- Relation of the Transition-State Structure for the Water-Catalyzed Hydrolysis of 1-Acetylimidazolium Ion to Solvent Hydrophobicity: Proton Inventories in Water-Acetonitrile Mixtures
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The transition-state structure for the water-catalyzed hydrolysis of 1-acetylimidazolium ion has been probed in solvent systems which may mimic the hydrophobic nature of an enzyme's active site.The kinetic solvent deuterium isotope effect kH2O/kD2O, are 2.58, 2.49, and 2.10 in water, in 0.5 vol fraction of acetonitrile in water, and in 0.9 vol fraction of acetonitrile in water, respectively.The proton inventory investigations suggest all three solvent system entertain a transition-state structure composed of a catalytic proton bridge between the reorganizing substrate and a water molecule acting as a general base-catalyst.A "compression" of the transition-state structure in the solvent system containing the largest amount of acetonitrile is suggested to be responsible for the diminished kinetic solvent deuterium isotope effect.The reaction has been shown to be second order with respect to water.
- Huskey, William P.,Hogg, John L.
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- Enthalpy Changes Accompanying Hydrolysis of 3-(2-Furyl)acryloylimidazole by α-Chymotrypsin
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A calorimetric analysis of the α-chymotrypsin-mediated hydrolysis of 3-(2-furyl)acryloylimidazole at pH 7.85 is presented and compared with the nonenzymatic hydrolysis.The enzyme-mediated hydrolysis is characterized by an apparent pKα for acylation of 6.60 and a deacylation pKα of 7.55.Activation enthalpy changes of 7.8+/-1.3 and 15.0+/-0.4 kcal/mol were determined for acylation (k2) and deacylation (k3), respectively.An enthalpy change of 0.04+/-0.85 kcal/mol for Michaelis complex formation was also determined from the temperature dependence of Ks.Heats of acylation (-10.1+/-0.2 kcal/mol) and deacylation (-1.2+/-0.55 kcal/mol) corrected for buffer ionization and product ionization heats were separately determined by making use of the large rate difference between acylation and deacylation (k2=1000k3) which exists at pH 7.85.The sum of these corrected enthalpy changes (-11.3+/-0.6 kcal/mol) agrees very well with the enthalpy change observed for nonenzymatic hydrolysis of furylacryloylimidazole (-11.3+/-0.5 kcal/mol) and validates the approach used.
- Slightom, J. L.,Bolen, D. W.
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- Catalysis of the methanolysis of acetylimidazole by lanthanum triflate
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Methanolysis of acetylimidazole (1) and N-acetylimidazolepentamine-Co(III) (2) was found to be markedly accelerated in the presence of La(OTf)3. Potentiometric titration of a solution of La3+(OTf-)3 gave a pKa for the metal bound CH3OH of 7.22. The kinetics of methanolysis of 1 and 2 were measured at 25°C at various pH under buffered conditions as a function of increasing La3+. Analysis of both the kinetic and potentiometric data indicates that the catalytically active species is a La3+-dimer, bridged by two methoxides, (CH3OH)nLa3+(CH3O-) 2La3+(CH3OH)n. The maximum second-order rate constants for attack of the dimer on 1 and 2 are 1.50 × 103 M-1 s-1 and 1.42 × 102 M-1 s-1 respectively and both processes adhere to titration of a La3+(CH3OH) to generate the active form. The results are explained in terms of a mechanism where the methoxy-bridged La3+ dimer transiently breaks a La3+-OCH3 bond to expose both a CH3O- nucleophile and a La3+ which can act as a Lewis acid. Unlike the situation in water, the methanol results indicate that the medium greatly stabilizes and solubilizes the active dimer without the necessity of creating specially designed ligands to stabilize the dinuclear core.
- Neverov, Alexei A.,Brown
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- Synthesis of 1-alkylimidazoles
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A mechanistic investigation of the synthesis of imidazole and 1- alkylimidazoles has led to an improved synthesis starting from glyoxal, formaldehyde and alkylammonium chlorides.
- Gridnev,Mihaltseva
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- The stability of N, N -carbonyldiimidazole toward atmospheric moisture
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N,N-Carbonyldiimidazole (CDI) is known to be sensitive to degradation by atmospheric moisture. This work details some mechanistic aspects of CDI degradation by atmospheric moisture along with the major contributing factors to degradation rate. Also, several analytical techniques for the measurement of CDI purity that are less cumbersome than the traditional gas-capture assay are described.
- Engstrom, Kenneth M.,Sheikh, Ahmad,Ho, Raimundo,Miller, Robert W.
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- Lc and nmr studies for identification and characterization of degradation byproducts of olmesartan acid, elucidation of their degradation pathway and ecotoxicity assessment
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The discovery of various sartans, which are among the most used antihypertensive drugs in the world, is increasingly frequent not only in wastewater but also in surface water and, in some cases, even in drinking or groundwater. In this paper, the degradation pathway of olmesartan acid, one of the most used sartans, was investigated by simulating the chlorination process normally used in a wastewater treatment plant to reduce similar emerging pollutants. The structures of nine isolated degradation byproducts (DPs), eight of which were isolated for the first time, were separated via chromatography column and HPLC methods, identified by combining nuclear magnetic resonance and mass spectrometry, and justified by a proposed mechanism of formation beginning from the parent drug. Ecotoxicity tests on olmesartan acid and its nine DPs showed that 50% of the investigated byproducts inhibited the target species Aliivibrio fischeri and Raphidocelis subcapitata, causing functional decreases of 18% and 53%, respectively.
- Di Fabio, Giovanni,Libralato, Giovanni,Luongo, Giovanni,Previtera, Lucio,Saviano, Lorenzo,Serafini, Sara,Siciliano, Antonietta,Zarrelli, Armando
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- Development of a method for the quantification of clotrimazole and itraconazole and study of their stability in a new microemulsion for the treatment of sporotrichosis
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Sporotrichosis occurs worldwide and is caused by the fungus Sporothrix brasiliensis. This agent has a high zoonotic potential and is transmitted mainly by bites and scratches from infected felines. A new association between the drugs clotrimazole and itraconazole is shown to be effective against S. brasiliensis yeasts. This association was formulated as a microemulsion containing benzyl alcohol as oil, Tween 60 and propylene glycol as surfactant and cosurfactant, respectively, and water. Initially, the compatibility between clotrimazole and itraconazole was studied using differential scanning calorimetry (DSC), thermogravimetric analysis (TG), Fourier transform infrared spectroscopy (FTIR), and X-ray powder diffraction (PXRD). Additionally, a simple and efficient analytical HPLC method was developed to simultaneously determine the concentration of clotrimazole and itraconazole in the novel microemulsion. The developed method proved to be efficient, robust, and reproducible for both components of the microemulsion. We also performed an accelerated stability study of this formulation, and the developed analytical method was applied to monitor the content of active ingredients. Interestingly, these investigations led to the detection of a known clotrimazole degradation product whose structure was confirmed using NMR and HRMS, as well as a possible interaction between itraconazole and benzyl alcohol.
- Ferreira, Patricia Garcia,de Souza Lima, Carolina Guimar?es,Noronha, Letícia Lorena,de Moraes, Marcela Cristina,de Carvalho da Silva, Fernando,Vi?osa, Alessandra Lifsitch,Futuro, Débora Omena,Ferreira, Vitor Francisco
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- KINETICS OF FORMATION OF THE ELECTON DONOR-ACCEPTOR COMPLEX BETWEEN IODINE AND IMIDAZOLE IN CHLOROBUTANE SOLUTION
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The kinetics of the formation of the electron donor-acceptor complex between iodine and imidazole in 1-chlorobutane at -64 deg C have been investigated by an improved microwave temperature-jump apparatus.The forward rate constant kf is (3.3+/-0.4)x1E9 dm3 mol-1 s-1.This is nearly the same as the diffusion-controlled value kD calculated from the simple Smoluchowsky model for reaction at every encounter between spherical molecules, without geometrical requirements, in a homogeneous fluid (kf/kD=0.8).
- Caldin, Edward,Field, John P.
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- EFFECT OF THE SURFACE AREA OF PLATINUM ON THE ACTIVITY OF A BIFUNCTIONAL ALUMINOPLATINUM CATALYST IN THE SYNTHESIS OF ALKYLIMIDAZOLES FROM DIAMINES AND CARBONYL ACIDS
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An investigation has been conducted into the effect of the acid and dehydrogenating functions of an aluminoplatinum catalyst on the synthesis of 2-methylimidazole from ethylenediamine and acetic acid.It has been established that formation of the intermediate 2-methylimidazoline involves the acid Al2O3 centers and its rate of formation is greater than the rate of its subsequent dehydrogenation to 2-methylimidazole on the Pt centers.The symbatic nature of the variations in the 2-methylimidazole yield and the surface area of the platinum in the aluminoplatinum catalyst has been demonstrated.Keywords: C-alkylimidazoles, 2-methylimidazole, aluminoplatinum catalyst.
- Gitis, K. M.,Raevskaya, N. I.,Zaitsev, A. V.,Borovkov, V. Yu.,Kozan, S. B.,Isagulyants, G. V.
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- Rate-Limiting Deprotonation in Tetrahedral Intermediate Breakdown
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A kinetic study in acetate and formate buffers is reported of the breakdown to β-hydroxyethyl benzoate of the hemiorthoester-type tetrahedral intermediate 2-phenyl-2-hydroxy-1,3-dioxolane.This species is generated as a transient intermediate in acid solutions in the hydrolysis of the amide acetals 2-phenyl-2-(dimethylamino)-1,3-dioxolane and 2-phenyl-2-(1-imidazolyl)-1,3-dioxolane.Plots of observed rate constant vs. buffer concentration exhibit pronounced curvature in dilute buffers suggestive of a change in rate-limiting step with changing buffer concentration.A mechanism is proposed involving deprotonation of the hydroxy group of the hemiorthoester to produce a highly reactive anion.In the absence of buffer and in very dilute buffers the deprotonation step is rate limiting, the anionic hemiorthoester going on to product at a rate faster than it is reprotonated.In more concentrated buffers the deprotonation step becomes reversible because of the availability of the acid component of the buffer for the reprotonation.A kinetic analysis is presented, providing a rate constant of approximately 5 x 107 s-1 for breakdown of the anionic hemiorthoester.This intermediate is comparable to that which would be encountered during the hydrolysis of a benzoate ester, and some consequences of the large reactivity are discussed.This is suggested to be a contributing factor behind the small amount of carbonyl (18)O exchange observed during the base hydrolysis of esters.It is also pointed out that with leaving groups significantly better than alcoxide, the lifetime may become so short that the tetrahedral intermediate anion could not exist.In this case an acyl transfer reaction proceeding via this anion would have to be regarded as being concerted with the anion as a transition state, not an intermediate.
- McClelland, Robert A.
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- Catalysis of the methanolysis of activated amides by divalent and trivalent metal ions. The effect of Zn2+, Co2+, and La3+ on the methanolysis of acetylimidazole and its (NH3)5CoIII complex
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The metal ions Zn2+, Co2+, and La3+ strongly catalyze the methanolysis of the activated amides acetylimidazole (1) and its ligand-exchange-inert CoIII complex, (NH3)5CoIII-AcIm (2). Studies of the kinetics of methanolysis are performed with s/spH measurement and control, and the metal ions are soluble in the medium throughout the s/spH regions where ionization of the Mx+(CH3OH)y occurs. Zn2+ and Co2+ act as Lewis acids toward 1, catalyzing attack of external methoxide on a 1:M2+ complex at values only 100-fold lower than the diffusion limit, the kOR values being 5.6 × 107 M-1 s-1 and 2.5 × 107 M-1 s-1, while that for CH3O- attack on 2 is 4.69 × 107 M-1 s-1. Since neither Zn2+ nor Co2+ promotes the methanolysis of 2, these metals appear to be acting through transient binding to the distal N of 1, which activates the C=O of the complex to external CH3O- attack. La3+ catalyzes the methanolysis of both 1 and 2, which occurs by a mechanism that is fundamentally different from that exhibited by Zn2+ and Co2+ in that the active species appears to be a bis-methoxy-bridged dimer (La3+)2(CH3O-)2 (CH3OH)x that interacts directly with the C=O unit of the substrate.
- Neverov,Montoya-Pelaez,Brown
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- Method for protecting sulfonyl of deamination amine
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The invention discloses a method for removing sulfenyl protection of amine. The method comprises the following steps: dissolving N - sulfonyl-protected amine and a base in a reaction solvent, then adding diphenylphosphine to uniformly mix and maintain 90 °C. When TCL detection reaction is complete, a recrystallization method or an extraction separation method is adopted to obtain the target product. The method disclosed by the invention adopts diphenylphosphine as an extraction reagent, is good in reaction activity, high in selectivity and wide in application range, and can replace the use of a hazardous reagent under the basic heating condition. Prodrug research and development and industrial production are of great significance.
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Paragraph 0048-0050
(2021/11/03)
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- Indirect reduction of CO2and recycling of polymers by manganese-catalyzed transfer hydrogenation of amides, carbamates, urea derivatives, and polyurethanes
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The reduction of polar bonds, in particular carbonyl groups, is of fundamental importance in organic chemistry and biology. Herein, we report a manganese pincer complex as a versatile catalyst for the transfer hydrogenation of amides, carbamates, urea derivatives, and even polyurethanes leading to the corresponding alcohols, amines, and methanol as products. Since these compound classes can be prepared using CO2as a C1 building block the reported reaction represents an approach to the indirect reduction of CO2. Notably, these are the first examples on the reduction of carbamates and urea derivatives as well as on the C-N bond cleavage in amides by transfer hydrogenation. The general applicability of this methodology is highlighted by the successful reduction of 12 urea derivatives, 26 carbamates and 11 amides. The corresponding amines, alcohols and methanol were obtained in good to excellent yields up to 97%. Furthermore, polyurethanes were successfully converted which represents a viable strategy towards a circular economy. Based on control experiments and the observed intermediates a feasible mechanism is proposed.
- Liu, Xin,Werner, Thomas
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p. 10590 - 10597
(2021/08/20)
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- Supramolecular Catalysis of Acyl Transfer within Zinc Porphyrin-Based Metal-Organic Cages
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To illustrate the supramolecular catalysis process in molecular containers, two porphyrinatozinc(II)-faced cubic cages with different sizes were synthesized and used to catalyze acyl-transfer reactions between N-acetylimidazole (NAI) and various pyridylcarbinol (PC) regioisomers (2-PC, 3-PC, and 4-PC). A systemic investigation of the supramolecular catalysis occurring within these two hosts was performed, in combination with a host-guest binding study and density functional theory calculations. Compared to the reaction in a bulk solvent, the results that the reaction of 2-PC was found to be highly efficient with high rate enhancements (kcat/kuncat = 283 for Zn-1 and 442 for Zn-2), as well as the different efficiencies of the reactions with various ortho-substituted 2-PC substrates and NAI derivates should be attributed to the cages having preconcentrated and preoriented substrates. The same cage displayed different catalytic activities toward different PC regioisomers, which should be mainly attributed to different binding affinities between the respective reactant and product with the cages. Furthermore, control experiments were carried out to learn the effect of varying reactant concentrations and product inhibition. The results all suggested that, besides the confinement effect caused by the inner microenvironment, substrate transfer, including the encapsulation of the reactant and the release of products, should be considered to be a quite important factor in supramolecular catalysis within a molecular container.
- Li, Lili,Yang, Linlin,Li, Xuezhao,Wang, Jing,Liu, Xin,He, Cheng
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supporting information
p. 8802 - 8810
(2021/06/28)
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- Electron Transfer Photoredox Catalysis: Development of a Photoactivated Reductive Desulfonylation of an Aza-Heteroaromatic Ring
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Herein, we report a protocol for desulfonylation of aza-heteroaromatic rings via photoinduced electron transfer and hydrogen atom transfer. This general protocol has a wide substrate range and moderate to good yields. The utility of the method was demonstrated by the chemoselective desulfonylation of a molecule containing both an aliphatic and an aromatic sulfonamide. (Figure presented.).
- Qiang-Liu,Liu, Yu-Xiu,Song, Hong-Jian,Wang, Qing-Min
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supporting information
p. 3110 - 3115
(2020/07/04)
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- Optimizing Multivariate Metal-Organic Frameworks for Efficient C2H2/CO2Separation
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Adsorptive separation of acetylene (C2H2) from carbon dioxide (CO2) promises a practical way to produce high-purity C2H2 required for industrial applications. However, challenges exist in the pore environment engineering of porous materials to recognize two molecules due to their similar molecular sizes and physical properties. Herein, we report a strategy to optimize pore environments of multivariate metal-organic frameworks (MOFs) for efficient C2H2/CO2 separation by tuning metal components, functionalized linkers, and terminal ligands. The optimized material UPC-200(Al)-F-BIM, constructed from Al3+ clusters, fluorine-functionalized organic linkers, and benzimidazole terminal ligands, demonstrated the highest separation efficiency (C2H2/CO2 uptake ratio of 2.6) and highest C2H2 productivity among UPC-200 systems. Experimental and computational studies revealed the contribution of small pore size and polar functional groups on the C2H2/CO2 selectivity and indicated the practical C2H2/CO2 separation of UPC-200(Al)-F-BIM.
- Fan, Weidong,Yuan, Shuai,Wang, Wenjing,Feng, Liang,Liu, Xiuping,Zhang, Xiurong,Wang, Xia,Kang, Zixi,Dai, Fangna,Yuan, Daqiang,Sun, Daofeng,Zhou, Hong-Cai
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supporting information
p. 8728 - 8737
(2020/12/25)
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- Reductive dehalogenation and dehalogenative sulfonation of phenols and heteroaromatics with sodium sulfite in an aqueous medium
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Prototropic tautomerism was used as a tool for the reductive dehalogenation of (hetero)aryl bromides and iodides, or dehalogenative sulfonation of (hetero)aryl chlorides and fluorides, using sodium sulfite as the sole reagent in an aqueous medium. This protocol does not require a metal or phase transfer catalyst and avoids using organic solvent as the reaction medium. This method is especially suitable for substrates that readily tautomerize (such as 2-or 4-halogenated aminophenols and 4-halogenated resorcinols), for which dehalogenation or sulfonation proceeds under mild reaction conditions (≤60 °C). As sodium sulfite is an inexpensive, safe, and environmentally less hazardous reagent, this method has at least three potential applications: (i) in the deprotection of halogens as protecting groups, using sodium sulfite as a reducing agent; (ii) in the sulfonation of aromatic halides under mild reaction conditions avoiding hazardous and corrosive reagents/solvents; and (iii) in the transformation of toxic halogenated aromatics into less harmful compounds.
- Tomanová, Monika,Jedinák, Luká?,Canka?, Petr
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supporting information
p. 2621 - 2628
(2019/06/03)
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- One-pot synthesis of 2-hydroxymethyl-5-methylpyrazine from renewable 1,3-dihydroxyacetone
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An efficient and green method for the synthesis of 2-hydroxymethyl-5-methylpyrazine was achieved from biomass derived 1,3-dihydroxyacetone and diammonium phosphate via a one-pot reaction. The product yield was as high as 72% under optimized conditions of pH = 8.0-9.1 at 90 °C for 1 hour in a dioxane and water mixture as a solvent. A possible reaction mechanism was proposed according to the reaction kinetics, NMR and in situ ATR-IR characterization studies.
- Song, Lei,Zheng, Mingyuan,Pang, Jifeng,Sebastian, Joby,Wang, Wentao,Qu, Minjie,Zhao, Jian,Wang, Xinhong,Zhang, Tao
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p. 3515 - 3519
(2017/08/15)
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- Overcoming the Hydrolytic Lability of a Reaction Intermediate in Production of Protein/Drug Conjugates: Conjugation of an Acyclic Nucleoside Phosphonate to a Model Carrier Protein
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Acquired immunodeficiency syndrome (AIDS) remains one of the most serious public health challenges and a significant cause of mortality for certain populations. Despite the large number of antiretrovirals developed in the past two decades, the inability of small molecule therapeutics to target HIV reservoirs directly creates a significant obstacle to their effective utilization. Indeed, achieving the desired therapeutic outcome in the absence of an effective means of targeted delivery must rely on dosage escalation, which frequently causes severe toxicity. This problem may be solved by conjugation of antiretroviral agents to endogenous proteins that are specifically recognized by HIV reservoirs (such as macrophages) for internalization and catabolism. However, conjugation of a large class of antiretroviral agents (acyclic nucleoside phosphonates, such as adefovir, tenofovir, and cidofovir) to a protein is challenging due to rapid degradation of the activated form of the drug (e.g., adefovir phosphonoimidazolide) in an aqueous environment. A novel synthetic strategy introduced in this work overcomes the instability of the activated form of adefovir by emulating the first step of its metabolic pathway (phosphorylation), making it highly reactive toward primary amine groups of proteins and, at the same time, less prone to hydrolysis by water. Efficient conjugation of the phosphorylated form of adefovir to a protein following activation with EDC (1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloride) and imidazole was demonstrated using a model protein. Mass spectrometry (MS) was used to identify conditions that favor formation of conjugates with minimal side products, and online ion exchange chromatography/MS analysis of the products revealed the presence of multiple positional isomers within the 1:1 protein/drug conjugates. Both liquid chromatography/MS data and the analysis of ions produced upon top-down fragmentation of the 1:1 conjugates suggest that conjugation of phosphorylated adefovir to the protein occurs not only at primary amines but also at hydroxyl groups. The new conjugation protocol can be used to attach adefovir and other acyclic nucleoside phosphonates to proteins recognized by the cell surface receptors specific to macrophages (such as the haptoglobin/hemoglobin complex), enabling targeted drug delivery directly to HIV reservoirs.
- Xu, Shengsheng,Kaltashov, Igor A.
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p. 2843 - 2851
(2017/08/14)
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- Coordination properties of μ-carbidodimeric iron(IV) 2,3,7,8,12,13,17,18-octapropyltetraazaporphyrinate and 5,10,15,20-tetraphenylporphyrinate in reactions with nitrogen-containing bases
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The equilibria of μ-carbidodimeric iron(IV) 2,3,7,8,12,13,17,18-octapropyltetraazaporphyrinate and 5,10,15,20-tetraphenylporphyrinate in reactions with nitrogen-containing bases in an inert solvent were studied spectrophotometrically. The equilibrium constants of the studied processes and the compositions of molecular complexes were determined. The effect of the electronic and conformation factors of a macrocycle and the nature of the base on the equilibrium constant was pointed out. A comparative analysis of the substrate specificity of the studied compounds was performed.
- Zaitseva,Zdanovich,Kudrik,Koifman
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p. 1257 - 1266
(2017/09/29)
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- High-Temperature Boc Deprotection in Flow and Its Application in Multistep Reaction Sequences
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A simplified Boc deprotection using a high-temperature flow reactor is described. The system afforded the qualitative yield of a wide variety of deprotected substrates within minutes using acetonitrile as the solvent and without the use of acidic conditions or additional workups. Highly efficient, multistep reaction sequences in flow are also demonstrated wherein no extraction or isolation was required between steps.
- Bogdan, Andrew R.,Charaschanya, Manwika,Dombrowski, Amanda W.,Wang, Ying,Djuric, Stevan W.
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supporting information
p. 1732 - 1735
(2016/05/19)
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- Easy removal of N-carboxybenzyl (Cbz) protective group by low-carbon alcohol
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Background: A new method for the removal of Cbz protective group was established. It is accomplished by using methanol, ethanol or t-butanol as a deprotective reagent, and the scope and limitations of this method were also preliminarily investigated. These results broaden utility of N-Cbz protective group in synthetic chemistry, especially in synthesis or use of imidazole, benzimidazole, pyrazole or their derivatives. Methods: Using N-Cbz-imidazole as a model compound, the feasibility of the deprotection method was investigated. We studied various reaction conditions including solvent, reaction temperature and catalyst on the influence of the deprotection reaction. Typical experimental procedure, N-Cbz-imidazole (0.40 g, 2.0 mmol) was added to a solution of methanol (30 mL), and the reaction mixture was stirred at room temperature. Hourly tracking and detection by HPLC analysis. Results: These results indicate that the deprotection method effectiveness is closely related with the substrate structure. In the explored scope, it is valid for some heterocyclic compounds, such as N-Cbz-protected imidazole, pyrazole compound, benzimidazole and benzimidazole derivatives, but possibly not for other amino chemicals. Further application of the method to other types of heterocyclic amine compounds is in progress in our labs. The novel deprotection approach can widen use of N-Cbz protective group in synthetic chemistry. There currently are many active pharmaceutical ingredients containing azole structures, for example: omeprazole, esomeprazole, lansoprazole, dexlansoprazole and pantoprazole etc. It has potential to be utilized in pharmaceutical industries and fine chemicals. Conclusion: In summary, this new method of removal of Cbz protective group using low-carbon alcohols of methanol, ethanol or tert-butanol as deprotective reagents is feasible and effective in the kind of heterocyclic amino compounds of imidazoles, pyrazoles and their derivatives. This new approach is simple and mild. Furthermore, removal of Cbz protective group does not affect other functional groups on the molecule, i.e., the structure remains unchanged.
- Song, Guo-Qiang,Qin, Feng,Huang, Xian-Feng,Lv, Xiao-Bing,Yang, Bei
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p. 177 - 180
(2016/02/26)
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- Reduction of Aryl Halides into Arenes with 2-Propanol Promoted by a Substoichiometric Amount of a tert-Butoxy Radical Source
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Aryl halides are reduced into the corresponding arenes in high yields, using 2-propanol, cesium carbonate, and di-tert-butyl peroxide (or di-tert-butyl hyponitrite) as a reductant/solvent, a base, and a radical initiator, respectively. This simple system reduces a wide variety of aryl bromides, chlorides, and iodides through single-electron-transfer mechanism with high functional-group tolerance.
- Ueno, Ryota,Shimizu, Takashi,Shirakawa, Eiji
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supporting information
p. 741 - 744
(2016/03/12)
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- Self-assembly and β-carotene loading capacity of hydroxyethyl cellulose-graft-linoleic acid nanomicelles
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A series of linoleic acid conjugated hydroxyethyl cellulose polymers (HEC-g-LA) were synthesized and characterized. And their solubilities in a variety of solvents were compared. The prepared HEC-g-LA polymers showed typical properties of amphiphilic polymers and were able to self-assemble into spherical nanomicelles in aqueous solution. The micelle sizes and critical micelle concentrations (CMC) were found correlated with the molecular structure of polymers, and were varied in the range of 20-50 nm and 1.92-21.76 μg/ml, respectively. Furthermore, the hydrophobic active component β-carotene (β-C) was successfully encapsulated into the HEC-g-LA micelles by sonication-dialysis method. The β-C encapsulation efficiency and loading content were found to be as high as 84.67% (w/w) and 4.23%. The results of in vitro release showed that the encapsulated β-C was continuously released from the micelles in phosphate buffered saline (PBS) medium for about 7 days. The self-assembled HEC-g-LA nanomicelles are potential nanocarriers of hydrophobic active compounds for functional food applications.
- Yang, Yang,Guo, Yanzhu,Sun, Runcang,Wang, Xiaohui
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- Reduction of (chloro)-μ-nitrido-bis[(tetra-tert-butyl-phthalocyaninato)iron(IV)] with organic N-bases
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The interaction of (chloro)-μ-nitrido-bis[(tetra-Tert-butyl-phthalocyaninato)iron(IV)] Cl(FePc)2N with organic N-bases L as electron-donors (L diethylamine, imidazole, 1-methylimidazole, 2-methylimidazole) with the formation of one-electron reduced species (L)PcFeIII-N?FeIVPc(L) was investigated in benzene at 298 K by UV-visible spectroscopy. The reaction was established to be stepwise process including fast reversible axial binding of two substrate molecules onto iron cations followed by slow one-electron metal-centered reduction. The results of IR, ESI-MS and EPR study support the formation of final product with Fe?3-N?Fe?4 unit and two substrate molecules in the first coordination sphere. The reaction kinetics was studied, the pre-equilibrium constants Keq and rate constants κ were obtained. The Keq and κ values were found to be linearly correlated with basicity of substrates pκa. The possibility of the transition Fe4?→Fe3??is promoted by electron-donor properties of substrate combined with the presence of both electron-rich macrocycle and φ-backdonation Fe →NPc.
- Zaitseva, Svetlana V.,Zdanovich, Sergei A.,Tyulyaeva, Elena Y.,Grishina, Ekaterina S.,Koifman, Oskar I.
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p. 639 - 646
(2016/07/11)
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- HETEROCYCLIC AMIDE COMPOUND
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The present invention provides a heterocyclic amide compound of Formula (1), and an agricultural chemical containing it, particularly a herbicide: in which Q is an aromatic heterocycle of any one of Q-1 to Q-5, W is an aromatic heterocycle oft-1, W-2, or W-3, X is an oxygen atom, etc., R 1a is a hydrogen atom, a halogen atom, or C 1-6 alkyl, etc., R 1b is a hydrogen atom, R 1c is C 1-6 alkyl, R 2a is a halogen atom, or C 1-6 alkyl, etc., R 2c is C 1-6 haloalkyl, R 3 is a hydrogen atom, etc., R 4a , R 4b , R 4c and R 4d are each independently a hydrogen atom, or C 1-6 alkyl, etc., R 5a , R 5b and R 5c are each independently a hydrogen atom, or C 1-6 alkyl, etc., and n is an integer of 0, 1, 2 or 3.
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Paragraph 0894; 1012-1015
(2016/10/07)
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- Exploiting the Imidazolium Effect in Base-free Ammonium Enolate Generation: Synthetic and Mechanistic Studies
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N-Acyl imidazoles and catalytic isothiourea hydrochloride salts function as ammonium enolate precursors in the absence of base. Enantioselective Michael addition–cyclization reactions using different α,β-unsaturated Michael acceptors have been performed to form dihydropyranones and dihydropyridinones with high stereoselectivity. Detailed mechanistic studies using RPKA have revealed the importance of the “imidazolium” effect in ammonium enolate formation and have highlighted key differences with traditional base-mediated processes.
- Young, Claire M.,Stark, Daniel G.,West, Thomas H.,Taylor, James E.,Smith, Andrew D.
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supporting information
p. 14394 - 14399
(2016/11/11)
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- Method for preparing an imidazole
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The invention discloses a preparation method for imidazole. 2,2-diethoxyethylamine and malonamide are employed for preparing biimidazole, and biimidazole is used to prepare imidazole. Compared with the prior art, the method has the total conversion rate of 91% through continuous optimization of reaction conditions and other reagent usage amount, and the total conversion rate is far higher than that of a conventional technology. The preparation method is mild in reaction conditions, a solvent and a catalyst employed in the reaction process can be recovered and reused, and the method is relatively low in cost and is practicable.
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Paragraph 0031; 0032; 0036-0038
(2017/03/14)
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- A protic ionic liquid catalyzed strategy for selective hydrolytic cleavage of tert-butyloxycarbonyl amine (N-Boc)
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A simple, mild and efficient strategy for selective hydrolytic cleavage of the N-tert-butyloxycarbonyl (Boc) group is devised using a protic ionic liquid as an efficient catalyst. The deprotection reaction proceeded well for N-Boc protected aromatic, heteroaromatic, aliphatic compounds, and chiral amino acid esters and peptides. A wide range of labile protecting groups such as tert-butyl ester, tert-butyl ether, benzyloxycarbonyl (Cbz), TBDMS, O-Boc and S-Boc remained unaffected under the reaction conditions. This journal is
- Majumdar, Swapan,De, Jhinuk,Chakraborty, Ankita,Roy, Dipanwita,Maiti, Dilip K.
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p. 3200 - 3205
(2015/02/03)
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- Deprotection of N-benzylbenzimidazoles and N-benzylimidazoles with triethylsilane and Pd/C
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The benzyl group is a protecting group for benzimidazoles and imidazoles that can survive acidic, basic, oxidizing, and reducing conditions. Deprotection, however, can require vigorous and potentially non-chemoselective methods. The triethylsilane–Pd/C reduction system is an exceptionally mild, convenient, and efficient method for deprotecting N-benzylbenzimidazoles that are unsubstituted at the 2- and 4-positions as well as suitably substituted N-benzylimidazoles.
- Graham, Thomas H.
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supporting information
p. 2688 - 2690
(2017/11/14)
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- Coordinating ability of rhodium(III) porphyrins toward organic bases
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Reactions of hydroxo(2,3,7,8,12,13,17,18-octaethylporphyrinato)rhodium(III) and acetylacetato-(5,10,15,20-tetraphenylporphyrinato)rhodium(III) with nitrogen-containing substrates were studied by spectrophotometry. The stability constants and compositions of the resulting molecular complexes were determined, and the effects of the macrocycle nature and substrate basicity on the stability constants were estimated. The structures of the isolated rhodium porphyrin molecules and their complexes with organic bases were optimized by the PM3 quantum chemical method. The degree of macrocycle deformation was found to change in the course of metal-substrate coordination. A correlation between the metal-substrate bond energy and equilibrium constant was revealed.
- Zaitseva,Zdanovich,Bryukhanova,Koifman
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p. 2786 - 2792
(2016/02/18)
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- Chemical transformations of diazoles in the reactions of carboxylation, N-siloxycarbonylation, and transsilylation
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The behavior of 3,5-dimethylpyrazole, 3(5)-methylpyrazole, imidazole and their trimethyl-silyl derivatives in carboxylation, N-siloxycarbonylation, and transsilylation reactions was studied. A new Nsiloxycarbonylation reagent, diazole trimethylsilyl derivative-carbon dioxide, was found. This reagent makes it possible to obtain easily O-silylurethanes starting from primary, secondary amines and hydrazine derivatives, as well as to develop a convenient one pot synthesis method for trimethylsiloxycarbonyldiazoles.
- Belova,Pletnev,Kirilin
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p. 1365 - 1368
(2013/09/23)
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- Synthesis and properties of polymeric materials prepared by polymerization of epoxy oligomers with N,N′-carbonyldiimidazole transformation products
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The reaction of N,N′-carbonyldiimidazole with ethanol and epoxy oligomers of diphenylolpropane diglycidyl ether and 4,4′- bis(glycidylamino)-3,3′-dichlorodiphenylmethane was studied by gas chromatography-mass spectrometry and differential scanning calorimetry. From these oligomers and N,N′-carbonyldiimidazole transformation products, epoxy polymers were synthesized, and their physicomechanical and adhesion properties were determined. Pleiades Publishing, Ltd., 2012.
- Fedoseev,Glushkov,Gorbunov,Derzhavinskaya,Oshchepkova
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experimental part
p. 456 - 459
(2012/08/08)
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- Synthesis of unsymmetrical biaryl ureas from N-carbamoylimidazoles: Kinetics and application
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N-Carbamoylimidazoles dissociate in solution to yield imidazole and an isocyanate that may be reacted with another aryl amine to form an unsymmetrical biaryl urea. This paper investigates the reaction kinetics and the influence of electron withdrawing/donating substituents on the reaction of N-carbamoylimidazoles with aniline. The overall reaction mechanism involves two zwitterionic intermediates, formed during dissociation and upon reaction of the liberated isocyanate with aniline. The rate limiting step for the reaction is a base catalysed proton transfer from the second zwitterionic intermediate. Although electron withdrawing substituents on the aryl group hinder dissociation, they significantly increase reaction rates compared to compounds bearing electron donating substituents. The imidazole liberated upon dissociation catalyses the rate determining step so that reactions of dissociated N-carbamoylimidazoles proceed more rapidly than those involving only isocyanates. In addition, the imidazole eliminates the need for anhydrous reaction conditions. The N-carbamoylimidazole methodology was demonstrated by preparing sorafenib, a biaryl urea kinase inhibitor, in good yield and excellent purity.
- Rawling, Tristan,McDonagh, Andrew M.,Tattam, Bruce,Murray, Michael
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experimental part
p. 6065 - 6070
(2012/09/22)
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- One-pot domino synthesis of polyvicinalamine monomers
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Imidazole was generated in situ via a domino reaction between glyoxal, formaldehyde, and two units of aqueous ammonia. Aqueous bicarbonate and a carboxylic anhydride or dialkyl dicarbonate were added, yielding the corresponding N, N′-diacyl or N,N′-dicarbalkoxy-2- hydroxyimidazoline. A Bamberger ring cleavage ensued, affording cis-1,2-di(acetamido)- ethene, cis-1,2-di(propylamido)ethene, cis-1,2-di(ethoxyamido)ethene, cis-1,2-di(tert-butoxyamido)ethene, or cis-1,2-di(benzamido) ethene as easily isolable solids. The convenience and generality offered by this one-pot approach implied a cost-effective route to the routine synthesis of oligo- and polyvicinalamine precursors.
- Kilic, Cem B.,Taralp, Alpay
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experimental part
p. 506 - 510
(2011/06/22)
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- A total synthesis of (±)-α-cyclopiazonic acid using a cationic cascade as a key step
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The indole alkaloid α-cyclopiazonic acid 1 has been synthesised by a route, which features at its core an acid-catalysed cationic cascade cyclisation terminated by a sulfonamide group.
- Griffiths-Jones, Charlotte M.,Knight, David W.
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experimental part
p. 8515 - 8528
(2011/11/29)
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- ACID-SENSITIVE LINKERS FOR DRUG DELIVERY
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The invention is in general directed to acid-sensitive linkers, and methods of use thereof, such as, for example, in drug delivery methods.
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Page/Page column 9-11
(2011/04/14)
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- PHOSPHORESCENT EMITTERS
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Compounds including a ligand with a dibenzo-fused 5-membered ring substituent are provided. In particular, the compounds may be iridium complexes including imidazole coordinated to the dibenzo-substituted ligand. The dibenzo-fused 5-membered ring moiety of the ligand may be twisted or minimally twisted out of plane with respect to the rest of the ligand structure. The compound may be used in organic light emitting devices, particularly as emitting dopants in blue devices. Devices comprising the compounds may demonstrate improved stability while maintaining excellent color.
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- Photo-induced self-cleaning functions on 2-anthraquinone carboxylic acid treated cotton fabrics
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Self-cleaning cotton fabrics were obtained via chemically incorporating photosensitive 2-anthraquinone carboxylic acid (2-AQC) onto the fibers through a mild and efficient esterification reaction. The 2-AQC structures on the treated cotton were confirmed by FTIR characterization. SEM images revealed that the cotton fiber surface became rougher than that of the original cotton fiber after the treatment. TGA analysis confirmed that thermal stability of the treated fibers was almost unchanged. The 2-AQC treated cotton fabrics demonstrated excellent photo-induced self-cleaning properties, including decomposition of 90% aldicarb in 3 hours of UVA exposure and inactivation of over 99% of both E. coli and S. aureus in 1 hour of the light exposure. The self-cleaning functions are a result of formation of reactive oxygen species on the light irradiated and 2-AQC treated cotton. The amount of H2O2 formed on the fabrics was determined by a titration method.
- Liu, Ning,Sun, Gang,Zhu, Jing
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scheme or table
p. 15383 - 15390
(2012/01/19)
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- COMBINATIONS COMPRISING BICYCLIC S1P LYASE INHIBITORS
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Methods and compositions for treating immunological and inflammatory diseases and disorders are disclosed. Particular methods and compositions comprise the administration of an agent that inhibits S1P lyase activity and at least one additional immunosuppr
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- PH-Sensitive, N-ethoxybenzylimidazole (NEBI) bifunctional crosslinkers enable triggered release of therapeutics from drug delivery carriers
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This paper presents a pH-sensitive bifunctional crosslinker that enables facile conjugation of small molecule therapeutics to macromolecular carriers for use in drug delivery systems. This N-ethoxybenzylimidazole (NEBI) bifunctional crosslinker was designed to exploit mildly acidic, subcellular environments to trigger the release of therapeutics upon internalization in cells. We demonstrate that an analog of doxorubicin (a representative example of an anticancer therapeutic) conjugated to human serum albumin (HSA, a representative example of a macromolecular carrier) via this NEBI crosslinker can internalize and localize into acidic lysosomes of ovarian cancer cells. Fluorescence imaging and cell viability studies demonstrate that the HSA-NEBI-doxorubicin conjugate exhibited improved uptake and cytotoxic activity compared to the unconjugated doxorubicin analog. The pH-sensitive NEBI group was also shown to be relatively stable to biologically-relevant metal Lewis acids and to serum proteins, supporting that these bifunctional crosslinkers may be useful for constructing drug delivery systems that will be stable in biological fluids such as blood.
- Luong, Alice,Issarapanichkit, Tawny,Kong, Seong Deok,Fong, Rina,Yang, Jerry
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supporting information; scheme or table
p. 5105 - 5109
(2010/12/25)
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- Boiling water-catalyzed neutral and selective N-Boc deprotection
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A general protocol for removing Boc groups from various types of nitrogen is reported and a preliminary investigation of the reaction mechanism indicates that water acts as a dual acid/base catalyst at elevated temperature. The Royal Society of Chemistry 2009.
- Wang, Jia,Liang, Yan-Liang,Qu, Jin
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supporting information; experimental part
p. 5144 - 5146
(2009/12/08)
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- Catalyst-free water-mediated N-Boc deprotection
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A catalyst-free water-mediated N-Boc deprotection of N-Boc-amines is reported. In the absence of any additional reagents, the free amines were formed from a variety of aromatic and aliphatic N-Boc-amines as well as from some N-Boc-amino acid derivatives.
- Wang, Gan,Li, Chunju,Li, Jian,Jia, Xueshun
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experimental part
p. 1438 - 1440
(2009/06/18)
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- Reduction of 1-pyrrolyl and 1-indolyl carbamates to hemiaminals
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Hemiaminals of pyrroles and indoles have been prepared from the lithium aluminum hydride reduction of 1-pyrrolyl and 1-indolyl carbamates with good yields (67-82%). These carbamates are more reactive than aliphatic amides and carbamates under the LAH reduction, but less reactive than esters.
- Hsu, He-Chu,Hou, Duen-Ren
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supporting information; experimental part
p. 7169 - 7171
(2010/03/03)
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- Reductive amine deallyl- and debenzylation with alkali metal in Silica Gel (M-SG)
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Alkali metals in silica gel (the M-SG materials) are effective reagents for reductive deallylation, debenzylation, debenzhydrylation, and detritylation of amines. As such, these reagents provide a convenient alternative to traditional metal ammonia solutions for this class of deprotections.
- Nandi, Partha,Dye, James L.,Jackson, James E.
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supporting information; experimental part
p. 3864 - 3866
(2009/09/28)
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- A novel synthesis of coumarins employing triphenyl(α-carboxymethylene)phosphorane imidazolide as a C-2 synthon
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A novel one-pot synthesis of coumarins via intramolecular Wittig cyclization from the reaction of phenolic compounds containing ortho-carbonyl group and triphenyl(α-carboxymethylene)phosphorane imidazolide is described.
- Upadhyay, Puspesh K.,Kumar, Pradeep
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scheme or table
p. 236 - 238
(2009/05/11)
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- Synthesis of 4,5-substituted imidazoles by a fast condensation of 1,2-diketones and urotropine in heterogeneous medium
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Starting from 1,2-diketones and urotropine in the presence of ammonium acetate, a simple and efficient solventless microwave-assisted synthesis of 4,5-disubstituted imidazoles was accomplished. Georg Thieme Verlag Stuttgart.
- Bratulescu, George
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experimental part
p. 2319 - 2320
(2010/02/28)
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- Ternary molybdenum-antimony-titanium oxide systems in catalytic synthesis of 2-imidazolinecarboxamide
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Catalytic ammonolysis of 2-methylimidazoline (lysidine) in the presence of a number of ternary molybdenum-antimony-titanium oxide systems was studied.
- Kagarlitskii,Sidoikin,Krichevskii
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p. 268 - 271
(2008/09/19)
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- Synthesis and evaluation of acylguanidine FXa inhibitors
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A series of acylguanidine derivatives were prepared and investigated as inhibitors of Factor Xa (FXa). These compounds were made by guanidine acylation with carboxylic acids using carbonyl diimidazole (CDI) as the coupling reagent. Conditions for the rapid synthesis and purification of these compounds are described along with their ability to inhibit FXa. The best FXa inhibitor is 1 with a FXa IC50 of 6 nM.
- O'Connor, Stephen P.,Atwal, Karnail,Li, Chi,Liu, Eddie C.-K.,Seiler, Steven M.,Shi, Mengxiao,Shi, Yan,Stein, Philip D.,Wang, Ying
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scheme or table
p. 4696 - 4699
(2009/04/06)
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- Novel N,S-phenacyl protecting group and its application for peptide synthesis
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The phenacyl group can be introduced onto amino and thio groups by N,S-alkylation reactions. Conversely, these groups are removed rapidly by employing magnesium in acetic acid. This protecting group was successfully applied to a short peptide synthesis of Boc-L-Cys-Gly-OMe. Georg Thieme Verlag Stuttgart.
- Tang, Guo,Ji, Tao,Hu, An-Fu,Zhao, Yu-Fen
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experimental part
p. 1907 - 1909
(2009/04/11)
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- Kinetics and mechanism of the nucleophilic cleavage of disulfide bond in 2,2′-dithio-diimidazoles with hydroxide ions
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Kinetics of the cleavage of disulfide bond of dithiobisdisulfides of diimidazoles to their parent imidazoles by hydroxide ion have been investigated spectrophotometrically. Rate equation and other observations suggest that the nucleophilic attack of hydroxide ion on one of the sulfur atoms of disulfide bond is a rate limiting step. This process is accompanied by much slower, parallel reaction with water as a nucleophile. Hence the full kinetic equation for nucleophilic cleavage of 2,2′-dithio-diimidazoles in aqueous alkaline solutions is a two-term equation: -(d[RSSR]/dt) = k1 [RSSR][OHl + k2[RSSR][H2O], where k1 > k2. The mechanism of the reaction is proposed.
- Kurzawa,Suszka
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p. 1487 - 1494
(2008/09/18)
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- 2,3,4,5-TETRAHYDRO-1H-1,5-BENZODIAZEPINE DERIVATIVE AND MEDICINAL COMPOSITION
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The present invention has its object to provide a 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine derivative represented with the Formula (1) , or the pharmaceutically acceptable salt, which is effective as a therapeutic and prophylactic agent for diabetes, diabetic nephropathy, or glomerulosclerosis.
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- ORGANIC COMPOUNDS
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A compound of formula (I) and their preparation and use as pharmaceuticals wherein R1, R2 and R3 are as defined herein.
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Page/Page column 20
(2008/06/13)
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- PURINE DERIVATIVES WITH ACTIVITY TO THE ADENOSINE A2A RECEPTOR
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A compound of formula (I) or stereoisomers or pharmaceutically acceptable salts thereof, and their preparation and use as pharmaceuticals wherein U, R1, R2 and R3 are as defined herein.
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Page/Page column 40-41
(2008/06/13)
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- ORGANIC COMPOUNDS
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A compound of formula (I) or stereoisomers or pharmaceutically acceptable salts thereof, and their preparation and use as pharmaceuticals wherein Rl, R2 and R3 are as defined herein.
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Page/Page column 49
(2008/06/13)
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- Deprotection of heteroaromatic carbamates via a base-catalyzed methanolysis
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A simple and mild method for the deprotection of heteroaromatic carbamates via methanolysis using a catalytic amount of base such as sodium methoxide, DBU, or Verkade's base (proazaphosphatranes) is presented. Carbamate protecting group of an aliphatic amine is not affected under these conditions.
- Shieh, Wen-Chung,Xue, Song,McKenna, Joe,Prasad, Kapa,Repi?, Oljan,Blacklock, Thomas
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p. 5645 - 5648
(2007/10/03)
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- PROCESS FOR PRODUCING N,N'-CARBONYLDIIMIDAZOLE
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The present invention provides a process for producing N,N'-carbonyldiimidazole, comprising: reacting phosgene, diphosgene, or triphosgene with imidazole in an inert solvent to produce N,N'-carbonyldiimidazole; to imidazole hydrochloride yielded as a by-product in the above step, adding a gaseous or liquid basic compound represented by the below-shown general formula (1) in an inert solvent to conduct neutralization reaction; and circulating the imidazole thus generated to use it as a starting material for N,N'-carbonyldiimidazole production. In the general formula (1), R 1 , R 2 , and R 3 each independently represents a hydrogen atom, a methyl group, or an ethyl group. The CDI produced by the production process of the invention is a compound useful in the fields of synthesis of pharmaceutical agents, synthesis of agricultural chemicals, peptide synthesis, and the like, e.g., intermolecular condensation reactions, intramolecular condensation reactions for synthesizing N-carboxylic anhydrides, production of activated esters, and the like. The compound is especially suitable for use in applications where colorlessness is required.
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Page/Page column 5
(2008/06/13)
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