Nucleophile water

Hydroxide is the nucleophile Water is the nucleophile Water is the nucleophile MeCl is the electrophile Nucleophile Base... 

On the other hand, it is found that only partial racemization occurs on alkaline hydrolysis of optical active 198 in aqueous methanol136) and no racemization takes place in the hydrolysis of 199 in dioxane/water137). Moreover, the latter reaction is only ca. 80 times faster at 29 °C than that of the analogous morpholide 200, for which a metaphosphorimidate mechanism is precluded a priori by the absence of an NH function and whose hydrolysis is likewise stereospecific,37). Clearly a free metaphosphorimidothioate of type 191 cannot be involved in this case. The experimental findings are compatible, however, with the hypothesis that the nucleophile water attacks a metaphosphorothioimidate/phenolate associate 201. The question of how free metaphosphates occur in solution is of a general nature it has also been considered in the previous Section. 

Thus solvolysis of (+)C6HsCHMeCl, which can form a stabilised benzyl type carbocation (cf. p. 84), leads to 98% racemisation while (+)C6H13CHMeCl, where no comparable stabilisation can occur, leads to only 34% racemisation. Solvolysis of ( + )C6H5CHMeCl in 80 % acetone/20 % water leads to 98 % racemisation (above), but in the more nucleophilic water alone to only 80% racemisation. The same general considerations apply to nucleophilic displacement reactions by Nu as to solvolysis, except that R may persist a little further along the sequence because part at least of the solvent envelope has to be stripped away before Nu can get at R . It is important to notice that racemisation is clearly very much less of a stereochemical requirement for S l reactions than inversion was for SN2. 

The protonated epoxide reacts with the weak nucleophile (water) to form a protonated glycol, which then transfers a proton to a molecule of water to form the... 

The case of 2-nitrofuran is especially interesting. The quantum yield of disappearance of starting material in the photocyanation reaction is 0.51 at 313 nm and not dependent on the cyanide ion concentration. The quantum yield of product formation, however, is dependent on the concentration of cyanide, a limiting value of 0.51 is reached at approximately 1 mole l i cyanide. Kinetics are in agreement with the formation of an intermediate X (the nature of which needs to be clarified) which is subsequently intercepted by a nucleophile. Water competes with cyanide in this product-forming step. This cyanation has been both sensitized and quenched, thus very likely it proceeds via a triplet state. 

In the range of leaving groups, fluorine has been recognized as a valuable substituent that has practically no heavy atom effect and that in many cases is smoothly replaced under the influence of irradiation (Brasem et al., 1972). With 2-fluoro-4-nitroanisole it even proved capable of efficient substitution by the weak nucleophile water, a reaction that has not been equalled by any other substituent. Curiously, the photosubstitution of fluorine by cyanide is generally less efficient than that by other nucleophiles. 

Subsequent to CO2 association in the hydrophobic pocket, the chemistry of turnover requires the intimate participation of zinc. The role of zinc is to promote a water molecule as a potent nucleophile, and this is a role which the zinc of carbonic anhydrase II shares with the metal ion of the zinc proteases (discussed in the next section). In fact, the zinc of carbonic anhydrase II promotes the ionization of its bound water so that the active enzyme is in the zinc-hydroxide form (Coleman, 1967 Lindskog and Coleman, 1973 Silverman and Lindskog, 1988). Studies of small-molecule complexes yield effective models of the carbonic anhydrase active site which are catalytically active in zinc-hydroxide forms (Woolley, 1975). In addition to its role in promoting a nucleophilic water molecule, the zinc of carbonic anhydrase II is a classical electrophilic catalyst that is, it stabilizes the developing negative charge of the transition state and product bicarbonate anion. This role does not require the inner-sphere interaction of zinc with the substrate C=0 in a precatalytic complex. 

In the high resolution crystal structure of the GTP form of Ras protein, a tightly bound water molecule is visible located in an optimal position for nucleophilic attack on the y-phosphate (Wittinghofer et al., 1993). The water molecule is fixed in a defined position by H-bridges with GIn61 and Hir35. As described in 5.4.4 for the a-subunits of the heterotrimeric G-proteins, GTP hydrolysis takes place by an in-line attack of the nucleophilic water molecule on the y-phosphate, for which a pentagonal, bipyramidal transition state is postulated. 

Mechanism. Addition of HgS04 generates a cyclic mercurinium ion, which is attacked by a nucleophilic water molecule on the more substituted carbon. Oxygen loses a proton to form a mercuric enol, which under work-up produces enol (vinyl alcohol). The enol is rapidly converted to 2- butanone. 

In chronological order, the next milestones in research were the studies by Fukuda and Utimoto on the addition of nucleophiles (water, alcohols and amines) to alkynes [13]. A decade later, Teles obtained notable turnover numbers (TONs) and turnover frequencies (TOFs) in the addition of alcohols to alkynes [14]. 

Silver ion also catalyzes nucleophilic reactions of thiol esters, including reactions of acetylhomocysteine thiolactone (12) and diethylethylphosphonothiolate (52). In the first reaction, an insoluble complex of silver ion and the substrate was first produced at pH 7.5, which then reacted with the nucleophile, in this case an amino group of a protein. In the second reaction silver ion complexes of the substrate were also postulated, on the basis that silver ion complexes with sulfur are much more stable than those with oxygen (I). The complexes postulated were 1 1 and 2 1 silver ion-substrate complexes. These complexes were suggested to react with the nucleophiles, water and fluoride ion, giving as products phos-phonic acid and phosphonyl fluoride, respectively, and silver mercaptide. It is evident that the last reaction at least must involve only the direct interaction of a silver ion with the sulfur atom of the thiol ester without chelate formation. Therefore it appears the metal ion-catalyzed reactions of thiol esters are unique, in that they involve complex formation, but not chelate formation in their catalytic mechanism. 

While there have been a considerable number of structural models for these multinuclear zinc enzymes (49), there have only been a few functional models until now. Czamik et al. have reported phosphate hydrolysis with bis(Coni-cyclen) complexes 39 (50) and 40 (51). The flexible binuclear cobalt(III) complex 39 (1 mM) hydrolyzed bis(4-nitro-phenyl)phosphate (BNP-) (0.05 mM) at pH 7 and 25°C with a rate 3.2 times faster than the parent Coni-cyclen (2 mM). The more rigid complex 40 was designed to accommodate inorganic phosphate in the in-temuclear pocket and to prevent formation of an intramolecular ju.-oxo dinuclear complex. The dinuclear cobalt(III) complex 40 (1 mM) indeed hydrolyzed 4-nitrophenyl phosphate (NP2-) (0.025 mM) 10 times faster than Coni-cyclen (2 mM) at pH 7 and 25°C (see Scheme 10). The final product was postulated to be 41 on the basis of 31P NMR analysis. In 40, one cobalt(III) ion probably provides a nucleophilic water molecule, while the second cobalt(III) binds the phosphoryl group in the form of a four-membered ring (see 42). The reaction of the phosphomonoester NP2- can therefore profit from the special placement of the two metal ions. As expected from the weaker interaction of BNP- with cobalt(in), 40 did not show enhanced reactivity toward BNP-. However, in the absence of more quantitative data, a detailed reaction mechanism cannot be drawn. 

In the presence of weak nucleophiles (water, acetic acid, methanol) in acetonitrile, F-Teda BF4 (6) reacts with styrene derivatives to introduce a fluorine atom and the nucleophile component on adjacent carbon atoms giving products 18.88,89... 

The occurrence of some substitution in the deamination of 2-amino-2-deoxy-/3-D-mannopyranosides131 152 (72), and its absence in the reaction of the a-D-pyranoside150 69, must be due to the steric effect of the axial anomeric substituent which (in the a-D-pyran-oside) hinders the approach of the nucleophile (water) to either the C-2 carbonium ion or to C-2 of the diazonium ion. The glucose and glucitol tentatively detected as minor products in the deamination of 72 (R = D-glucose residue and R = D-glucitol residue) presumably arose by way of a hydride shift of H-l to C-2. 2-Deoxy-D-glucono-1,5-lactone (75) was not detected, as it would probably have. o,... 

Scheme 9.11 depicts trans addition of the external nucleophile water resulting in a transoid P-hydroxyethylpalladium intermediate (66).498 Studies with stereoiso-meric DHC=CHD molecules support this view.509,510 Results with D20, however, indicates no deuterium incorporation into the product molecule. This is consistent with an intramolecular cis addition of HO-, namely, ethylene insertion into the Pd-O bond [70 to 71, Eq. (9.101)] ... 

Intramolecular lactonization has been studied on cobalt(III) complexes (Scheme 44).144 The reaction is catalyzed by general acid and the attack of coordinated water occurs at a greater rate than that of coordinated hydroxide ion. Presumably, the relatively non-nucleophilic water is assisted by hydrogen bonding to the carboxyl group to become a pseudo-hydroxide ion. 

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