- One pot synthesis of barbiturates on reaction of barbituric acid with aldehydes under microwave irradiation using a variety of catalysts
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The condensation of barbituric acid with aldehydes under microwave irradiation in dry media has been investigated in the presence of NH 4OAc/AcOH (4/3, w/w) (41-54%), Montmorillonite K-10 (49-60%), Silica gel (52-63%), basic Al2O3 (56-67%), NaCl (57-69%), Montmorillonite KSF (62-70%), and KSF + NaCl (1:1, w/w) (70-89%).
- Dewan, Sharwan K.,Singh, Ravinder
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- Knoevenagel condensation in aqueous media promoted by 2,2′-bipyridinium dihydrogen phosphate as a green efficient catalyst
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A 2,2′-Bipyridine-based ionic compound named 2,2′-bipyridinium dihydrogen phosphate was synthesized by addition of phosphoric acid to a solution of 2,2′-Bipyridine in dichloromethane. After the characterization using FT-IR, mass, 1H, 13C and 31P NMR techniques, it was used as a Bronsted dicationic acidic catalyst for the promotion of the synthesis of 2-arylidene malononitrile and 5-arylidene barbituric acid derivatives via Knoevenagel condensation reaction in water. Some of the advantages of this method are the utilization of an easy preparable, cost-effective and eco-friendly organic salt as a catalyst within high rates and yields of the reactions, simple and quick work-up and acceptable reusability of the catalyst.
- Darvishzad, Shila,Daneshvar, Nader,Shirini, Farhad,Tajik, Hassan
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p. 2973 - 2984
(2021/04/19)
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- Comparison of the efficiency of two imidazole-based dicationic ionic liquids as the catalysts in the synthesis of pyran derivatives and Knoevenagel condensations
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In the present work, 3,3′-(butane-1,4-diyl)bis(1-methyl-1H-imidazol-3-ium) dichloride ([C4(MIm)2]·2Cl) and 3,3′-(butane-1,4-diyl)bis(1-methyl-1H-imidazol-3-ium) hydrogen sulfate ([C4(MIm)2]·2HSO4) were prepared via adequate, solvent-free methods and characterized using FT-IR, 1H NMR, 13C NMR, and potentiometric titration techniques. These reagents were investigated in the synthesis of 5-arylidene (thio)barbituric acids, 2-arylidene malononitriles, 4H-pyrans, and pyrano[2,3-d] pyrimidineones, and their catalytic activities were compared in the promotion of these reactions. Based on the obtained results, we found that [C4(MIm)2]·2Cl showed more catalytic efficiency where a basic or weak acidic media is needed. In contrast, [C4(MIm)2]·2HSO4 is a powerful catalyst in reactions needing acidic catalysts to enhance the reaction rate. Using these reagents, the products were formed under mild and eco-friendly conditions in excellent yields during short reaction times without needing column chromatography for work-up.
- Sharifi, Zahra,Daneshvar, Nader,Langarudi, Mohaddeseh Safarpoor Nikoo,Shirini, Farhad
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p. 4941 - 4958
(2019/07/03)
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- Verjuice as a green and bio-degradable solvent/catalyst for facile and eco-friendly synthesis of 5-arylmethylenepyrimidine-2,4,6-trione, pyrano[2,3-d]pyrimidinone and pyrimido[4,5-d]pyrimidinone derivatives
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Verjuice (unripe grape juice), a natural mixture of organic acids, which is identified by pH-metric and TGA analysis, is efficiently used for the promotion of the synthesis of 5-arylmethylenepyrimidine-2,4,6-triones, via Knovenagel condensation reaction between barbituric or thiobarbituric acid and aldehydes. Verjuice is also employed for the effective synthesis of pyrano[2,3-d]pyrimidinone derivatives via a three-component reaction of barbituric acid or its thio analogue, aldehydes and malononitrile. In the same way, pyrimido[4,5-d]pyrimidinone derivatives are simply produced via the reaction of barbituric acid, aldehydes and urea or thiourea in the presence of verjuice. This green methodology rewards notable advantages including simple procedures, acceptable reaction times, easy work-up, high yields, circumventing the use of any expensive starting materials, volatile and hazardous organic solvents during the reaction and work-up process, and use of a natural, low-cost, reusable, and bio-degradable catalyst.
- Safari, Niloufar,Shirini, Farhad,Tajik, Hassan
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p. 887 - 897
(2019/03/27)
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- Trisubstituted barbiturates and thiobarbiturates: Synthesis and biological evaluation as xanthine oxidase inhibitors, antioxidants, antibacterial and anti-proliferative agents
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Barbituric and thiobarbituric acid derivatives have become progressively attractive to medicinal chemists due to their wide range of biological activities. Herein, different series of 1,3,5-trisubstituted barbiturates and thiobarbiturates were prepared in moderate to excellent yields and their activity as xanthine oxidase inhibitors, antioxidants, antibacterial agents and as anti-proliferative compounds was evaluated in vitro. Interesting bioactive barbiturates were found namely, 1,3-dimethyl-5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6c) and 1,3-dimethyl-5-[1-[2-(4-nitrophenyl)hydrazinyl]ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6e), which showed concomitant xanthine oxidase inhibitory effect (IC50 values of 24.3 and 27.9 μM, respectively), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (IC50 values of 18.8 and 23.8 μM, respectively). In addition, 5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6d) also revealed DPPH radical scavenger effect, with an IC50 value of 20.4 μM. Moreover, relevant cytotoxicity against MCF-7 cells (IC50 = 13.3 μM) was observed with 5-[[(2-chloro-4-nitrophenyl)amino]methylene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (7d). Finally, different 5-hydrazinylethylidenepyrimidines revealed antibacterial activity against Acinetobacter baumannii (MIC values between 12.5 and 25.0 μM) which paves the way for developing new treatments for infections caused by this Gram-negative coccobacillus bacterium, known to be an opportunistic pathogen in humans with high relevance in multidrug-resistant nosocomial infections. The most promising bioactive barbiturates were studied in silico with emphasis on compliance with the Lipinski's rule of five as well as several pharmacokinetics and toxicity parameters.
- Figueiredo, Joana,Serrano, Jo?o L.,Cavalheiro, Eunice,Keurulainen, Leena,Yli-Kauhaluoma, Jari,Moreira, Vania M.,Ferreira, Susana,Domingues, Fernanda C.,Silvestre, Samuel,Almeida, Paulo
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p. 829 - 842
(2017/12/13)
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- The introduction of two new imidazole-based bis-dicationic Br?nsted acidic ionic liquids and comparison of their catalytic activity in the synthesis of barbituric acid derivatives
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In this article, the preparation of bis-imidazolium hydrogen sulfate and bis-imidazolium perchlorate as two new bis-dicationic Br?nsted acidic ionic liquids based on imidazole is reported. After characterization by FT-IR, mass and NMR spectroscopy and pH titration, the applicability of these reagents is studied in the promotion of the synthesis of 5-arylidene barbituric acids and pyrano[2,3-d] pyrimidinone derivatives. These methods possess some advantages such as ease of preparation of the catalyst, simple work-up procedure, short reaction times, excellent yields, and use of nonorganic solvents during all steps of the reactions and good reusability of the catalysts.
- Daneshvar, Nader,Nasiri, Mitra,Shirzad, Maryam,Safarpoor Nikoo Langarudi, Mohaddeseh,Shirini, Farhad,Tajik, Hassan
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p. 9744 - 9756
(2018/06/18)
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- Butane-1-sulfonic acid immobilized on magnetic Fe3O4@SiO2 nanoparticles: A novel and heterogeneous catalyst for the one-pot synthesis of barbituric acid and pyrano[2,3-d] pyrimidine derivatives in aqueous media
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Butane-1-sulfonic acid immobilized on magnetic Fe3O4@SiO2 nanoparticles (Fe3O4@SiO2-Sultone) was easily prepared via direct ring opening of 1,4-butanesultone with nanomagnetic Fe3O4@SiO2. The prepared reagent was characterized and used for the efficient promotion of the synthesis of barbituric acid and pyrano[2,3-d] pyrimidine derivatives. All reactions were performed under mild and completely heterogeneous reaction conditions affording products in good to high yields. The catalyst is easily isolated from the reaction mixture by magnetic decantation and can be reused at least eight times without significant loss in activity.
- Pourghasemi-Lati,Shirini,Alinia-Asli,Rezvani
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- 4-(4-Propylpiperazine-1-yl)butane-1-sulfonic acid-modified silica-coated magnetic nanoparticles: A novel and recyclable catalyst for the synthesis of 5-arylidinebarbituric acids and pyrano[2,3-d]pyrimidinedione derivatives in aqueous media
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A mild, simple and efficient procedure for the preparation of barbituric acid and pyrano[2,3-d]pyrimidine derivatives in aqueous media is described using 4-(4-propylpiperazine-1-yl)butane-1-sulfonic acid-modified silica-coated magnetic nanoparticles as a novel and reusable catalyst. The catalyst was easily isolated from the reaction mixture by magnetic decantation using an external magnet and reused at least eight times without significant degradation in activity.
- Pourghasemi-Lati,Shirini,Alinia-Asli,Rezvani
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- A synthetic route to novel 3-substituted-2,1-benzisoxazoles from 5-(2-nitrobenzylidene)(thio)barbiturates
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2,1-Benzisoxazoles, also called anthranils, are one of the two types of aromatic bicyclic heterocycles having a benzene ring fused with an isoxazole, which are particularly recognized as valuable intermediates in organic synthesis. Nevertheless several methods can be found in the literature to prepare 2,1-benzisoxazoles, we herein report a new, efficient, simple, mild, and alternative procedure to prepare 3-substituted-2,1-benzisoxazoles from 5-(2-nitrobenzylidene)barbiturates in moderate to good yields (51–82%). All the novel benzisoxazoles showed spectral data fully consistent with the assigned structures, which were unequivocally confirmed by single crystal X-ray analysis. A possible mechanism of the reaction is proposed. In addition, a screening of the bioactivity of these benzisoxazoles as xanthine oxidase inhibitors, antioxidants, and cytotoxic compounds was performed. The benzisoxazole formed from barbituric acid revealed moderate xanthine oxidase inhibitory effects (IC50 = 22.10 μM).
- Serrano, Jo?o L.,Cavalheiro, Eunice,Barroso, Sónia,Rom?o, Maria J.,Silvestre, Samuel,Almeida, Paulo
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p. 990 - 995
(2017/11/27)
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- Succinimidinium hydrogensulfate ([H-Suc]HSO4) as an efficient ionic liquid catalyst for the synthesis of 5-arylidenepyrimidine-2,4,6(1H,3H,5H)-trione and pyrano-pyrimidinones derivatives
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In this work, succinimidinium hydrogensulfate ([H-Suc]HSO4), a newly reported Br?nsted acidic ionic liquids is used as an efficient, homogeneous and reusable catalyst for the synthesis of 5-arylidenepyrimidine-2,4,6(1H,3H,5H)-trione and pyrano[2,3-d]-pyrimidine dione derivatives. The products were formed in excellent yields over short reaction times and the catalyst can be reused several times without any appreciable loss in its activity.
- Goli-Jolodar, Omid,Shirini, Farhad,Seddighi, Mohadeseh
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p. 457 - 463
(2016/01/30)
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- DABCO-based ionic liquids: Green and recyclable catalysts for the synthesis of barbituric and thiobarbituric acid derivatives in aqueous media
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A new and straightforward method for the synthesis of 5-arylidine barbituric and thiobarbituric acids through a reaction between barbituric acid and its thio-analogue with aldehydes using 1,4-disulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium dihydrogen sulfate ([DABCO](SO3H)2(HSO4)2) as an efficient catalyst has been reported. In this project, also the preparation of pyrano[2,3-d]-pyrimidinediones via the reaction of barbituric or thiobarbituric acid, malononitrile and aldehydes in the presence of this reagent and 1,4-disulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium chloride ([DABCO](SO3H)2(Cl)2) has been investigated. The structure of the products was characterized using IR, 1H NMR and 13C NMR spectroscopy. The present methodologies suggests several advantages such as ease of the preparation and handling of the catalysts, high yields, simple and green procedures, low cost, short reaction times, easy work-up and preformation of the reaction in water as a green solvent.
- Seyyedi, Narges,Shirini, Farhad,Nikoo Langarudi, Mohaddeseh Safarpoor
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p. 44630 - 44640
(2016/06/09)
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- SHIKIMATE PATHWAY INHIBITORS AND THE USE THEREOF
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The present invention relates to methods of inhibiting shikimate pathway, comprising administering to a subject a pharmaceutically acceptable composition comprising a compound having a formula: or pharmaceutically acceptable salts thereof. The present invention also provides a synergistic antibacterial composition containing compound
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Paragraph 0041;0042
(2015/05/26)
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- Bi-SO3H functionalized ionic liquid based on DABCO as a mild and efficient catalyst for the synthesis of 1,8-dioxo-octahydro-xanthene and 5-arylmethylene-pyrimidine-2,4,6-trione derivatives
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1,8-Dioxo-octahydro-xanthenes are easily prepared via the condensation of aldehydes with 1,3-cyclohexadione and/or dimedone using N-sulfonated DABCO as a new and efficient catalyst. This reagent is also efficiently able to catalyze the condensation of aldehydes with barbituric acid leading to 5-arylmethylene-pyrimidine-2,4,6-triones. The structure of the products was characterized by their IR, 1H NMR, and 13C NMR spectroscopy. The present methodology offers several advantages such as ease of preparation and handling of the catalyst, high yields, simple and green procedure, low cost, short reaction times, easy work-up, and preformation of the reaction in the absence of solvent or in water as a green solvent.
- Shirini, Farhad,Langarudi, Mohaddeseh Safarpoor Nikoo,Seddighi, Mohadeseh,Jolodar, Omid Goli
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p. 8483 - 8497
(2015/01/30)
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- Nuclear magnetic resonance and molecular modeling study of exocyclic carbon-carbon double bond polarization in benzylidene barbiturates
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Benzylidene barbiturates are important materials for the synthesis of heterocyclic compounds with potential for the development of new drugs. The reactivity of benzylidene barbiturates is mainly controlled by their exocyclic carbon-carbon double bond. In this work, the exocyclic double bond polarization was estimated experimentally by NMR and correlated with the Hammett σ values of the aromatic ring substituents and the molecular modeling calculated atomic charge difference. It is demonstrated that carbon chemical shift differences and NBO charge differences can be used to predict their reactivity.
- Figueroa-Villar, J. Daniel,Vieira, Andreia A.
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p. 310 - 317
(2013/03/13)
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- New strategy for the synthesis of 5-Aryl-1H,1′H-spiro[furo[2,3-d] pyrimidine-6,5′-pyrimidine]2,2′,4,4′,6′(3H,3'H,5H) -pentaones and their sulfur analogues
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Reaction of barbituric acid (BA), 1,3-dimethyl barbituric acid (DMBA) and 2-thiobarbituric acid (TBA) with cyanogen bromide and aldehydes in the presence of L-(+)-tartaric acid afforded a new route for the synthesis of stable heterocyclic 5-aryl-1H,1′H-spiro[furo[2,3-d]pyrimidine-6,5′- pyrimidine]2,2′,4,4′,6′(3H,3′H,5H)- pentaones which is a dimeric form of barbiturate (uracil and thiouracil derivative). In the reaction of 1,3-diethyl thiobarbituric acid (DETBA) the Knoevenagel condensation and then Michael adducts were obtained under the same condition. Structure elucidation is carried out by 1H NMR, 13C NMR, FT-IR and Mass analyses. Mechanism of the formation is discussed.
- Jalilzadeh, Mohammad,Pesyan, Nader Noroozi
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experimental part
p. 3382 - 3388
(2012/01/19)
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- Synthesis and antimicrobial activities of novel 5-substituted pyrimidin-2,4,6-triones
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5-Benzylpyrimidin-2,4,6-triones (3a-c), 5-((furan-2-yl)methyl)pyrimidin-2, 4,6-trione (3g) and 5-((3-aryl-1-phe-nyl-1H-pyrazol-4-yl)methyl)pyrimidin-2,4,6- triones (3h-j) were obtained in two steps. Reaction of barbituric acid (1) with various substituted aromatic aldehydes, furfuraldehyde and 3-aryl-1-phenyl-1H- pyrazole-4-carbaldehydes in methanol yielded the corresponding chalcones 2a-m in 48-85% yield. These chalcones on reduction with sodium borohydride in isopropyl alcohol furnished desired novel compounds 3a-c and 3g-j in 55-85% yield. The structure of all the synthesized compounds have been established by various spectral studies and elemental analysis. All the synthesized compounds have been screened for antimicrobial activity.
- Goudgaon,Patil,Rahaman,Upendar Reddy
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experimental part
p. 743 - 748
(2011/08/09)
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- Synthesis of barbiturate-based methionine aminopeptidase-1 inhibitors
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The syntheses of a new class of barbiturate-based inhibitors for human and Escherichia Coli methionine aminopeptidase-1 (MetAP-1) are described. Some of the synthesized inhibitors show selective inhibition of the human enzyme with high potency.
- Haldar, Manas K.,Scott, Michael D.,Sule, Nitesh,Srivastava,Mallik, Sanku
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p. 2373 - 2376
(2008/09/20)
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- Microwave assisted Knoevenagel condensation: A facile method for the synthesis of 5-arylidine barbituric acid derivatives under solvent free conditions
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Several benzaldehydes were condensed with barbituric acid under microwave irradiation in absence of solvent affording the corresponding 5-arylidine barbituric acid derivatives in short reaction period with high yields.
- Pandit,Jejurkar,Harde
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p. 1035 - 1036
(2008/09/19)
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- Reaction of hexahydropyirimidine-2,4,6-trione with naphthalen-2-amine and benzaldehydes
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Previously unknown 12-aryl-7,8,9,10,11,12-hexahydrobenzo[f]pyrimido[4,5-b] quinoline-9,11-diones were synthesized by three-component condensation of naphthalen-2-amine with substituted benzaldehydes and barbituric acid through intermediate 5-benzylidenebarbituric acids. Nauka/Interperiodica 2007.
- Kozlov,Basalaeva
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p. 432 - 438
(2007/10/03)
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- Organic reactions in ionic liquids: Ionic liquid promoted Knoevenagel condensation of aromatic aldehydes with (2-thio)barbituric acid
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The Knoevenagel condensation of aromatic aldehydes with (2-thio)barbituric acid proceeded efficiently in reusable ionic liquids, EAN, BmimBF4, and BmimPF6 at room temperature in the absence of any catalyst with high yields.
- Hu, Yi,Chen, Zhen-Chu,Le, Zhang-Gao,Zheng, Qin-Guo
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p. 4521 - 4529
(2007/10/03)
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- An unexpected linear Bronsted correlation
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The reaction of barbiturate and 1,3-dimethylbarbiturate ions with o-, p- and 2,4-dinitrobenzaldehyde was studied. The reactions of barbiturate anion with o- and p-nitrobenzaldehyde exhibit a pH-rate profile different to that the corresponding to the reactions of barbiturate and 1,3-dimethylbarbiturate ions with 2,4-dinitrobenzaldehyde. The dependence of the rate constant on the viscosity of the medium in the pH range 2-4, for all the reactions, indicates the contribution of a diffusion-controlled proton transfer from the hydronium ion to an addition intermediate, T-, in the rate-determining step. Surprisingly, in the reaction of 2,4-dinitrobenzaldehyde with barbiturate and 1,3-dimethylbarbiturate anions, the Bronsted plot for general acid catalysis for carboxylic acids of pKa between 2 to 5 gives a linear relationship with a = 0-707 (r = 0.991), whereas a = 0 is expected, considering the pKa of the addition intermediate T-. On the other hand, the point for the rate constant, considering water as a general acid catalyst, falls approximately 105 times above the corresponding Bronsfed line. The tautomerism existing in the intermediate T- permits these surprising facts to be explained.
- Baumann, Klaus D.,Brighente, Ines M.C.,Pizzolatti, Moacir G.,Yunes, Rosendo A.
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p. 545 - 551
(2007/10/03)
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