Synthesis and crystal structure of...

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Polyhedron 25 (2006) 2055–2064

Synthesis and crystal structure of 2,4-dihydro-4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)imino]-5-methyl-2-phenyl-

3H-pyrazol-3-one and its copper(II) complex

Giselle Cerchiaro a, Ana M. Da Costa Ferreira a,*, Aline B. Teixeira b, Hugo M. Magalhaes b,Anna C. Cunha b, Vitor F. Ferreira b, Leonardo S. Santos c, Marcos N. Eberlin c,

Janet M.S. Skakle d, Solange M.S.V. Wardell e, James L. Wardell f

a Departamento de Quımica Fundamental, Instituto de Quımica, Universidade de Sao Paulo, P.O. Box 26077, 05513-970 Sao Paulo, SP, Brazilb Departamento de Quımica Organica, Instituto de Quımica, Universidade Federal Fluminense, Campus do Valonguinho, 24210-150 Niteroi, RJ, Brazil

c Laboratorio Thomson de Espectrometria de Massas, Instituto de Quımica, Universidade Estadual de Campinas,

13083-970 Campinas, SP, Brazild Department of Chemistry, University of Aberdeen, Meston Walk, Old Aberdeen, AB24 3UE, Scotland, UK

e FAR-MANGUINHOS, Rua Sizenando Nabuco 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazilf Departamento de Quımica Inorganica, Instituto de Quımica, Universidade Federal do Rio de Janeiro P.O. Box 68563,

21945-970 Rio de Janeiro, RJ, Brazil

Received 15 August 2005; accepted 3 January 2006Available online 20 February 2006

Abstract

2-Diazo-3-methyl-1-phenyl-5-pyrazolone (2) and 2,4-dihydro-4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)imino]-5-methyl-2-phenyl-3H-pyrazol-3-one (3) were obtained in a one-pot reaction from 3-methyl-1-phenylpyrazol-5-one (1), mesyl azide, and K2CO3 inMeOH or CH2Cl2 solution. NMR, IR and ESI mass spectra as well as the crystal structure are reported for red colored 3. The crystal struc-ture determined at 150 K reveals that the corresponding bonds in the two phenylpyrazol-5-one moieties in each of the two independent ‘‘U’’shaped molecules have essentially the same lengths, with an extensive delocalization in the central O–C–C–N–C–C–O fragment of the mol-ecule. In particular, the hydrogen atom, formally a part of a hydroxyl group, is found near-midway [O1–HY and O11–HY = 1.24(4) and1.19(4) A, in molecule 1, and O21–HX and O31–HY = 1.203(4) and 1.19(4) A, in molecule 2] between the two oxygen atoms (formally in acarbonyl and a hydroxy group), with near linear O–H–O bond angles of 173.8(4)� and 172.7(4)� in the two independent molecules. All C–Obond lengths are in the narrow range of 1.271(3)–1.288(3) A. Further, since this compound shows different coordinating groups, its bindingability towards copper(II) ions was investigated. A dark red complex 4, obtained by reaction of 3 with copper(II) ions at stoichiometricratio, was characterized as a neutral 1:1 species, [3:CuCl2], involving tautomeric forms, by ESI-MS, ESI-MS/MS, IR, UV/Vis and EPRspectra. Interestingly, copper coordination to ligand 3 occurs solely by oxygen atoms, in spite of the presence of nitrogen donor centers.The deprotonation of 4 was monitored by UV/Vis, and a corresponding pKa value was determined as (5.6 ± 0.2).� 2006 Elsevier Ltd. All rights reserved.

Keywords: Pyrazole derivatives; Copper complex; Structural characterization; EPR and NMR spectroscopy; ESI mass spectrometry

1. Introduction

The chemistry of pyrazolone and its derivatives is partic-ularly interesting because of their potential application in

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doi:10.1016/j.poly.2006.01.002

* Corresponding author. Tel.: +55 11 3091 2151; fax: +55 11 3815 5579.E-mail address: [email protected] (A.M. Da Costa Ferreira).

medicinal chemistry as analgesic [1], anti-inflammatory[2], and therapeutic agents [3,4]. As an example, edaravone(3-methyl-1-phenyl-2-pyrazolin-5-one) has been recentlyshown to produce marked attenuation of brain damagecaused by ischemia-reperfusion [5], and its pharmacologi-cal actions were attributed to its antioxidant activity, as apotent hydroxyl radical scavenger [6]. Diazocarbonyl

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2056 G. Cerchiaro et al. / Polyhedron 25 (2006) 2055–2064

compounds [7,8] as precursors of heterocyclic molecules[9–11], including N-arylpyrazole derivatives have beenstudied by some of us owing to their wide applications inthe pharmaceutical and agrochemical industries [12–14].

On the other hand, pyrazolyl and pyrazolyl-derivedligands can form relevant coordination compounds withdifferent metal ions. Copper complexes have been exten-sively studied, especially dinuclear and polynuclear species,as mimics of the proteins hemocyanin and tyrosinase [15]or as compounds with interesting catalytic and magneticproperties [16–18]. In most of these complexes, copper ionsare linked by N,N 0-bridging pyrazolato anions, or coordi-nated by one nitrogen atom of the pyrazole ring [19]. How-ever, recently an unusual coordination mode of this type ofligand was described, where nitrogen atoms of the pyrazolerings are not bound to copper, but involved in strong intra-molecular hydrogen bonds [20]. Additionally, pyrazolonederivatives have interesting spectroscopic and structuralproperties owing to its keto-enol tautomerism [21].Recently, some Schiff bases derived from 3-methyl-1-(4 0-methylphenyl)-2-pyrazolin-5-one and aromatic amineswere prepared and had their molecular structures deter-mined. These ligands can exist in three tautomeric forms:keto-imine, imine-ol, and keto-amine, although the keto-amine form is predominant in the solid state [22]. Theircorresponding mononuclear copper(II) complexes werealso prepared and characterized by spectroscopic tech-niques, indicating a tetragonal geometry around thecopper(II) ion, N,O coordinated.

Herein, we report a new method for preparing 4-(5-hydroxy-4-pyrazolylimino)-2-pyrazolin-5-one (3), from2-pyrazolin-4,5-dione (1), in an one-step diazo-transferprocess (see Scheme 1), and its corresponding crystal struc-ture, that showed a near-linear intramolecular H-bonding.Further, since this compound shows different coordinatinggroups its binding ability towards copper(II) ions wasinvestigated. A dark red complex 4 was obtained by reac-

NN O

H3C

K2CO3/CH3SO2N3 NN

H3C

CH2Cl2 or CH3OH

1 2

Scheme 1. Synthetic route used f

tion of 3 with copper(II) ions at stoichiometric ratio, in eth-anol/water solution, at pH 4–5 adjusted with HCl.Compound 4 has been characterized as a neutral 1:1 spe-cies, [3:CuCl2], involving tautomeric forms, by ESI-MS,ESI-MS/MS, IR, UV/Vis and EPR spectra, in additionto conductivity and elemental analysis. The deprotonationof 4, in which the copper(II) ion is coordinated to ligand 3

solely by oxygen atoms, was monitored by UV/Vis, and acorresponding pKa value was determined.

2. Experimental

2.1. Reagents and techniques

Melting points were determined on a Fisher–Johnsapparatus and are uncorrected. Column chromatographywas performed on silica gel 60 (Merck 70–230 mesh). Infra-red spectra were recorded on Perkin–Elmer 1420 andBOMEM 3.0 instruments in the range 4000–400 cm�1, inKBr pellets. NMR spectra were recorded with a VarianUnity Plus 300 spectrometer, operating at 300 MHz (1H)and 75 MHz (13C), with tetramethylsilane as the internalstandard. Elemental analyses were performed at Central

Analıtica of the Instituto de Quımica-USP, using a Per-kin–Elmer 2400 CHN Elemental Analyzer. Electronic spec-tra were recorded on an Olis modernized-Aminco DW2000 instrument, using a thermostated cell compartment,and standard 1.00 cm quartz cells. The pH of the solutionswas monitored using a Digimed DMPH-2 instrument, cou-pled to a combined pH electrode either from Ingold orRadiometer. Appropriate buffer solutions were used to cal-ibrate the instrument. Conductivity experiments of1 mmol dm�3 aqueous solutions were carried out on a Dig-imed DM-31 instrument, using a 10.0-mmol dm�3 KClsolution as standard (specific conductivity = 1412.0 lScm�1 for aqueous solution, or 0.141 lS cm�1 for organicsolutions, both at 298 K) [23]. EPR spectra were recorded

O

N2

HCl + Cu(H2O)6.(ClO4)2

OH

O

NNN N

N

CH3CH3

CuCl Cl

OH O

NNN N

N

CH3CH3

+

3

EtOH/CH2Cl2

4

or obtaining compounds 2–4.

G. Cerchiaro et al. / Polyhedron 25 (2006) 2055–2064 2057

on a Bruker EMX instrument, operating at X-band fre-quency, using standard Wilmad quartz tubes, at 77 K.DPPH (a,a 0-diphenyl-b-picrylhydrazyl) was used as fre-quency calibrant (g = 2.0036) with samples in frozenCH3CN:water (8:1, v/v) solutions, at 77 K. Usual condi-tions used in these measurements were 2.83 · 104 receivergain, and 15G modulation amplitude. ESI mass and tan-dem mass spectrometric measurements were made using aMicromass (Manchester – UK) QTof instrument of ESI-QqTof configuration with 7.000 mass resolution in theTOF mass analyzer. The following typical operating condi-tions were used: 3 kV capillary voltage, 40 V cone voltageand dessolvation gas temperature of 100 �C. TandemESI-MS/MS spectra were collected after 15–20 eV collisioninduced dissociation (CID) of mass-selected ions withargon. Mass-selection was performed by Q1 using a unitarym/z window, and collisions were performed in the rf-onlyquadrupole collision cell, followed by mass analysis ofproduct ions by the high-resolution orthogonal-reflectronTof analyzer.

2.2. Synthetic procedures

2.2.1. 2-Diazo-3-methyl-1-phenyl-5-pyrazolone (2) and

2,4-dihydro-4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-

4-yl)imino]-5-methyl-2-phenyl-3H-pyrazol-3-one (3)

To a stirred suspension of potassium carbonate(2.5 mmol) in anhydrous dichloromethane (or methanol)(5 mL) under nitrogen at room temperature, was added asolution of 1 (1.0 mmol) in anhydrous dichloromethane(or methanol) (4 mL). After stirring the ice-cooled mixturefor 0.5 h, a solution of mesyl azide (1.4 mmol) in dichloro-methane (or methanol) (1 mL) was added dropwise. Thereaction mixture was then stirred for other 3 h at roomtemperature, and the solvent was removed under vacuumto leave a red oily residue, which was separated by columnchromatography on silica gel, using 40% dichloromethanein hexane as eluent to give 2 and 3.

Compound 2. 1H NMR (CDCl3) d: 2.39 (s, Me), 7.20 (tt,1H, J 1.2 and 7.5 Hz, H–Ar), 7.37–7.43 (m, 2H, H–Ar),7.87–7.91 (m, 2H, H–Ar) . 13C NMR (CDCl3) d: 13.9(CH3), 66.4 (C@N2), 119.1(C-2 0), 125.1 (C-4 0), 128.7(C-3 0), 138.4 (C-1 0), 141.8 (C-4), 163.0 (C@O). IR (KBr,cm�1) mC@O 1681; mN–N 2133. EIMS (m/z) 200 [M+,100%]. UV/Vis (CH2Cl2, nm) kmax: 251 (e1 = 5.3 · 104),and 332 (e2 = 2.3 · 103).

Compound 3. M.p. 183–184 �C (lit. 183 �C). ElementalAnal. Calc. for C20H17N5O2 Æ 3H2O: C, 58.10; H, 5.61; N,16.94. Found: C, 57.20; H, 5.04; N, 17.14%; 1H NMR(CDCl3) d: 2.37 (s, 2Me), 7.30 (tt, 2H, J 1.2 and 7.5 Hz,H–Ar), 7.43–7.49 (m, 4H, H–Ar), 7.89–7.93 (m, 4H,H–Ar), 17.97 (s, 1H, OH). 13C NMR (CDCl3) d: 11.8(CH3), 120.5 (C2 0), 125.7 (C4), 126.7 (C4 0), 128.8 (C3 0),137.4 (C1 0), 152.1 (C3), 154.3 (C5). IR (KBr, cm�1) mC@O,1729; mOH 2922, 2852. EIMS (m/z) 359 [M+, 88%]. UV/Vis(CH2Cl2) kmax/nm (e/mol�1 dm3 cm�1): 250 (e3 = 3.2 ·103), 359 (e2 = 1.4 · 103) and 460 (e1 = 1.3 · 103); UV/Vis

(CH3CN) kmax/nm (e/mol�1 dm3 cm�1): 204 (4.9 · 104),240 (3.2 · 104), 368 (1.3 · 104) and 445 (2.6 · 104).

2.2.2. Preparation of the copper(II) complex (4)

A solution of Cu(ClO4)2 Æ 6H2O (0.150 g, 0.4 mmol) inH2O (0.5 mL) was added at room temperature and understirring to a solution of 3 (0.165 g, 0.4 mmol) in ethanol(10 mL). The apparent pH of the reaction mixture wasadjusted to 4–5 by dropwise addition of aqueous HCl solu-tion (�1 M). After stirring for 6 h, tiny brownish-red crys-tals were collected, washed with cold ethanol and ether,and dried under reduced pressure over P2O5 to yield0.122 g (60%) of the complex 4.

Elemental Anal. Calc. for [C20H18N5O2CuCl2]: C, 48.54;H, 3.67; N, 14.15; Cu, 12.84; Cl, 14.33. Found: C, 48.28/48.62; H, 3.34/3.59; N, 13.74/14.60; Cu, 11.88; Cl,13.80%. KM = 21 S cm2 mol�1 in water solution, 17 Scm2 mol�1 in CH3OH, and 0 S cm2 mol�1 in CH2Cl2. IR(KBr, cm�1): mOH, 3432 (m); mCsp3–H, 3065 (w); mCsp2–C

2924 (w); dCsp2–C, 995–775; mC@O, 1614 (s); mC@N, 1596(m); mC–N, 1532 (w). UV/Vis (CH3CN) kmax/nm(e/mol�1 dm3 cm�1): 203 (8.9 · 104), 255 (8.8 · 104), 348(3.0 · 104) and 540 (2.4 · 104).

2.3. X-ray crystallography data collection and processing

Room temperature data were collected on a BrukerSMART area CCD diffractometer whilst low temperaturedate were collected on a Enraf Nonius KappaCCD diffrac-tometer at the UK’s EPSRC X-ray crystallographic service,based at the University of Southampton. The structure wassolved by direct methods with SHELXS-97 and refined usingSHELXL-97 [24] in the triclinic spacegroup P�1. Two dimerswere present in each asymmetric unit to give 4 in the unitcell. The data completeness for the low temperature dataset was somewhat lower than that of the room temperatureset, as shown in Table 1, so discussion will concentrate onthe room temperature data, although no major differenceswere discernable between the two results. All H atoms werelocated from difference maps and then treated as riding

atoms, with C–H distances of 0.96 A (methyl) or 0.93 A(aromatic) and Uiso(H) values of 1.5Ueq(methyl) or1.2Ueq(aromatic). The exceptions were the hydrogen atomsbridging two oxygen atoms, H11 and H31, which wereallowed to refine freely. Conformational and H-bondinganalysis was performed using PLATON [25].

3. Results and discussion

3.1. Compounds 2 and 3

Our synthetic route to 2–4 is shown in Scheme 1. Pyraz-olone 1 on reaction with mesyl azide or tosyl azide in thepresence of a base at room temperature furnished thediazo-pyrazolone 2 and the bis-pyrazole 3. The diazo trans-fer reaction was attempted under a variety of conditions(Table 2), but most of the experimental conditions

Table 1Crystal data and structure refinement data for 4-(5-hydroxy-4-pyrazolylimino)-2-pyrazolin-5-one (3) at room temperature and at 120 K

292 K data 120 K data

Formula C40H34N10O4 C40H34N10O4

Formula weight 718.77 718.77Wavelength (A) 0.71073 0.71073Crystal system, space group triclinic, P�1 triclinic, P�1Unit cell dimensions

A (A) 9.7844(13) 9.6488(5)B (A) 9.9517(12) 9.8123(6)C (A) 18.630(2) 18.4526(13)a (�) 80.677(3) 81.091(2)b (�) 84.281(3) 83.933(2)c (�) 88.120(3 87.039(5)

Volume (A3) 1780.9(4) 1715.18(18)Z, Calculated density (Mg/m3) 2, 1.337 2Absorption coefficient (mm�1) 0.091 0.094F(000) 752 752Crystal size (mm) 0.50 · 0.14 · 0.07 0.15 · 0.10 · 0.04h Range for data collection (�) 2.07–32.61 3.30–27.46Index ranges �14 6 h 6 13, �15 6 k 6 11, �28 6 l 6 27 �12 6 h 6 12, �12 6 k 6 12, �23 6 l 6 23Reflections collected/unique [Rint] 16661/12168 [0.0392] 20717/7307 [0.1437]Completeness to h (%) 27.50, 98.4 27.46, 92.8Absorption correction semi-empirical from equivalents empiricalTmax and Tmin 0.9281 and 0.7723 1.00855 and 0.99083Data/restraints/parameters 12166/0/499 7307/0/499Refinement method full-matrix least-squares on F2 full-matrix least-squares on F2

Goodness-of-fit on F2 0.855 0.885Final R indices [I > 2r(I)] R1 = 0.0703, wR2 = 0.1178 R1 = 0.0697, wR2 = 0.1099R indices (all data) R1 = 0.2748, wR2 = 0.1577 R1 = 0.2593, wR2 = 0.1570Largest peak and hole (e/A3) 0.199 and �0.190 0.270 and �0.281

Table 2Conditions used for the preparation of 2 and 3 by a diazo-transfer process:(1) + RN3 + Base! (2) + (3)

Entry 1

(mmol)RN3

(mmol)Base Solvent Diazo 2

(%)3

(%)

1 1 MsN3/0.9 Et3N CH2Cl2 81 22 1 MsN3/2.0 Et3N CH2Cl2 80 13 2 MsN3/1.0 Et3N CH2Cl2 834 1.0 MsN3/1.0 DMAP CH2Cl2 72 25 1.0 TsN3/1.0 Et3N CH2Cl2 636 1.0 TsN3/1.0 DMAP CH2Cl2 68 17 1.0 MsN3/1.0 K2CO3 CH2Cl2 868 1.0 MsN3/1.4 K2CO3 MeOH 55


provided the diazo-pyrazolone 2 in moderate to good yield(entries 1–7) with only traces of 3. However, when thediazo transfer reaction was performed in methanol, only3 was isolated in moderate yield (entry 8). Several otherconditions were tested but led mostly to 2. Mesyl azideappears to be a more convenient reagent than tosyl azidefor 3 (entries 1–7).

A different preparation of 3 was published by Hansel in1976 [26], following a much earlier article in 1887 [27].Hansel’s synthesis employed 5 and 2-pyrazolin-4,5-dione(6) [28]. However, as only the m.p. of 3 was given, we pres-ent herein selected spectral details for 3 as well as its crystalstructure.

Compounds 2 and 3 were characterized by IR, 1H, 13CNMR spectroscopies and ESI mass spectrometry. In the

IR spectrum of 2, the N@N absorption appears at2133 cm�1 and the C@O stretch at 1682 cm�1 [29]. IR spec-trum of 3 shows a reactively weak C@O absorption band at1729 cm�1, a cluster of bands between 2970 and 2850 cm�1,with maxima at 2922 and 2851 cm�1, the most intensebands in the spectrum, and a broad weak absorption bandcentered at 3400 cm�1. The NMR spectrum of 3 indicatesone set of chemical shifts for the two halves of the mole-cule. Of some significance is the d1H (OH) value in CDCl3solution at �50 �C of 17.95 ppm.

Usually, direct diazo transfers alpha to carbonyl are per-formed via reaction of sulfonyl azides on enolates [30,31].Without success, we attempted to convert diazo-pyrazolone2–3 under different reaction conditions. Therefore, weconclude that 3 must be formed from a different precursor.We speculate (Scheme 2) that 3 is produced by a secondattack of the pyrazolone carbanion (I) on the intermediate(II). Participation of intermediate (II) in other side reac-tions has already been reported [32].

3.2. Crystallographic data for 3

Fig. 1 shows the numbering scheme and atom arrange-ments for 3. As shown by the selected data in Table 3,the two independent molecules exhibit only subtle differ-ences in bond angles and lengths. Each molecule exhibitsextensive delocalization and overall the molecule exhibitsa structure almost midway between the two canonical

++

Et3NH+

Et3NH+

MsNHNH2

N

N

PhO

Me

NHMe

OPh

NN

N NMs

H H

OH

O

N

N

N N

N

Me

Ph

Me

Ph

N

N

Ph

O

Me

NN

NHMe

O

Ph

NN Ms

H

H

Et3N

N

N

Ph

O

Me

H

NN

NHMe

O

Ph

NN Ms

H

HEt3NH+

N

N

Ph

O

Me

H

N

N

NHMe

O

Ph

NN Ms

H

+

NN

Ph

O

Me H

MsNH2

Et3N

NN

Ph

O

MeN

N

N

Ms

H

NN

Ph

O

Me HN

N

N

Ms

H

Et3NH+

NN

Ph

O

Me HN

N

N

MsN

N

Ph

O

Me HN

N

N

Ms

MsN3

Et3N

Ms

N

N

NEt3NH+

NN

Ph

O

Me H

NN

Ph

O

Me

1

3 2

III

3

NN

Ph

O

Me N2

Et3NH+

Scheme 2. Proposed mechanism for formation of 3.

Fig. 1. Atom arrangements and the numbering scheme for the twoindependent molecules of 3; probability ellipsoids are dawn at the 30%level. Intramolecular hydrogen bonds are shown as dotted lines.

Table 3Selected bond lengths (A), and angles (�) for 3 (room temperature data)

C(11)–O(11) 1.290(3) C(31)–O(31) 1.279(3)C(11)–N(12) 1.344(3) C(31)–N(32) 1.349(3)C(11)–C(12) 1.435(3) C(31)–C(32) 1.441(3)C(12)–N(13) 1.330(3) C(32)–N(33) 1.319(3)C(12)–C(13) 1.440(3) C(32)–C(33) 1.442(4)C(13)–N(11) 1.304(3) C(33)–N(31) 1.304(3)C(13)–C(13) 1.490(3) C(33)–C(331) 1.493(3)N(11)–N(12) 1.407(3) N(31)–N(32) 1.418(3)N(12)–C(14) 1.432(3) N(32)–C(34) 1.425(3)

N(13)–C(22) 1.316(3) N(33)–C(42) 1.327(3)C(21)–O(21) 1.274(3) C(41)–O(41) 1.271(3)C(21)–N(22) 1.348(3) C(41)–N(42) 1.347(3)C(21)–C(22) 1.449(3) C(41)–C(42) 1.452(3)C(22)–C(23) 1.441(4) C(42)–C(43) 1.439(4)C(23)–N(21) 1.298(3) C(43)–N(41) 1.302(3)N(21)–N(22) 1.423(3) N(41)–N(42) 1.419(3)N(22)–C(24) 1.433(3)

O(11)–C(11)–C(12) 131.9(3) O(31)–C(31)–C(32) 131.4(3)N(13)–C(12)–C(11) 134.7(2) N(33)–C(32)–C(31) 135.4(3)C(22)–N(13)–C(12) 133.9(2) C(32)–N(33)–C(42) 134.6(2)O(21)–C(21)–C(22) 130.7(3) O(41)–C(41)–C(42) 131.1(3)N(13)–C(22)–C(21) 135.5(3) N(33)–C(42)–C(41) 134.8(3)

O(11)–H(21) 1.28(4) O(31)–H(41) 1.23(4)O(21)–H(21) 1.15(4) O(41)–H(41) 1.20(4)

O(11)–H(21)–O(21) 170(4) O(31)–H(41)–O(41) 175(3)C(11)–O(11)–H(21) 112.9(16) C(31)–O(31)–H(41) 114.4(15)C(21)–O(21)–H(21) 115.4(18) C(41)–O(41)–H(41) 115.4(15)


forms IIIA and IIIB, Scheme 3, with a very strong, nearlinear O–H–O hydrogen bond closing a 8-membered cen-tral ring (see values in Table 3). This situation is similarto those found in several 3-aryl-pentane-2,4-diones, inwhich the 6-membered rings in the enol tautomers areremarkably symmetrical and with O-- -O distances of ca.2.4–2.5 A [33]. The C–O bond lengths in the two indepen-dent molecules of 3 are in the region 1.271(3)–1.290(3) A –values between those expected for single and double bonds.Neither of the two molecules has a plane of symmetry inthe solid state, but as shown by the single set of chemical

O

N

O

NN N

NPh

Me Me

PhH

O

N

O

NN N

NPh

Me Me

PhH

O

N

O

NN N

NPh

Me Me

PhH

IIIA IIIB

3

N

HN N

NO

N

OHCu

Cl Cl

PhPh

MeMe4

N

N NH

NHO

N

OCu

Cl Cl

PhPh

MeMe

Scheme 3. Structures of 3 and 4.


shift values for the atoms in the diazole rings in each of the1H and 13C NMR spectra, in solution the molecule issymmetrical.

Further intramolecular C–H-- -O and C–H-- -N hydro-gen bonds (Fig. 1) provide extra rigidity to the structureof 3. Intermolecular interactions involve both the C16-H16- - -O11i hydrogen bond, which forms a dimer centredon (0.5,0.5, 0.5) with motif R2

4ð10Þ, Fig. 2, (symmetry oper-ation: i: �x + 1, �y + 1, �z + 1) and p� � �p interactionswhich lead to a ‘‘chain’’ of molecules along [100] as seenin Fig. 3. These involve the rings defined by N41–N42–C41–C42–C43 and C24–C25–C26–C27–C28–C29. Thereare also p� � �p interactions between the two molecules ofthe asymmetric unit.

Finally, the IR spectrum of 3 in KBr discs exhibits onlya medium intensity band in the carbonyl region, at1728 cm�1.

3.3. Copper complex 4

The complex 4 was obtained by the 1:1 reaction of 3

with copper(II) perchlorate hexahydrate in ethanol/aqueous HCl at pH 4–5, as tiny red-brown crystals. Whilein Scheme 1, complex 4 is drawn as a localized structure, itis considered much more likely to exist as a tautomericcompound, as shown in Scheme 3. Since suitable crystalsfor X-ray structure determination could not be grown, dif-ferent spectroscopic techniques have been employed tocharacterize this complex. Confirmation of the presenceof copper in the complex 4 came both from ESI-MS-(/MS) data and from UV/Vis and EPR spectra.

The ESI mass spectrum of an acetonitrile solution of 4

reveals a cluster of four major isotopologue ions of m/z463, 464, 465, and 466 with abundance ratios of

Fig. 2. Intra- and inter-molecular hydrogen bonds, shown as dotted lines,within the unit cell of 3 showing formation of a dimer. Geometricparameters are included as Supplementary Material.

Fig. 3. p–p Interactions in 3, forming a ‘‘chain’’ of molecules along [100].

1:0.26:0.48:0.12 that is expected for a mono-nuclear Cuspecies of formula [C22H20N6O2Cu]+, i.e., ion 4A (Scheme4), a chloride free Cu(I) complex coordinated to a singleacetonitrile ligand. Collision-induced dissociation of the63Cu-isotopologue ion of m/z 463 shows that 4A dissociatesmainly by the loss of acetonitrile to form 4B of m/z 422,and subsequently by the loss of a neutral species of

O O

NNN N

N

CH3CH3

Cu

H3CCN

m/z 463 (63Cu)

O O

NNN N

N

CH3CH3

Cu H

m/z 422( 63Cu)

- CH3CN

CID

4A 4B

H

- 63CuOH

m/z 342

O

N

NN N N

CH3H3C

Scheme 4. Dissociation patterns for the singly charged ions of m/z 463from ESI-MS/MS of 4.

200 400 6000.0

0.5

1.0

1.5

2.0

2.5

f

a

Abs

orba

nce

λ, nm

λ, nm200 400 600

0

1

2

3

g

a

Abs

orba

nce

A

B

Fig. 4. Electronic spectra of: (A) compound 3 and (B) complex 4 inCH3CN solution. For spectra in (A) a: 0.62 · 10�6, b: 1.0 · 10�5,c: 1.7 · 10�5, d: 0.29 · 10�4, e: 0.48 · 10�4, f: 0.80 · 10�4 mol dm�3. Forspectra in (B) a: 4.0 · 10�5, b: 0.81 · 10�5, c: 0.16 · 10�4, d: 0.32 · 10�4,e: 0.46 · 10�4, f: 0.65 · 10�4, g: 1.3 · 10�4 mol dm�3.


80 Da, 63CuOH, to form the fragment ion of m/z 342 ion.This last fragmentation provides evidence for Cu–O coor-dination in 4.

Conductivity measurements of solutions of 4 in CH3OHand in CH2Cl2, at 298 K, indicate a non-electrolyte. Mea-surements in water are unexpected low, probably due tothe very low solubility of this complex in aqueous solution.In the IR spectrum in KBr pellets, fail to observe strongbands near 1090 and 625 cm�1 suggests the absence ofnon-coordinated perchlorate ions. The addition of HCl tothe reaction mixture during the synthesis of 4 clearlyfavored the involvement of Cl� rather than ClO4

� in theisolated complex. The C, H, N elemental analyses of solid4 gave C, 48.28/48.62; H, 3.34/3.59; N, 13.74/14.60; Cu,11.88; Cl, 13.80%, which is in excellent agreement withthose expected for the complex, [LCuCl2], which requiresC, 48.54; H, 3.67; N, 14.15; Cu, 12.84; Cl, 14.33%.

Other evidence that copper(II) ion binds to ligand 3 viaoxygen atoms comes from the shift of the medium intensityband found at 1726 cm�1 in 3 to a much more intense bandat 1614 cm�1 in 4. Furthermore, the m(C@N) bands at1599 cm�1 for 3 and 1596 cm�1 for 4 suggest that Cu isnot coordinated to the imine nitrogens. The bands ataround 3074–2920 cm�1, for both 3 and 4, are assignedto m(Csp3–H) and m(Csp2–H), whereas the correspondingbending modes are observed in the 995–755 cm�1 range.

Analogously, a copper(II) complex with a new pyrazole-based ligand, Na[Cu(bdmpb)2(OOCCH3)H2O], whereHbdmpb = 1,3-bis(3,5-dimethylpyrazol-1-yl)-2-butanoicacid, has been recently prepared, and its crystal structuredetermined by X-ray analysis indicated that the nitrogenatoms of the pyrazole rings do not coordinate to the metalcenter. Instead, these nitrogen atoms are involved in strongintramolecular hydrogen bonds, and the copper ion iscoordinated by four nearly coplanar oxygen atoms [20].In this complex, as well as in our complex 4 there are

methyl substituents that provide some steric hindrancearound the nitrogen atoms in the pyrazole moiety.

Electronic spectra of 3 and 4 (Fig. 4) were obtained inCH3CN solution. The absorption bands for the ligand 3

were observed at 204, 240, 368 and 445 nm (see Section2). Analogous bands were observed for complex 4; how-ever, the maximum of the characteristic d–d band(T2g Eg) for 4 is probably hidden under the dominantand overlapping LMCT transition band, at 540 nm. Onthe other hand, spectral changes in aqueous solution of 4

at different pHs were also verified, by appropriate additionof either HCl or NaOH solutions (0.1 mol dm�3). TheLMCT transition band for 4, detected at 540 nm atpH P 5.5, shift to the maximum absorption correspondingto free ligand transition at 445 nm, in more acidic medium(Fig. 5A), with an isosbestic point at 475 nm. A concomi-tant variation of the solution color was observed, from yellowto purple. A plot of pH versus log [(A � Amin)/(Amax� A)],

2600 2800 3000 3200 3400 3600 3800

EP

R s

igna

l / a

.u.

Magnetic Field / G

Fig. 6. EPR spectrum of the copper(II) complex 4 (0.5 mmol dm�3), inCH3CN:H2O (8:1, v:v), at 77 K. Conditions: 2.83 · 104, receiver gain;15 G, modulation amplitude; 20.48 s, time constant; 8 scans.

400 450 500 550 600 650

0.40

0.45

0.50

0.55

f

a

f

a

Abs

orba

nce

λ, nm

-1.2 -1.0 -0.8 -0.6 -0.4 -0.2 0.0 0.2 0.4 0.6 0.84

5

6

7

8

9

10

pKa = 5.4

pH

log [(A-Amin

)/(Amax

-A)]

-0.2 -0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6

5

6

7

8

9

10

pKa = 5.8

pH

log [(A-Amin

)/(Amax

-A)]

A

B C

Fig. 5. (A) UV/Vis spectra of the complex 4 (20 lmol dm�3), in water, at different pH values (a–f): (a) 3.0; (b) 5.5; (c) 6.5; (d) 7.3; (e) 9.6; (f) 10.5. (B) Plotof pH versus log [(A � Amin)/(Amax � A)], at k = 440 nm. (C) Plot of pH versus log [(A � Amin)/(Amax � A)], at k = 540 nm.


where A = absorbance of the band at k = 440 nm (Fig. 5B)or at k = 540 nm (Fig. 5C), led to the calculation of apKa = (5.6 ± 0.2) as expressed simplistically below:

[LCu]2þ+ OH�� [LH�1)Cu]þ+ H2O Ka

Similar equilibria have been recently observed with isa-tin-Schiff base copper(II) compounds, and for these com-plexes different tautomers were isolated, depending on theligand [34]. On the other hand, the acid dissociation con-stants determined for acylpyrazolone derivatives indicateda pKa around 4 [35].

The EPR spectrum of 4 (Fig. 6) in frozen CH3CN:watersolution (8:1, v:v) shows a characteristic profile of an axialenvironment around the copper(II) center, with gi > g^.The EPR parameters were determined as Ai = 140.9 ·10�4 cm�1, gi = 2.389, A^ = 12.7 G and g^ = 2.077. Theempirical ratio gi/Ai has been used to evaluate tetrahedraldistortions in tetragonal structures of Cu(II) compounds,where a gi/Ai value close to 100 cm indicates a roughlysquare planar or tetragonal structure around the copper(II)ion, and values between 170 and 250 cm are indicative of a


distorted tetrahedral copper(II) symmetry [36]. Based onthese data, 4 exhibits a geometry closely to a distorted tet-rahedron from the gi/Ai value of 169 cm. Evidence for sub-stitution of chloride ligands by the CH3CN solvent wasobtained by inspection of EPR spectra. Duplication of cop-per hyperfine structure, gi = 2.375 and 2.343, with corre-sponding Ai = 149 and 163 · 10�4 cm�1, respectively, wasobserved at apparent pH P 7 (data not shown). Further-more, evidence of a gradual reduction of Cu(II) to Cu(I)(an EPR silent ion) was detected at higher pH values, withconsequent decreases in the intensity of the EPR signal,estimated by double integration of the bands, and concom-itant oxidation of the ligand, similarly to what occurs dur-ing the ESI-MS/MS experiment (see Scheme 4). Reductionto provide the stable [CuI(CH3CN)4]+ ion is a strong pos-sibility [37].

4. Conclusions

A new route to 4-(5-hydroxy-4-pyrazolylimino)-2-pyraz-olin-5-one, 3, is reported, via an one-pot diazo transfer reac-tion of pyrazolin-5-one (1). The structure of 3 has beendetermined by X-ray crystallography and by NMR. Bothin solution and in the solid state, 3 exhibits extensivedelocalization with a very strong near-linear, near-symmet-rical O–H–O hydrogen bond closing the central 8-memberedring. In the 1H NMR spectrum in CDCl3 solution the d1H(OH) value is 17.95 ppm. A mononuclear copper complex4 was obtained on reaction of 3 with copper(II) ions in eth-anol/water/HCl (pH 4–5) and structurally characterized asthe complex [LCuCl2], via elemental analysis, FT-IR, UV/Vis, EPR, ESI-MS, and ESI-MS/MS spectra. IR spectraprovided strong evidence for coordination of Cu(II) toligand 3 via the C–O groups, replacing the bridging H atom.EPR data indicated a distorted tetrahedral environment tocopper(II) ion. The pKa value of 4, determined by UV/Visspectroscopy, was calculated to be (5.6 ± 0.2).

Acknowledgements

This work was supported by the Brazilian agenciesCNPq, FAPESP and FAPERJ. Fellowships granted toGC (FAPESP), ABT (CNPq-PIBIC), HMM (CNPq-PI-BIC), and to AMCF, VFF, MNE and JLW (CNPq) aregratefully acknowledged. The authors thank the EPSRCX-ray Crystallographic Service, at the University of South-ampton, GB, for the low temperature data collection, andthe University of Aberdeen for funding the SMART CCDdiffractometer.

Appendix A. Supplementary material

Supplementary data are available from the CCDC, 12Union Road, Cambridge, CB2 1EZ, UK, fax: +44 1223366 033, e-mail: [email protected] or on the web www:http://www.ccdc.cam.ac.uk on request, quoting the Depo-sition Nos. 266268 (for room temperature data) and

266269 (for data at 120 K). Supplementary data associatedwith this article can be found, in the online version, atdoi:10.1016/j.poly.2006.01.002.

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