58th Annual Report on Research 2013 Under Sponsorship of the ACS Petroleum Research Fund

Since the discovery of "click chemistry" to synthesize substituted 1,2,3-triazoles via copper-catalyzed alkyne–azide 1,3-dipolar addition, these species have come to the forefront as important heterocycles in chemistry and biology.  However, fundamental studies on the properties of 1,2,3-triazoles are scarce. In this funding period, we studied benzotriazoles. Such species are important precursors to functionalized triazoles, as well as novel ligands for gold catalysts.

 

Having characterized the parent benzotriazole, we moved on this past year to a system that might be useful synthetically, 1-phenylbenzotriazoles. We were interested in characterizing a series of phenylbenzotriazoles with varying substitution, to assess the effect of that substitution on proton affinity.  Also, we were interested in whether substrate proton affinity and binding to gold would be related, in which case the proton affinity could be used as a guide for designing effective ligands for gold catalysts.  We examined the proton affinity of the parent 1-phenylbenzotriazole, as well as the 4'-nitro-, fluoro-, methyl-, and methoxy substituted derivatives, using both calculations and experiments.  Results are summarized in Table 1.

Table 1. Calculated (B3LYP/6-31+G(d); 298 K) and experimental proton affinity data for 1-phenylbenzotriazoles, in kcal mol^-1.

Substrate	Calculated value	Experimental valuea
4'-nitro-1-phenylbenzotriazole	215.4	216
4'-fluoro-1-phenylbenzotriazole	221.7	222
1-phenylbenzotriazole	224.0	223
4'-methyl-1-phenylbenzotriazole	225.6	226
4'-methoxy-1-phenylbenzotriazole	226.9	226

^aExperimental value is obtained by bracketing; error is ± 3 kcal mol^-1.

We would ultimately like to be able to assess the utility of triazoles as ligands for transition metal catalysis. As a first step toward understanding the correlation (if any) between ligand basicity and catalyst efficacy, we conducted a study comparing our proton affinity data with triazole binding affinity data. ³¹P-NMR shifts for the binding of the 1-phenylbenzotriazoles to AuPPh₃ in chloroform  were measured. A strong correlation between the triazole PA and the ³¹P-NMR shift was observed: as PA increases, so too does the chemical shift. These results show that gas phase proton affinity can be used as a predictor of ligand binding, which is useful for ligand design.  The NMR experiments are not nearly as simple to carry out as a gas phase PA calculation, so this correlation is potentially quite useful.