Redox‐Active Guanidines in Proton‐Coupled Electron‐Transfer Reactions: Real Alternatives to Benzoquinones?

Abstract Guanidino‐functionalized aromatics (GFAs) are readily available, stable organic redox‐active compounds. In this work we apply one particular GFA compound, 1,2,4,5‐tetrakis(tetramethylguanidino)benzene, in its oxidized form in a variety of oxidation/oxidative coupling reactions to demonstrate the scope of its proton‐coupled electron transfer (PCET) reactivity. Addition of an excess of acid boosts its oxidation power, enabling the oxidative coupling of substrates with redox potentials of at least +0.77 V vs. Fc+/Fc. The green recyclability by catalytic re‐oxidation with dioxygen is also shown. Finally, a direct comparison indicates that GFAs are real alternatives to toxic halo‐ or cyano‐substituted benzoquinones.


General protocol (NMR experiments)
In an NMR tube, the reactants 1(BF 4 ) 2 / 1(PF 6 ) 2 ) or (1+2H)(BF 4 ) 4 , and in some experiments also NH 4 PF 6 were dissolved (with HMB) in an Ar atmosphere in 0.45 mL CD 3 CN. Then a benzylamine solution (10% in CH 3 CN) was added dropwise via microliter injection and the reaction mixture heated to 60 °C. The conversion was followed by NMR measurements (at room temperature). The overall reaction time refers to the time at 60 °C.

General protocol
In a Schlenk flask, 0.5 mL of a HBF 4 ·Et 2 O solution (5% in CH 3 CN) was added under ice cooling in an Ar atmosphere to the reactants 1(BF 4 ) 2 / 1(PF 6 ) 2 ) and triphenylamine. The reaction was stirred for several minutes under ice cooling and then allowed to warm up to room temperature. The reaction was stopped by the addition of an aqueous saturated NaHCO 3 solution.
The small amount of CH 3 CN was removed under high-vacuum. Then an aqueous diluted solution of NaOH (8%) was added (pH > 9), converting all formed (1+4H) 4+ to (1+2H) 2+ (for subsequent transfer into the organic phase). A clear solution was obtained that was extracted several times with CH 2 Cl 2 . The combined organic phases were dried over Na 2 SO 4 , filtrated and condensed.

Separation of 1(BF 4 ) 2 / [(1+2H)(BF 4 ) 2 ]
The residue was collected in diethylether and filtrated, allowing the isolation of the coupling product in the filtrate. The residue in the filter, consisting of

Reaction in an NMR tube (entry A)
In an NMR tube, the reactants 1(BF 4 ) 2 and triphenylamine (and HMB) were dissolved in an Ar atmosphere in 0.45 mL CD 3 CN. An NMR spectrum was recorded, showing that no reaction took place. Then 0.05 mL of a HBF 4 ·Et 2 O solution (5% in CD 3 CN) were dropwise added with a syringe and an NMR spectrum taken from the reaction mixture. After a second (dropwise) addition of 0.27 mL of the HBF 4 ·Et 2 O solution (5% in CD 3 CN) another NMR spectrum was recorded.

Reactions in Schlenk flasks (entries B -D)
In a Schlenk flask, a HBF 4 ·Et 2 O solution (5% in CH 3 CN) was added with a syringe under ice cooling in an Ar atmosphere to a solution of the reactants 1(BF 4 ) 2 / 1(PF 6 ) 2 ) and triphenylamine in 1 mL CH 3 CN. The reaction was stirred for several minutes under ice cooling and then allowed to warm up to room temperature for further reaction.

Work-up (entries B -D)
The reaction was stopped by the addition of an aqueous saturated NaHCO 3 solution.
The small amount of CH 3

General protocol
Entries A and B: In a Schlenk flask, 0.5 mL of a HBF 4 ·Et 2 O solution (5% in CH 3 CN) was added with a syringe under ice cooling in an Ar atmosphere to a solution of 1(BF 4 ) 2 / 1(PF 6 ) 2 ) and 4,4'-dibromotriphenylamine in 1 mL CH 3 CN. The reaction was stirred for several minutes under ice cooling and then allowed to warm up to room temperature for further reaction. In a Schlenk flask, 0.11 mL (40.1 µmol) of a HBF 4 ·Et 2 O solution (5% in CH 3 CN) was added with a syringe in an Ar atmosphere to a solution of 1(PF 6 ) 2 ) and 4,4'dibromotriphenylamine in 0.6 mL CH 3 CN. The reaction was stirred for 23 h at room temperature.

Work-up (for all experiments):
The reaction was stopped by the addition of an aqueous saturated NaHCO 3 solution.
The small amount of CH 3 CN was removed under high-vacuum. An aqueous diluted solution of NaOH (8%) was added (pH > 9), converting all formed (1+4H) 4+ to (1+2H) 2+ (for subsequent transfer into the organic phase). A clear solution was obtained that was extracted several times with CH 2 Cl 2 . The combined organic phases were dried over Na 2 SO 4 , filtrated and condensed.

General protocol
In a Schlenk flask, 0.5 mL of a HBF 4 ·Et 2 O solution (5% in CH 3 CN) was added under ice cooling in an Ar atmosphere to the reactants 1(BF 4 ) 2 / 1(PF 6 ) 2 ) and 4nitrotriphenylamine. The reaction was stirred for several minutes under ice cooling and then allowed to warm up to room temperature for further reaction. The reaction was stopped by the addition of an aqueous saturated NaHCO 3 solution.
The small amount of CH 3 CN was removed under high-vacuum. Then an aqueous diluted solution of NaOH (8%) was added (pH > 9), converting all formed (1+4H) 4+ to (1+2H) 2+ (for subsequent transfer into the organic phase). A clear solution was obtained that was extracted several times with CH 2 Cl 2 . The combined organic phases were dried over Na 2 SO 4 , filtrated and condensed.

Conclusions from the experiments
With a substrate/GFA ratio of 1:1 the reactions proceeded almost quantitatively, without side products under the applied conditions. In the case of a substrate: GFA ratio of 1:0.65 the reactions were slower and substrate was still present when the reaction time was doublet.
The NMR spectra taken for the experiments with only small amounts of HBF 4 either show still the presence of unreacted substrate (for small reaction times) or the products of additional coupling (for longer reaction times). The reaction with 4,4'dibromtriphenylamine was an exception, since formation of additional coupling products is prohibited by the bromo substituents. In this case the reaction time can be increased without the observation of further products. However, the reaction was much slower and not quantitative.   . These calculations relied on the TURBOMOLE program. [1,2,3] The B3LYP functional [4,5] was used in combination with the def2-SV(P) or def2-TZVP basis set. [6] The influence of a polarizable environment was considered by the conductor-like screening model (COSMO). [7] Compound

Analysis of the influence of the relative solvent permittivity (dielectric constant)  r on the reaction energy
The reaction between dihydro-benzoquinones and 1 2+ / 1(BF 4 ) 2 was chosen to study the solvent effect in more detail.
A) Calculations without anions ("single-point" calculations at the optimized structure at  r = 1) If the structurs are optimized at each  r value (with inclusion of the anions), the E vs.  r curve (starting with E = 9.9 kJ mol 1 at  r = 1) passes through a maximum (E = 15.8 kJ mol 1 at  r = 5), and then slightly decreases to E = 12.5 kJ mol 1 at  r = 80. The maximum results from the change of the position/orientation of the anions.

Overall conclusion:
The dependence of the reaction energy E on the  r value is relatively small. The inclusion of the anions also has only a small effect. Finally, the difference between the E values from single-point calculations at the optimized structure at  r = 1 and the E values for optimized structures at each  r value is also quite small.