- Deoxygenative hydroboration of primary, secondary, and tertiary amides: Catalyst-free synthesis of various substituted amines
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Transformation of relatively less reactive functional groups under catalyst-free conditions is an interesting aspect and requires a typical protocol. Herein, we report the synthesis of various primary, secondary, and tertiary amines through hydroboration of amides using pinacolborane under catalyst-free and solvent-free conditions. The deoxygenative hydroboration of primary and secondary amides proceeded with excellent conversions. The comparatively less reactive tertiary amides were also converted to the corresponding N,N-diamines in moderate yields under catalyst-free conditions, although alcohols were obtained as a minor product.
- An, Duk Keun,Jaladi, Ashok Kumar,Kim, Hyun Tae,Yi, Jaeeun
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- Selective Synthesis of Secondary and Tertiary Amines by Reductive N-Alkylation of Nitriles and N-Alkylation of Amines and Ammonium Formate Catalyzed by Ruthenium Complex
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A new ruthenium catalytic system for the syntheses of secondary and tertiary amines via reductive N-alkylation of nitriles and N-alkylation of primary amines is proposed. Isomeric complexes 8 catalyze transfer hydrogenation and N-alkylation of nitriles in ethanol to give secondary amines. Unsymmetrical secondary amines can be produced by N-alkylation of primary amines with alcohols via the borrowing hydrogen methodology. Aliphatic amines were obtained with excellent yields, while only moderate conversions were observed for anilines. Based on kinetic and mechanistic studies, it is suggested that the rate determining step is the hydrogenation of intermediate imine to amine. Finally, ammonium formate was applied as the amination reagent for alcohols in the presence of ruthenium catalyst 8. Secondary amines were obtained from primary alcohols within 24 hours at 100 °C, and tertiary amines can be produced after prolonged heating. Secondary alcohols can only be converted to secondary amines with moderate yield. Based on mechanistic studies, the process is suggested to proceed through an ammonium alkoxy carbonate intermediate, where carbonate acts as an efficient leaving group.
- Alshakova, Iryna D.,Nikonov, Georgii I.
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p. 5370 - 5378
(2019/06/14)
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- Selective N-alkylation of amines using nitriles under hydrogenation conditions: Facile synthesis of secondary and tertiary amines
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Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH4OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields. Under the same reaction conditions, aromatic nitro compounds instead of the aromatic primary amines could be directly transformed into secondary amines via a domino reaction involving the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N-monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N-monoalkylation of the aliphatic primary amines and additional Pd/C-catalyzed alkylation of the resulting secondary aliphatic amines could selectively prepare aliphatic tertiary amines possessing three different alkyl groups. According to the mechanistic studies, it seems reasonable to conclude that nitriles were reduced to aldimines before the nucleophilic attack of the amine during the first step of the reaction.
- Ikawa, Takashi,Fujita, Yuki,Mizusaki, Tomoteru,Betsuin, Sae,Takamatsu, Haruki,Maegawa, Tomohiro,Monguchi, Yasunari,Sajiki, Hironao
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supporting information; experimental part
p. 293 - 304
(2012/02/01)
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- Pyrano-[2,3b]-pyridines as potassium channel antagonists
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The design and synthesis of a series of highly functionalized pyrano-[2,3b]-pyridines is described. These compounds were assayed for their ability to block the IKur channel encoded by the gene hKV1.5 in patch-clamped L-929 cells. Six of the compounds in this series showed sub-micromolar activity, the most potent being 4-(4-ethyl-benzenesulfonylamino)-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3b]-pyridine-6-carboxylic acid ethyl-phenyl-amide with an IC50 of 378 nM.
- Finlay, Heather J.,Lloyd, John,Nyman, Michael,Conder, Mary Lee,West, Tonya,Levesque, Paul,Atwal, Karnail
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p. 2714 - 2718
(2008/12/21)
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- Treating urinary incontinence using (S)-desethyloxybutynin
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A method for treating urinary incontinence while avoiding concomitant liability of adverse effects associated with racemic oxybutynin is disclosed. The method comprises administering a therapeutically effective amount of (S)-oxybutynin, (S)-desethyloxybut
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- Central cholinergic agents. I. Potent acetylcholinesterase inhibitors, 2-[ω-[N-alkyl-N-(ω-phenylalkyl)amino]alkyl]-1H-isoindole-1,3(2H)-dion es, based on a new hypothesis of the enzyme's active site
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It has been suggested that the active site of acetylcholinesterase contains a hydrophobic binding site (HBS-1), which is closely adjacent to both the anionic and the esteratic sites. In this paper, we assumed that there exists another hydrophobic binding site (HBS-2), some distance removed from the anionic site. On this assumption, a new working hypothesis was proposed for the design of acetylcholinesterase inhibitors. A series of 2-[ω-[N-alkyl-N-(ω-phenylalkyl)amino]alkyl]-1H-isoindole-1,3(2H)-dion es was designed based on this hypothesis and tested for its inhibitory activities on acetylcholinesterase. Some in this series were revealed to be more potent than physostigmine. Optimum activity was found to be associated with a five carbon chain length separating the benzylamino group from the 1H-isoindole-1,3(2H)-dione (phthalimide) moiety. Quantitative study of substitution effect on the phthalimide moiety revealed that hydrophilic and electron-withdrawing groups enhance the activity.
- Ishihara,Kato,Goto
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p. 3225 - 3235
(2007/10/02)
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- Cross Interaction Constants As a Measure of Transition State structure. Part 7. Aminolysis of Alkyl Benzenesulphonates
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Kinetic studies of the reactions of methyl and ethyl benzenesulphonates with anilines and benzylamines in methanol and acetonitrile at 65.0 deg C have been reported.The magnitudes of cross-interaction constants between substituents in the nucleophile (X) and the leaving group (Z),ρxz and βxz, were found to be greater for the ethyl series which indicates a tighter transition state for ethyl rather than methyl derivatives.This unexpected trend has been rationalized by making the assumption that the small electron-donating polar effect, of the α-methyl substituent in the ethyl compounds, requires a tighter transition-state structure in addition to the major effect of steric repulsion on the activation barrier which is present in all SN2 reactions taking place at a carbon centre.
- Lee, Ikchoon,Choi, Young Hoon,Rhyu, Keun Woo,Shim, Chang Sub
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p. 1881 - 1886
(2007/10/02)
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- Reactions of N-Chlorobenzylalkylamines with Sodium Methoxide in Methanol. Steric Effects in Elimination Reactions
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Reactions of N-chlorobenzylalkylamines in which the alkyl group is Me, Et, i-Pr, t-Bu, and sec-Bu with MeONa-MeOH have been investigated kinetically.The eliminations are quantitative and regiospecific, producing only benzylidenealkylamines.The reactions are first order in base and first order in substrate, and an E2 mechanism is evident.The relative rates of elimination at 25 deg C are 1/0.5/0.3/0.2/0.01 for Me/Et/i-Pr/sec-Bu/t-Bu alkyl substituents, respectively.The results are attributed to repulsive interaction between the alkyl group and the base in the transition state.Hammett ρ and kH/kD values decreased, but the ΔH(excit.) and ΔS(excit.) values increased with bulkier alkyl substituents.Changes in the transition-state parameters with the substrate steric effect are interpreted with variation in structure of the imine-forming transition states.
- Cho, Bong Rae,Maeng, Jun Ho,Yoon, Jong Chan,Kim, Tae Rin
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p. 4752 - 4756
(2007/10/02)
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- Benzylamines: Synthesis and evaluation of antimycobacterial properties
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The synthesis of benzylamines with various N-alkyl chains and substituents in the aromatic system as well as their evaluation on Mycobacterium tuberculosis H 37 Ra are described. The most active compounds in this test, N-methyl-3-chlorobenzylamine (MIC 10.2 μg/mL), N-methyl-3,5-dichlorobenzylamine (93, MIC 10.2 μg/mL), and N-butyl-3,5-difluorobenzylamine (MIC 6.4 μg/mL), also exhibited a marked inhibitory effect on Mycobacterium marinum and Mycobacterium lufu used for the determination of antileprotic properties. The combination of 93 with aminosalicylic acid, streptomycin, or dapsone exert marked supra-additive effects on M. tuberculosis H 37 Ra.
- Meindl,Von Angerer,Schonenberger,Ruckdeschel
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p. 1111 - 1118
(2007/10/02)
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- N,N'-Dialkyl-1,2-bis(hydroxyphenyl)ethylenediamines and N,N'-Dialkyl-4,5-bis(4-hydroxyphenyl)imidazolidines: Syntheses and Evaluation of Their Mammary Tumor Inhibiting Activity
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Diastereomeric N,N'-dialyl-1,2-bis(hydroxyphenyl)ethylenediamines (5) were synthesized and tested for their affinity for the estradiol receptor.Only the (+/-)-1,2-bis(4-hydroxyphenyl)ethylenediamines with the alkyl groups C3H7 a=1.1
- Angerer, Erwin von,Egginger, Guenter,Kranzfelder, Gerhard,Bernhauer, Horst,Schoenenberger, Helmut
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p. 832 - 837
(2007/10/02)
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