Hydroxide intramolecular attack

The behavior of 7-bromo-2,3,7-trideoxy-D-amfe/ o-heptono- 1,4-lactone (205) and 7-bromo-2,7-dideoxy- (208) and 7-bromo-3,7-dideoxy-D-g/Mco-heptono-1,4-lactone (211) toward aqueous base has also been studied (229). The 6,7-epoxide is formed by potassium carbonate treatment of each bro-modeoxy heptonolactone. With potassium hydroxide, epoxide migration occurs giving mixtures of epoxides that undergo intramolecular attack by the... 

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... 

N-acylamino acids does not appear to have been studied previously. In solution, N-acyl-N-nitroso-a-amino acids are moderately stable to weak bases, such as triethylamine or sodium carbonate, but are decomposed rapidly at 0° to expel nitrogen on addition of sodium hydroxide (43). For example, treatment of N-nitroso-N-benzoyl-D,L-pheny1-alanine LXIIb with an aqueous sodium hydroxide solution at 0 gives benzoic acid and 1-hydroxy-3-phenylpropanoic acid LXVa in a 93% yield. The facile base-catalysed formations of a-hydroxy acids LXV are a general reaction and probably occur by intramolecular attack as shown in LXII->LXIII->LXIV. Oxadiazolone LXIV can decompose by various possible pathways to give LXV among which the carbonium ion pathway is least likely. 

With sodium hydroxide, methyl 2,3-anhydro-a-D-allopyranoside yields methyl 3,6-anhydro-a-D-glucopyranoside by intramolecular attack on the epoxide ring by the 6-hydroxyl group.72 Methyl 2,3-anhydro-a-D-gulopyranoside behaves similarly, and its intermediacy accounts for the conversion of methyl 3,4-anhydro-a-D-galactopyrano-side into methyl 3,6-anhydro-a-D-galactopyranoside on treatment with alkali.67... 

Cobalt-coordinated amide nucleophiles have also been observed to attack coordinated phosphate esters (equation 38),148 disulfides (Scheme 47)149 150 and nitriles (Scheme 48).151>152 Chelated amides can also be formed by intramolecular attack of cobalt hydroxides.153... 

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... 

Intramolecular attack by coordinated hydroxide (7) appears unlikely in this system in view of the relatively low rate accelerations observed, and the fact that the reaction shows a first order dependence on the hydroxide ion concentration up to pH 8. 

Although intramolecular attack by coordinated hydroxide ion (21) could occur in these systems, this pathway in not supported by the experimental evidence.86... 

A number of complexes of the general type (CoN4(OH)(OH2)]2+ (N4 = a system of four nitrogen donors) stoichiometrically cleave the N-terminal amino acid from di-or tri-peptides. Reactions have been described for N4 = en2,164-165 trien166 167 and tren.168,186 In the case of trien complexes, the proposed mechanism for peptide hydrolysis is shown in Scheme 7. Hydrolysis can occur by two pathways (a) attack by external hydroxide on the O-bonded chelated peptide, and (b) intramolecular attack of coordinated hydroxide on the N-bonded peptide. 

The hydrolysis of j8,y-[Co(NH3)4H2P3Oi0] (89) is greatly accelerated in the presence of cis-[Co(cyclen)(OH2)2]3+ (Cyclen = 1,4,7,10-tetratazacyclododecane) and the intermediate (90) has been suggested as the active complex.289 31P NMR studies have now provided evidence in support of such an intermediate,290 hydrolysis occurring via intramolecular attack by coordinated hydroxide. 

The enzyme aconitase catalyzes the isomerization of citric acid to isocitric acid via the intermediate cis-aconitic acid (Scheme 46),530 and various attempts have been made to model this reaction.21 The cobalt Ill) complexes derived from methyl maleate (171) and methyl fumarate (172) have been prepared531 to study intramolecular attack by coordinated hydroxide on the alkene. Generation of the hydroxo species of the maleic acid complex leads to rapid cyclization to give the... 

At first sight these reactions are simple examples of metal-activated nucleophilic attack upon the nitrile carbon atom. However, the geometry of the co-ordinated chelating ligand is such that the nitrile nitrogen atom is not co-ordinated to the metal ion (4.3 and 4.4) It was initially thought that this provided evidence for a mechanism involving intramolecular attack by co-ordinated water or hydroxide (Fig. 4-10). However, detailed mechanistic studies of the pH dependence of the reaction have demonstrated that the attack is by external non-co-ordinated water (or hydroxide) (Fig. 4-11). 

Figure 4-49. Hydrolysis of a monodentate phosphate resulting from intramolecular attack by a coordinate hydroxide nucleophile.

The intramolecular attack of hydroxide upon the monodentate ester (Fig. 5-67) would give the same observed product as the other mechanism. 

Although the above discussion has concentrated upon the hydrolysis of amino acid esters, very similar mechanisms have been demonstrated for the hydrolysis of amino acid amides. A very wide range of intramolecular reactions of this type are now known to occur by intramolecular attack by hydroxide, with most having been demonstrated at non-labile... 

Figure 5-70. The hydrolysis of the ester 5.32 is accelerated by copper(n) salts. The initial step is the formation of the chelated copper(n) complex, followed by intramolecular attack of co-ordinated hydroxide upon the co-ordinated ester group.

Figure 5-71. The hydrolysis of the tridentate ligand 5.33 is accelerated by co-ordination to a metal ion. The two reaction involves intramolecular attack by co-ordinated hydroxide.

The considerable increase in rate constant associated with this process has been attributed to the induced intramolecular attack in adduct 5 compared to the intermolecular attack of hydroxide ion that is entropically unfavorable [42], The cyclic intermediate 6 readily rearranges into open-chain imine 7. The similarity between this kind of mechanism and enzymatic catalysis has been associated with the use of binding energy to compensate for the entropy cost while coupling the carbonyl compound to the amino group [44] in a way that is similar to the utilization of favorable interaction with non-reacting portion of the substrates by enzymes [45]. 

The answer must be a mechanism related to the one we have just seen for epichlorohydrin. Attack by hydroxide on CCI3 is almost unknown and it is much more likely that intramolecular attack by alkoxide to give an epoxide should occur. The carboxylate anion can then invert the stereogenic centre by intramolecular S>j2 displacement at the central carbon atom. Notice that the tether ensures attack at the central atom. The second four-membered lactone also hydrolyses by attack at the carbonyl group. 

Two mechanisms of cobalt(III)-mediated peptide-bond cleavage have been investigated. The first one involves hydrolysis of a directly activated amino acid ester, or peptide (equation 4). The other mechanism involves the intramolecular attack of an amino acid ester or peptide by a cis coordinated hydroxide or water molecule (equation 5). In both cases, the cobalt(III) complex must have two open coordination sites cis to each other. For the directly activated mechanism, these sites are needed to bind the amino acid ester or peptide. The intramolecular reaction requires one site for coordination of the ester or peptide, and one site for the coordination of the hydroxy or water molecnle. One of the initial cobalt(III) complexes to be investigated was... 

Hendry P, Sargeson AM. Metal ion promoted phosphate ester 43. hydrolysis. Intramolecular attack of coordinated hydroxide ion. 

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