Nucleophilic attack, of water molecules

Variations in the Nucleophilic Attack of Water Molecules on the Cations of Pteridines... 

Scheme 1 describes a typical mechanism for chemical oxidation polymerization of pyrrole. In the initiation step, radical cations (C4NH5+) are generated by the oxidation of pyrrole monomer. A radical-radical coupling occurs between two radical cations, and forms a dimer with deprotonation, leading to a bipyrrole. The bipyrrole is reoxidized and couples with other radical cations. This process is repeated consecutively during the propagation step. The termination takes place due to the nucleophilic attack of water molecules or impurities in the polymer chains. 

Increasing humidity of the surrounding atmosphere induces a dedoping reaction in POT, probably because of a nucleophilic attack of water molecules, and therefore a decrease of radical cationic centers the electrical conductivity increases in dry air [324,547, 548],... 

Protonation of the carbonyl oxygen as emphasized earlier makes the carbonyl group more susceptible to nucleophilic attack A water molecule adds to the carbonyl group of the protonated ester m step 2 Loss of a proton from the resulting oxonium ion gives the neutral form of the tetrahedral intermediate m step 3 and completes the first stage of the mechanism... 

Acid-catalysed hydrolysis. The carbonyl group of an ester is not sufficiently electrophilic to be attacked by water. The acid catalyst protonates the carbonyl oxygen, and activates it towards nucleophilic attack. The water molecule attacks the protonated carbonyl carbon, and forms a tetrahedral intermediate. Proton transfer from the hydronium ion to a second molecule of water yields an ester hydrate. The intramolecular proton transfer produces a good leaving group as alcohol. A simultaneous deprotonation by the water and loss of alcohol gives a carboxylic acid. 

The main principles of metal alkoxide hydrolysis were formulated by Livage in his reviews [1020]. On the addition of water or a water-alcohol mixture to the solutions of alkoxides in organic solvents, nucleophillic attack of H20 molecule at the positively charged metal atom occurs (a), which leads to an intermediate state (b) ... 

Thus pseudobase formation occurs via nucleophilic attack of a molecule of water on the cation at low pH or via attack by hydroxide ion in more basic solutions, or the kinetic equivalents of these mechanisms. More detailed consideration of the mechanisms of these reactions is given in Section IV,B. 

The proposed mechanism for enzymatic hydrolysis of hyaluronan involves nucleophilic attack of water at the anomeric carbon of the d-G1cNAc moiety via an oxazolinium ion intermediate (see Figure 9.16b). A water molecule can nucle-ophilically attack the oxazolinium anomeric carbon atom to open the oxazolinium ring, resulting in the formation of the hydrolysis products of a shortened HA molecule (see Figure 9.16c). 

In one of the most often proposed mechanisms, the Glu(270) carboxylate makes nucleophilic attack at the carbonyl carbon of the substrate (R). In other widely proposed mechanisms, the Glu(270) carboxylate acts as a general base to assist the attack of water molecule (S) or the Zn(II)-bound water molecule (T) at the carbonyl group. The mechanisms of S and T do not involve the covalent intermediate, whereas that of R produces an anhydride intermediate formed between the acyl portion of the substrate and Glu(270). 

Wacker process A process for the manufacture of ethanal by the air oxidation of ethene. A mixture of air and ethene is bubbled through a solution containing palla-dium(II) chloride andcopper(II) chloride. The Pd + ions form a complex with the ethene in which the ion is bound to the pi electrons in the C=C bond. This decreases the electron density in the bond, making it susceptible to nucleophilic attack by water molecules. The complex formed breaks down to ethanal and palladium metal. The Cu + ions oxidize the palladium back to Pd +, being reduced to Cu+ ions in the process. 

The currently accepted mechanism involves attack of a free water molecule from the solvent on the coordinated ethylene with inversion of the stereochemistry at one of the carbons, a common organometallic reaction type. The loss of two Cl ions from [PdC ] is needed to provide a site for the alkene to bind and to remove the anionic charge from the metal, which would otherwise prevent the nucleophilic attack of water from taking place. Figure 6 shows the sequence of events as now understood. This mechanism implies that an [H2 O] term should be present in the rate equation, and if it could have been seen, the mechanistic problem would have been solved earlier, but one cannot normally alter the concentration of a solvent and get meaningful rate data, because changing the solvent composition leads to vmpredictable solvent effects on the rate. 

The chemical production of aminophenols via the reduction of nitrobenzene occurs in two stages. Nitrobenzene [98-95-3] is first selectively reduced with hydrogen in the presence of Raney copper to phenylhydroxylamine in an organic solvent such as 2-propanol (37). With the addition of dilute sulfuric acid, nucleophilic attack by water on the aromatic ring of /V-phenylhydroxylamine [100-65-2] takes place to form 2- and 4-aminophenol. The by-product, 4,4 -diaminodiphenyl ether [13174-32-8] presumably arises in a similar manner from attack on the ring by a molecule of 4-aminophenol (38,39). Aniline [62-53-3] is produced via further reduction (40,41). 

All these 3,4-dihydro-2H-1 -benzopyran-2-ones 17 and 18 are substrates of class A and class C (3-lactamases. They are thus the first 8-lactones that are hydrolyzed by [3-lactamases. The kcat values for these substrates are generally smaller than those of the analogous acyclic phenaceturates suggesting that the tethered leaving group obstructs the attack of water on the acyl-enzyme. Despite the apparent advantage of the long-lived acyl-enzymes, the irreversible inhibition by the functionalized compounds is no better than that of acyclic molecules 16. Thus, even the tethered QM cannot efficiently trap a second nucleophile at the [3-lactamase active site, at least as placed as dictated by the structure of compounds 18.70... 

The one exception to this observation is the hydrolysis of bis( p-nitrophenyl) methylphosphonate which, in the presence of cycloheptaamylose, produces only 1.7 moles of phenol. Probably two competitive pathways are available for the hydrolysis of the included substrate (1) nucleophilic attack by an ionized cycloheptaamylose hydroxyl group, and (2) nucleophilic attack by a water molecule or a hydroxide ion from the bulk solution. Whereas the former process produces two moles of phenol and yields a phos-phonylated cycloheptaamylose, the latter process produces only one mole of phenol and a relatively stable p-nitrophenyl methylphosphonate anion. The appearance of less than two moles of phenol may be explained by a combination of these two pathways. Since the amount of p-nitrophenyl methylphosphonate produced in this reaction is considerably larger than expected from an uncatalyzed pathway, attack of water may be catalyzed by the cycloheptaamylose alkoxide ions, acting as general bases (Brass and Bender, 1972). 

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