Base hydrolysis proton exchange

Methylene groups adjacent to coordinated nitrile carbon are acidic (e.g. for R = CH2CN, P= 5.7) and rapidly undergo base-catalyzed proton exchange (for R = Me this is faster than hydrolysis), and addition of electrophiles other than H+ to the resulting carbanion (35 Scheme 19). 

In much of the early kinetic work on macrocyclic complexes the stereochemical complexities were largely ignored. Fortunately in basic solution the diastereoisomers will equilibrate (by base catalysed proton exchange) to give the most thermodynamically stable trans-lll diastereoisomer which has chair six-membered and gauche five-membered chelate rings. As a result the base hydrolysis kinetics reported for [14]aneN4 and its alkyl substituted derivatives probably relate to the trans-III diastereoisomer,(3.12)... 

Proton transfer reactions on the aqua oxo complex are described by Eq. (8) (acid catalysis or protolysis), Eq. (9) (base catalysis or hydrolysis), and Eq. (10) (direct proton exchange). 

Similarly, the proton transfer on the hydroxo oxo complex is illustrated by Eqs. (13)-(15), based on the Eigen model (Scheme 4), and can again be due to protolysis, hydrolysis, or direct proton exchange... 

One important feature of the ligands shown in Fig. 18 is that they both contain the py—CH2—R functional group. Jackson et al. (117) have shown that for several Co(III) systems, these -CH2- protons can exchange in alkaline D20 at rates comparable to those of base hydrolysis. Consequently, there are three possible mechanisms for the OH-dependence in these complexes without NH protons (i) reversible Cr—N bond rupture (118) (ii) conjugate base formation at the methylene protons and subsequent electron delocalization through the chelated pyridine ring (117) and (iii) direct bimolecular attack. 

The mechanism provides (in equation 1) a pathway for proton exchange in amine complexes. (In fact, it was the observation that proton exchange in [Co(NH3)6]3+313 and the base hydrolysis of (Co(NH3)5Br]2+298 had the same kinetic form that led Garrick to propose this mechanism in 1937.314) The pathway for base catalyzed solvolysis is made up of (1) + (2) + (3) and the pathway for base catalyzed substitution is (1) + (2) + (4). It was the observation of base catalyzed ligand substitution that provided the first strong evidence for the dissociative nature of the process.315... 

Hydrolysis of monodentate phosphate is also very slow and Com-OP03H species (n = 3-0) can be considered inert at room temperature (ka, Table 44). As expected, hydrolysis occurs by substitution at the metal and without exchange into the phosphate (equation 117). Acid catalysis is interpreted in terms of aquation of the acid conjugate of the complexed phosphate (Table 44). [Co OP(OH)3 (NH3)5]3+ (p a — 0.7) hydrolyzes some 102 times slower than [Co OP(OMe)3 (NH3)5]3+, which suggests that protonation at the bound O atom is not important. Base hydrolysis is also very slow (Table 44), occurs via substitution at the metal, and an S lcb process is likely via prior deprotonation of an ammine ligand (equation 118). 

It has been observed that the lithium salts of phosphono acetates (497) and (498) undergo base catalysed D/H proton exchange and C-OR esterolysis as well as acidic hydrolysis mediated by Th and (Figure 95). ... 

Until the early 1960s it was assumed that proton transfer would always be much faster than the overall base hydrolysis. However, in 1968 it was shown that, at 0 °C, proton exchange and base hydrolysis of rrans-[Co(R55R-cyclam)Cl2] had similar rates. Under these circumstances, k i w k2, and, in the limit when 2 > k i, the expression reduces to kg so deprotonation... 

The systems where k2> k-i offer a direct demonstration of the conjugate base mechanism. In the reactions of the trans-RS and trans-RR(SSp isomers of the [Co(2,3,2-tet)Cl2] complex, examination of the reaction product showed that the act of base hydrolysis was accompanied by the exchange of one secondary amine proton. All other exchange was shown to take place after this product was formed. Comparison of the amount of proton exchange in recovered unreacted tra 5-[Co(en)2Cl2] with that in the recovered reaction product likewise indicated that an act of base hydrolysis required the removal of one amine proton. 

Comparison of base hydrolysis, racemisation, and proton exchange rates for [CoX(trenen)] +, where X = Cl , N3-, or OHg, and trenen is the quinquedentate ligand (19) indicates an nlcb mechanism for base hydrolysis. The demonstration of linear free energy plots (AG vs. AC ) of... 

It is now generally accepted that the base hydrolysis pathway occurs by a l cB (SnICB) mechanism. During the period 1955-65 there was a lively controversy on the topic, an account of which has been written by Basolo [5] and by Pearson [18]. The currently accepted Dcb mechanism was first proposed in 1937 by Garrick [6] on the basis of the similarity of the kinetics of these reactions to those of proton exchange of amine complexes. The mechanism was revived and developed by Basolo and Pearson in the 1950 s [7]. The Dqb mechanism is outlined by the set of equations (1-3). Hydroxide ion acts as a base rather than as a nucleophile and removes a proton from a... 

O vs. N Protonation.—Controversy over the site of protonation of amides has been raised anew by Liler. Using u.v. spectroscopy, she has suggested that benzamide is 50 50 O N protonated in 80 % sulphuric acid. However, a considerable weight of evidence has been produced to indicate that protonation or Lewis acid complexation of amides consistently occurs by co-ordination with oxygen. Studies have included the acidity-dependent changes in the tt-tt and n-it u.v. absorption bands of aliphatic amides kinetic evidence based on rate data for acid-catalysed amide hydrolysis in both dilute and concentrated acid an n.m.r. study of proton exchange rates, where for A -methylacetamide the molar ratio of 0 N protonated species exceeds 10 a n.m.r. study of adducts of boron trifluoride and antimony pentachloride with N-labelled ureas, where the hybridization-dependent —H coupling constants were inconsistent with N-co-ordination ... 

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