Bis(pyrazol-1-yl)acetic Acid Bearing Ferrocenyl Substituents

Article pubs.acs.org/Organometallics

Bis(pyrazol-1-yl)acetic Acid Bearing Ferrocenyl Substituents Stefan Tampier,† Sascha M. Bleifuss,† Mokhles M. Abd-Elzaher,‡ Jörg Sutter,† Frank W. Heinemann,† and Nicolai Burzlaff*,† †

Department of Chemistry and Pharmacy & Interdisciplinary Center for Molecular Materials (ICMM), University of Erlangen-Nürnberg, Egerlandstraße 1, D-91058 Erlangen, Germany ‡ Inorganic Chemistry Department, National Research Center, P.O. 12622 Dokki, Cairo, Egypt S Supporting Information *

ABSTRACT: The new compound 4-ferrocenyl-3,5-dimethylpyrazole (4; fcdmpzH) has been synthesized from 4-iodo-3,5-dimethyl-1-tritylpyrazole (2) via a Negishi type cross-coupling reaction and subsequent deprotection of the intermediate 4-ferrocenyl-3,5-dimethyl-1-tritylpyrazole (3; fcdmpzTrt). Reaction of the pyrazole 4 with dichloromethane, base, and phase transfer catalyst results in the chelating N,N ligand bis(4-ferrocenyl3,5-dimethylpyrazol-1-yl)methane (5; bfcdmpzm). Bis(4-ferrocenyl-3,5dimethylpyrazol-1-yl)ketone (6; bfcdmpzk) is obtained by reacting 4 with NEt3 and triphosgene. The N,N,O heteroscorpionate ligand bis(4ferrocenyl-3,5-dimethylpyrazol-1-yl)acetic acid (7; H[bfcdmpza]) can be accessed by reacting pyrazole 4 with dibromoacetic acid, KOtBu, and phase transfer catalyst and subsequent acidic workup. The heteroscorpionate ligand H[bfcdmpza] (7) is suitable to bind metal ions in a κ3 coordination mode, as could be proven by the formation of a the bis-ligand complex [Fe(bfcdmpza)2] (8). The molecular structures of 3, 5, 6, and 8 have been obtained by single-crystal X-ray structure determination. The electrochemical properties of the four ferrocenyl-substituted compounds 3−6 have been studied by cyclic voltammetric measurements and discussed as well.

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Asp205 is crucial for enzymatic activity.10,11 The two required electrons to activate dioxygen as a peroxide are delivered one each from the active site iron(II) and the Rieske center. The redox potential of Rieske clusters ranges from −150 to +400 mV vs SHE (standard hydrogen electrode). This variation of the potential is caused by the different electrostatic environments in the Rieske clusters proteins and the dependence on the purpose of the Rieske dioxygenase.12 Two functional models have been established so far: chlorido[3-(dipyridin-2-ylmethyl)-1,5,7-trimethyl-2,4-dioxo-3-azabicyclo[3.3.1]nonane-7carboxylato]iron(II) and bis[benzoyl(dipyrid-2-yl)methylamine]iron(II).13 The redox potentials of model complexes for the Rieske [2Fe-2S] cluster are about −1.5 V up to −1.0 V (vs Cp*2Fe/Cp*2Fe+) and thus are shifted cathodically in comparison to real Rieske ferredoxine clusters.14 Ferrocene exhibits a redox potential at about +400 mV vs SHE,15 which reaches into the redox potential region of Rieske [2Fe-2S] clusters. In conjunction with a model complex of the active site of a Rieske dioxygenase based on a bis(pyrazol-1yl)acetato iron complex, electron transport between a ferrocenyl substituent and a bis(pyrazol-1-yl)acetato bound

INTRODUCTION Bis(pyrazol-1-yl)acetic acid (H[bpza]) and bis(3,5-dimethylpyrazol-1-yl)acetic acid (H[bdmpza]) are now well-established N,N,O scorpionate ligands structurally related to the wellknown hydridotris(pyrazol-1-yl)borate (Tp) ligand.1 Since they were introduced to coordination chemistry in 1999 by Otero,2 efficient syntheses for various bis(pyrazol-1-yl)acetic acids have been developed over the years.2,3 Several transition-metal complexes bearing these tripodal, κ3-N,N,O-binding ligands have been reported during the past decade.4,5 Among these are ferrous and ferric model complexes for the active site of nonheme iron oxygenases.6−8 For example the cis hydroxylation during the bacterial degradation of aromatic substances via the activation of molecular oxygen is catalyzed by Rieske dioxygenases, which are classified according to their substrate preferences, such as naphthalene, benzoate, phthalate, and toluene/biphenyl dioxygenases.9 In the following, the structural configuration of the naphthalene 1,2-dioxygenase (NDOS; PDB: 1NDO) is briefly described (Figure 1).10 The active site by which molecular oxygen is activated and the substrate is oxidized consists of a 2-His-1-carboxylate motif that binds to an iron(II) center. Adjacent to this, a Rieske [2Fe2S] ferredoxin cluster is apparent, which delivers electrons for the reduction of the iron(III) center formed during catalysis, as well as for the reduction and activation of oxygen itself. This whole moiety has a size of about 12 Å, and the conjunction by © XXXX American Chemical Society

Special Issue: Ferrocene - Beauty and Function Received: May 30, 2013

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dx.doi.org/10.1021/om400495f | Organometallics XXXX, XXX, XXX−XXX

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promoted substitutions of the Ullmann type are possible and in this way ferrocene has been functionalized with various moieties leading to monodentate N, O, and S ligands.27 Monodentate building blocks containing N donors such as ferrocenylpyridines,28 ferrocenylpyrazoles,29 ferrocenylpyrimidines,30 ferrocenylpyrazines, ferrocenylimidazoles,31 and ferrocenyltriazoles29b,32 as shown in Figure 3 are accessible by various methods. 3-Ferrocenylpyrazole was obtained by a different approach starting from acetylferrocene.33

Figure 1. Rieske [2Fe-2S] cluster (right) connected by Asp205 to the active site (left) of naphthalene 1,2-dioxygenase (NDOS, PDB:1NDO) (top, cutout of protein structure; bottom, schematic presentation).10

Figure 3. Heteroaryl-substituted ferrocene derivatives: (i) ferrocenylpyridines; (ii) ferrocenylpyrazoles; (iii) 2-ferrocenyl-4,6-dimethylpyrimidine; (iv) N-ferrocenylpyrazole; (v) N-ferrocenyl-3,5-dimethylpyrazole; (vi) 2-ferrocenylpyrazine; (vii) 5-ferrocenylpyrimidine; (viii) 4ferrocenylpyrimidine; (ix) 1-ferrocenyl-1,2,3-triazole.

redox center might be achieved, delivering the electrons necessary for the oxidation/reduction processes (Figure 2).

In general, N-ferrocene derivatives are accessible by an Ullmann type substitution reaction promoted by copper salts,29b,c and ferrocene triazole compounds are synthesized by Click chemistry.32 In contrast, C−C-coupled ferrocene compounds are obtainable by Kumada or Negishi type couplings, so done in the case of ferrocenylpyrazole or ferrocenylpyridine.28,30c,34 The Kumada type coupling reactions start from bromoferrocene, which is first converted to ferrocenylmagnesium bromide. The combination of this Grignard reagent with the required aryl bromide in the presence of a Ni(II) catalyst, such as [NiCl2(dppp)], leads to the corresponding ferrocenylarene. In Negishi type C−C-coupling reactions, ferrocene is first lithiated with t-BuLi at low temperatures and transmetalated by the addition of ZnCl2 to form a ferrocenylzinc chloride. In the presence of a palladium catalyst, e.g. [PdCl2(PPh3)2], this intermediate is then treated with an appropriate aryl halide, such as 5-bromopyrimidine or 4-iodo-1-tritylpyrazole, to produce ferrocenylpyrimidine and ferrocenylpyrazole (Scheme 1).29a As mentioned before, the redox properties belong to the most remarkable and widely tunable characteristics of ferrocene-containing compounds. It is possible to change the redox potential of such compounds depending on their substituents. 4-Ferrocenylpyrazole exhibits a quasi-reversible

Figure 2. Schematic presentation of the electron transfer from a ferrocene moiety to the redox center of an iron(II) bis(pyrazol-1yl)acetato complex.

Ferrocene and its derivatives have been used in organometallic chemistry for more than 50 years. The ferrocenyl substituent is thereby used as a tunable electron reservoir within ligands coordinated to transition metals.16 The particular interest in heterocyclic ferrocene derivatives arises from their unique photophysical,17 magnetic,18 and redox19 properties along with the possibility of their application in medicinal chemistry.20 These unique properties of ferrocene have been shown to influence the reactivity of the resulting compounds.21 Hence, we decided to combine these ferrocenyl qualities with N,N,O scorpionate ligands based on, for example, the bis(pyrazol-1-yl)acetic acids, to gain more insight into the electronic properties of such a class of ligands. The aromatic rings of ferrocene allow multiple reactions known from organic aromatic systems, such as acylations, borylation,22 mercuration,23 and lithiation,24 followed by nucleophilic substitution. Direct electrophilic substitution, such as nitration, is impossible because of the simultaneous oxidation of ferrocene.25 Bromo- or iodoferrocenes are key starting materials for many other conversions. Ferrocene reacts with BBr3 to give dibromoborylferrocene, which is hydrolyzed to ferrcenylboronic acid that is suitable for Suzuki type coupling reactions with many halide-substituted aromatic compounds but can also be converted into iodoferrocene by reaction with N-iodosuccinimide.26 Starting from bromoferrocene, copper-

Scheme 1. Negishi Type Coupling Reaction To Synthesize 4Ferrocenyl-1-tritylpyrazole

B


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wave at E1/2 = −0.04 V and 4-ferrocenyl-1-tritylpyrazole at E1/2 = −0.03 V (acetonitrile; vs Cp 2 Fe/Cp 2 Fe*). This is considerably lower than the potentials observed for other heteroarylferrocenes: e.g., 5-ferrocenylpyrimidine (0.14 V),35 ferrocenyltetrazole (0.21 V), and ferrocenyltriazole (0.27 V).36

Table 1. Selected NMR Data (ppm) of Heterocycles Bearing Ferrocenyl Residues 1 H Cp

compd

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RESULTS AND DISCUSSION As recently reported by Mochida et al.,29a Negishi type coupling reactions were successfully employed for the preparation of 4-ferrocenylpyrazole. Following this concept, the synthesis of the new building block 4-ferrocenyl-3,5dimethyl-1-tritylpyrazole (3) was carried out as described in Scheme 2. In the initial step, 4-iodo-3,5-dimethylpyrazole, Scheme 2. Realized Synthetic Pathway to 4-Ferrocenyl-3,5dimethyl-1-tritylpyrazole (3)

fcdmpzTrt (3)

4.07

fcdmpzH (4)

4.09

bfcdmpzm (5)

4.11

bfcdmpzk (6)

4.13

H[bfcdmpza] (7)

4.11

4-ferrocenylpyridine28b

4.08


4.06


4.07

4-ferrocenyl-1methylpyrazole29a 4-ferrocenyl-1tritylpyrazole29a 4-ferrocenyl-1pyrazole29a

4.04

a

which was gained by oxidative iodination of 3,5-dimethylpyrazole according to literature procedures, was protected at the amine functionality by reacting it with triphenylmethyl chloride (trityl chloride, TrtCl).37 For the coupling reaction ferrocene was first lithiated at 0 to −20 °C. Zinc chloride was then added to generate the reactive chloridozinc intermediate, which was subsequently allowed to interact with 4-iodo-3,5-dimethyl-1-tritylpyrazole (2) in the presence of catalytic amounts of [PdCl2(PPh3)2].38 After quenching with water and aqueous workup, the crude product was purified by column chromatography, yielding 4-ferrocenyl3,5-dimethyl-1-tritylpyrazole (3; fcdmpzTrt) as an orange solid in moderate yield. The 1H NMR spectrum agrees with the formation of a monosubstituted ferrocene compound. The hydrogen atoms at the substituted Cp ring generate a misleadingly simple AA′BB′ spin system, i.e. two virtual triplets, which are slightly shifted downfield to 4.24 and 4.42 ppm (vs CDCl3) in comparison to the ferrocene singlet. The signal of the unsubstituted cyclopentadienyl ring appears at 4.07 ppm. In comparison to the 1H resonances of 2 the methyl groups of the pyrazole substituent are also shifted downfield from 1.47 to 1.76 ppm and from 2.41 to 2.12 ppm, respectively. This agrees well with the data reported for other ferrocenyl-substituted heterocycles, such as ferrocenylpyridine and ferrocenylpyrazole (Table 1).28b,29a Crystals of this compound were obtained by slow evaporation of the eluent from the preceding column chromatography. The molecular structure is depicted in Figure 4. The compound crystallizes in the space group P21/n with Z = 4. The Cp rings are staggered with an average angle δ of 14.1°. The least-squares planes of both cyclopentadienyl rings are tilted by 2.5° to each other. The dihedral angle between the least-squares planes of the pyrazole ring and the attached cyclopentadienyl ring is 22.6°. The distances of the iron atoms from the Cp rings are 1.64 and 1.65 Å and thus are shorter than

3.99 4.05

1 H Cpsubst

4.24, 4.42 4.25, 4.42 4.25, 4.37 4.30, 4.39 4.26, 4.38 4.61, 4.82 4.37, 4.67 4.37, 4.70 4.20, 4.41 4.16, 4.37 4.22, 4.45

13

C ferrocenyl moiety

67.5, 69.1, 78.2/68.0, 68.0, 69.5, 80.7a 67.1, 67.6, 69.1, 79.9 67.4, 67.6, 69.1, 79.8 69.4, 69.5, 70.1, 71.6 68.1, 68.2, 69.0, 69.2a 67.96, 70.46, 72.02 64.87, 67.85, 68.05 69.92, 69.56, 66.83 n.d. n.d. n.d.

In CD2Cl2.

Figure 4. Molecular structure of fcdmpzTrt (3). Thermal ellipsoids are drawn at the 50% probability level; hydrogen atoms have been omitted for clarity. Selected bond lengths (Å) and angles (deg): N(2)−C(12) = 1.331(2), N(2)−N(1) = 1.365(2), C(2)−C(13) = 1.472(3), Fe(1)− Cp = 1.6448(15), Fe(1)−Cp = 1.6462(15); C(12)−N(2)−N(1) = 104.83(14), N(2)−N(1)−C(13) = 112.07(15), ∠Cp−pz = 22.60(11), ∠Cp−Cp = 2.49(12).

in ferrocene.39 The bond length between the pyrazole and the cyclopentadienyl ring is 1.472(3) Å and is thus slightly shorter than a C−C single bond. Acidic deprotection of 4-ferrocenyl-3,5-dimethyl-1-tritylpyrazole (3) was achieved with trifluoroacetic acid and water in dichloromethane within 1 day according to published procedures (Scheme 3).40 The product was isolated by column chromatography, yielding 4-ferrocenyl-3,5-dimethylpyrazole (4; fcdmpzH) in a moderate yield of 71%. The compound was fully characterized by microanalysis, mass spectrometry, IR, and NMR spectroscopy (1H, 13C{1H}). The 1H NMR spectrum still shows the virtual triplet signals for the substituted cyclopentadienyl ring at 4.25 and 4.42 ppm and a singlet signal at 4.09 ppm for the unsubstituted ring. The first two methyl signals coincide with one signal more downfield at C


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with an isomer shift of δ = 0.54(1) mm s−1, a quadrupole splitting parameter of ΔEQ = 2.40(1) mm s−1, and a line width of Γfwhm = 0.32(1) mm s−1. These parameters are characteristic for low-spin FeII in ferrocenes and comparable to those of other substituted -ferrocene compounds, i.e. ferrocenylruthenocene and -ruthenocenophanes (δ (with respect to α-iron) ≈ 0.4−0.6 mm s−1, ΔEQ = 2.20−2.40 m ms−1), or ferrocene (δ (with respect to α-iron) = 0.41 mm s−1, ΔEQ = 2.41 mm s−1) itself.41 The recorded cyclic voltammogram of fcdmpzH (4) is shown in Figure 6. 4-Ferrocenyl-3,5-dimethylpyrazole (4) exhibits a reversible redox process with an oxidation peak at +0.003 V and a reduction peak at −0.083 V (0.3 V/s; vs Fc/ Fc+), which corresponds to the redox potentials of the ferrocenyl moiety. This results in a half-wave potential of E1/2 = −0.040 V (vs Fc/Fc+). This is considerably lower in comparison to the heteroaryl-substituted 4-, 3-, and 2ferrocenylpyridines (E1/2 = +0.206, +0.168, +0.155 V vs Fc/ Fc+)28b and is in the range of 4-ferrocenyl-1-tritylpyrazole (E1/2 = −0.03 V vs. Fc/Fc+) and 4-ferrocenylpyrazole (E1/2 = −0.04 V vs. Fc/Fc+).29a Starting from 4-ferrocenyl-3,5-dimethylpyrazole (4), syntheses of a variety of polydentate ligands, suitable for coordination chemistry, are possible. An overview of possible and conceivable reactions is given in Scheme 4. With the 4ferrocenyl-3,5-dimethylpyrazole (4) building block it might be possible to cover the coordination chemistry of all kinds of polypyrazole-based ligands, such as bis(pyrazol-1-yl)methane, bis(pyrazol-1-yl)ketone, tris(pyrazol-1-yl)methane, bis(pyrazol1-yl)acetic acid, and hydrotris(pyrazol-1-yl)borate. Most of them should be available by base-assisted substitution reactions at suitable electrophilic centers such as dichloromethane, phosgene or other carbonyl synthons, and chloroform or, in the case of the borates, by a stoichiometric reaction with potassium borohydride.42 The potential N,N and N,N,O ligands bis(pyrazol-1-yl)methane, bis(pyrazol-1-yl) ketone, and bis(pyrazol-1-yl)acetic acid bearing the 4-ferrocenyl-3,5dimethylpyrazole (4) moiety are described in the following. The most likely chelating N,N ligand bis(4-ferrocenyl-3,5dimethylpyrazol-1-yl)methane (5) is easily accessible from 4ferrocenyl-3,5-dimethylpyrazole (4) by base-assisted substitu-

Scheme 3. Deprotection of fcdmpzTrt (3) to fcdmpzH (4)

2.45 ppm, due to dimer formation and tautomerism of the amine functionality. A broad signal at 10.2 ppm is assigned to the pyrazole N−H signal. The 13C NMR spectrum is in agreement with the 1H NMR spectrum. The spectroscopically indistinguishable methyl groups generate one averaged signal at 12.9 ppm. The 13C NMR signals for the pyrazolyl carbon atoms also coincide at 113.0 (Cpz) and 134.7 ppm (Cpz-Me) due to their equality. The peaks at m/z 280 in the FAB+ and FD+ mass spectra correspond to the M+ peak of the target compound 4. Experimental and simulated zero-field Mössbauer spectra of 4-ferrocenyl-3,5-dimethylpyrazole (4) are presented in Figure 5. The least-squares fit (solid line), assuming a Lorentzian line

Figure 5. Zero-field Mössbauer spectrum of fcdmpzH (4) (dots) at 77 K vs 57Fe and a least-squares fit (solid line): δ = 0.54(1) mm s−1, ΔEQ = 2.40(1) mm s−1, Γfwhm = 0.32(1) mm s−1.

shape, to the spectrum of the crystalline sample of 4-ferrocenyl3,5-dimethylpyrazole at 77 K displays a quadrupole doublet

Figure 6. Cyclic voltammograms of fcdmpzH (4) in acetonitrile purged with nitrogen at 25 °C. Conditions: concentration of fcdmpzH, 5 × 10−4 mol L−1; concentration of [NBu4][PF6], 0.1 mol L−1, scan rates (A) 0.1 V s−1, (B) 0.2 V s−1, (C) 0.3 V s−1, (D) 0.4 V s−1, (E) 0.5 V s−1. D


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Scheme 4. Synthesis of Bis(4-ferrocenyl-3,5dimethylpyrazol-1-yl)methane (5; bfcdmpzm), Bis(4ferrocenyl-3,5-dimethylpyrazol-1-yl)ketone (6; bfcdmpzk), and Bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)acetic Acid (7; H[bfcdmpza])

Figure 7. Molecular structure of bfcdmpzm (5). Thermal ellipsoids are drawn at the 50% probability level; hydrogen atoms have been omitted for clarity. Selected bond lengths (Å) and angles (deg): C(12)−N(21) = 1.327(3), C(13)−C(30) = 1.481(3), C(1)−N(11) = 1.448(3), C(1)−N(12) = 1.449(3), C(23)−C(40) = 1.505(3), C(22)−N(22) = 1.329(3), CpC45−C49−Fe(1) = 1.651(1), Fe(1)−CpC40−C44 = 1.652(1), CpC35−C39−Fe(2) = 1.650(1), Fe(2)−CpC30−C34 = 1.651(1); N(11)− C(1)−N(12) = 113.6(2), C(14)−N(11)−N(21) = 112.60(19), C(24)−N(12)−N(22) = 112.33(19), C(12)−N(21)−N(11) = 104.98(19), C(22)−N(22)−N(12) = 105.03(19), ∠CpC40−C44−pz = 19.44(15), ∠CpC30−C34−pz = 29.28(13), ∠CpC40−C44−CpC45−C49 = 3.77(21), ∠CpC30−C34−CpC35−C39 = 0.91(19).

pyrazole bond at room temperature. In particular, the distance between the pyrazole and the cyclopentadienyl rings are 1.481(3) and 1.505(3) Å and are thus within the range of Csp2− Csp2 single bonds. The dihedral angle between least-squares planes of the pyrazole rings and the attached cyclopentadienyl rings are 19.44(15) and 29.28(13)°, respectively. The bond lengths and angles within these moieties remained mainly unchanged, in comparison to 3, whereas one ferrocenyl substituent has slightly tilted cyclopentadienyl rings (C40− C49, 3.77(21)°) and the rings of the second ferrocenyl group are almost parallel to each other (0.91(19)°). While the more tilted ferrocenyl moiety shows a more staggered geometry (C40−C49, 16°), the rings aligned more in parallel exhibit a less staggered geometry (C30−C39, 8.4°). The recorded cyclic voltammogram of bfcdmpzm (5) is depicted in Figure 8. Bis(4-ferrocenyl-3,5-dimethylpyrazol-1yl)methane (5) exhibits one reversible redox process with an oxidation peak at +0.034 V and a reduction peak at −0.052 V (0.3 V/s; vs Fc/Fc+), which corresponds to the redox potentials of the ferrocenyl moiety. This results in a half-wave potential of E1/2 = −0.009 V (vs Fc/Fc+). These values are comparable to those of fcdmpzH (4) and fcdmpzk (6) as well. Bfcdmpzm (5) shows only one reversible redox process within the measured range of −2 to +2 V, despite containing two redox-active reaction centers. This might indicate that these two centers are too far away from each other to establish an electronic transfer, as recently reported for bis(ferrocenyl) compounds bridged by conjugated double bonds.44 With increasing chain length a decrease in the peak separation values (ΔE1/2) between the two iron centers was noticed. The Fc(CHCH)nFc compounds exhibit a ΔE1/2 value from 170 mV for n = 1 down to ∼100 mV for n = 3. For n = 4−6 only one distinct redox process is visible.45 Similar behavior was also reported for the acetylenic compounds Fc(CC)nFc (n = 1, 2).46 As outlined above, a carbonyl-bridged bis(pyrazolyl) compound should also be available. Therefore, 4-ferrocenyl3,5-dimethylpyrazole (4) was reacted with triphosgene (Cl3COCOOCCl3) in the molar ratio 6:1 in the presence of 6 equiv of triethylamine. The reaction conditions sketched in Scheme 4 were kept analogously to those reported by Manzano et al. for the synthesis of bis(3,5-dimethylpyrazol-1-yl)ketone.47

tion at dichloromethane (Scheme 4). Reaction conditions (3 days at reflux temperature) were kept similar to published procedures for bis(3,5-dimethylpyrazol-1-yl)methane, except that triethylbenzylammonium chloride (TEBAC) rather than tetrabutylammonium hydrogen sulfate was used as the phase transfer catalyst.43 After neutralization and aqueous workup the crude product was purified by column chromatography on silica gel with chloroform as eluent. No monosubstitution of dichloromethane was observed. The NMR spectra reveal the formation of bis(4-ferrocenyl3,5-dimethylpyrazol-1-yl)methane (5; bfcdmpzm). 1H and 13C singlet signals at 6.13 and 79.8 ppm, respectively, were assigned to the bridging CH2 group. The former single methyl signal of the pyrazole split into two 1H NMR signals at 2.40 and 2.61 ppm, thus indicating alkylation of the nitrogen atom. The signals for the substituted cyclopentadienyl ring remained more or less unchanged, in comparison to 4 or 3, due to the free rotation along the C−C bond. The 1H resonances of the substituted and unsubstituted cyclopentadienyl ring at 4.11, 4.25, and 4.37 ppm agree well with those of 4-ferrocenyl-3,5dimethylpyrazole (4) itself (4.09, 4.25, and 4.42 ppm) or bis(4ferrocenyl-3,5-dimethylpyrazol-1-yl)acetic acid (7; H[bfcdmpza]), which is described later. An overview of the NMR data for the cyclopentadienyl groups for all related compounds is given in Table 1. Crystals suitable for single-crystal structure analysis were grown by slow evaporation of a chloroform solution. The structural model is shown in Figure 7. The substance crystallized in the space group P1̅ with Z = 2. The structural parameters of the ferrocenylpyrazole unit are largely unchanged, in comparison to fcdmpzTrt (3) or bis(4ferrocenyl-3,5-dimethylpyrazol-1-yl)ketone (6), except for the dihedral angles and the distance between the conjunct groups. The reason for this must be crystal-packing effects, because the NMR data clearly indicate free rotation around the ferrocene− E


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Figure 8. Cyclic voltammogram of bfcdmpzm (5) in acetonitrile purged with nitrogen at 25 °C. Conditions: concentration of bfcdmpzm, 5 × 10−4 mol L−1; concentration of [NBu4][PF6], 0.1 mol L−1; scan rates, (A) 0.1 V s−1, (B) 0.2 V s−1, (C) 0.3 V s−1, (D) 0.4 V s−1, (E) 0.5 V s−1.

packing effects. The tilting of the rings within the ferrocenyl residues is 2.62(12)°. The N−C−N angle of the carbonyl bridge is 113.86(19)° and is thus considerably lower than the ideal 120° expected for an sp2-hybridized carbon atom, which agrees well with the expected VSEPR considerations. Bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)ketone (6) exhibits a reversible redox process with an oxidation peak at +0.037 V and a reduction peak at −0.061 V (0.3 V/s; vs Fc/Fc+), which corresponds to the potentials of the ferrocenyl moiety (Figure 10).15 The additional reduction peak at −0.565 V presumably arises from the irreversible reduction of the ketone functionality. This results in a half-wave potential of E1/2 = −0.012 V (vs Fc/Fc+). A comprehensive overview of the electrochemical data of the compounds covered in this work is summarized in Table 2. The synthesis of bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)acetic acid (7) was attempted by different methods. Similar to the preparation of the sterically more demanding bis(3,5-di-tertbutylpyrazol-1-yl)acetato ligand,3 bis(3,5-dimethylpyrazol-1-yl)methane can be lithiated at the bridging CH2 carbon atom and subsequently carboxylated to produce bis(3,5-dimethylpyrazol1-yl)acetic acid, as described by Otero et al.48 However, this approach was not successful for the synthesis of bis(4ferrocenyl-3,5-dimethylpyrazol-1-yl)acetic acid (7; Hbfcdmpza) starting from bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)methane (5). Carboxylation was not observed nor was the reactant recovered. Attempts to react dichloroacetic acid with 4-ferrocenyl-3,5-dimethylpyrazole likewise failed. Finally, the reaction of 4 with dibromoacetic acid in the presence of a phase transfer catalyst, similar to the synthesis of bis(3,5-dimethylpyrazol-1-yl)acetic acid2,3 but by using KOtBu instead of KOH as a base (Scheme 4), gave a product which has been identified as the desired product bis(4-ferrocenyl-3,5-dimethylpyrazol-1yl)acetic acid (7; H[bfcdmpza]) by means of NMR and mass spectra. The 1H NMR spectrum shows the singlet signal of the methine proton at the bridgehead carbon at 7.05 ppm (CD2Cl2) or 6.88 ppm (CDCl3). The signals for the ferrocenyl moiety can be assigned to peaks at 4.11, 4.26, and 4.38 ppm (CD2Cl2) or 4.11, 4.27, and 4.39 ppm (CDCl3) and are similar to those for the other bis(4-ferrocenyl-3,5-dimethylpyrazol-1-

The crude product was recrystallized from dichloromethane and pentane to yield bis(3,5-dimethylpyrazol-1-yl)ketone (6; bfcdmpzk) as orange-red needles. The spectral data confirm formation of the desired product. In comparison to the NMR data of 5, the 1H NMR spectrum of 6 reveals an only marginal shift of the Cp resonances from 4.11, 4.25, and 4.37 ppm to 4.13, 4.30, and 4.39 ppm as well as of the methyl signals (from 2.40 and 2.61 ppm to 2.47 and 2.61 ppm). In the 13C NMR spectrum the CO carbon atom gives rise to an additional signal at 152.2 ppm, in comparison to 5. Orange-red crystals of this compound suitable for singlecrystal structure analysis were collected from a dichloromethane solution layered with pentane. A structural model is shown in Figure 9. The substance crystallizes in the space group

Figure 9. Molecular structure of bfcdmpzk (6). Thermal ellipsoids are drawn at the 50% probability level; hydrogen atoms have been omitted for clarity. Selected bond lengths (Å) and angles (deg): C(1)−O(1) = 1.202(3), C(1)−N(11) = 1.4068(18), N(11)−N(12) = 1.3815(18), CpC21−C25−Fe = 1.649(1), ∠Cp−Cp = 2.62(12), Fe−CpC31−C35 = 1.6571(8), C(12)−N(12) = 1.3194(19), C(13)−C(21) = 1.471(2); N(11)−C(1)−N(11A) = 113.86(19), N(12)−N(11)−C(14) = 112.39(12), C(12)−N(12)−N(11) = 104.38(12), ∠CpC21−C25−pz = 29.51(9).

C2/c with Z = 4. The molecule resides on a C2 axis through the keto group. Distances and angles are largely unchanged in comparison to the 4-ferrocenyl-3,5-dimethylpyrazol-1-yl groups of similar substances covered in this work. The dihedral angle between the cyclopentadienyl ring and the attached pyrazolyl system is 29.51(9)°. As the NMR spectra indicate free rotation of the ferrocene group, this angle is probably caused by crystalF


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Figure 10. Cyclic voltammogram of bfcdmpzk (6) in acetonitrile purged with nitrogen at 25 °C. Conditions: concentration of bfcdmpzk, 5 × 10−4 mol L−1; concentraton of [NBu4][PF6], 0.1 mol L−1; scan rates (A) 0.1 V s−1, (B) 0.2 V s−1, (C) 0.3 V s−1, (D) 0.4 V s−1, (E) 0.5 V s−1.

Table 2. Comprehensive Overview of Redox Properties of Ferrocenylpyrazole Compounds

a

compd

Eox (V)a

Ered (V)a

ΔE (V)

E1/2 (V)a

fcdmpzH (4) bfcdmpzm (5) bfcdmpzk (6)

+0.003 +0.034 +0.037

−0.083 −0.052 −0.061

0.086 0.086 0.098

−0.040 −0.009 −0.012

Versus Fc/Fc+ at 0.3 V/s.

yl) compounds. The 13C NMR spectrum displays the resonances of the bridgehead carbon at 71.4 ppm and the carboxylate carbon at 167.6 ppm (CD2Cl2). The FD+ mass spectrum shows peaks appropriate for the desired product (m/z 616 (50%)), the reactant 4, and the decarboxylated product (m/z 280 (100%); m/z 572 (40%)). Because of contamination with reactant no reliable microanalytical data were obtained. During attempted purification by recrystallization from a chloroform/methanol solution, single crystals were collected, the X-ray structure of which revealed that the iron(II) bis(ligand) complex [Fe(bfcdmpza)2] (8) rather than the desired ligand 7 was isolated. The molecular structure of 8 is depicted in Figure 11. The substance crystallizes in the space group P1̅ with Z = 2: i.e., two crystallographically independent molecules reside on centers of inversion. All ferrocenyl moieties are turned away from the coordinated metal center. The dihedral angles between ferrocenyl and pyrazolyl groups measure about 30° overall. The trans angles of the donor atoms and the iron metal centers are intrinsically 180°. The iron metal centers are coordinated in a slightly distorted octahedral fashion by two ligand molecules each. The cis angles of the coordinated ligands in the range of about 85−95° show evidence of this distortion. This behavior is also observed for [Fe(bdmpza)2] as well as for [Fe(bpza)2].3,6 The molecular structure of [Fe(bfcdmpza)2] (8) shows that H[bfcdmpza] (7) is a κ3-N,N,O ligand analogously to H[bdmpza] coordinating facially to the metal center and is therefore a structural mimic for the 2-His-1-carboxylate moiety found at the active site of Rieske dioxygenases.

Figure 11. Molecular structure of one of the independent molecules of [Fe(bfcdmpza)2] (8). Thermal ellipsoids are drawn at the 50% probability level; hydrogen atoms and cocrystallized solvent have been omitted for clarity. Selected bond lengths (Å) and angles (deg): Fe(1)−O(1) = 2.077(3), Fe(1)−N(11) = 2.154(4), Fe(1)−N(21) = 2.188(4); O(1A)−Fe(1)−N(11) = 94.87(14), O(1)−Fe(1)−N(11) = 85.13(14), O(1A)−Fe(1)−N(21) = 93.96(14), O(1)−Fe(1)−N(21) = 86.04(14), N(11)−Fe(1)−N(21) = 82.14(14), N(11A)−Fe(1)− N(21) = 97.86(14).

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SUMMARY The trityl-protected pyrazole 4-ferrocenyl-3,5-dimethyl-1-tritylpyrazole (3; fcdmpzTrt) has been synthesized from 4-iodo-3,5dimethyl-1-tritylpyrazole (2) via a Negishi type cross-coupling reaction. Subsequent acidic deprotection yields 4-ferrocenyl3,5-dimethylpyrazole (4; fcdmpzH). A phase transfer catalyzed reaction of the pyrazole 4 with base and dichloromethane results in the N,N ligand bis(4-ferrocenyl-3,5-dimethylpyrazol1-yl)methane (5; bfcdmpzm). Another N,N ligand, bis(4ferrocenyl-3,5-dimethylpyrazol-1-yl)ketone (6; bfcdmpzk), is gained by reacting 4 with triethylamine and triphosgene. The new N,N,O heteroscorpionate ligand bis(4-ferrocenyl-3,5dimethylpyrazol-1-yl)acetic acid (7; H[bfcdmpza]) can be obtained by reacting fcdmpzH (4) with dibromoacetic acid, KOtBu, and phase transfer catalyst and subsequent acidic workup. The heteroscorpionate ligand H[bfcdmpza] (7) prefers a κ3-N,N,O coordination mode, as indicated by the molecular structure of the bis(ligand) complex [FeG


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chloride precipitated. Solvent was removed in vacuo, and the residue was washed with water and diethyl ether several times, giving 4-iodo3,5-dimethyl-1-tritylpyrazole (2). Yield: 18.2 g (39.1 mmol, 40%). 1H NMR (CDCl3, 300 MHz): δ 1.47 (s, 3H, Me), 2.12 (s, 3H, Me), 7.01−7.04 (m, 6H, Ph), 7.16−7.20 (m, 9H, Ph) ppm. 13C NMR (CDCl3, 75.5 MHz): δ 14.8 (s, Me), 15.9 (s, Me), 67.1 (s, CI), 79.1 (s, CTrt), 127.5 (s, p-Ph), 127.6 (s, o-Ph), 130.4 (s, m-Ph), 142.7 (s, CpzMe), 143.0 (s, i-Ph), 147.7 (s, Cpz-Me) ppm. FAB MS (NBOH): m/z (%) 464 (5) [M+], 243 (100) [CPh3+]. Anal. Calcd for C24H21IN2 (464.34): C, 62.08; H, 4.56; N, 6.03. Found: C, 62.28; H, 4.54; N, 6.32. Synthesis of 4-Ferrocenyl-3,5-dimethyl-1-tritylpyrazole (3; fcdmpzTrt). A flask was charged with ferrocene (5.42 g, 29.1 mmol) which was suspended in dry tetrahydrofuran (20 mL) and cooled to 0 °C. Successively tert-butyllithium (18.1 mL, 29.1 mmol, 1.6 M in pentane) and anhydrous zinc chloride (3.96 g, 69.3 mmol) dissolved in dry tetrahydrofuran (50 mL) were slowly added. The solution was warmed to ambient temperature and was stirred for 1 h. To this solution were added successively a tetrahydrofuran suspension (20 mL) of bis(triphenylphosphine)palladium chloride (1.02 g, 1.45 mmol, 5 mol %) as catalyst and a tetrahydrofuran solution (100 mL) of 4iodo-3,5-dimethyl-1-tritylpyrazole (2; 13.5 g, 29.1 mmol). After the solution was stirred for 3 days, the reaction was quenched by adding water (10 mL), and all insoluble materials were removed by filtration. The filtrate was evaporated to dryness, and the residue was extracted with diethyl ether (500 mL). The organic layer was washed with water and brine and dried with sodium sulfate. After the solvent was removed under reduced pressure, the residue was purified by column chromatography (d = 6 cm, l = 25 cm, silica gel, eluent gradient from pure n-hexane to n-hexane/dichloromethane 1/1). The second colored fraction yielded the desired product 3 as a brown powder. Crystals suitable for single-crystal structure analysis could be obtained by slow evaporation of the eluent. Yield: 9.59 g (18.4 mmol, 63.1%). 1H NMR (CDCl3, 300 MHz): δ 1.76 (s, 3H, Me), 2.41 (s, 3H, Me), 4.07 (s, 5H, Cp), 4.24 (vt, 2H, Cppz, JHH = 1.7 Hz), 4.42 (vt, 2H, Cppz, JHH = 1.7 Hz), 7.18−7.22 (m, 6H), 7.28−7.35 (m, 9H) ppm. 1H NMR (CD2Cl2, 300 MHz): δ = 1.75 (s, 3H, Me), 2.38 (s, 3H, Me), 4.05 (s, 5H, Cp), 4.23 (vt, 2H, Cp, JHH = 1.8 Hz), 4.40 (vt, 2H, Cp, JHH = 1.7 Hz), 7.17 (m, 6H, Ph), 7.29 (m, 9H, Ph) ppm. 13C NMR (CDCl3, 75.5 MHz): δ 14.8 (s, 2 × Me), 67.5 (s, Cp), 69.1 (s, Cp), 78.2 (s, CTrt), 80.5 (s, Cp), 115.7 (s, Cpz), 127.3 (s, Ph), 127.6 (s, Ph), 130.5 (s, Ph), 138.5 (s, Ph), 143.7 (s, Cpz-Me), 144.0 (s, Cpz-Me) ppm. 13C NMR (CD2Cl2, 75.5 MHz): δ = 14.7 (s, Me), 15.1 (s, Me), 68.0 (s, Cp), 68.0 (s, Cp), 69.5 (s, Cp), 78.5 (s, Cp), 80.7 (s, CPh3), 116.3 (s, Cpz), 127.7 (s, Ph), 127.9 (s, Ph), 130.8 (s, Ph), 138.9 (s, Ph), 144.2 (s, Cpz-Me), 144.2 (s, Cpz-Me) ppm. FD MS: m/z (%) 522 (100) [M+]. FAB MS (NBOH): m/z (%) 522 (60) [M+], 243 (100) [CPh3+]. UV/vis (CH2Cl2): λmax (log ε) 450 (3.4), 274 nm (5.3). Anal. Calcd for (C34H30FeN4) (522.46): C, 78.16, H, 5.79, N, 5.36. Found: C, 78.60, H, 5.75; N, 5.37. Mp: 213 °C. Synthesis of 4-Ferrocenyl-3,5-dimethyl-1H-pyrazole (4; fcdmpzH). To a solution of 4-ferrocenyl-3,5-dimethyl-1-tritylpyrazole (3; 13.11 g, 25.1 mmol) in dichloromethane (900 mL) were added trifluoroacetic acid (2.89 g, 26.0 mmol) and water (9 mL), and the resulting mixture was stirred for 1 day. The organic phase was neutralized with a saturated solution of sodium bicarbonate, washed twice with water, and dried with sodium sulfate. After the solvent was removed under reduced pressure, the residue was purified by column chromatography (d = 6 cm, l = 25 cm, silica gel, first chloroform to remove reactant and byproduct and then chloroform/acetone 9/1) to give 3,5-dimethyl-4-ferrocenyl-1H-pyrazole (4) as a yellow powder. Yield: 4.97 g (17.7 mmol, 71%). 1H NMR (CDCl3, 300 MHz): δ 2.45 (s, 6H, Me), 4.09 (s, 5H, Cp), 4.25 (br s, 2H, Cppz), 4.42 (br s, 2H, Cppz), 10.2 (bs, 1H, NH) ppm. 13C NMR (CDCl3, 75.5 MHz): δ 12.9 (s, Me), 67.1 (s, Cp), 67.6 (s, Cp), 69.1 (s, Cp), 79.9 (s, Cp), 113.2 (s, Cpz), 134.7 (s, Cpz-Me) ppm. FD MS: m/z (%) 280 (100) [M+]. FAB MS (NBOH): m/z (%) 280 (100) [M+]. UV/vis (CH2Cl2): λmax (log ε) 450 (3.2), 270 nm (5.0). Anal. Calcd for C15H16FeN2 (280.15): C, 64.31; H, 5.76, N, 10.00. Found: C, 64.00, H, 5.72, N, 9.85. Mp: 177 °C dec.

(bfcdmpza)2] (8), and might thus be suitable for structural model complexes regarding the 2-His-1-carboxylate facial triad of non heme iron oxygenases. The redox potentials of 4ferrocenyl-3,5-dimethylpyrazole (4), bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)methane (5), and bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)ketone (6) correspond well to the values found for 4-ferrocenylpyrazole, reported earlier by Mochida et al., and reach into the redox potential region of Rieske [2Fe-2S] clusters. Thus, bis(ferrocenylpyrazol-1-yl)methane or -acetato ligands might be suitable for future model complexes regarding Rieske dioxygenases by mimicking the oxidation/reduction processes of these dioxygenases.

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EXPERIMENTAL SECTION

4-Iodo-3,5-dimethylpyrazole was synthesized via oxidative iodination starting from 3,5-dimethylpyrazole according to literature procedures.37 All other reagents and solvents were purchased from commercial sources and were used as received. Solvents (analyticalgrade purity) were degassed and stored under an inert gas atmosphere prior to use. The preparation and handling of air-sensitive materials were carried out under an inert gas atmosphere by using standard Schlenk and vacuum-line techniques. X-ray data sets were collected on a Bruker Smart APEX2 and Bruker-Nonius KappaCCD diffractometers. IR spectra were recorded on a Varian EXCALIBUR FTS-3500 FT-IR spectrometer with a CaF2 cuvette (d = 0.1 mm) or KBr matrix. Intensities are rated with the common abbreviations s (strong), sh (shoulder), m (medium), w (weak), br (broad), v (very), and combinations of them. UV/vis spectra were recorded on a Varian Cary 50 UV/vis spectrometer with a quartz glass cuvette (d = 10,00 mm). Melting points were determined using an electrothermal digital melting point apparatus (capillary). 1H, 13C{1H}, and 31P{1H} NMR spectra were measured on a Bruker DPX300 AVANCE spectrometer. All chemical shifts (1H and 13C{1H}; δ (ppm), multiplicity) were reported relative to the residual solvent signals as internal standard: chloroform (1H 7.26 (1); 13C 77.2 (3)), dichloromethane (1H 5.32 (3); 13C 54.00 (5)). CHN analyses were performed with Euro EA 3000 (Euro Vector) and EA 1108 (Carlo Erba) instruments. Mass spectra were measured on a JEOL JMS-700 mass spectrometer. The 57Fe Mössbauer spectra were recorded on a WissEl Mössbauer spectrometer (MRG-500) at 77 K in constant acceleration mode. 57 Co/Rh was used as the radiation source. WinNormos for Igor Pro software has been used for the quantitative evaluation of the spectral parameters (least-squares fitting to Lorentzian peaks). The minimum experimental line width was 0.20 mm s−1. The temperature of the samples was controlled by an MBBC-HE0106 Mössbauer He/N2 cryostat within an accuracy of ±0.3 K. Isomer shifts were determined relative to α-iron at 298 K. Cyclic voltammetric measurements were carried out using an Autolab PGSTAT 100 potentiostat or an Autolab PGSTAT 30 (in the case of 3). A three-electrode cell was used, using a gold-disk working electrode, a platinum-wire counter electrode, and a silver-wire pseudo reference electrode. Cyclic voltammetry was performed in MeCN solution (complex 5 × 10−4 mol L−1) containing 0.1 mol L−1 [nBu4N][PF6] as supporting electrolyte. All solutions were deoxygenated with N2 before each experiment, and a blanket of N2 was used over the solution during the experiment. Potentials are referenced to the ferrocenium/ferrocene (Fc+/Fc) couple used as an internal standard (for 4−6). In the case of compound 3 E1/2 = −0.09 V vs Fc/Fc+ was assigned by applying a correction of −0.42 V for the Ag/AgCl electrode used in this experiment. All experiments were performed at room temperature. Synthesis of 4-Iodo-3,5-dimethyl-1-tritylpyrazole (2). A flask was charged with 21.9 g (98.5 mmol) of 4-iodo-3,5-dimethylpyrazole (1) that was dissolved in dry tetrahydrofuran (150 mL). The dark solution was treated with sodium hydride (5.52 g, 138 mmol, 60% in mineral oil) in small portions and was stirred for at least 1 h at ambient temperature. Triphenylmethyl chloride (27.5 g, 98.5 mmol) was then added and the solution stirred for 3 days; it became sticky and sodium H


Organometallics

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Table 3. Crystal Data and Details of the Crystal Structure Determinations for 3, 5, 6, and 8 empirical formula fw cryst color cryst syst space group, Z a (Å) b (Å) c (Å) α (deg) β (deg) γ (deg) V (Å3) dcalcd (g cm−3) T (K) θ range (deg) no. of rflns collected no. of unique rflns no. of obsd rflns (>2σ(I)) R1, wR2 (obsd) R1, wR2 (overall) diff peak/hole (e/Å3) GOF on F2

fcdmpzTrt (3)

bfcdmpzm (5)

bfcdmpzk (6)

[Fe(bfcdmpza)2] (8)

C34H30FeN2 522.45 orange monoclinic P21/n, 4 12.9473(12) 9.840 (7) 20.4773(18) 90 91.025(8) 90 2608.5(19) 1.33 150 2.79−28.52 72515 6612 4806 0.0418, 0.0895 0.0707, 0.0997 0.339/−0.293 1.015

C31H32Fe2N4 572.31 orange triclinic P1̅, 2 8.0709(1) 11.1448(2) 15.1349(3) 76.147(1) 74.759(1) 81.735(1) 1270.52(4) 1.496 220 1.43−28.27 26288 6185 4843 0.0407, 0.1063 0.056, 0.1143 0.749/−0.528 1.02

C31H30Fe2N4O 586.29 orange monoclinic C2/c, 4 27.538(3) 7.5557(10) 13.5237(15) 90 116.878(8) 90 2509.9(5) 1.552 150 2.82−29.01 36492 3332 2855 0.0277, 0.0695 0.0363, 0.0735 0.388/−0.399 1.123

C64H62Fe5N8O4 × 4 CHCl3 × CH3OH 1795.98 orange triclinic P1̅, 2 13.2993(6) 14.4632(6) 21.5123(10) 85.7450(10) 78.1370(10) 68.1430(10) 3758.4(3) 1.587 150 0.97−27.85 58814 17444 10721 0.0698, 0.1955 0.1134, 0.2254 1.3/−1.634 1.061

Synthesis of Bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)methane (5; bfcdmpzm). To a solution of 4-ferrocenyl-3,5dimethyl-1H-pyrazole (4; 4.17 g, 14.9 mmol) in dichloromethane (150 mL) were added potassium hydroxide (1.29 g, 23.0 mmol), potassium carbonate (3.17 g, 23.0 mmol), and benzyltriethylammonium chloride (262 mg, 1.15 mmol) as phase transfer catalyst. The suspension was refluxed for 3 days. The organic phase was neutralized with half-concentrated hydrochloric acid, washed with water, and dried over sodium sulfate. After the solvent was removed under reduced pressure, the residue was purified by column chromatography (d = 2 cm, l = 20 cm, silica gel, chloroform) to give bis(4-ferrocenyl-3,5dimethyl-pyrazol-1-yl)methane (5) as an orange powder. Crystals suitable for single-crystal structure analysis could be obtained from a solution in chloroform by slow evaporation. Yield: 2.42 g (4.23 mmol, 56%). 1H NMR (CDCl3, 300 MHz): δ 2.40 (s, 6H, Me), 2.61 (s, 6H, Me), 4.11 (s, 10H, Cp), 4.25 (s, 4H, Cppz), 4.37 (s, 4H, Cppz), 6.13 (s, 2H, CH2) ppm. 13C NMR (CDCl3, 75.5 MHz): δ 11.2 (s, Me), 13.9 (s, Me), 61.2 (s, CH2), 67.4 (s, Cp), 67.6 (s, Cp), 69.1 (s, Cp), 79.8 (s, Cp), 114.9 (s, Cpz), 137.3 (s, Cpz-Me), 146.7 (s, Cpz-Me) ppm. FD MS: m/z (%) 572 (100) [M+]. UV/vis (CH2Cl2): λmax (log ε) 456 (3.6), 270 nm (5.6). Anal. Calcd for C31H32Fe2N4 (572.30): C, 65.06; H, 5.64, N, 9.79. Found: C, 64.74, H, 5.61, N, 9.58. Mp: 216 °C dec. Synthesis of Bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)ketone (6; bfcdmpzk). To a suspension of 4-ferrocenyl-3,5dimethyl-1H-pyrazole (4; 1.25 g, 4.47 mmol) in tetrahydrofuran (15 mL) were added successively triethylamine (0.60 mL, 8.3 mmol) and triphosgene (221 mg, 0.745 mmol). The suspension was stirred for 16 h at room temperature. The white solid was filtered off and washed with a few milliliters of tetrahydrofuran. The tetrahydrofuran fractions were combined, and all volatiles were removed in vacuo. Recrystallization from dichloromethane and pentane gave the product 6 as orange crystals. Yield: 240 mg (0.409 mmol, 18.3%). 1H NMR (CDCl3, 300 MHz): δ 2.47 (s, 6H, Me), 2.62 (s, 6H, Me), 4.13 (s, 10H, Cp), 4.30 (br s, 4H, Cppz), 4.39 (br s, 4H, Cppz) ppm. 13C NMR (CDCl3, 75.5 MHz): δ 13.0 (s, Me), 14.3 (s, Me), 68.1 (s, Cp), 68.2 (s, Cp), 69.0 (s, Cp), 69.2 (s, Cp), 120.4 (s, Cpz), 140.6 (s, Cpz-Me), 148.0 (s, Cpz-Me), 152.2 (s, CO) ppm. IR (KBr): ν̃ 3101 w, 2931 w, 2498 w, 1723 s (CO), 1506 m, 1472 w, 1438 m, 1372 s, 1341 m, 1106 m, 1079 w, 1032 w, 992 m, 925 m, 783 m, 737 m, 505 w cm−1. IR (CH2Cl2): ν̃ 2553 w, 2291 w, 1728 s (CO), 1508 w, 1439 w, 1376 s, 1356 s, 993 m, 932 m cm−1. UV/vis (CH2Cl2): λmax (log ε) 360 (5.6), 299 (6.1), 264 nm (6.2). Anal. Calcd for C31H30Fe2N4O

(586.29): C, 63.51; H, 5.16; N, 9.56. Found: C, 63.38; H, 5.06; N, 9.54. Mp: 230 °C dec. Synthesis of Bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)acetic acid (7; H[bfcdmpza]). To a solution of 4-ferrocenyl-3,5dimethyl-1H-pyrazole (4; 1.12 g, 3.98 mmol) in tetrahydrofuran (35 mL) were added dibromoacetic acid (434 mg, 1.99 mmol), potassium tert-butoxide (670 mg, 5.98 mmol), and benzyltriethylammonium chloride (40 mg, 0.18 mmol), and the reaction mixture was refluxed for 3 days. All volatiles were removed in vacuo. The residue was redissolved in chloroform and water (50 mL) and acidified to pH 2 with half-concentrated hydrochloric acid. The organic phase was dried over sodium sulfate, and the solvent was removed in vacuo to give the crude product 7, which showed contamination with 4. 1H NMR (CDCl3, 300 MHz): δ 2.43 (s, 6H, Me), 2.50 (s, 6H, Me), 4.11 (s, 10H, Cp), 4.26 (s, 4H, Cp), 4.38 (s, 4H, Cp), 7.05 (s, 1H, CH) ppm. 1 H NMR (CD2Cl2, 300 MHz): δ 2.41 (s, 6H, Me), 2.50 (s, 6H, Me), 4.11 (s, 10H, Cp), 4.27 (br s, 4H, Cppz), 4.39 (br s, 4H, Cppz), 6.88 (s, 1H, CH) ppm. 13C NMR (CD2Cl2, 75.5 MHz): δ 11.4 (s, Me), 14.1 (s, Me), 68.1 (s, Cp), 68.3 (s, Cp), 69.6 (s, Cp), 71.4 (s, CH), 79.4 (s, Cp), 116.2 (s, Cpz), 138.3 (s, Cpz-Me), 147.5 (s, Cpz-Me), 167.6 (s, COOH) ppm. FD MS: m/z (%) 280 (100) [fcdmpzH+], 616 (50) [M+], 572 (40) [bfcdmpzm+]. X-ray Structure Determinations. For X-ray structure analysis single crystals of the compounds were mounted on a glass fiber with perfluorinated ether. Data sets were collected on a Bruker Smart APEX2 or a Bruker-Nonius KappaCCD diffractometer using graphitemonochromated Mo Kα radiation (λ = 0.71073 Å). Lorentz and polarization effects were taken into account during data reduction, and semiempirical absorption corrections were performed on the basis of multiple scans using SADABS.49 The structures were solved by direct methods and refined with full-matrix least squares against F2 (SHELX97). Weighting schemes w = 1/[σ2(Fo2) + (aP)2 + bP] and P = [2Fc2 + max(Fo2,0)]/3 were applied in the last steps of the refinement.50 All other hydrogen atoms were included in their calculated positions and likewise refined in riding models. All details and parameters of the measurements are summarized in Table 3. CCDC 939993 (3), 939994 (5), 939995 (6), and 940303 (8) contain supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Center via www.ccdc.cam. ac.uk/data_request/cif. The structures were visualized with Diamond 2.1e.51 Crystals were grown by slow diffusion of dichloromethane I


Organometallics

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solutions of the compounds in n-hexane solvent (in the case of 3 and 6), from chloroform (in the case of 5), and from chloroform/methanol (in the case of 8). In the structure model of [Fe(bfcdmpza)2] (8), three of the cocrystallized chloroform molecules (C10, C20, and C30) showed disorder over two positions each. Their occupancies were fixed to 50/50, and SADI, ISOR, SIMU, and DELU restraints were applied for a stable refinement.

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(13) (a) Oldenburg, P. D.; Ke, C. Y.; Tipton, A. A.; Shteinman, A. A.; Que, L. Angew. Chem., Int. Ed. 2006, 45, 7975−7978. (b) Oldenburg, P. D.; Shteinman, A. A.; Que, L. J. Am. Chem. Soc. 2005, 127, 15672− 15673. (14) (a) Ballmann, J.; Albers, A.; Demeshko, S.; Dechert, S.; Bill, E.; Bothe, E.; Ryde, U.; Meyer, F. Angew. Chem., Int. Ed. 2008, 47, 9537− 9541. (b) Ballmann, J.; Dechert, S.; Demeshko, S.; Meyer, F. Eur. J. Inorg. Chem. 2009, 3219−3225. (15) Connelly, N. G.; Geiger, W. E. Chem. Rev. 1996, 96, 877−910. (16) (a) Siemeling, U. Z. Anorg. Allg. Chem. 2005, 631, 2957−2966. (b) Atkinson, R. C. J.; Gibson, V. C.; Long, N. J. Chem. Soc. Rev. 2004, 33, 313−328. (17) Kalita, D.; Morisue, M.; Kobuke, Y. New J. Chem. 2006, 30, 77− 92. (18) Juergens, O.; Vidal-Gancedo, J.; Rovira, C.; Wurst, K.; Sporer, C.; Bildstein, B.; Schottenberger, H.; Jaitner, P.; Veciana, J. Inorg. Chem. 1998, 37, 4547−4558. (19) Lopez, J. L.; Tárraga, A.; Espinosa, A.; Velasco, M. D.; Molina, P.; Lloveras, V.; Vidal-Gancedo, J.; Rovira, C.; Veciana, J.; Evans, D. J.; Wurst, K. Chem. Eur. J. 2004, 10, 1815−1826. (20) Fouda, M. F. R.; Abd-Elzaher, M. M.; Abdelsamaia, R. A.; Labib, A. A. Appl. Organomet. Chem. 2007, 21, 613−625. (21) (a) Lorkovic, I. M.; Duff, R. R.; Wrighton, M. S. J. Am. Chem. Soc. 1995, 117, 3617−3618. (b) Gregson, C. K. A.; Gibson, V. C.; Long, N. J.; Marshall, E. L.; Oxford, P. J.; White, A. J. P. J. Am. Chem. Soc. 2006, 128, 7410−7411. (22) Ruf, W.; Renk, T.; Siebert, W. Z. Naturforsch., B: Chem. Sci. 1977, 31, 1028−1034. (23) Fish, R. W.; Rosenblum, M. J. Org. Chem. 1965, 30, 1253−1254. (24) (a) Guillaneux, D.; Kagan, H. B. J. Org. Chem. 1995, 60, 2502− 2505. (b) Sanders, R.; Mueller-Westerhoff, U. T. J. Organomet. Chem. 1996, 512, 219−224. (c) Rebiere, F.; Samuel, O.; Kagan, H. B. Tetrahedron Lett. 1990, 31, 3121−3124. (25) Siemeling, U. Ferrocenes 2008, 141−176. (26) Kamounah, F. S.; Christensen, J. B. J. Chem. Res., Synop. 1997, 150−150. (27) Atkinson, R. C. J.; Long, N. J. Ferrocenes 2008, 3−32. (28) (a) Rajput, J.; Hutton, A. T.; Moss, J. R.; Su, H.; Imrie, C. J. Organomet. Chem. 2006, 691, 4573−4588. (b) Rajput, J.; Moss, J. R.; Hutton, A. T.; Hendricks, D. T.; Arendse, C. E.; Imrie, C. J. Organomet. Chem. 2004, 689, 1553−1568. (29) (a) Mochida, T.; Shimizu, F.; Shimizu, H.; Okazawa, K.; Sato, F.; Kuwahara, D. J. Organomet. Chem. 2007, 692, 1834−1844. (b) Purecha, V. H.; Nandurkar, N. S.; Bhanage, B. M.; Nagarkar, J. M. Tetrahedron Lett. 2008, 49, 1384−1387. (c) Ö zçubukçu, S.; Schmitt, E.; Leifert, A.; Bolm, C. Synthesis 2007, 39, 389−392. (30) (a) Xu, C.; Wang, Z.-Q.; Fu, W.-J.; Lou, X.-H.; Li, Y.-F.; Cen, F.F.; Ma, H.-J.; Ji, B.-M. Organometallics 2009, 28, 1909−1916. (b) Chupakhin, O. N.; Utepova, I. A.; Kovalev, I. S.; Rusinov, V. L.; Starikova, Z. A. Eur. J. Org. Chem. 2007, 857−862. (c) Horikoshi, R.; Nambu, C.; Mochida, T. Inorg. Chem. 2003, 42, 6868−6875. (31) Zapata, F.; Caballero, A.; Espinosa, A.; Tárraga, A.; Molina, P. J. Org. Chem. 2009, 74, 4787−4796. (32) (a) Köster, S. D.; Dittrich, J.; Gasser, G.; Hüsken, N.; Henao Castañeda, I. C.; Jios, J. L.; Della Védova, C. O.; Metzler-Nolte, N. Organometallics 2008, 27, 6326−6332. (b) Romero, T.; Caballero, A.; Tárraga, A.; Molina, P. Org. Lett. 2009, 11, 3466−3469. (33) Niedenzu, K.; Serwatowski, J.; Trofimenko, S. Inorg. Chem. 1991, 30, 524−527. (34) Mochida, T.; Okazawa, K.; Horikoshi, R. Dalton Trans. 2006, 693−704. (35) Mochida, T.; Shimizu, H.; Okazawa, K. Inorg. Chim. Acta 2007, 360, 2175−2180. (36) Mochida, T.; Shimizu, H.; Suzuki, S.; Akasaka, T. J. Organomet. Chem. 2006, 691, 4882−4889. (37) (a) Rodrı ́guez-Franco, M. I.; Dorronsoro, I.; HernándezHigueras, A. I.; Antequera, G. Tetrahedron Lett. 2001, 42, 863−865. (b) Sammelson, R. E.; Casida, J. E. J. Org. Chem. 2003, 68, 8075−

ASSOCIATED CONTENT

S Supporting Information *

CIF files giving crystallographic data for 3, 5, 6, and 8. This material is available free of charge via the Internet at http:// pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*N.B.: tel, (+49) 9131-85-28976; fax, (+49) 9131-85-27387; email, nicolai.burzlaff@fau.de. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the Deutsche Forschungsgemeinschaft DFG (SFB 583) and the German Academic Exchange Service (DAAD).

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ABBREVIATIONS H[bpza], bis(pyrazol-1-yl)acetic acid; H[bdmpza], bis(3,5dimethylpyrazol-1-yl)acetic acid; bfcdmpzm, bis(4-ferrocenyl3,5-dimethylpyrazol-1-yl)methane; bfcdmpzk, bis(4-ferrocenyl3,5-dimethylpyrazol-1-yl)ketone; H[bfcdmpza], bis(4-ferrocenyl-3,5-dimethylpyrazol-1-yl)acetic acid

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REFERENCES

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Bis(pyrazol-1-yl)acetic Acid Bearing Ferrocenyl Substituents

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