Trifluoromethyl-substituted tetrathiafulvalenes

A series of tetrathiafulvalenes functionalized with one or two trifluoromethyl electron-withdrawing groups (EWG) is obtained by phosphite coupling involving CF3-substituted 1,3-dithiole-2-one derivatives. The relative effects of the EWG such as CF3, CO2Me and CN on the TTF core were investigated from a combination of structural, electrochemical, spectrochemical and theoretical investigations. Electrochemical data confirm the good correlations between the first oxidation potential of the TTF derivatives and the σmeta Hammet parameter, thus in the order CO2Me < CF3 < CN, indicating that, in any case, the mesomeric effect of the substituents is limited. Besides, crystal structure determinations show that the deformation of the unsymmetrically substituted dithiole rings, when bearing one, or two different EWG, and attributed to the mesomeric effect of ester or nitrile groups, is not notably modified or counter-balanced by the introduction of a neighboring trifluoromethyl group. DFT calculations confirm these observations and also show that the low energy HOMO–LUMO absorption band found in nitrile or ester-substituted TTFs is not found in TTF-CF3, where, as in TTF itself, the low energy absorption band is essentially attributable to a HOMO→LUMO + 1 transition. Despite relatively high oxidation potentials, these donor molecules with CF3 EWG can be involved in charge transfer complexes or cation radical salts, as reported here for the CF3-subsituted EDT-TTF donor molecule. A neutral charge transfer complex with TCNQ, (EDT-TTF-CF3)2(TCNQ) was isolated and characterized through alternated stacks of EDT-TTF-CF3 dimers and TCNQ in the solid state. A radical cation salt of EDT-TTF-CF3 is also obtained upon electrocrystallisation in the presence of the FeCl4− anion. In this salt, formulated as (EDT-TTF-CF3)(FeCl4), the (EDT-TTF-CF3)+• radical cations are associated two-by-two into centrosymmetric dyads with a strong pairing of the radical species in a singlet state.


Introduction
Following three decades of extensive work toward the elaboration of conducting radical cation salts from tetrathiafulvalene (TTF) derivatives with electron-rich alkyl (tetramethyltetrathiafulvalene: TMTTF, tetramethyltetraselenafulvalene: TMTSF) or thioalkyl (ethylenedithiotetrathiafulvalene: EDT-TTF, bis(ethylenedithio)tetrathiafulvalene: BEDT-TTF) substituents [1], investigations of radical cation salts of tetrathiafulvalenes functionalized by electron-withdrawing groups (EWG) are less documented, essentially because the presence of such substituents as halogen, acyl, ester, amide or nitrile on the TTF redox core dramatically increases its oxidation potential and destabilizes the radical cation form. This strong anodic shift is particularly noticeable in tetrasubstituted TTFs such as TTF(CO 2 Me) 4 [2][3][4], TTFCl 4 [5], TTF(CF 3 ) 4 [2], or TTF(CN) 4 [3], which oxidize into the radical cation at 0.80, 0.83, 1.05 or 1.12 V vs SCE respectively, to be compared with TTF itself which oxidizes at 0.33 V vs SCE. The associated instability of these radical species in moist air hindered in most cases their isolation in cation radical salts. This is all the more unfortunate since the electronegative atoms (O, N, Hal) within such EWG are expected to be able to engage, in the solid state at the organic-inorganic interface, in a variety of secondary nonbonding interactions such as hydrogen or halogen bonding [6,7], an issue of current strong interest in organic solid state chemistry [8,9]. However, it was also recognized that the introduction of only one or two of such EWG on the TTF core could limit this anodic shift, and accordingly, several tetrathiafulvalenes bearing only one or two ester [10], nitrile [11][12][13][14], amide [7,[15][16][17], thioamide [18][19][20], or halogen [5] substituents were successfully engaged in radical cation salts by electrocrystallization, with intermolecular hydrogen [21][22][23] of halogen bond interactions [24][25][26][27]. Within such TTF derivatives, as reported by Bryce [28], an internal charge transfer (ICT) between the TTF and the EWG moieties increases the hydrophilicity of the TTF head groups and facilitates monolayer formation on the water surface for the preparation of Langmuir-Blodgett films. The structural and electronic properties of a series of ester [15], thioester [29,30], tertiary amide and thioamide [12] TTF derivatives have been then rationalized, based on: (i) the sizeable contribution of the mesomeric form B (Scheme 1) and, (ii) an ICT from the TTF-based HOMO to the EWG-based LUMO, also observed in primary and secondary amides [10]. Another consequence of the contribution of the B form is the shortening of the C-S bond opposite to the EWG, experimentally observed in the structures of such molecules. More recently, we have reported another series of TTFs functionalized at various positions with the electron-withdrawing -CF 3 (trifluoromethyl) group such as EDT-TTF(CF 3 ) (1c) or EDT-TTF(CF 3 ) 2 (2cc) (Scheme 2) [31]. Single-crystal X-ray diffraction measurements revealed the recurrent formation of layered structures with a strong segregation of the fluorinated moieties and formation of fluorine bilayers [32,33], attributed to the amphiphilic character of those TTF derivatives upon CF 3functionalization. A strong anodic shift of the first oxidation potential was also noted for 1c and 2cc, when compared with the unsubstituted EDT-TTF molecule.

Scheme 2: Investigated TTF derivatives bearing EWG.
This work has been extended here to several novel disubstituted tetrathiafulvalenes bearing one CF 3 group and one ester or nitrile group at the neighboring position as in 2ac and 2bc (Scheme 2). These derivatives offer an invaluable opportunity to evaluate the influence of the nature of the EWG on the structural and electronic properties of the TTF redox moiety, taking advantage of the marked differences between the three EWG now available: (i) the strongly electron withdrawing -CN group, (ii) the weaker -CO 2 Me group, both with important mesomeric effects, and, (iii) the -CF 3 group, expected to exhibit essentially a strong −I inductive effect. Among the nine possible combinations 1 and 2 described above (Scheme 2), the unsymmetrically disubstituted 2ab and 2ac have not been reported to date. We describe here the syntheses of 2ac from 2bc and the single-crystal X-ray structure determinations of both 2ac and 2bc molecules. The preparation of the two positional isomers of bis(trifluoromethyl)-bis(carboxymethyl)tetrathiafulvalene 3bc and 4bc is also reported. The evolutions of (i) the geometry of the dithiole ring bearing the EWG, (ii) the electrochemical properties, (iii) the optical absorption (UV-vis) properties will be analyzed within the series, in order to evaluate the role of the CF 3 group as electron-withdrawing substituent on the structural and electronic properties of the tetrathiafulvalene core, by comparison with that of the -CO 2 Me or -CN substituents. Furthermore, from the mono-substituted trifluoromethyl derivative 1c, we were also able to isolate a charge transfer complex with TCNQ and a cation radical salt with FeCl 4 − . The structures of both compounds will be de-scribed, and the geometrical evolutions of the TTF core upon oxidation analyzed by comparison with the structure of neutral 1c.

Syntheses
The reported preparation of 2bc is based on the coupling reaction of the trithiocarbonate 5 with the dithiocarbonate 6bc, affording also the symmetrical coupling product 4bc (Scheme 3) [31]. Further decarboxylation of 2bc with LiBr/DMF afforded 1c while reaction with NH 3 in MeOH gives the corresponding primary amide 7 in 63% yield. Its dehydration with POCl 3 in sulfolane gives 2ac in 60% yield. A similar phosphite-based cross-coupling reaction between the bis(trifluoromethyl)-1,3-dithiole-2-one derivative 9cc and the diester derivative 10bb gave the TTF 3bc in 15% yield (Scheme 4). With these extensive series at hand, it is now interesting to evaluate the role of the CF 3 group as electron-withdrawing substituent on the structural and electronic properties of the tetrathiafulvalene core and to compare them with those of the -CO 2 Me or -CN substituents. This will be done here following two different approaches. First, we report the redox and optical absorption properties of the TTFs in solution, correlated with the electron-withdrawing character of the different substituents. Then, the relative effect of the three EWG on the solid state geometry of the dithiole ring will be described, based on the X-ray crystal structure analyses of four neutral TTF derivatives, i.e., the EDT-TTF derivatives 2ac and 2bc and the tetrasubstituted derivatives 3bc and 4bc.

Redox properties
Cyclic voltammetry was used to evaluate the evolution of the donor strength with the nature and number of EWG. All derivatives exhibit two reversible oxidation waves. The E 1/2 values for the EDT-TTF derivatives with one or two EWG are collected in Table 1. Compared with the unsubstituted EDT-TTF parent compound, redox potentials are shifted toward more anodic potentials with the introduction of the EWG with the following order CO 2 Me < CF 3 ≤ CN. Note that this order is also confirmed by the evolution of the redox potentials of the tetrasubstituted TTF derivatives collected in Table 2.
Earlier electrochemical investigations of various tetrathiafulvalene derivatives have shown that the best correlations between the first oxidation potential and the Hammet parameters [39-41] were actually found with the σ meta constant of each substituent on the TTF core [20,42], indicating that, in any case, the mesomeric effect of the substituents was small. A similar satisfactory correlation with all TTF derivatives described here is shown in Figure 1 and demonstrates that the trifluoromethyl   group anodic shift observed in the order CO 2 Me < CF 3 < CN correlate well with the σ meta Hammet constant.

Optical properties
The evolution of the lowest energy absorption bands is also reported for the different TTF derivatives in Table 1 and Table 2. We note that the introduction of the trifluoromethyl group induces a blue shift of these absorptions, by comparison with EWG such as CO 2 Me or CN which move the absorption bands toward lower energies This point is actually correlated to the observed color difference, as the trifluoromethyl-substituted TFF derivatives are lightly orange colored, while the ester and cyano TTFs are dark red compounds. In order to rationalize these evolutions, we have performed TD-DFT calculations on the model molecules TTF, TTF-CF 3 , TTF-CO 2 Me and TTF-CN. The results are shown in Figure 2 and collected in Table 3, where a good correlation is found with the observed absorption bands experimentally observed in the four EDT-TTF derivatives, namely EDT-TTF, EDT-TTF-CF 3 (1c), EDT-TTF-CO 2 Me (1b) and EDT-TTF-CN (1a).
Several points need to be emphasized. In pristine TTF as in TTF-CF 3 , the strongest, low energy transition is not the HOMO→LUMO transition but the HOMO→LUMO + 1 transition. Indeed, the LUMO in both molecules has a σ character while the LUMO + 1 has a π character. By contrast, the ester and cyano groups (−M EWG) are strongly conjugated with the π system to such a point that the order of the two lowest unoccupied orbitals is inverted. This inversion, with now a LUMO of π character, allows for a direct HOMO→LUMO optical tran-  Table 3). sition in the two latter compounds. Besides, the −I inductive effect of the trifluoromethyl group stalilizes HOMO, LUMO and LUMO + 1 of TTF. As a consequence, its lower energy absorptions are only slightly shifted by comparison with TTF, as experimentally observed. On the other hand, the strong stabilization of the LUMO in the ester-or cyano-substituted TTFs leads to a large red shift of the low energy absorption of these molecules. Note also that the relative energy of the HOMO of the four different model TTFs is well correlated with the ranking deduced from the electrochemical measurements. The stabilization of the HOMO, associated with the anodic shift of the first oxidation potential is indeed strongest with the cyano group, with the following ordering H < CO 2 Me < CF 3 < CN, as discussed above (Table 1 and Table 2).

X-ray crystal structures of the neutral donor molecules
As mentioned in the Introduction, the substitution of one hydrogen atom on the TTF core by one EWG such as ester or cyano group is known to distort the dithiole ring, as illustrated in Scheme 1. In the following, we want to evaluate the extent of this effect in the case of the trifluoromethyl group, and its evolution in competitive situations where two different EWG are on the same dithiole ring. For that purpose, we could obtain   good quality crystals of the trifluoromethyl-substituted EDT-TTF derivatives with either one ester (in 2ac) or one cyano group (in 2bc) in ortho position to the CF 3 group. 2ac crystallizes in the monoclinic system, space group P2 1 , with one molecule in general position in the unit cell (Figure 3), affected by disorder on the ethylene bridge. On the other hand, 2bc crystallizes in the triclinic system, space group P−1, with one molecule in general position in the unit cell ( Figure 4). The ester group is coplanar with the TTF core and adopts a s-trans conformation. In both compounds, the CF 3 group is not disordered as usually observed but adopts a fixed conformation with one fluorine atoms in the TTF mean plane, away from the other substituent. Bond lengths and angles are in the expected range. A dissymmetry of the C-S bonds (b, b′ in Table 4) in the dithiole ring bearing the different EWG is observed, with in both cases a shortening of the C−S bond close to the CF 3 group. This polarization of the dithiole ring bearing one such EWG has been rationalized by Bryce on the basis of a sizeable contribution of a zwitterionic mesomeric form due to the influence of the EWG of −M character (Scheme 1) [8,17,18]. The fact that in both 2ac and 2bc molecules, this shortening affects the C−S bond closest to the CF 3 group demonstrates unambiguously that the mesomeric electron-withdrawing effect of the CN or CO 2 Me groups is indeed stronger than that of CF 3 .
A similar effect is also observed on the structure of the symmetrical TTF 4bc, which was obtained as symmetrical coupling product of 6bc during the preparation of 2bc (Scheme 2). 4bc crystallizes in the orthorhombic system, space group Pbam, with two crystallographically independent molecules, each of them located on a mirror plane and on an inversion center ( Figure 5). In both molecules, a shorter C−S bond length is observed opposite to the CO 2 Me groups (Table 3), demonstrating again here that the (−M) mesomeric effect of the ester group exercises a stronger effect than the (−I) inductive effect of the CF 3 group.
Another interesting insight is provided by the X-ray crystal structure of the other isomer 3bc, where each dithiole ring is substituted with the same substituents, two CF 3 or two CO 2 Me groups ( Figure 6). We note first that the C-S bond distances (b) are now equal within the estimated standard deviations. We also observe that the localization of two CF 3 moieties in ortho position to each other leads to a strong positional disorder of the fluorine atoms, at variance with the other structures described  above. Furthermore, the two ester groups are not coplanar, one of them lies flat with the TTF core while the other one is almost perpendicular.

Charge-transfer complex and radical cation salt
The relatively low oxidation potential of the mono(trifluoromethyl) derivative 1c (+0.21 V vs Fc + /Fc) prompted us to investigate the formation of cation radical salts upon chemical or electrochemical oxidation of 1c. Indeed, treatment of a solution of 1c with TCNQ afforded black, crystalline elongated plates which were analyzed to be a 2:1 complex, i.e., (1c) 2 (TCNQ). Electrocrystallization experiments were conducted with 1c as well as 2cc with a variety of anions, be they linear such as AuBr 2 − , I 3 − , ICl 2 − , tetrahedral (ReO 4 − , InBr 4 − ) or octahedral (AsF 6 − ). In most cases however, the electrochemically generated salts were extremely soluble, a consequence of the presence of the CF 3 groups and there was no crystal growth on the anode. However, with 1c as electroactive donor molecule and (n-Bu 4 N)(FeCl 4 ) as electrolyte, layering of the CH 2 Cl 2 solutions after electrolysis with pentane afforded crystals of a 1:1 phase formulated as (1c)(FeCl 4 ).
(1c) 2 (TCNQ) crystallizes in the monoclinic system, space group P2 1 /c. One TCNQ molecule located on an inversion center and the EDT-TTF-CF 3 molecule in general position in the unit cell generate molecular triads (1c)(TCNQ)(1c) which stack along the b axis (Figure 7).
The degree of charge-transfer within this system can be anticipated to be close to zero from the comparison of the redox potentials of EDT-TTF-CF 3 (E ox 1/2 = 0.21 V vs Fc + /Fc) and TCNQ (E red 1/2 = −0.23 V vs Fc + /Fc, 0.17 V vs SCE) [43]. This is also confirmed from the intramolecular bond lengths (Table 5) within the central C 2 S 4 core of the donor molecule, close to those observed in neutral EDT-TTF-CF 3 (2) itself. The geometry of TCNQ can also give another evaluation of the degree of charge transfer. Based on the large number of reported TCNQ salts, three different correlations between the charge of the molecule and the bond lengths have been reported [44][45][46]. Applying those three correlations to the TCNQ bond lengths in (1c) 2 (TCNQ), averaged in D 2h symmetry, gives calculated charges of −0.08, +0.11 and −0.16, confirming that we are here in presence of a neutral charge-transfer complex rather than a charge-transfer salt.
Note also that this donor-acceptor interaction leads to a strong planarization of the dithiole rings of 1c in (1c) 2 (TCNQ) with folding angles along the S … S hinge of the two dithiole rings amounting now to 10.13(17)° and 1.90(16)° on the dithioethylene and CF 3 sides, respectively. By comparison, in the neutral donor molecule 1c, the folding angles amount to 20.59(5) and 19.00(5)° respectively [31]. Such π-π interactions have been shown to derive from quadrupolar interactions between the π systems of both donor and acceptor moieties [47], and their geometrical characteristics to favor the strongest electrostatic interactions between the most electron-rich and electron-poor regions of both partners. In that respect, it appears here that the TCNQ acceptor essentially overlaps with the dithiole ring bearing the dithioethylene substituent, a likely consequence of the electron-withdrawing effect of the CF 3 group on the other dithiole ring (Figure 8).
In the 1:1 salt of EDT-TTF-CF 3 (1c) with FeCl 4 − , that is (1c +• )(FeCl 4 − ), oxidation to the radical cation state strongly   affects the central C 2 S 4 core of the donor (Table 4) with a lengthening of the C=C central double bond a, and an associated shortening of the C central −S bonds b, b′, c, c′). Note that this effect is stronger on the (c, c′) C central -S bonds of the most electron-rich dithiole ring bearing the dithioethylene substituent.
In the solid state (Figure 9), the molecules are separated from each other by the FeCl 4 − anions in the (b,c) plane. Along the a axis, they interact only laterally with long S … S intermolecular (>3.74 Å) into uniform spin chains. This solid-state arrange-ment is reminiscent of that observed with the analogous nitrile substituted EDT-TTF, that is EDT-TTF-CN, in the similar 1:1 (EDT-TTF-CN +• )(FeBr 4 − ) salt [9], demonstrating that the CF 3 moiety does not play here a crucial role in the solid state organization. Note that both charge transfer complex (2) 2 (TCNQ) and cation radical salt (2)(FeCl 4 ) are expected to behave as insulators, because of zero charge transfer in the former and full charge-transfer in the latter. We were not able to determine the magnetic response of the FeCl 4 − salt as the crystals are polluted with the starting electrolyte, due to the precipitation technique used to recover these highly soluble salts.

Conclusion
Compared with other EWG such as -CN or -CO 2 Me, the CF 3 substituent plays on the TTF electroactive core a peculiar role.
From an electrochemical point of view, comparison of the relative role of the CN, CO 2 Me and CF 3 EWG shows that, the electron-withdrawing nature of the CF 3 moiety is intermediate between that of the CN and the CO 2 Me ones. On the other hand, the structural distortions introduced on the dithiole ring upon substitution with the CN and CO 2 Me (−M) EWG are not offset by the competing CF 3 group, confirming its much weaker mesomeric effect on the conjugated dithiole core. Optical prop- erties and theoretical calculations have shown that the HOMO-LUMO gap is not much modified in the CF 3 -substituted molecules, in sharp contrast with those TTF derivatives with CN or CO 2 Me EWG. In the latter indeed, the large stabilization of the LUMO localized on the EWG leads to a strongly decreased HOMO-LUMO gap associated with the well known dark color of these derivatives. Despite relatively high oxidation potentials, these donor molecules with CF 3 EWG can be involved in charge transfer complexes or cation radical salts, as reported here for the CF 3 -substituted EDT-TTF donor molecule, in its 2:1 neutral CT complex with TCNQ, (1c) 2 (TCNQ) or its cation radical salt with FeCl 4 − . The high solubility brought by the trifluoromethyl substituent strongly limits the isolation of such salts by crystallization.  Preparation of (1c)(FeCl 4 ): The electrocrystallization of 1c (11 mg) in a CH 2 Cl 2 solution (15 mL) of (Et 4 N)(FeCl 4 ) (208 mg) as electrolyte did not afford any crystals. Further layering of the solution recovered from the anodic compartment with pentane afforded dark crystals of a 1:1 phase formulated as (1c)(FeCl 4 ), polluted with the yellow crystals of (Et 4 N)(FeCl 4 ).

Crystallography
Single crystals were mounted on the top of a thin glass fiber. Data were collected either on a Stoe-IPDS at room temperature or on a Nonius KappaCCD diffractometer at 150 K, both equipped with graphite-monochromated Mo Kα radiation (λ = 0.71073 Å). Structures were solved by direct methods (SHELXS-97) and refined (SHELXL-97) [48] by full-matrix least-squares methods, as implemented in the WinGX software package [49]. Absorption corrections were applied. Hydrogen atoms were introduced at calculated positions (riding model), included in structure factor calculations, and not refined. Crystallographic data are summarized in Table 6.

Computational details
DFT [50,51] calculations were performed with the hybrid Becke-3 parameter exchange functional [52][53][54] and the Lee-Yang-Parr nonlocal correlation functional [55] (B3LYP) implemented in the Gaussian 03 (revision D.02) program suite [56], using the 6-31G(d) basis set and a quadratically convergent self-consistent field procedure with the default convergence criteria implemented in the program. The X-ray diffraction data of model compounds were used as a starting point for initial geometry optimization calculations. Final geometries are given in Supporting Information File 1. Representation of frontier orbitals included in Figure 2 were generated with Molekel 4.3 [57]. TD-DFT calculations were performed at the B3LYP/6-311G** level of theory, on the previously converged geometries.

Supporting Information
Supporting Information File 1 Optimized geometries of the model molecules TTF, TTF-CN, TTF-CF 3 and TTF-CO 2 Me and results of the TD-DFT calculations.