141-97-9Relevant academic research and scientific papers
Synthesis and tautomerism of substituted pyrazolo[4,3-c]pyrazoles
Kadam, Shivaji S.,Maier, Lukas,Kostakis, Ioannis,Pouli, Nicole,Tousek, Jaromir,Necas, Marek,Marakos, Panagiotis,Marek, Radek
, p. 6811 - 6822 (2013)
Fused five-membered nitrogen heterocycles comprise a very important group of compounds frequently utilized in pharmaceutical applications. In this study, we report the first systematic synthesis of substituted pyrazolo[4,3-c]pyrazoles and three regioisomers of their N-methyl derivatives. All compounds were fully characterized by NMR spectroscopy in solution and selected compounds also were studied by X-ray diffraction in the solid state. 1H, 13C, and 15N NMR spectroscopic data for all isomers were interpreted by DFT calculations of nuclear shielding constants and indirect spin-spin coupling constants. The N-methyl isomers were used in the following steps as model compounds to investigate a potential N1-H/N4-H, N2-H/N4-H, and N1-H/N5-H tautomerism of 3,6-substituted pyrazolo[4,3-c]pyrazoles by using low-temperature NMR spectroscopy. All bases were shown to occur predominantly in the N1-H/N4-H tautomeric form and the structure of minor form was governed by the substituents at positions 3 and 6. Stabilities of individual tautomeric forms are calculated by DFT methods and discussed. A relationship between the tautomeric populations and the ratios among N-methyl isomers obtained upon methylation of selected bases in solution are investigated. The stability of various tautomeric forms of substituted pyrazolo[4,3-c]pyrazoles characterized by low-temperature NMR spectroscopy can be qualitatively explained by electronic and steric effects of substituents in positions 3 and 6 in individual tautomers, as revealed by the DFT calculations. Copyright
REFORMATSKY INTERMEDIATE. A C-METALLED SPECIES.
Orsini, F.,Pelizzoni, F.,Ricca, G.
, p. 3945 - 3948 (1982)
13C-NMR and 1H-NMR spectra of the Reformatsky reagent from t-butylbromoacetate, evidence a C-metalled species: within the limits of detectability of the methods, no O-metallated species can be detected in solution.
UV-Vis spectroscopic studies of solute-solvent and solute-cosolvent interactions in supercritical carbon dioxide
Lu, Jie,Han, Buxing,Yan, Haike
, p. 3269 - 3276 (1999)
The keto-enol tautomeric equilibria of ethyl acetoacetate in supercritical (SC) CO2 with and without ethanol cosolvent were investigated over the pressure range from 75.9 to 185 bar at 308.2 K using UV-Vis spectroscopy. In order to obtain the local densities of solvent and cosolvent about the solute, we correlated the standard Helmholtz free energy of the tautomerization with a solvent parameter based on the Onsager reaction field theory. In both SC CO2 and SC CO2-ethanol, the local density enhancement of CO2 in the vicinity of the solute is most remarkable at the reduced density close to unity. The highest degree of aggregation of cosolvent about the solute takes place at the lowest pressure investigated, which is slightly above the critical pressure. Moreover, the clustering of ethanol with the solute competes with that of CO2. In addition, the local concentration enhancement of ethanol was studied in the concentration range of 0 to 6 mol%. It was found that the local concentration of ethanol is enhanced significantly at lower cosolvent concentrations.
Palladium-catalyzed synthesis of N-vinyl pyrroles and indoles
Movassaghi, Mohammad,Ondrus, Alison E.
, p. 8638 - 8641 (2005)
A stereospecific palladium-catalyzed N-vinylation of aza-heterocycles with vinyl inflates is described. Cyclic and acyclic vinyl triflates along with nonnucleophilic azaheterocycles were found to be substrates for this palladium-catalyzed synthesis of N-vinyl pyrrole and indole derivatives.
Diastereoselective Formal Synthesis of Polycyclic Meroterpenoid (±)-Cochlearol A
Venkatesh, Telugu,Mainkar, Prathama S.,Chandrasekhar, Srivari
, p. 5412 - 5416 (2021)
A formal synthesis of (±)-cochlearol A was accomplished. The synthesis features Suzuki coupling and Friedel-Crafts cyclization as a convergent strategy to the functionalized tetralone ring and an intramolecular construction of the C/D ring involving seque
Revisiting ageless antiques; synthesis, biological evaluation, docking simulation and mechanistic insights of 1,4-Dihydropyridines as anticancer agents
Sidhom, Peter A.,El-Bastawissy, Eman,Salama, Abeer A.,El-Moselhy, Tarek F.
supporting information, (2021/06/21)
The historic DHP nucleus was serendipitously discovered by Arthur Hantzsch about 130 years ago and is still considered a hidden treasure for various pharmacological activities. Twenty-one DHP analogues were synthesized using the expedient one pot Hantzsch synthesis for screening as anticancer agents. Initially, the in vitro anti-proliferative single dose against a panel of 18 cancer cell lines showed that compounds 11b and 8f were the superlative candidates regarding their antitumor effect (GI% mean = 66.40% and 50.42%, correspondingly) compared to cisplatin (GI% mean = 65.58%) and doxorubicin (GI% mean = 74.56%). Remarkably, compound 11b showed a remarkable MDA-MB-468 anticancer activity (GI%=80.81%), higher than cisplatin (64.44%) and doxorubicin (76.72%), as well as strong antitumor activity against lung cancer A549 (GI%= 83.02%), more powerful than both cisplatin and doxorubicin. Compound 11b exhibited an exceptional anticancer activity against lung cancer cell line (A549) as its GI50 in nanomolar was (540 nM) with a 9-fold increase greater than cisplatin (GI50 = 4.93 μM) and with a selectivity index = 131 to cancer cells over normal cells. Further mechanistic investigations proved that DHPs anticipate simultaneously TOPI and RTKs (VEGFR-2, HER-2 and BTK) which can stimulate BAX/BAK and the executioner caspases via rtPCR studies.
Electrochemical Oxidative Cyclization: Synthesis of Polysubstituted Pyrrole from Enamines
Chen, Zhiwei,Shi, Guang,Tang, Wei,Sun, Jie,Wang, Wenxing
supporting information, p. 951 - 955 (2021/02/03)
A conceptually novel method for the preparation of pyrrole is described by electrochemical-oxidation-induced intermolecular annulation via enamines. In a simple undivided cell, based on a sodium acetate-facilitated, polysubstituted pyrrole derivations has been facilely synthesized under external oxidant-free condition. This electrosynthetic approach providing an environmentally benign protocol for C?C bond cross-coupling and oxidative annulation, which features unparalleled broad scope of substrates and practicality.
A straightforward synthesis of 5-sulfonamidomethyl substituted 4,7-dihydroazolo[1,5-a]pyrimidines
Shvets, Elena H.,Pidvorotnia, Anastasiia V.,Kulyk, Olesia G.,Mazepa, Alexander V.,Kolosov, Maksim A.
, p. 114 - 122 (2020/10/02)
4,7-Dihydroazolo[1,5-a]pyrimidin-5-ylmethanesulfonamides are side-products of the three-component Biginelli-like reaction of aminoazoles, aldehydes and N,N-dialkyl-2-ketomethanesulfonamides. Herein, we report a straightforward synthesis of 5-sulfonamidomethyl substituted 4,7-dihydroazolo[1,5-a]pyrimidines by a two-component condensation of aminoazoles and N,N-dialkyl(cinnamoyl)methanesulfonamides in DMF at reflux. The starting N,N-dialkyl-2-ketomethanesulfonamides can be obtained by either lithiation of N,N-dialkylmethanesulfonamides and reaction with aldehydes followed by oxidation of the resulting alcohols or by Claisen condensation of N,N-dialkylmethanesulfonamides with the corresponding esters. The chemical structures of all synthesized compounds are supported by 1H and 13C NMR-spectroscopy, mass spectrometry and elemental analysis.
Amide/Ester Cross-Coupling via C-N/C-H Bond Cleavage: Synthesis of β-Ketoesters
Chen, Jiajia,Joseph, Devaneyan,Xia, Yuanzhi,Lee, Sunwoo
, p. 5943 - 5953 (2021/04/02)
Activated primary, secondary, and tertiary amides were coupled with enolizable esters in the presence of LiHMDS to obtain good yields of β-ketoesters at room temperature. Notably, this protocol provides an efficient, mild, and high chemoselectivity method
Transesterification of Methyl 2-Nitroacetate to Superior Esters
Corsi, Massimo,Machetti, Fabrizio,Magnolfi, Stefano
, (2020/03/19)
Methyl 2-nitroacetate and methyl acetoacetate have in common the presence of an electron-withdrawing substituent geminal to the methyl ester function but the well-known ease of thermal transesterification of methyl acetoacetate has not been found in methyl 2-nitroacetate. The latter gives uncatalysed thermal transesterification only in low yield and at a temperature higher than that of methyl acetoacetate. Comparative experiments provided further insight into the reactions; protic and Lewis acid catalysts promoted the smooth exchange of the alkanoyl groups, observing first the transesterification of methyl 2-nitroacetate with ethanol, already proved difficult to proceed. Dibutyltin(IV)oxide (DBTO) catalyst offered the spur to set up a convenient synthetic methodology from methyl 2-nitroacetate, encompassing higher molecular weight and functionalised alcohols: aliphatic, unsaturated and oxidation sensitive species were suited to react, delivering the corresponding 2-nitroacetate esters in good yields in most cases.
