Conformational state of β-hydroxynaphthylamides: Barriers for the rotation of the amide group around CN bond and dynamics of the morpholine ring

Article abstract of DOI:10.1016/j.saa.2015.04.052

Three β-hydroxynaphthylamides (morpholine, pyrrolidine and dimethylamine derivatives) have been synthesized and their conformational state was analyzed by NMR, X-ray and DFT calculations. In aprotic solution the molecules contain intramolecular OHO hydrogen bonds, which change into intermolecular ones in solid state. The energy barriers for the amide group rotation around the CN bond were estimated from the line shape analysis of ¹H and ¹³C NMR signals. A tentative correlation between the barrier height and the strength of OHO bond was proposed. Calculations of the potential energy profiles for the rotations around CC and CN bonds were done. In case of morpholine derivative experimental indications of additional dynamics: chair-chair 'ring flip' in combination with the twisting around CC bond were obtained and confirmed by quantum chemistry calculations.

Full text of DOI:10.1016/j.saa.2015.04.052

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 149 (2015) 254–262
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Conformational state of b-hydroxynaphthylamides: Barriers
for the rotation of the amide group around CN bond and dynamics
of the morpholine ring
c
b
c
Tomasz Kozlecki a, Peter M. Tolstoy b, , Agnieszka Kwocz , Mikhail A. Vovk , Andrzej Kochel ,
⇑
Izabela Polowczyk a, Peter Yu. Tretyakov d, Aleksander Filarowski c,e,
⇑
a Wroclaw University of Technology, Faculty of Chemistry, Division of Chemical Engineering, 50-373 Wrocław, Poland
b St. Petersburg State University, Center for Magnetic Resonance, 198504 St. Petersburg, Russia
c Faculty of Chemistry, University of Wrocław, 50-383 Wrocław, Poland
d University of Architecture and Civil Engineering, 625001 Tyumen, Russia
e The Joint Institute for Nuclear Research, Frank Laboratory of Neutron Physics, 141980 Dubna, Russia
h i g h l i g h t s
g r a p h i c a l a b s t r a c t
ꢀ
Morpholine, pyrrolidine and
dimethylamine derivatives of
ortho-hydroxynaphthalene
(non-planar, OHO bonded).
ꢀ
ꢀ
ꢀ
Dynamic NMR study: CN rotation
barriers 13–19 kcal/mol.
Intramolecular OHO bond strength
influences CN rotation barrier height.
Morpholine chair–chair ‘ring flips’
(ca. 5 kcal/mol barrier) evidence by
1H NMR and DFT.
a r t i c l e i n f o
a b s t r a c t
Article history:
Three b-hydroxynaphthylamides (morpholine, pyrrolidine and dimethylamine derivatives) have been
synthesized and their conformational state was analyzed by NMR, X-ray and DFT calculations. In aprotic
solution the molecules contain intramolecular OHO hydrogen bonds, which change into intermolecular
ones in solid state. The energy barriers for the amide group rotation around the CN bond were estimated
from the line shape analysis of 1H and 13C NMR signals. A tentative correlation between the barrier height
and the strength of OHO bond was proposed. Calculations of the potential energy profiles for the rotations
around CC and CN bonds were done. In case of morpholine derivative experimental indications of addi-
tional dynamics: chair–chair ‘ring flip’ in combination with the twisting around CC bond were obtained
and confirmed by quantum chemistry calculations.
Received 18 March 2015
Received in revised form 14 April 2015
Accepted 16 April 2015
Available online 28 April 2015
Keywords:
b-Hydroxynaphthylamides
Amide group rotation
Intramolecular hydrogen bond
Conformational isomerism
Solvent effects
Ó 2015 Elsevier B.V. All rights reserved.
DNMR
Introduction
Conformational research of amide group has been of constant
⇑
Corresponding authors at: Faculty of Chemistry, University of Wrocław, 50-383
Wrocław, Poland (A. Filarowski).
scientific interest for many years because this type of formation
composes fragments of the peptide bond in proteins [1–4].
Conformational research of aryl amides has also attracted
E-mail addresses: peter.tolstoy@spbu.ru (P.M. Tolstoy), aleksander.filarowski@
chem.uni.wroc.pl (A. Filarowski).
http://dx.doi.org/10.1016/j.saa.2015.04.052
1386-1425/Ó 2015 Elsevier B.V. All rights reserved.

T. Kozlecki et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 149 (2015) 254–262
255
3-hydroxy-N,N-dimethylnaphthalene-2-carboxamide 3 (Scheme 2)
dissolved in various organic solvents. The experimental and
theoretical approaches used in this work are well-established and
applied here as a tool to study the new set of compounds.
a
b
R
R
O
R
R
N
R
R
O
N
O
N
O
H
OH
Materials and methods
O
H
Synthesis
ortho-hydroxyaryl
intra- and intermolecular
amide
hydrogen bonds
The studied compounds were synthesized under microwave
irradiation from methyl 3-hydroxy-2-naphthoate and an excess
of appropriate amine. The reactions were carried out using a
CEM Discover Synthesis Unit (CEM Corp., Matthews, NC) and per-
formed in 10 mL glass vessels sealed with a septum. The pressure
was controlled by a load cell connected to the vessel for an indirect
measurement. The temperature was monitored using a calibrated
infrared temperature control. The synthesis was carried out using
the magnetic stirring. Reaction progress was monitored using
c
d
R
R
O
R
R
O
N
N
OH
OH
CC rotaꢀon
CN rotaꢀon
chemical ionization mass spectrometry on
Engine, with methane as a reagent gas.
a HP 5989A MS
Scheme 1. Generalstructureofortho-hydroxyarylamides(a) andsomeof thepossible
dynamic processes: an equilibrium between intra- and intermolecular hydrogen
bonds (b) and rotation of the amide group around CC bond (c) or CN bond (d).
For the synthesis of 1 a mixture of methyl 3-hydroxy-2-naph-
thoate (501 mg, 2.48 mmol) and morpholine (1.5 mL) was placed
in the pressure vial and irradiated for 5 min at 175 °C/275 psi with
maximum microwave power set at 100 W. Reaction mixture was
cooled down, dissolved in chloroform (75 mL) and extracted first
with aqueous hydrochloric acid (3 Â 75 mL) and then with water
(2 Â 75 mL). Organic phase was dried over magnesium sulfate
and filtered, then the solvent was evaporated and the remaining
substance was purified by column chromatography (silica gel 60,
70–230 mesh; eluent: ethyl acetate). As some impurities were
detected by TLC, chromatography was repeated (silica gel 60, 70–
230 mesh; eluent: ethyl acetate-heptane, 1:1). Purified product
was recrystallized from methanol.
Synthesis of 2 was carried out as described above, using methyl
3-hydroxy-2-naphthoate (499 mg, 2.47 mmol) and pyrrolidine
(1.5 mL). A single chromatographic column (silica gel 60, 70–230
mesh; eluent: ethyl acetate) was sufficient to purify the product,
which was then recrystallized from methanol.
Synthesis of 3 was carried out in a similar fashion. A mixture of
methyl 3-hydroxy-2-naphthoate (499 mg, 2.47 mmol), dioxane
(2 mL) and 40% aqueous diethylamine (1.5 mL) was irradiated.
The purification was carried out as described above, single chro-
matographic purification (silica gel 60, 70–230 mesh; eluent: ethyl
acetate) was sufficient, after which the product was recrystallized
from methanol.
significant attention and such compounds can even be considered
one of the classical examples for study of conformational equilib-
rium [5–10] ortho-hydroxyaryl amides (‘a’ in Scheme 1) add to this
some complexity due to the ability of the OH group to form various
hydrogen bonds [11–14]. Such compounds are subject to several
dynamic processes: an equilibrium between intra- and intermolec-
ular hydrogen bonds (‘b’ in Scheme 1), and – similar to other
amides – rotation of the amide group around CC and CN bonds
(‘c’ and ‘d’ in Scheme 1) [15–20].
Note that ortho-hydroxyaryl amides do not exhibit intramolecu-
lar proton transfer despite the strong acid-base interaction between
the hydroxyl group and the carbonyl group of the amide [15]. A dif-
ferent situation is observed for ortho-hydroxyaryl Schiff [21,22],
Mannich bases [23,24] and ortho-hydroxy arylaza derivatives
[25–27] where the geometry of the intramolecular H-bond depends
to a great extent on the electron-donating and electron-accepting
properties of the substituents on the nitrogen atom and on the phe-
nolic moiety [28] However, these conformational transformations
are not characteristic for salicylamides. It has been proposed that
the most significant factor contributing to the conformational state
of salicylamides is the steric interaction between phenolic moiety
and bulky substituents of the amide group [15]. It is also needed to
be pointed out that the basicity of the amide nitrogen is generally
too low for the intramolecular OHN hydrogen bond to form with
the OH proton (after a 180° rotation around the CC bond).
DFT calculations
In this paper we present the synthesis and studies of three ortho-
hydroxynaphthalene amides by means of variable-temperature
NMR spectroscopy, X-ray diffraction and quantum-mechanical cal-
culations. The main goal is to study conformation and dynamics of
the (3-hydroxynaphthalen-2-yl)(morpholin-4-yl)methanone 1, (3-
Quantum mechanical calculations were carried out using
GAUSSIAN09 program [29] at the DFT (B3LYP) level of theory
[30,31] with the 6-31+G(d,p) basis set [32], suitable for the
H-bonded systems [33] potential energy profiles were calculated
by changing and fixing the corresponding angles in 10-degree
steps, and optimizing all other geometric parameters.
hydroxynaphthalen-2-yl)(pyrrolidin-1-yl)methanone
2
and
O
N
O
N
O
N
O
O
H
O
H
H
O
1
2
3
Scheme 2. Structures of ortho-hydroxynaphthyl amides studied in this work (the hydrogen bonded state and the non-planarity of the structures is discussed in the text).

256
T. Kozlecki et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 149 (2015) 254–262
X-ray diffraction studies of 1 and 3
and tetrahydrofuran-d8 were purchased from Prikladnaja Khimija
(Russia) and used without further purification. NMR measure-
ments were performed at the Center for Magnetic Resonance, St.
Petersburg State University. The 1H and 13C{1H} NMR spectra were
The intensity data were collected at 100 K using a X-Calibur
Ruby diffractometer and graphite-monochromated MoK
a
(0.71073 Å) radiation generated from an X-ray tube operating at
50 kV and 35 mA. The images were indexed, integrated, and scaled
using the Oxford Diffraction data reduction package [34]. The
experimental details together with crystallographic data for both
recorded on
a
Bruker Avance III 500 MHz spectrometer
(500.03 MHz for 1H, 125.73 MHz for 13C). The spectra were mea-
sured using the solvent peak as internal reference, and the chemi-
cal shifts were converted to the conventional TMS scale. The pulse
delay for 30° pulses was 1–2 s for 1H and 2 s for 13C{1H}
power-gated NMR spectra. The number of scans varied between
128–256 for 1H and 1024–4096 for 13C{1H} NMR spectra. Sample
temperature was stabilized with the precision of 1 °C. Spectra
were processed using Topspin 3.2 Software and line shape analysis
was performed using the built-in program DNMR and Origin 9.0.
compounds are given in Supplementary data (Table S1).
A
multi-scan absorption correction was applied. The structure was
solved by direct methods using SHELXS97 [35] and refined by
the full-matrix least-squares method on all F2 data (SHELXL97)
[36]. Non-hydrogen atoms were refined with anisotropic thermal
parameters; hydrogen atoms were included from
Dq maps and
refined isotropically. The Supplementary crystallographic data for
this paper are under CCDC No. 960172 for (3-hydroxynaphthale
n-2-yl)(morpholin-4-yl)methanone (1) and CCDC No. 960171 for
3-hydroxy-N,N-dimethylnaphthalene-2-carboxamide (3). These
data can be obtained free of charge via www.ccdc.cam.ac.
uk/conts/retrieving.html (or from the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 IEZ, UK: fax: (+44)
1123-336-033. e-mail: deposit@ccdc.cam.ac.uk).
Results and discussion
NMR spectroscopy is often a method of choice to study
H-bonding, specific molecular conformations and hindered inter-
nal
rotations
in
solution
[37–40].
For
example,
variable-temperature 1H, 13C and 15N NMR has been previously
successfully used to study hydrogen bond geometries in polar
aprotic environment [41,42], inter- and intramolecular proton tau-
tomerism [25,43], conformational isomerism [44,45] and other
phenomena. In this work we also start our discussion with the
temperature-dependent 1H and 13C NMR spectra of compounds
NMR measurements
Samples for NMR measurements were prepared by placing 8 mg
of substance (4 mg in case of poorly soluble compounds) in a stan-
dard 5 mm NMR sample tube and adding 0.7 mL of a solvent using
Eppendorf pipette. Deuterated solvents CDCl3, (CD3)2CO, CD3OD
1,
2
and
3
dissolved in CDCl3, (CD3)2CO, CD3OD or
tetrahydrofuran-d8 (THF-d8), presented in Fig. 1 and in Figs. S1–
S5 of Supplementary data. Here we describe in details the spectra
1
Fig. 1. Parts of variable-temperature 1H and 13C{1H} NMR spectra of 1 dissolved in (CD3)2CO. Assignment of signals to particular nuclei of alkyl group is given by black circles.

T. Kozlecki et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 149 (2015) 254–262
257
Fig. 2. The molecular structures and atom labeling scheme of 1 and 3 obtained by X-ray diffraction.
Table 1
of 1 dissolved in (CD3)2CO, while other spectra can be analyzed in a
X-ray crystallographic hydrogen bond parameters for 1 and 3 [Å and degrees].
similar way. Note that due to the low solubility not all
combinations of compounds and solvents have been studied in this
work.
Compound Type of H-bond (OHN)
r(OÁ Á ÁH) r(HÁ Á ÁO) r(OÁ Á ÁO)
H
1
3
O(1)–H(1O)Á Á ÁO(2)
0.82
1.86
1.88
2.673(2) 175
2.693(2) 169
O(11)–H(11O)Á Á ÁO(12) 0.82
The chemical shift of the OH proton signal of 1 of about 10 ppm
indicates that this group is involved in a medium-strong hydrogen
bond. Judging from the similar values of OH chemical shifts of 1 in
other solvents (9–11 ppm, see Figs. S1 and S2), absence of
concentration-dependence of OH chemical shifts, quantum
mechanical calculations (see below) and steric considerations,
the hydrogen bond is intramolecular OHÁ Á ÁO bond. The OH signal
shifts from 9 ppm at 330 K to 10 ppm at 220 K, which reflects
H-bond strengthening upon cooling [46]. Most probably, this is
because in the molecule with stronger (shorter) H-bond due to
the electron transfer the local polarity of the OHO bridge is larger
(indeed, the hypothetical limiting structure is O+HÁ Á ÁOÀ) [40,47],
which leads to the preferential stabilization of such structures at
lower temperatures, when solvent polarity (dielectric constant)
increases [48]. For 1 dissolved in other solvents, as well as for 2
and 3 in various solvents, the sensitivity of the OH chemical shifts
to temperature is comparable. There are no spectral indications of
the amide group rotation around the CC bond, which would lead to
the breakage of OHÁ Á ÁO bond and possible formation of an
intramolecular OHÁ Á ÁN bond, which is unlikely due the low basicity
of the nitrogen atom. Besides, there is no interaction of OH protons
of 1 with OH protons of residual water: in the whole temperature
range the H2O and HDO signals are resolved, relatively sharp and
shift to 3.6 ppm upon cooling. To summarize, we arrive to the con-
formation of 1 as shown in Scheme 2, with an intramolecular OHO
hydrogen bond. For 2 and 3 the reasoning is similar. It should be
pointed out that the presence of OHO hydrogen bonds does not
mean that the molecules are planar. In fact, there is enough evi-
dence of their non-planarity (see below). The intramolecular
OHO bonds for 1 and 3 are broken in crystalline state (see Fig. 2;
visualized using the program Mercury CSD version 2.2) [49], where
these molecules form infinite H-bonded chains. Crystallographic
parameters for these intermolecular hydrogen bonds are collected
in Table 1. In other words, the H-bonding and conformational state
of molecules such as 1–3 is dependent of their immediate sur-
roundings and both experimental and computational efforts are
valuable in tackling this issue.
O(2)–H(1O)Á Á ÁO(1) 0.94
1.73
2.638(1) 163
rates of the hindered rotation at each temperature. Arrhenius plot
of these rates is presented in Fig. 3.
Estimated barrier height is about Ea = 15.4 0.6 kcal/mol. Note,
that the estimation of the barrier height requires extrapolation of
the temperature dependence of intrinsic chemical shifts to higher
temperatures, the procedure which is illustrated in Fig. S6 of the
Supplementary data. Similar process of line shape analysis and
Arrhenius plot fitting was repeated for 1H and 13C NMR spectra
of 1, 2 and 3 dissolved in other solvents (the chemical shift extrap-
olation was polynomial and minimal power of the polynomial was
chosen every time, usually a straight line or a parabola). In some
solvents at low temperatures the signals of CH2 protons of 1 and
2 are split into multiplets due to spin–spin couplings and further
on due to the chemical non-equivalence induced by the
non-planarity of the molecule (see below). As was mentioned
above, at intermediate temperatures there is no indication of rota-
tion around C–C bond: OHO hydrogen bond appears to be intact
over the whole temperature range and even if there would be a
rotation around CC bond we do not expect to see its effect on the
signals of CH2 protons (a full 360° rotation would not interchange
them and a 180° rotation requires an OHN hydrogen bond, which is
unlikely). However, the line broadening at lowest temperatures
might be associated with some dynamics involving rotation
around the CC bond, a topic to which we will return below.
Plots of fitted chemical shifts as well as rate constants of CN
rotation can be found in Figs. S7–S19 of Supplementary data. The
results on the amide group rotational barrier heights are collected
in Table 2. The trend obtained for Ea correlates pretty well with the
data obtained previously for salicylamide, see Ref. [15] (some dif-
ference might be explained by an arguably less accurate method
in the determination of Ea used in Ref. [15]). There are at least three
effects which can influence the barrier height for the rotation
around the CN bond. Firstly, the more bulky substituents on the
amide nitrogen atom might sterically hinder the rotation due to
the interaction with the aromatic proton on the naphthalene
group. Secondly, the partial electron transfer to the carbonyl oxy-
gen atom due to the formation of the intramolecular OHÁ Á ÁO
hydrogen bond would increase the double-bond character of the
CN bond and further slow down the amide rotation. Finally, the
non-specific interaction with the solvent might influence the bar-
rier height. Though the body of data presented in this work is
The 1H and 13C NMR spectra clearly show that protons and car-
bon atoms of the morpholine group of 1 are involved in a hindered
rotation around CN bond. This dynamic process is fast in NMR time
scale at room temperature and gradually slows down when the
temperature is lowered. At 250 K signals of OCH2 and NCH2 carbon
atoms of the morpholine group split into pairs; at the same time,
four proton signals become visible in the 1H NMR spectrum. Line
shape analysis of the OCH2 carbon signals resulted in the estimated

258
T. Kozlecki et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 149 (2015) 254–262
19
18
N
1
2
17
16
15
14
13
12
11
10
1
1
2
3
3
1
1
CDCl3 at 220 K
(CD3)2CO at 190 K
THF-d8 at 170 K
CD3OD at 190 K
1
11.5
11.0
10.5
10.0
9.5
9.0
(OH), ppm
Fig. 4. Activation energies Ea for the rotation around amide CN bonds in 1, 2 and 3
dissolved in various solvents, obtained by line shape analysis of NMR data, versus
experimental values of OH chemical shifts.
Fig. 3. Arrhenius plot of the rate constants of the amide group rotation around CN
bond of 1 dissolved in (CD3)2CO, obtained by line shape analysis of 13C NMR spectra.
Solid line represents a least square linear fit.
into account further dynamics which is possible in the molecule.
Firstly, the morpholine ring is not planar and it can undergo con-
formational isomerism (sort of chair–chair ‘ring-flip’), shown as
‘a’ in Scheme 3, where the molecule is oriented in such a way that
the naphthalene ring – shown as a gray bar – is perpendicular to
the plane of the paper (the amide fragment is planar, but this plane
does not coincide with the naphthalene plane). Adding this chair–
chair ‘ring flip’ to the rotation around the CN bond we arrive to the
dynamics scheme shown as ‘b’ in Scheme 3 (as in this scheme we
focus on the morpholine moiety, the rest of the molecule is
depicted simply as R).
Secondly, the amide group can pass through the naphthalene
plane as a result of an incomplete rotation around the CC bond,
in fact a twisting around the CC bond by 60–70° without breaking
the OHO hydrogen bond. Adding this to Scheme 3 we get the over-
all dynamics as shown in Scheme 4, where one of the CH2 groups is
marked with an asterisk to make it easier to follow the CN rotation.
When the ‘ring flip’ and ‘CC twisting’ dynamic processes slow
down in NMR time scale, the signals of CH2 protons should split
and the chemical shift difference is likely to be the largest for those
protons which are closest to the naphthalene rings and affected by
its ring currents. In our experiments temperature was sufficiently
low to broaden the signals but not low enough to actually see
the splitting.
Morpholine ring dynamics can be further corroborated by DFT
calculations. Fully optimized (B3LYP/6-31+G(d,p)) structures of 1,
2 and 3 are shown in Fig. 5. Atom labeling is added to key atoms
which will be used in discussion below. In global minimum all
three molecules exhibit intramolecular OHO hydrogen bonds. As
mentioned above, the amide group, which is planar by itself, is
located out of the plane of naphthalene rings and so is the OHO
hydrogen bond.
Besides, both conformational isomers shown in Scheme 3a can
be optimized as local energy minima on the conformational land-
scape; additional minimum corresponds to the intermediate struc-
ture with partially inverted morpholine ring (see structures A, C
and B in Fig. 6).
Table 2
Energy barriers Ea (in kcal/mol) for the hindered rotation of the amide groups of 1, 2
and 3 around the CN bond, estimated by the line shape analysis of 1H and 13C NMR
spectra.
Compound
Solvent
Observed nucleus
Observed group
Ea
1
(CD3)2CO
CDCl3
13C
13C
13C
1H
OCH2
OCH2
NCH2
CH2
15.4 0.6
13.5 0.5
12.9 0.4
THF-d8
CD3OD
16
1
1H
CH2
17.1 0.2
2
3
(CD3)2CO
THF-d8
1H
1H
NCH2
NCH2
17.0 0.3
15.8 0.5
(CD3)2CO
CDCl3
1H
1H
CH3
CH3
13.9 0.7
15.3 0.5
insufficient to address this multi-parametric problem in full, in
Fig. 4 we plot the experimentally estimated barrier heights as a
function of OH chemical shift, which can be considered as a mea-
sure for the hydrogen bond strength (shortness) [43]. For this plot
we have selected the OH chemical shifts measured at lowest tem-
perature for each solvent, so that the values are less influenced by
any possible residual fast equilibria, associated with opening/clos-
ing of intramolecular OHO bond. The complete dataset of temper-
ature dependent OH chemical shift can be found in Tables S2–S4 of
Supplementary data. From Fig. 4 it follows that the energy barrier
has a tendency to increase together with the hydrogen bond
strength (electronic effect). Though the dependence of the rota-
tional barrier height on the strength of the hydrogen bond has been
previously observed in some cases, Refs. [14–18], caution should
be used in interpretation of the plot in Fig. 4, as steric hindrances
and solvent interactions could also be quite substantial. Fig. 4
shows noticeable data point scattering and works better as a gen-
eral trend rather than a predictive tool for each individual com-
pound. Further discussion of the rotational barriers will be given
below based on DFT calculations.
Conformers A and C are very close in energy and both are not
too far from conformer B if the OHO hydrogen bond is intact (top
row in Fig. 6). The energy separation between all three conformers
increases noticeably if OHO is broken (bottom row in Fig. 6).
Potential energy profiles for the rotation of the amide group
around C11–N1 (CN) or C2–C11 (CC) bonds of 1, 2 and 3 are plotted
as ‘a’ and ‘b’ in Fig. 7, respectively. As rotational coordinates we
have chosen C2–C11–N1–C12 and C1–C2–C11–N1 dihedral angles.
Some roughness of the given datasets is due to the fact that during
An interesting spectral feature can be seen at lowest tempera-
tures in 1H NMR spectra presented in Fig. 1. When the temperature
is lowered below 250 K all four signals of CH2 groups of morpho-
line ring become somewhat broader, but the one at the lowest field
broadens to such an extent that at 220 K it becomes almost invis-
ible. A rationalization of this phenomenon can be achieved taking

T. Kozlecki et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 149 (2015) 254–262
259
O
a
O
N
N
O
O
H
O
H
O
amide rotaꢀon
(slows at intermediate T)
b
O
O
N
N
R
O
O
R
chair-chair
“ring flip”
chair-chair
“ring flip”
(starts to slow at lowest T)
(starts to slow at lowest T)
O
O
N
N
O
R
O
amide rotaꢀon
(slows at intermediate T)
R
Scheme 3. (a) Chair–chair ‘ring flip’ of the morpholine ring suggested for 1. (b) Dynamics scheme including both the rotation around the CN bond and the chair–chair
isomerism of morpholine.
slows down
at intermediate T
starts to slow down at lowest T
starts to slow down at lowest T
O
O
O
*
*
O
*
*
passing through
passing through
rotation around
the CN bond
rotation around
the CN bond
the naphthalene plane
rotation around
the CN bond
the naphthalene plane
N
N
N
(twisting around the CC bond)
N
(twisting around the CC bond)
...
...
O
O
O
O
H
O
H
O
H
O
H
O
chair-chair
chair-chair
chair-chair
chair-chair
O
*
O
*
O
*
O
*
passing through
the naphthalene plane
(twisting around the CC bond)
passing through
the naphthalene plane
(twisting around the CC bond)
rotation around
the CN bond
rotation around
the CN bond
rotation around
the CN bond
N
N
N
N
...
...
O
O
O
O
H
O
H
O
H
O
H
O
Scheme 4. Overall dynamics of the morpholine ring suggested for 1: the rotation around the CN bond slows down at intermediate temperatures, the chair–chair ‘ring flip’ and
twisting around the CC bond start to slow down at lowest temperatures.
the course of the calculations only one parameter (dihedral angle)
was fixed and all other parameters were optimized. Such approach
is well suited for the determination of the energy barriers [19]
though some artefacts on the energy profile might occur due to
the applied geometric restrictions.
Table 3, together with the calculated geometric parameters of
OHÁ Á ÁO hydrogen bonds: r(OÁ Á ÁH), r(HÁ Á ÁO) and r(OÁ Á ÁO) distances.
Activation energies increase in the sequence 1-3-2 (13.2, 17.0,
18.9 kcal/mol). Above, Fig. 4 suggested that the barrier height for
the C–N rotation is dependent on the strength of the intramolecu-
lar H-bond, which in turn is dependent on the solvent (via its
polarity, steric restrictions etc.). Thus, in DFT calculations, which
Rotation around CN bond (‘a’ in Fig. 7) quite expectedly gives
two maxima and the values of activation energies as listed in

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T. Kozlecki et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 149 (2015) 254–262
Fig. 5. Optimized structures (B3LYP/6-31+G(d,p)) of 1, 2 and 3.
Fig. 6. Calculated (B3LYP/6-31+G(d,p)) optimized structures of the conformational isomers of 1, corresponding to three steps of the morpholine ring inversion.
do not take solvent into account, we do not expect to see the
numerical coincidence with the experiment, but roughly the calcu-
lated Ea values are similar to the experimental ones. Unfortunately,
there is no apparent correlation between the energy barriers and
the hydrogen bond strength (shortness), represented either as
the r(OÁ Á ÁO) or as the sum r(OÁ Á ÁH) + r(HÁ Á ÁO) [43].
320°) corresponds to structures with rather unstable OHN bonds.
These are 5–8 kcal/mol higher than the global minimum.
Interestingly, the calculated barrier height for the complete 360°
rotation around the CC bond is comparable with the CN rotation
barrier, so that under experimental conditions at room tempera-
ture one could expect to observe both rotations happening at
comparable rates. However, fast 360° turns do not affect NMR
spectra and we cannot confirm or disconfirm this computational
finding.
In summary, the hypothesis of the morpholine ring dynamics is
fairly justified by computational results. Comparing experimental
and computed value of the CN rotation activation barrier and com-
puted energy barriers for chair–chair ‘ring flip’ or a ‘CC twist’ we
can indeed conclude that upon cooling first the CN rotation should
slow down and then the ‘chair flip’/‘CC twist’.
Rotation around the CC bond leads to a potential energy curve
with several minima and maxima (‘b’ in Fig. 7). These extrema
have clear physical meaning. Two minima at ca. 140° and 210°
correspond to the structures with OHO hydrogen bonds. These
minima are separated by a 70° turn around the CC bond without
breaking the OHO bond and a barrier of 3–4 kcal/mol, which
reflects the steric repulsion when the amide group comes into
the plane of naphthalene rings (the process which was called
‘CC twist’ above). Second pair of energy minima (ca. 40° and

T. Kozlecki et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 149 (2015) 254–262
261
Dihedral angle C1-C2-C11-N1, degree
Dihedral angle C2-C11-N1-C12, degree
Fig. 7. Calculated (B3LYP/6-31+G(d,p)) potential energy curves for the rotation of amide group around (a) CN and (b) CC bond in 1, 2 and 3. For atom labeling see Fig. 5. Data
points are connected by smooth curves.
measurements, St. Petersburg State University (Russia) and
Wroclaw University (Poland) for travel grants, RFBR Grant
14-03-00111 (P.T.; NMR studies, DNMR analysis) and the grant of
the Polish Plenipotentiary in JINR Nr 118 from 05.02.2014, p.7 for
partial financial support.
Table 3
Energy barriers Ea (in kcal/mol) for the hindered rotation of the amide groups of 1, 2
and 3 around the CN bond, calculated at B3LYP/6-31+G(d,p) level of theory as well as
interatomic distances in the intramolecular OHO hydrogen bonds (in Å).
Compound Ea
r(OÁ Á ÁH) r(HÁ Á ÁO) r(OÁ Á ÁO) r(OÁ Á ÁH) + r(HÁ Á ÁO)
1
2
3
13.2 0.2 0.987
18.9 0.4 0.988
17.0 0.2 0.981
1.737
1.719
1.770
2.614
2.600
2.635
2.724
2.707
2.751
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.saa.2015.04.052.
Conclusions
Conformational dynamics and hydrogen bonding – anticipated
phenomena for all compounds involving amide groups – have been
studied here for a new set of compounds, beta-hydroxynaphthy-
lamides. On the basis of variable-temperature 1H and 13C NMR
spectra and DFT calculations we conclude that in polar aprotic
medium (solution-state, experiment) and in vacuum (gas-phase,
calculations) the energetically preferred conformers of
b-hydroxynaphthylamides 1, 2 and 3 are the non-planar structures
with intramolecular OHÁ Á ÁO hydrogen bonds. In contrast, in the
solid state 1 and 3 form intermolecularly OHÁ Á ÁO hydrogen bonded
chains. Energy barriers for the amide group rotation around the CN
bond were experimentally estimated; the barrier heights lie in the
region 13–19 kcal/mol and appear to correlate with the hydrogen
bond strength, measured as OH proton NMR chemical shift. Such
interdependence can be explained as the result of the partial elec-
tron transfer to the carbonyl oxygen atoms, which increases the
double bond character of the CN bond and thus increases the rota-
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