Water nucleophilic attack

The catalytic cycle proposed for ethylene to acetaldehyde is shown in Fig. 8.2. The tetrachloro palladium anion 8.1 is used as the precatalyst. Conversion of 8.1 to 8.3 involves substitution of two chloride ligands by ethylene and water. Nucleophilic attack on coordinated ethylene leads to the formation of 8.4. The latter then undergoes substitution of another Cl- ligand. Conversion of 8.5 to 8.6 involves /3-hydride abstraction and coordination by vinyl alcohol. Intramolecular hydride attack to the coordinated vinyl group leads to the formation of 8.7. The latter eliminates acetaldehyde, proton, and CF and in the process is reduced to a palladium complex of zero oxidation state. 

In an industrial plant for EP, 1,3-DCP and DCP are converted into EP with Ca(OH)2/water or CaO/water. The chiral DCP is essentially converted into EP by the same reaction. However, under certain conditions chiral EP racemizes very readily, especially in the presence of Cl via an exchange reaction. For example, racemization occurred during epoxidation of DCP to EP when Ca(OH)2 was used as the alkali or when EP was not quickly extracted into the solvent [27], because Cl reacted with EP and symmetrical 1,3-DCP was formed, which yields EP more promptly than 2,3-DCP. Less racemization occurs at low temperature (Fig. 20). Furthermore, EP and GLD gradually react with water. Nucleophilic attack on EP usually occurred at the Cl position and partly at the C2 position. For example, pure optically active EP was opened by boiling water/acid, and the % ee values decreased to 88% ee. Epoxides are also unstable because polymerization gradually proceeds. As a consequence, EP and GLD can not be kept for a long time, but these epoxides are useful and reactive synthesis units. CPD is racemized by heating, but the stability is far better than that of EP and GLD, and is considered useful for practical applications. 

Upon exposure to water, nucleophilic attack of water onto the iminophosphorane phosphorus atom leads to a cascade of proton transfers that ultimately yield the primary amine and phosphine oxide. 

The postulated mechanism for the formation of esters from the Ugi products is depicted in Scheme 7.64. Internal nucleophihc attack of the amide nitrogen lone pair onto the protonated ester carbonyl of 183 (derived from isocyanide) forms the intermediate 184, which equilibrates with 185. Electron-donating groups on the phenyl ring accelerate the formation of intermediate 186 and help stabilize it by forming intermediate 187 after the loss of water. Nucleophilic attack by the solvent used at the amide carbonyl of 187 (derived from isocyanide) provides the desired esters 181. 

Fig. 11.37 Free energy profile for the nucleophilic attack of water on CO2 (a) in aqueous solution and (b) in the enzyme carbonic anhydrase. (Graphs redrawn from Aqvist J, M Fothergill and A Warshel 1993. Computer Simulai of the COj/HCOf Interconversion Step in Human Carbonic Anhydrase I. Journal of the American Chemical Society 115 631-635.)...

This thesis has been completely devoted to catalysis by relatively hard catalysts. When aiming at the catalysis of Diels-Alder reactions, soft catalysts are not an option. Soft catalysts tend to coordinate directly to the carbon - carbon double bonds of diene and dienophile, leading to an activation towards nucleophilic attack rather than to a Diels-Alder reaction . This is unfortunate, since in water, catalysis by hard catalysts suffers from a number of intrinsic disadvantages, which are absent for soft catalysts. 

Formation of carboxylic acids ami their derivatives. Aryl and alkenyl halides undergo Pd-catalyzed carbonylation under mild conditions, offering useful synthetic methods for carbonyl compounds. The facile CO insertion into aryl- or alkenylpalladium complexes, followed by the nucleophilic attack of alcohol or water affords esters or carboxylic acids. Aromatic and a,/ -unsaturated carboxylic acids or esters are prepared by the carbonylation of aryl and alkenyl halides in water or alcohols[30l-305]. 

Step 2 Nucleophilic attack by water on carbon of the oxonium ion The carbon-oxygen bond of the ring is broken in this step and the ring opens... 

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... 

FIGURE 27 19 Proposed mechanism of hydrolysis of a peptide catalyzed by carboxypeptidase A The peptide is bound at the active site by an ionic bond between its C terminal ammo acid and the positively charged side chain of arginine 145 Coordination of Zn to oxygen makes the carbon of the carbonyl group more positive and increases the rate of nucleophilic attack by water... 

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). 

Bromine in chloroform and bromine in acetic acid are the reagents used most often to brominate pyrazole. When nitric acid is used as a solvent, both bromine and chlorine transform pyrazoles into pyrazolones (Scheme 24). Thus 3-methyl-l-(2,4-dinitrophe-nyOpyrazole is brominated at the 4-position (309). The product reacts with chlorine and nitric acid to give the pyrazolone (310). The same product results from the action of bromine and nitric acid on (311). The electrophilic attack of halogen at C-4 is followed by the nucleophilic attack of water at C-5 and subsequent oxidation by nitric acid. 

S-Substituted thiiranium ions react with water and alcohols to give trans ring opening (Scheme 72). A report that oxygen nucleophiles attack sulfur as well as carbon has been shown to be incorrect (79ACR282). The intermediate thiiranium ion (57) in the presence of lithium perchlorate readily yields the carbenium ion which undergoes a transannular hydride... 

GTPases hydrolyze GTP through nucleophilic attack by a water molecule... 

Notwithstanding the expected and also observed high reactivity of the intermediate immonium ions, the stabilization of the exocyclic double bond in the pyrrolidino derivative evidently prevents rapid nucleophilic attack of water and the hydration of this ion to the amino alcohol becomes a slow general base-catalyzed process in weakly acidic solutions [Eq. (6)]. 

FIGURE 16.27 A mechanism for the aspartic proteases. In the first step, two concerted proton transfers facilitate nucleophilic attack of water on the substrate carbonyl carbon. In the third step, one aspartate residue (Asp" " in pepsin) accepts a proton from one of the hydroxyl groups of the amine dihydrate, and the other aspartate (Asp" ) donates a proton to the nitrogen of the departing amine. 

The mechanism of this reaction is not straightforward but the crucial step appears to be nucleophilic attack by water or OH" on the eoordinated ethene to give rr-bonded —CH2CH2OH which then rearranges and is eventually eliminated as MeCHO with loss of a proton. 

Insertion of a methyl group at the site where nucleophilic attack (by OH or H2O) occurs during hydration considerably hinders the addition of water, thus lowering the percentage of the hydrated... 

Because the anioas of nitroalkanes are stable, retro-acyladoc smoothly In the presence of a base catalyst. This type of reacdo organic synthesis." Nucleophilic attack of water or alcohol to ct-the ring cleavage v/ith the formadon of Oj-nitro acids and Oj-niti... 

Nucleophilic attack of water on the carbocation forms a C-0 bond and yields a protonated mercury-containing enol. 

Acid-catalyzed ester hydrolysis can occur by more than one mechanism, depending on the structure of the ester. The usual pathway, however, is just the reverse of a Fischer esterification reaction (Section 21.3). The ester is first activated toward nucleophilic attack by protonation of the carboxyl oxygen atom, and nucleophilic addition of water then occurs. Transfer of a proton and elimination of alcohol yields the carboxylic acid (Figure 21.8). Because this hydrolysis reaction is the reverse of a Fischer esterification reaction, Figure 21.8 is the reverse of Figure 21.4. 

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