- Time-Resolved Crystallography of the Reaction Intermediate of Nitrile Hydratase: Revealing a Role for the Cysteinesulfenic Acid Ligand as a Catalytic Nucleophile
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The reaction mechanism of nitrile hydratase (NHase) was investigated using time-resolved crystallography of the mutant NHase, in which βArg56, strictly conserved and hydrogen bonded to the two post-translationally oxidized cysteine ligands, was replaced by lysine, and pivalonitrile was the substrate. The crystal structures of the reaction intermediates were determined at high resolution (1.2-1.3?). In combination with FTIR analyses of NHase following hydration in H218O, we propose that the metal-coordinated substrate is nucleophilically attacked by the O(SO-) atom of αCys114-SO-, followed by nucleophilic attack of the S(SO-) atom by a βArg56-activated water molecule to release the product amide and regenerate αCys114-SO-.
- Yamanaka, Yasuaki,Kato, Yuki,Hashimoto, Koichi,Iida, Keisuke,Nagasawa, Kazuo,Nakayama, Hiroshi,Dohmae, Naoshi,Noguchi, Keiichi,Noguchi, Takumi,Yohda, Masafumi,Odaka, Masafumi
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- Hydration of Cyanohydrins by Highly Active Cationic Pt Catalysts: Mechanism and Scope
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Cyanohydrins (α-hydroxy nitriles) are a special type of nitriles that readily decompose into hydrogen cyanide (HCN) and the corresponding carbonyl compounds. Hydration of cyanohydrins that are readily available through cyanation of aldehydes and ketones provides the most straightforward route to valuable α-hydroxyamides. However, due to low stability of cyanohydrins and deactivation of the catalysts by the released HCN, catalytic direct hydration of cyanohydrins still remains largely unsolved. As a general trend, cyanohydrins containing bulkier substituents, such as α,α-diaryl cyanohydrins, degrade more quickly and thus are more difficult to be hydrated. Here, we report development of cationic platinum catalysts that exhibit high reactivity for hydration of various cyanohydrins. Detailed mechanistic investigations for hydration of nitriles by (PμP)Pt(PR2OH)X(OTf) reveal a catalytic cycle involving the formation of a five-membered metallacyclic intermediate and subsequent hydrolysis via attacking on the phosphorus of the secondary phosphine oxide (PR2OH) ligand by H2O. We discovered that Pt catalyst A bearing the electron-rich, appropriately small-bite-angle bisphosphine ligand provides super reactivity for hydration of cyanohydrins. The hydration reactions catalyzed by A proceed at ambient temperatures and occur with a wide variety of cyanohydrins, including the most difficult α,α-diaryl cyanohydrins, with good turnover numbers.
- Li, Chengcheng,Chang, Xiao-Yong,Huo, Luqiong,Tan, Haibo,Xing, Xiangyou,Xu, Chen
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p. 8716 - 8726
(2021/07/26)
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- Ru(ii)- And Ru(iv)-dmso complexes catalyze efficient and selective aqueous-phase nitrile hydration reactions under mild conditions
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New water-soluble ruthenium(ii)- and ruthenium(iv)-dmso complexes [RuCl2(dmso)2(NH3)(CH3CN)] (1), [RuCl2(dmso)3(CH3CN)] (2), and [RuCl2(dmso)3(NH3)]·PF6·Cl (3) have been synthesized and characterized using elemental analyses, IR, 1H and 31P NMR, and electronic absorption spectroscopy. The molecular structures of complexes 1-3 were determined crystallographically. The reactivity of complexes 1-3 has been tested for aqueous-phase nitrile hydration at 60 °C in air, and good efficiency and selectivity are shown for the corresponding amide derivatives. Best performance is achieved with complex 3. Amide conversions of 56-99% were obtained with a variety of aromatic, alkyl, and vinyl nitriles. The reaction tolerated hydroxyl, nitro, bromo, formyl, pyridyl, benzyl, alkyl, and olefinic functional groups. Amides were isolated by simple decantation from the aqueous-phase catalyst. A catalyst loading down to 0.0001 mol% was examined and turnover numbers as high as 990?000 were observed. The catalyst was stable for weeks in solution and could be reused more than seven times without significant loss in catalytic activity. The gram-scale reaction was also performed to produce the desired product in high yields. This journal is
- Dubey, Santosh Kumar,Kaur, Gurmeet,Rath, Nigam P.,Trivedi, Manoj
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p. 17339 - 17346
(2021/10/08)
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- Hydration of Aliphatic Nitriles Catalyzed by an Osmium Polyhydride: Evidence for an Alternative Mechanism
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The hexahydride OsH6(PiPr3)2 competently catalyzes the hydration of aliphatic nitriles to amides. The main metal species under the catalytic conditions are the trihydride osmium(IV) amidate derivatives OsH3{κ2-N,O-[HNC(O)R]}(PiPr3)2, which have been isolated and fully characterized for R = iPr and tBu. The rate of hydration is proportional to the concentrations of the catalyst precursor, nitrile, and water. When these experimental findings and density functional theory calculations are combined, the mechanism of catalysis has been established. Complexes OsH3{κ2-N,O-[HNC(O)R]}(PiPr3)2 dissociate the carbonyl group of the chelate to afford κ1-N-amidate derivatives, which coordinate the nitrile. The subsequent attack of an external water molecule to both the C(sp) atom of the nitrile and the N atom of the amidate affords the amide and regenerates the κ1-N-amidate catalysts. The attack is concerted and takes place through a cyclic six-membered transition state, which involves Cnitrile···O-H···Namidate interactions. Before the attack, the free carbonyl group of the κ1-N-amidate ligand fixes the water molecule in the vicinity of the C(sp) atom of the nitrile.
- Babón, Juan C.,Esteruelas, Miguel A.,López, Ana M.,O?ate, Enrique
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p. 7284 - 7296
(2021/05/29)
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- Ring Opening/Site Selective Cleavage in N-Acyl Glutarimide to Synthesize Primary Amides
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A LiOH-promoted hydrolysis selective C-N cleavage of twisted N-acyl glutarimide for the synthesis of primary amides under mild conditions has been developed. The reaction is triggered by a ring opening of glutarimide followed by C-N cleavage to afford primary amides using 2 equiv of LiOH as the base at room temperature. The efficacy of the reactions was considered and administrated for various aryl and alkyl substituents in good yield with high selectivity. Moreover, gram-scale synthesis of primary amides using a continuous flow method was achieved. It is noted that our new methodology can apply under both batch and flow conditions for synthetic and industrial applications.
- Govindan, Karthick,Lin, Wei-Yu
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supporting information
p. 1600 - 1605
(2021/03/03)
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- Unlocking Amides through Selective C–N Bond Cleavage: Allyl Bromide-Mediated Divergent Synthesis of Nitrogen-Containing Functional Groups
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We report a new set of reactions based on the unlocking of amides through simple treatment with allyl bromide, creating a common platform for accessing a diverse range of nitrogen-containing functional groups such as primary amides, sulfonamides, primary amines, N-acyl compounds (esters, thioesters, amides), and N-sulfonyl esters. The method has potential industrial applicability, as demonstrated through gram-scale syntheses in batch and in a continuous flow system.
- Govindan, Karthick,Chen, Nian-Qi,Chuang, Yu-Wei,Lin, Wei-Yu
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supporting information
p. 9419 - 9424
(2021/11/30)
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- Half-Sandwich Iridium Complexes for the One-Pot Synthesis of Amides: Preparation, Structure, and Diverse Catalytic Activity
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Several types of air-stable N,O-coordinate half-sandwich iridium complexes containing Schiff base ligands with the general formula [Cp*IrClL] were synthesized in good yields. These stable iridium complexes displayed a good catalytic efficiency in amide synthesis. A variety of amides with different substituents were obtained in a one-pot procedure with excellent yields and high selectivities through the amidation of aldehydes with NH2OHHCl and nitrile hydration under the catalysis of complexes 1-4. The excellent and diverse catalytic activity, mild conditions, broad substance scope, and environmentally friendly solvent make this system potentially applicable in industrial production. Half-sandwich iridium complexes 1-4 were characterized by NMR, elemental analysis, and IR techniques. Molecular structures of complexes 2 and 3 were confirmed by single-crystal X-ray analysis.
- Fan, Xiao-Nan,Deng, Wei,Liu, Zhen-Jiang,Yao, Zi-Jian
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p. 16582 - 16590
(2020/11/13)
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- One-pot reductive amination of carboxylic acids: a sustainable method for primary amine synthesis
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The reductive amination of carboxylic acids is a very green, efficient and sustainable method for the production of (bio-based) amines. However, with current technology, this reaction requires two to three reaction steps. Here, we report the first (heterogeneous) catalytic system for the one-pot reductive amination of carboxylic acids to amines, with solely H2 and NH3 as the reactants. This reaction can be performed with relatively cheap ruthenium-tungsten bimetallic catalysts in the green and benign solvent cyclopentyl methyl ether (CPME). Selectivities of up to 99% for the primary amine could be achieved at high conversions. Additionally, the catalyst is recyclable and tolerant for common impurities such as water and cations (e.g. sodium carboxylate).
- Coeck, Robin,De Vos, Dirk E.
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supporting information
p. 5105 - 5114
(2020/08/25)
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- Pyridine-Enabled C-N Bond Activation for the Rapid Construction of Amides and 4-Pyridylglyoxamides by Cooperative Palladium/Copper Catalysis
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A pyridine-enabled C-N bond activation of peptidomimetics employing cooperative palladium/copper catalysis in water is developed. Diverse amides and 4-pyridylglyoxamides are simultaneously synthesized through two steps from commercially available materials in a rapid, environmentally friendly, and high atom-economical manner.
- Song, Liangliang,Claessen, Sander,Van Der Eycken, Erik V.
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p. 8045 - 8054
(2020/07/15)
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- Amine-boranes as Dual-Purpose Reagents for Direct Amidation of Carboxylic Acids
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Amine-boranes serve as dual-purpose reagents for direct amidation, activating aliphatic and aromatic carboxylic acids and, subsequently, delivering amines to provide the corresponding amides in up to 99% yields. Delivery of gaseous or low-boiling amines as their borane complexes provides a major advantage over existing methodologies. Utilizing amine-boranes containing borane incompatible functionalities allows for the preparation of functionalized amides. An intermolecular mechanism proceeding through a triacyloxyborane-amine complex is proposed.
- Choudhary, Shivani,Hamann, Henry J.,Ramachandran, P. Veeraraghavan
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supporting information
(2020/11/13)
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- Direct synthesis of amides from nonactivated carboxylic acids using urea as nitrogen source and Mg(NO3)2or imidazole as catalysts
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A new method for the direct synthesis of primary and secondary amides from carboxylic acids is described using Mg(NO3)2·6H2O or imidazole as a low-cost and readily available catalyst, and urea as a stable, and easy to manipulate nitrogen source. This methodology is particularly useful for the direct synthesis of primary and methyl amides avoiding the use of ammonia and methylamine gas which can be tedious to manipulate. Furthermore, the transformation does not require the employment of coupling or activating agents which are commonly required.
- Blacker, A. John,Chhatwal, A. Rosie,Lomax, Helen V.,Marcé, Patricia,Williams, Jonathan M. J.
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p. 5808 - 5818
(2020/06/21)
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- Hydration of nitriles using a metal-ligand cooperative ruthenium pincer catalyst
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Nitrile hydration provides access to amides that are important structural elements in organic chemistry. Here we report catalytic nitrile hydration using ruthenium catalysts based on a pincer scaffold with a dearomatized pyridine backbone. These complexes catalyze the nucleophilic addition of H2O to a wide variety of aliphatic and (hetero)aromatic nitriles in tBuOH as solvent. Reactions occur under mild conditions (room temperature) in the absence of additives. A mechanism for nitrile hydration is proposed that is initiated by metal-ligand cooperative binding of the nitrile.
- Guo, Beibei,Otten, Edwin,De Vries, Johannes G.
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p. 10647 - 10652
(2019/12/02)
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- A continuous-flow synthesis of primary amides from hydrolysis of nitriles using hydrogen peroxide as oxidant
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A continuous-flow synthesis of primary amides from hydrolysis of nitriles using hydrogen peroxide as oxidant has been developed. Using this procedure, a variety of nitriles could be smoothly transformed into the desired primary amides in good to excellent yields. The mild reaction conditions and the flowing reaction system greatly improved the safety and make the reaction easy to scale up.
- Zhan, Wei,Ji, Ling,Ge, Ze-mei,Wang, Xin,Li, Run-tao
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p. 1527 - 1532
(2018/02/21)
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- Copper(II)-Catalyzed Reactions of α-Keto Thioesters with Azides via C-C and C-S Bond Cleavages: Synthesis of N-Acylureas and Amides
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Cu(II)-catalyzed reaction of α-keto thioesters with trimethylsilyl azide (TMSN3) proceeds with the transformation of the thioester group into urea through C-C and C-S bond cleavages, constituting a practical and straightforward synthesis of N-acylureas. When diphenyl phosphoryl azide (DPPA) is used instead as the azide source in an aqueous environment, primary amides are formed via substitution of the thioester group. The reactions are proposed to proceed through Curtius rearrangement of the initially formed α-keto acyl azide to generate an acyl isocyanate intermediate, which reacts further with an additional amount of azide or water and rearranges to afford the corresponding products. To demonstrate the potentiality of the method, one-step syntheses of pivaloylurea and isovaleroylurea, displaying anticonvulsant activities, have been carried out.
- Maity, Rajib,Naskar, Sandip,Das, Indrajit
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p. 2114 - 2124
(2018/02/23)
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- Amidation of carboxylic acids via the mixed carbonic carboxylic anhydrides and its application to synthesis of antidepressant (1S,2R)-tranylcypromine
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Primary amidations of carboxylic acids 1 or 3 with NH4Cl in the presence of ClCO2Et and Et3N were developed to afford the corresponding primary amides in 22% to quantitative yields. Additionally, we have applied the amidation to the preparation of various amides containing hydroxamic acids and achieved the synthesis of (1S,2R)-tranylcypromine as an antidepressant medicine via Lossen rearrangement.
- Ezawa, Tetsuya,Kawashima, Yuya,Noguchi, Takuya,Jung, Seunghee,Imai, Nobuyuki
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p. 1690 - 1699
(2017/11/14)
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- Selective hydration of nitriles to amides catalysed by PCP pincer supported nickel(ii) complexes
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The (PCP)Ni-OH complexes 2R (R = iPr, tBu, Cy) are effective catalyst precursors for the selective hydration of nitriles to the corresponding amides under relatively mild conditions (80 °C) and low catalyst loadings (0.05-0.5%). Substrate scope includes aliphatic, vinylic and aromatic nitriles, but substrates with protic groups poison the catalyst abruptly. The catalysts are effective because the electron rich nature of the PCP ligands and their steric bulk renders the hydroxo group labile.
- Borau-Garcia,Gutsulyak,Burford,Piers
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p. 12082 - 12085
(2016/01/15)
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- Hydration of nitriles to amides by a chitin-supported ruthenium catalyst
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Chitin-supported ruthenium (Ru/chitin) promotes the hydration of nitriles to carboxamides under aqueous conditions. The nitrile hydration can be performed on a gram-scale and is compatible with the presence of various functional groups including olefins, aldehydes, carboxylic esters and nitro and benzyloxycarbonyl groups. The Ru/chitin catalyst is easily prepared from commercially available chitin, ruthenium(III) chloride and sodium borohydride. Analysis of Ru/chitin by high-resolution transmission electron microscopy indicates the presence of ruthenium nanoparticles on the chitin support.
- Matsuoka, Aki,Isogawa, Takahiro,Morioka, Yuna,Knappett, Benjamin R.,Wheatley, Andrew E. H.,Saito, Susumu,Naka, Hiroshi
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p. 12152 - 12160
(2015/02/19)
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- Selective NaOH-catalysed hydration of aromatic nitriles to amides
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The selective synthesis of aromatic and heteroaromatic amides through base-catalysed hydration of nitriles was achieved using inexpensive and commercially available NaOH as the only catalyst. A wide range of nitriles was selectively converted to their corresponding amides. Kinetic studies show that the double hydration of nitriles towards undesirable carboxylic acids is negligible under our reaction conditions.
- Schmid, Thibault E.,Gómez-Herrera, Alberto,Songis, Olivier,Sneddon, Deborah,Révolte, Antoine,Nahra, Fady,Cazin, Catherine S. J.
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p. 2865 - 2868
(2015/05/27)
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- Ammonolysis of anilides promoted by ethylene glycol and phosphoric acid
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Ethylene glycol (EG) and phosphoric acid have been found to promote the ammonolysis of a variety of diverse anilides as well as N-aryl carbamate, phthalimide, and urea substrates in the absence of transition metals or other Lewis acid promoters.
- Stephenson, Nickeisha A.,Gellman, Samuel H.,Stahl, Shannon S.
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p. 46840 - 46843
(2014/12/10)
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- The nonenzymatic decomposition of guanidines and amidines
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To establish the rates and mechanisms of decomposition of guanidine and amidine derivatives in aqueous solution and the rate enhancements produced by the corresponding enzymes, we examined their rates of reaction at elevated temperatures and used the Arrhenius equation to extrapolate the results to room temperature. The similar reactivities of methylguanidine and 1,1,3,3-tetramethylguanidine and their negative entropies of activation imply that their decomposition proceeds by hydrolysis rather than elimination. The influence of changing pH on the rate of decomposition is consistent with attack by hydroxide ion on the methylguanidinium ion (k2 = 5 × 10 -6 M-1 s-1 at 25 C) or with the kinetically equivalent attack by water on uncharged methylguanidine. At 25 C and pH 7, N-methylguanidine is several orders of magnitude more stable than acetamidine, urea, or acetamide. Under the same conditions, the enzymes arginase and agmatinase accelerate substrate hydrolysis 4 × 1014-fold and 6 × 1012-fold, respectively, by mechanisms that appear to involve metal-mediated water attack. Arginine deiminase accelerates substrate hydrolysis 6 × 1012-fold by a mechanism that (in contrast to the mechanisms employed by arginase and agmatinase) is believed to involve attack by an active-site cysteine residue.
- Lewis, Charles A.,Wolfenden, Richard
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supporting information
p. 130 - 136
(2014/01/23)
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- NITRILE HYDRATION CATALYZED BY RECYCLABLE RUTHENIUM COMPLEXES
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A method for hydrating a nitrile derivative to generate an amide derivative is provided. The method includes mixing the nitrile derivative with a ruthenium catalyst complex in an aqueous solution to form a mixture, and reacting the nitrile derivative with water in the aqueous solution and in the presence of the ruthenium catalyst complex to form a reacted mixture comprising the amide derivative. The ruthenium catalyst complex is represented by the following structural formula: RuX2(L)n, wherein X is an anionic ligand, L is a bifunctional phosphine ligand, and n is 3 or 4.
- -
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Paragraph 0030; 0031; 0032; 0033; 0034
(2013/04/24)
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- Hemilabile β-aminophosphine ligands derived from 1,3,5-triaza-7- phosphaadamantane: Application in aqueous ruthenium catalyzed nitrile hydration
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A series of β-aminophosphines derived from 1,3,5-triaza-7- phosphaadamantane (PTA) are described. PTA-CHPhNHPh (1), PTA-CH(p-C 6H4OCH3)NHPh (2), and PTA-CPh2NHPh (3) were prepared in good yield (62-77%) by reaction of lithiated PTA with the corresponding imine followed by hydrolysis. Compounds 1 and 2 were synthesized as pairs of diastereomers which were separated by successive recrystallization from THF/hexane. Compounds 1-3 are somewhat soluble in water (S 25o = 4.8 (1), 4.9 (2), 2.7 (3) g/L). Upon coordination to Ru(II) arene centers both monodentate (κ1-P) [RuCl 2(η6-toluene)(1-3)] and bidentate (κ 2-P,N) [RuCl(η6-toluene)(1-3)]Cl coordination modes were observed. Ru(II) arene complexes 4-6 exhibited hemilabile behavior transitioning between κ1-P and κ2-P,N coordination upon change in solvent or addition of a coordinating ligand such as Cl- or CH3CN. Complexes (4-6) were found to be active air stable catalysts for the aqueous phase hydration of various nitriles with TOF up to 285 h-1 and TON of up to 97 000 observed.
- Lee, Wei-Chih,Sears, Jeremiah M.,Enow, Raphel A.,Eads, Kelly,Krogstad, Donald A.,Frost, Brian J.
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p. 1737 - 1746
(2013/03/29)
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- Mechanistic investigations and secondary coordination sphere effects in the hydration of nitriles with [Ru(η6-arene)Cl2PR 3] complexes
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The mechanism of the nitrile-to-amide hydration reaction using [Ru(η6-arene)Cl2(PR3)] complexes as catalysts was investigated (η6-arene = C6H 6, p-cymene, C6Me6; R = NMe2, OMe, OEt, Et, iPr). Experiments showed that the mechanism involves the following general sequence of reactions: substitution of a chloride ligand by the nitrile substrate, intermolecular nucleophilic attack by water to form an amidate intermediate, and dissociation of the resulting amide. The effects of secondary coordination sphere interactions on the rates and yields of the hydration reaction were investigated. Ligands that are capable of acting as hydrogen bond acceptors with the entering water molecule result in faster rates and higher yields than non-hydrogen-bonding ligands. The faster rates are attributable to the H-bonding-facilitated deprotonation of the water as the oxygen of the water bonds to the coordinated nitrile. DFT calculations on the proposed H-bonding intermediates support this interpretation. Most homogeneous catalysts will not hydrate cyanohydrins because of the equilibrium amounts of cyanide that are present in solutions of cyanohydrins; the cyanide poisons the catalyst. Because of its increased catalytic reactivity due to secondary coordination sphere effects, the [Ru(η6-arene)Cl2(P(NMe2) 3)] catalyst gives significant yields of cyanohydrin hydration products with glycolonitrile, lactonitrile, acetone cyanohydrin, and mandelonitrile. A Taft plot showed that an increase in the steric bulk of the nitrile results in a decrease in the hydration rate, and a Hammett plot showed that electron-withdrawing groups facilitate nitrile hydration. The decrease in rate as the size of the cyanohydrin increases is likely due to both increased steric bulk and to the addition of electron-donating groups on the nitrile. The [Ru(η6-arene)Cl2(PR3)] catalysts are initially less susceptible to cyanide poisoning than other homogeneous nitrile hydration catalysts because [Ru(η6-p-cymene)(CN)(Cl)(P(NMe 2)3)] forms in the presence of cyanide. The electron-withdrawing cyanide ligand facilitates nucleophilic attack of water on a coordinated nitrile in this molecule.
- Knapp, Spring Melody M.,Sherbow, Tobias J.,Yelle, Robert B.,Zakharov, Lev N.,Juliette, J. Jerrick,Tyler, David R.
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supporting information
p. 824 - 834
(2013/03/28)
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- Catalytic nitrile hydration with [Ru(η6- p -cymene)Cl 2(PR2R′)] complexes: Secondary coordination sphere effects with phosphine oxide and phosphinite ligands
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The rates of nitrile hydration reactions were investigated using [Ru(η6-p-cymene)Cl2(PR2R′)] complexes as homogeneous catalysts, where PR2R′ = PMe 2(CH2P(O)Me2), PMe2(CH 2CH2P(O)Me2), PPh2(CH 2P(O)Ph2), PPh2(CH2CH 2P(O)Ph2), PMe2OH, P(OEt)2OH. These catalysts were studied because the rate of the nitrile-to-amide hydration reaction was hypothesized to be affected by the position of the hydrogen bond accepting group in the secondary coordination sphere of the catalyst. Experiments showed that the rate of nitrile hydration was fastest when using [Ru(η6-p-cymene)Cl2PMe2OH]: i.e., the catalyst with the hydrogen bond accepting group capable of forming the most stable ring in the transition state of the rate-limiting step. This catalyst is also active at pH 3.5 and at low temperatures - conditions where α-hydroxynitriles (cyanohydrins) produce less cyanide, a known poison for organometallic nitrile hydration catalysts. The [Ru(η6-p-cymene) Cl2PMe2OH] catalyst completely converts the cyanohydrins glycolonitrile and lactonitrile to their corresponding α-hydroxyamides faster than previously investigated catalysts. [Ru(η6-p-cymene) Cl2PMe2OH] is not, however, a good catalyst for acetone cyanohydrin hydration, because it is susceptible to cyanide poisoning. Protecting the -OH group of acetone cyanohydrin was shown to be an effective way to prevent cyanide poisoning, resulting in quantitative hydration of acetone cyanohydrin acetate.
- Knapp, Spring Melody M.,Sherbow, Tobias J.,Yelle, Robert B.,Juliette, J. Jerrick,Tyler, David R.
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supporting information
p. 3744 - 3752
(2013/07/26)
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- Convenient preparation of primary amides via activation of carboxylic acids with ethyl chloroformate and triethylamine under mild conditions
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Primary amides were easily prepared in 22-99% yields from the corresponding carboxylic acids 1 or 5 with NH4Cl via activation with ClCO 2Et and Et3N. The enantiomers of the corresponding primary amides of Cbz-, Boc-, or Fmoc-α-amino acids can be separated by using a chiral column.
- Noguchi, Takuya,Sekine, Masahiro,Yokoo, Yuki,Jung, Seunghee,Imai, Nobuyuki
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p. 580 - 582
(2013/07/05)
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- Aqueous and biphasic nitrile hydration catalyzed by a recyclable Ru(ii) complex under atmospheric conditions
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[RuCl2(PTA)4] (PTA = 1,3,5-triaza-7- phosphaadamantane) was found to be a highly active catalyst for aqueous phase nitrile hydration at 100 °C in air. Near quantitative conversion of aromatic, alkyl, and vinyl nitriles to their corresponding amides was observed. The reaction tolerated ether, hydroxyl, nitro, bromo, formyl, pyridyl, benzyl, alkyl, and olefinic functional groups. Some amides were isolated by simple decantation from the aqueous phase catalyst. Catalyst loading down to 0.001 mol% was examined with turnover numbers as high as 22000 observed. The catalyst was stable for weeks in solution and could be reused more than five times without significant loss of activity.
- Lee, Wei-Chih,Frost, Brian J.
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supporting information; experimental part
p. 62 - 66
(2012/03/26)
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- Bifunctional water activation for catalytic hydration of organonitriles
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Treatment of [Rh(COD)(μ-Cl)]2 with excess tBuOK and subsequent addition of 2 equiv of PIN?HBr in THF afforded [Rh(COD)(κC2-PIN)Br] (1) (PIN = 1-isopropyl-3-(5,7-dimethyl-1, 8-naphthyrid-2-yl)imidazol-2-ylidene, COD = 1,5-cyclooctadiene). The X-ray structure of 1 confirms ligand coordination to "Rh(COD)Br" through the carbene carbon featuring an unbound naphthyridine. Compound 1 is shown to be an excellent catalyst for the hydration of a wide variety of organonitriles at ambient temperature, providing the corresponding organoamides. In general, smaller substrates gave higher yields compared with sterically bulky nitriles. A turnover frequency of 20 000 h-1 was achieved for the acrylonitrile. A similar Rh(I) catalyst without the naphthyridine appendage turned out to be inactive. DFT studies are undertaken to gain insight on the hydration mechanism. A 1:1 catalyst-water adduct was identified, which indicates that the naphthyridine group steers the catalytically relevant water molecule to the active metal site via double hydrogen-bonding interactions, providing significant entropic advantage to the hydration process. The calculated transition state (TS) reveals multicomponent cooperativity involving proton movement from the water to the naphthyridine nitrogen and a complementary interaction between the hydroxide and the nitrile carbon. Bifunctional water activation and cooperative proton migration are recognized as the key steps in the catalytic cycle.
- Daw, Prosenjit,Sinha, Arup,Rahaman, S. M. Wahidur,Dinda, Shrabani,Bera, Jitendra K.
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experimental part
p. 3790 - 3797
(2012/06/18)
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- Lead discovery, chemistry optimization, and biological evaluation studies of novel biamide derivatives as CB2 receptor inverse agonists and osteoclast inhibitors
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N,N′-((4-(Dimethylamino)phenyl)methylene)bis(2-phenylacetamide) was discovered by using 3D pharmacophore database searches and was biologically confirmed as a new class of CB2 inverse agonists. Subsequently, 52 derivatives were designed and synthesized through lead chemistry optimization by modifying the rings A-C and the core structure in further SAR studies. Five compounds were developed and also confirmed as CB2 inverse agonists with the highest CB2 binding affinity (CB2Ki of 22-85 nM, EC50 of 4-28 nM) and best selectivity (CB 1/CB2 of 235- to 909-fold). Furthermore, osteoclastogenesis bioassay indicated that PAM compounds showed great inhibition of osteoclast formation. Especially, compound 26 showed 72% inhibition activity even at the low concentration of 0.1 μM. The cytotoxicity assay suggested that the inhibition of PAM compounds on osteoclastogenesis did not result from its cytotoxicity. Therefore, these PAM derivatives could be used as potential leads for the development of a new type of antiosteoporosis agent.
- Yang, Peng,Myint, Kyaw-Zeyar,Tong, Qin,Feng, Rentian,Cao, Haiping,Almehizia, Abdulrahman A.,Alqarni, Mohammed Hamed,Wang, Lirong,Bartlow, Patrick,Gao, Yingdai,Gertsch, Jürg,Teramachi, Jumpei,Kurihara, Noriyoshi,Roodman, Garson David,Cheng, Tao,Xie, Xiang-Qun
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p. 9973 - 9987
(2013/01/16)
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- Double molecular recognition with aminoorganoboron complexes: Selective alcoholysis of β-dicarbonyl derivatives
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Double duty: Aminoorganoboron (AOB) complexes recognize alcohol and β-dicarbonyl units, and thereby facilitate chemo- and site-selective alcoholysis of the latter (see scheme). The complex activates both reaction partners. This strategy enables C-C, C-N, and C-O bond cleavage in addition/elimination reactions under near neutral pH conditions and provides a new method for functional group conversions. Copyright
- Oishi, Shunsuke,Saito, Susumu
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supporting information; experimental part
p. 5395 - 5399
(2012/06/18)
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- Efficient hydrolysis of nitriles to amides with hydroperoxide anion in aqueous surfactant solutions as reaction medium
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Aliphatic and aromatic nitriles are converted to corresponding amides in a single step via hydrolysis with basic H2O2 in aqueous solution of the surfactant Cetyltrimethylammonium methanesulfonate (CTAOMs). The method has several advantages: use and recycle of water as reaction medium, use of environmentally benign oxidant H2O2, easy product isolation, short reaction time, high yields and selectivity, mild conditions.
- Brinchi, Lucia,Chiavini, Lisa,Goracci, Laura,Di Profio, Pietro,Germani, Raimondo
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experimental part
p. 175 - 179
(2010/04/23)
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- Synthesis and evaluation of antiallodynic and anticonvulsant activity of novel amide and urea derivatives of valproic acid analogues
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Valproic acid (VPA, 1) is a major broad spectrum antiepileptic and central nervous system drug widely used to treat epilepsy, bipolar disorder, and migraine. VPA's clinical use is limited by two severe and lifethreatening side effects, teratogenicity and hepatotoxicity. A number of VPA analogues and their amide, N-methylamide and urea derivatives, were synthesized and evaluated in animal models of neuropathic pain and epilepsy. Among these, two amide and two urea derivatives of 1 showed the highest potency as antineuropathic pain compounds, with ED50 values of 49 and 51 mg/kg for the amides (19 and 20) and 49 and 74 mg/kg for the urea derivatives (29 and 33), respectively. 19, 20, and 29 were equipotent to gabapentin, a leading drug for the treatment of neuropathic pain. These data indicate strong potential for the above-mentioned novel compounds as candidates for future drug development for the treatment of neuropathic pain. 2009 American Chemical Society.
- Kaufmann, Dan,Bialer, Meir,Shimshoni, Jakob Avi,Devor, Marshall,Yagen, Boris
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experimental part
p. 7236 - 7248
(2010/07/04)
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- RhI-catalyzed hydration of organonitriles under ambient conditions
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(Chemical Presented) New scoop on scope and selectivity: The hydration of organonitriles catalyzed by a RhI(OMe) species under nearly pH-neutral and ambient conditions (25°C, 1 atm) is chemoselective and high-yielding (93 to 99%), has a broad substrate scope, and may thus be complementary to enzymatic hydration methods for the introduction of a terminal amido group (CONH2) onto a carbon chain.
- Goto, Akihiro,Endo, Kohei,Saito, Susumu
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p. 3607 - 3609
(2008/12/23)
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- Generation of nitrene by the photolysis of N-substituted iminodibenzothiophene
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(Chemical Equation Presented) To evaluate the ability of dibenzothiophene N-substituted sulfilimines as photochemical nitrene sources, their photolyses in the presence of several trapping reagents, such as sulfides, olefins, and phosphorus compounds, were performed. In the reactions, the corresponding imino-transfer compounds, namely sulfilimines, aziridines, and iminophosphoranes, were formed in good yields, indicating dibenzothiophene N-tosyl and N-acylsulfilimines have a potent nature as nitrogen sources.
- Morita, Hiroyuki,Tatami, Atsushi,Maeda, Tetsuo,Byung, Ju Kim,Kawashima, Wataru,Yoshimura, Toshiaki,Abe, Hitoshi,Akasaka, Takeshi
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scheme or table
p. 7159 - 7163
(2009/04/18)
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- Ceric ammonium nitrate (CAN) promoted efficient solid phase synthesis of amide derivatives: A green approach
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Ceric ammonium nitrate (CAN) has been found to be an efficient catalyst for the solid phase synthesis of amide derivatives of a wide range of substituted carboxylic acids and urea in excellent yields under microwave irradiation conditions. High yields are achieved even on a gram scale, while reaction times are considerably shortened. This method displays both economic and environmental advantages.
- Reddy, Ch. Sanjeeva,Raghu,Nagaraj
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p. 315 - 318
(2008/09/20)
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- Direct preparation of primary amides by reaction of carboxylic acids and ammonia in alcohols using DMT-MM
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A simple and mild method for the direct conversion of carboxylic acids to primary amides has been developed by using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)- 4-methylmorpholim'um chloride (DMT-MM). The reaction proceeds by adding DMT-MM to a mixture of carboxylic acids and an ammonia source in methanol, 2-propanol, or THF without any additives. The present method is quite practical in that aqueous ammonia or ammonium chloride/triethylarnine can be used as an ammonia source. Methanol or 2-propanol is an ideal polar solvent because it is inexpensive, can be removed by rotary evaporator, and solubilizes many kinds of polar or nonpolar compounds.
- Mizuhara, Tsukasa,Hioki, Kazuhito,Yamada, Megumi,Sasaki, Hideaki,Morisaki, Daiki,Kunishima, Munetaka
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experimental part
p. 1191 - 1192
(2009/12/01)
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- Platinum-Catalyzed Selective Hydration of Hindered Nitriles and Nitriles with Acid- or Base-Sensitive Groups
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Hindered tertiary nitriles can be hydrolyzed under neutral and mild conditions to the corresponding amides using platinum(II) catalysts with dimethylphosphine oxide or other secondary phosphine oxides (SPOs, phosphinous acids) as ligands. We have found that this procedure also works well for nitriles with acid- or base-sensitive groups, which is unprecedented in terms of yield and selectivity. The catalyst loading can be as low as 0.5 mol %. Amides are isolated as the only product in high yield, and no further hydrolysis to the corresponding acids takes place. Reactions are carried out at 80 °C but take place even at room temperature. When enantiopure secondary phosphine oxide ligands are used in the hydrolysis of racemic nitriles, no kinetic resolution is observed, presumably due to racemization of the ligand during the reaction.
- Jiang, Xiao-Bin,Minnaard, Adriaan J.,Feringa, Ben L.,De Vries, Johannes G.
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p. 2327 - 2331
(2007/10/03)
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- 4,4-DISUBSTITUTED-1,4-DIHYDRO-2H-3,1-BENZOXAZIN-2-ONES USEFUL AS HIV REVERSE TRANSCRIPTASE INHIBITORS AND INTERMEDIATES AND PROCESSES FOR MAKING THE SAME
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The present invention relates to benzoxazinones of formula I, or stereoisomeric forms or mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, and to pharmaceutical compositions and diagnostic kits comprising the same, methods of using same for treating viral infection or as an assay standard or reagent, and intermediates and processes for making the same.
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- Direct conversion of aldehydes to amides, tetrazoles, and triazines in aqueous media by one-pot tandem reactions
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A variety of aldehydes reacted with iodine in ammonia water at room temperature to give the nitrile intermediates, which were trapped by addition of hydrogen peroxide, sodium azide, or dicyandiamide to produce their corresponding amides, tetrazoles, and 1,3,5-triazines in modest to high yields. The one-pot tandem reactions were conducted in water media, and the products were obtained simply by extraction or filtration.
- Shie, Jiun-Jie,Fang, Jim-Min
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p. 1158 - 1160
(2007/10/03)
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- Niobium pentachloride promoted conversion of carboxylic acids to carboxamides: Synthesis of the 4-aryl-1,2,3,4-tetrahydroisoquinoline alkaloid structures
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A practical method for the conversion of carboxylic acids to the corresponding carboxamides mediated by niobium pentachloride under mild conditions is described. The synthesis of the 4-aryl-1,2,3,4-tetrahydroisoquinoline alkaloid structures was accomplished via benzylic lithiation of N-methyl-3,4-dimethoxy-2-(4′-methoxybenzyl)benzamide.
- Nery, Marcelo S.,Ribeiro, Renata P.,Lopes, Claudio C.,Lopes, Rosangela S. C.
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p. 272 - 276
(2007/10/03)
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- Potassium trimethylsilanolate mediated hydrolysis of nitriles to primary amides
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Treatment of nitriles with potassium trimethylsilanolate under mild anhydrous conditions readily yields the corresponding primary amides after a simple aqueous workup. (C) 2000 Elsevier Science Ltd.
- Merchant, Kevin J.
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p. 3747 - 3749
(2007/10/03)
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- 5,5-disubstituted-1,5-dihydro-4,1-benzoxazepin-2 (3H)-ones useful as HIV reverse transcriptase inhibitors
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The present invention relates to benzoxazepinones of formula I: STR1 or stereoisomeric forms or mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, and to pharmaceutical compositions and diagnostic kits comprising the same and methods of using the same for treating viral infection or as an assay standard or reagent.
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- Efficient synthesis of primary amides using 2-mercaptopyridone-1-oxide-based uronium salts
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S-(1-Oxido-2-pyridinyl)-1,1,3,3-tetramethylthiouronium tetrafluoroborate (TOTT) and hexafluorophosphate (HOTT) are cheap and convenient reagents for the rapid and high-yielding preparation of primary amides when reacted with carboxylic acids and ammonium chloride in the presence of diisopropylethylamine. The reaction is chemoselective and undesired ammonolysis of other sensitive functional groups is not observed. (C) 2000 Elsevier Science Ltd.
- Bailen,Chinchilla,Dodsworth,Najera
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p. 9809 - 9813
(2007/10/03)
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- 4,4-disubstitued-1,4-dihydro-2H-3,1-benzoxazin-2-ones useful as HIV reverse transcriptase inhibitors and intermediates and processes for making the same
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The present invention relates to benzoxazinones of formula I: STR1 or stereoisomeric forms or mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, and to pharmaceutical compositions and diagnostic kits comprising the same, methods of using the same for treating viral infection or as an assay standard or reagent, and intermediates and processes for making the same.
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- An efficient and convenient synthesis of formamidines
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A set of new reagents, aryl sulfonyl chlorides, were used as coupling agents in the syntheses of formamidines from primary amines and N,N-dimethyl formamide in excellent yields.
- Han, Ying,Cai, Lisheng
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p. 5423 - 5426
(2007/10/03)
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- ρ-heteroatom-substituted phenols and uses thereof
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The present invention provides an antiproliferative p-heteroatom-substituted phenol compound having the structure formula STR1 wherein m is 0 to 3, n is 0 to 4 when Het is nitrogen, wherein R is selected from the group consisting of hydrogen, alkyl, arylmethyl and acyl; R1 is alkyl; R2 is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of alkyl and acyl when Het is nitrogen, R4 is selected from the group consisting of hydrogen and alkyl; R5 is selected from the group consisting of hydrogen and alkyl; and R6 and R7 are selected from the group consisting of hydrogen, alkyl and R6 and R7 together may represent oxygen. Also provided are various methods for the treatment of a pathological cell proliferative disease comprising administering to an animal) a pharmacologically and therapeutically effective dose of a pharmaceutical composition comprising a p-heteroatom-substituted phenols or an analog thereof.
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- The reactions of phenyldimethylsilyllithium with nitriles
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Phenyldimethylsilyllithium reacts with nitriles by several substantially different pathways depending upon the structure of the nitrile. The products include the acylsilane 2 from pivalonitrile (1), cumylsilane 5 from 2-phenylisobutyronitrile (4), the α-anion from phenylacetonitrile (9), and a mixture of benzil (15) and 2,4,5-triphenylimidazole (17) from benzonitrile (13).
- Fleming, Ian,Solay, Monica,Stolwijk, Frederik
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p. 121 - 124
(2007/10/03)
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- Reactions of N-acylaziridines with sodium metal and sodium naphthalenide. Elimination of olefines
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Reactions of N-acylaziridines 1a-g (N-benzoyl except 1d) with sodium or naphthalenide N.- in THF provide a variety of products that usually arise via the aziridino ketyls 2. Homolytic ring opening of 2 generates the amidatoalkyl radicals 3. Only with a very short reaction time were small amounts of benzil or benzoylnaphthalenes obtained indicating a reversible trapping of 2 by dimerization or coupling with N.-. Homolysis of 2 produced always the more stable 3 apart from reactions of monomethylaziridines 1c,d where the primary radical i-3c,d is kinetically favoured. The amides R1CONHCHR4CHR2R3 (9, isopropylamides i-9c,d from 1c,d) were usually the main products. 9 arise from 3 either by H atom abstraction from THF (probably in sodium metal runs) or by reduction of 3 to carbanions 5 that abstract a proton from THF (N.- runs). Addition of 5a (R2-4 = H) to 1a gives finally the ketone 8a. Self reaction of primary radical 3a is dimerization. Self reaction of tertiary or secondary radicals is disproportionation when an allylamide arises. This isomerizes to an enamide unless it is conjugated. R2R3C=CHR4 and R1CONH2 arise (probably) always. The mechanism, possibly a cyclic process of anion 6, is not clear. Johann Ambrosius Barth 1996.
- Lin, Pen-Yuan,Bellos, Konstantinos,Werry, Juergen,Assithianakis, Petros,Weiss, Rainer,Mall, Thomas,Bentz, Gunther,Stamm, Helmut
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p. 270 - 278
(2007/10/03)
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- The Acid-Catalyzed and Uncatalyzed Hydrolysis of Nitriles on Unactivated Alumina
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Nitriles are selectively converted into amides on unactivated alumina, with the surface hydroxyl groups serving as the source of water.
- Wilgus, Catherine Pala,Downing, Susan,Molitor, Erich,Bains, Satinder,Pagni, Richard M.,Kabalka, George W.
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p. 3469 - 3472
(2007/10/02)
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- Method for converting amides to nitriles and nitriles to amides
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A process which comprises contacting and catalytically reacting under essentially anhydrous conditions in the liquid phase an amide with a nitrile according to the equation: where R and R1 are not the same and are each selected from (1) H, hydrocarbyl, a hydrocarbyl group substituted with: one or more of F, Cl, Br, I, amido, cyano, formyl, hydrocarbylcarbonyl, hydrocarbyloxy, hydrocarbyloxycarbonyl, hydrocarbylcarbonyloxy and dihydrocarbylamino, and (2) any of group (1) where one or more H atoms are substituted by a deuterium atom,
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- Multigram Preparation of 2-Alkylpyrimidines in the Vapor Phase from Carboxylic Acids and 1,3-Diaminopropane over a Dual Catalyst System
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2-Alkylpyrimidines 2 were obtained from cofeeding a carboxylic acid such as pivalic acid (3a) or propionic acid (3b) and 1,3-diaminopropane (4) over first an alumina catalyst at 250-290 deg C and second a palladium dehydrogenation catalyst at 300-340 deg C to give 2 directly in 56-68percent overall yields.On the alumina bed, initial amidation of organic acid occurs to give the monoacyltrimethylenediamine 5, followed by ring closure to the tetrahydropyrimidine intermediate 6.An equilibrium between 5, 6, and water is established on the alumina bed, with an apparent equilibrium constant of 53 +/- 7 mol/kg at 290 deg C.The high temperature of the alumina bed shifts the equilibrium in favor of 6, which is directly dehydrogenated to 2 over the palladium catalyst.The method avoids the need to isolate and purify solid intermediates.The presence of low levels of sulfur acts as a strong palladium catalyst deactivator.Gradual decline of palladium catalyst activity was observed due to carbon buildup.No decline in alumina catalyst activity was observed.The continuous process allows for the preparation of multigram quantities of 2 with a laboratory-scale reactor.
- Hull, John W.,Otterson, Kari
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p. 2925 - 2929
(2007/10/02)
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