5459-04-1Relevant articles and documents
METHOD FOR PREPARATION OF ACETOACETYLATED POLYOLS
-
Page/Page column 5; 6, (2020/10/20)
The invention disloses a method for preparation of an acetoacetylated polyol by reaction of a polyol with deketene in the presence of a base and in the absence of a solvent.
Chemoselective transesterification of β-keto esters under neutral conditions using NBS as a catalyst
Bandgar,Uppalla,Sadavarte
, p. 1715 - 1718 (2007/10/03)
Facile and selective transesterification of β-keto esters using N-bromosuccinimide (NBS) as an efficient and neutral catalyst is described.
Selective Catalytic Transesterification, Transthiolesterification, and Protection of Carbonyl Compounds over Natural Kaolinitic Clay
Ponde, Datta E.,Deshpande, Vishnu H.,Bulbule, Vivek J.,Sudalai, Ammugam,Gajare, Anil S.
, p. 1058 - 1063 (2007/10/03)
Transesterification and transthiolesterification of β-keto esters with variety of alcohols and thiols and selective protection of carbonyl functions with various protecting groups catalyzed by natural kaolinitic clay are described. The clay has been found to be an efficient catalyst in transesterifying long chain alcohols, unsaturated alcohols, and phenols to give their corresponding β-keto esters in high yields. For the first time, transthiolesterification of β-keto esters with a variety of thiols has been achieved under catalytic conditions. Clay also catalyzes selective transesterification of β-keto esters by primary alcohols in the presence of secondary and tertiary alcohols giving corresponding β-keto esters. A systematic study involving the reactivity of different nucleophiles (alcohols, amines, and thiols) toward β-keto esters is also described. Sterically hindered carbonyl groups as well as α,β-unsaturated carbonyl groups underwent protection without the deconjugation of the double bond. Chemoselective protection of aldehydes in the presence of ketones has also been achieved over natural kaolinitic clay.
Synthesis, biological evaluation, calcium channel antagonist activity, and anticonvulsant activity of felodipine coupled to a dihydropyridine- pyridinium salt redox chemical delivery system
Yiu, Sai-Hay,Knaus, Edward E.
, p. 4576 - 4582 (2007/10/03)
3-(2-Hydroxyethyl) 5-methyl 1,4-dihydro-2,6-dimethyl-4-(2,3- dichlorophenyl)-3,5-pyridinedicarboxylate (7) was prepared using a modified Hantzsch reaction, which was then elaborated to 3-[2-[[(1-methyl-1,4- dihydropyrid-3-yl)carbonyl]oxy]ethyl] 5-methyl 1,4-dihydro-2,6-dimethyl-4- (2,3-dichlorophenyl)-3,5-pyridinedicarboxylate [10, felodipine-chemical delivery system (CDS)]. The equipotent 3-(2-hydroxyethyl) 7 (IC50 = 3.04 x 10-8 M) and felodipine-CDS (10, IC50 = 3.10 x 10-8 M) were, respectively, 2- and 21-fold less potent calcium channel antagonists than the reference drugs nimodipine (IC50 = 1.49 x 10-8 M) and felodipine (IC50 = 1.45 x 10-9, M). Compounds 7, 10, nimodipine, and felodipine are highly lipophilic (K(p) = 236, 366, 187, and 442, respectively). 3-(2-Hydroxyethyl) 7, felodipine-CDS (10), and felodipine provided protection against maximal electroshock-induced seizures in mice but were inactive in the subcutaneous metrazol anticonvulsant screen. In vitro incubation studies of felodipine with rat plasma and 20% brain homogenates showed felodipine was very stable in both biological media. Similar incubations of felodipine-CDS showed its rate of biotransformation followed psuedo-first-order kinetics with half- lives of 15.5 h in rat plasma and 1.3 h in 20% rat brain homogenates. In vivo biodistribution of felodipine and felodipine-CDS was studied. Uptake of felodipine in brain produced a peak brain concentration of 5 μg/g of brain tissue at 5 min, after which it rapidly egressed from brain resulting in undetectable levels at 60 min. Peak blood concentrations of 10 occurred at about 7 min followed by a rapid decline to a near undetectable concentration by 17 min. The pyridinium salt species 9, resulting from oxidation of 10, also reached peak concentrations at about 7 min but it slowly decreased to undetectable concentrations at 2 h. 3-(2-Hydroxyethyl) 7 remained at near undetectable concentrations throughout a 2 h time period. Localization of 10 in brain provided a peak concentration of 4.2 μg/g of brain tissue at 5 min and then decreased to negligible concentrations at 15 min. The concentration of oxidized pyridinium species 9 in brain remained high providing detectable concentrations up to 4 days. In contrast, the concentration of the 3-(2- hydroxyethyl) hydrolysis product 7 in brain remained at very low levels throughout the study. The slow hydrolysis rate of the pyridinium ester 9 to the 3-(2-hydroxyethyl) 7 and the rapid egression of felodipine-CDS from brain are believed to contribute to the moderate anticonvulsant activity exhibited by the felodipine-CDS (10).
Acetoacetylation with 2,2,6-Trimethyl-4H-1,3-dioxin-4-one: A Convenient Alternative to Diketene.
Clemens, Robert J.,Hyatt, John A.
, p. 2431 - 2435 (2007/10/02)
The diketene/acetone adduct, 2,2,6-trimethyl-4H-1,3-dioxin-4-one, efficiently acetoacetylates aliphatic and aromatic alcohols, amines, and thiols.These acetoacetylation reactions are fast and stoichiometric, require no catalysis, and give only volatile byproducts.
The Hantzsch 1,4-Dihydropyridine Synthesis as a Route to Bridged Pyridine and Dihydropyridine Crown Ethers
Kellogg, Richard M.,Bergen, T. J. van,Doren, Henk van,Hedstrand, David,Kooi, J.,et al.
, p. 2854 - 2862 (2007/10/02)
Mono-, di-, tri-, and tetraethylene glycols were transesterified with ethyl acetoacetate to give the bis(acetoacetate esters) 1a-d.On treatment of 1c,d with formaldehyde and excess (NH4)2CO3 in H2O a crude mixture of 1,4-dihydropyridines was obtained from which, after dehydrogenation to the pyridine form, the 3,5-bridged 2,6-dimethylpyridines 2c,d were isolated along with dimers 7c,d.Similar reaction of 1a gave only dimer 7a.The bridged pyridine 2d was methylated to give pyridinium salt 3d, which was reduced with Na2S2O4 to give 1,4-dihydropyridine 4d.Stable sodium salts of 4d and 6d were isolated.Bridged pyridines 10a-c substituted with, respectively, methyl, phenyl, and 2-furyl at the γ position of the pyridine ring have also been prepared, using 1d, (NH4)2CO3, and acetaldehyde, benzaldehyde, and 2-furfuraldehyde and Hantzsch condensation followed by dehydrogenation and chromatographic separation.Protection of the 1,3-dicarbonyl system of ethyl 4-bromo-3-oxobutanoate as its Na chelate followed by nucleophilic substitution with the bisalkoxides from tetra-, penta-, and hexaethylene glycols gave 4-substituted bis(acetoacetate esters) 16a-c.These on Hantzsch condensation yielded in low yield 2,6-bridged Hantzsch 1,4-dihydropyridines (17a-c).Treatment of 17a,b with alkali metal hydrides gave insoluble materials thought to be the internally solvated alkali metal salts of the (vinylogous) amide nitrogen of the 1,4-dihydropyridine.
