Covalent hydration kinetic studies

The effect of substituents in the 5-, 6-, 7-, or 8-position of quinazo-line was summed up in the earlier review.38 In general, (—1) substituents promote hydration of the 3,4-bond by lowering the electron density on C-4. Later it was found that a (—1) substituent in the 2-position had the opposite effect. The addition of the negatively charged pole of a water molecule to C-4 is favored by the polarization of the 3,4-bond in this sense —C4 =N—4V But a (—1) group in the 2-position can oppose this polarization. In a study of twenty 2-substituted quinazolines,23 it was found that hydration was helped by (+1) substituents, not greatly affected by (+M), and much diminished by (—I) substituents. The pH rate profile (first-order kinetics) for the hydration of 2-aminoquinazoline, measured from pH 2 to 10, was parabolic,23 typical of molecules that undergo reverse covalent hydration.315... 

A parallel study of aqueous bromination of pyrimidin-4(3//)-one and its /V-methyl derivatives also pointed to an addition-elimination process involving cationic intermediates. The kinetic results for these substrates differed from those of 39 (in which the pseudo bases dehydrate as neutral molecules) in that the intermediates dehydrated in cationic forms (79JOC3256). Again, the covalent hydrates, though present to only a minor extent (—0.0003%), were the reactive species in the bromination process. Pyrimidin-4(3//)-one, as its covalent hydrate, reacts 600 times faster than it does itself the rate enhancement is even greater O 104) for the 2-isomer, which exhibits a higher degree (—0.05%) of covalent hydration. 

Pteridine Studies. Part XXIV. Competitive Covalent Hydration of 2,6-Dihydroxypteridine Kinetics and Equilibria. 

The covalent addition of water to C=N in an N—0=N system to form a stable hydrate is rare in heterocyclic chemistry. Two examples are known in the quinazoline series, and these are 2-methyl- and 2-phenyltetra-zolo[l,5-c]quinazoline. In these compounds water addition across the 3,4 double bond is not possible because of ring fusion. When these were treated with hydroxides, the hydrates (7 R = Me and Ph) were isolated and characterized. - Undoubtedly such hydrates must be involved as intermediates in the syntheses or hydrolytic degradation of quinazolines in which the C-2, N-3 bond is made or broken. Indirect evidence that a 1,2-covalent hydrate was a necessary intermediate in the bromination of quinazolin-4-one came from judicious kinetic studies. The kinetic order, acidity dependence or rates, inverse dependence of rates on bromide ion, and the relative reactivities of quinazolin-4(3//)-one, 3-methylquinazolin-4-one and l,3-dimethyl-4-oxoquinazolinium perchlorate were consistent with a mechanism in which the rate-determining step was attack of molecular bromine on the 1,2-covalent hydrate, i.e., 8 -> 9. ... 

Other Studies.— The kinetics and mechanisms of reactions of tptz (5) complexes of cobalt(ii), copper(ii), and nickel(u) with water and with hydroxide have been established and compared. Covalent hydrates are believed to be important intermediates in aquation of the [M(tptz)(OH2)3] + complexes. Kinetics of aquation of the anions [M(acac)a] (M = Co, Cr, or Ru) have been studied in pulse radiolysis experiments. All three steps were monitored for the cobalt(n) complex, but the first step for the chromium(ii) complex was too fast to follow and, predictably, all steps for the ruthenium(ir) complex were too slow to follow by this technique. The mechanism of acac loss is thought to involve equilibrium... 

Several references deal with slow or relatively slow substitution at iron(III), while a few are directly relevant to analogous iron(II) systems discussed in Sections 8.2.1 and 8.2.2. Indeed iron(III)-diimine complexes have already been mentioned in connection with covalent hydration (Section 8.2.2.4). " " Substitution at [Fe(phen)3] is a very much less popular area of study than that of its iron(II) analogue (Section 8.2.2). Dissociation of the iron(III) complex in aqueous acetone is claimed to be first order with respect to [Fe(phen)3] ", second order with respect to acetone, and reciprocal first order with respect to This information is derived from observations at 620 nm a more complicated picture emerged from kinetic studies carried out at 470 nm The interpretation offered rather conceals the key role of acetone in solvating the leaving 1,10-phenanthroline, though this is mentioned in the final sentence. " It is regrettable that the authors do not report their primary experimental results, namely their rate constants. 

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