- Photocatalytic continuous bromination method
-
The invention provides a photocatalytic continuous bromination method. The method comprises the following steps: carrying out a first-stage photocatalytic continuous bromination reaction on a materialcontaining an aromatic substrate with a structural general formula I and a bromination reagent in a first continuous illumination reactor to form a first continuous system; overflowing the obtained first continuous system into a second continuous illumination reactor for a second-stage photocatalytic continuous bromination reaction to form a second continuous system; and purifying the second continuous system, wherein the structural general formula I is shown in the specification, R is selected from any one of carboxyl, ester group, NO2, CN, C1 to C8 alkyl and alkoxy, and R1 is C1 to C8 alkyl; n is 1 or 2; X is N or C, and the bromination reagent is Nbromo succinimide or dibromohydantoin. According to the bromination reagent, the selectivity of a product is improved, so the yield of the product is improved; the photocatalytic continuous bromination reaction of the two stages effectively relieves the reaction heat accumulation, and enhances the yield of the target product.
- -
-
Paragraph 0064-0065
(2021/04/03)
-
- AMINOPEPTIDASE A INHIBITORS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
-
The present invention relates to a novel compound, to a composition comprising the same, to methods for preparing the compound, and the use of this compound in therapy. In particular, the present invention relates to compound that is useful in the treatment and prevention of primary and secondary arterial hypertension, ictus, myocardial ischaemia, cardiac and renal insufficiency, myocardial infarction, peripheral vascular disease, diabetic proteinuria, Syndrome X and glaucoma.
- -
-
Page/Page column 43
(2020/06/10)
-
- Photochemical benzylic bromination in continuous flow using BrCCl3 and its application to telescoped p-methoxybenzyl protection
-
BrCCl3 represents a rarely used benzylic brominating reagent with complementary reactivity to other reagents. Its reactivity has been revisited in continuous flow, revealing compatibility with electron-rich aromatic substrates. This has brought about the development of a p-methoxybenzyl bromide generator for PMB protection, which was successfully demonstrated on a pharmaceutically relevant intermediate on 11 g scale, giving 91% yield and a PMB-Br space-time-yield of 1.27 kg L?1 h?1
- Otake, Yuma,Williams, Jason D.,Rincón, Juan A.,De Frutos, Oscar,Mateos, Carlos,Kappe, C. Oliver
-
supporting information
p. 1384 - 1388
(2019/02/14)
-
- Enantioselective Halo-oxy- and Halo-azacyclizations Induced by Chiral Amidophosphate Catalysts and Halo-Lewis Acids
-
Catalytic enantioselective halocyclization of 2-alkenylphenols and enamides have been achieved through the use of chiral amidophosphate catalysts and halo-Lewis acids. Density functional theory calculations suggested that the Lewis basicity of the catalyst played an important role in the reactivity and enantioselectivity. The resulting chiral halogenated chromans can be transformed to α-Tocopherol, α-Tocotrienol, Daedalin A and Englitazone in short steps. Furthermore, a halogenated product with an unsaturated side chain may provide polycyclic adducts under radical cyclization conditions.
- Lu, Yanhui,Nakatsuji, Hidefumi,Okumura, Yukimasa,Yao, Lu,Ishihara, Kazuaki
-
supporting information
p. 6039 - 6043
(2018/05/14)
-
- PYRIMIDINE COMPOUNDS CONTAINING ACIDIC GROUPS
-
The present disclosure relates to a class of pyrimidine derivatives having immunomodulating properties that act via TLR7 which are useful in the treatment of viral infections and cancers.
- -
-
Paragraph 1078; 1079
(2018/06/15)
-
- Rapid and reversible hydrazone bioconjugation in cells without the use of extraneous catalysts
-
The amenability of hydrazone linkages to disassemble via either hydrolysis in mildly acidic aqueous solutions or transimination upon treatment with amine nucleophiles renders them extremely attractive for applications in chemical biology, drug delivery and materials science. Unfortunately, however, the use of hydrazones is hampered by the extremely slow intrinsic rates of their formation from their hydrazine and carbonyl precursors. Consequently, hydrazone formation is typically performed in the presence of a large excess of cytotoxic aniline-based nucleophilic catalysts, rendering hydrazones unsuitable for biological applications that entail their formation in cells. Herein, we report a hydrazine scaffold - o-amino benzyl hydrazine - that rapidly forms hydrazones via intramolecular nucleophilic catalysis, thereby obviating the use of extraneous catalysts. We demonstrate the use of this scaffold for rapid and reversible peptide and protein hydrazone bioconjugation and also for reversible fluorescent labeling of sialylated glycoproteins and choline lipids in mammalian cells.
- Nisal, Rahul,Jose, Gregor,Shanbhag, Chitra,Kalia, Jeet
-
p. 4304 - 4310
(2018/06/22)
-
- Interaction of α-Thymidine Inhibitors with Thymidylate Kinase from Plasmodium falciparum
-
Plasmodium falciparum thymidylate kinase (PfTMK) is a critical enzyme in the de novo biosynthesis pathway of pyrimidine nucleotides. N-(5′-Deoxy-α-thymidin-5′-yl)-N′-[4-(2-chlorobenzyloxy)phenyl]urea was developed as an inhibitor of PfTMK and has been reported as an effective inhibitor of P. falciparum growth with an EC50 of 28 nM [Cui, H., et al. (2012) J. Med. Chem. 55, 10948-10957]. Using this compound as a scaffold, a number of derivatives were developed and, along with the original compound, were characterized in terms of their enzyme inhibition (Ki) and binding affinity (KD). Furthermore, the binding site of the synthesized compounds was investigated by a combination of mutagenesis and docking simulations. Although the reported compound is indicated to be highly effective in its inhibition of parasite growth, we observed significantly lower binding affinity and weaker inhibition of PfTMK than expected from the reported EC50. This suggests that significant structural optimization will be required for the use of this scaffold as an effective PfTMK inhibitor and that the inhibition of parasite growth is due to an off-target effect.
- Chen, Mengshen,Sinha, Kaustubh,Rule, Gordon S.,Ly, Danith H.
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p. 2868 - 2875
(2018/05/14)
-
- Method for preparing benzyl bromide
-
The invention provides a method for preparing benzyl bromide. The method comprises the following steps: by taking bromine released from a redox reaction between bromates and negative bromide ions in the presence of an acid as a bromine source in an organic solvent, carrying out a benzyl radical substitution reaction with a methylbenzene compound shown as a formula I under initiation of an initiator, thereby obtaining a corresponding benzyl bromide compound shown a formula II, wherein in the formula II, m represents the number of Br and is equal to 1 or 2; when m is equal to 1, the formula II shows a benzyl monobromo compound; and when m is equal to 2, the formula II shows a benzyl dibromo compound. The reaction is carried out in an organic solvent, the initiator is combined and used, the radical substitution reaction is high in selectivity and wide in substrate application range, the substituent group replacing methylbenzene may be an electron-withdrawing group or an electron-donating group and can give extremely high yield on strong electron-donating groups (such as methoxy group). Moreover, the method disclosed by the invention is also applicable to preparation of benzyl dibromo compounds, and the product yield is high.
- -
-
Paragraph 0064-0066
(2017/10/05)
-
- Total Synthesis of the Labdane Diterpenes Galanal A and B from Geraniol
-
The first total synthesis of galanal A and B has been achieved from naturally occurring geraniol. Key steps in this synthesis are the use of a Lewis acid assisted chiral Br?nsted acid (chiral LBA) mediated cationic polyene cyclization and a titanocene-mediated radical cyclization for the asymmetric assembly of the "AB" ring and the construction of the all-carbon quaternary center at the junction of the "BC" ring, respectively.
- Lin, Shih-Che,Chein, Rong-Jie
-
p. 1575 - 1583
(2017/02/10)
-
- 2-ALKYLOXY BENZENE FORMYL ARYLAMINE COMPOUND AND PHARMACEUTICAL USE THEREOF
-
The present invention relates to 2-alkoxy benzene formyl arylamine compounds as scheme I , in which the R, G, X, Y, Z are consistent with the detailed description in the patent claim. The compounds can act as sphingomyelin synthase (SMS) inhibitors to treat diseases caused by abnormal increasing of sphingomyelin(SM). This invention also includes compounds as scheme I , their pharmaceutically acceptable salts, pharmaceutical compositions as the active ingredients, and their application in drugs which can prevent and cure diseases caused by SM level abnormal increase. These diseases include atherosclerosis, fatty liver, obesity, type II diabetes, and other metabolic syndromes.
- -
-
-
- Nucleophilic Amination of Methoxy Arenes Promoted by a Sodium Hydride/Iodide Composite
-
A method for the nucleophilic amination of methoxy arenes was established by using sodium hydride (NaH) in the presence of lithium iodide (LiI). This method offers an efficient route to benzannulated nitrogen heterocycles. Mechanistic studies showed that the reaction proceeds through an unusual concerted nucleophilic aromatic substitution.
- Kaga, Atsushi,Hayashi, Hirohito,Hakamata, Hiroyuki,Oi, Miku,Uchiyama, Masanobu,Takita, Ryo,Chiba, Shunsuke
-
supporting information
p. 11807 - 11811
(2017/09/20)
-
- Synthesis of Chiral 1,4-Benzodioxanes and Chromans by Enantioselective Palladium-Catalyzed Alkene Aryloxyarylation Reactions
-
A highly enantioselective alkene aryloxyarylation led to the high-yielding formation of a series of 1,4-benzodioxanes, 1,4-benzooxazines, and chromans containing quaternary stereocenters with excellent enantioselectivity. The sterically bulky and conformationally well defined chiral monophosphorus ligand L4 or L5 was responsible for the high reactivity and enantioselectivity of these transformations. The application of this method to the synthesis of the chiral chroman backbone of α-tocopherol was demonstrated. One P is plenty: A sterically bulky and conformationally well defined chiral monophosphorus ligand enabled the highly enantioselective synthesis of a series of Oheterocycles containing a quaternary stereocenter by alkene aryloxyarylation (see scheme; X=O, C, N). The application of this transformation to the synthesis of the chiral chroman backbone of α-tocopherol is demonstrated.
- Hu, Naifu,Li, Ke,Wang, Zheng,Tang, Wenjun
-
supporting information
p. 5044 - 5048
(2016/04/26)
-
- Visible-Light-Induced Cyclization of Electron-Enriched Phenyl Benzyl Sulfides: Synthesis of Tetrahydrofurans and Tetrahydropyrans
-
A new approach to the preparation of tetrahydrofurans and tetrahydropyrans through a photoredox catalytic process is described. The introduction of a phenylsulfanyl auxiliary group permits the substrates to be readily oxidized to form cationic intermediates for sequential intramolecular cyclization. The method features mild reaction conditions and operational simplicity.
- Li, Wei,Yang, Chao,Gao, Guo-Lin,Xia, Wujiong
-
supporting information
p. 1391 - 1396
(2016/06/01)
-
- Discovery and structural optimization of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-ones as RORc inverse agonists
-
Aim: Retinoic acid receptor-related orphan nuclear receptors (RORs) are orphan nuclear receptors that show constitutive activity in the absence of ligands. Among 3 subtypes of RORs, RORc is a promising therapeutic target for the treatment of Th17-mediated autoimmune diseases. Here, we report novel RORc inverse agonists discovered through structure-based drug design. Methods: Based on the structure of compound 8, a previously described agonist of RORa, a series of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-one derivatives were designed and synthesized. The interaction between the compounds and RORc was detected at molecular level using AlphaScreen assay. The compounds were further examined in 293T cells transfected with RORc and luciferase reporter gene. Thermal stability shift assay was used to evaluate the effects of the compounds on protein stability. Results: A total of 27 derivatives were designed and synthesized. Among them, the compound 22b was identified as the most potent RORc inverse agonist. Its IC50 values were 2.39 μmol/L in AlphaScreen assay, and 0.82 μmol/L in inhibition of the cell-based luciferase reporter activity. Furthermore, the compound 22b displayed a 120-fold selectivity for RORc over other nuclear receptors. Moreover, a molecular docking study showed that the structure-activity relationship was consistent with the binding mode of compound 22b in RORc. Conclusion: 4-(4-(Benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-one derivatives are promising candidates for the treatment of Th17-mediated autoimmune diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis.
- Wu, Xi-Shan,Wang, Rui,Xing, Yan-Li,Xue, Xiao-Qian,Zhang, Yan,Lu, Yong-Zhi,Song, Yu,Luo, Xiao-Yu,Wu, Chun,Zhou, Yu-Lai,Jiang, Jian-Qin,Xu, Yong
-
p. 1516 - 1524
(2016/11/11)
-
- Clay-Supported Cu(II) Catalyst: An Efficient, Heterogeneous, and Recyclable Catalyst for Synthesis of 1,4-Disubstituted 1,2,3-Triazoles from Alloxan-Derived Terminal Alkyne and Substituted Azides Using Click Chemistry
-
A novel series of alloxan-derived 1,4-disubstituted 1,2,3-triazoles was synthesized in excellent yields under catalytic conditions using a click reaction strategy through 1,3-dipolar cycloaddition. Their structures have been ascertained on the basis of spectroanalytical and elemental analysis data. Synthesis of hybrid compounds with varying substitutions in the triazole ring was achieved by reaction between alloxan-derived terminal alkyne and a pertinent azide derivative in the presence of clay-Cu(II) as the catalyst in methanolic medium. Also, comparative evaluation of various catalytic systems [viz., CuI, CuSO4, CuI-zeolite, K10Ti, and clay-Cu(II)] was investigated. Of these catalytic systems, clay-Cu(II) was observed to be the best. The catalyst was recyclable for several runs without showing significant loss in its activity. The good selectivity, cost-efficiency, short reaction time, milder reaction conditions, and simple workup procedure are the added salient features of this synthetic protocol.
- Dubey, Nitin,Sharma, Pratibha,Kumar, Ashok
-
p. 2608 - 2626
(2015/11/28)
-
- One-pot transformation of methylarenes into aromatic aldehydes under metal-free conditions
-
On the basis of studies of the transformation of benzylic bromides into the corresponding aromatic aldehydes by treatment with N-methylmorpholine N-oxide, various methylarenes were treated either with DBDMH in the presence of AIBN in acetonitrile at reflux (Method A) or with NBS in CCl4 under irradiation with a tungsten lamp at 30 °C (Method B), followed by treatment with N-methylmorpholine N-oxide to provide aromatic aldehydes in good yields. These methods could be adopted in one-pot transformations of methylarenes into aromatic aldehydes under conditions free of less toxic reagents and transition metals. Copyright
- Tabata, Masayuki,Moriyama, Katsuhiko,Togo, Hideo
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p. 3402 - 3410
(2014/06/09)
-
- Direct oxidative conversion of methylarenes into aromatic nitriles
-
A variety of methylarenes were successfully converted into the corresponding aromatic nitriles in good to moderate yields by the treatment with NBS or DBDMH in the presence of a catalytic amount of AIBN or BPO, followed by the reaction with molecular iodine in aq NH3 in a one-pot procedure. The present reaction is a useful and practical transition-metal-free method for the preparation of aromatic nitriles from methylarenes.
- Tsuchiya, Daisuke,Kawagoe, Yuhsuke,Moriyama, Katsuhiko,Togo, Hideo
-
supporting information
p. 4194 - 4197
(2013/09/12)
-
- Synthesis of combretastatin A4 analogues on steroidal framework and their anti-breast cancer activity
-
Combretastatin A4 analogues were synthesized on steroidal framework from gallic acid with a possibility of anti-breast cancer agents. Twenty two analogues were synthesized and evaluated for cytotoxicity against human breast cancer cell lines (MCF-7 & MDA-MB 231). The best analogue 22 showed potent antitubulin effect. Docking experiments also supported strong binding affinity of 22 to microtubule polymerase. In cell cycle analysis, 22 induced apoptosis in MCF-7 cells significantly. It was found to be non-toxic up to 300 mg/kg dose in Swiss albino mice in acute oral toxicity. This article is part of a Special Issue entitled "Synthesis and biological testing of steroid derivatives as inhibitors".
- Parihar, Swati,Kumar, Amit,Chaturvedi, Amit K.,Sachan, Naresh Kumar,Luqman, Suaib,Changkija, Bendangla,Manohar, Murli,Prakash, Om,Chanda,Khan, Feroz,Chanotiya,Shanker, Karuna,Dwivedi, Anila,Konwar, Rituraj,Negi, Arvind S.
-
p. 332 - 344
(2013/11/19)
-
- Overturning established chemoselectivities: Selective reduction of arenes over malonates and cyanoacetates by photoactivated organic electron donors
-
The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate-metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor 5 selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates.
- Doni, Eswararao,Mondal, Bhaskar,O'Sullivan, Steven,Tuttle, Tell,Murphy, John A.
-
supporting information
p. 10934 - 10937
(2013/08/23)
-
- Practical and highly selective sulfur ylide-mediated asymmetric epoxidations and aziridinations using a cheap and readily available chiral sulfide: Extensive studies to map out scope, limitations, and rationalization of diastereo- and enantioselectivities
-
The chiral sulfide, isothiocineole, has been synthesized in one step from elemental sulfur, γ-terpinene, and limonene in 61% yield. A mechanism involving radical intermediates for this reaction is proposed based on experimental evidence. The application of isothiocineole to the asymmetric epoxidation of aldehydes and the aziridination of imines is described. Excellent enantioselectivities and diastereoselectivities have been obtained over a wide range of aromatic, aliphatic, and α,β-unsaturated aldehydes using simple protocols. In aziridinations, excellent enantioselectivities and good diastereoselectivities were obtained for a wide range of imines. Mechanistic models have been put forward to rationalize the high selectivities observed, which should enable the sulfide to be used with confidence in synthesis. In epoxidations, the degree of reversibility in betaine formation dominates both the diastereoselectivity and the enantioselectivity. Appropriate tuning of reaction conditions based on understanding the reaction mechanism enables high selectivities to be obtained in most cases. In aziridinations, betaine formation is nonreversible with semistabilized ylides and diastereoselectivities are determined in the betaine forming step and are more variable as a result.
- Illa, Ona,Namutebi, Mariam,Saha, Chandreyee,Ostovar, Mehrnoosh,Chen, C. Chun,Haddow, Mairi F.,Nocquet-Thibault, Sophie,Lusi, Matteo,McGarrigle, Eoghan M.,Aggarwal, Varinder K.
-
supporting information
p. 11951 - 11966
(2013/09/02)
-
- Oxidative cyclizations, the synthesis of aryl-substituted c-glycosides, and the role of the second electron transfer step
-
Anodic oxidation reactions have been used to synthesize aryl- and biaryl-substituted C-glycosides. The reactions take advantage of the tendency for alcohol nucleophiles to trap nonpolar radical cations. The addition of the alcohol to the radical cation appears to be reversible, and the success of the cyclizations is dependent on the ease with which the resulting benzylic radical is oxidized.
- Smith, Jake A.,Moeller, Kevin D.
-
supporting information
p. 5818 - 5821
(2013/12/04)
-
- Unequivocal experimental evidence for a unified lithium salt-free wittig reaction mechanism for all phosphonium ylide types: Reactions with β-heteroatom-substituted aldehydes are consistently selective for cis-oxaphosphetane-derived products
-
The true course of the lithium salt-free Wittig reaction has long been a contentious issue in organic chemistry. Herein we report an experimental effect that is common to the Wittig reactions of all of the three major phosphonium ylide classes (non-stabilized, semi-stabilized, and stabilized): there is consistently increased selectivity for cis-oxaphosphetane and its derived products (Z-alkene and erythro-β-hydroxyphosphonium salt) in reactions involving aldehydes bearing heteroatom substituents in the β-position. The effect operates with both benzaldehydes and aliphatic aldehydes and is shown not to operate in the absence of the heteroatom substituent on the aldehyde. The discovery of an effect that is common to reactions of all ylide types strongly argues for the operation of a common mechanism in all Li salt-free Wittig reactions. In addition, the results are shown to be most easily explained by the [2+2] cycloaddition mechanism proposed by Vedejs and co-workers as supplemented by Aggarwal, Harvey, and co-workers, thus providing strong confirmatory evidence in support of that mechanism. Notably, a cooperative effect of ortho-substituents in the case of semi-stabilized ylides is confirmed and is accommodated by the cycloaddition mechanism. The effect is also shown to operate in reactions of triphenylphosphine-derived ylides and has previously been observed for reactions under aqueous conditions, thus for the first time providing evidence that kinetic control is in operation in both of these cases.
- Byrne, Peter A.,Gilheany, Declan G.
-
supporting information; experimental part
p. 9225 - 9239
(2012/07/14)
-
- Diiron complexes with pendant phenol group(s) as mimics of the diiron subunit of [FeFe]-hydrogenase: Synthesis, characterisation, and electrochemical investigation
-
Four diiron hexacarbonyl complexes, [Fe2(μ-SCH 2-o-C6H4OMe)2(CO)6] (4a), [Fe2{μ-SCH2-o,m-C6H3(OMe) 2}2-(CO)6] (4b), [Fe2{μ-SCH 2-o,o′-C6H3(CO2Me)(OMe)} 2(CO)6] (4c) and the demethylated form of complex 4a, [Fe2(μ-SCH2-o-C6H4OH) 2(CO)6] (5a), were synthesised and fully characterised. Complexes 4b and 4c were also structurally analysed. Electrochemical investigations revealed that the integrity of the bridging linkages of the examined diiron complexes significantly affect their reduction reversibility and catalysis through a coupled chemical reaction in a unique ECE mechanism, widely adopted by complexes with the core {Fe2(CO)4-6}. Demethylation of complexes 4a and 1Me, [Fe2(μ-SCH 2)2CMe(CH2-o-C6H4OMe)(CO) 6], by BBr3 led to complexes (5a and 1H, [Fe 2(μ-SCH2)2CMe(CH2-o-C 6H4OH)-(CO)6]) with pendant phenol group(s), a weak acid. Deprotonation of the two complexes produced the pendant phenolate, which instantly intramolecularly substitutes the bound CO to yield species of the coordination form FeI-OR (R = phenolic moiety). Electrochemical investigation revealed that the pendant phenol groups in complexes 1H and 5a do not seem to improve their catalytic efficiency in proton reduction in the medium acetic acid/dichloromethane.
- Tang, Ying,Wei, Zhenhong,Zhong, Wei,Liu, Xiaoming
-
experimental part
p. 1112 - 1120
(2011/06/10)
-
- Synthesis of benzyl bromides with hexabromoacetone: An alternative path to drug intermediates
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A series of benzyl bromides were efficiently prepared from the corresponding alcohols with Br3CCOCBr3/PPh3 at low temperatures and under neutral conditions. The present protocol was applied to the heterocyclic analogues and to the successful synthesis of the precursor of the antiulcer drug omeprazole, thus furnishing an alternate, mild method for the preparation of these drug intermediates. A significant steric factor was observed throughout both series supporting a SN2 mechanism.
- Joseph, Kara M.,Larraza-Sanchez, Isabel
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experimental part
p. 13 - 16
(2011/02/25)
-
- Iridium(I) complexes with hemilabile N-heterocyclic carbenes: Efficient and versatile transfer hydrogenation catalysts
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A series of neutral and cationic rhodium and iridium(I) complexes based on hemilabile O-donor- and N-donor-functionalized NHC ligands having methoxy, dimethylamino, and pyridine as donor functions have been synthesized. The hemilabile fragment is coordinated to the iridium center in the cationic complexes [Ir(cod)(MeImR)]+ (R = pyridin-2-ylmethyl, 3-dimethylaminopropyl) but remains uncoordinated in the complexes [MBr(cod)(MeImR)], [M(NCCH3)(cod)(MeImR)]+ (M = Rh, Ir; R = 2-methoxyethyl and 2-methoxybenzyl) and [IrX(cod)(MeImR)] (X = Br, R = pyridin-2-ylmethyl; X = Cl, R = 2-dimethylaminoethyl, 3-dimethylaminopropyl). The structure of [IrBr(cod)(MeIm(2-methoxybenzyl))] has been determined by X-ray diffraction. The iridium complexes are efficient precatalysts for the transfer hydrogenation of cyclohexanone in 2-propanol/KOH. A comparative study has shown that cationic complexes are more efficient than the neutral and also that complexes having O-functionalized NHC ligands provide much more active systems than the corresponding N-functionalized ligands with TOFs up to 4600 h -1. The complexes [Ir(NCCH3)(cod)(MeImR)]+ (R = 2-methoxyethyl and 2-methoxybenzyl) have been successfully applied to the reduction of several unsaturated substrates as ketones, aldehydes, α,β-unsaturated ketones, and imines. The investigation of the reaction mechanism by NMR and MS has allowed the identification of relevant alkoxo intermediates [Ir(OR)(cod)(MeImR)] and the unsaturated hydride species [IrH(cod)(MeImR)]. The β-H elimination in the alkoxo complex [Ir(OiPr)(cod)(MeIm(2-methoxybenzyl))] leading to hydrido species has been studied by DFT calculations. An interaction between the β-H on the alkoxo ligand and the oxygen atom of the methoxy fragment of the NHC ligand, which results in a net destabilization of the alkoxo intermediate by a free energy of +1.0 kcal/mol, has been identified. This destabilization facilitates the β-H elimination step in the catalytic process and could explain the positive effect of the methoxy group of the functionalized NHC ligands on the catalytic activity.
- Jimenez, M. Victoria,Fernandez-Tornos, Javier,Perez-Torrente, Jesus J.,Modrego, Francisco J.,Winterle, Sonja,Cunchillos, Carmen,Lahoz, Fernando J.,Oro, Luis A.
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experimental part
p. 5493 - 5508
(2011/12/13)
-
- Synthesis and characterization of chroman-containing compounds and their preliminary assessment of cytotoxicity toward two human cancer cell lines
-
A series of chroman derivatives were synthesized by employing o-methyl phenol as a precursor. These compounds were fully characterized using IR, NMR spectroscopic techniques, and elemental analysis. Mechanisms for the formation of the chroman moiety of these compounds were also proposed. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to estimate their cytotoxicity toward two cancer cell lines: human ovarian cancer (A2780) and human cervical cancer (Hela).
- Tang, Ying,Wei, Jie,Zhong, Wei,Liu, Xiaoming
-
experimental part
p. 423 - 429
(2011/07/08)
-
- A rare bond between a soft metal (FeI) and a relatively hard base (RO-, R = phenolic moiety)
-
Reacting a bidentate ligand H2L, 2-(2-methoxybenzyl)-2- methylpropane-1,3-dithiol, with Fe3(CO)12 formed a diiron hexacarbonyl complex (1Me) from which a diiron hexacarbonyl complex (1H) pendant with a phenolic group was derived via in-situ demethylation. Further deprotonation of complex 1H gave a diiron pentacarbonyl species (1) in which a rare bond between the soft metal FeI and the relatively hard base phenolate formed, FeI-OR (R = phenolic moiety). This bonding may be a suitable mimic of the bonding feature, {FeIFeI}R-OH/ OH2 found in the [FeFe]-hydrogenase.
- Zhong, Wei,Tang, Ying,Zampella, Giuseppe,Wang, Xiufeng,Yang, Xinlei,Hu, Bin,Wang, Jiang,Xiao, Zhiyin,Wei, Zhenhong,Chen, Huanwen,De Gioia, Luca,Liu, Xiaoming
-
scheme or table
p. 1089 - 1092
(2011/01/11)
-
- Resorcin[4]arene-derived mono- And diphosphines in suzuki cross-coupling
-
Three resorcin[4]arene cavitands (1-3) having either one or two resorcinolic C-2 atoms substituted by a -CH2PPh2 podand arm were assessed in the Suzuki arylation of aryl bromides with phenylboronic acid. Using P:Pd ratios of 2:1 and operating in dioxane at 100°C with a catalyst loading of 0.001 mol% resulted in highly efficient catalytic systems. For example, TOFs up to 34570 mol(converted ArBr)-mol(Pd)-1.h -1 were obtained with the proximally-disubstituted cavitand 3 when using 4-bromotoluene as substrate. The performance was shown to vary in the following order: monophosphine 1diphosphine 2 diphosphine 3 (where 2 is the distally disubstituted cavitand). A comparison of the catalytic properties of monophosphine-cavitand 1 with those of benzyldiphenylphosphine and o-anisylmethyldiphenyl phosphine suggests that 1 functions as a hemilabile phosphine, the oxygen atoms close to the phosphorus atom behaving as donors able to temporarily increase the electron density on the metal and/ or favour the formation of mono-ligand Pd(O) species.
- Moll, Hani El,Semeril, David,Matt, Dominique,Toupet, Loic
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experimental part
p. 901 - 908
(2010/07/05)
-
- Palladium-catalyzed cross coupling reaction of benzyl bromides with diazoesters for stereoselective synthesis of (E)-α,β-diarylacrylates
-
(Chemical Equation Presented) A Pd-catalyzed cross-coupling reaction of benzyl bromides with α-aryldiazoesters is described, and E-α,β-diarylacrylates were obtained in good yields and excellent E-to-Z selectivity (>20:1).
- Yu, Wing-Yiu,Tsoi, Yuk-Tai,Zhou, Zhongyuan,Chan, Albert S. C.
-
supporting information; experimental part
p. 469 - 472
(2009/07/11)
-
- Highly efficient total synthesis of the marine natural products (+)-avarone, (+)-avarol, (-)-neoavarone, (-)-neoavarol and (+)-aureol
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Biologically important and structurally unique marine natural products avarone (1), avarol (2), neoavarone (3), neoavarol (4) and aureol (5), were efficiently synthesized in a unified manner starting from (+)-5-methyl-Wieland- Miescher ketone 10. The synthesis involved the following crucial steps: i) Sequential BF3·Et2O-in-duced rearrangement/ cyclization reaction of 2 and 4 to produce 5 with complete stereoselectivity in high yield (2 → 5 and 4 → 5); ii) strategic salcomine oxidation of the phenolic compounds 6 and 8 to derive the corresponding quinones 1 and 3 (6 → 1 and 8 →3); and iii) Birch reductive alkylation of 10 with bromide 11 to construct the requisite carbon framework 12 (10 + 11 → 12). An in vitro cytotoxicity assay of compounds 1-5 against human histiocytic lymphoma cells U937 determined the order of cytotoxic potency (3 > 1 > 5 > 2 > 4) and some novel aspects of structure-activity relationships.
- Sakurai, Junji,Oguchi, Takamasa,Watanabe, Kazuhiro,Abe, Hideki,Kanno, Syu-Ichi,Ishikawa, Masaaki,Katoh, Tadashi
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p. 829 - 837
(2008/12/23)
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- The effect of boronic acid acidity on performance of viologen-based boronic acids in a two-component optical glucose-sensing system
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A two-component saccharide sensing system using the fluorescent dye, hydroxypyrene trisulfonic acid, combined with a boronic acid functional viologen as a receptor/quencher in pH 7.4 buffer solution has been further investigated. The effect of substituents on the acidity of the boronic acid was measured. The boronic acid pKa changed in the expected manner when electron donating or withdrawing groups were present. The glucose binding constants were dependent on pKa, but no simple correlation was observed for the Stern-Volmer quenching constants and the fluorescence signal modulation.
- Sharrett, Zachary,Gamsey, Soya,Fat, Jonathan,Cunningham-Bryant, Daniel,Wessling, Ritchie A.,Singaram, Bakthan
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p. 5125 - 5129
(2008/02/10)
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- On the functionalization of [2.2](1,4)phenanthrenoparacyclophane
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Two routes for preparing functionalized [2.2](1,4) phenanthrenoparacyclophanes are described: either the parent system 2 is subjected to electrophilic substitution (bromination, Friedel-Crafts acylation, Rieche formylation: preparation of 5, 6, 7, 11 and 12) or the desired substituents are incorporated in the early stages of the synthesis by the preparation of the corresponding functionalized styryl paracyclophanes and their photocyclization to the respective phenanthrenocyclophanes. By these specific routes various bronudes (22a,b), ethers (28a-c) and phenols (29a,b) were synthesized. The latter derivatives, on oxidation, furnish para-(31) and ortho-quinonophanes (30, 32, 33), useful substrates for the preparation of cyclophanes containing phenazine subunits (36). The stilbene → phenanthrene photocyclization can also be employed for the preparation of benzothiophenophanes, e.g. 43 and 44, from the respective precursors. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Hopf, Henning,Hucker, Joachim,Ernst, Ludger
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p. 1891 - 1904
(2008/02/06)
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- 1,2-BIS-(SUBSTITUTED-PHENYL)-2-PROPEN-1-ONES AND PHARMACEUTICAL COMPOSITIONS THEREOF
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The invention relates to compounds, pharmaceutical compositions and methods of using compounds of the general formula (I), or its pharmaceutically acceptable salt or ester, wherein the substituents are defined in the application.
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Page/Page column 122
(2010/02/15)
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- Efficient synthesis of 2-substituted imidazoles by palladium-catalyzed cross-coupling with benzylzinc reagents
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Substituted benzylzinc reagents have been used in novel cross-coupling reactions with 2-iodo imidazoles to form compounds containing both a phenol and an imidazole moiety. The intramolecular hydrogen-bonding properties of these compounds were subsequently studied. Georg Thieme Verlag Stuttgart.
- Utas, Josefin E.,Olofsson, Berit,?kermark, Bj?rn
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p. 1965 - 1967
(2008/02/08)
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- Functionalized benzylic magnesium reagents through a sulfur-magnesium exchange
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(Chemical Equation Presented) Switch it: lodobiphenyl thioethers readily undergo an iodine-magnesium exchange followed by, after the addition of tBuOLi, an intramolecular sulfur-magnesium exchange, which provides benzylic magnesium reagents in excellent yield through a fragmentation reaction.
- Stoll, Armin H.,Krasovskiy, Arkady,Knochel, Paul
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p. 606 - 609
(2007/10/03)
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- A simple and efficient iodination of alcohols on polymer-supported triphenylphosphine
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A simple, mild, and high-yielding procedure for the iodination of allylic, benzylic, and other primary alcohols using a combination of iodine and imidazole on polymer-supported triphenyl phosphine is described.
- Anilkumar, Gopinathan,Nambu, Hisanori,Kita, Yasuyuki
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p. 190 - 191
(2013/09/06)
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- PIPERAZINO DERIVATIVES AS NEUROKININ ANTAGONISTS
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The invention relates to compounds of the formulas STR1 wherein Z, R c, y, x, l 1, l 2, l 3, u, R 4,R c', n, R 1, R 2, and R 3, are as described herein. These compounds are neurokinin antagonists. These compounds are useful in the treatment of chronic airway diseases such as asthma.
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- Synthesis of chirally pure 2,5-disubstituted diketopiperazines derived from trisubstituted phenylalanines
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Some new chirally pure 2,5-substituted diketopiperazines were synthesized starting from 2-methoxybenzyl alcohol. This multistep synthesis proceeds through the enzymatic synthesis of chirally pure amino acids, protection and dipeptide coupling, cyclization of dipeptide ester formates, and nitration of the resulting diketopiperazines.
- Danthi, Satyavijayan Narasimhan,Hill, Ronald A.
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p. 835 - 844
(2007/10/03)
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- Nuclear versus Side-Chain Bromination of Methyl-Substituted Anisoles by N-Bromosuccinimide
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The reactions of methyl-substituted anisoles with N-bromosuccinimide in CCl4 are reported.In the absence of a catalyst and under irradiation, some of these substrates undergo nuclear bromination in competition with the well-known side-chain bromination.With 2-methylanisole and with 2,6-dimethylanisole, nuclear bromination is not observed, whereas with 3,5-dimethylanisole, nuclear bromination at the 4-position is the dominating reaction.Investigation of the reactivity of several other methyl-substituted anisoles revealed the following general trend: methyl-substituted anisoles are attacked at the position para to the methoxy group rather than at the side chain when (at least) two methyl groups are present at positions 3 and 5.When positions 2 and 6 are both occupied, nuclear bromination is retarded; in 2,6-dimethylanisole and 2,3,6-trimethylanisole, only side-chain bromination is observed.In contrast, in 2,3,5,6-tetramethylanisole, the 4-position is sufficiently reactive to be brominated, because the decrease in reactivity by the presence of two methyl groups at positions 2 and 6 is overruled by the two additional methyl groups at positions 3 and 5; as a result, both nuclear and side-chain bromination occur.The observed chemospecificity can be rationalized by a difference in mechanism: the side-chain bromination is radical reaction, while the nuclear bromination is an electrophilic aromatic substitution reaction, which is so far contrary to expectation, as irradiation had been expected to favor radical processes.
- Gruter, Gert-Jan M.,Akkerman, Otto S.,Bickelhaupt, Friedrich
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p. 4473 - 4481
(2007/10/02)
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- ORGANIC PHOSPHORUS COMPOUNDS 91. SYNTHESIS AND PROPERTIES OF 1-AMINO-2-ARYLETHYLPHOSPHONIC AND -PHOSPHINIC ACIDS AS WELL AS -PHOSPHINE OXIDES
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The preparation, physical and spectroscopic properties of 1-amino-2-arylethylphosphonic, and -phosphinic acids as well as -phosphine oxides, the phosphorus analogues of phenylalanine are described, and the reactions of 1-amino-2-(4-fluorophenyl)ethylphosphonates with acetals, isocyanides, esters, acid anhydrides, activated aromatic nitro- and halogen compounds, and with N-protected alanine are reported.It is shown that several of the 1-amino-2-arylethylphosphonic acids are strong inhibitors of PAL and anthocyanin synthesis and also are quite active botryticides.Among the active compounds were 1-amino-2-(4-fluorophenyl)ethylphosphonic acid, 3f, and the methyl-substituted compounds 3k, 3l, and 3m.The fluoroderivative 3f was also effective as a seed-dressing agent in barley showing a 100percent protection against the fungus Fusarium nivale at 600 ppm.
- Maier, Ludwig
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- Synthesis and antirhinovirus activity of 6-(dimethylamino)-2-(trifluoromethyl)-9-(substituted benzyl)-9H-purines
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A series of 6-(dimethylamino)-2-(trifluoromethyl)-9-(substituted benzyl)purines was synthesized and tested for antirhinovirus activity. Most of the compounds were synthesized by alkylation of 6-chloro-2-(trifluoromethyl)-9H-purine with the appropriate benzyl halide followed by displacement of the chloro group with dimethylamine. Alternatively, 6-(dimethylamino)-2-(trifluoromethyl)purine was alkylated with the appropriate benzyl halide. Although several different aryl substituents provided compounds with IC50's = 0.03 μM against rhinovirus serotype 1B, no congener was significantly more active than the parent 2. Twenty-three compounds were tested against 18 other serotypes, but none exhibited a uniform profile of activity.
- Kelley,Linn,Selway
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p. 1757 - 1763
(2007/10/02)
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