Diferrocenyl tosyl hydrazone with an ultrastrong NHFe hydrogen bond as double click switch

Tosyl hydrazones have found increasing applications in organic synthesis as safe reagents for diazo compound generation. The redoxactive diferrocenyl tosylhydrazone 2 had been previously employed for the in situ generation of the highly reactive and elusive diferrocenyl carbene. Some spectroscopic data of 2 have been reported before but no further interpretations were given. N,N-Dimethyl diferrocenyl hydrazone and diferrocenyl hydrazone have been reported previously by Bildstein, but no unusual properties have been reported either. 2 is prepared straightforwardly from the diferrocenyl ketone 1 and p-toluenesulfonyl hydrazide (Scheme 1). Initially, we were mainly interested in the redox properties of 2. However, we were puzzled by some unexpected spectroscopic data of 2. The absorption band for the NH stretching vibration of 2 is found at 3101 cm 1 in the solid state, significantly lower than that of the analogous diphenyl tosylhydrazone 3 (3219 cm ; with intermolecular NH OS hydrogen bonds in the solid state; ESI†). The NH stretch of 2 is clearly identified by HD exchange and the appearance of the ND stretching absorption at 2317 cm 1 (ESI†). Similarly, in CD2Cl2 solution this band of 2 occurs at 3118 cm 1 while the corresponding band of 3 is detected at significantly higher energies (3267 cm 1 in CD2Cl2). These data clearly advocate intramolecular interactions in 2 but not in 3. Similarly, the resonance of the NH proton of 2 (d = 10.45 ppm) appears at significantly lower field than that of 3 (d = 7.35 ppm) in CDCl3. Especially intriguing is the NOE contact NH Cp(H) (Scheme 1 and Fig. 1) as the NH group then necessarily points towards a C5H5 ring and hence towards an iron(II) centre. Indeed, DFT calculations suggest that the conformer with an intramolecular NH Fe hydrogen bond (Fe N distance 3.55 Å; Fe H distance 2.67 Å) is more stable by 10 kJ mol 1 with respect to a non-hydrogen bonded conformer. The conceivable zwitterionic species with protonated iron and deprotonated hydrazone is higher in energy by more than 160 kJ mol . Hence full proton transfer from the hydrazone to ferrocene is thermodynamically unfeasible. Furthermore, protonation at iron should yield a high-field proton resonance around d = 2 ppm which is not observed for 2. Final proof of the suspected hydrogen bond also in the solid state is provided by an XRD analysis of a single crystal of 2 (Fig. 2). Indeed, the NH vector points to the iron(II) centre Fe2 of one ferrocenyl substituent forming a six-membered ring Fe2–C12–C11– N1–N2–H2N with an Fe2 N2 distance of 3.46 Å (Fig. 2). The sixmembered ring has already been shown to promote the strongest intramolecular OH Fe bond in ferrocenyl alcohols. To the best of our knowledge the N Fe distance in 2 is among the shortest hydrogen bond donor to iron distances in iron complexes observed so far. Furthermore, 2 features the first NH Fe hydrogen bond with a six-membered ring as the only three previously reported NH Fe hydrogen bonds comprise five-membered rings. The Cp rings of the hydrogen bonded ferrocenyl substituent are tilted by 6.21 accommodating the NH group. The Cp rings of the other ferrocenyl substituent are essentially coplanar. Scheme 1 Synthesis of diferrocenyl tosylhydrazone 2 from diferrocenyl ketone 1.

Tosyl hydrazones have found increasing applications in organic synthesis as safe reagents for diazo compound generation. 1 The redoxactive diferrocenyl tosylhydrazone 2 had been previously employed for the in situ generation of the highly reactive and elusive diferrocenyl carbene. 2 Some spectroscopic data of 2 have been reported before but no further interpretations were given.2a N,N-Dimethyl diferrocenyl hydrazone and diferrocenyl hydrazone have been reported previously by Bildstein, but no unusual properties have been reported either. 32 is prepared straightforwardly from the diferrocenyl ketone 1 and p-toluenesulfonyl hydrazide (Scheme 1).Initially, we were mainly interested in the redox properties of 2.
However, we were puzzled by some unexpected spectroscopic data of 2. The absorption band for the NH stretching vibration of 2 is found at 3101 cm À1 in the solid state, significantly lower than that of the analogous diphenyl tosylhydrazone 3 (3219 cm À1 ; with intermolecular NHÁ Á ÁOS hydrogen bonds in the solid state; 5 ESI †).The NH stretch of 2 is clearly identified by HD exchange and the appearance of the ND stretching absorption at 2317 cm À1 (ESI †).Similarly, in CD 2 Cl 2 solution this band of 2 occurs at 3118 cm À1 while the corresponding band of 3 is detected at significantly higher energies (3267 cm À1 in CD 2 Cl 2 ).These data clearly advocate intramolecular interactions in 2 but not in 3. Similarly, the resonance of the NH 6 proton of 2 (d = 10.45 ppm) appears at significantly lower field than that of 3 (d = 7.35 ppm) in CDCl 3 .
Especially intriguing is the NOE contact NH 6 Á Á ÁCp(H 11 ) (Scheme 1 and Fig. 1) as the NH group then necessarily points towards a C 5 H 5 ring and hence towards an iron(II) centre.Indeed, DFT calculations suggest that the conformer with an intramolecular NHÁ Á ÁFe hydrogen bond (FeÁ Á ÁN distance 3.55 Å; FeÁ Á ÁH distance 2.67 Å) is more stable by 10 kJ mol À1 with respect to a non-hydrogen bonded conformer.The conceivable zwitterionic species with protonated iron and deprotonated hydrazone is higher in energy by more than 160 kJ mol À1 .Hence full proton transfer from the hydrazone to ferrocene is thermodynamically unfeasible.Furthermore, protonation at iron should yield a high-field proton resonance around d = À2 ppm 6 which is not observed for 2.
Final proof of the suspected hydrogen bond also in the solid state is provided by an XRD analysis of a single crystal of 2 (Fig. 2).Indeed, the NH vector points to the iron(II) centre Fe2 of one ferrocenyl substituent forming a six-membered ring Fe2-C12-C11-N1-N2-H2N with an Fe2Á Á ÁN2 distance of 3.46 Å (Fig. 2).The sixmembered ring has already been shown to promote the strongest intramolecular OHÁ Á ÁFe bond in ferrocenyl alcohols. 7To the best of our knowledge the NÁ Á ÁFe distance in 2 is among the shortest hydrogen bond donor to iron distances in iron complexes observed so far. 8,9Furthermore, 2 features the first NHÁ Á ÁFe hydrogen bond with a six-membered ring as the only three previously reported NHÁ Á ÁFe hydrogen bonds comprise five-membered rings.8g-i The Cp rings of the hydrogen bonded ferrocenyl substituent are tilted by 6.21 accommodating the NH group.The Cp rings of the other ferrocenyl substituent are essentially coplanar.
The different symmetry and coordination of the ferrocene sites is not reflected in the Mo ¨ßbauer parameters and only a sharp doublet is obtained (d = 0.4484/0.5273mm s À1 ; DE Q = 2.300/2.3080mm s À1 both at 293 K and 90 K, respectively; ESI †) which is rather common in substituted ferrocene derivatives.
From the 1 H NMR and IR data it is obvious that the hydrogen bond persists in chloroform and dichloromethane solution.Moreover, in THF solution the NH vibration of 2 remains essentially unaffected (ESI †).This is in stark contrast to 3 which forms strong NHÁ Á ÁO hydrogen bonds to THF (Dn E 200 cm À1 , ESI †).Similarly, in DMSO the NH proton resonance of 3 is shifted to lower field (Dd E 3 ppm) while that of 2 in DMSO remains essentially unaffected (ESI †).Hence, the NHÁ Á ÁFe hydrogen bond of 2 is even resistant towards THF and DMSO as strong hydrogen bond acceptors.Remarkably, the strongest intramolecular OHÁ Á ÁFe bond of ferrocenyl alcohols (namely 2-ferrocenyl ethanol) is fully disrupted already by the weak hydrogen bond acceptor diethylether.7a Enthalpies of XHÁ Á ÁY hydrogen bonds have been empirically correlated to Dn of the respective XH vibration.‡ 10 As the free NH stretch is unavailable for 2 we estimate it from that of 3 in CD 2 Cl 2 (3267 cm À1 ).Hence, Dn E 149 cm À1 and ÀDH E 13 kJ mol À1 , a reasonable value in comparison to the thermodynamic data obtained from DFT calculations (see above).The exceptional resistance of the intramolecular NHÁ Á ÁFe hydrogen bond towards splitting by THF or DMSO yielding an intermolecular hydrogen bond is believed to be based both on enthalpic and entropic effects (chelate effect).
Due Diferrocenes linked by a single atom bridge have found considerable interest due to the intramolecular electron transfer within the corresponding mixed-valent ferrocene-ferrocenium systems.Hence, the electron transfer between the slightly different redox sites with/without an NHÁ Á ÁFe hydrogen bond within 2 + was probed.Expectedly, 2 is reversibly oxidized to 2 + and 2 2+ (at 115 and 595 mV vs. ferrocene, respectively; ESI †).The difference between the potentials for 2 + (DE = 480 mV) is larger than the potential difference of the more symmetric ketone 1 + (DE = 345 mV; ESI †).First it is mandatory to establish the site of primary oxidation.2][13][14][15] Upon titration of 2 with substoichiometric amounts of iodine only resonances of protons H 13 , H 14 and H 15 (Scheme 1, ESI †) are affected suggesting spin density at the non-hydrogen bonded iron site.This is fully confirmed by DFT calculations on 2 + showing spin density at the non-hydrogen bonded iron site (FeÁ Á ÁN distance 3.54 Å; FeÁ Á ÁH distance 2.66 Å; Fig. 3).The non-hydrogen bonded conformer of 2 + is calculated 4 kJ mol À1 higher in energy (Fig. 3, ESI †).Upon further oxidation (0.4 eq.iodine) the NH 6 proton resonance is broadened and shifted to higher field (ESI †) suggesting the onset of appreciable disproportionation of 2 + into 2 and 2 2+ .DFT calculations of 2 2+ suggest that the hydrogen bonded conformer is now destabilized by 6 kJ mol À1 (Fig. 3, ESI †).An opening of hydrogen bonds due to accumulation of positive charges has been previously established in oligoferrocenyl peptides featuring conventional NHÁ Á ÁO hydrogen bonds in the ligand domain. 12,13Similarly, an anionic [1.1]diborataferrocenophane has been shown to bind Li +   This journal is © The Royal Society of Chemistry 2015 between the iron centres, while oxidation of the ferrocenes releases the entrapped Li + ion. 16ndeed, oxidation of 2 with one equivalent AgSbF 6 in CD 2 Cl 2 (E 1/2 = 650 mV 17 ) to 2 + leaves the energy of the NH vibration essentially unperturbed (ESI †).Oxidation of 2 to 2 2+ with two equivalents AgSbF 6 in CD 2 Cl 2 yields a new band at 3274 cm À1 (ESI †).This energy is very similar to that of 3 in CD 2 Cl 2 without a hydrogen bond (vide supra).This experimental observation strongly confirms the opening of the NHÁ Á ÁFe hydrogen bond in the dication 2 2+ but not in the monocation 2 + as suggested by the DFT calculations.
According to time-dependent DFT calculations the intervalence charge transfer band (IVCT) 18 of 2 + is calculated at 718 nm originating from the charge transfer between the d orbitals of the different ferrocene and ferrocenium sites (ESI †).For the similar mixed-valent ketone 1 + lacking the hydrogen bond this band is calculated at significantly lower energy (1147 nm, ESI †).The latter is a typical value for symmetric mixed-valent ferrocene-ferrocenium complexes with short bridges (Robin-Day class II) 18 while the former is quite high in energy.The NHÁ Á ÁFe hydrogen bond lowers the ferrocene d orbitals in 2 + and hence significantly increases the energy required for Fc(Á Á ÁHN) -Fc + intervalence charge transfer.Possibly, electron transfer within 2 + approaches the Robin-Day class I regime. 18xperimentally, a weak near-infrared band is observed for 1 + at E1244 nm (IVCT) while no near-infrared band is discernible for 2 + (ESI †).However, the UV/Vis spectrum of 2 + is not exactly the average spectrum of 2 and 2 2+ in the visible region and an additional band can be suspected from the difference spectrum at around E665 nm which might be assignable to a high energy IVCT (ESI †).With this interpretation of the absorption bands the activation barriers for the thermal electron transfer 18b within the mixed-valent cations 1 + and 2 + are estimated from DG a ET = l/4 + DG 0 /2 + (DG 0 ) 2 /(4(l À 2H AB )) À H AB + H AB 2 /(l + DG 0 ) with l = E op À DG 0 as DG a ET = 22 AE 2 and 46 AE 2 kJ mol À1 , respectively (assuming H AB r 300 cm À1 (ref.13, 14 and 19)).§ Hence, the intramolecular electron transfer barrier in 2 + is substantially higher than that in 1 + .
In summary, the diferrocenyl hydrazone 2 features an ultrastrong intramolecular NHÁ Á ÁFe hydrogen bond.To the best of our knowledge, this NHÁ Á ÁFe hydrogen bond is one of the strongest reported so far for ferrocenyl hydrogen bond acceptors.This hydrogen bond confines charge and spin in the ground state of the mixed-valent cation 2 + to the non-hydrogen bonded site.Electron transfer between ferrocene and ferrocenium in 2 + requires quite high energies due to the electronic dissymmetry.Upon double oxidation of 2 to 2 2+ the NHÁ Á ÁFe hydrogen bond is fully disrupted.Hence, the redox sequence 2 -2 + -2 2+ constitutes a switch with a structural response at the NHÁ Á ÁFe hydrogen bond after two redox events.The exceptional hydrogen bond strength allows accessing and exploiting the NHÁ Á ÁFe hydrogen bond in terms of modulating (intramolecular) electron transfer (2 + ) and vice versa in terms of modulating NHÁ Á ÁFe hydrogen bonding by (intermolecular) electron transfer (2/2 2+ ) resulting in a redox-stimulated switch.
to the hindered rotation around the CQN double bond and the NHÁ Á ÁFe hydrogen bond the two sites in the diferrocene 2 are chemically different.No coalescence of ferrocenyl proton resonances and no significant shift of the NH 6 resonance are found up to 70 1C in C 6 D 6 (400 MHz) suggesting a high activation barrier for the rotation around the CQN double bond and a persistent NHÁ Á ÁFe hydrogen bond (ESI †).

Fig. 1
Fig. 1 NOE spectrum of 2 in CDCl 3 .Relevant correlations involving H 6 are indicated by red dotted lines (the asterisk denotes a solvent resonance).