Selective Hydrogenation of Azobenzene to Hydrazobenzene via Proton-Coupled Electron Transfer from a Polyoxotungstate Cluster

In this report, we describe proton-coupled electron transfer (PCET) reactivity at the surface of the Keggin-type polyoxotungstate cluster [nBu4N]3[PWVI12O40] (PW12) in acetonitrile. Bond dissociation free energies (BDFEs) of the O–H groups generated upon reduction of PW12 in the presence of acid are determined through the construction of a potential–pKa diagram. The surface O–H bonds are found to be weak (BDFE(O–H)avg < 48 kcal mol–1), comparable to the BDFE of H2. This is consistent with the observed formation of H2 upon addition of a suitably strong organic acid, H2NPh2+ (pKa MeCN = 5.98), to the reduced form of the cluster. The one-electron reduced form of PW12 is isolated and used in conjunction with acid to realize the stoichiometric semihydrogenation of azobenzene via PCET from the surface of the reduced cluster.

H ydrogenation is a fundamental transformation in the chemical industry.Prominent examples of catalysts that facilitate hydrogenation reactions include noble metal complexes (e.g., Ru, Ir, Pd, etc.), 1−4 frustrated Lewis pairs, 5,6 and extended metal surfaces (e.g., Raney nickel and Pd/C). 7,8hile ubiquitous, these catalysts are often expensive, or otherwise produce stoichiometric byproducts that are challenging to recycle. 9,10Furthermore, high-pressure H 2 gas produced from methane cracking is often used�this process requires large energy inputs and possesses a large carbon footprint. 11ccordingly, the development of inexpensive hydrogenation catalysts that facilitate selective small molecule reductions through H atoms sourced from nonfossil feedstocks remains an important objective.
A strategy to bypass the technological and economic limitations of H 2 is the use of protons and chemical or electrochemical reducing equivalents as the hydrogen source. 12,13−16 One class of materials that exhibits PCET reactivity is reducible metal oxides (e.g., ceria, NiO, ZnO, and TiO 2 ).−22 Extended metal oxides can insert H atoms, presenting the challenge in mechanism assignment that possible reactivity originates from the bulk versus being mediated surface-bound H atom equivalents.Similarly, extended metal oxide materials possess a wide range of surface terminations, leaving open the possibility that a small minority of surface sites (e.g., defects) are responsible for the observed reactivity.−25 To address these gaps in knowledge, our research team is investigating the reactivity of molecular tungsten oxide assemblies as atomically precise models for H atom uptake and transfer at the surfaces of extended tungsten oxide materials (Figure 1a).Polyoxotungstates (POTs) are soluble cluster complexes with multiple redox-active tungsten oxyanions linked together by bridging oxide units (Figure 1b).The surface structure of POTs is reminiscent of extended tungsten oxides�both are composed of W VI O 6 octahedra bound together with bridging oxygens.
The electrochemical properties of POTs depend strongly on the identity and chemical activities of cations in solution. 26For example, the Keggin-type POT cluster [ n Bu 4 N] 3 [PW VI 12 O 40 ] (PW 12 ), in acetonitrile exhibits four reversible 1e − redox events (Figure 1c) in aprotic electrolytes.However, upon addition of an excess of acid, these processes collapse into two positively shifted multielectron redox events.This behavior is broadly consistent with PCET, a hallmark of which entails reduction potentials that shift with the chemical activity of protons in solution.This observation suggests that reduced and protonated forms of PW 12 possess reactive H atom equivalents at their surfaces. 27Unfortunately, the understanding of the thermodynamics of surface hydroxides at reduced POT clusters is limited by the challenge of isolating protonated forms of electron-rich polyoxometalates.These clusters are thought to be prone to disproportion reactions or hydrogen evolution as a result of exceptionally weak O−H bonds. 28,29o circumvent challenges measuring the BDFE(O−H) values of isolated, reduced forms of PW 12 , we used electrochemical measurements to map out the stable compositions using a potential−pK a diagram. 30The electrochemical profile of PW 12 in acetonitrile in the presence of organic acids with pK a values ranging from 5 to 38 was assessed via cyclic voltammetry (CV; Figure 2, Figure S1, see the SI for additional details).The observed shifts in reduction potentials (E°) of PW 12 in the presence of the selected range of organic acids indicate that electron transfer to the cluster is coupled to proton transfer under appropriate conditions (Figure 2b).The slopes of each multielectron event (55.5, 57.5 mV/pK a unit) are near the theoretical value of 59 mV/ pK a unit for an n-electron, n-proton transfer.Locating the intersections of acid dependent and independent regions yields acid dissociation constants of 34.8 ± 0.6 (pK a 1, eq S1), 25.9 ± 0.4 (pK a 2, eq S2), 17.4 ± 0.4 (pK a 3, eq S3), and 8.3 ± 0.2 (pK a 4, eq S4).
With the reduction potentials and pK a values of reduced clusters in hand, the average BDFE(O−H) values for the observed multielectron/multiproton redox events can be calculated using the Bordwell equation (eq 1).
where pK a and E°are experimentally determined and C g is a constant associated with the reduction of protons in acetonitrile.BDFE(O−H) avg values of 48.1 and 43.7 kcal mol −1 are determined for the reduced and protonated forms of PW 12 (see eq 2 and 3).−36 This trend is also broadly consistent with differences between the onset potentials for incipient Hinsertion in bulk vanadium and tungsten oxides.
Based on the experimentally determined potential−pK a diagram of PW 12 , we hypothesized that isolation of a monoor bis-hydroxide substituted form of the POT cluster, [ n Bu 4 N] 3 [PW 12 O 40−x (OH) x ] (x = 1, 2), would be possible upon addition of a chemical reductant (E 1/2 < −0.8 V vs Fc +/0 ) to the Keggin ion in the presence of an appropriate acid (pK a < 10).Instead, addition of a strong organic acid (e.g., H 2 NPh 2 + , pK a MeCN = 5.98) to singly or doubly reduced forms of the  cluster results in spontaneous formation of H 2 (δ = 4.57 ppm) and reoxidation of the tungsten oxide assembly over the course of 3 h (Figure 3a, Figures S8 and S9).We note that the estimated BDFE(O−H) avg of 48.1 kcal mol −1 is similar to that of H 2 (BDFE(H−H) = 51.2kcal mol −1 in acetonitrile). 22,41,42his suggests a thermodynamic equilibrium for H 2 production from the surface of the reduced POT cluster in the presence of protons and further suggests that the activation barrier for unior bimolecular H−H bond formation is not prohibitively high.
Given the observed instability of the 1e − /1H + reduced form of the POT cluster, we hypothesized that in situ proton uptake at the reduced PW 12 cluster would serve as a source of H atoms for hydrogenation reactions.To isolate the reduced form of PW 12 , one equivalent of tetrabutylammonium borohydride ( n Bu 4 NBH 4 ) was added to a solution of the cluster in acetonitrile.An immediate color change from colorless to blue was observed.The singly reduced POT, [ n Bu 4 N] 4 [PW V W VI 11 O 40 ] (1e − -PW 12 ) can be isolated from the reaction mixture via recrystallization (Figure 3a, Figure S4, see the SI for more information).In the electronic absorption spectrum 1e − -PW 12 , a band centered at 765 nm (ε = 1855 M −1 cm −1 ) and a shoulder located at 494 nm (ε = 914 M −1 cm −1 ) are observed, which are both consistent with intervalence charge transfer (IVCT) bands. 43 31P NMR spectroscopy serves as an additional characterization method to distinguish the fully oxidized and one-electron reduced species (Figure S3).
With the reduced cluster in hand, we next targeted the hydrogenation of azobenzene to assess the feasibility of H atom transfer reactions using PW 12 as the mediator (Figure 3a).Azobenzene can be reduced by 2e − /2H + to form hydrazobenzene or by 4e − /4H + to generate two equiv of aniline via N�N bond cleavage.−47 But it is still challenging to achieve high conversion and selectivity for hydrazobenzene without sacrificing reaction rate.
Experimental conditions for the hydrogenation reactions are as follows: 1 equiv of azobenzene and 2 equiv of organic acid were combined with two equiv of prereduced 1e − -PW 12 in CD 3 CN, with mesitylene as the internal standard.First, azobenzene and 1e − -PW 12 are mixed (blue trace in Figure 3b).Upon the addition of a strong organic acid, H 2 NPh 2 + (pK a MeCN = 5.98), the mixture turns pale yellow within seconds, consistent with regeneration of the parent PW 12 .The 1 H NMR spectrum, as shown as a green trace in Figure 3b, reveals the complete conversion of azobenzene and deprotonation of the organic acid.Although mixing 1e − -PW 12 and strong organic acid can generate dihydrogen gas, the larger difference in BDFE between hydrazobenzene (BDFE(N−H) = 60.9 kcal mol −1 ) and PW 12 drives the more thermodynamically favored hydrogenation reaction over hydrogen evolution. 21,22,42urther kinetic experiments were conducted to probe the selectivity for azobenzene hydrogenation over hydrogen evolution.The difference in electronic absorption profiles of 1e − -PW 12 and PW 12 enables monitoring of the reaction progression via the loss of the W(V) → W(VI) IVCT band of 1e − -PW 12 (λ = 765 nm).Azobenzene semihydrogenation is observed to proceed >1000 times faster than H 2 formation even when the former is carried out at 60 °C lower temperature and 4-fold lower concentration of reagents (Figure S10).Additional kinetic measurements varying the initial concentration of reactants in azobenzene hydrogenation (see Kinetics section in the SI, Figures S11−S30) indicate that the hydrogenation reaction proceeds only in the presence of reduced cluster and acid, and the rate of azobenzene hydrogenation is dictated by the concentration of whichever of these two species is the limiting reagent.
To further rule out the possibility of stepwise reactivity involving sequential proton/electron transfer steps, NMR studies were conducted to probe for reactions between H 2 NPh 2 + and azobenzene and between 1e − -PW 12 and azobenzene.No changes in the NMR spectra were observed in either case.This is broadly consistent with the thermodynamic properties of each species: electron transfer from 1e − -PW 12 to azobenzene is significantly endergonic, (ΔG ET = +24.9kcal mol −1 , Figure S34) and Ph 2 NH 2 + is not a strong enough acid to protonate azobenzene (the pK a of protonated azobenzene is −2.95 in water). 48hese observations lead us to conclude that the dominant pathway entails rapid formation of a reactive intermediate comprising the reduced and protonated POT bearing labile O−H bonds, followed by rate-determining H atom transfer to azobenzene.In the absence of azobenzene, formation of the same POT intermediate results in H−H bond formation and H 2 evolution, albeit at a much slower rate.As to the identity of the POT intermediate, the potential vs pK a relationships outlined in Figure 2 shows the singly reduced POT is unstable toward disproportionation (to form the doubly reduced/ protonated cluster and PW 12 ) in the presence H 2 NPh 2 + .Hence, the reactive POT intermediate may be the 2e − /2H + transfer disproportionation product or a metastable 1e − /1H + transfer product.Notably, analytical methods used in this study do not enable straightforward differentiation between these species.
The observed selectivity for azobenzene hydrogenation over hydrogen evolution is broadly consistent with markedly different observed rates of the respective reactions, which can in turn be attributed to the much larger driving force for substrate hydrogenation compared to hydrogen evolution� that is, hydrogenated azobenzene is the thermodynamic product.However, full hydrogenation of azobenzene to aniline is also more thermodynamically favorable than semihydrogenation.Thus, thermodynamics alone cannot explain the selective production of hydrazobenzene.An alternative rationale is that the full hydrogenation reaction proceeds sequentially through hydrazobenzene, so conditions involving the addition of only two equiv of hydrogen (via 1e − -PW 12 and Ph 2 NH 2 + ) self-limit at the semihydrogenation product.However, we observe no aniline formation even in the presence of 4 equiv of 1e − -PW 12 and Ph 2 NH 2 + (Figure S33).Instead, after converting azobenzene into hydrazobenzene, the remaining 1e − -PW 12 and acid react to generate dihydrogen rather than to further hydrogenate the hydrazobenzene.This leaves only kinetic control�i.e., markedly higher activation energies for hydrazobenzene hydrogenation compared to azobenzene hydro-genation�as the most plausible explanation for the observed selectivity.
To summarize, we have leveraged PCET reactivity of PW 12 for the stoichiometric semihydrogenation of azobenzene by independently controlling the availability of electrons (via chemical formation of the singly reduced cluster 1e − -PW 12 ) and protons (via control over the concentration and pK a of the organic acid).This type of control was enabled through a complete mapping of the potential−pK a relationships (Figure 2b) associated with proton/electron transfer to the cluster.This approach further allowed us to identify reaction conditions under which the cluster could be used to deliver quantitative semihydrogenation of the model H-acceptor azobenzene, where the exclusion of H 2 and aniline as byproducts can be attributed to thermodynamic and kinetic effects, respectively.

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* sı Supporting Information

Figure 1 .
Figure 1.(a) Molecular structure of WO 3 (monoclinic form stable at 25 °C).(b) Molecular structure of PW 12 .(c) Cyclic voltammogram of PW 12 obtained in acetonitrile (black, 100 mM n Bu 4 NPF 6 with a scan rate of 200 mV/s) and in the presence of 4 equiv of Ph 2 NH 2 BF 4 (pK a = 5.98; red, 100 nM n Bu 4 NPF 6 with a scan rate of 200 mV/s).

Figure 2 .
Figure 2. (a) CVs of 1 mM PW 12 (black) and in the presence of 4 mM 4-trifluoromethylphenol (red, pK a MeCN = 25.5),2,6-lutidinium tetrafluoroborate (blue, pK a MeCN = 14.16), and diphenylammonium tetrafluoroborate (green, pK a MeCN = 5.98) in acetonitrile with 100 mM n Bu 4 NPF 6 at a scan rate of 200 mV/s.(b) Potential−pK a diagram for PW 12 .All of the potentials are calibrated by using Fc +/0 as the internal standards.Each data point represents a CV collected in the presence of one acid; all other CVs are listed in Figure S1.

Figure 3 .
Figure 3. (a) Reaction scheme from PW 12 to protonated, reduced cluster through 1e − -PW 12 , semihydrogenation of azobenzene to hydrazobenzene, and spontaneous H 2 formation through PCET processes.(b) 1 H NMR spectra of the mixture of azobenzene and 1e − -PW 12 before and after the addition of the acid Ph 2 NH 2 BF 4 .The yellow-shaded region is the chemical shift for azobenzene, and the blue-shaded region is for hydrazobenzene.The triangles and asterisks indicate the internal standard mesitylene, and diphenylamine formed from Ph 2 NH 2 BF 4 .