- Dynamics in Catalytic Asymmetric Diastereoconvergent (3 + 2) Cycloadditions with Isomerizable Nitrones and α-Keto Ester Enolates
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Reaction design in asymmetric catalysis has traditionally been predicated on a structurally robust scaffold in both substrates and catalysts, to reduce the number of possible diastereomeric transition states. Herein, we present the stereochemical dynamics in the Ni(II)-catalyzed diastereoconvergent (3 + 2) cycloadditions of isomerizable nitrile-conjugated nitrones with α-keto ester enolates. Even in the presence of multiple equilibrating species, the catalytic protocol displays a wide substrate scope to access a range of CN-containing building blocks bearing adjacent stereocenters with high enantio- and diastereoselectivities. Our computational investigations suggest that the enantioselectivity is governed in the deprotonation process to form (Z)-Ni-enolates, while the unique syn addition is mainly controlled by weak noncovalent bonding interactions between the nitrone and ligand.
- Adachi, Masaya,Akakabe, Mai,Ezawa, Tetsuya,Hashizume, Daisuke,Koshino, Hiroyuki,Sodeoka, Mikiko,Sohtome, Yoshihiro
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supporting information
p. 9094 - 9104
(2021/07/01)
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- Iron-catalyzed reductive strecker reaction
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Strecker reaction is widely applied for the synthesis of amino acids from aldehydes, amines and cyanides. Herein, we report the FeI2-catalyzed reductive Strecker type reaction of formamides instead of aldehydes to produce amino acetonitriles. The challenging capture of carbinolamine intermediates by CN? was achieved via Fe catalysis. This approach afforded better yields than the use of Ir- or Rh-catalysts. The application ability of this methodology is demonstrated by 1) one-pot construction of (13C labeled) complex molecules from CO2 via amino acetonitrile intermediates and 2) convenient production of homologated carboxylic acids from aldehydes.
- Yan, Fachao,Huang, Zijun,Du, Chen-Xia,Bai, Jian-Fei,Li, Yuehui
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p. 188 - 194
(2021/02/03)
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- Nano cobalt-copper ferrite catalyzed regioselective α-C(sp3)–H cyanation of amines: Secondary, tertiary, and drug molecules
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Oxidative cyanation of sp3C–H bonds at the α position of amines was achieved using CoCuFe2O4 as a catalyst and NaCN as an inexpensive cyanide source at room temperature. CoCuFe2O4 was found to be an active catalyst for Csp [3]-Csp coupling, efficiently delivering valuable α-aminonitriles from tertiary/secondary amines in good yields. The corresponding products were obtained with high selectivity toward α position. In addition, functional group tolerance offered the opportunity for application in late-stage functionalization of biologically active molecules. This transformation proceeds convenient on a gram-scale, and the catalyst can be reused for several runs with consistent catalytic activity.
- Heidarian, Mahdi,Moghaddam, Firouz Matloubi,Pourkaveh, Raheleh
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- Covalently hooked EOSIN-Y in a Zr(IV) framework as visible-light mediated, heterogeneous photocatalyst for efficient C–H functionalization of tertiary amines
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Herein, we report the synthesis of a novel heterogeneous photo-catalyst by utilizing post-synthetic modification of an amine functionalized Zr(IV) metal-organic framework (UiO-66-NH2) through covalent hooking of EOSIN-Y via dehydrating coupling. The characterization of the catalyst was accomplished by FT-IR, XRD, BET surface analysis, TGA, as well as TEM, SEM, XPS, DRS-UV–visible, and NMR spectroscopy, confirming successful covalent linking of EOSIN-Y with the pendent –NH2 functionality in the framework. That post-modified EY@UiO-66-NH2 acts as simple and green visible light mediated photo-catalyst for the C–H activation of tertiary amines with excellent yields. Importantly, the activity of dye incorporated heterogeneous photo-catalyst is found superior to that for the homogeneous photo-catalyst EOSIN-Y. Thus, separation difficulty of homogeneous catalysis, as well as the environmental adverse effects of toxic EOSIN-Y can be excluded by developing such photo-catalyst. Moreover, EY@UiO-66-NH2 catalyst could be consistently recycled up to 10 cycles, without any significant loss in activity. Based on literature report and experimental findings, we also propose a plausible mechanism for the reaction.
- Kumar, Gaurav,Solanki, Pratik,Nazish, Mohd,Neogi, Subhadip,Kureshy, Rukhsana I.,Khan, Noor-ul H.
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p. 298 - 304
(2019/02/26)
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- A process for preparing aniline base second grade nitrile system and method
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The invention relates to a method for preparing n-system and method. First, the invention provides an improved pipe-type continuous reaction system, the system through the flow or mass of material entering the system of the shunt to measure to control the material reaction, and the introduction of a new feeding mode and take with a mixing element of the reactor, so that the system can enhance the mass transfer of the reaction raw materials, the reaction efficiency is improved. In addition, the invention also provides a method for preparing n-method, the method utilizing the above-mentioned reaction system to realize, this method can reduce the hydroxy acetonitrile to aniline disubstituted formation of impurities, can also reduce the hydroxy acetonitrile in the alkaline catalyst under the influence of the polymerization, the product quality is improved and the reaction yield.
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Paragraph 0043-0046
(2019/05/28)
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- Decarboxylative Cyanation of Aliphatic Carboxylic Acids via Visible-Light Flavin Photocatalysis
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An operationally simple method is disclosed for the decarboxylative cyanation of aliphatic carboxylic acids at room temperature. Riboflavin tetraacetate, which is an inexpensive organic photocatalyst, promotes the oxidation of carboxylic acids upon visible-light activation. After decarboxylation, the generated radicals are trapped by TsCN, yielding the desired nitriles without any further additive, in a redox-neutral process. Importantly, this protocol can be adapted to flow conditions.
- Ramirez, Nieves P.,K?nig, Burkhard,Gonzalez-Gomez, Jose C.
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supporting information
(2019/03/08)
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- Design and Synthesis of Iminosydnones for Fast Click and Release Reactions with Cycloalkynes
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Emerging applications in the field of chemical biology are currently limited by the lack of bioorthogonal reactions allowing both removal and linkage of chemical entities on complex biomolecules. We recently discovered a novel reaction between iminosydnones and strained alkynes leading to two products resulting from ligation and fragmentation of iminosydnones under physiological conditions. We now report the synthesis of a panel of substituted iminosydnones and the structure reactivity relationship between these compounds and strained alkyne partners. This study identified the most relevant substituents, which allow to increase the rate of the transformation and to develop a bifunctional cleavable linker with improved kinetics.
- Riomet, Margaux,Decuypere, Elodie,Porte, Karine,Bernard, Sabrina,Plougastel, Lucie,Kolodych, Sergii,Audisio, Davide,Taran, Frédéric
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supporting information
p. 8535 - 8541
(2018/05/30)
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- A aniline acetate preparation method
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The invention discloses an anilino-acetate preparation method, which comprises the steps of synthesis of n-phenylglycinenitrile, separation of n-phenylglycinenitrile, recovery of hydroxy acetonitrile and preparation of anilino-acetate. The preparation technology has the advantages of economy and environmental protection, hydroxy acetonitrile and aniline consumption can be reduced, waste water generation amount is reduced, flow is simplified, and product quality is increased.
- -
-
Paragraph 0026; 0027
(2017/08/26)
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- Bioorthogonal Click and Release Reaction of Iminosydnones with Cycloalkynes
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We report the discovery of a new bioorthogonal click-and-release reaction involving iminosydnones and strained alkynes. This transformation leads to two products resulting from the ligation and fragmentation of iminosydnones under physiological conditions. Optimized iminosydnones were successfully used to design innovative cleavable linkers for protein modification, thus opening up new areas in the fields of drug release and target-fishing applications. This click-and-release technology offers the possibility of exchanging tags on proteins for functionalized cyclooctynes under mild and bioorthogonal conditions.
- Bernard, Sabrina,Audisio, Davide,Riomet, Margaux,Bregant, Sarah,Sallustrau, Antoine,Plougastel, Lucie,Decuypere, Elodie,Gabillet, Sandra,Kumar, Ramar Arun,Elyian, Jijy,Trinh, Minh Nguyet,Koniev, Oleksandr,Wagner, Alain,Kolodych, Sergii,Taran, Frédéric
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supporting information
p. 15612 - 15616
(2017/12/02)
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- High-yielding automated convergent synthesis of no-carrier-added [11C-carbonyl]-labeled amino acids using the strecker reaction
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A new variant of the Strecker synthesis using no-carrier-added [11C]cyanide for the synthesis of radiolabeled amino acids is described. The protocol is fully automated using a radiochemistry synthesis module and applied to the production of a number of new PET radiotracers. [11C-Carbonyl]sarcosine, [11C-carbonyl]methionine, [11C-carbonyl]-N-phenylglycine, and [11C-carbonyl]glycine are all synthesized in moderate to good radiochemical yields. The synthesis of [11C-carbon-yl]sarcosine has been validated for production of doses for clinical use, and preliminary evaluation of the new radiotracer in PC3 tumor-bearing mice is also reported.
- Xing, Junhao,Brooks, Allen F.,Fink, Dylan,Zhang, Huibin,Piert, Morand R.,Scott, Peter J.H.,Shao, Xia
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supporting information
p. 371 - 375
(2017/02/10)
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- Cs2CO3-Promoted Direct N-Alkylation: Highly Chemoselective Synthesis of N-Alkylated Benzylamines and Anilines
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Herein is described an efficient and chemoselective method for the synthesis of diversely substituted secondary amines in yields up to 98 %. Direct mono-N-alkylation of primary benzylamines and anilines with a wide range of alkyl halides is promoted by a cesium base in the absence of any additive or catalyst. The basicity and solubility of cesium carbonate in anhydrous N,N-dimethylformamide not only enables mono-N-alkylation of primary amines but also suppresses undesired dialkylation of the desired amines.
- Castillo, Juan-Carlos,Orrego-Hernández, Jessica,Portilla, Jaime
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p. 3824 - 3835
(2016/08/20)
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- A method for preparing n-phenylglycinonitrile
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The invention relates to a method for preparing n-phenylglycinenitrile. The method is characterized in that condensation reaction is continuously performed for aniline and glycolonitrile by a micro-channel reactor to obtain n-phenylglycinenitrile; the pH of glycolonitrile is pre-regulated to be 1.5 to 7 through a basic catalyst; the molar ratio of aniline to glycolonitrile is 1.00: 1.00-1.30. The method for preparing n-phenylglycinenitrile has the advantages that the process route is simple, and the reaction is fast, so that the working efficiency and production capacity can be ensured, and moreover, the production and operation safety of the process can also be ensured; with the adoption of the process method, the purity of a n-phenylglycinenitrile product exceeds 98.0% and the yield exceeds 99.9%.
- -
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Paragraph 0042-0048
(2017/04/03)
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- A method for preparing n-phenylglycinonitrile
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The invention discloses a preparation method of n-phenylglycinenitrile. The preparation method includes steps of subjecting aniline and hydroxyacetonitrile to reaction in the existence of catalyst until aniline content is smaller than 1.0%; splitting phase to obtain organic phase on the lower layer of reactant liquid with heat, atomizing, cooling and granulating to obtain products. The preparation method of n-phenylglycinenitrile is low in cost and environment-friendly, consumption of hydroxyacetonitrile is reduced, generation of wastewater is reduced, content of n-phenylglycinenitrile is increased, water content of the products is reduced, appearance of n-phenylglycinenitrile is improved, clotting due to air temperature or pressing during storage and transport is avoided, mobility of materials is good and the products are convenient to use.
- -
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Paragraph 0031-0035
(2017/03/14)
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- A method for preparing n-phenylglycinonitrile
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The invention discloses a method for preparing n-phenylglycinenitrile. The method comprises the following steps: enabling aniline and hydroxyl acetonitrile to react in the presence of a catalyst until the content of aniline is smaller than a certain value; separating out the organic phase at the lower layer of a reaction liquid while the reaction liquid is hot, adding fresh water or a crystallization mother liquid, cooling to crystallize, separating, and drying the solid to obtain a product, and continuously using the crystallization mother liquid for crystallization of a next batch of products; analyzing the content of hydroxyl acetonitrile in the water phase of a n-phenylglycinenitrile reaction liquid, adding aniline and the catalyst according to a ratio, heating to react, cooling, separating the phase, feeding the organic phase into a crystallization kettle, treating the water phase, and discharging out the treated water phase. Compared with the prior art, the process for preparing n-phenylglycinenitrile is relatively economic and environment-friendly, the appearance quality of the product can be improved, and the content of the product can be increased.
- -
-
Paragraph 0016; 0027-0029
(2018/02/04)
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- Preparation method for alpha-cyanoamine
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The invention discloses a preparation method for alpha-cyanoamine. According to the method, the product alpha-cyanoamine is prepared through nucleophilic substitution in a mixed solvent in the presence of an oxidizing agent with an amine compound and cyanoacetic acid as reactants, iodide as a catalyst and sodium acetate as alkali. The catalyst used in the method has high reactivity; reaction conditions are mild; the application scope of a substrate is wide; post-treatment is convenient; the yield of the target product is high; preparation process is simple, green and environment-friendly; and used raw materials are widely available.
- -
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Paragraph 0088; 0089
(2016/10/07)
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- Synthesis of tetrazole compounds as a novel type of potential antimicrobial agents and their synergistic effects with clinical drugs and interactions with calf thymus DNA
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A series of tetrazole derivatives were synthesized and characterized by NMR, IR, MS and HRMS spectroscopy. The bioactive assay manifested that most of the target compounds exhibited good antifungal activity, especially compound 6g displayed comparable or even stronger antifungal efficiency in comparison with the reference drug Fluconazole. The combination of tetrazole derivative 6g with antibacterials Chloromycin and Norfloxacin, or antifungal Fluconazole respectively was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive Aspergillus flavus. Further research revealed that compound 6g could effectively intercalate into Calf Thymus DNA to form a 6g-DNA complex which might block DNA replication to exert its good antimicrobial activities. This journal is
- Dai, Ling-Ling,Zhang, Hui-Zhen,Nagarajan, Sangaraiah,Rasheed, Syed,Zhou, Cheng-He
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p. 147 - 154
(2015/03/03)
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- Cyanoacetic Acid as a Masked Electrophile: Transition-Metal-Free Cyanomethylation of Amines and Carboxylic Acids
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Using cyanoacetic acid as a masked electrophile, a new cyanomethylation reaction of amines and carboxylic acids was developed, producing a variety of α-aminonitriles and cyanomethyl esters with good yields and excellent functionality tolerance. This protocol features simple manipulation, inexpensive reagents, and a wide substrate scope. Iodoacetonitrile was generated in situ from the iodination-decarboxylation of cyanoacetic acid in this transformation.
- Wang, Hongxiang,Shao, Ying,Zheng, Hao,Wang, Hanghang,Cheng, Jiang,Wan, Xiaobing
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supporting information
p. 18333 - 18337
(2015/12/24)
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- Magnetic graphitic carbon nitride: Its application in the C-H activation of amines
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Magnetic graphitic carbon nitride, Fe@g-C3N4, has been synthesized by adorning a graphitic carbon nitride (g-C3N4) support with iron oxide via non-covalent interaction. The magnetically recyclable catalyst showed excellent reactivity for the expeditious C-H activation and cyanation of amines.
- Verma, Sanny,Nasir Baig,Han, Changseok,Nadagouda, Mallikarjuna N.,Varma, Rajender S.
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supporting information
p. 15554 - 15557
(2015/10/28)
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- Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment
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A series of analogues of the non-steroidal anti-inflammatory drug (NSAID) sulindac 1 were synthesised tethered to nitric oxide (NO) donating functional groups. Sulindac shows antiproliterative effects against immortal PC3 cell lines. It was previously demonstrated that the effect can be enhanced when tethered to NO releasing groups such as nitrate esters, furoxans and sydnonimines. To explore this approach further, a total of fifty-six sulindac-NO analogues were prepared and they were evaluated as NO-releasing cytotoxic agents against prostate cancer (PCa) cell lines. Compounds 1k and 1n exhibited significant cytotoxic with IC50 values of 6.1 ± 4.1 and 12.1 ± 3.2 μM, respectively, coupled with observed nitric oxide release.
- Nortcliffe, Andrew,Ekstrom, Alexander G.,Black, James R.,Ross, James A.,Habib, Fouad K.,Botting, Nigel P.,O'Hagan, David
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p. 756 - 761
(2014/01/23)
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- A TiO2 immobilized Ru(ii) polyazine complex: A visible-light active photoredox catalyst for oxidative cyanation of tertiary amines
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A chemically functionalized nanocrystalline TiO2 grafted ruthenium(ii) polyazine complex was found to be an efficient visible light photoredox catalyst for the oxidative cyanation of tertiary amines to the corresponding α-aminonitriles in high to excellent yields, using molecular oxygen as an oxidant and sodium cyanide in acetic acid as a cyanide source. The developed photoredox catalyst could be easily recovered by simple filtration and reused for several runs with consistent catalytic activity.
- Kumar, Pawan,Varma, Sanny,Jain, Suman L.
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p. 4514 - 4519
(2014/03/21)
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- Amphiphilic methyleneamino synthon through organic dye catalyzed- decarboxylative aminoalkylation
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The utilization of a photo-induced synthon generated from N-phenyl glycine by an organic dye and visible light irradiation is disclosed. The intermediate could be coupled with either a radical or a nucleophile in a simple operation to afford several natural product-like compounds.
- Chen, Li,Chao, Chin Sheng,Pan, Yuanhang,Dong, Sheng,Teo, Yew Chin,Wang, Jian,Tan, Choon-Hong
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supporting information
p. 5922 - 5925
(2013/09/12)
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- Novel amino acids: Synthesis of furoxan and sydnonimine containing amino acids and peptides as potential nitric oxide releasing motifs
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The incorporation of furoxan and sydnonimine ring systems into amino acid side chains is demonstrated with the preparation of four novel amino acids which carry these nitric oxide-releasing motifs. N-((4-Nitrophenoxy)carbonyl)-3- phenylsydnonimine 9 and bis(phenylsulfonyl)furoxan 10 are the key intermediates for introducing the heterocycle side chains onto appropriate amine and alcohol functionalities respectively. Furoxan 5 and 7 both displayed NO release based on determination of nitrite production. Orthogonal amino acid protecting group strategies were deployed to demonstrate that the amino acids could be incorporated into peptide frameworks. By way of demonstration the amino acids were placed centrally into several tripeptide motifs. Griess test assays showed that these amino acids released NO in the presence of γ-glutathione (GST). is
- Nortcliffe, Andrew,Botting, Nigel P.,O'Hagan, David
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p. 4657 - 4671
(2013/07/26)
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- A ruthenium-carbamato-complex derived from a siloxylated amine and carbon dioxide for the oxidative α-cyanation of aromatic and cyclic tertiary amines
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The ruthenium carbamate complex derived from 3-trimethoxysilyl-1-propyl amine and carbon dioxide was found to be a novel catalyst for the oxidative cyanation of aromatic and cyclic tertiary amines to corresponding α-amino nitriles in high to excellent yields by using hydrogen peroxide and molecular oxygen as enviro-economic oxidants. The developed protocol suggested an efficient alternative for recycling carbon dioxide.
- Kumar, Subodh,Kumar, Pawan,Jain, Suman L.
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p. 24013 - 24016
(2013/11/19)
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- Iron nanoparticles supported on graphene oxide: A robust, magnetically separable heterogeneous catalyst for the oxidative cyanation of tertiary amines
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Well-dispersed iron nanoparticles supported on chemically derived graphene oxide containing uniform distribution of iron nanoparticles (FeNPs) throughout the surface was synthesized and was used as a heterogeneous catalyst for oxidative cyanation of tertiary amines to the corresponding α- aminonitriles in high to excellent yields using hydrogen peroxide with sodium cyanide in acetic acid. After the reaction the catalyst could easily be separated by the influence of an external magnet and reused for several runs without any significant change in the catalytic activity and without leaching of the metal during the reaction. Copyright
- Verma, Deepak,Verma, Sanny,Sinha, Anil K.,Jain, Suman L.
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p. 860 - 865
(2013/09/02)
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- SUBSTITUTED QUINAZOLINE DERIVATIVES AND THEIR USE AS INHIBITORS
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The use of a compound of formula (I) 1 or a salt, ester or amide thereof; where X is O, or S, S(O) or S(O)2, or NR6 where R6 is hydrogen or C1-6 alkyl,; R5 is an optionally substituted 5-membered heteroaromatic ring, R1, R2 ,R3, R4 are independently selected from various specified moieties, in the preparation of a medicament for use in the inhibition of aurora 2 kinase. Certain compounds are novel and these, together with pharmaceutical compositions containing them are also described and claimed
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- Methods for producing enantiomerically pure alpha-substituted carboxylic acids
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In accordance with the present invention there are provided methods for producing enantiomerically pure α-substituted carboxylic acids, such as, for example, α-amino acids and α-hydroxy acids, said method comprising combining an aldehyde or ketone with a cyanide and ammonia or an ammonium salt or an amine, in the presence of a nitrilase or a polypeptide having nitrilase activity which stereoselectively hydrolyzes the amino nitrile or cyanohydrin intermediate under conditions sufficient to produce the carboxylic acid.
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- Palladium-catalyzed chemoselective intramolecular cyclization of bromoanilinoalkenenitriles
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α-(o-Bromoanilino)alkenenitriIes 1a-f and 2a-e and α-(N-alkenylamino)-β-(o-bromophenyl)-propanenitriles 7a-c and 8a-c undergo palladium-catalyzed conversion into o-(methylamino)benzonitrile 12, o-[(alkenylamino)ethenyl]benzonitriles 24a-c, N-alkenylanilines 26b, 26c, 3-benzazepines 29a, 29c, 31a and 32a, γ-carbolines 36 and pyrrolo[3,2-b]indole 45. The reactions involve intramolecular additions of arylpalladium to the cyano group and subsequent processes such as cyano group transposition, hydrolysis, electrocyclization, ethyl group transfer and oxidative aromatization. A general mechanism for the palladium-catalyzed arylation of a cyano group is proposed.
- Yang, Chau-Chen,Tai, Huo-Mu,Sun, Pei-Jiun
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p. 2843 - 2850
(2007/10/03)
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- Synthesis of a new series of 2,7-diazaspirononan-1-ones and study of their cholinergic properties
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A new series of substituted 2,7-diazaspirononan-1-ones (1a-l), structurally related to the muscarinic agonist RS-86, has been synthesized and tested for cholinergic properties both in vitro and in vivo.None of the compounds showed significant cholinergic properties at either the central or peripheral level.A possible explanation for the lack of activity is given.Alzheimer's disease / cholinergic system / RS-86 / muscarinic agonists
- Cignarella, G.,Villa, S.,Barlocco, D.
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p. 115 - 120
(2007/10/02)
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- Synthesis of a new series of N-substituted-3-[1-alkyl(aryl)-4- piperidyl]azetidin-2-ones as possible muscarinic agents
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A new series of N-substituted-3-[1-alkyl(aryl)-4-piperidyl]azetidin-2- ones 2a-j structurally related to the previously reported 2,7- diazaspiro[3,5]nonan-1-ones 1 have been synthesized and tested for their activity as muscarinic agents, both in vitro and in vivo. Preliminary pharmacological results showed that compounds 2 are devoid of significant cholinergic properties.
- Cignarella,Villa,Barlocco
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p. 1337 - 1340
(2007/10/02)
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- Synthesis and pharmacological evaluation of 2,3-dialkylindoles, 'in vitro' inhibitors of thrombin-induced platelet aggregation
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A series of 2,3-dialkylindoles (1-5) have been prepared and tested as antithrombotic agents. The whole class showed in vitro interesting activity in the inhibition of thrombin-induced aggregation. Among these compounds some ones showed activity comparable to standards also in the inhibition of collagen-induced aggregation. Owing to a very fast metabolic degradation through a beta-oxidative mechanism, a drastic decrease of activity in several tests ex vivo or in vivo was observed.
- Arcari,Aveta,Brandt,Cecchetelli,Corsi,Solinas
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p. 405 - 425
(2007/10/02)
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- TiCl4 induced N-methyleneamine equivalents: A new route to aminoacetonitriles
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TiCl4 induced N-methyleneamine equivalents from hexahydro-1,3,5-triazines or N-(methoxymethyl)amines were reacted with trimethylsilyl cyanide to give aminoacetonitriles in 40-90% yield.
- Ha,Nam,Park
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p. 155 - 160
(2007/10/02)
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