Azide ion clock

The determinations of absolute rate constants with values up to ks = 1010 s-1 for the reaction of carbocations with water and other nucleophilic solvents using either the direct method of laser flash photolysis1 or the indirect azide ion clock method.8 These values of ks (s ) have been combined with rate constants for carbocation formation in the microscopic reverse direction to give values of KR (m) for the equilibrium addition of water to a wide range of benzylic carbocations.9 13... 

Values of (s ) for reaction of the more stable tertiary carbocations X-2+ with a solvent of 50 50 (v/v) water/trifluoroethanol, determined using the azide ion clock, were used to establish a good linear logarithmic relationship between k (s ) for reaction of X-2+ and the first-order rate constants fcobsd (s ) for their formation as intermediates in the stepwise reaction of X-2-C1 in the same solvent (Eq. 2 and Scheme 2.5)." ... 

Absolute values of the rate constants ks (s ) and kp (s ). In most cases these rate constants were determined from the values of kaz/ks (M 1) or kaz/kp (M-1) for partitioning of the carbocation between reaction with azide ion and solvent, by using the diffusion-limited reaction of azide ion, kaz = 5 x 109m 1s, as a clock for the slower reactions of solvent.7 8 13 32 82... 

Recognizing this, Richard and Jencks, proposed using azide ion as a clock for obtaining absolute reactivities of less stable cations. The basic assumption is that azide ion is reacting at the diffusion limit with the cation. Taking 5 x 10 M s as the second-order rate constant for this reaction, measurement of the selectivity fcaz Nu for the competition between azide ion and a second nucleophile then provides the absolute rate constant since feaz is known. The clock approach has now been applied to a number of cations, with measurements of selectivities by both competition kinetics and common ion inhibition. Other nucleophiles have been employed as the clock. The laser flash photolysis (LFP) experiments to be discussed later have verified the azide clock assumption. Cations with lifetimes in water less than about 100 ps do react with azide ion with a rate constant in the range 5-10x10 M- s-, " which means that rate constants obtained by a clock method can be viewed with reasonable confidence. 

One specific embodiment of this approach has been to use the azide (az) clock method (Fig. 13.62). ° Azide ion (N3 ) is a very strong nucleophile (Nu) and is thus assumed to react with most arylnitrenium ions at the diffusion—limited rate. 

For benzene, it has not been possible to measure directly the rate constant kv for deprotonation of the benzenonium ion in order to complete the determination of Ka (— kp/kg). However, this has been possible for 1-protonated naphthalene,106 9-protonated phenanthrene,25 9-protonated anthracene, and 2-protonated benzofuran.75 In the case of the naphthalene, Thibblin and Pirinccioglu showed that the naphthalene hydrate is sufficiently reactive to form the naphthalenonium ion in aqueous azide buffers (pH 4-5).106 Formation of this ion leads to competition between loss of a proton and trapping by azide ion to form the 2-azido-l,2-dihydronaphthalene. From the trapping ratio kp is determined as 1.6xlOlos 1 by the usual clock method. 

As has been discussed elsewhere, Fig. 7 demonstrates the basis for using reactions with azide ion as a clock for determining values of log kH2o in the range pATR = -5 to —15. However, the discussion above cautions against too narrow an interpretation of this figure. The correlations apply to benzhydryl cations and trityl cations and, as we have seen, other families of cations can lead to less ideal dependences of kn2o and, presumably, kAz on p/fR. 

The reaction of azide ions with carbocations is the basis of the azide clock method for estimating carbocation lifetimes in hydroxylic solvents (lifetime = 1 lkiy where lq, is the first-order rate constant for attack of water on the carbocation) this is analogous to the radical clock technique discussed in Chapter 10. In the present case, a rate-product correlation is assumed for the very rapid competing product-forming steps of SN1 reactions (Scheme 2.24). Because the slow step of an SN1 reaction is formation of a carbocation, typical kinetic data do not provide information about this step. Furthermore, the rate constant for the reaction of azide ion with a carbocation (kaz) is assumed to be diffusion controlled (ca. 5 x 109 M 1 s 1). The rate constant for attack by water can then be obtained from the mole ratio of azide product/solvolysis product, and the molar concentrations of azide (Equation 2.18, equivalent to Equation 2.14) [48]. The reliability of the estimated lifetimes was later... 

Values of k.v, = 5 X 109 M-1 s 1 have been determined for diffusion-controlled addition of azide ion to a variety of ring-substituted benzhydryl24 and a-substituted 4-methoxybenzyl25 carbocations. This rate constant have seen extensive use as a clock to determine absolute rate constants for addition of a variety of nucleophiles to benzylic carbocations.5 Relative rate constants for addition of azide ion... 

A mechanism that explains some of the more important observations in the acid-catalyzed hydrolysis of epoxides 49a-d is outlined in Scheme 15. The cis/trans diol product ratios from the acid-catalyzed hydrolysis of 49a-c, which have either hydrogen- or electron-donating groups in the para position of the phenyl ring, are 74 26, 83 17 and 65 35, respectively. An intermediate carbocation 52a is trapped by azide ion in the acid-catalyzed hydrolysis of 49a and the rate constant for reaction of 52a with water in 10 90 dioxane-water solvent is estimated, by the azide clock technique, to be 1.7 x 108 s 1. Azide ion also traps an intermediate 52b in the acid-catalyzed hydrolysis of 49b, but somewhat less efficiently. The rate constant ks for reaction of 52b with solvent is estimated to be 2 x 109 s-1. The somewhat greater reactivity of 52b compared to that of 52a is consistent with the observation that... 

The Jencks clock was developed into a technique whereby the lifetimes of a whole range of oxocarbenium and carbenium ions of moderate stability could measured. Azide ion replaced thiosulfate, as the products were non-ionic and more stable, although the diifusional rate constant for anion-cation recombination of 5 X 10 s in water at 25 °C still applied, and was later confirmed... 

Addition of bromine in methanol gives exclusive trans addition (to 2-deoxy-2-bromomethyl glycosides) in approximately equal amounts, except for tribenzylgalactal, which, as expected from the steric restrictions imposed by 04, gives tribenzyl-2-bromo-2-deoxymethyl p-galactoside and tribenzyl-2-bromo-2-deoxymethyl a-L-talopyranoside in a 2.3 1 ratio. Only in the case of the bromomethoxylation of triacetylglucal was it possible to intercept the oxocarbenium ion with azide ion. The Jencks clock, using a value of 7 x 10 s ... 

Figure 13.62. Azide clock method for determining arylnitrenium ion reaction rate constants.

The application of the azide clock methodology to nitrenium ions was made by Fishbein and McClelland who showed that NJ trapped a reactive intermediate identified as the nitrenium ion 75m, during the Bamberger rearrangement of N-(2,6-dimethylphenyl)hydroxylamine (Scheme 33)7 Kinetic studies showed that the NJ-solvent partitioning occurred after the rate-limiting step of the reaction so an Sn2 process could be eliminated. The selectivity ratio, was determined to be 7.5 M . Assuming that k is... 

Azide/solvent selectivity data in predominately aqueous solution have been collected for over 30 nitrenium ions either by the azide clock method or by direct measurement of k - and k on ions generated by laser flash... 

Conditions 5% CH3CH-H2O, = 0.5 (NaC104), T = 20°C, unless otherwise indicated. If and are reported, the rate constants were directly measured from photochemically generated ions. If only log 5 is reported, the selectivity was measured by the azide clock procedure. X is the observed [azide adduct]/[hydration product] ratio extrapolated to 1 M NJ. 

Effects of the aryl substituents X on knuc for alcohols and H2O were different from those expected for arylcarbenium ions, but were very similar to those deduced for from azide-clock experiments on similarly substituted nitrenium ions generated by solvolysis reactions in... 

Shortly after Anderson and Falvey reported the first observation of a shortlived nitrenium ion in CH3CN by UV spectroscopy, Novak and McClelland and co-workers demonstrated that the nitrenium ions 75h and 75o could be observed in aqueous solution after LFP of the pivalic acid ester 76h, the sulfuric acid ester 76o, and its N-chloro analogue N-chloro-4-phenylacetanilide. The transients with A ax of ca. 450 nm were identified as singlet nitrenium ions, based on the kinetics of their decomposition in the presence of NJ, the equivalence of kaz/ks determined by the azide clock method and by direct observation, the lack of sensitivity of the transients to O2, product studies that showed similar products from solvolytic and photolytic decomposition of N-chloro-4-phenylacetanilide, and identical transient UV spectra for 75o derived either from 76o or its N-chloro analogue. A comparison of azide/solvent selectivity data obtained by azide clock and direct observation of 7Sh and 75o is presented in Table 1. 

A further indication of aromatic stability is provided by measurement of pAR for the cycloheptadienyl cation 35. This ion is a homolog of the cyclohex-adienyl cation (pAR = -2.3) and might have been expected to have a similar stability. In practice, measurements in aqueous solution using the azide clock show that pAR is —11.6, which corresponds to a decrease in stability of 12.5kcalmol-1.88 It seems unlikely that this difference arises solely from strain in the cycloheptadienyl ring. Moreover, for the dibenzocycloheptadienyl cation, 36, a pAR = -8.7 can be deduced from measurements in aqueous trifluoroacetic acid (Scheme 25).170 Despite the difference in solvents it seems clear that in this case and in contrast to its effect in Scheme 24 dibenzoannelation strongly stabilizes the cation. 

Scheme 2.24 The azide clock involving competitive trapping of a carbenium ion by water and azide.

---