Hydroxide ion, attack

IS a two step process m which the first step is rate determining In step 1 the nucleophilic hydroxide ion attacks the carbonyl group forming a bond to carbon An alkoxide ion is the product of step 1 This alkoxide ion abstracts a proton from water m step 2 yielding the gemmal diol The second step like all other proton transfers between oxygen that we have seen is fast... 

Once It was established that hydroxide ion attacks the carbonyl group in basic ester hydrolysis the next question to be addressed concerned whether the reaction is concerted or involves a tetrahedral intermediate In a concerted reaction the bond to the leaving group breaks at the same time that hydroxide ion attacks the carbonyl... 

Hydrolysis of aspirin in H2 0 leads to no incorporation of into the product salicylic acid, ruling out the anhydride as an intermediate and thereby excluding mechanism 1. The general acid catalysis of mechanism III can be ruled out on the basis of failure of other nucleophiles to show evidence for general acid catalysis by the neighboring carboxylic acid group. Because there is no reason to believe hydroxide should be special in this way, mechanism III is eliminated. Thus, mechanism II, general base catalysis of hydroxide-ion attack, is believed to be the correct description of the hydrolysis of aspirin. 

Deactivation (weak) from the adjoining ring does not prevent facile disubstitution of 4-methyl- and 4-phenyl-2,7-dichloro-1,8-naphthyridines wdth alkoxides (65°, 30 min), p-phenetidine (ca. 200°, 2 hr), hydrazine hydrate (100°, 8 hr), or diethylaminoethylmer-captide (in xylene, 145°, 24 hr) mono-substitution has not been reported. Nor does stronger deactivation prevent easy 2-oxonation of 5,7-dimethoxy-l-methylnaphthyridinium iodide wdth alkaline ferricyanide via hydroxide ion attack adjacent to the positive charge and loss of hydride ion by oxidation. 

The ratios of these slopes for L- and D-esters are shown in Table 12. The kL/kD values of the acylation step in the CTAB micelle are very close to those in Table 9, as they should be. It is interesting to note that the second deacylation step also occurs enantioselectively. Presumably it is due to the deacylation ocurring by the attack of a zinc ion-coordinated hydroxide ion which, in principle, should be enantioselective as in the hydroxyl group of the ligand. Alternatively, the enantioselectivity is also expected when the free hydroxide ion attack the coordinated carbonyl groups of the acyl-intermediate with the zinc ion. At any rate, the rates of both steps of acylation and deacylation for the L-esters are larger than those for the D-esters in the CTAB micelle. However, in the Triton X-100 micelle, the deacylation step for the D-esters become faster than for the L-esters. 

The issue of the acidity of a-hydrogens in thiirene oxides and dioxides is dealt with only in the dioxide series, since neither the parent, nor any mono-substituted thiirene oxide, is known to date. Thus the study of the reaction of 2-methylthiirene dioxide (19c) with aqueous sodium hydroxide revealed that the hydroxide ion is presumably diverted from attack at the sulfony 1 group (which is the usual pattern for hydroxide ion attack on thiirene dioxides) by the pronounced acidity of the vinyl proton of this compound113 (see equation 14). 

Although we have shown the hydroxide ion attacking the carbocation from the left-hand side, it could equally well have attacked from the right-hand side (see below). This is a consequence of the carbocation having a planar arrangement of bonds around the central carbon atom. 

The nucleophilic hydroxide ion attacks the C atom in the bromoethane from the side opposite to the C-Br bond and begins to form a covalent bond with it. At the same time, the C-Br bond begins to break. A transition state is then reached in which the new 0-C bond is partially formed and the C-Br bond is partially broken. The reaction is completed by the formation of the full 0-C bond and the complete break-up of the C-Br bond. 

Neighbouring phenoxide ion will act as an intramolecular general base in situations where nucleophilic attack is precluded. Bender et al. (1963) found such catalysis in the hydrolysis of p-nitrophenyl 5-nitrosalicylate. Mechanism [40] was favoured over the kinetically equivalent hydroxide ion attack on the neutral species, the reason... 

In this case, the nucleophile is the hydroxide ion. The process begins with the hydroxide ion attacking the carbon atom at one end of the carbon-Ccirbon bond. This is a lone pair-to-bond step. Next, a pair from the Ji-bond shifts to form another re-bond on the other side of the Ccirbon atom. This is a bond-to-bond transfer. Finally, a bond-to-lone pair transfer takes place. 

The Dow Process utilizes an elimination/addition reaction to convert chlorobenzene to phenol. The proposed mechanism for this reaction is shown in Figure 8-3. The high-temperature reaction begins with chlorobenzene and aqueous sodium hydroxide. Note that this mechanism starts with the hydroxide attacking as a base, beginning dehydrohalogenation to form benzyne. The second hydroxide ion attacks as a nucleophile to form a carbanion intermediate, which behaves as a base in the last step to yield the final product. 

Base-catalysed hydrolysis. The hydroxide ion attacks the nitrile carhon, followed hy protonation on the unstable nitrogen anion to generate an imidic acid. The imidic acid tautomerizes to the more stable amide via deprotonation on oxygen and protonation on nitrogen. The base-catalysed amide is converted to carboxylic acid in several steps as discussed earlier for the hydrolysis of amides. 

So in the presence of enough bromine, the ketone is converted rapidly into the tri-bromo ketone. But the reaction doesn t stop, even here. Do you remember that we singled out CBr3 as one of the rare stable simple car-banions How could another molecule of hydroxide ion attack the product to give this anion ... 

Other kinetically allowed mechanistic models, i.e. hydroxide ion attack on the monoanion, can be rejected on the grounds that the required rate coefficients far exceed that found for alkaline hydrolysis of phosphate triesters. At pH > 9 two new reactions appear, one yielding a 1,6-a.nhydro sugar by nucleophilic attack through a five-membered transition state of the 1-alkoxide ion upon C-6 with expulsion of phosphate trianion. The second is apparently general-base catalysis by 1-alkoxide of water attack on C-6 or phosphorus through greater than six-membered cyclic transition states. 

Although the products differ considerably in these two reactions, presumably the mechanisms are not drastically different The negative hydroxide ion attacks the most positive atom in the organic iodide. In methyl iodide this is the carbon atom (, > jyc) and the iodide ion is displaced. In Ihe trifluoromethy) iodide the fluorine atoms induce a positive charge on the carbon which increases its electronegativity until it is greater than that of iodine and thus induces a positive charge on the iodine. The latter is thus attacked hy the hydroxide km with the formation of hypoiodous acid, which then loses an H+ in the alkaline medium to form IO . 

For open-chain compounds, back-side displacement has been established conclusively with the aid of stereoisomers, particularly those with chiral atoms. Inspection of the enantiomers of 2-chlorobutane, shown in Figure 8-2, demonstrates that front-side displacement of chloride by hydroxide ion will give an enantiomer of 2-butanol of the same configuration as the original chloride, whereas back-side displacement will give the alcohol of the opposite, or inverted, configuration. Experiments using either of the two enantiomers show that hydroxide ion attacks 2-chlorobutane exclusively by back-side... 

Hydroxide ion attack, again leading to a nitro complex, has been observed in a ruthenium system. The process is reversed in the presence of H+ (equation 21). 

Many more recent stoichiometric studies of cobalt(III) complexes have been responsible for most of the developments in this area of research. Cobalt(III) ammine complexes effect hydrolysis of ethyl glycinate in basic conditions via intramolecular attack of a coordinated amide ion hydrolysis by external hydroxide ion attack also occurs (equation 74).341 Replacement of ammonia ligands by a quadridentate or two bidentate ligands allows the formation of aquo-hydroxo complexes and enables intramolecular hydroxide ion attack on a coordinated amino ester, amino amide... 

Somewhat similar effects are seen in the copper(II)-promoted hydrolysis of O-acetyl-2-pyridinecarboxaldoxime (47) (equation 20).215 In this case, water attack and hydroxide ion attack are accelerated by 1.1x10 and 2.2 xlO7 times respectively. Detailed analysis indicates that Cuu-bound water or hydroxide reacts with the carbonyl carbon of the ester as shown in (48). Promotion includes contributions from increases in the effective nucleophile concentration in addition to an enhancement in the leaving group ability. General base catalysis in the attack of coordinated water is also observed. 

Kice, however, has suggested that this ieO exchange experiment is inconclusive.72 If hydroxide ion attacks 14, the most likely first intermediate would be 17, in which the five-membered ring spans an apical and an equatorial position and in which O and the electron pair (which are less electronegative than OH73) occupy equatorial positions. This intermediate is not isoenergetic with 18, the... 

The nucleophile (hydroxide ion) attacks the less hindered carbon of the epoxide ring. 

Because of the introduction of a bonds, one may consider a transition state as possessing such bonds and thus assign nomenclature that reflects this temporary state. For example, consider the Sn2 reaction of a hydroxide ion attacking bromomethane OH" + CH3Br > Br + CH3OH... 

Connectivity matrix for transition state of hydroxide ion attacking bromomethane... 

Basic hydrolysis of esters, called saponification, avoids the equilibrium of the Fischer esterification. Hydroxide ion attacks the carbonyl group to give a tetrahedral intermediate. Expulsion of alkoxide ion gives the acid, and a fast proton transfer gives the carboxylate ion and the alcohol. This strongly exothermic proton transfer drives the saponification to completion. A full mole of base is consumed to deprotonate the acid. 

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