Synthesis and structural study of a series of amides derived from 4α- and 4β-amino-1-azaadamantanes as potential 5-HT3 receptor antagonists

Journal of Molecular Structure 509 (1999) 105–114 www.elsevier.nl/locate/molstruc

Synthesis and structural study of a series of amides derived from 4a- and 4b-amino-1-azaadamantanes as potential 5-HT3 receptor antagonists q I. Iriepa a,*, F.J. Villasante a, E. Ga´lvez a, J. Bellanato b a

Departamento de Quı´mica Orga´nica, Universidad de Alcala´ de Henares, Madrid, Spain b Instituto de Estructura de la Materia (CSIC), Serrano 121, 28006, Madrid, Spain Received 1 March 1999; accepted 29 March 1999

Abstract A series of amides derived from 4a-(2b–5b) and 4b-amino-1-azaadamantane (2a–5a) were synthesized and studied by IR, H, 13C, 2D NMR spectroscopy and NOE 1D experiments. The combined use of COSY, 1H– 13C correlation spectra and double resonance experiments helped in the unambiguous and complete assignment of the bicyclic carbon and proton resonances. IR, 1 H and 13C NMR data show the presence of an intramolecular N–H…O–CH3 hydrogen bond in compounds 3a and 3b. Moreover, the IR spectra of compounds 4a and 4b show a strong intermolecular hydrogen bond N–H (indole)…N. q 1999 Elsevier Science B.V. All rights reserved. 1

Keywords: Azaadamantane derivatives; Amides; IR Spectroscopy; NMR Spectroscopy

1. Introduction As a part of a research program aimed at the development of new antagonists for the 5-HT3 receptor [1], we are currently involved in studies in which the 1azaadamantane ring system is utilized as a conformationally restricted framework, bearing in mind the importance of conformational effects in the ligandbiological receptor interaction. Thus, a series of new amides derived from 4-amino-1-azaadamantane (1) have been synthesized. In this paper we report the

q

In honour of Professor Peter Klæboe on the occasion of his 70th birthday. * Corresponding author. Tel.: 1 34-91-8854651; fax: 1 34-918854686. E-mail address: [email protected] (I. Iriepa)

configurational study of compounds 2a–5a and 2b– 5b (Scheme 1) by IR and NMR spectroscopy. The unambiguous assignment of all bicyclic proton and carbon resonances was achieved by the combined analysis of 1H– 1H COSY, 1H– 13C correlation spectra, NOE 1D experiments, DEPT experiments and double resonance experiments. 2. Experimental The IR spectra for compounds 2a–5a and 2b–5b were recorded on a Perkin–Elmer FTIR 1725X spectrophotometer, assisted by a computer, in the solid state (KBr) in the 4000–400 cm 21 and in CDCl3 solution (0.07 M) in the 4000–900 cm 21 region using 0.2 mm NaCl cells. Spectra for very dilute CCl4 solutions were taken in the 4000–2500 cm 21 region with

0022-2860/99/$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. PII: S0022-286 0(99)00214-8

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Scheme 1.

4 cm quartz cells. The reported wave-numbers are estimated to be accurate to within ^3 cm 21. 1 H NMR spectra were recorded on a Varian UNITY-300 spectrometer (299.949 MHz). Spectral parameters included sweep width of 4000 Hz in 24 K memory and acquisition times of 3 s over 64 transients. Resolution enhancement using lb ˆ 20.80; gf ˆ 0.50 and gfs ˆ 0.20 was followed by zero filling into 32 K memory prior to Fourier transformations. The double resonance experiments involved the use of conventional irradiation. The 2D experiments were performed on a Varian UNITY-500 spectrometer, using standard pulse sequences and a sine bell window function was applied in both domains. The 13C NMR were obtained at 75.429 MHz on a Varian UNITY-300 spectrometer. The information

about the number of C-attached protons was obtained from DEPT experiments. 2.1. Synthesis Compounds 2a–5a and 2b–5b were prepared by reaction of the appropriate acid chloride with the epimeric mixture of 1 in dry pyridine. After 16 h stirring at room temperature a KOH solution was added and extracted with chloroform. The organic layer was separated, dried (sodium sulfate) and the solvent evaporated under reduced pressure. The solid obtained was chromatographed on silica gel (compounds 3–5) and basic aluminum oxide (compound 2) with the appropriate solvent system to separate the epimeric mixture of the desired amides 2a–5a and 2b–5b.

Table 1 1 H NMR chemical shifts (d , ppm) and multiplicities (J, Hz) for compounds 2a–5a at 300 MHz (abbreviations: brs, broad singlet; d, doublet; dd, doublet of doublets; m, multiplet; s, singlet; t, triplet) 2a a

3a a

4a a

4a b

5a a

H4 H2(9)ax

4.36 (m) 3.27 (d) JH2(9)ax –H2(9)eq ˆ 213.9 3.16 (brs) 3.09 (d) 2.06 (d) JH6(10)ax –H6(10)eq ˆ 212.6 2.14 (d) 1.85 (brs) 1.73 (brs) 6.37 (m)

4.43 (m) 3.27 (d) JH2(9)ax –H2(9)eq ˆ 213.9 3.14 (brs) 3.07 (d) 2.06 (d) JH6(10)ax –H6(10)eq ˆ 212.6 2.09 (d) 1.81 (brs) 1.69 (brs) 8.48 (d) JNH–H4 ˆ 6.2 – – – 6.98 (d) 7.44 (m) 7.08 (m) 8.20 (dd) – 3.98 (s)

4.49 (m) 3.56 (d) JH2(9)ax –H2(9)eq ˆ 213.2 3.22 (brs) 3.12 (d) 2.11 (brs)

4.30 (m) 3.54 (d) JH2(9)ax –H2(9)eq ˆ 213.0 3.23 (brs) 3.12 (d) 2.10 (d) JH6(10)ax –H6(10)eq ˆ 211.7 2.18 (d) 2.07 (brs) 1.86 (brs) –

4.39 (m) 3.28 (d) JH2(9)ax –H2(9)eq ˆ 213.2 3.15 (brs) 3.08 (d) 2.09 (d) JH6(10)ax –H6(10)eq ˆ 211.7 2.11 (d) 1.86 (brs) 1.71 (brs) 6.47 (m)

7.62 (brs)

– 8.10 (brs)

– 7.78 (m)

– 7.70 (m) 7.62 d(m) 7.49 d (m) 7.53 (m) –

– 8.06 (m) 7.16 (m) 7.16 (m) 7.42 (m) –

7.47 (m) 7.47 (m) 7.47 (m) 7.78 (m) – –

H8 H2(9)eq H6(10)ax H6(10)eq H3(5) H7 NH

NH (indole) – H2 0 7.62 (d) JH2 0 (6 0 )–H4 0 ˆ 1.8 – H3 0 H4 0 7.49 (t) H5 0 – H6 0 7.62 (d) – H7 0 CH3O –

2.11 (brs) 2.03 (brs) 1.87 (brs) 6.34 (m) c

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d (ppm)

a

In CD3Cl. In CD3OD. c Not determined. d These signals may be interchanged. b

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3. Results and discussion

Table 2 The 13C chemical shifts (d , ppm) for compounds 2a–5a

d (ppm)

2a a

3a a

4a b

5a a

3.1. NMR spectra

C8 C2(9) C4 C3(5) C6(10) C7 CyO C1 0 C2 0 C3 0 C4 0 C5 0 C6 0 C7 0 C8 0 C9 0 CH3O

58.8 53.2 53.5 30.8 35.9 26.0 164.5 137.8 125.5 135.5 131.4 121.4 125.5 – – – –

58.9 53.6 52.6 31.1 36.0 26.2 164.2 121.9 157.4 111.4 132.6 121.4 132.2 – – – 56.2

58.6 53.1 53.9 31.8 36.1 27.3 168.6 – 129.4 111.8 127.3 122.0 123.5 121.7 112.8 138.1 –

58.8 53.3 53.0 30.9 36.0 26.1 166.9 134.9 126.8 128.6 131.4 128.6 126.8 – – – –

The 1H and 13C NMR data of compounds 2a–5a and 2b–5b are shown in Tables 1–4. Assignments of proton resonances have been made on the basis of the literature data for 4-oxo-1-azaadamantane, 4a(b)hydroxy-1-azaadamantane [2] and 4a(b)-p-chlorobenzoyloxy-1-azaadamantane [3]. The configuration of C4 was confirmed by a series of NOE 1D experiments. In the case of 13C NMR assignments, substituent steric and electronic effects on 13C chemical shifts and signal multiplicity obtained from DEPT experiments were taken into consideration.

a b

In CDCl3. In CD3OD.

3.1.1. Spectral analysis 3.1.1.1. Compounds 2a–5a. To clarify the assignment of the signals and to deduce the proton magnetic

Table 3 The 1H NMR chemical shifts (d , ppm) and multiplicities (J, Hz) for compounds 2b–5b in CDCL3 at 300 MHz (abbreviations: brs, broad singlet; d, doublet; dd, doublet of doublet; m, multiplet; s, singlet; t, triplet)

d (ppm)

2b

3b

4b

5b

H4 H2(9)ax

4.38 (m) 3.20 (d) JH2(9)ax –H2(9)eq ˆ 213.4 3.15 (brs) 3.28 (d) 2.02 (m) JH6(10)ax –H6(10)eq ˆ 212.1 1.94 (m) 1.92 (m) 1.76 (brs) 6.33 (m) JNH–H4 ˆ 7.0

4.46 (m) 3.20 (d)

4.50 (m) 3.22 (d) JH2(9)ax –H2(9)eq ˆ 213.7 3.17 (brs) 3.29 (d) 2.12 (d) JH6(10)ax –H6(10)eq ˆ 213.2 1.98 (m) 1.98 (m) 1.72 (brs) 6.42 (d)

4.41 (m) 3.21 (d) JH2(9)ax –H2(9)eq ˆ 213.5 3.15 (brs) 3.28 (d) 2.04 (d)

– 7.62 (d)

– –

10.04 (brs) 7.79 (s)

7.78 (m)

– JH3 0 –H4 0 ˆ 8.1 7.49 (t) JH4 0 –H6 0 ˆ 1.8 – 7.62 (d) JH6 0 –H5 0 ˆ 7.7 – –

6.99 (d)

–

7.47 (m)

7.45 (m)

7.88 (m)

7.47 (m)

7.09 (m) 8.22 (dd)

7.26 (m) 7.26 (m)

7.47 (m) 7.78 (m)

– 4.00 (s)

7.43 (m) –

– –

H8 H2(9)eq H6(10)ax H6(10)eq H3(5) H7 NH NH (indole) H2 0 JH2 0 (6 0 )–H4 0 ˆ 1.8 H3 0 H4 0 H5 0 H6 0 H7 0 CH3O

3.14 (brs) 3.27 (d) 2.03 (d) 1.92 (d) 1.90 (brs) 1.66 (brs) 8.44 (d) JNH–H4 ˆ 7.7

1.94 (d) 1.95 (m) 1.68 (brs) 6.44 (m)

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Table 4 The 13C chemical shifts (d , ppm) for compounds 2b–5b

d (ppm)

2b a

3b a

4b b

5b a

C8 C2(9) C4 C6(10) C3(5) C7 CyO C1 0 C2 0 C3 0 C4 0 C5 0 C6 0 C7 0 C8 0 C9 0 CH3O

58.7 58.2 53.4 31.1 31.0 26.3 164.2 138.0 125.5 135.6 131.3 135.6 125.5 – – – –

58.8 58.3 52.6 31.3 31.3 26.5 164.1 122.1 157.5 111.4 132.6 121.5 132.3 – – – 56.2

58.8 58.3 52.5 31.4 31.3 26.4 164.8 – 128.8

58.6 58.1 52.8 31.0 31.0 26.2 166.8 135.0 126.8 128.6 131.44 128.6 126.8 – – – –

a b

124.4 121.7 122.8 119.2 112.4 136.7 –

In CDCl3. In CD3OD.

parameters, double resonance experiments in deuteriochloroform for compound 3a were performed at 300 MHz. By irradiation of the H4 signal (4.43 ppm), the doublet at 8.48 ppm simplifies to a singlet and, therefore, this signal can be assigned to the NH. The broad singlet at 1.81 ppm is also affected, and this fact permits to assign this signal to H3(5). By saturation of the signal at 3.27 ppm, the doublet at 3.07 ppm simplifies to a singlet. Taking into account the anisotropic and steric effects exerted by the amide group, the signal at lower field has been

Fig. 1. Relevant NOE enhancements used to prove the position of the amide group in compound 2a.

Fig. 2. Compound 3a showing an intramolecular hydrogen bond.

assigned to H2(9)ax and the signal at higher field at H2(9)eq. On saturation the signal assigned to H2(9)eq (3.07 ppm) the doublet at 3.27 ppm (H2(9)ax) collapses to a singlet and the multiplet at 4.43 ppm (H4) collapses to a doublet of triplets with splittings of 2.8 and 7.5 Hz because of their couplings with H3(5) and the NH. The simplification of the signal of H4 is due to the loss of a W long-range coupling (1.5 Hz). This last coupling is the key to distinguish the a- from the b-amides. Saturation of the signal corresponding to H3(5) (1.81 ppm) simplifies the signal assigned to H4 and the signals at 2.06 and 2.09 ppm. These two last signals must correspond to H6(10)ax and H6(10)eq. The assigned stereochemistry has been unambiguosly confirmed by NOE 1D experiments in compound 2a. Fig. 1 shows the most relevant NOE enhancements used in these assignments. Bearing in mind the similarity of the 1H NMR spectra for the b-amides, and the double resonance experiments performed in compound 3a, a similar behavior can be assumed. This fact allows the complete and unambiguous assignment of the individual protons for the tricyclic system of b-amides (2a– 5a). The major difference between compound 3a and compounds 2a, 4a, and 5a is the chemical shift value for the amide proton. In compound 3a this signal appears as a doublet at 8.48 ppm while in compounds 2a, 4a and 5a appears at 6.37, 6.34 and 6.47 ppm, respectively. This fact is in agreement with the existence of an intramolecular hydrogen bond between the N–H and the oxygen of the methoxy group, forming a pseudo six-membered ring (Fig. 2). The chemical shift of the amide NH signal in CDCl3

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Fig. 3. Contour plot of the proton COSY-90 spectrum for compound 5b.

was independent of concentration, a result consistent with an intramolecularly hydrogen bonded structure. 3.1.1.2. Compounds 2b–5b. The 1H NMR spectra of a-amides 2b–5b are very similar. At 300 MHz in CDCl3 solution the signals due to the N–H, H4, H8, H2(9)ax, H2(9)eq and the aromatic protons appear well differentiated in all cases. The region of the spectra at 1.90–2.10 ppm is more complex and signals appear partially overlapped. In this region the H3(5), H6(10)ax and H6(10)eq signals appear. The assignment of all bicyclic proton and carbon resonances have been achieved through the application

of two-dimensional NMR techniques –homonuclear (COSY-90) and heteronuclear 1H– 13C correlation spectroscopy-, double resonance experiments and NOE 1D experiments. Fig. 3 shows the contour plot of the proton COSY90 spectrum for compound 5b. The interpretation of this spectrum is based on the unambiguous assignment of the signal at lower field in the aliphatic region to H4. The analysis of the COSY (Fig. 3) reveals the correlation between H4 and the signals centered at 6.45 and 1.94 ppm that correspond to the N–H and H3(5), respectively. The observed correlation between H3(5) and the

I. Iriepa et al. / Journal of Molecular Structure 509 (1999) 105–114

Fig. 4. Relevant NOE enhancements used to prove the position of the amide group in compound 2b.

doublets at 3.28 and 3.21 ppm leads to the assignment of these signals to C2(9) protons. The differentiation between the signals corresponding to H2(9)ax and H2(9)eq is based on the NOE enhancements. Saturation of the H4 proton shows a NOE enhancement on the signal at 3.21 ppm, and consequently, we can assign this signal to H2(9)ax and the doublet at 3.28 ppm to H2(9)eq. The singlet at 3.15 ppm is assigned to C8 protons owing to the shape and chemical shift value. The observed correlation between H8 and the singlet at 1.68 ppm leads to the assignment to H7. The COSY connectivity patterns show correlation between the signal corresponding to H7 and the doublets centered at 2.04 and 1.94 ppm; hence, we can assign these two signals to the C6(10) protons. The differentiation between the signals corresponding to H6(10)ax and H6(10)eq is based in the observed correlation between the signal centered at 3.21 ppm with that centered at 2.04 ppm, attributed to the W long-range coupling between H2(9)ax and H6(10)ax. The H6(10)ax and H6(10)eq are distinguished by double resonance experiments (DR). Thus, the saturation of the multiplet centered at 3.21 ppm corresponding to

111

Fig. 5. Compound 3b showing an intramolecular hydrogen bond.

H2(9)ax simplifies the signal at 2.04 ppm into a sharper doublet showing the loss of a small “W” long-range coupling. There is not doubt, therefore, about the assignment of the resonance at 2.04 ppm to H6(10)ax. Further interpretation of DR experiments confirms the above considerations about the assignment of the signals. The assigned stereochemistry has been unambiguosly confirmed by NOE 1D experiments in compound 2b. Fig. 4 shows the most relevant NOE enhancements used in these assignments. In a-amides (2b–5b), as in the case of b-amides (2a–5a), the chemical shift value for the amide proton is 8.44 ppm for compound 3b and 6.33, 6.42 and 6.44 ppm for compounds 2b, 4b and 5b, respectively. This fact is in agreement with the existence of an intramolecular hydrogen bond between the N–H and the oxygen of the methoxy group, forming a pseudo six-membered ring (Fig. 5). For the assignment of the 13C NMR chemical shifts, the similarity of the spectra for the compounds 2b– 5b, the analysis of the DEPT experiments performed in all cases and the HETCOR spectrum of 5b (Fig. 6) were taken into consideration. Moreover, the heteronuclear 1H– 13C correlation spectrum confirms the previous proton assignments.

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Fig. 6. The 1H– 13C correlation spectrum for compound 5b.

3.1.2. Conformational study By comparison of a- and b-amides we can conclude that: Dd C2(9)(a-amides)–C2(9)(b-amides) ,5 ppm C6(10)(b-amides)–C6(10)(a-amides) and Dd ,5 ppm are attributed to the anisotropic and steric syn-diaxial effect exerted by the N–H group on H2(9) and H6(10) respectively. The Dd H2(9)ax(bamides)–H2(9)ax(a-amides) ,0.07 ppm and Dd H6(10)ax(a-amides)–H6(10)ax(b-amides) ,0.04 ppm are explained in the same way. d H2(9)eq(a-amides) . d H2(9)eq(b-amides) and d H6(10)eq(b-amides) . d H6(10)eq(a-amides); this is attributed to the W arrangement of the equatorial

proton with respect to the electron-withdrawing group. 3.2. Infrared spectra Data for the infrared spectra of amides 2a–5a and 2b–5b in the N–H and double bond stretching regions are included in Table 5. 3.2.1. Compounds 2a and 2b Compound 2a in the solid state presented a medium to strong band at 3290 cm 21 which upon dilution shifted to 3446 in CDCl3 (0.07 M) and to 3452 cm 21 in CCl4 (0.0005 M), indicating the presence of

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Table 5 Infrared frequencies (cm 21) of compounds 2–5 (abbreviations: s, strong; m, medium; w, weak; sh, shoulder, v, very; br, broad) Compound

Medium

n (N–H) Free

2a

KBr

3290 s 3446 vw

CCl4 KBr

3452 vw

CDCl3

3447 vw

3330 vw

3454 vw

4a

CCl4 KBr CDCl3 CCl4 KBr CDCl3 CCl4 KBr

3335 vvw 3400 s c 3402 m c 3417 m c 3391 s c 3405 m c 3419 m c 3283 s t 2150 d,e

4b

KBr

3a

3b

5a

5b

3331 s

3467 m-s

CCl4 KBr

3479 s

CDCl3

3451 w

CCl4 KBr

3459 w

CDCl3

3454 w

CCl4

3461 w

Amide II

1643 sh 1625 vs 1663 s

1588 w a 1566 s-vs a 1588 vw a 1568 s-vs a

1540 s-vs

b

b

b

1590 w a 1564 s-vs a 1590 sh 1568 s-vs a

1537 vs 1508 vs

b

b

b

1653 vs 1646 vs

1599 m a 1601 m a

1537 s 1540 vs

b

b

b a

1603 m 1601 m a

1535 vs 1537 vs

b

b

b

1600 vs

1583 m d 1510 sh d 1579 m d 1508 s d 1578 w d 1501 vs d

1537 s-vs

1625 vs t 3210 br d t 3217 br d

1508 vs

1643 sh 1628 vs 1663 s

1653 vs 1644 vs

f

CDCl3

Ring

Bonded

CDCl3

2b

Amide I

1638 vs b

1535 vs 1545 vs

t 3175 br d 3343 m

b

1632 vs

–

1654 vs b

b

b

3315 m

1654 w 1636 vs 1655 vs

1602 vw a 1579 w a 1603 vw a 1580 w a

1534 s-vs

b

b

b

1601 vw 1578 w a 1602 w a 1580 w a

b a

1526 s-vs 1514 vs

1574 vs

a

Aromatic ring. Not measured. c Intramolecular bond. d Heterocycle. e Transmission maximum of the double band system. f Not assigned. b

intermolecular hydrogen bonding in the solid. In the carbonyl region compound 2a showed two strong bands at 1625 and 1540 cm 21 which are respectively assigned to the amide I and amide II bands. The amide I band changed from 1625 to 1663 cm 21 upon dilution in CDCl3, thus indicating that CyO groups are implicated in hydrogen bonding with the N–H groups. Results for compound 2b in the n (N–H) region

indicate that the hydrogen bond is weaker than in epimer 2a. Results in carbonyl region are similar. The weak absorption observed at 3330–3335 cm 21 even at high dilution in CCl4 solution reveals the presence of intermolecular bonding in solution. 3.2.2. Compounds 3a and 3b Contrary to the spectroscopic results obtained for

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2a and 2b, in the case of compounds 3a and 3b, the n (N–H) and the amide I CyO band did not change much upon dilution in CDCl3 solution suggesting the existence of intramolecular bonding, most probably with the vicinal OCH3 group (N–H…O). This conclusion agrees with that obtained from NMR results described above. 3.2.3. Compounds 4a and 4b The infrared spectrum of compound 4a in the solid state is characterized by the presence of two broads bands at about 2640 and 1885 cm 21 with the transmission maximum of the double bond system at about 2150 cm 21. As interpreted in the cases of some azabicyclospirohydantoins [4–6], these absorptions are attributed to Fermi resonance of n (N–H) with overtones and/or combination frequency modes, the phenomenon indicating the existence of a strongly hydrogen-bonded system. In the present case the strong intermolecular hydrogen bond is formed between the indole N–H group and the basic nitrogen of the azaadamantane (N–H…N). The low solubility of compound 4a, probably due to the existence of strong intermolecular bonding, did not allow to study it in solution in CDCl3 and CCl4. Compound 4b presented a broad absorption centered at about 3210 cm 21 in the solid state which did not change much in solution and is also assigned to strong hydrogen bonding N–H…N. The existence of this bond could also be deduced from 1H NMR results in CDCl3.

3.2.4. Compounds 5a and 5b These compounds presented a spectroscopic behavior similar to that of compounds 2a and 2b (see Table 5). The spectra in the solid state revealed the presence of intermolecular bonding between N–H and amide CyO groups which disappeared in dilute solution. In the present case this bond is stronger in 5b.

Acknowledgements We thank the University of Alcala´ de Henares (Grant UAH-035/96) for partial support of this research.

References [1] B.A. Whelan, I. Iriepa, E. Ga´lvez, A. Orjales, A. Berisa, L. Labeaga, A.G. Garcı´a, G. Uceda, J. Sanz-Aparicio, I. Fonseca, J. Pharm. Sci. 84 (1995) 101. [2] E. Ga´lvez, M.J. Ferna´ndez, J.A. Soler, I. Iriepa, A. Lorente, J. Heterocylic Chem. 26 (1989) 307. [3] E. Ga´lvez, M.J. Ferna´ndez, A. Lorente, J.A. Soler, F. Florencio, J. Sanz-Aparicio, J. Heterocylcic Chem. 26 (1989) 349. [4] J. Bellanato, C. Avendan˜o, P. Ballesteros, M. Martı´nez, Spectrochim. Acta 35A (1979) 807. [5] J. Bellanato, E. Ga´lvez, M. Espada, G.G. Trigo, J. Mol. Struct. 67 (1980) 211 and references therein. [6] J. Bellanato, E. Ga´lvez, J. Mol. Struct. 101 (1983) 105.