Molecular Structure and Photoinduced Intramolecular Hydrogen Bonding in 2-Pyrrolylmethylidene Cycloalkanones

Article abstract of DOI:10.1021/acs.joc.5b01604

The structures of pyrrolylmethylidene derivatives of 2,3-dihydro-1H-inden-1-one (3), 3,4-dihydro-naphthalen-1(2H)-one (4), and cycloalkanones (5-7) were studied for the first time in the solid state and solution by NMR, IR, and UV spectroscopies supported

Full text of DOI:10.1021/acs.joc.5b01604

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Article
Molecular structure and photoinduced intramolecular
hydrogen bonding in 2-pyrrolylmethylidene cycloalkanones
Mark Sigalov, Bagrat A. Shainyan, Nina N. Chipanina, Larisa
P. Oznobikhina, Natalia Strashnikova, and Irina Sterkhova
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b01604 • Publication Date (Web): 12 Oct 2015
Downloaded from http://pubs.acs.org on October 15, 2015
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Molecular structure and photoinduced intramolecular
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hydrogen bonding in 2ꢀpyrrolylmethylidene cycloalkanones
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a)
b)
b)
b)
Mark Sigalov,* Bagrat Shainyan, Nina Chipanina, Larisa Oznobikhina,
a)
b)
Natalia Strashnikova , Irina Sterkhova
Department of Chemistry, BenꢀGurion University of the Negev, 84105 BeerꢀSheva,
a)
Israel, msigalov@bgu.ac.il
b)
A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Division of Russian Academy of
Sciences, 664033 Irkutsk, Russia
Abstract
The structure of pyrrolylmethylidene derivatives of 2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3) , 3,4ꢀ
dihydroꢀnaphthalenꢀ1(2H)ꢀone (4) and cycloalkanones (5–7) was studied at the first time
in solid state and in solution by NMR, IR and UV spectroscopy supported by DFT
quantum mechanical calculations. It was shown that all studied compounds except
cycloheptanone derivative 7 both in crystal and in solution exist in the form of dimers
where single Eꢀ or E,Eꢀconfiguration with respect to the exocyclic C=C bond is stabilized
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by intermolecular hydrogen bonds NꢀHꢀO=C. UVꢀirradiation at wavelength 365 nm
of MeCN or DMSO solutions of 3ꢀ6 results, depending on the exposition time and
solvent, in partial to complete isomerization to the Zꢀ or Z,Eꢀisomers (in the case of 6,
also the Z,Zꢀisomer). The NMR and IR spectroscopy data show the existence of a
strong intramolecular hydrogen bond NꢀHꢀO=C in the Zꢀmoieties of isomerized
compounds. The studied compounds are protonated by trifluoroacetic acid at the
carbonyl oxygen, in spite of the reverse order of basicity and nucleophilicity of the
carbonyl group and the pyrrole ring. Investigation of the behavior of compound 6 with
respect to acetate and fluoride anions allows to consider it as perspective fluoride
sensor.
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INTRODUCTION
Chemistry of chalcones including their cyclic analogs 1 and crossꢀconjugated α, α’ꢀbisꢀ
(arylmethylidene) derivatives of cyclic ketones (dienones) 2 is an extensively growing
area at present time. Numerous representatives of these classes of unsaturated
compounds have a vast field of applications in biology, medicine, optics, rocket
engineering and as building blocks in the synthesis of heterocyclic compounds and
thermostable polymeric materials1–18. Their methods of synthesis, structure, physicoꢀ
chemical properties and characteristic reactions are summarized in the recent review 19.
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The main method of synthesis of 1 and 2 is the aldol condensation of cyclic ketones with
appropriate aldehydes in the presence of bases, Lewis acids and other miscellaneous
catalysts19. It is wellꢀknown that aldol condensation is a stereoselective process and its
products normally contain the double bond in the transꢀconfiguration 20–22. The same is
true for bis(arylꢀmethylidene)cyclanones 2, the most stable isomers of which are E,Eꢀ
isomers, as depicted in the Scheme above. The lower stability of Zꢀisomers was
explained by strong steric repulsion of aryl group and carbonyl oxygen23.
Surprisingly, among hundreds studies of arylꢀ and heteroaryl derivatives the pyrrole
analogs were undeservedly ignored: there are only two published papers 11, 24
mentioning enones 1 and 2, (Ar = 2ꢀpyrrolyl, n = 1,2). No structural information was
given.
At the same time, these compounds containing the pyrrole motif are of special interest
because possible formation of intramolecular hydrogen bond(s) can influence their
structure and isomeric composition by stabilization of the Zꢀisomers (Scheme 1):
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Scheme 1. EꢀZ isomerism of 2ꢀpyrrolylideneꢀcycloalcanones.
Recently, we have studied the properties of similar hydrogen bonds in the 2ꢀ
pyrrolylidene substituted 1,3ꢀundandione and its derivatives 25 . Besides, we have found
that these indandione derivatives can act as color sensors for fluoride and acetate
anions, and that this ability is based on deprotonation of the pyrrole NH group 26.
Here we report on the synthesis of the series of compounds 3–7 and the study of their
structure by Xꢀray (3–5), NMR and IR spectroscopy supported with DFT quantum
chemical calculations.
Results and Discussion
Synthesis
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Synthesis of compounds 3–7 was carried out by condensation of 1Hꢀpyrroleꢀ2ꢀ
carbaldehyde with corresponding cyclic ketones by heating at reflux in aqueous ethanol
in the presence of potassium hydroxide, as shown below.
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CH
2 n
CH
2 n
KOH
EtOH
+
NH
CHO
N
H
O
O
3 (n=1), 4 (n=2).
CH
2 n
CH2
n
KOH
EtOH
+
2
NH
HN
CHO
N
H
O
O
5 (n=1), 6 (n=2).
Scheme 2. Synthesis of studied compounds 3 ꢀ 6
The reaction of cyclopentanone or cyclohexanone with two equivalents of the aldehyde
during 3 h of heating results in the formation of a single product, the diadduct, whereas
cycloheptanone reacts in more complex way and much more slowly. The conversion
after 48 h reflux with 3ꢀfold excess of 2ꢀpyrrolylcarbaldehyde was 70% and 30% of the
starting aldehyde was recovered. In the reaction mixture four compounds were
identified: two monoadducts (Z)ꢀ and (E)ꢀ2ꢀ((1Hꢀpyrrolꢀ2ꢀyl)methylene)cycloheptanones
(7a and 7c, respectively) and two diadducts (2Z,7E)ꢀ and (2E,7E)ꢀ2,7ꢀbis((1Hꢀpyrrolꢀ2ꢀ
yl)methylene)ꢀcycloheptanones (7b and 7d, respectively). Compounds 7a and 7b
containing Zꢀmoieties were isolated by column chromatography on silica gel using
CH2Cl2 as an eluent. The mixture of 7c and 7d was not separated, but the structure of
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its components was unequivocally proved and the ratio determined by 1H and C NMR
5
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spectroscopy (vide infra).
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Scheme 3. Isolated products of reaction of cycloheptanones with 2ꢀpyrrolylaldehyde
Compounds 3–6 are highꢀmelting solids of yellow, orange or red color, obtained in a
good yield (up to 93%).
X-ray analysis
The Xꢀray data of compound 3 confirm the Eꢀconfiguration of the molecule (Fig. 1a). In
the crystal, of C2h symmetry are formed with NꢀH———O=C hydrogen bonds of 2.0210(13)
Å length (Fig. 1b). Molecule 3 is practically planar and the dimers are arranged in one
plane. Note a reduced contact of ca. 2.8 Å between the orthoꢀhydrogen atom of the
benzene ring of one molecule and the βꢀcarbon atoms of the pyrrole ring of the other
molecule of the dimer (Fig. 1c). The intersection angle between the planes of the
molecules is ca. 54˚ (Fig. 1с) leading to the soꢀcalled ‘parquet packing’ (Fig. 1d).
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a
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c
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Figure 1. The molecular and crystal structure of compound 3: molecular structure (a,
ORTEP, 50% probability contours), the ‘inꢀlayer’ Hꢀbonded dimer structure (b), the
‘betweenꢀlayer’ coordination (c), the ‘parquet packing’ in the crystal of 3 (d).
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Similar to compound 3, the molecules of compound 4 (Fig. 2a) form dimers in the crystal
(Fig. 2b). Unlike in compound 3, the molecules of 4 are not planar. The N–H———O=C
intermolecular hydrogen bonds in 4 are 0.05 Å shorter than in 3. The dimers form
lamellar structure with the interlamellar distance of 2.691 Å (Fig. 2c). The layers are
linked by weak interaction between one of the СН2 hydrogen atoms and the carbonyl
oxygen of the second molecule.
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b
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Figure 2. The molecular and crystal structure of compound 4: molecular structure (a,
ORTEP, 50% probability contours), the ‘inꢀlayer’ Hꢀbonded dimer structure (b), the
‘betweenꢀlayer’ coordination (c).
According to Xꢀray data, the elementary cell of compound 6 contains two molecules with
the E,Eꢀconfiguration differing by orientation of the pyrrole rings to the rest of the
molecule, the orientation being the same in the 6ꢁE,Eꢁcis,cis conformation and the
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opposite in the 6ꢁE,Eꢁcis,trans conformation (Figure 3):
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6ꢁE,Eꢁcis,cis
6ꢁE,Eꢁcis,trans
Figure 3. Two conformations of 6ꢁE,E in the solid state
Asymmetric part of unit cell of compound 6 is shown in Fig. 4a. The structural motif of
the crystals includes four molecules connected by hydrogen bonds (Fig. 4b). The
oxygen atoms of the cis,cisꢀisomer form bifurcate hydrogen bonds with the NH groups of
the cis,transꢀisomer and another molecule of the cis,cisꢀisomer forming the tetramer
depicted in Fig. 3b. The hydrogen bond lengths are: N1–H———O2=C 2.0060(19) Å, N2–
H———O1=C 2.025(2) Å, N3–H———O1=C 2.0120(18) Å. Note, that the bifurcate bonds N2–
H———O1=C and N3–H———O1=C are expectedly longer than the twoꢀcentered hydrogen
bond N1–H———O2=C. Note also that the second NH group of the cis,transꢀisomer is not
involved in hydrogen bonding.
.
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a
b
Figure 4. The molecular and crystal structure of compound 6: asymmetric unit of
molecular structure (a, ORTEP, 50% probability contours), the Hꢀbonded tetramer
structure (b).
NMR spectroscopy study
According to 1H NMR spectra, the studied molecules retain their Eꢀconfiguration on
going from solid state to solution. The spectra of compounds 3–6 (Fig.S7ꢀS10 ) contain
the signal of the olefinic proton =CH at 7.3–7.9 ppm in CDCl3 or DMSOꢀd6 solution,
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which, in full agreement with the earlier observations 19 is indicative of the antiꢀ
orientation of the 2ꢀpyrrolyl substituent relative to the carbonyl group. The chemical
shifts of the NH proton of all compounds in CDCl3 solution lie in the range 8–9 ppm. In
DMSOꢀd6, due to formation of intermolecular hydrogen bond with solvent molecules, the
NH signal is shifted to approximately 11 ppm.
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Formation of hydrogenꢀbonded associates in solution, similar to the aboveꢀmentioned
solidꢀstate dimers, is also proved by 1H NMR spectra. Consecutive dilution of the CDCl3
solution of 3 (Fig. 5) results in a highꢀfield shift of the NH and =CH signals by 0.50 and
0.11 ppm, respectively, whereas all the rest of the signals remain unchanged. These
changes are a direct consequence of cleavage of the dimeric complex.
c)
9.00
8.50
8.00
7.50
7.00
6.50
b)
9.00
8.50
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7.00
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a)
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8.50
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ppm
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Figure 5. 1H NMR spectra of 3 in CDCl3. a) saturated solution; b) 3ꢀfold dilution; c) 10ꢀ
fold dilution.
6
7
8
9
The 1H NMR spectra of both the E,E and Z,Eꢀisomers of 6 in CDCl3 show similar
changes (see below), except that 10ꢀfold dilution of the saturated solutions leads to only
0.06 ꢀ 0.08 ppm displacement of the NH signal (Fig. S15 and S16). Due to the lower
solubility of 6 in CDCl3, the concentration of the dimer is much less than in the case of 3.
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Photo-induced Z,E-isomerization and hydrogen bonding
The ability of chalcones and their cyclic analogs for photoisomerization and
photodimerization is wellꢀknown in the literature 27ꢀ29
.
UV irradiation of the solutions of the Eꢀisomers of compounds 3, 4 as well as of the E,Eꢀ
isomers of compounds 5 and 6, leads to isomerization around the double bonds with the
formation of Zꢀisomers (for the first pair of compounds) and Z,E and Z,Zꢀisomers (for the
second one) containing intramolecular NHꢁꢁꢁO=C hydrogen bonds (Scheme 4):
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Scheme 4. The photoꢀisomerization products
5
6
7
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9
The main characteristic feature of the Zꢀisomers of all studied compounds is a lowꢀfield
signal of NH protons in the range 12–13 ppm, which is displaced downfield by 3–3.5
ppm relative to the signals in the Eꢀisomers, thereby indicating the existence of a strong
hydrogen bond N–HꢁꢁꢁO. On the other hand, the signal of the olefin proton in the Zꢀ
moiety, due to its remoteness from the carbonyl group, is displaced upfield by about 1
ppm.
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As an example, the 1H NMR spectrum of compound 3 after UV irradiation is given in Fig.
S17.
The structure of the Z,Eꢀisomers is proved by the appearance of two new signals of
pyrrolic NH protons (see Fig. 6 for compound 5) at 13.20 (intramolecularly hydrogen
bonded) and 11.56 ppm (intermolecularly Hꢀbonded with the solvent molecule); besides,
two sets of signals are observed belonging to the Eꢀpart and Zꢀpart of the molecule: six
signals of the pyrrole rings and two signals of olefinic protons at 7.40 (Eꢀpart) and 6.82
ppm (Zꢀpart).
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*
*
b)
*
*
*
*
*
*
*
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7.50
7.00
6.50
13.00
12.50
12.00
11.50
a)
13.00
12.50
12.00
11.50
7.50
7.00
6.50
ppm
ppm
Figure 6. 1H NMR spectra of 5 in DMSOꢀd6: a) without irradiation; b) after 3.5 hours of
UV irradiation at 365 nm. Nonꢀoverlapping signals of 5ꢁZ,E isomer are marked by
asterisks.
Formation of the Z,Zꢀisomer upon UV irradiation was observed for the cyclohexanone
derivative 6. Fig. 7 shows the 1H NMR spectrum of 6 in CD3CN after 3.5 h exposure at
365 nm wavelength. The mixture consists of 6ꢁE,Z isomer as the predominant
compound (about 90%) and 10% of the minor 6ꢁZ,Z isomer. The 6ꢁE,E isomer is not
observed. In another experiment, the isolated 6ꢁE,Z isomer was irradiated in CD2Cl2
solution for 2 h; the resulted mixture consisted of ca. 75% of 6ꢁE,Z and 25% of 6ꢁZ,Z
isomers, but the concentration of the latter compound was significantly diminished (to
10%) after standing overnight.
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The low content of the 6ꢁZ,Z isomer and its relatively quick reconversion is indicative of
its lower stability with respect to the 6ꢁZ,E isomer, in spite of expected stabilization by
the two intramolecular hydrogen bonds.
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*
*
c)
b)
3.00
ppm
2.50
2.00
13.0
12.0
11.0
10.0
9.0
ppm
*
*
*
*
a)
7.50
7.00
6.50
ppm
Figure 7. 1H NMR spectrum of 6 in CD3CN irradiated at 365 nm for 3.5 hours: a)
aromatic region; b) NH region, c) alkyl region. The signals of 6ꢁZ,Z are marked by
asterisks.
The isomerization process is strongly dependent on the nature of the compound and
solvent (Table 1). Thus, irradiation of the solution of 5 in DMSOꢀd6 during 6 hours results
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in conversion of only 9% of the 5ꢁE,E isomer to 5ꢁZ,E, whereas compound 6 under the
same conditions gives about 20% of 6ꢁZ,E isomer. Similarly, compound 3 in DMSO
isomerizes only partially (40% during 45 min of irradiation), whereas in acetonitrile
during the same exposition time the amount of isomerized compound is two times larger
(76%). For compound 6 in acetonitrile solution, isomerization is also fast: it almost
completely isomerizes after 2 hours of irradiation, and besides Z,Eꢀisomer (predominant)
some amount of Z,Zꢀisomer is also formed. On the other hand, the reverse
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transformation from Zꢀ to Eꢀisomers in acetonitrile solution is very slow (Table 1, Fig.
S9); it is worth to mention that the concentration of 6ꢁZ,E remains almost constant
during 10 days. Apparently, this is indicative of the twoꢀstep isomerization, Z,Z → Z,E
and Z,E → E,E, when the loss of concentration of the intermediate 6ꢁZ,E isomer in the
second step is compensated by its accumulation in the first step.
Table 1. Interconversion of isomers of 3, 5, and 6 subjected to UVꢀirradiationa).
3, CD3CN,
3, DMSOꢀ
Time after
irradiation
5, DMSOꢀ 6, DMSOꢀ
6, CD3CN, 2 hc)
45 minb)
d6, 45 min b)
d6, 6 hb)
d6, 6 h b)
0.76
0.51
0.43
0.40
0.33
0.29
0
0.09
0.20
0.82/0.013/0.16
0.83/0.022/0.14
0.84/0.025/0.13
0.84/0.04/0.11
24 hours
48 hours
72 hours
0.07
0.15
0.05
0.12
0.05
0.08
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0.38
0.27
0.05
96 hours
0.06
0.83/0.07/0.10
0.82/0.1/0.08
240 hours
9
a)
Substrate, solvent, and exposition time are indicated.
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b)
c)
Numbers represent the fraction of Zꢀisomer (for 3) or Z,Eꢀisomer (for 5 and 6).
Numbers represent the fractions of Z,Eꢀ, E,E – and Z,Zꢀisomer respectively (for 6).
The drastic solvent influence on the EꢀZꢀisomerization rates may have following
reasons. It is known that EꢀZ photoisomerization of transꢀstilbenes is slowing down on
going from nonꢀpolar solvents to polar ones 30. Besides, weakening of hydrogen bonds
in the excited states is a wellꢀdocumented phenomenon 31. In the case of studied
compounds 3–7 the hydrogenꢀbonded dimers break down under UV irradiation and the
monomer molecules are expected to isomerize more easily to more stable Zꢀisomers
(see below). The two effects may also act synergistically.
The chemical shifts of hydrogenꢀbonded NH deserve a special attention because they
are directly related to the strength of the hydrogen bond. The corresponding values of
NH chemical shifts are collated in Table 2.
Table 2. NH proton chemical shifts for Z, Eꢀisomers of 5ꢀ7
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CD2Cl2
DMSOꢀd6
5
6
7
8
δ (NHꢂO)
δ (NHꢂO)
Entry
δ (NH) free
δ (NH) free
9
intramol.
13.08
intramol.
13.20
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5ꢀZ,E
6ꢀZ,E
7ꢀZ,E
8.72
8.97
8.66
11.56
11.49
11.34*
13.02
12.80
11.80
11.34*
*Overlapping signal with integral intensity of 2H
From the comparison of the chemical shifts it unambiguously follows that hydrogen
bonds in compounds 5 and 6 are of equal strength and significantly exceed that in
compound 7 (corresponding chemical shift difference values are of 1.28 and 1.22 ppm).
For compounds 6 and 7, dissolution in DMSOꢀd6 results in that the initially weaker
hydrogen bond in cycloheptanone derivative 7 suffers a stronger weakening by the
action of DMSO than in 5 and 6. These findings will be discussed below in connection
with theoretical calculations.
Interaction with fluoride and acetate anions
In this section the behavior of the E,E and Z,Eꢀisomers of compound 6 in the presence
of tetrabutylammonium fluoride (TBAF) and acetate (TBAA) is described. Recently [26],
we have shown that 2ꢀpyrrolylidene derivatives of 1,3ꢀindandione in the presence of
these salts undergo NHꢀdeprotonation, which is accompanied by the change of the
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solution color from yellow to orange and by drastic changes in the 1H NMR spectra
indicating that the intramolecular hydrogen bond N–HꢁꢁꢁO in the neutral molecule is
replaced by the C–HꢁꢁꢁO hydrogen bond in the anion.
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O
O
O
X-
HX
O
N
N
O
O
H
N
H
X = F, AcO
Scheme 5. Interaction of 2ꢀpyrrolylideneꢀ1,3ꢀindandione with acetate and fluoride anions
This finding allowed us to consider these indandione derivatives as potential sensors of
fluoride and acetate anions 26. Based on close structural similarity of these compounds
and 2–6 one can expect the manifestation of anion sensor properties also for the last
series.
However, the addition of TBAA to DMSOꢀd6 solution of 6ꢁE,E revealed neither color
variations, nor noticeable changes in the 1H NMR spectrum, except for a downfield shift
of the NH signal from 11.5 to 13.5 ppm, indicating the formation of a hydrogen bond with
acetate ion.
In a similar manner behaves the 6ꢁZ,E isomer, which also does not change its color
upon addition of TBAA and shows almost the same variations in the 1H NMR spectrum
(a downfield shift of the free NH proton by 2.2 ppm. At the same time, the signal of
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intramolecular hydrogen bonded NH proton of the Zꢀmoiety remains almost unchanged
(Fig. 8).
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*
c)
14.0
13.0
12.0
11.0
10.0
9.0
8.0
7.0
6.0
ppm
*
b)
14.0
13.0
12.0
11.0
10.0
9.0
8.0
7.0
6.0
ppm
*
a)
14.0
13.0
12.0
11.0
10.0
9.0
8.0
7.0
6.0
ppm
Figure 8. 1H NMR spectra of 6ꢁZ,E in DMSOꢀd6: without (a)) and with consecutive
additions (b) and c)) of tetrabutylammonium acetate. The NH signal of Eꢀmoiety is
marked by asterisks.
In contrast, addition of TBAF to the solution of 6ꢁE,E in DMSOꢀd6 changes the color of
the solution from yellow to darkꢀred. Addition of TBAF has a slight effect on the 1H NMR
signals of aromatic and olefinic protons, but causes disappearance of the NH signal at
–
11.45 ppm and appearance of a characteristic triplet of HF2 at 16.1 ppm (J = 122 Hz)
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indicating the deprotonation of one of the pyrrole rings (Fig. S19). The other NH proton
is not observed, most probably because of fast exchange.
7
8
9
The similar color changes occur upon TBAF addition to DMSOꢀd6 solution of 6ꢁZ,E, but
the 1H NMR spectrum of 6ꢁZ,E in the presence of TBAF, apart from the appearing of the
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–
HF2 triplet at 16.1 ppm, is quite different (Fig. 9):
16.50 16.00 15.50 15.00 14.50 14.00 13.50
b)
8.00
7.50
7.00
6.50
13.00
12.50
12.00
8.00
11.50
a)
7.50
7.00
6.50
ppm
Figure 9. Aromatic and NH regions of 1H NMR spectra of 6ꢁZ,E in DMSOꢀd6 (a) and with
excess of Bu4NF (b).
The NH signal at 11.49 belonging to the Eꢀmoiety (hydrogen bonded with the solvent)
disappears whereas the signal of the intermolecularly bonded NH moves downfield to
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13.74 ppm which being compared with its chemical shift of 12.80 ppm in the neutral
molecule indicates the strengthening of the hydrogen bond in the anion:
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Scheme 6. Strengthening hydrogen bond NꢀHꢂO by anion formation
The signals of the olefinic protons of the E and Zꢀmoieties are shifted by 0.25 to low field
and by 0.3 ppm to high field respectively, the former one being broadened; the shifts of
other protons are less affected (Fig. 9).
Due to the difference in behavior of the studied compounds with respect to acetate and
fluoride anions (sharp color change in the last case) one can suppose that these
compounds possess a higher selectivity towards the fluoride ion than the earlier
described 1,3ꢀindandione derivatives 26.
IR spectroscopic study
In the IR spectra of compounds 3 and 4 in the solid state the intermolecular hydrogen
bonds NH⋅⋅⋅O=C are characterized by the νNH bands at 3269 and 3278 cm–1 and the
νC=O bands at 1674 (Figure 10) and 1651 cm–1, respectively. In CCl4 solution, these
bonds are partly dissociated and the spectrum contains both the above associated
bands and the bands of free C=O groups of 3 and 4 at 1697 and 1666 cm–1,
respectively. The doublet bands of vibrations of the free NH groups at 3496 and 3471
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cm–1 suggest the presence in the solution of two conformers of the Eꢀisomer with the
opposite orientation of the pyrrole ring. Complete dissociation of the NH⋅⋅⋅O=C hydrogen
bond occurs in solutions of 3 and 4 in CH2Cl2. The IR spectra of both compounds
contain doublet bands of free NH groups at 3490 and 3450 cm–1 each, and free C=O
groups at 1689 (3) and 1660 cm–1 (4).
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In the IR spectrum of the irradiated compound 3 in CH2Cl2 (Figure 10), along with the
bands belonging to the starting Eꢀisomer, an intense band at 1665 cm–1 is observed. Its
frequency is lower than that of the band of associated C=O groups appearing at 1674
cm–1 in the spectrum of solid compound. Appearance of this lowꢀfrequency ν(C=O) band
is related with the formation of the Zꢀisomer of compound 3 with the intramolecular
NH⋅⋅⋅O=C bond belonging to the category of strong resonanceꢀassisted hydrogen bonds
[32,33]. This explains the absence of the corresponding ν(NH) band in IR spectrum.
The IR spectrum of compound 5 in the solid state contains two lowꢀfrequency νNH
bands: an intense band at 3264 cm–1 and a weak band at 3377 cm–1. They correspond,
respectively, to vibrations of NH groups forming a twoꢀcenter hydrogen bond NH⋅⋅⋅O=C
and a less strong bifurcate (NH)2⋅⋅⋅O=C intermolecular hydrogen bond. The band of
vibrations of associated C=O groups appears at 1670 cm–1. In the spectrum of a diluted
solution of 5 in CH2Cl2 only the bands of free NH groups of the two conformational
isomers are observed at 3480 and 3450 cm–1 and the band of the free C=O group at
1704 cm–1.
Most strong intermolecular hydrogen bonds NH⋅⋅⋅O=C are formed in compound 6. As a
result, the ν(C=O) frequency in the IR spectrum of solid 6 is drastically decreased, so
that the ν(C=O) and ν(C=C) vibrations become mixed and are characterized by a
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common doublet band with maxima at 1589 and 1574 cm–1(Figure 10). In the ν(NH)
vibration range, weak bands at 3498 and 3471 cm–1 are observed, in agreement with the
presence of free NH groups in the conformers of E,E isomer of 6 differing by the N–C2'–
Cα–H angle (0 or 180º). Besides, a wide band is observed, with poorly resolved maxima
at 3254 and 3215 cm–1, belonging to vibrations of the associated NH groups. The
spectrum of a dilute solution of 6 in CH2Cl2 contains a single intense band at 1599 cmꢀ1,
apparently belonging to mixed vibrations ν(C=O) and ν(C=C). This may be indicative of
retention of the intermolecular NH...O=C hydrogen bonds in the dimer even upon dilution
in CH2Cl2.
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After UV irradiation in acetonitrile solution, the free C=O group band in the IR spectrum
of compound 6 in CH2Cl2 appears at 1702 cm–1 (Figure 10). According to the NMR data
(vide supra), irradiation results in the formation of the Z,E isomer. A low intense band at
1645 cm–1 in the spectrum is caused by the presence of a small amount of the
conformer with intramolecular hydrogen bond NH⋅⋅⋅O=C in the solution. Note, that in
CCl4 solution of 6 the low frequency ν(C=O) band becomes more intense than the band
of the free C=O group.
The IR spectrum of compound 5 in the solid state contains two lowꢀfrequency νNH
bands: an intense band at 3264 cm–1 and a weak band at 3377 cm–1. They correspond,
respectively, to vibrations of NH groups forming a twoꢀcenter hydrogen bond NH⋅⋅⋅O=C
and a less strong bifurcate (NH)2⋅⋅⋅O=C intermolecular hydrogen bond similar to that in
compound 6. The band of vibrations of associated C=O groups appears at 1670 cm–1. In
the spectrum of a diluted solution of 5 in CH2Cl2 only the bands of free NH groups of the
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two conformational isomers are observed at 3480 and 3450 cm–1 and the band of the
free C=O group at 1704 cm–1.
6
7
8
9
The IR spectrum of the CCl4 solution of compound 7, which is formed as a mixture of the
hydrogenꢀbonded and nonbonded conformers of the Z,E isomer directly from the
synthesis, without UV irradiation, contains two ν(C=O) bands – a weak one at 1703 cm–1
belonging to the nonbonded conformer and a more intense at 1644 cm–1 belonging to
the intramolecularly Hꢀbonded conformer.
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a
a
1581
1615
1589
1574
1674
b
b
1584
1689
1599
1622
c
c
1645
1584
1665
1689
1702
3
6
1586
1622
1700
1600
1700
1600
Wavenumber, cm-1
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Figure 10. IR spectra of compounds 3, 6 in the region 1800–1500 cm–1: a – solid
compounds in KBr, b – solutions in CH2Cl2, c – solutions in CH2Cl2 after UV irradiation.
6
7
8
Protonation
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The molecules of the studied compounds contain several potential sites of protonation –
the carbonyl oxygen and the pyrrole ring carbons Cꢀ3 and Cꢀ5. These sites have
different basicity and nucleophilicity: carbonyl oxygen is very weak base and can be
protonated only with strong acids like 96% sulfuric acid 34 or super acids 35. On the other
hand, the pyrrole ring due to its rather high basicity undergoes protonation even with
36,
relatively weak acids, for example trifluoroacetic (TFA) or HCl in nonꢀaqueous media
37. For the studied compounds, the site of protonation can be easily determined by H
1
NMR spectroscopy because the spectral patterns in the case of the pyrrolium cation
formation and protonation of the carbonyl oxygen should be quite different.
Upon addition of excess TFA to the solution of 6ꢀE,E in CD3CN the bright yellow color
1
turns deepꢀblue. In the H NMR spectrum the number of signals and their multiplicity
does not change but all of them are shifted to low field. Similar changes are observed in
13
the C NMR spectrum: both pyrrolic and olefinic carbon signals are shifted to low field
by 4–10 ppm, except the carbonyl carbon which shows a highꢀfield shift (Table 3). This
fact unambiguously indicates that protonation of compound 6 occurs at the carbonyl
oxygen atom. Addition of TFA to the solution of the isolated 6ꢁZ,Eꢀisomer also changes
the color to darkꢀblue and simultaneously the compound is completely isomerized to 6ꢁ
E,E. In the IR spectrum, the addition of TFA results in a gradual decrease (down to
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vanishing) of the ν(C=O) band at 1599 cm–1 and appearance of a very strong band of
protonated carbonyl group at 1553 cm–1.
6
7
8
9
Interaction of the monosubstituted analog of 6, compound 4, with TFA is visually
different from the previous one. The color of the acetonitrile solution changes from
yellow to orangeꢀred, and the variations of the chemical shifts are smaller (Table 3).
Compound 4 also undergoes the ZꢀE isomerization, the ratio (Z/E) being 1:6.
Interestingly, this ratio remains the same when TFA is added to the preliminarily
irradiated sample of 4 in CD3CN, in which the Zꢀisomer predominates. The observed
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1
13
lowꢀfield shift of the H and C signals of the pyrrolylmethyl moiety is notably less in 4
as compared to 6 (Table 3). It may be due to the fact that the incipient positive charge
appears on the benzylic (with respect to the phenyl group) carbon atom in 4 and,
therefore, is mainly stabilized by direct conjugation with the aromatic system. In 6, all
stabilization comes from donation from the two pyrrolyl groups, which results in larger
lowꢀfield shift of the corresponding signals.
Table 3. Effect of protonation on 1H and 13C NMR chemical shifts of compounds 4 and 6
4
6
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