Analysis of vibrational spectra of some new E- andZ-4-arylidene-3-isochromanones

Gabor Kereszturya,*, Sandor Hollya, Tom Sundiusb, Tamas Lorandc

aChemical Research Center, Hungarian Academic Science, P.O. Box 17, H-1525 Budapest, HungarybDepartment of Physics, University of Helsinki, P.O. Box 64, FIN-00014 Helsinki, Finland

cDepartment of Medical Chemistry, University Medical School of Pecs, H-7624 Pecs, Hungary

Received 31 August 2001; received in revised form 14 November 2001; accepted 14 November 2001

Abstract

The solid and vapor phase IR and the solid phase Raman spectra of partially or fully resolved E- and Z-isomers of seven

isochromanone derivatives were measured and analyzed with the aim of determining the differences in the vibrational behavior

of the main rotational isomers. To aid spectral interpretation, quantum chemical and normal coordinate calculations were carried

out for the 20-furyl-substituted derivative, codenamed IK-14. The optimized molecular structures and corresponding force fields

were calculated for four minimum energy configurations using the DFT/B3LYP/6-31� method. The vibrational frequencies and

IR intensities were then calculated and fitted to the measured ones by the SQM force field approach. The calculations were

highly successful in reproducing the frequencies and in clarifying the trends of changes brought about by cis–trans isomerism

and other conformational changes. This resulted in a detailed vibrational assignment, and a common set of scale factors

preferable for work with this type of molecules. # 2002 Elsevier Science B.V. All rights reserved.

Keywords: Vibrational spectra; DFT force field; Cis–trans isomerism; Rotamers; Isochromanones

1. Introduction

Recently, we have reported on our antifungal stu-

dies involving E-2-arylmethylene-1-tetralones, E-3-

arylmethylenechroman-4-ones and E-3-arylmethy-

lene-1-thiochroman-4-ones homoisoflavones [1].

These compounds were screened against human

pathogenic yeasts as Cryptococcus neoformans, Can-

dida albicans, etc. As a continuation of these studies

we extended our investigations to the isomeric 4-

arylmethylene-3-isochromanones to gain a deeper

understanding of the structure–activity relationships.

The title compounds were synthesized by base-

catalyzed aldol condensation (Scheme 1).

The reaction is usually stereospecific, providing

either the E- or the Z-isomer, but depending on the

aromatic aldehyde, it may occasionally yield a mixture

of the two isomers that can be separated by means of

column chromatography.

A systematic study of the FT-IR and FT-Raman

spectra of the rotational isomers of seven different aryl

derivatives ðAr ¼ 20-ð1-methylÞ-pyrrolyl, 20-pyrrolyl,

20,60-Cl2–C6H3, 20-Cl–C6H4, 20-NO2–C6H4, 20-furyl,

and 20-OH–C6H4) confirmed the structure of the pro-

ducts. However, due to the wide variety of the sub-

stituents and their many spectral features spread

throughout the spectrum, we had difficulties in estab-

lishing a firm relation between the spectra and the

Vibrational Spectroscopy 29 (2002) 53–59

* Corresponding author. Tel.: þ36-1-438-4141x228;

fax: þ36-1-325-7554.

E-mail address: kergabor@chemres.hu (G. Keresztury).

0924-2031/02/$ – see front matter # 2002 Elsevier Science B.V. All rights reserved.

PII: S 0 9 2 4 - 2 0 3 1 ( 0 1 ) 0 0 1 7 7 - 1

molecular conformation. The theoretical investigation

presented here is aimed at clarifying the spectral

manifestation of cis–trans isomerism and conforma-

tional changes of the substituent, beginning with the

smallest member of this family, the 20-furyl-substi-

tuted derivative, IK-14.

2. Methods

2.1. Experimental

The IR spectra of polycrystalline E- and Z-isomers

of IK-14 were recorded as KBr pellets in the 4000–

400 cm�1 region at 2 cm�1 resolution on a Nicolet

Magna 750 FT-IR spectrometer equipped with a

DTGS detector.

The vapor phase IR spectra were measured at

190 8C in the 4000–600 cm�1 region on a Nicolet

170sx GC/FT-IR system equipped with an MCT-A

detector, at a resolution of 4 cm�1. In the commercial

Nicolet GC/IR interface a 15 cm long, 1 mm i.d.

standard light pipe (an electrically heated, gold-coated

Pyrex tube with KBr end windows) was used as

sample cell, and the measurement was done ‘‘on-

the-fly’’ [2,3], at a flow rate of 6 cm3/min and nearly

atmospheric pressure, with helium used as carrier gas.

The sample in chloroform solution (60 mg/2.5 ml) was

introduced into the injector section of the gas chro-

matograph kept at 250 8C. After GC separation from

the solvent, 50 scans were accumulated from the

middle of the chromatographic peak of the sample

to be measured.

The Raman spectra of the polycrystalline powders

were measured at 2 cm�1 resolution by means of a

Nicolet 950 FT-Raman instrument equipped with a

liquid-N2-cooled Ge detector, using the 1064 nm line

of a Nd:YAG laser at 150 mW output power for

excitation.

2.2. Theoretical

Structure optimization (search for local minimum

with relaxation of all parameters) and calculation of

the corresponding vibrational frequencies and IR

intensities were carried out by means of the Gaus-

sian94 program package [4] for four stable conformers

of IK-14 (including two cis- and two trans-isomers) by

the density functional (DFT) method using B3LYP

type functionals and standard 6-31G� basis sets.

A full normal coordinate analysis was performed by

means of the MOLVIB program (written by Sundius

[5,6]). This included transformation of the raw DFT

force field to natural internal coordinates and scaling

the quadratic force field (according to Pulay’s method

[7]) by a set of scale factors (common to all molecular

configurations) refined in a least-squares procedure to

achieve a better agreement between the calculated and

observed frequencies. The force field obtained this

way was then used to recalculate the normal modes

and the corresponding theoretically expected IR inten-

sities to predict the full IR spectra.

3. Results

For IK-14, the DFT structure optimization gave two

stable conformations of each of the two structural

isomers, i.e. four stable configurations: Z1, Z2, E1,

and E2, depicted schematically in Fig. 1. The corre-

sponding torsion angles and energies obtained at the

DFT/B3LYP/6-31G� level of theory are listed in

Table 1. These ‘‘real’’ structures are not planar, due

to the non-planar B-ring containing a methylene group

with sp3 carbon atom (C7). Nevertheless, most atoms

of the molecule lie approximately in one of two planes

making an angle of about 308 with each other in all

four configurations. This is illustrated in Fig. 2 by the

example of the E1 configuration. One plane contains

Scheme 1.

54 G. Keresztury et al. / Vibrational Spectroscopy 29 (2002) 53–59

the six-membered aromatic A-ring and the methylene

carbon atom (C7), while the other comprises of the

furyl group together with the olephinic C=C bond; the

carbonyl group sticks out only a little from the latter

plane, while atom O8 is in-between the two planes.

The measured IR and Raman spectra of the resolved

E- and Z-isomers of IK-14 are shown in Figs. 3 and 4,

respectively. At first sight they seem almost identical,

but at closer examination a number of small differ-

ences (of 2–5 cm�1) can be observed in band positions

and somewhat greater variations in relative band

intensities. Perhaps the most apparent differences

can be found in the 1500–1300 cm�1 region, where

the Z-isomer has more prominent bands in the IR

spectrum than the E-isomer. Also, the intensity ratio of

the two strongest bands in the IR vapor spectra, the

n(C=O) near 1760 and the nas(C–O–C) at about

1140 cm�1 is considerably different in the two iso-

mers.

From the observed spectra alone it would be hard to

say anything about the influence of the internal rota-

tion of the furyl group on the normal modes and

frequencies. At this point theoretical calculations

stepped in. Comparison of the theoretically predicted

IR spectra of the four configurations to the measured

spectra showed the greatest discrepancies for the least

stable Z1 conformer (in which the furyl oxygen and

carbonyl oxygen atoms would come too close to each

other): it failed to reproduce the frequencies of the two

strongest IR bands satisfactorily, consequently, Z1 may

not be present in the vapor phase. At the same time, for

the lowest energy Z2 conformer an extremely good

frequency agreement was obtained with the measured

vapor spectrum.

For the E-isomer, an almost equally good agreement

was obtained for both conformers E1 and E2. Of the

latter two, E1 has an only slightly lower energy, while

E2 could be preferred on the grounds of a slightly

better fit of IR intensities. Thus, it seems probable that

these two conformers coexist in vapor phase, just as in

the crystal [8].

The calculated IR absorption spectra are compared

with the measured vapor spectra for the two lowest

energy configurations, E1 and Z2, graphically in Figs. 5

and 6, respectively. The calculated bands represented

by narrow bars are overlaid with the observed spec-

trum. It is apparent that the likelihood is very great

indeed, especially as far as the frequencies are con-

cerned: the rms frequency error of the calculation is

6.25 cm�1. This result was achieved in simultaneous

refinement of a common set of 11 scale factors (see

Table 2) for the two most stable conformers, E1 and Z2,

using 67 and 69 observed frequencies, respectively

(i.e. 136 frequency values in all) out of the possible

Fig. 1. Schematic pictures of the four minimum energy config-

urations of IK-14.

Table 1

Stable conformers of IK-14 and their energies calculated at DFT/B3LYP/6-31G� level

Conformer C13–C5 approximate configuration,

fft(C13–C12 ¼ C10–C5) (8)O17–C10 approximate configuration,

fft(O17–C13–C12 ¼ C10) (8)E (Hartree) DE (kcal/mol),

relative to Z2

E1 Trans, �171.98 Cis, 0.89 �765.155285468 1.218

E2 Trans, �170.62 Trans, �174.78 �765.153921075 2.074

Z1 Cis, �6.89 Cis, �4.83 �765.150582529 4.164

Z2 Cis, 1.34 Trans, 171.44 �765.157226950 0

G. Keresztury et al. / Vibrational Spectroscopy 29 (2002) 53–59 55

Fig. 2. Two projections of the optimized structure E1 to represent the spatial structure.

Fig. 3. Observed vibrational spectra of the E-isomer of IK-14: (A) vapor phase IR spectrum; (B) solid phase IR spectrum in KBr pellet; and

(C) FT-Raman spectrum of polycrystalline powder.

56 G. Keresztury et al. / Vibrational Spectroscopy 29 (2002) 53–59

Fig. 4. Observed vibrational spectra of the Z-isomer of IK-14: (A) vapor phase IR spectrum; (B) solid phase IR spectrum in KBr pellet; and

(C) FT-Raman spectrum of polycrystalline powder.

Fig. 5. Comparison of the measured gas phase IR spectrum of the E-isomer to the theoretically predicted IR spectrum of the E1 conformer of

IK-14.

G. Keresztury et al. / Vibrational Spectroscopy 29 (2002) 53–59 57

maximum of 75 per molecule. (Most of the missing

observed values belonged to low frequency torsional

modes and a couple of CH stretches).

At the same time, the relative band intensities were

not so well reproduced. A surprising weak point of this

calculation is that it does not yield the observed

medium-strong intensity for the band of the aromatic

C–H out-of-plane bending vibrations near 740 cm�1

(although there may be accidental degeneracy, i.e.

overlapping of bands there, which would increase

the calculated intensities compared to the bar plots

in Figs. 5 and 6). Note also that while the relative

intensities of the two strongest IR bands are not quite

well predicted by the calculation (in the Z2 conformer

the n(C=O) near 1760 cm�1 is calculated to be weaker

than the nas(C–O–C) near 1140 cm�1), the trends of

changes brought about by cis–trans isomerism

(namely, that in the E-isomer the n(C=O) band

becomes much more intense than in the Z-isomer)

are reproduced correctly.

There are many further fine details connected to

spectral changes brought about by isomerism and

conformational differences that we cannot discuss

here properly for lack of space. Detailed frequency

tables for the conformers studied and a more complete

analysis of the normal modes will be published else-

where.

4. Conclusion

Vibrational frequency and normal mode calcula-

tions based on scaled quantum mechanical (SQM)

force fields performed at the DFT/B3LYP/6-31G�

level of theory prove to be invaluable in clarifying

the fine spectral differences brought about by of cis–

trans isomerism and conformational changes in large

molecules like isochromanones.

Fig. 6. Comparison of the measured gas phase IR spectrum of the Z-isomer to the theoretically predicted IR spectrum of the Z2 conformer of

IK-14.

Table 2

Scaling factors used with the B3LYP/6-31� force field

Internal coordinates Scale factors

Initial [9] Refined

CH stretch (aromatic, olefinic) 0.920 0.918

CH stretch (furyl) 0.920 0.910

CH stretch (aliphatic) 0.920 0.912

C=O, C–O, C–C stretch 0.922 0.931

CH bend 0.950 0.939

CCC bend (aromatic, furyl) 0.990 1.000

C=O bend 0.990 1.022

bCCC 0.990 0.982

CH oop bend 0.976 0.977

C=O, CC oop bend 0.976 0.986

All torsionsa 0.935 0.935

a Excluded from refinement.

58 G. Keresztury et al. / Vibrational Spectroscopy 29 (2002) 53–59

Acknowledgements

The authors are grateful to Dr. Zoltan Pinter (Uni-

versity Medical School of Pecs) for GC–MS exam-

ination of the purity of the samples. G.K. is indebted to

Prof. G. Fogarasi for rendering of his program for

automatic construction of natural internal coordinates

to check some data. This work has been supported in

part by a research grant (OTKA T-034776) to G.K.

from the Hungarian Scientific Research Fund.

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