- Novel starch-polyalkane composite materials
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The polymerisation of dibromoalkanes adsorbed in potato starch leads to a novel class of hydrophobic starch-polyalkane composite materials with very high capacity for surface derivitisation.
- Hardy,Clark,Rhodes,Wilson
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Read Online
- Late-Stage Intermolecular Allylic C-H Amination
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Allylic amination enables late-stage functionalization of natural products where allylic C-H bonds are abundant and introduction of nitrogen may alter biological profiles. Despite advances, intermolecular allylic amination remains a challenging problem due to reactivity and selectivity issues that often mandate excess substrate, furnish product mixtures, and render important classes of olefins (for example, functionalized cyclic) not viable substrates. Here we report that a sustainable manganese perchlorophthalocyanine catalyst, [MnIII(ClPc)], achieves selective, preparative intermolecular allylic C-H amination of 32 cyclic and linear compounds, including ones housing basic amines and competing sites for allylic, ethereal, and benzylic amination. Mechanistic studies support that the high selectivity of [MnIII(ClPc)] may be attributed to its electrophilic, bulky nature and stepwise amination mechanism. Late-stage amination is demonstrated on five distinct classes of natural products, generally with >20:1 site-, regio-, and diastereoselectivity.
- Clark, Joseph R.,Dixon, Charlie F.,Feng, Kaibo,Han, Wei,Ide, Takafumi,Koch, Vanessa,Teng, Dawei,Wendell, Chloe I.,White, M. Christina
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supporting information
p. 14969 - 14975
(2021/10/01)
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- Synthesis of spiro[cycloalkane-pyridazinones] with high Fsp3 character
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Background: Nowadays, in course of the drug design and discovery much attention is paid to the physicochemical parameters of a drug candidate, in addition to their biological activity. Disadvantageous physicochemical parameters can hinder the success of a drug candidate. Objective: Lovering et al. introduced the Fsp3 character as a measure of carbon bond saturation, which is related to the physicochemical paramethers of the drug. The pharmaceutical research focuses on the synthesis of compounds with high Fsp3 character. Method: To improve the physicochemical properties (clogP, solubility, more advantageous ADME profile, etc.) of drug-candidate molecules one possibility is the replacement of all-carbon aromatic systems with bioisoster heteroaromatic moieties, e.g. with one or two nitrogen atom containing systems, such as pyridines and pyridazines, etc. The other option is to increase the Fsp3 character of the drug candidates. Both of these aspects were considered in the design the new spiro[cycloalkanepyridazinones], the synthesis of which is described in the present study. Results: Starting from 2-oxaspiro[4.5]decane-1,3-dione or 2-oxaspiro[4.4]nonane-1,3-dione, the corresponding ketocarboxylic acids were obtained by Friedel-Crafts reaction with anisole or veratrole. The ketocarboxylic acids were treated by hydrazine, methylhydrazine or phenylhydrazine to form the pyridazinone ring. N-Alkylation reaction of the pyridazinones resulted in the formation of further derivatives with high Fsp3 character. Conclusion: A small compound library was obtained incorporating compounds with high Fsp3 characters, which predicts advantageous physico-chemical parameters (LogP, ClogP and TPSA) for potential applications in medicinal chemistry.
- Für, Csilla Sepsey,Riszter, Gergo,Gerencsér, János,Szigetvári, áron,Dékány, Miklós,Hazai, László,Keglevich, Gy?rgy,B?lcskei, Hedvig
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p. 731 - 744
(2020/06/22)
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- Overcoming Selectivity Issues in Reversible Catalysis: A Transfer Hydrocyanation Exhibiting High Kinetic Control
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Reversible catalytic reactions operate under thermodynamic control, and thus, establishing a selective catalytic system poses a considerable challenge. Herein, we report a reversible transfer hydrocyanation protocol that exhibits high selectivity for the thermodynamically less favorable branched isomer. Selectivity is achieved by exploiting the lower barrier for C-CN oxidative addition and reductive elimination at benzylic positions in the absence of a cocatalytic Lewis acid. Through the design of a novel type of HCN donor, a practical, branched-selective, HCN-free transfer hydrocyanation was realized. The synthetically useful resolution of a mixture of branched and linear nitrile isomers was also demonstrated to underline the value of reversible and selective transfer reactions. In a broader context, this work demonstrates that high kinetic selectivity can be achieved in reversible transfer reactions, thus opening new horizons for their synthetic applications.
- Bhawal, Benjamin N.,Ehinger, Christian,Morandi, Bill,Reisenbauer, Julia C.
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supporting information
p. 10914 - 10920
(2020/07/13)
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- Johnson-Corey-Chaykovsky fluorocyclopropanation of double activated alkenes: Scope and limitations
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Johnson-Corey-Chaykovsky fluorocyclopropanation of double activated alkenes utilizing S-monofluoromethyl-S-phenyl-2,3,4,5-tetramethylphenylsulfonium tetrafluoroborate is an efficient approach to obtain a range of monofluorocyclopropane derivatives. So far, fluoromethylsulfonium salts have displayed the broadest scope for direct fluoromethylene transfer. In contrast to more commonly used fluorohalomethanes or freon derivatives, diarylfluoromethylsulfonium salts are bench stable, easy-to use reagents useful for the direct transfer of a fluoromethylene group to alkenes giving access to the challenging products-fluorocyclopropane derivatives. Interplay between the reactivity of the starting materials and stability of the fluorocyclopropanes formed determines the outcome of the process.
- Kazia, Armands,Melngaile, Renate,Mishnev, Anatoly,Veliks, Janis
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supporting information
p. 1384 - 1388
(2020/03/03)
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- Preparation method of 1-cyanocyclohexyl acetonitrile
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The invention provides a method for preparing 1-cyanocyclohexyl acetonitrile by a 'one-pot method', which mainly comprises the following steps: reacting cyclohexanone with alkyl cyanoacetate in the presence of weak base salt and optional acid in a proper organic solvent; after the reaction is completed, adding cyanide, water and a phase transfer catalyst into the reaction system without treatment,and continuing the reaction to obtain 1-cyanocyclohexyl acetonitrile. According to the 1-cyanocyclohexyl acetonitrile obtained by the method, the purity and yield of the product are greatly improved,and the method is low in production cost, simple to operate and suitable for industrial production.
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Paragraph 0009; 0033-0034; 0036-0037; 0039-0040; 0045-0046
(2020/07/08)
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- Distal γ-C(sp3)?H Olefination of Ketone Derivatives and Free Carboxylic Acids
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Reported herein is the distal γ-C(sp3)?H olefination of ketone derivatives and free carboxylic acids. Fine tuning of a previously reported imino-acid directing group and using the ligand combination of a mono-N-protected amino acid (MPAA) and an electron-deficient 2-pyridone were critical for the γ-C(sp3)?H olefination of ketone substrates. In addition, MPAAs enabled the γ-C(sp3)?H olefination of free carboxylic acids to form diverse six-membered lactones. Besides alkyl carboxylic acids, benzylic C(sp3)?H bonds also could be functionalized to form 3,4-dihydroisocoumarin structures in a single step from 2-methyl benzoic acid derivatives. The utility of these protocols was demonstrated in large scale reactions and diversification of the γ-C(sp3)?H olefinated products.
- Fan, Zhoulong,Park, Han Seul,Yu, Jin-Quan,Zhu, Ru-Yi
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supporting information
p. 12853 - 12859
(2020/06/10)
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- Prolinamide functionalized polyacrylonitrile fiber with tunable linker length and surface microenvironment as efficient catalyst for Knoevenagel condensation and related multicomponent tandem reactions
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A series of new prolinamide polyacrylonitrile fiber catalysts with tunable length of alkyl linker and different linker group were prepared by covalent bonding for the first time and well characterized by mechanical strength, FT-IR, XRD, EA, TGA, SEM and water contact angel. The catalytic activities of these fiber catalysts were evaluated in Knoevenagel condensation and one-pot Knoevenagel-Michael multicomponent tandem reactions to synthesize α, β-unsaturated nitrile and 2-amino-4H-chromene derivatives in water. The result show that the suitable linker length attaching amines to fiber matrix as well as the constructed hydrophobic microenvironment by linker group within the surface layers of fiber materials effectively promotes the reactions. In addition, the good swollen capacity of fiber in solvent ensure that the reaction proceed well. Fiber catalyst PANPA?2F modified by prolinamide with a C2 alkyl chain exhibited the best catalytic performance and can be easily recovered and reused for at least ten consecutive cycles without significant loss of catalytic activity and active sites leaching.
- Zhu, Hai,Xu, Gang,Du, Huimin,Zhang, Chenlu,Ma, Ning,Zhang, Wenqin
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p. 217 - 229
(2019/05/16)
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- Amino Acid Amide based Ionic Liquid as an Efficient Organo-Catalyst for Solvent-free Knoevenagel Condensation at Room Temperature
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Abstract: Ionic liquids of amino acid amide were synthesized and used as an efficient catalyst for solvent-free Knoevenagel condensation. Synthesized ionic liquids are an environmentally benign, inexpensive, metal free and plays the dual role of solvent as well as an efficient catalyst for Knoevenagel condensation. A wide range of aliphatic, aromatic and heteroaromatic aldehydes easily undergo condensation with malononitrile and ethyl cyanoacetate. The reaction proceeds at room temperature without using any organic solvent and is very fast with good to excellent yield. Additionally, the catalyst is easily separable and recyclable without loss of activity. Graphic Abstract: [Figure not available: see fulltext.].
- Burate, Pralhad A.,Javle, Balasaheb R.,Desale, Pranjal H.,Kinage, Anil K.
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p. 2368 - 2375
(2019/06/17)
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- Vanadium-Catalyzed Condensation of Ethyl Cyanoacetate with Ketones
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Vanadium compounds and complexes activated by pyridine or morpholine catalyze condensation of ethyl cyanoacetate with ketones and aldehydes leading to alkylidenecyanoacetates in 75–100% yield.
- Khusnutdinov,Shchadneva,Mayakova, Yu. Yu.
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p. 403 - 409
(2018/04/24)
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- Polyoxoniobates as a superior Lewis base efficiently catalyzed Knoevenagel condensation
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The outstanding basicity of negative charged Lindqvist type Polyoxoniobate K7HNb6O19·13H2O (Nb6) have been proved experimentally as well as by theoretical NBO calculations, the results insights high electron density on terminal and bridging oxygen atoms of niobate anion. The most negative Natural Bond Orbital charge (NBO) of oxygen in Nb6 is ?1.001, which is a much more negative value than those reported in other polyoxometalates, that corroborates its high basicity thus likely to be employed as a strong base catalyst. Experimental study suggests that Nb6 can efficiently catalyze Knoevenagel condensation of various carbonyl compounds with active methylene compounds neglecting the steric and electronic effect of aromatic aldehydes under mild conditions. Kinetic test shows that Knoevenagel condensation of benzaldehyde with ethyl cyanoacetate exhibits second-order kinetics in the presence of Nb6 and the calculated activation energy is 43.3 kJ mol?1. Meanwhile, a proper mechanism according to the NBO study speculates that the most negative charged terminal oxygens in Nb6 would be pivotal in this transformation.
- Xu, Qiaofei,Niu, Yanjun,Wang, Guan,Li, Yingguang,Zhao, Yuan,Singh, Vikram,Niu, Jingyang,Wang, Jingping
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- Carbon chain shape selectivity by the mouse olfactory receptor OR-I7
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The rodent OR-I7 is an olfactory receptor exemplar activated by aliphatic aldehydes such as octanal. Normal alkanals shorter than heptanal bind OR-I7 without activating it and hence function as antagonists in vitro. We report a series of aldehydes designed to probe the structural requirements for aliphatic ligand chains too short to meet the minimum approximate 6.9 ? length requirement for receptor activation. Experiments using recombinant mouse OR-I7 expressed in heterologous cells show that in the context of short aldehyde antagonists, OR-I7 prefers binding aliphatic chains without branches, though a single methyl on carbon-3 is permitted. The receptor can accommodate a surprisingly large number of carbons (e.g. ten in adamantyl) as long as the carbons are part of a conformationally constrained ring system. A rhodopsin-based homology model of mouse OR-I7 docked with the new antagonists suggests that small alkyl branches on the alkyl chain sterically interfere with the hydrophobic residues lining the binding site, but branch carbons can be accommodated when tied back into a compact ring system like the adamantyl and bicyclo[2.2.2]octyl systems.
- Liu, Min Ting,Ho, Jianghai,Liu, Jason Karl,Purakait, Radhanath,Morzan, Uriel N.,Ahmed, Lucky,Batista, Victor S.,Matsunami, Hiroaki,Ryan, Kevin
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supporting information
p. 2541 - 2548
(2018/04/12)
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- Amide-Group-Directed Protonolysis of Cyclopropane: An Approach to 2,2-Disubstituted Pyrrolidines
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Regioselective protonolytic C-C bond cleavage of acylated aminomethyl cyclopropanes can be achieved using trifluoroacetic acid. The intermediate tertiary carbenium ion undergoes an intramolecular amination to give 2,2-substituted pyrrolidines. The strength of the acid and the amine substituent are important factors to achieve high regioselectivity, suggesting intramolecular proton transfer from the protonated amide function. Preliminary mechanistic studies revealed that cyclopropane cleavage proceeds with retention of configuration at the carbon to which the proton is attached. This observation is consistent with the "edge" protonation trajectory of the C-C bond.
- Skvorcova, Marija,Jirgensons, Aigars
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supporting information
p. 2478 - 2481
(2017/05/24)
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- Tetrahydro benzothiophene derivative and application thereof to preparation of glycogen synthase kinase 3 beta inhibitor
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The invention discloses a tetrahydro benzothiophene derivative and the application thereof to the preparation of a glycogen synthase kinase 3 beta inhibitor. The tetrahydro benzothiophene derivative, pharmaceutically acceptable salt, optical active body or racemate thereof has a chemical structure as shown in a formula I. Experiments show that the compound has good GSK-3 beta inhibitory activity. In addition, the invention further provides a method for preparing a tetrahydro benzothiophene compound. The method is short in synthesis route, simple in preparation process and easy to operate, and can meet the requirements of large-scale industrial production.
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Paragraph 0071; 0072; 0073
(2017/10/25)
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- NOVEL SIGMA-2 RECEPTOR BINDERS AND THEIR METHOD OF USE
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Pharmaceutical compositions of the invention comprise functionalized lactone derivatives having a disease-modifying action in the treatment of diseases associated with dysregulation of sigma-2 receptor activity.
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Paragraph 0293
(2016/11/28)
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- COMPOUNDS USEFUL AS MODULATORS OF TRPM8
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The present invention includes compounds useful as modulators of TRPM8, such as compounds of Formulae (Ia), (Ib) and (Ic), and the subgenus and species thereof; personal products containing those compounds; and the use of those compounds and the personal products, particularly the use of increasing or inducing chemesthetic sensations, such as cooling or cold sensations.
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Paragraph 0452
(2016/03/29)
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- Base-free Knoevenagel condensation catalyzed by copper metal surfaces
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For the first time Knoevenagel condensation has been catalyzed by elemental copper with unexpected activity and excellent isolated yields. Inexpensive, widely available copper powder was used to catalyze the condensation of cyanoacetate and benzaldehyde under mild conditions. To ensure general applicability, a wide variety of different substrates was successfully reacted.
- Schneider,Zeltner,Kr?nzlin,Grass,Stark
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supporting information
p. 10695 - 10698
(2015/06/30)
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- Aqueous DABCO, an efficient medium for rapid organocatalyzed Knoevenagel condensation and the Gewald reaction
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In the presence of water and 1,4-diazabicyclo[2.2.2]octane, several aldehydes and cyclic ketones underwent efficient Knoevenagel condensation with malononitrile and ethyl cyanoacetate to produce the respective α.β-unsaturated systems within fairly short time periods. As a result, high yields of conjugated products were easily obtained. Products could be engaged in a Gewald reaction, either stepwise or in situ, to produce efficiently their respective 2-aminothiophenes within 4-7 h. TUeBITAK.
- Abaee, Mohammad Saeed,Cheraghi, Somayeh
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p. 650 - 660
(2014/07/07)
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- NOVEL 5-HYDROXYTRYPTAMINE RECEPTOR 7 ACTIVITY MODULATORS AND THEIR METHOD OF USE
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Pharmaceiiticai compositions of the invention comprise functionalized lactone derivatives having a disease-modifying action in the treatment of diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity.
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Paragraph 0246
(2014/10/18)
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- A simple, efficient and green procedure for Knoevenagel condensation in water or under solvent-free conditions
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1,4-Diazabicyclo[2.2.2]octane was used as an efficient catalyst in the Knoevenagel condensation reaction of various kinds of aromatic/aliphatic/ heterocyclic/α,β-unsaturated aldehydes and ketones with active methylene compounds. This is a convenient and rapid method for Knoevenagel condensation, which affords the corresponding substituted electrophilic alkenes in excellent yields. The reaction condition is mild and the method is operationally simple. The products, only E-isomers were detected, did not need to be purified. The use of water as the reaction mediummakes the process environmentally benign. The catalysts can be recycled six times without activity loss.
- Yu, Ya-Qin,Wang, Zhong-Liang
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p. 288 - 292
(2013/07/27)
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- Polystyrene-immobilized DABCO as a highly efficient and recyclable organocatalyst for the Knoevenagel condensation reaction
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Polystyrene-immobilized DABCO was used for the first time as a basic organocatalyst for carbon-carbon bond formation reactions. The supported catalyst could be used as a reusable catalyst in the Knoevenagel condensation of a wide range of aromatic/heterocyclic/α,β-unsaturated aldehydes and ketones with active methylene compounds. The reaction conditions are mild and the method is operationally simple. The reactions proceed in a short time period and with 100% selectivity. The catalyst could be easily separated from the reaction by filtration and recycled ten times without activity loss. Based on the catalyst, a continuous flow process was also developed.
- Xu, Da-Zhen,Shi, Sen,Wang, Yongmei
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p. 23075 - 23079
(2013/11/19)
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- Novel inhibitors of bacterial virulence: Development of 5,6-dihydrobenzo[h]quinazolin-4(3H)-ones for the inhibition of group A streptococcal streptokinase expression
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Resistance to antibiotics is an increasingly dire threat to human health that warrants the development of new modes of treating infection. We recently identified 1 (CCG-2979) as an inhibitor of the expression of streptokinase, a critical virulence factor in Group A Streptococcus that endows blood-borne bacteria with fibrinolytic capabilities. In this report, we describe the synthesis and biological evaluation of a series of novel 5,6-dihydrobenzo[h] quinazolin-4(3H)-one analogs of 1 undertaken with the goal of improving the modest potency of the lead. In addition to achieving an over 35-fold increase in potency, we identified structural modifications that improve the solubility and metabolic stability of the scaffold. The efficacy of two new compounds 12c (CCG-203592) and 12k (CCG-205363) against biofilm formation in Staphylococcus aureus represents a promising additional mode of action for this novel class of compounds.
- Yestrepsky, Bryan D.,Xu, Yuanxi,Breen, Meghan E.,Li, Xiaoqin,Rajeswaran, Walajapet G.,Ryu, Jenny G.,Sorenson, Roderick J.,Tsume, Yasuhiro,Wilson, Michael W.,Zhang, Wenpeng,Sun, Duxin,Sun, Hongmin,Larsen, Scott D.
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p. 1880 - 1897
(2013/05/08)
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- Activity of amino-functionalised mesoporous solid bases in microwave-assisted condensation reactions
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Aminopropylated functionalised hexagonal mesoporous silicas (HMS) and SBA-15 materials with different amino-loadings (5-30 wt.% NH2)were synthesized, characterised and their catalytic activitieswere subsequently investigated in the microwave-assisted Knoevenagel condensation of cyclohexanone and ethyl cyanoacetate as well as in the Michael reaction between 2-cyclohexen-1-one and nitromethane. The effects of the quantity of the catalyst in the reaction as well as a variety of microwave parameters including the power, temperature and time of microwave irradiation were optimised. High activities and selectivities to the condensation product could be achieved at short times of microwave irradiation for both base-catalysed processes. The low loaded HMS-5%NH2 and higher loaded SBA-15-20%NH2 were found to give the best activities in the reactions. This observation seems to be related to the significant deterioration observed in textural properties of HMS materials at amino-loadings larger than 10%.
- Pineda, Antonio,Balu, Alina Mariana,Campelo, Juan Manuel,Romero, Antonio Angel,Luque, Rafael
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- Synthesis of a thermostable polymer-supported strongly basic catalyst and its catalytic activity
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A novel strongly basic polymer-supported catalyst with guanidine groups has been synthesized and its thermal stability has been investigated. To obtain a thermally stable, cross-linked structure, guanidine groups bound to a polystyrene matrix were allowed to react in a nucleophilic manner with p-xylylene dichloride. Compared with the conventional strongly basic anion-exchange resin 201, it possesses higher thermal stability when placed in deionized water at 95°C for 60h. This was confirmed by thermogravimetric analysis. The excellent thermal stability can be attributed to the unique structure of guanidine and the cross-linking connection mode between this base and the polymeric matrix. The obtained resin was found to efficiently catalyze Knoevenagel condensation reactions with remarkably high yields. Furthermore, the catalytic efficiency of the resin was found to remain unaffected for seven cycles, whereas that of 201 resin was reduced by 25% owing to degradation of the strongly basic groups.
- Zan, Huining,Hou, Zhiai,Shi, Rongfu,Wang, Chunhong
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p. 913 - 920
(2013/09/12)
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- A highly negatively charged γ-Keggin germanodecatungstate efficient for Knoevenagel condensation
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A tetra-n-butylammonium (TBA) salt of a γ-Keggin -6-charged germanodecatungstate, [γ-H2GeW10O36] 6- (I), could act as an efficient homogeneous catalyst for Knoevenagel condensation of active methylene compounds with carbonyl compounds.
- Sugahara, Kosei,Kimura, Toshihiro,Kamata, Keigo,Yamaguchi, Kazuya,Mizuno, Noritaka
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supporting information
p. 8422 - 8424
(2012/10/29)
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- Novel basic ionic liquid based on alkylammonium as efficient catalyst for Knoevenagel reaction
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The typical Knoevenagel condensation was carried out smoothly in the presence of a basic ionic liquid of N,N,N′,N′-tetramethyl-N′- hexyl-ethylenediammonium tetrafluoroborate ([TMHEDA]BF4), and 99% of yield was obtained using ethyl cyanoacetate and benzaldehyde as substrates at 60 °C for 1 h. Four reuses of the ionic liquid without dramatic decrease in catalytic activity for Knoevenagel condensation demonstrated the good stability and operability of the ionic liquid. Moreover, the typical nucleophilic addition reactions were also accomplished by the same ionic liquid to check its feasibility. The dual function of the basic ionic liquid both as solvent and catalyst, combined with simple product separation and recycling, is expected to contribute to the development of a green and environmentally friendly strategy. Copyright Taylor & Francis Group, LLC.
- Zhou, Shuai,Liu, Lu,Wang, Bo,Ma, Mingguo,Xu, Feng,Sun, Runcang
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experimental part
p. 1384 - 1391
(2012/04/10)
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- NOVEL CARBOXAMIDE DERIVATIVES AS HIV INHIBITORS
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The present invention relates to carboxamide derivatives of Formula (I), where B1, B2, X, L, n, R, R1, R2, Z1, Z2, Rx and Ry are as defined in the claims, as compounds and compositions for inhibiting Human Immunodeficiency Virus (HIV) and process for making the compounds.
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Page/Page column 33
(2011/06/19)
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- Improved synthesis of γ-lactones from cyclopropyl cyanoesters
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Cyclopropyl cyanoesters 2 were reliably converted to c-lactones 4 on treatment with aqueous sulfuric acid. The cyanoesters could be easily prepared from ketones or aldehydes in two steps, making this process particularly attractive from an efficiency standpoint. Copyright
- Patel, Nandini C.,Schwarz, Jacob B.,Islam, Khondaker,Miller, Whitney,Tran, Tuan P.,Wei, Yunjing
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experimental part
p. 2209 - 2215
(2011/07/07)
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- Silica grafted polyethylenimine as heterogeneous catalyst for condensation reactions
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Primary amine groups were attached to a silica surface by using α,ω-diamines derivatives and (3-glycidyloxypropyl)-trimethoxysilane activation. The same activation was used to graft polyethylenimine, which also contains secondary and tertiary amine groups. These silica aminated structures were tested as heterogeneous catalysts in nitroaldol condensation with nitromethane, the derivative with the polyethylenimine moiety being the more active catalyst. This catalyst also showed efficiency in the Knoevenagel condensation of benzaldehydes with ethyl cyanoacetate under very mild reaction conditions and showed much the same efficiency when used in consecutive reaction runs. A reaction mechanism with participation of the several amine groups of the catalysts is discussed.
- Ribeiro, Sonia M.,Serra, Arménio. C.,Gonsalves, A.M. D'A. Rocha
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experimental part
p. 126 - 133
(2012/02/01)
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- Synthesis and anxiolytic activity of some novel 5-oxo-1, 4-oxazepine derivatives
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A novel synthetic procedure for a series of 4-Aryl-3-phenyl-6,7,8,9- tetrahydro-benzothieno[3,2- f][l,4]oxazepin-5(4H)-one 8a-s derivatives had been described. Six compounds 8a,b,h,j,m,s were selected and submitted to pharmacological evaluation for anxiolytic activity in the open field test. All the test compounds except 8b significantly reduced the exploratory activity and the emotionality of the rats in the open-field. These inhibitory results are in agreement with the effect of reference standard chlorpromazine as a tranquillizer and anxiolytic in the same conditions.
- AbdelFattah, Bothiana A.,Khalifa, Maha M.A.,El-Sehrawi, Hend,Fayed, Eman,Bayoumi, Ashraf,Said, Makarem
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scheme or table
p. 330 - 338
(2012/05/05)
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- Chloride ion pairs as catalysts for the alkylation of aldehydes and ketones with C-H acidic compounds
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Chloride anions associated with various soft cations (like tetraalkyl ammoniums, alkyl imidazoliums or pyridiniums) were shown to be able to promote the alkylation of carbonyl derivatives with acidic compounds, as exemplified on Knoevenagel and aldol condensations under relatively mild conditions. This activity was attributed to an enhanced nucleophilicity of the chlorine anion, originating from a softness/hardness mismatch between the anion and the cation.
- Carrignon, Camille,Makowski, Philippe,Antonietti, Markus,Goettmann, Frédéric
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supporting information; experimental part
p. 4833 - 4837
(2009/10/26)
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- Facile regioselective green synthesis of triazolo [4,3-a] pyrimidines in aqueous medium
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Regioselectivity is investigated in multi-component reaction of amino triazole, carbonyl compounds and α-cyano esters derivative and exclusive synthesis of triazolopyrimidines is developed in aqueous medium in excellent yields in shorter period using microwaves or ultrasonic waves. Path and mechanism of the reaction has also been discussed. The operational simplicity, environmental friendly conditions, regioselective formation of target product, high yield in significantly very short reaction time, are major benefits.
- Dandia, Anshu,Singh, Ruby,Singh, Dharmendra,Arya, Kapil
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scheme or table
p. 100 - 105
(2010/04/23)
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- First example of organocatalysis by polystyrene-supported PAMAM dendrimers: Highly efficient and reusable catalyst for knoevenagel condensations
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This paper describes the first use of polystyrene-supported poly(amidoamine) (PAMAM) dendrimers as heterogeneous basic organocatalysts for carbon-carbon bond formation. Polystyrene-supported PAMAM dendrimers of first, second and third generations have been used as reusable base catalysts in Knoevenagel condensations of carbonyl compounds with active methylene compounds. The reactions proceed in short periods of time and with 100% selectivity. This novel catalyst eliminates the use of aromatic and halogenated solvents, as well as complex purification processes. The catalysts can be recycled ten times. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Krishnan, G. Rajesh,Sreekumar, Krishnapillai
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supporting information; experimental part
p. 4763 - 4768
(2009/05/07)
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- Development of pharmaceutical drugs, drug intermediates and ingredients by using direct organo-click reactions
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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, 2008.
- Ramachary, Dhevalapally B.,Kishor, Mamillapalli,Reddy, Y. Vijayendar
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body text
p. 975 - 993
(2009/04/11)
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- Nitrilase-catalyzed selective hydrolysis of dinitriles and green access to the cyanocarboxylic acids of pharmaceutical importance
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To further explore its synthetic applications, the nitrilase bll6402 from Bradyrhizobium japonicum strain USDA110 has been examined toward the hydrolysis of various dinitriles. It has been found that nitrilase bll6402 effectively hydrolyzed α,ω-dinitriles to ω-cyanocarboxylic acids, and the selectivity was independent of the substrate chain length. This feature is distinct from all the known nitrilases of various sources. Nitrilase bll6402 was thus applied to the synthesis of 1-cyanocycloalkaneacetic acids, the useful precursors for the synthesis of gabapentin and its analogues.
- Zhu, Dunming,Mukherjee, Chandrani,Biehl, Edward R.,Hua, Ling
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p. 1667 - 1670
(2008/02/11)
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- Carboxylate bioisosteres of gabapentin
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A series of carboxylate bioisosteres of structures related to gabapentin 1 have been prepared. When the carboxylate was replaced by a tetrazole, this group was recognized by the α2-δ protein. Further characterization of α2-δ binding compounds 14a and 14b revealed a similar pattern of functional in vitro and in vivo activity to gabapentin 1.
- Burgos-Lepley, Carmen E.,Thompson, Lisa R.,Kneen, Clare O.,Osborne, Simon A.,Bryans, Justin S.,Capiris, Thomas,Suman-Chauhan, Nirmala,Dooley, David J.,Donovan, Cindy M.,Field, Mark J.,Vartanian, Mark G.,Kinsora, Jack J.,Lotarski, Susan M.,El-Kattan, Ayman,Walters, Karen,Cherukury, Madhu,Taylor, Charles P.,Wustrow, David J.,Schwarz, Jacob B.
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p. 2333 - 2336
(2007/10/03)
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- HEPATITIS C INHIBITOR DIPEPTIDE ANALOGS
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The present invention relates to compounds of formula (I): wherein R1, R2, R4, n and m are as defined herein and R3 is selected from: (i) -C(O)OR31 wherein R31 is (C1-6)alkyl or aryl, wherein the (C1-6)alkyl is optionally substituted with one to three halogen substituents; (ii) -C(O)NR32R33, wherein R32 and R33 are each independently selected form H, (C1-6)alkyl, and Het; (iii) -SOvR34, wherein v is 1 or 2 and R34 is selected from: (C1-6)alkyl, aryl, Het, and NR32R33 wherein R32 and R33 are as defined above; and (iv) -CO(O)-R35, wherein R35 is selected from (C1-8)alkyl, (C3-7)cycloalkyl-(C1-4)alkyl, aryl, aryl-(C1-6)alkyl, Het and Het-(C1-6)alkyl, each of which are optionally substituted with one or more substituents each independently selected from halo, (C1-6)alkyl, (C3-7)cycloalkyl, aryl, Het, hydroxyl, -O-(C1-6)alkyl, -S-(C1-6)alkyl, -SO-(C1-6)alkyl, -SO2-(C1-6)alkyl, -O-aryl, -S-aryl, -SO-aryl and -SO2-aryl, wherein the aryl portion of the -O-aryl, -S-aryl, -SO-aryl and -SO2-aryl are each optionally substituted with one to five halo substituents. The present invention further relates to pharmaceutical compositions containing the compounds of formula (I) and methods for using these analogs in the treatment of HCV infection.
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Page/Page column 83
(2008/06/13)
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- Environmentally friendly one-pot synthesis of α-alkylated nitriles using hydrotalcite-supported metal species as multifunctional solid catalysts
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A ruthenium-grafted hydrotalcite (Ru/HT) and hydrotalcite-supported palladium nanoparticles (Pdnano/ HT) are easily prepared by treating basic layered double hydroxide, hydrotalcite (HT, Mg6Al 2(OH)16CO3) with aqueous RuCl 3·n H2O and K2[PdCl4] solutions, respectively, using surface impregnation methods. Analysis by means of X-ray diffraction, and energydispersive X-ray, electron paramagnetic resonance, and X-ray absorption fine structure spectroscopies proves that a monomeric RuIV species is grafted onto the surface of the HT. Meanwhile, after reduction of a surface-isolated PdII species, highly dispersed Pd nanoclusters with a mean diameter of about 70 A is observed on the Pdnano/HT surface by transmission electron microscopy analysis. These hydrotalcite-supported metal catalysts can effectively promote α-alkylation reactions of various nitriles with primary alcohols or carbonyl compounds through tandem reactions consisting of metal-catalyzed oxidation and reduction, and an aldol reaction promoted by the base sites of the HT. In these catalytic α-alkylations, homogeneous bases are unnecessary and the only by-product is water. Additionally, these catalyst systems are applicable to one-pot syntheses of glutaronitrile derivatives.
- Motokura, Ken,Fujita, Noriaki,Mori, Kohsuke,Mizugaki, Tomoo,Ebitani, Kohki,Jitsukawa, Koichiro,Kaneda, Kiyotomi
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p. 8228 - 8239
(2007/10/03)
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- Development of drug intermediates by using direct organocatalytic multi-component reactions
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Development of drug intermediates by using direct amino acid organocatalytic multi-component reaction was investigated. Hydrogenations of double-bond containing compounds including carbonyls, imines and olefins are important for living organisms as well as for the industrial production of chemicals. Amino acid catalysis has emerged as a powerful green synthetic tool for the development of both achiral and chiral catalysis of condensations and cycloadditions and the 1,2- and 1,4-additions of enals, enones and ketones including electrophiles. It was found that the amino acid proline 4a catalyzes the Knoevenagel condenstion of cyclohexanone 1a with the CH-acid ethyl cyanoacetate 2a to furnish the active olefin 9aa. This simple and environmentally friendly approach can be used to construct highly substituted hydrogenated products in a regioselective fashion with good yields.
- Ramachary, Dhevalapally B.,Kishor,Reddy, G. Babul
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p. 1641 - 1646
(2008/02/03)
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- Use of a solid hydrotalcite structure incorporating fluorides for basic catalysis of michael or knoevenagel reactions
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The invention concerns the use of a solid basic catalyst comprising a hydrotalcite structure wherein part at least of the compensating anions are fluoride anions F? for producing Knoevenagel of Michael condensation reactions. The invention also concerns novel solid basic catalysts comprising a hydrotalcite structure characterised by a Mg/Al molar ratio ranging between 2.5 and 3.8 wherein at least part of the compensating anions are fluoride anions F?, and methods for preparing said novel catalysts.
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Page/Page column 5
(2008/06/13)
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- Organic Reactions in Ionic Liquids: Knoevenagel Condensation Catalyzed by Ethylenediammonium Diacetate
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The moisture and air stable ionic liquids 1-butyl-3-methylimidazonium tetrafluoroborate [bmim]BF4 and 1-butyl-3-methylimidazonium hexafluorophosphate [bmim]PF6 were used as 'green' recycle alternatives to volatile organic solvents (VOCs) for ethylenediammonium diacetate (EDDA) catalyzed Knoevenagel condensation between aldehydes or ketones with active methylene compounds. Both aldehydes and ketones gave satisfactory results. The ionic liquids containing catalyst EDDA were recycled several times with no decrease in yields and reaction rates. In the case of 2-hydroxybenzaldehyde, the reactions led to the formation of 3-substituted coumarins under standard reaction conditions.
- Su, Ce,Chen, Zhen-Chu,Zheng, Qin-Guo
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p. 555 - 559
(2007/10/03)
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- Steric effects in high pressure Knoevenagel reactions
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The pressure effect in Knoevenagel condensations involving ketones and ethyl cyanoacetate is studied. The reactions are diversely affected. For cyclic ketones there is a small effect on the reaction yield. However, in the case of acyclic ketones, the sensitivity of the reaction to pressure increases with increasing steric congestion of the ketone. Such a result highlights the synthetic utility of high pressure for the preparation of hindered functionalized alkenes.
- Jenner, Gérard
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p. 243 - 245
(2007/10/03)
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- High catalytic activity of as-synthesized, ordered porous silicate-quaternary ammonium composite for Knoevenagel condensation
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The Knoevenagel condensation of carbonyl compounds with active methylene compounds catalyzed by as-synthesized, ordered porous silicate-quaternary ammonium composite materials gave corresponding α,β-unsaturated esters in high yields under very mild liquid phase conditions.
- Kubota, Yoshihiro,Nishizaki, Yusuke,Sugi, Yoshihiro
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p. 998 - 999
(2007/10/03)
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- Aldol and Knoevenagel condensations catalysed by modified Mg-Al hydrotalcite: a solid base as catalyst useful in synthetic organic chemistry
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Aldol and Knoevenagel condensations were performed with suitably activated Mg-Al hydrotalcite as catalyst in quantitative yields in the liquid phase under mild reaction conditions at a faster rate for the first time.
- Kantam, M. Lakshmi,Choudary, B. M.,Reddy, Ch. Venkat,Rao, K. Koteswara,Figueras, F.
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p. 1033 - 1034
(2007/10/03)
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- Aminopropylated MCMs as base catalysts: A comparison with aminopropylated silica
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Aminopropyl-functionalised MCMs, prepared via a one-pot method, are found to be effective base catalysts for the Knoevenagel reaction, with significant improvements in terms of turnover number and solvent dependence to the ostensibly similar aminopropylsilica.
- Macquarrie, Duncan J.,Jackson, Dominic B.
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p. 1781 - 1782
(2007/10/03)
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- Ruthenium-catalyzed aldol and Michael reactions of nitriles. Carbon-carbon bond formation by α-C-H activation of nitriles
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The ruthenium(II)-catalyzed reaction of nitriles with carbonyl compounds proceeds highly efficiently under neutral and mild conditions to give α,β-unsaturated nitriles. Under similar reaction conditions, nitriles react with olefins bearing electron-withdrawing groups to give the corresponding Michael adducts. The efficiency of the reaction is illustrated by the selective additions to α,β-unsaturated aldehydes and acetylenes bearing electron-withdrawing groups, which are difficult to perform using conventional bases. Chemoselective aldol and Michael reactions of nitriles can be performed in the presence of other active methylene compounds. Tandem Michael and Michael-aldol condensations of nitriles 30 can be performed with high diastereoselectivity. These reactions can be rationalized by assuming oxidative addition of ruthenium(0) to the α-C-H bond of nitriles and subsequent insertions to carbonyl compounds or olefins. As the key intermediates and active catalysts hydrido(N-bonded enolato)ruthenium(II) complexes, mer-RuH(NCCHCO2R)(NCCH2CO2R)(PPh3)3 (R = Me (41a), Et (41b), n-Bu (41c)) have been isolated upon treatment of RuH2(PPh3)4 (3) or RuH(C2H4)(PPh3)2(PPh2C6H4) (4) with alkyl cyanoacetates. Kinetic study of the catalytic aldol reaction of ethyl cyanoacetate with benzaldehyde indicates that the rate-determining step is the reaction of enolato complex 41 with aldehydes.
- Murahashi, Shun-Ichi,Naota, Takeshi,Taki, Hiroshi,Mizuno, Masahiko,Takaya, Hikaru,Komiya, Sanshiro,Mizuho, Yuji,Oyasato, Naohiko,Hiraoka, Makiko,Hirano, Masafumi,Fukuoka, Atsushi
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p. 12436 - 12451
(2007/10/03)
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- Synthesis and local anaesthetic activity of some 2-aminoacetylamino-3-carbetoxy/anilido-4,5,6,7-tetrahydro-benzothiophenes
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Twenty new 2-substituted aminoacetylamino-3-carbetoxy/anilido-4,5,6,7-tetrahydrobenzothiophenes (4a-4t) have been synthesised with a view to studying the effect of structural modification of carticaine (B) on the local anaesthetic activity and evaluated by Sollman's method as well as Bulbring and Wajda method using lignocaine hydrochloride as a standard.All the tested compounds show moderate to good activity and 4a has been found to be the most active drug comparable to the standard.
- Gadad, A K,Kumar, Hemant,Shishoo, C J,Khazi, I M,Mahajanshetti, C S
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p. 298 - 301
(2007/10/02)
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- Transition metal polyhydrides-catalyzed addition of activated nitriles to aldehydes and ketones via Knoevenagel condensation
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Transition metal polyhydrides and dihydrogen complexes catalyze Knoevenagel addition of cyanoacetate to aldehydes and ketones under neutral and mild conditions, the adducts undergo dehydration to give substituted (E)-2-cyano-α,β-unsaturated esters exclusively.
- Lin, Yingrui,Zhu, Xianchao,Xiang, Min
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p. 215 - 218
(2007/10/02)
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- Acid-base catalysts derived from weakly acidic ion exchange resin: Efficiency in the Knoevenagel condensation
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Weakly acidic cation-exchange resins in H+ form, partially neutralized with H2N(CH2)(n)N+Me3 OH- (n = 2-5), have been shown to catalyze the Knoevenagel condensation. The efficiency of catalysis depends on the aminoalkyl chain length and extent of neutralization.
- Saito,Goto,Honda,Fujii
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p. 7535 - 7538
(2007/10/02)
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