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Meldrum's Acid (meldrum + acid)
Selected AbstractsDevelopment of Pharmaceutical Drugs, Drug Intermediates and Ingredients by Using Direct Organo-Click ReactionsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 6 2008Dhevalapally B. Ramachary Abstract Here we report on our studies of the use of combinations of amino acids, amines, K2CO3 or Cs2CO3 and CuSO4/Cu for catalysing green cascade reactions. We aimed to prepare the highly reactive and substituted olefin species 7 and 8, under very mild and environmentally friendly conditions, thus giving the hydrogenated products 10 and 12 through the action of Hantzsch ester (4) by self-catalysis through decreasing the HOMO,LUMO energy gaps between olefins 7/8 and Hantzsch ester (4) through biomimetic reductions. Highly useful compounds 10 to 14 were assembled from simple substrates such as aldehydes 1, ketones 2, CH acids 3, Hantzsch ester (4) and alkyl halides 5 by diversity-oriented green synthesis involving cascade olefination/hydrogenation (O/H), olefination/hydrogenation/alkylation (O/H/A) and hydrogenation/olefination/hydrogenation (H/O/H) reaction sequences in one-pot fashion with stereospecific organo- and organo-/metal-carbonate catalysis. Highly functionalized diverse compounds such as 10 to 14 are biologically active products and have found wide applications as pharmaceutical drugs, drug intermediates and drug ingredients. For the first time in organocatalysis, we report the O/H/A/TE reaction to furnish high yields of transesterification products 11 by simply mixing the reactants under proline/K2CO3 catalysis conditions. Additionally, a novel organocatalytic H/O/H reaction sequence for the synthesis of alkyl-substituted aromatics has been developed. Furthermore, for the first time we have developed organocatalysed cascade olefination/hydrogenation/hydrolysis (O/H/H) reactions to furnish highly useful materials such as 2-oxochroman-3-carboxylic acid (14kc) and 2-amino-4H -chromene-3-carbonitrile (14kj) in good yields. Experimentally simple and environmentally friendly organocatalytic two-carbon homologation through cascade O/H/H reactions of aldehydes 1, Meldrum's acid (3c), Hantzsch ester (4) and acetic acid/triethylamine in ethanol has been demonstrated. Additionally, we have developed a green synthesis of the highly substituted 1,2,3-triazole 17 from simple substrates through a two-step combination of olefination/hydrogenation/alkylation and Huisgen cycloaddition reaction sequences under stereospecific organocopper catalysis conditions. In this paper we have found strong support for our hypothesis that, "decreasing the HOMO,LUMO energy gap between olefins 7/8 and Hantzsch ester (4) will drive the biomimetic hydrogenation reaction by self-catalysis". This self-catalysis was further confirmed with many varieties of examples.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Rhodium(II)-Catalyzed Inter- and Intramolecular Cyclopropanations with Diazo Compounds and Phenyliodonium Ylides: Synthesis and Chiral AnalysisHELVETICA CHIMICA ACTA, Issue 2 2005Ashraf Ghanem Different classes of cyclopropanes derived from Meldrum's acid (=2,2-dimethyl-1,3-dioxane-4,6-dione; 4), dimethyl malonate (5), 2-diazo-3-(silyloxy)but-3-enoate 16, 2-diazo-3,3,3-trifluoropropanoate 18, diazo(triethylsilyl)acetate 24a, and diazo(dimethylphenylsilyl)acetate 24b were prepared via dirhodium(II)-catalyzed intermolecular cyclopropanation of a set of olefins 3 (Schemes,1 and 4,6). The reactions proceeded with either diazo-free phenyliodonium ylides or diazo compounds affording the desired cyclopropane derivatives in either racemic or enantiomer-enriched forms. The intramolecular cyclopropanation of allyl diazo(triethylsilyl)acetates 28, 30, and 33 were carried out in the presence of the chiral dirhodium(II) catalyst [Rh2{(S)-nttl)4}] (9) in toluene to afford the corresponding cyclopropane derivatives 29, 31 and 34 with up to 37% ee (Scheme,7). An efficient enantioselective chiral separation method based on enantioselective GC and HPLC was developed. The method provides information about the chemical yields of the cyclopropane derivatives, enantioselectivity, substrate specifity, and catalytic activity of the chiral catalysts used in the inter- and intramolecular cyclopropanation reactions and avoids time-consuming workup procedures. [source] An efficient and green synthesis of 1,4-dihydropyridine derivatives through multi-component reaction in ionic liquidHETEROATOM CHEMISTRY, Issue 5 2006Xue Sen Fan Through multi-component condensation of aldehydes, 1,3-dione, Meldrum's acid, and ammonium acetate in an ionic liquid ([bmim][BF4]), a series of 1,4-dihydropyridine derivatives were prepared in excellent yields in the absence of any additional catalysts. In addition, [bmim][BF4] can be recovered and reused effectively for at least six times without obvious decrease of its efficiency. Advantages of this novel protocol include simple operational process, environmental benignancy, and high efficiency. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:382,388, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20221 [source] An efficient and clean synthesis of pyrido[2,3- d]pyrimidine-4,7-dione derivatives in aqueous mediaJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 6 2009Da-Qing Shi A series of 2-amino-5-aryl-5,6-dihydropyrido[2,3- d]pyrimidine-4,7(3H,8H)-dione derivatives were synthesized via the three-component reaction of aromatic aldehyde, 2,6-diaminopyrimidine- 4(3H)-one, and Meldrum's acid in water in the presence of triethylbenzylammonium chloride (TEBAC). This protocol has the advantages of easier work-up, milder reaction conditions, and environmentally benign procedure. J. Heterocyclic Chem., (2009). [source] The synthesis of some 3-acylindoles revisitedJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2007Vedran Hasimbegovic A study probing the scope of acylation of indoles with dicarboxylic acids in acetic anhydride has been performed, resulting in products incorporating 3-acylindole- or 1-acylindole motifs depending on the choice of the acid reactant. Synthetically useful results were only obtained from reactions involving malonic acid or Meldrum's acid. Correlations to previous studies have also been made and discussed. [source] Synthesis of 2-amino-1,4-dihydro-4-quinolinones and diaminomethylene meldrum's acids derivatives as potential potassium channel openersJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 1 2002Béanéadicte Erb Starting from 5-bismethylthiomethylene Meldrum's acid, the synthesis of 5-diaminomethylene Meldrum's acids and 2-aminoquinolone derivatives, structurally related to potassium channels openers pinacidil and diazoxide, is described. [source] Synthesis of [quinoline-3- 14C]-SSR97193 (ferroquine) from [2- 14C]-malonic acidJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2004Alan McNeill Abstract The antimalarial [quinoline-3- 14C]-SSR97193 (ferroquine) (8), an analogue of chloroquine (CQ) (1), was synthesized from [2- 14C]-malonic acid with an overall radiochemical yield of 15%. The synthetic route via [14C]-Meldrum's acid (9) was designed to minimize the intermediacy of radiolabelled volatiles. This synthesis involves a four-step route to labelled 4,7-dichloroquinoline, which is the key intermediate for the synthesis of many analogues of CQ. Copyright © 2004 John Wiley & Sons, Ltd. [source] Thioenols and thioamides substituted by two , -EWGs.JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 6 2008Comparison with analogous amides, enols Abstract Condensation of organic isothiocyanates with active methylene compounds gave nine thioamides RNHCSCHYY, or their isomeric thioenols RNHC(SH),=,CYY, for substrates in which Y and Y, are electron-withdrawing groups (EWG). These included derivatives of Meldrum's acid (MA) which showed 100% thioenol in all solvents. For other compounds the percentages of thioenol in CDCl3 when R,=,Ph are 100% when Y,=,CN and Y,,=,CO2Me or Y,,=,CO2CH2CCl3, 6% when Y,=,Y,,=,CO2CH2CF3, and 0% when Y,=,Y,,=,CO2Me. The chemical shift of SH (highest values 12.0,16.0,ppm) served as a probe for the thioenol structures and also for the extent of hydrogen bonding to the SH group. In contrast to simple ketones and thioketones in which thioenolization is favored over enolization by factors as large as 106, for intramolecular competition KThioenol/KEnol ratios are much lower than for systems not substituted by , -EWGs. X-ray crystallography of the 5-anilido-MA derivative shows a hydrogen-bonded thioenol structure. ,(OH), ,(NH), KEnol, and crystallographic data for analogous thioenol and enol systems are compared. Copyright © 2008 John Wiley & Sons, Ltd. [source] N -Isopropyl enols of carboxylic acid amides,JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 8 2003Yi Xiong Lei Abstract Eight N -isopropyl compounds of the formal structure YY,CHCONHPr- i (6), Y,Y,,=,CO2Me, CO2CH2CF3, CN; YY,,=,Meldrum,s acid residue; Y,=,CO2Me, Y,,=,CO2CH2CF3, CN; Y,=,CO2CH2CF3, CO2CH(CF3)2, Y,,=,CN, and the N - t -butyl derivative of Meldrum's acid were prepared and their structures were investigated in the solid state and in solution. The x-ray diffraction data indicate that in the solid state the structure is that of the amide 6, when Y,=,Y,,=,CO2Me, whereas when Y,=,CO2Me, Y,,=,CN or YY,,=,Meldrum,s acid residue the structure is that of the enol (5) YY,C=C(OH)NHPr- i. The solid-state 13C spectra indicate structure 6 when Y,=,CO2Me, Y,,=,CO2R, R,=,Me, CH2CF3 and an enol structure for the other compounds studied. 1H, 13C and when available 19F NMR spectra showed that the enol/amide composition in solution is structure and solvent dependent, in analogy with the previously investigated N -Ph analogs. The percentage of enol (and KEnol) decrease in the order of solvents CCl4,>,CDCl3,>,THF- d8,>,CD3CN,>,DMSO- d6, DMF- d7. For Y,Y, the percentage of enol increases when the number of fluorine atoms in R of the CO2R increases, when CN replaces a CO2R group or for the cyclic Meldrum's acid derivative. Both E - and Z -enols were observed when Y,,,Y,, mostly at low temperature. The ,(OH) values increase with increased polarity of the medium and with increased strength of the hydrogen bonds in which they are involved. In THF- d8 and DMF- d7 the Z -enol/E -enol and the amide/enol ratios increase with increase in temperature. A main conclusion from the work is that the percentage of the enol increases, but not drastically, when the N -substituent is changed from Ph to i -Pr. Copyright © 2003 John Wiley & Sons, Ltd. [source] The nitro anomaly and Brønsted ,nuc values in SN2 reactions on chlorine,JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 8 2002Linoam Eliad Abstract The kinetics of chlorine transfer reactions between N -chlorosuccinimide (NCS) and four carbon nucleophiles (the conjugated bases of phenyldinitromethane, Meldrum's acid, phenylmalononitrile and phenylnitro-methane) in water were determined. A plot of log k for the SN2 reactions vs the pKa of the first three conjugated acids of the nucleophiles gave a straight line with a slope (,nuc) of 1.8. The data point for the mononitro derivative, phenylnitromethane, deviates negatively from the line by 6.7 log units. This deviation is typical of proton transfer reactions and was recently shown to occur also in SN2 reactions on bromine. Copyright © 2002 John Wiley & Sons, Ltd. [source] Synthesis, psychotropic and anticancer activity of 2,2-dimethyl-5-[5,-trialkylgermyl(silyl)-2,-hetarylidene]-1,3-dioxane-4,6-diones and their analoguesAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 12 2003Edmunds Lukevics Abstract A series of 2,2-dimethyl-5-(5,-R-hetarylidene)-1,3-dioxane-4,6-diones has been synthesized for examing a structure,activity relationship. Furyl and thienyl derivatives of Meldrum's acid possess neurotropic activity comprising both depriming and activating components. Comparison of acute toxicity of carbon, silicon and germanium analogues in the furan series of the compounds has demonstrated that the germanium derivative is 11.5 times less toxic than the carbon analogue and four times less toxic than the silicon derivative. 2,2-Dimethyl-5-(5,-triethylsilyl-2,-thenylidene)-1,3-dioxane-4,6-dione has moderate toxicity with the highest neurotropic and cytotoxic activity Copyright © 2003 John Wiley & Sons, Ltd. [source] Synthesis of 2-amino-1,4-dihydro-4-quinolinones and diaminomethylene meldrum's acids derivatives as potential potassium channel openersJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 1 2002Béanéadicte Erb Starting from 5-bismethylthiomethylene Meldrum's acid, the synthesis of 5-diaminomethylene Meldrum's acids and 2-aminoquinolone derivatives, structurally related to potassium channels openers pinacidil and diazoxide, is described. [source] | ||||||||||