reaction Conditions
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An electrochemical On-Off method for phenolic ester synthesis from N-alkoxyamides has been reported. This one-pot protocol begins with rapid and selective electrodimerization of the amide using n-Bu4NI (TBAI) as an electrocatalyst. The reaction proceeds further in the absence of current via Zn catalyzed C?N bond activation of the amide dimer followed by its coupling with phenol to form the ester. The present methodology is ligand-free and takes place under mild reaction conditions. This transformation incorporates a wide variety of phenols and amide substrates leading to the formation of functionalized esters highlighting its versatility. (Figure presented.).
- Subramanian, Kripa,Yedage, Subhash L.,Bhanage, Bhalchandra M.
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p. 2511 - 2521
(2018/05/14)
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- Palladium-Catalyzed Oxidative Carbonylation of Aryl Hydrazines with CO and O2 at Atmospheric Pressure
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Palladium-catalyzed aerobic oxidative aminocarbonylation and alkoxycarbonylation reactions with aryl hydrazines as coupling partners have been developed. The oxidative carbonylation of aryl hydrazines proceeded smoothly at atmospheric pressure CO, employi
- Tu, Yongliang,Yuan, Lin,Wang, Tao,Wang, Changliu,Ke, Jiamei,Zhao, Junfeng
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p. 4970 - 4976
(2017/05/12)
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- Palladium Catalyzed Carbonylative Coupling for Synthesis of Arylketones and Arylesters Using Chloroform as the Carbon Monoxide Source
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We describe a modular, palladium catalyzed synthesis of aryl(hetero)aryl benzophenones and aryl benzoates from aryl(hetero)aryl halides using CHCl3 as the carbonyl source in the presence of KOH. The reaction occurs in tandem through an initial carbonylation to generate an aroyl halide, which undergoes coupling with arylboronic acids, bornonates, and phenols. Direct carbonylative coupling of indoles at the third position has also been accomplished under slightly modified reaction conditions by in situ activation of the C-H bond. Notably, CHCl3 is a convenient and safe alternation of CO gas, provides milder reaction conditions with high functional group tolerance, and gives the products in moderate to good yields.
- Sharma, Poonam,Rohilla, Sandeep,Jain, Nidhi
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p. 1105 - 1113
(2018/06/18)
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- Highly Active Manganese-Mediated Acylation of Alcohols with Acid Chlorides or Anhydrides
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To explore further the practical uses of highly active manganese (Mn?), a variety of alcohols were treated with Mn?, and the resulting complexes were coupled with acid chlorides and/or acetic anhydride in the absence of any extra catalyst. The subsequent reactions took place smoothly under mild conditions, providing the corresponding O-acylation products in good to excellent isolated yields.
- Joo, Seong-Ryu,Youn, Young-Jin,Hwang, Young-Ran,Kim, Seung-Hoi
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p. 2665 - 2669
(2017/10/07)
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- Series of high spin mononuclear iron(III) complexes with Schiff base ligands derived from 2-hydroxybenzophenones
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The reaction of various phenols with benzoyl chloride afforded the derivatives of phenyl benzoate that subsequently underwent Fries rearrangement. The obtained 2-hydroxybenzophenone analogues were combined with linear aliphatic triamines, which afforded pentadentate Schiff base ligands. Moreover, nine new iron(iii) complexes with the general formula [Fe(Ln)X] (where, Ln is the dianion of the pentadentate Schiff base ligand, N,N′-bis((2-hydroxy-5-methylphenyl)phenyl)methylidene-1,5-diamino-3-azapentane = H2L1, N,N′-bis((2-hydroxy-3,5-dimethylphenyl)phenyl)methylidene-1,5-diamino-3-azapentane = H2L2, N,N′-bis((2-hydroxy-5-chlorophenyl)phenyl)methylidene-1,5-diamino-3-azapentane = H2L3, N,N′-bis((2-hydroxy-4-methylphenyl)phenyl)methylidene-1,5-diamino-3-azapentane = H2L4, N,N′-bis((2-hydroxy-5-bromophenyl)phenyl)methylidene-1,7-diamino-4-azaheptane = H2L5, N,N′-bis((2-hydroxy-5-bromophenyl)phenyl)methylidene-1,7-diamino-4-methyl-4-azaheptane = H2L6 and X is the chlorido, azido or isocyanato terminal ligand) were synthesized and characterized via elemental analysis, and IR and UV-VIS spectroscopy; in addition, the crystal structures of all the complexes were determined by X-ray diffraction. Magnetic investigation reveals high spin state behaviour in all the reported compounds. DFT calculations and analysis of the magnetic functions allowed to extract absolute values of the zero field splitting parameters and exchange coupling constants.
- Pogány, Luká?,Moncol, Ján,Pavlik, Ján,?alitro?, Ivan
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supporting information
p. 5904 - 5915
(2017/07/10)
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- The heteropolyacid catalyzed phenol method for synthesizing Arylester
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The invention discloses a synthesis method of phenol by aromatic esterification by using heteropoly acid as a catalyst. The method comprises the following steps: adding fatty acid substituted phenol ester I, substituted benzoic acid II, reaction solvent and heteropoly acid into a reaction vessel provided with a thermometer, a water separator and a stirrer, reacting at 110-170 DEG C for 0.5-10 hours, wherein the reaction progress is monitored by TLC (thin layer chromatography) in the reaction process; and after the reaction is finished, centrifuging the reaction solution, taking the supernate, washing to remove the solvent, and carrying out recrystallization or column chromatography on the crude product to obtain the aromatic ester compound III. By using the heteropoly acid as the catalyst, compared with the traditional esterification reaction, the method disclosed by the invention has the advantages of simple after-treatment, and low pollution and environment friendliness due to use of a small amount of acid. The heteropoly acid is a solid acid, and can be recycled by filtration after the reaction is finished. The aromatic esterification reaction of exchanging ester with phenol is adopted to avoid the side reaction caused by high oxidation tendency of the substituted phenol in the reaction, so that the method is simpler to operate and has higher yield.
- -
-
Paragraph 0024; 0025
(2016/11/09)
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- A novel nickel-catalyzed synthesis of thioesters, esters and amides from aryl iodides in the presence of chromium hexacarbonyl
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This study describes our findings on a novel and cheap NiCl2 catalytic system under ligand-free conditions for the efficient thiocarbonylation, alkoxycarbonylation and amidocarbonylation reactions of aryl iodides in the presence of Cr(CO)6 as the solid source of carbon monoxide under air. A variety of aryl iodides tolerated the reaction conditions and structurally different thiols, alcohols and amines were used efficiently. The corresponding thioesters, esters and amides were obtained in good to excellent yield at atmospheric pressure under mild reaction conditions.
- Iranpoor, Nasser,Firouzabadi, Habib,Etemadi-Davan, Elham,Nematollahi, Arash,Firouzi, Hamid Reza
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p. 6445 - 6452
(2015/08/11)
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- Reactions of aryl benzoates with potassium aryloxides: Solvent effects on reaction pathway and kinetics
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Temperature dependences of the relative reactivity of potassium aryloxides XC6H4O-K+ toward 2,4-dinitrophenyl benzoate in 50 mol% dimethylformamide (DMF)-50 mol% H2O mixture have been studied using the competitive reactions technique. Correlation analyses of the relative rate constants kX/kH and differences in the activation parameters (ΔΔCyrillic capital letter en≠ and ΔΔS≠) of the competitive reactions have revealed the existence of two isokinetic series of the reactions of 2,4-dinitrophenyl benzoate with potassium aryloxides with electron-donating substituent (EDS) and electron-withdrawing substituent (EWS), respectively. We have investigated the effect of the substituent X on the activation parameters for each isokinetic series and concluded that the mechanism of the reactions of 2,4-dinitrophenyl benzoate with potassium aryloxides XC6H4O-K+ in 50 mol% DMF-50 mol% H2O mixture is the same as in DMF. Analysis of the obtained data with using the method of two-dimensional reaction coordinate diagram leads to the conclusion that the variation of the solvent from DMF to 50 mol% DMF-50 mol% H2O mixture affects the reaction pathway. The rate constant kX for the reaction of 3-nitrophenyl benzoate with potassium 4-methoxyphenoxide and the relative rate constants kX/kH for the reaction of 3-nitrophenyl benzoate with potassium aryloxides XC6H4O-K+ with EDS were measured in 50 mol% DMF-50 mol% H2O mixtures at 25C, and it has been shown that the addition of water to DMF does not change the mechanism but slows down these reactions.
- Khalfina, Irina A.
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p. 302 - 314
(2015/04/14)
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- Palladium supported on triphenylphosphine functionalized porous organic polymer: A highly active and recyclable catalyst for alkoxycarbonylation of aryl iodides
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An efficient method for the alkoxycarbonylation of aryl iodides using palladium supported on triphenylphosphine functionalized porous organic polymer (Pd@KAPs(Ph-PPh3)) as the catalyst is reported. Under balloon pressure of CO, various aryl iodides on carbonylation with alcohols and phenols give the corresponding products in moderate to excellent yields (74-96%). The catalyst can be easily separated by simple filtration process and recycled up to ten times without significant decrease in activity. The salient features of this protocol are the simplicity in handling of the catalyst, low CO pressure, negligible palladium leaching and good catalyst recyclability.
- Lei, Yizhu,Wu, Linjuan,Zhang, Xuefeng,Mei, Hui,Gu, Yanlong,Li, Guangxing
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p. 164 - 169
(2015/02/19)
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- Study on the aromatic transesterification reaction catalyzed by phosphotungstic acid
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A practical phosphotungstic acid-catalyzed aromatic transesterification reaction for the preparation of aryl benzoates has been developed. The transesterification method avoids the oxidation of the corresponding phenols to quinone compounds with easy operations, environmentally benign conditions and high yields of the products. It is noteworthy that in this process phosphotungstic acid can be reused and recycled.
- He, Hong-Qiang,Chang, Yu-Wei,Xu, Wei-Ming
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supporting information
p. 280 - 282
(2015/06/22)
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- Ligand-free palladium-catalyzed aerobic oxidative coupling of carboxylic anhydrides with arylboronic acids
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We report a new, effective and environmentally friendly protocol for selective aerobic oxidative coupling of arylboronic acids with carboxylic anhydrides in the presence of ligand-free palladium catalyst. The aryl benzoates are obtained in good to excellent yields.
- Yin, Weiyan,He, Haifeng,Zhang, Yani,Long, Tong
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p. 2402 - 2406
(2014/10/15)
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- Alkoxycarbonylation and phenoxycarbonylation reactions catalyzed by a palladium(II) organometallic complex encaged in y zeolite
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Catalytic routes for synthesis of alkyl benzoates by alkoxycarbonylation reactions and aryl benzoates by phenoxycarbonylation reactions of aryl iodides are described using a palladium-1,10-phenanthroline complex encaged in Y zeolite. Moderate to excellent yields (40-99 %) of various benzoates were obtained at low Pd loadings of 0.6 mol%. The catalyst could be effectively removed from the reaction mixture by a simple filtration process and was reused four times with only minor loss of activity. Furthermore, its catalytic activity was further highlighted by a comparison with another two supported Pd catalysts. The protocol has the advantages of easy handing, moderate to excellent yield, and catalyst recyclability. Graphical Abstract: [Figure not available: see fulltext.]
- Mei, Hui,Xiao, Se,Zhu, Tianwu,Lei, Yizhu,Li, Guangxing
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p. 443 - 450
(2014/05/20)
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- Nucleophilic substitution reactions of Y-Substituted-Phenyl Benzoates with Potassium Ethoxide in Anhydrous Ethanol: Reaction Mechanism and Role of K+ Ion
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Pseudo-first-order rate constants (kobsd) have been measured spectrophotometrically for the reactions of Ysubstituted-phenyl benzoates (5a-j) with potassium ethoxide (EtOK) in anhydrous ethanol at 25.0 ± 0.1 °C. The plots of kobsd vs. [EtOK] curve upward regardless of the electronic nature of the substituent Y in the leaving group. Dissection of kobsd into the second-order rate constants for the reactions with the dissociated EtOV and ion-paired EtOK (i.e., kEtO-and kEtOK, respectively) has revealed that the ion-paired EtOK is more reactive than the dissociated Et-V. The Bronsted-type plots for the reactions with the dissociated Et-V and ion-paired EtOK exhibit highly scattered points with βlg = -0.5 ± 0.1. The Hammett plots correlated with ao constants result in excellent linear correlations, indicating that no negative charge develops on the O atom of the leaving Ysubstituted-phenoxide ion in transition state. Thus, it has been concluded that the reactions with the dissociated EtOV and ion-paired EtOK proceed through a stepwise mechanism, in which departure of the leaving group occurs after the RDS, and that K+ ion catalyzes the reactions by increasing the electrophilicity of the reaction center through a four-membered cyclic TS structure.
- Kim, Song-I,Cho, Hyo-Jin,Um, Ik-Hwan
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p. 177 - 181
(2014/02/14)
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- Enthalpy-entropy correlations in reactions of aryl benzoates with potassium aryloxides in dimethylformamide
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Temperature dependences of the relative reactivity of potassium aryloxides XC6H4O-K+ toward 4-nitrophenyl (1), 3-nitrophenyl (2), 4-chlorophenyl (3), and phenyl (4) benzoates in dimethylformamide (DMF) were studied using the competitive reactions technique. The rate constants kX for the reactions of 1 with potassium 4-cyanophenoxide, 2 with potassium 3-bromophenoxide, 3 with potassium 3-bromo-, 4-bromo-, and unsubstituted phenoxides, 4 with potassium 4-methoxy- and 3-methylphenoxides were measured at 25°C. Correlation analysis of the relative rate constants kX/kH(3-Me) and differences in the activation parameters (δδH≠and δ δS ≠) of competitive reactions revealed the existence of six isokinetic series. We investigated the substituent effect of X on the activation parameters for each isokinetic series and concluded that the reactions of aryl benzoates PhCO2C6H4Y with potassium aryloxides in DMF proceed via a four-step mechanism. The large ρ0(Y) and ρXY values at 25°C obtained for the reactions of 1-3 with potassium aryloxides with an electron-donating substituent refer to the rate-determining formation of the spiro-σ-complex. The Hammett plots for the reactions of 1 and 2 exhibit a downward curvature, causing the motion of the transition state for the rate-determining step according to a Hammond effect as the substituent in aryloxide changes from electron-donating to electron-withdrawing. Analysis of data in the terms of two-dimensional reaction coordinate diagrams leads to the conclusion that significant anti-Hammond effects arise in the cases of ortho-substituted and unsubstituted substrates. It was shown that the isokinetic and compensation effects observed for the reactions of aryl benzoates with potassium aryloxides in DMF can be interpreted in the terms of the electrostatic bonding between the reaction centers.
- Khalfina, Irina A.,Vlasov, Vladislav M.
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p. 266 - 282
(2013/05/21)
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- Palladacycle-catalyzed carbonylation of aryl iodides or bromides with aryl formates
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An efficient palladacycle-catalyzed aromatic carbonylation reaction of aryl formates with aryl iodides or bromides has been developed. Commercially available and easily prepared aryl formates were employed as carbonyl sources without the use of external carbon monoxide. The present catalytic system shows broad functional group tolerance and affords aryl benzoate derivatives in good to excellent yields. Copyright
- Chen, Guangwei,Leng, Yuting,Yang, Fan,Wang, Shiwei,Wu, Yangjie
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p. 1488 - 1494
(2014/01/06)
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- Palladium-catalyzed aerobic oxidative coupling of acyl chlorides with arylboronic acids
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The first example of a palladium-catalyzed aerobic oxidative coupling of acyl chlorides with arylboronic acids has been developed, leading to a wide range of aryl benzoates in good to excellent yields. This catalytic system shows broad functional group tolerance. Preliminary mechanistic experiments using deuterium labeling showed that the oxygen atom was derived from dioxygen. Copyright
- Chen, Jiuxi,Peng, Yong,Liu, Miaochang,Ding, Jinchang,Su, Weike,Wu, Huayue
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supporting information
p. 2117 - 2122
(2012/11/07)
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- Enthalpy-entropy correlations in reactions of 2,4-dinitrophenyl benzoate with phenols in the presence of potassium hydrogen carbonate and with potassium phenoxides in dimethylformamide
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Temperature dependences of the relative reactivity of substituted phenols RC6H4OH in the presence of potassium hydrogen carbonate and of potassium phenoxides RC6H4O-K + toward 2,4-dinitrophenyl benzoate in dimethylformamide were studied using the competitive reactions technique. Correlation analysis of the relative rate constants kR/kH and differences in the activation parameters (ΔΔH{double barred pipe} and ΔΔS{double barred pipe}) of competitive reactions revealed the existence of two isokinetic series for each type of nucleophiles. The mechanism of transesterification was interpreted in terms of an approach based on analysis of the effect of substituent in the nucleophile on the activation parameters. Pleiades Publishing, Ltd., 2011.
- Khalfina,Vlasov
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experimental part
p. 845 - 854
(2011/10/19)
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- Cu(OTf)2-mediated Chan-Lam reaction of carboxylic acids to access phenolic esters
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A Cu(OTf)2-mediated Chan-Lam reaction of carboxylic acids with arylboronic acids is described. It represents a facile and practical methodology to access phenolic esters in moderate to good yields. The procedure tolerates a series of functional groups, such as methoxycarbonyl, acetoxy, free phenolic hydroxyl, vinyl, nitro, trifluoromethyl, methoxyl, bromo, chloro, iodo, and acetyl groups.
- Zhang, Lingli,Zhang, Guoying,Zhang, Manli,Cheng, Jiang
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experimental part
p. 7472 - 7474
(2011/01/03)
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- Pd(II)-catalyzed C-H activation/aryl-aryl coupling of phenol esters
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(Chemical Equation Presented) Although nitrogen-containing group-directed cyclopalladation reactions have been well-known, Pd(II) insertion into C-H bonds promoted by coordination of an oxygen-only group to the palladium remains rather rare. In the present study, the first cyclopalladation complex formed from a simple phenol ester was characterized by X-ray crystallography. A promising protocol for the ortho C-H activation/aryl-aryl coupling of phenol esters that was not sensitive to moisture or air was then established. The utility of the reaction was demonstrated for the synthesis of useful phenol derivatives. Copyright
- Xiao, Bin,Fu, Yao,Xu, Jun,Gong, Tian-Jun,Dai, Jian-Jun,Yi, Jun,Liu, Lei
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supporting information; experimental part
p. 468 - 469
(2010/03/25)
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- Kinetics and mechanism of nucleophilic displacement reactions of Y-substituted phenyl benzoates with cyanide Ion
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Second-order rate constants (kCN-) have been measured for nucleophilic substitution reactions of Y-substituted phenyl benzoates (1a-r) with CN- ion in 80 mol % H2O/20 mol % DMSO at 25.0 ± 0.1 °C. The Bronsted-type plot is linear with βlg = -0.49, a typical βlg value for reactions reported to proceed through a concerted mechanism. Hammett plots correlated with σo and σ-constants exhibit many scattered points. In contrast, the Yukawa-Tsuno plot for the same reaction exhibits excellent linearity with pY = 1.37 and r = 0.34, indicating that a negative charge develops partially on the oxygen atom of the leaving aryloxide in the rate-determining step (RDS). Although two different mechanisms are plausible (i.e., a concerted mechanism and a stepwise pathway in which expulsion of the leaving group occurs at the RDS), the reaction has been concluded to proceed through a concerted mechanism on the basis of the magnitude of βlg and pY values.
- Kim, Song-I,Kim, Eun-Hee,Um, Ik-Hwan
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experimental part
p. 689 - 693
(2010/08/19)
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- Discovery of a novel class of potent coumarin monoamine oxidase B inhibitors: Development and biopharmacological profiling of 7-[(3-chlorobenzyl) oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate (NW-1772) as a highly potent, selective, reversible, and orally active monoamine oxidase B inhibitor
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In an effort to discover novel selective monoamine oxidase (MAO) B inhibitors with favorable physicochemical and pharmacokinetic profiles, 7-[(m-halogeno)benzyloxy]coumarins bearing properly selected polar substituents at position 4 were designed, synthesized, and evaluated as MAO inhibitors. Several compounds with MAO-B inhibitory activity in the nanomolar range and excellent MAO-B selectivity (selectivity index SI > 400) were identified. Structure-affinity relationships and docking simulations provided valuable insights into the enzyme-inhibitor binding interactions at position 4, which has been poorly explored. Furthermore, computational and experimental studies led to the identification and biopharmacological characterization of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)-methyl]-2H-chromen-2-one methanesulfonate 22b (NW-1772) as an in vitro and in vivo potent and selective MAO-B inhibitor, with rapid blood-brain barrier penetration, short-acting and reversible inhibitory activity, slight inhibition of selected cytochrome P450s, and low in vitro toxicity. On the basis of this preliminary preclinical profile, inhibitor 22b might be viewed as a promising clinical candidate for the treatment of neurodegenerative diseases.
- Pisani, Leonardo,Muncipinto, Giovanni,Miscioscia, Teresa Fabiola,Nicolotti, Orazio,Leonetti, Francesco,Catto, Marco,Caccia, Carla,Salvati, Patricia,Soto-Otero, Ramon,Mendez-Alvarez, Estefania,Passeleu, Celine,Carotti, Angelo
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experimental part
p. 6685 - 6706
(2010/04/04)
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- A simple and efficient recyclable phosphine-free catalytic system for alkoxycarbonylation and carbonylative Sonogashira coupling reactions of aryl iodides
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Using palladium on charcoal (Pd/C) and triethylamine as a novel, efficient, versatile, recyclable, and phosphine-free catalytic system, we carried out the alkoxycarbonylation of aryl iodides (alcohols or phenols as nucleophiles) and the carbonylative Sonogashira coupling reaction of aryl iodides with terminal alkynes, affording the corresponding aryl esters and α, β-alkynyl ketones in good to excellent yields under mild conditions. We found that both electron-withdrawing and electron-donating substituents on phenol enhanced the phenoxycarbonylation of iodobenzene. The recyclability of Pd/C was also demonstrated.
- Liu, Jianhua,Chen, Jing,Xia, Chungu
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- TiO2: A simple and an efficient catalyst for esterification of phenols under solvent-free condition
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In the presence of catalytic amount of titanium oxide (TiO2), without any additional solvent at 25°C, phenols are conveniently acylated by acid chlorides to get phenolic esters in excellent yields. The TiO2 powder can be reused three times after simple washing with CH2Cl 2.
- Pasha, Mohamed Afzal,Manjula, Krishnappa
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p. 597 - 600
(2008/09/19)
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- PhCOCI-Py/basic alumina as a versatile reagent for benzoylation in solvent-free conditions
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A solvent-free procedure using PhCOCl-Py/basic alumina under microwave irradiation has been developed for N-, O- and S-benzoylation.
- Paul, Satya,Nanda, Puja,Gupta, Rajive
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p. 374 - 380
(2007/10/03)
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- Preparation of hydroxybenzophenones using silica-gel supported ferric chloride
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The synthesis of commercially important hydroxybenzophenones by condensing phenols with benzotrichloride has been reported. Benzoylation is catalyzed by silica supported ferric chloride under solvent-free conditions. Hydroxybenzophenones are isolated in low to moderate yields.
- Bendale, Pravin M.,Khadilkar, Bhushan M.
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p. 1738 - 1739
(2007/10/03)
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- Determination of aromaticity indices of thiophene and furan by nuclear magnetic resonance spectroscopic analysis of their phenyl esters
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A series of m- and p-substituted phenyl benzoates, 2-thienoates, and 2-furoates were prepared and their 1H and 13C nmr spectroscopic characteristics were examined. In general, good correlations were observed between the chemical shift values of protons and carbons of the acyl aromatic rings and the Hammett σ. Plots of the chemical shift values of the carbonyl carbons of the benzoates against those of the 2-thienoates and 2-furoates gave an excellent correlation and the values of the slopes are 0.85 and 0.75, respectively, in dimethyl sulfoxide-d6 and 0.90 and 0.78, respectively, in chloroform-d. The values could be considered as a set of aromaticity indices.
- Lee, Chang Kiu,Yu, Ji Sook,Lee, Hye-Jin
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p. 1207 - 1217
(2007/10/03)
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- Hypolipidemic 1,4-benzothiazepine derivative
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The invention is concerned with a novel hypolipidemic compound, which is of (3R,5R)-3-Butyl-3-ethyl-2,3,4,5-tetrahydro-7-methoxy-5-phenyl-1,4-benzothiazepin-8-ol 1,1-dioxide; or a salt, solvate, or physiologically functional derivative thereof, with processes for its preparation, pharmaceutical compositions containing it and with its use in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions, such as athersclerosis.
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- P2O5/SiO2 as an efficient reagent for esterification of phenols in dry media
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A simple and efficient method for esterification of carboxylic acid with phenols using P2O5/SiO2 reagent in dry media is reported.
- Eshghi,Rafei,Karimi
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p. 771 - 774
(2007/10/03)
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- Inhibition of monoamine oxidases by functionalized coumarin derivatives: Biological activities, QSARs, and 3D-QSARs
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A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory activity. Most of the compounds acted preferentially on MAO-B with IC50 values in the micromolar to low-nanomolar range; high inhibitory activities toward MAO-A were also measured for sulfonic acid esters. The most active compound was 7-[(3,4-difluorobenzyl)oxy]-3,4-dimethylcoumarin, with an IC50 value toward MAO-B of 1.14 nM. A QSAR study of 7-X-benzyloxy meta-substituted 3,4-dimethylcoumarin derivatives acting on MAO-B yielded good statistical results (q2 = 0.72, r2 = 0.86), revealing the importance of lipophilic interactions in modulating the inhibition and excluding any dependence on electronic properties. CoMFA was performed on two data sets of MAO-A and MAO-B inhibitors. The GOLPE procedure, with variable selection criteria, was applied to improve the predictivity of the models and to facilitate the graphical interpretation of results.
- Gnerre,Catto,Leonetti,Weber,Carrupt,Altomare,Carotti,Testa
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p. 4747 - 4758
(2007/10/03)
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- Structure-activity relationship studies on 1-[2-(4- phenylphenoxy)ethyl]pyrrolidine (SC-22716), a potent inhibitor of leukotriene A4 (LTA4) hydrolase
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Leukotriene B4 (LTB4) is a pro-inflammatory mediator that has been implicated in the pathogenesis of a number of diseases including inflammatory bowel disease (IBD) and psoriasis. Since the action of LTA4 hydrolase is the rate-limiting step for LTB4 production, this enzyme represents an attractive pharmacological target for the suppression of LTB4 production. From an in- house screening program, SC-22716 (1, 1-[2-(4- phenylphenoxy)ethyl]pyrrolidine) was identified as a potent inhibitor of LTA4 hydrolase. Structure-activity relationship (SAR) studies around this structural class resulted in the identification of a number of novel, potent inhibitors of LTA4 hydrolase, several of which demonstrated good oral activity in a mouse ex vivo whole blood assay.
- Penning, Thomas D.,Chandrakumar, Nizal S.,Chen, Barbara B.,Chen, Helen Y.,Desai, Bipin N.,Djuric, Stevan W.,Docter, Stephen H.,Gasiecki, Alan F.,Haack, Richard A.,Miyashiro, Julie M.,Russell, Mark A.,Yu, Stella S.,Corley, David G.,Durley, Richard C.,Kilpatrick, Brian F.,Parnas, Barry L.,Askonas, Leslie J.,Gierse, James K.,Harding, Elizabeth I.,Highkin, Maureen K.,Kachur, James F.,Kim, Suzanne H.,Krivi, Gwen G.,Villani-Price, Doreen,Pyla, E. Yvonne,Smith, Walter G.,Ghoreishi-Haack, Nayereh S.
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p. 721 - 735
(2007/10/03)
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- Hypolipidemic 1,4-benzothiazepine-1,1-dioxides
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The invention is concerned with novel hypolipidemic compounds of formula (I), with processes and novel intermedites for their preparation, pharmaceutical compositions containing them and with their use in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions, such as atherosclerosis. STR1
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- Studies of reactions within molecular complexes: Alkaline hydrolysis of substituted phenyl benzoates in the presence of xanthines
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Complexation with caffeine and theophylline-7-acetate depresses the rate of alkaline hydrolysis of substituted phenyl benzoates and is consistent with the formation of molecular complexes with 1:1 stoichiometry between the hosts and esters; stacking of the xanthines is excluded as an explanation in the range of concentrations studied. Bronsted-type correlations have been determined for the rate and complexation constants and for the transition-state binding constants. Development of effective charge in the transition state of the reactions in bulk solvent is slightly less than that in the host-ester complex, consistent with a similar electronic environment in both states. The negative Bronsted β values for Ks indicate that the interactions between ester and hosts involve electron donation to the host from the ester. Inhibition of hydrolysis is attributed to repulsion of the hydroxide ion from the host-ester complex by the extra hydrophobicity engendered by the xanthine host, as well as by the weaker binding of the transition state to the host compared with that in the host-ester complex.
- Pirinccioglu, Necmettin,Williams, Andrew
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- Phosphonic acid derivatives
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A phosphonic acid derivative which is useful for medically treating hyperlipemia, represented by the following general formula (I) or a pharmacologically acceptable salt thereof: STR1 Representative example of the compound according to the present invention is one represented by the following formula: STR2
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- REGIOSELECTIVITY OF COMPLEXATIONS OF SUBSTITUTED PHENYL BENZOATES AND PHENYL PHENYLACETATES WITH Cr(CO)6
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Selectivity of complexation of substituted phenyl benzoates is very low.In most cases, comparable yields of both regioisomeric complexes are isolated.Exception is 4-chlorophenyl ester, where benzoic acid moiety is complexed nearly exclusively.Very high regioselectivity of complexation was observed with substituted phenyl phenylacetates.The substituent of substituted phenols has not any effect on the complexation, and only phenylacetic acid moiety is complexed.This observation supports the recently proposed mechanism of the catalytic activity of the esters at arene complexation.
- Hrnciar, Pavol,Cernak, Peter,Gajda, Vladimir,Toma, Stefan
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p. 2095 - 2102
(2007/10/02)
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- Antiosteoporotic imidazo[4,5-c]pyridines
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This invention relates to 2-substituted-imidazo[4,5 -c]pyridines, to the process for their preparation, to pharmaceutical compositions containing said 2-substituted-imidazo]4,5-c]pyridines and to the use of said 2-substituted-imidazo[4,5-c]pyridines for modifying the balance between bone production and bone resorption in a host animal, including man.
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- A REEXAMINATION OF THE RETRO-FRIES REARRANGEMENT OF SOME o-HYDROXYKETONES
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The retro-Fries rearrangement, catalyzed by protic and Lewis acids, was studied for some o-hydroxyketones.The results are consistent with the mechanism of an heterolytic cleavage and rearrangement.It appears that, in general, Lewis acids do not induce the retro-Fries rearrangement of o-hydroxyketones.However, in certain cases, it may be brought about the presence of a protic acid generated in situ, from a solvent-catalyst interaction.
- Martin, Robert,Lafrance, Jean Ronald,Demerseman, Pierre
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p. 539 - 548
(2007/10/02)
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- PHOTOREARRANGEMENT OF ARYL ESTERS IN MICELLAR MEDIUM
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Effect of micelle (SDS ) on the photorearrangement of aryl esters have been investigated.Thus, phenyl, p- and m-cresyl, and 2-naphthyl benzoates yielded the corresponding o-hydroxybenzophenones as a major product in high yield.Phenyl cinnamate gave 2-hydroxychalcone. 2,4,6-Tri-t-butyl-phenylbenzoate, however, underwent decarboxylation yielding 2,4,6-tri-t-butyl biphenyl in quantitative yield.
- Singh, Anil K.,Sonar, Sanjay M.
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p. 1113 - 1122
(2007/10/02)
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- PALLADIUM-CATALYZED OXIDATIVE COUPLING OF AROMATIC COMPOUNDS WITH OLEFINS USING t-BUTYL PERBENZOATE AS A HYDROGEN ACCEPTER
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Benzene and furans undergo oxidative coupling with olefins with an aid of t-butyl perbenzoate and a catalytic amount of Pd salts.The perbenzoate acts as a hydrogen accepter.In the absence of olefins, Pd catalyzed benzoxylation of aromatic compounds takes place.
- Tsuji, Jiro,Nagashima, Hideo
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p. 2699 - 2702
(2007/10/02)
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- 13C-NMR study of cresyl benzoates
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The proton-decoupled 13C FT-NMR spectra of para-, meta- and ortho-cresyl benzoates have been recorded and the observed signals have been assigned following the substituent additivity rule.The important features of diagnostic value of these spectra are discussed.
- Srivastava, S. P.,Bhatnagar, A. K.,Joshi, G. C.
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p. 713 - 716
(2007/10/02)
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- The Fries Rearrangement as an Equilibrium Reaction
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The Fries rearrangement of arylbenzoates 1, in 1,2-dichloroethane in the presence of trifluoromethanesulfonic acid (TFMS) as catalyst, to ortho- and para-hydroxyaryl ketones (2 and 3, resp.) is reversible at 170 deg C; an equilibrium of the compounds 1, 2, and 3 is established.The equilibrium is achieved starting from the aryl esters 1 as well as from the hydroxyaryl ketones 2 and 3, respectively.The higher stability of the ortho-compounds 2 compared to the para-compounds 3 can be explained by greater resonance interaction between the carbonyl group and the aromatic ring in 2.The torsion angles Θ, which are good indicators of this interaction, can be determined from 13C NMR spectra.A dissociative mechanism is proposed for the acryl group migration.
- Effenberger, Franz,Gutmann, Rainer
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p. 1089 - 1102
(2007/10/02)
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- A Novel Synthesis of Phenyl Carboxylates
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The direct synthesis of phenyl carboxylates from phenols and carboxylic acids is reported.The reactions proceeded easily when triphenylphosphine and carbon tetrachloride were used as dehydrating agents in the presence of a tertiary amine at room temperature, thus giving esters in high yields.
- Hashimoto, Shizunobu,Furukawa, Isao
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p. 2227 - 2228
(2007/10/02)
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