Neighboring Group Reactions. I. Nucleophilic Attack by Alkoxide and Hydroxide Ion on 3-(ι-Haloalkyl)-3-phenyl-2-benzofuranones. A New Synthesis of 1-Benzoxacycloalkanes

1961 ◽  
Vol 26 (12) ◽  
pp. 4821-4828 ◽  
Author(s):  
HAROLD E. ZAUGG ◽  
ROBERT W. De NET ◽  
RAYMOND J MICHAELS
Keyword(s):  
Nucleophilic Attack ◽  
Hydroxide Ion ◽  
Neighboring Group ◽  
New Synthesis

Kinetics of the Imidazolium Ring-Opening of mRNA 5'-cap Analogs in Aqueous Alkali

2006 ◽  
Vol 71 (4) ◽  
pp. 567-578 ◽  
Author(s):  
Alicja Stachelska ◽  
Zbigniew J. Wieczorek ◽  
Janusz Stępiński ◽  
Marzena Jankowska-Anyszka ◽  
Harri Lönnberg ◽  
...  
Keyword(s):  
Electrostatic Interaction ◽  
Ring Opening ◽  
Nucleophilic Attack ◽  
Amino Groups ◽  
Hydroxide Ion ◽  
Methyl Group ◽  
Structural Modifications ◽  
Alkyl Groups ◽  
Imidazolium Ring ◽  
Kinetics Of

Second-order rate constants for the hydroxide-ion-catalyzed imidazolium ring-opening of several mono- and dinucleosidic analogs of mRNA 5'-cap have been determined. Intramolecular stacking of the two nucleobases in the dinucleosidic analogs, m7GpppN (m7G = 7-methylguanosine, N = 5'-linked nucleoside), and electrostatic interaction between the N-alkylated imidazolium ring and phosphate moiety have been shown to shield the m7G moiety against the nucleophilic attack of hydroxide ion. In addition, the effect of methylation of the nucleobase amino groups and replacement of the 7-methyl group with other alkyl groups have been studied. The influence of all the structural modifications studied turned out to be modest, the cleavage rates of the most and least reactive analogs (with the exception of non-phosphorylated nucleosides) differing only by a factor of 5.

Nucleophilic photosubstitutions of o-methoxynitrobenzenes

1989 ◽  
Vol 67 (2) ◽  
pp. 220-226 ◽  
Author(s):  
Nigel J. Bunce ◽  
Karen Labonte Stephenson
Keyword(s):  
Nitro Group ◽  
Methoxy Group ◽  
Second Order ◽  
Hydroxide Ion ◽  
Aromatic Substrates ◽  
New Synthesis

We report a new synthesis of 3-nitroveratrole, based on the directed lithiation of veratrole, and photochemical substitutions of both 3-nitroveratrole and o-nitroanisole with several nucleophiles. Both aromatic substrates undergo photocyanation meta to the nitro group. With hydroxide ion, 3-nitroveratrole reacts meta to the nitro group, but 2-nitroanisole undergoes replacement of either substituent, the proportion of reaction at each site depending upon the OH− concentration. 3-Nitroveratrole undergoes an inefficient reaction with butylamine at each methoxy group; this reaction is apparently second order in amine. The reaction between o-nitroanisole and diethylamine results only in photohydrolysis. Keywords: photosubstitution, nucleophilic, 3-nitroveratrole, o-nitroanisole.

Interpretation of neighboring group interactions in crystal structures. A solid state and quantum-chemical study of "incipient nucleophilic attack" in 2-diazonium benzoic acid and its benzoate

1996 ◽  
Vol 74 (6) ◽  
pp. 1200-1214 ◽  
Author(s):  
Rainer Glaser ◽  
Christopher J. Horan
Keyword(s):  
Electronic Structure ◽  
Electron Density ◽  
Nucleophilic Attack ◽  
Neighboring Group ◽  
Group Interactions ◽  
Diazonium Ions ◽  
Attraction Model ◽  
Density Analysis ◽  
Bridging Attraction ◽  
Electron Density Analysis

The concept of the Bürgi–Dunitz angle of attack on carbonyls is compatible with the electronic structure of carbonyls. However, it is argued here that the generalization asserted to describe the interaction of nucleophiles with diazonium ions is inappropriate. Distortions in crystal structures of diazonium ions with proximate nucleophiles were interpreted by an incipient nucleophilic attack (INA) on the formally positive-charged Nα. This "Nα attraction model" relies on the assumption that the formal charge in the most commonly used Lewis structure of diazonium ions represents actual charge. We proposed that the close approach of the proximate nucleophile to the diazonium group occurs to enhance attractive 1,3-(C,Nβ)-bridging interactions and despite repulsion between Nα and the proximate oxygen (Opr). The present study combines theoretical analysis of rotamers of 2-diazonium benzoic acid and its conjugate base with experimental results on the same system to provide compelling evidence that the more general conclusions drawn from analyses of neighboring group interactions in propenoic acid models are fully warranted. The crystallographic record is more fully consistent with the "1,3-bridging attraction model." Combined analysis of solid state and gas phase structures reveals the intrinsic features due to INA. Both electrostatic models can account for these features but with different postulates about the electron density distribution. While the structural analysis alone cannot distinguish between the alternative interpretations, the study of the electronic structure allows one to clearly differentiate between these competing interpretations. A method (ESI) for the quantitative evaluation of electrostatic neighboring group interactions has been devised and this ESI concept employs atomic electrical moments (charges, dipoles, and quadrupoles) determined via topological electron density analysis. The results of the ESI analysis support the 1,3-bridging attraction model and eliminate the Nα attraction model. Key words: electrostatic interactions, electron density analysis, atoms in molecules. X-ray crystallography, ab initio molecular orbital theory, incipient nucleophilic attack, bonding models, ESI analysis.

On the Determination and Use of Reduction Potentials of Short-Lived Radicals. A Review

2000 ◽  
Vol 65 (6) ◽  
pp. 829-843 ◽  
Author(s):  
Henning Lund ◽  
Karen Skov ◽  
Steen Uttrup Pedersen ◽  
Torben Lund ◽  
Kim Daasbjerg
Keyword(s):  
Aqueous Solution ◽  
Electron Transfer ◽  
Reaction Mechanisms ◽  
Nucleophilic Attack ◽  
Grignard Reaction ◽  
Hydroxide Ion ◽  
Reduction Sequence ◽  
Reduction Potentials ◽  
Srn1 Reaction

A method, the "competition method", for the determination of reduction potentials and estimation of standard potentials for short-lived radicals is reviewed. Applications of the reduction potentials of radicals as arguments for reaction mechanisms are presented for the Grignard reaction, the photoreduction of ketones with alcohols, and the SRN1 reaction. Reductions induced by hydroxide ions are discussed in more detail, and the classic reaction between nitrosobenzene and hydroxide ion in aqueous solution is used as an example of such a reaction. A nucleophilic attack by hydroxide ion rather than an electron transfer initiates the reduction sequence. A review with 26 references.

Correlation of rates of uncatalyzed and hydroxide-ion catalyzed ketene hydration. A mechanistic application and solvent isotope effects on the uncatalyzed reaction

2000 ◽  
Vol 78 (4) ◽  
pp. 508-515
Author(s):  
John Andraos ◽  
A Jerry Kresge
Keyword(s):  
Carbon Atom ◽  
Rate Constants ◽  
Isotope Effects ◽  
Nucleophilic Attack ◽  
Carbonyl Carbon Atom ◽  
Basic Solution ◽  
Carbonyl Carbon ◽  
Hydroxide Ion ◽  
Solvent Isotope ◽  
Solvent Isotope Effects

Rates of hydration of a number of ketenes were measured in neutral and basic solution using flash photolytic techniques, and rate constants for their uncatalyzed, kuc, and hydroxide-ion catalyzed, kHO, reactions were determined. These results, plus additional data from the literature, were found to provide the remarkably good correlation log kuc = -3.21 + 1.14 log kHO, which spans 10 orders of magnitude in reactivity and includes 31 ketenes. This good correlation implies that uncatalyzed and hydroxide-ion catalyzed ketene hydraton occur by similar reaction mechanisms, which for the hydroxide-ion catalyzed process is known to involve nucleophilic attack on the carbonyl carbon atom of the ketene. Rate constants for phenylhydroxyketene, on the other hand, do not fit this correlation, which suggests that the mechanistic assignment upon which these rate constants are based may not be correct. Solvent isotope effects on these uncatalyzed ketene hydrations are weak; most are less than kH/kD = 2. It is argued that these isotope effects are largely, if not entirely, secondary in nature and that they are consistent with both a reaction mechanism in which nucleophlic attack of a single water molecule on the ketene carbonyl carbon atom produces a zwitterionic intermediate and also a mechanism that avoids this intermediate by passing through a cyclic transition state involving several water molecules.Key words: ketene hydration, rate correlation, nucleophilic attack, solvent isotope effects, phenylhydroxyketene.

scholarly journals A Potential Substrate Binding Conformation of β-Lactams and Insight into the Broad Spectrum of NDM-1 Activity

2012 ◽  
Vol 56 (10) ◽  
pp. 5157-5163 ◽  
Author(s):  
Qinghui Yuan ◽  
Lin He ◽  
Hengming Ke
Keyword(s):  
Broad Spectrum ◽  
Nucleophilic Attack ◽  
Klebsiella Pneumonia ◽  
New Delhi ◽  
Binding Modes ◽  
Carboxylic Group ◽  
Hydroxide Ion ◽  
Content Type ◽  
Key Enzyme ◽  
Almost All

ABSTRACTNew Delhi metallo-β-lactamase 1 (NDM-1) is a key enzyme that the pathogenKlebsiella pneumoniauses to hydrolyze almost all β-lactam antibiotics. It is currently unclear why NDM-1 has a broad spectrum of activity. Docking of the representatives of the β-lactam families into the active site of NDM-1 is reported here. All the β-lactams naturally fit the NDM-1 pocket, implying that NDM-1 can accommodate the substrates without dramatic conformation changes. The docking reveals two major binding modes of the β-lactams, which we tentatively name the S (substrate) and I (inhibitor) conformers. In the S conformers of all the β-lactams, the amide oxygen and the carboxylic group conservatively interact with two zinc ions, while the substitutions on the fused rings show dramatic differences in their conformations and positions. Since the bridging hydroxide ion/water in the S conformer is at the position for the nucleophilic attack, the S conformation may simulate the true binding of a substrate to NDM-1. The I conformer either blocks or displaces the bridging hydroxide ion/water, such as in the case of aztreonam, and is thus inhibitory. The docking also suggests that substitutions on the β-lactam ring are required for β-lactams to bind in the S conformation, and therefore, small β-lactams such as clavulanic acid would be inhibitors of NDM-1. Finally, our docking shows that moxalactam uses its tyrosyl-carboxylic group to compete with the S conformer and would thus be a poor substrate of NDM-1.

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