SN2 Substitution Reactions at the Amide Nitrogen in the Anomeric Mutagens, N-Acyloxy-N-alkoxyamides

2009 ◽  
Vol 62 (7) ◽  
pp. 700 ◽  
Author(s):  
Katie L. Cavanagh ◽  
Stephen A. Glover ◽  
Helen L. Price ◽  
Rhiannon R. Schumacher
Keyword(s):  
Kinetic Studies ◽  
Model Reaction ◽  
Side Chain ◽  
Carboxylate Group ◽  
Amide Nitrogen ◽  
Substitution Reactions ◽  
Sn2 Reactions ◽  
Leaving Group ◽  
Rate Of Substitution

N-Acyloxy-N-alkoxyamides 1a are unusual anomeric amides that are pyramidal at the nitrogen because of bis oxyl substitution. Through this configuration, they lose most of their amide character and resemble α-haloketones in reactivity. They are susceptible to SN2 reactions at nitrogen, a process that is responsible for their mutagenic behaviour. Kinetic studies have been carried out with the nucleophile N-methylaniline that show that, like SN2 reactions at carbon centres, the rate constant for SN2 displacement of carboxylate is lowered by branching β to the nitrogen centre, or bulky groups on the alkoxyl side chain. Branching or bulky groups on the carboxylate leaving group, however, do not impact on the rate of substitution, which is mostly controlled by the pKA of the departing carboxylate group. These results are in line with computed properties for the model reaction of ammonia with N-acetoxy-N-methoxyacetamide but are in contrast to the role of steric effects on their mutagenicity.

Basicity, nucleophilicity, and nucleofugality in the elimination–substitution reactions of β-phenylmercaptoethyl phenolates in DMSO–ethanol media

1994 ◽  
Vol 72 (2) ◽  
pp. 448-453 ◽  
Author(s):  
Hai-Qi Xie ◽  
Nguyen Truong ◽  
Erwin Buncel ◽  
J. Garfield Purdon
Keyword(s):  
Reaction Rate ◽  
Phenyl Group ◽  
Kinetic Studies ◽  
Substitution Reactions ◽  
Leaving Group ◽  
Partial Completion ◽  
Comparison Of The Results ◽  
Pure Dmso ◽  
Phenyl Vinyl

Kinetic studies have been performed on the base-promoted 1,2-elmination reactions of a series of β-phenylmercaptoethyl phenolates with potassium ethoxide in EtOH–DMSO media, yielding phenyl vinyl sulfide. The E2 mechanism was indicated by the absence of H/D exchange in the substrate when the reaction in EtOD–DMSO-d6 containing EtO− was carried to partial completion. The Brønsted coefficient values (βLG, effect of nucleofugality on reaction rate) of ca• 0.30 and ca• 0.98 were estimated for the reaction in pure DMSO and ethanol, respectively. Comparison of the results with reported reactions of substrates of similar structure revealed the important role of the phenyl group on sulfur, the leaving-group nucleofugality, and the medium basicity, in controlling the reaction pathways (elimination versus substitution).

Mechanisms of aromatic nucleophilic substitution by the ambident thiocyanate ion

1973 ◽  
Vol 26 (2) ◽  
pp. 273 ◽  
Author(s):  
DE Giles ◽  
AJ Parker
Keyword(s):  
Nucleophilic Substitution ◽  
Transition States ◽  
Reactivity Ratio ◽  
Substitution Reactions ◽  
Aromatic Nucleophilic Substitution ◽  
Thiocyanate Ion ◽  
Sn2 Reactions ◽  
Leaving Group ◽  
Electrophilic Reactivity ◽  
Saturated Carbon Atom

Sulphur/nitrogen reactivity ratios in a series of aromatic nucleophilic substitution reactions of ambident thiocyanate ion have been determined. There are profound differences from the pattern found in SN2 reactions at a saturated carbon atom. Abnormal transition states, involving interactions between entering and leaving group, are likely in the bond-breaking step of the intermediate complex in reactions of thiocyanate ion with 1-fluoro-2,4-dinitrobenzene and with 2,4- dinitrophenyl 4-toluenesulphonate. The nitro-substituted aryl thiocyanates are shown to be tri-functional electrophiles, with reactive centres at aromatic carbon, at cyanide carbon, and at sulphur. Aryl 4-toluenesulphonates are bifunctional electrophiles with reactive centres at aryl carbon and sulphonyl sulphur. The site of attack by nucleophiles depends on the nature of the nucleophile. The sulphur/nitrogen reactivity ratio of ambident SCN-, and the electrophilic reactivity of tri- and bi-functional substrates, are in most instances consistent with the Hard and Soft Acids and Bases principle. Exceptions to the principle in some instances reveal differences between the SNAr and SN2 mechanisms, and in others indicate abnormal transition states.

Empirical σ Molecular Orbital Parameters and their Correlation with Rates of Substitution Reactions in Quadrate Cr(III) and Co(III) Complexes

1971 ◽  
Vol 49 (9) ◽  
pp. 1497-1501 ◽  
Author(s):  
C. H. Langford
Keyword(s):  
Field Theories ◽  
Complete Analysis ◽  
Substitution Reactions ◽  
Spectral Parameters ◽  
Empirical Measures ◽  
Orbital Parameters ◽  
Spectral Bands ◽  
Leaving Group ◽  
The Relationship

Empirical measures of σ bonding involving metal 3d orbitals are derived from Perumareddi's (4) complete analysis of the quartet spectral bands of quadrate complexes in the families Cr(NH3)5Xn+ and Cr(OH2)5Xn+. These are shown to correlate with lability of X in the Cr(III) complexes and in Co(NH3)5Xn+ complexes in a sense indicating that relative reactivity is controlled by variation of ligand metal 3d σ interaction. The relationship between the two Cr(III) series implies that the non-labile ligands can labilize the leaving group in proportion to their σ donor capacities. This observation bears on some well-known difficulties in crystal field theories of reactivity. In evaluating the correlation of spectral parameters with reactivity, the role of solvation in reactivity of Cr(III) and Co(III) complexes is discussed with emphasis on the surprisingly small solvent effects that have been observed.

Investigating the role of halogen-bonded complexes in microsolvated Y−(H2O)n + CH3I SN2 reactions

2021 ◽  
Author(s):  
Xiaoyan Ji ◽  
Chongyang Zhao ◽  
Jing Xie
Keyword(s):  
Nucleophilic Substitution ◽  
Back Side ◽  
Front Side ◽  
Substitution Reactions ◽  
Nucleophilic Substitution Reactions ◽  
Sn2 Reactions ◽  
Bonded Complexes

A halogen-bonded complex pathway is computed for Y−(H2O)n + CH3I (Y = HO, F, Cl, Br, and I) ion–molecule nucleophilic substitution reactions and is compared with back-side and front-side attack pathways.

Role of Lys-226 in the Catalytic Mechanism ofBacillus StearothermophilusSerine HydroxymethyltransferaseCrystal Structure and Kinetic Studies†,‡

Biochemistry ◽  
2005 ◽  
Vol 44 (18) ◽  
pp. 6929-6937 ◽  
Author(s):  
Siddegowda Bhavani ◽  
V. Trivedi ◽  
V. R. Jala ◽  
H. S. Subramanya ◽  
Purnima Kaul ◽  
...  
Keyword(s):  
Catalytic Mechanism ◽  
Kinetic Studies

scholarly journals “Newton’s cradle” proton relay with amide–imidic acid tautomerization in inverting cellulase visualized by neutron crystallography

2015 ◽  
Vol 1 (7) ◽  
pp. e1500263 ◽  
Author(s):  
Akihiko Nakamura ◽  
Takuya Ishida ◽  
Katsuhiro Kusaka ◽  
Taro Yamada ◽  
Shinya Fushinobu ◽  
...  
Keyword(s):  
Glycoside Hydrolases ◽  
Side Chain ◽  
Enzymatic Reactions ◽  
X Ray Diffraction ◽  
Peptide Bonds ◽  
Proton Relay ◽  
Newton’S Cradle ◽  
Dynamics Simulations ◽  
Hydrolysis Of

Hydrolysis of carbohydrates is a major bioreaction in nature, catalyzed by glycoside hydrolases (GHs). We used neutron diffraction and high-resolution x-ray diffraction analyses to investigate the hydrogen bond network in inverting cellulase PcCel45A, which is an endoglucanase belonging to subfamily C of GH family 45, isolated from the basidiomycete Phanerochaete chrysosporium. Examination of the enzyme and enzyme-ligand structures indicates a key role of multiple tautomerizations of asparagine residues and peptide bonds, which are finally connected to the other catalytic residue via typical side-chain hydrogen bonds, in forming the “Newton’s cradle”–like proton relay pathway of the catalytic cycle. Amide–imidic acid tautomerization of asparagine has not been taken into account in recent molecular dynamics simulations of not only cellulases but also general enzyme catalysis, and it may be necessary to reconsider our interpretation of many enzymatic reactions.

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