C 2005) Structural Chemistry, Vol. 16, No. 5, October 2005 (
DOI: 10.1007/s11224-005-4467-4

The Unusual Transformation of an Aromatic 1H-Imidazole into a Non-Aromatic 2H-Imidazole Antonio de la Hoz,1,2 Ana S´anchez-Migall´on,1 Mar´ıa del Carmen Mateo,2 Pilar Prieto,1 Lourdes Infantes,2 and Jos´e Elguero3,4 Received January 11, 2005; accepted March 21, 2005

2H-Imidazole derivative 5 has been synthesized and characterized by the X-ray diffraction (XRD) method. The compound crystallizes in the monoclinic space group Cc with cell parameters a = 19.398(1), b = 8.890(1), c = 10.247(1), β = 110.76(1), Z = 4. The molecules are inter-linked through C–H· · ·O and C–H· · ·π interactions forming infinite chains. KEY WORDS: Imidazoles; crystal structure; NMR; DFT calculations; aromaticity.

INTRODUCTION

The present paper describes the results obtained in the methylation of 1 including the X-ray structure of the resulting compound and the theoretical calculations aimed at interpreting the obtained results.

In a previous paper we determined the structure of N1 -hydroxylophine N3 -oxide (or 1-hydroxy-2,4,5triphenyl-1H-imidazole 3-oxide) 1 from X-ray powder diffraction data [1]. The two independent molecules in the asymmetric unit form chains by O H· · ·O hydrogen bonds. The HB is so strong that the proton is in the middle (low-barrier hydrogen bond). To have a model of 1 lacking the intermolecular HB, it was decided to prepare the corresponding O-methyl derivative 2.

RESULTS AND DISCUSSION When attempting to prepare 2 by methylation of 1, a different compound was formed that was identified by Xray crystallography as being 5. The product was obtained by solid–liquid phase transfer catalysis using dimethyl sulfate and sodium hydroxide in equimolar amounts. After crystallization from methanol or ethanol, compound 5 was isolated in 17% yield. Attempts to prepare 2 by other methylation procedures failed and always afforded complex mixtures where compound 5 was the only identifiable compound. The fact that using ethanol as crystallization solvent, the same derivative 5 was obtained proves that the methyl of the methoxy group comes from the dimethyl sulfate. The desired compound 2 was probably formed as an intermediate (Scheme 1). Then, either a migration of the methoxy group directly (TS) or through an oxaziridine intermediate (Scheme 1, path a), or by reaction through a series of ionic derivatives (3, 4) followed by a last methylation step (Scheme 1, path b) affords 5 (this is not a true methoxy migration). The transformation of 2 into 5 is counterintuitive since 2 is aromatic and 5 is not. We have carried out DFT calculations on the stabilities of model compounds 6 and

1 Departamento

de Qu´ımica Inorg´anica, Org´anica y Bioqu´ımica, Facultad de Ciencias Qu´ımicas, Universidad de Castilla-La Mancha, E-13071 Ciudad Real, Spain. 2 Departamento de Cristalograf´ıa, Instituto de Qu´ımica F´ısica ‘Rocasolano’, Serrano, 119, E-28006 Madrid, Spain. 3 Instituto de Qu´ımica M´ edica (C.S.I.C.), Juan de la Cierva 3, E-28006 Madrid, Spain. 4 To whom all correspondence should be addressed; e-mail: iqmbe17@ iqm.csic.es

485 C 2005 Springer Science+Business Media, Inc. 1040-0400/05/1000-0485/0


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Scheme 1.

7 (Scheme 2). The B3LYP/6-31G∗ energies including the ZPE correction are: 6 −415.71644 and 7 −415.76722 hartrees. Thus, isomer 7 is 133 kJ mol−1 more stable than isomer 6. This very large difference explains why we have not isolated 2. The atom-labeling scheme of compound 5 is depicted in Fig. 1 [7]. Compound 5 crystallizes in a space group with symmetry plane elements, both enantiomers being present in the ordered solid state. Selected geometric parameters are given in Table I. The imidazole ring is not planar (χ 2 = 196.84 vs. the tabulated value of 5.99). The conformation of the imidazole ring is between an envelope and a half chair, where the C1 atom is that which is out of the plane defined by the other four atoms. The Cremer and Pople parameters [8] for the ring are q2 = 0.063(5) ˚ and φ2 = 9(4)◦ versus φ2 = 0◦ and 18◦ for the ideal A envelope and half-chair conformations. There are no strong hydrogen bond donor atoms in the molecular structure of compound 5 and the crystal is formed through weak CH· · ·O hydrogen bonds and hydrofobic contacts between the phenyl rings, Table II. The molecules are interlinked forming an infinite chain along the c-axis and these catemers display a hexagonal topology in the crystal structure (Fig. 2). There are no

Scheme 2.

voids in the structure and the total packing coefficients is 0.71. Having established that the compound has the structure 5 we have verified that it has not been reported in the literature. The most similar structure has been published by Clark et al. in 1975 [2]. Kirilyuk and Volodarsky have been working on 2H-imidazole N-oxides for some years discovering the important properties as materials of these compounds [3]. Experimental Part 2-Methoxy-2,4,5-triphenyl-2H-imidazole 1-oxide (5). To a solution of 1-hydroxy-2,4,5-triphenyl-1Himidazole 3-oxide (1) (0.82 g, 2.5 mmol) in dichloromethane (5 mL), 0.5 M aqueous NaOH (5 mL) and tetrabutylammonium hydrogen sulfate (TBAS) (42.4 mg, 0.125 mmol) were added and the mixture stirred. Then Me2 SO4 (0.235 mL, 2.5 mmol) was added and the mixture was stirred at 40◦ C for 10 min. The mixture was filtered and the filtrate was extracted with dichloromethane (3 × 5 mL). The organic fraction was dried over magnesium sulfate and the solvent was evaporated in vacuo. The remaining oil (a very complex mixture according to the 1 H NMR spectrum) was dissolved in diethyl ether (3 mL), and addition of cold EtOH (5 mL) produced the precipitation of the pure product (142 mg, 16%). Mp (EtOH) = 164.8–166.6◦ C. Exact mass calculated for C22 H18 N2 O2 , 342.1368. Found, 342.1796. The melting point (uncorrected) was determined using a Gallenkamp melting point apparatus. The EI-mass spectrum was recorded on a VG AutoSpec apparatus (SIDI-UAM). Crystals were grown from a methanol (or ethanol) solution by slow evaporation of the solvent.

Transformation of an Aromatic 1H-Imidazole into Non-Aromatic 2H-Imidazole

487

Fig. 1. ORTEP of molecule 5 at 50% probability. 1

H and 13 C NMR spectra of compound 5. The spectra were recorded at 499.769 MHz in a Varian Innova 500 instrument using CDCl3 as solvent. 1D and 2D experiments were used to assign most signals but those corresponding to 13 C NMR marked with an asterisk remain unassigned (Scheme 3).

Structure Determination of Compound 5 A single crystal of 5 of dimensions 0.57 mm × 0.13 mm × 0.10 mm was chosen for X-ray diffraction (XRD) studies. The measurements were made on a Kappa CCD system with graphite monochromated radiation

˚ ◦) Table I. Geometric X-Ray Parameter (A, N1 N1 C2 N2 N2 C1 N2 C1 N1 C2 C3 O1 O1 O1 N1 N2 C1 C1 N2 C1 N1 C2 C3 C2 C2

C1 C2 C3 C3 C1 C11 C1 N1 N1 C2 C2 C3 C3 N2 N2 C1 C1 N1 C1 N2 C1 C11 C1 C11 C1 C11 O1 C4 C11 C16 C1 N1 C2 N1 C2 C3 C2 C3 N2 C3 N2 C1 N2 C1 N1 N1 C1 O1 N1 C1 C11

1.553 (7) 1.301 (7) 1.484 (7) 1.287 (7) 1.447 (7) 1.531 (7) 102.8 (4) 109.9 (4) 104.9 (4) 114.1 (4) 108.0 (4) 110.3 (4) 114.4 (4) 109.6 (4) 107.5 (4) 111.8 (4) 113.8 (4) 119.7 (4) −6.9 (5) 4.9 (5) −1.0 (5) −3.6 (5) 6.0 (5) −129.3 (4) 111.2 (4)

O1 O1 O2 C2 C3

C1 C4 N1 C21 C31

1.373 (6) 1.444 (7) 1.252 (6) 1.483 (7) 1.487 (7)

C1 O2 O2 N1 C3 C2 C2 C2 N2 C3 C3

C11 C12 N1 C1 N1 C2 C2 C21 C2 C21 C21 C22 C21 C26 C3 C31 C3 C31 C31 C36 C31 C32

120.1 (4) 120.5 (4) 129.6 (4) 123.7 (4) 131.4 (4) 121.4 (4) 118.9 (4) 124.9 (4) 121.0 (4) 121.4 (5) 118.1 (4)

N1 N1 C3 N2 C3 C1 N2

C1 C1 C2 C3 C2 N2 C3

O1 C4 C11 C12 N1 O2 C2 C21 C21 C22 C3 C31 C31 C32

56.9 (6) 95.3 (5) −176.6 (4) −179.9 (5) −51.6 (7) 178.5 (4) −38.7 (6)

488

Hoz, S´anchez-Migall´on, Mateo, Prieto, Infantes, and Elguero ˚ and Angles, Table II. Geometry Intermolecular Contacts (Distances, A Compound 5

C16 H16· · ·O2 (x, −y, z−1/2) C32 H32· · ·c1116 (x, −y, z−1/2) C13 H13· · ·c2126 (x−1/2, y−1/2, z)

◦)

for

D H

H· · ·A

D· · ·A

D H· · ·A

0.93(−) 0.97(−) 0.98(−)

2.36(−) 2.87(−) 2.96(−)

3.124(7) 3.767(5) 3.727(6)

139(−) 155(−) 136(−)

Note. ci1i6 represents the centroids of the rings (Ci1, Ci2, . . ., Ci6) (i = 1–3).

(CuKα ). Image processing and data reduction were done by using Denzo [9]. The peaks were indexed successfully with monoclinic primitive lattice. The structure was solved by direct methods using SIR97 [10] and refined with SHELXL97 [11] programs. All the non-hydrogen atoms were revealed in the first map itself. Initially full matrix least-squares refinement using 1345 reflections with isotropic temperature factors for all the nonhydrogen atoms was carried out. Subsequent refinements were carried out with anisotropic thermal parameters for non-hydrogen atoms and isotropic temperature factors for the hydrogen atoms, which were placed at chemically acceptable positions, except for the hydrogen in the methyl group which were located in difference maps. The hydrogen atoms in the phenyl rings have been refined with a riding model constraint where only the C H distances are allowed to refine. The hydrogen isotropic displacement parameters have been constrained to be 1.5 and 1.2 times the equivalent isotropic U of the bonded atom for methyl and phenyl hydrogens, respectively. Details of crystal data and refinement are given in Table III. “CCDC-258614 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/ retrieving.html [or from the Cambridge Crystallographic Data Centre (CCDC), 12 Union Road, Cambridge

CB2 1EZ, UK; fax: +44(0)1223-336033; e-mail: [email protected]].”

COMPUTATIONAL METHODS The calculations have been carried out with the Gaussian-03 program [4] at the hybrid HF-DFT method, B3LYP [5], with the 6-31G∗ basis set [6]. The minimum nature of the optimized geometries of all the systems has been confirmed by frequency calculations. ZPE corrections have been carried out on the final energies.

Table III. Experimental X-Ray Crystallography Data at Room Temperature Empirical formula Formula weight Temperature (K) ˚ Wavelength (A) Crystal system Space group Cell dimensions ˚ a (A) ˚ b (A) ˚ c (A) β (◦ ) ˚ 3) Volume (A Z Density (calculated) (mg m−3 ) Absorption coefficient (mm−1 ) F (0 0 0) Crystal size (mm) θ range for data collection (◦ ) Index ranges

Reflections collected Independent reflections Refinement method Data/restraints/parameters Goodness-of-fit on F2 Final R indices [I > 2σ (I)] R indices (all data) Largest diff. peak and hole (eA−3 ) Scheme 3.

C22 H18 N2 O2 342.38 293(2) 1.54180 Monoclinic Cc 19.3978(10) 8.8904(10) 10.2474(10) 103.76(1) 1716.5(3) 4 1.325 0.686 720 0.57 × 0.13 × 0.10 4.69–62.80 0 ≤ h ≤ 22 0 ≤ k ≤ 10 −11 ≤ l ≤ 11 1345 [Rint =] Full-matrix least-squares on F2 1345/2/260 1.064 R1 = 0.0682, wR2 = 0.1593 R1 = 0.0711, wR2 = 0.1628 0.362 and −0.332

Transformation of an Aromatic 1H-Imidazole into Non-Aromatic 2H-Imidazole

Fig. 2. Packing of molecules 5 down the (a) b-axis and (b) c-axis.

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Hoz, S´anchez-Migall´on, Mateo, Prieto, Infantes, and Elguero

ACKNOWLEDGMENTS The authors thank the financial support of the Ministerio de Sanidad (Project No. SAF-2003-08003-C0202) and the Consejer´ıa de Ciencia y Tecnolog´ıa JCCM (Project PAI-02-019).

4.

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