- Size-Driven Inversion of Selectivity in Esterification Reactions: Secondary Beat Primary Alcohols
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Relative rates for the Lewis base-mediated acylation of secondary and primary alcohols carrying large aromatic side chains with anhydrides differing in size and electronic structure have been measured. While primary alcohols react faster than secondary ones in transformations with monosubstituted benzoic anhydride derivatives, relative reactivities are inverted in reactions with sterically biased 1-naphthyl anhydrides. Further analysis of reaction rates shows that increasing substrate size leads to an actual acceleration of the acylation process, the effect being larger for secondary as compared to primary alcohols. Computational results indicate that acylation rates are guided by noncovalent interactions (NCIs) between the catalyst ring system and the DED substituents in the alcohol and anhydride reactants. Thereby stronger NCIs are formed for secondary alcohols than for primary alcohols.
- Mayr, Stefanie,Marin-Luna, Marta,Zipse, Hendrik
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p. 3456 - 3489
(2021/03/01)
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- Efficient synthesis of symmetrical anhydrides by cross dehydrogenative coupling of aryl aldehydes over CuFe2O4 nanoparticles
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Nano copper ferrite catalyst is prepared and characterized by scanning electron microscopy, energy dispersive X-ray, X-ray diffraction, vibrational sample magnetometry, and Fourier transform infrared. The catalytic activity is probed for cross-dehydrogenative coupling of aromatic aldehydes in the presence of tert-butyl hydroperoxide as the oxidant. This catalytic protocol appears as a simple, rather cheap, clean, and efficient practical strategy for the synthesis of symmetrical anhydrides, with proper efficiency (66%). The catalyst can be easily separated from the reaction mixture by an external magnet and reused several times in subsequent reactions, without any measurable loss of its efficiency. Graphic abstract: [Figure not available: see fulltext.]
- Eidi, Esmaiel,Kassaee, Mohamad Z.,Nasresfahani, Zahra
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p. 461 - 468
(2021/04/09)
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- PPh3/Selectfluor-Mediated Transformation of Carboxylic Acids into Acid Anhydrides and Acyl Fluorides and Its Application in Amide and Ester Synthesis
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By taking the advantage of PPh3/Selectfluor system, carboxylic acids are efficiently converted into the pivotal intermediates acyloxyphosphonium ions that can selectively react with a second carboxylic acid or fluoride to in situ yield the corresponding acid anhydrides or acyl fluorides. The developed protocol features commercially availabile reagents, no involvement of base, room temperature conditions, and simple experimental procedure. Additionally, various amides or esters are readily achieved, respectively, with the addition of amines or alcohols.
- Yang, Zhen,Chen, Siwei,Yang, Fang,Zhang, Chenxi,Dou, You,Zhou, Qiuju,Yan, Yizhe,Tang, Lin
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p. 5998 - 6002
(2019/08/21)
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- Organocatalytic Desymmetrisation of Fittig's Lactones: Deuterium as a Reporter Tag for Hidden Racemisation
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Highly enantioselective desymmetrisation of Fittig's lactones with alcohols is promoted by bifunctional cinchona squaramides. The reactions were carried out with monodeuterated methanol to detect possible hidden racemisation of the stereogenic centre. Current evidence suggests that racemisation was not a relevant process for most substrates; partial erosion of enantioselectivity was only detected with ortho -substituted aryl derivates. The resultant glutaric acid derivatives possess a scaffold that is common in natural products and the compounds are also useful chiral building blocks for further synthetic endeavours.
- Spránitz, Péter,Soregi, Petra,Botlik, Bence Béla,Berta, Máté,Soós, Tibor
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p. 1263 - 1272
(2019/02/26)
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- TBHP/ n -Bu 4 PBr-Promoted Oxidative Cross-Dehydrogenative Coupling of Aryl Methanols: A Facile Synthesis of Symmetrical Carboxylic Anhydride Derivatives
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A transition-metal-free oxidative cross-dehydrogenative coupling reaction has been developed for the preparation of symmetrical carboxylic anhydrides through self-coupling dual C-O bond formations of aryl methanols. In the presence of a catalytic amount of tetrabutylphosphonium bromide (TBPB) as transfer agent and aqueous tert -butyl hydroperoxide (TBHP) as oxidant and reactant, methylene groups of aryl methanols were efficiently oxidized to C=O and coupled with the peroxide oxygen from TBHP to form a diverse array of symmetrical carboxylic anhydride derivatives.
- Adib, Mehdi,Pashazadeh, Rahim
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supporting information
p. 136 - 140
(2017/12/27)
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- Synthesis, molecular docking, and pharmacological evaluation of N-(2-(3,5-dimethoxyphenyl)benzoxazole-5-yl)benzamide derivatives as selective COX-2 inhibitors and anti-inflammatory agents
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A series of N-(2-(3,5-dimethoxyphenyl)benzoxazole-5-yl)benzamide derivatives (3am) was synthesized and evaluated for their in vitro inhibitory activity against COX-1 and COX-2. The compounds with considerable in vitro activity (IC50 50 values in the range of 0.06–0.71 μM. The in vivo anti-inflammatory activity of these six compounds (3a, 3b, 3d, 3g, 3j, and 3k) was assessed by the carrageenan-induced rat paw edema method. Compounds 3d (84.09%), 3g (79.54%), and 3a (70.45%) demonstrated significant anti-inflammatory activity compared to the standard drug ibuprofen (65.90%) and were also found to be safer than ibuprofen, by ulcerogenic studies. A docking study was done using the crystal structure of human COX-2, to understand the binding mechanism of these inhibitors to the active site of COX-2.
- Kaur, Avneet,Pathak, Dharam P.,Sharma, Vidushi,Wakode, Sharad
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- Synthesis, biological evaluation and docking study of a new series of di-substituted benzoxazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents
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A new series of substituted-N-(3,4-dimethoxyphenyl)-benzoxazole derivatives 13a–13p was synthesized and evaluated in vitro for their COX (I and II) inhibitory activity, in vivo anti-inflammatory and ulcerogenic potential. Compounds 13d, 13h, 13k, 13l and 13n exhibited significant COX-2 inhibitory activity and selectivity towards COX-2 over COX-1. These selected compounds were screened for their in vivo anti-inflammatory activity by carrageenan induced rat paw edema method. Among these compounds, 13d was the most promising analogs of the series with percent inhibition of 84.09 and IC50 value of 0.04 μM and 1.02 μM (COX-2 and COX-1) respectively. Furthermore, ulcerogenic study was performed and tested compounds (13d, 13h, 13k, 13l) demonstrated a significant gastric tolerance than ibuprofen. Molecular docking study was also performed with resolved crystal structure of COX-2 to understand the binding mechanisms of newly synthesized inhibitors in the active site of COX-2 enzyme and the results were found to be concordant with the biological evaluation studies of the compounds. These newly synthesized inhibitors also showed acceptable pharmacokinetic profile in the in silico ADME/T analyses.
- Kaur, Avneet,Pathak, Dharam P.,Sharma, Vidushi,Wakode, Sharad
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p. 891 - 902
(2018/01/22)
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- Synthesis, biological evaluation and docking study of N-(2-(3,4,5-trimethoxybenzyl)benzoxazole-5-yl) benzamide derivatives as selective COX-2 inhibitor and anti-inflammatory agents
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A series of N-(2-(3,4,5-trimethoxybenzyl)-benzoxazole-5-yl)benzamide derivatives (3a–3n) was synthesized and evaluated for its in vitro inhibitory activity against COX-1 and COX-2. The compounds with considerable in vitro activity (IC50 50 in the range of 0.14–0.69 μM. In vivo anti-inflammatory activity of these six compounds (3b, 3d, 3e, 3h, 3l and 3m) was assessed by carrageenan induced rat paw edema method. The compound 3b (79.54%), 3l (75.00%), 3m (72.72%) and 3d (68.18%) exhibited significant anti-inflammatory activity than standard drug ibuprofen (65.90%). Ulcerogenic activity with histopathological studies was performed, and the screened compounds demonstrated significant gastric tolerance than ibuprofen. Molecular Docking study was also performed with resolved crystal structure of COX-2 to understand the interacting mechanisms of newly synthesized inhibitors with the active site of COX-2 enzyme and the results were found to be in line with the biological evaluation studies of the compounds.
- Kaur, Avneet,Pathak, Dharam P.,Sharma, Vidushi,Narasimhan, Balasubramanian,Sharma, Prateek,Mathur, Rajani,Wakode, Sharad
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p. 191 - 202
(2018/08/23)
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- Synthesis, cyclooxygenase-2 inhibition, anti-inflammatory evaluation and docking study of substituted-n-(3,4,5-trimethoxyphenyl)-benzo[d]oxazole derivatives
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Background: Non-steroidal anti-inflammatory drugs are widely used for many years, but the chronic use of NSAID’s leads to gastric side effects, ulceration and kidney problems. These side effects are due to non-selective inhibition of COX-2 along with COX-1. Therefore, it is imperative to develop novel and selective COX-2 inhibitors. Objective: In this paper wehave synthesized a series of novel hybrids comprising of substituted-N-(3,4,5-trimethoxyphenyl)-benzo[d]oxazole derivatives and screened for the treatment of inflammation. Methods: The structures of the obtained compounds were elucidated by elemental and spectral analysis (ATR-FTIR,1 H NMR,13 C NMR, Mass spectroscopy). All of the compounds were evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activity by in vitro enzymatic assay. The compound which showed COX-2 activity (3a-3e, 3g – 3h, 3k, 3m and 3o) was further screened for in vivo anti-inflammatory activity and ulcerogenic liability. Molecular docking study was also performed with resolved crystal structure of COX-2 to understand the binding mechanism of newly synthesized inhibitors in the active site of COX-2enzyme. Results: The in vitro COX-1 and COX-2 inhibitory studies showed that the synthesized compounds potentially inhibited COX-2 (IC50 = 0.04 – 26.41 μM range) over COX-1 (IC50 = 0.98 – 33.33 μM range). The in vivo studies predicted that compounds 3c (70.9%, 0.6±0.22), 3m (68.1%, 1.9±0.41) and 3o (70.4%, 1.7±0.27) produced more efficacy against carrageenan induced paw edema and less ulcerogenic effect, as compared to standard ibuprofen (65.9%, 2.2±0.44). The results of docking studies were found to be concordant with the biological evaluation studies of the prepared compound. Conclusion: Among all the tested compounds, 2-Chloro-N-(2-(3,4,5-trimethoxyphenyl)-benzo[d]oxazol-5-yl)-benzamide (3c) was the most potent anti-inflammatory agent and has less ulcerogenic potential. This series of compound can be explored more for development of safer and more active anti-inflammatory agents.
- Kaur, Avneet,Wakode, Sharad,Pathak, Dharam P.,Sharma, Vidushi,Shakya, Ashok K.
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p. 660 - 673
(2018/11/06)
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- Cu-MOF: An efficient heterogeneous catalyst for the synthesis of symmetric anhydrides: Via the C-H bond activation of aldehydes
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In this paper, an efficient and straightforward synthetic approach for the preparation of a number of symmetric carboxylic anhydrides was reported using Cu2(BDC)2(DABCO) as an efficient heterogeneous catalyst via the C-H bond activation of aldehydes with excellent yields and simple work up. This C-H bond activation reaction appears simple and convenient, has a wide substrate scope and makes use of cheap, abundant, and easily available reagents. The Cu-MOF catalyst was recycled and reused four times without any loss of catalytic activity.
- Ahmadzadeh, Zahra,Mokhtari, Javad,Rouhani, Morteza
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p. 24203 - 24208
(2018/07/25)
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- Acid anhydrides and the unexpected N,N-diethylamides derived from the reaction of carboxylic acids with Ph3P/I2/Et3N
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The formation of acid anhydrides from the phosphorous-mediated activation of carboxylic acids was investigated. Under various systems, activation of benzoic acid in the presence of base led to the formation of benzoic anhydride at different rates depending on the reactivity of the reagents. Using the Ph3P-I2/Et3N combination, most aryl acids were converted into the corresponding anhydrides in high yields within 5-10 min. However, for nitro-substituted derivatives, unexpectedly, N,N-diethylamides were isolated without anhydride formation. These results indicated the pronounced effect of substituents in governing these potential side reactions which can significantly affect the yields of acylation reactions promoted by phosphonium species.
- Phakhodee, Wong,Duangkamol, Chuthamat,Wangngae, Sirilak,Pattarawarapan, Mookda
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supporting information
p. 325 - 328
(2016/01/12)
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- Metal-free cross-dehydrogenative coupling of aryl aldehydes to give symmetrical carboxylic anhydrides promoted by the TBHP/nBu4PBr system
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A novel, efficient, and metal-free dual C–O bond formation reaction for the synthesis of carboxylic anhydrides from aryl aldehydes via cross-dehydrogenative coupling is described. Heating a mixture of aromatic aldehydes and an aqueous solution of tert-butyl hydroperoxide as oxidant in the presence of catalytic nBu4PBr in chlorobenzene at 80?°C for 3?h afforded the corresponding carboxylic anhydrides in good to excellent yields.
- Adib, Mehdi,Pashazadeh, Rahim,Rajai-Daryasarei, Saideh,Mirzaei, Peiman,Jamal Addin Gohari, Seyed
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supporting information
p. 3071 - 3074
(2016/07/06)
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- Carboxylic acid anhydrides via Pd-catalyzed carbonylation of aryl halides at atmospheric CO pressure
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A convenient method has been developed, which allows for the direct transformation of aryl iodides into the corresponding carboxylic acid anhydrides via Pd-catalyzed carbonylation under atmospheric CO pressure. The Royal Society of Chemistry 2012.
- Li, Yang,Xue, Dong,Wang, Chao,Liu, Zhao-Tie,Xiao, Jianliang
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supporting information; experimental part
p. 1320 - 1322
(2012/02/04)
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- Synthesis of symmetric anhydrides using visible light-mediated photoredox catalysis
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A new approach to anhydride formation is reported via activation of C-O bonds by the Vilsmeier-Haack reagent formed by Ru(bpy)3Cl2 and CBr4 in DMF. Various aryl and alkyl carboxylic acids are converted to the corresponding anhydrides in excellent yields.
- Konieczynska, Marlena D.,Dai, Chunhui,Stephenson, Corey R. J.
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supporting information; experimental part
p. 4509 - 4511
(2012/07/31)
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- Substrate activity screening: A fragment-based method for the rapid identification of nonpeptidic protease inhibitors
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A new fragment-based method for the rapid development of novel and distinct classes of nonpeptidic protease inhibitors, Substrate Activity Screening (SAS), is described. This method consists of three steps: (1) a library of N-acyl aminocoumarins with diverse, low molecular weight N-acyl groups is screened to identify protease substrates using a simple fluorescence-based assay, (2) the identified N-acyl aminocoumarin substrates are optimized by rapid analogue synthesis and evaluation, and (3) the optimized substrates are converted to inhibitors by direct replacement of the aminocoumarin with known mechanism-based pharmacophores. The SAS method was successfully applied to the cysteine protease cathepsin S, which is implicated in autoimmune diseases. Multiple distinct classes of nonpeptidic substrates were identified upon screening an N-acyl aminocoumarin library. Two of the nonpeptidic substrate classes were optimized to substrates with >8000-fold improvements in cleavage efficiency for each class. Select nonpeptidic substrates were then directly converted to low molecular weight, novel aldehyde inhibitors with nanomolar affinity to cathepsin S. This study demonstrates the unique characteristics and merits of this first substrate-based method for the rapid identification and optimization of weak fragments and provides the framework for the development of completely nonpeptidic inhibitors to many different proteases.
- Wood, Warren J. L.,Patterson, Andrew W.,Tsuruoka, Hiroyuki,Jain, Rishi K.,Ellman, Jonathan A.
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p. 15521 - 15527
(2007/10/03)
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- PHOSPHORANES AS COUPLING AGENTS AND THEIR PREPARATION
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Provided is a use as a coupling agent for condensation reactions of a compound of formula (I): wherein each of R1, R2, and R3 is independently H, hydrocarbyl, or hydrocarbyloxy, provided that not more than one of R1, R2, and R3 is H ; and at least one of Y1 and Y2 is an electron-withdrawing group and the other, if not an electron-withdrawing group, is H or a group that has no electron-donating properties, with the proviso that when one of Y1 and Y2 is H, the other is not -CN. Some of the compounds of formula (I) are novel, and methods of their preparation are also provided.
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- Palladium-promoted One-step Synthesis of Aromatic Acid Anhydrides from Aromatic Compounds with Carbon Monoxide
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The one-step synthesis of aromatic acid anhydrides from aromatic compounds such as benzene, toluene, anisole, chlorobenzene, furan, and thiophen has been carried out using carbon monoxide, 1,2-dibromoethane, and palladium acetate
- Fujiwara, Yuzo,Kawata, Itaru,Kawauchi, Tomio,Taniguchi, Hiroshi
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p. 132 - 133
(2007/10/02)
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