Synthesis and vibrational spectroscopic investigation of methyl l-prolinate hydrochloride: A computational insight

Article abstract of DOI:10.1080/00387010.2013.834456

In our present work, methyl L-prolinate hydrochloride has been synthesized from L-proline amino acid and characterized by Fourier transform infrared and Fourier transform Raman spectra via experimental and computational methods. Ab initio Hartree-Fock and density functional theory (B3LYP) calculations have been made for the structure, and atomic charge distributions were also predicted for the title compound by using the 6-311++G(d,p) basis set. Predicted vibrational frequencies have been assigned and compared with experimental Fourier transform infrared and Fourier transform Raman spectra. The thermodynamic properties such as heat capacity, enthalpy, entropy, and Gibbs energy have been calculated at different temperatures. The calculated highest occupied molecular orbital and lowest unoccupied molecular orbital energy show the charge transfer behavior within the molecule.

Full text of DOI:10.1080/00387010.2013.834456

Spectroscopy Letters, 47:676–689, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0038-7010 print=1532-2289 online
DOI: 10.1080/00387010.2013.834456
Synthesis and Vibrational Spectroscopic
Investigation of Methyl L-Prolinate
Hydrochloride: A Computational Insight
V. Balachandran1,
M. Boobalan2,3
,
ABSTRACT In our present work, methyl L-prolinate hydrochloride has been
synthesized from L-proline amino acid and characterized by Fourier transform
infrared and Fourier transform Raman spectra via experimental and computa-
tional methods. Ab initio Hartree-Fock and density functional theory (B3LYP)
calculations have been made for the structure, and atomic charge distributions
were also predicted for the title compound by using the 6-311þþG(d,p) basis
set. Predicted vibrational frequencies have been assigned and compared with
experimental Fourier transform infrared and Fourier transform Raman spectra.
The thermodynamic properties such as heat capacity, enthalpy, entropy, and
Gibbs energy have been calculated at different temperatures. The calculated
highest occupied molecular orbital and lowest unoccupied molecular orbital
energy show the charge transfer behavior within the molecule.
M. Amaladasan2,
and S. Velmathi4
1P.G. & Research Department of
Physics, Arignar Anna
Government Arts College,
Tiruchirappalli, India
2Department of Chemistry,
St. Joseph’s College,
Tiruchirappalli, India
3Department of Chemistry,
Roever Engineering College,
Perambalur, India
4Department of Chemistry,
National Institue of Technology,
Tiruchirappalli, India
KEYWORDS density functional theory, Hartree-Fock, highest occupied
molecular orbital, lowest unoccupied molecular orbital, methyl L-prolinate
hydrochloride, synthesis, thermodynamic functions
INTRODUCTION
L-Proline is an amino acid, which has one secondary amine and a
carboxylic acid functional group with a chiral center. It is not an essential
amino acid because the human body can synthesize it. L-Proline is one
DNA-encoded amino acid out of 20 amino acids. It is a five-member hetero
ring system having one nitrogen and four carbon annular atoms, and this
contributes to it having a rigid ring structure, which leads to its special
characteristic features such as the bending template effect in peptide chains.
The synthetic products of L-proline derivatives show significant biological
activity and organo catalytic behavior. Especially, they are used in enantio-
selective aldol, Mannich, and Michael addition reactions and in the synthesis
of certain macrocyclic molecular systems.[1–5]
Received 27 December 2012;
accepted 10 August 2013.
Address correspondence to
M. Boobalan, Department of
Chemistry, St. Joseph’s College,
Tiruchirappalli 620002, India.
E-mail: Jerry.Fedrick@gmail.comand
Department of Chemistry, Roever
Engineering College, Perambalur
621212, India
L-Proline is the derivative of glutamine amino acid. It has a significant role
in the human biological system. It contributes to the healthy functioning of
the bone, muscles, skin, and immune system. A deficiency in this amino acid
might lead an individual to have tears in tissues and very slow healing ability.
Color versions of one or more of the
figures in the article can be found
online at www.tandfonline.com/lstl.
676

This paucity can be rectified by a healthy and balanced
diet and supplements suggested by a physician.[6]
The various computational investigations have
been made on several derivatives of L-proline and
L-proline individual residue.[7] For instance, Wagner
et al.[8] investigated the vibrational frequencies of
the copper complex of L-proline. Sheena Mary
et al.[9] reported the vibrational spectra such as
Fourier transform infrared (FT-IR), Fourier transform
Raman (FT-Raman), and surface-enhanced Raman
spectral (SERS) studies of L-proline. Recently,
vibrational spectra of L-proline and its hydrated com-
plex have been reported based on density functional
theory (DFT) and MP2 theories.[10] To the best of our
knowledge, we can say that there is not any scientific
communication on methyl L-prolinate hydrochloride
under vibrational spectroscopic computation. The
vibrational spectroscopic techniques such as FT-IR
and FT-Raman are believed to be an effective experi-
mental technique to understand the structural and
vibrational behavior of the molecule. So the methyl
L-prolinate hydrochloride has been critically exam-
ined based on these spectral techniques and special
attention given to explain all the remarkable qualitat-
ive and quantitative differences in these spectra. The
possible rotational isomers of methyl L-prolinate
hydrochloride have been searched. There are eight
different rotational isomers found for this title com-
pound. The optimized geometry and vibrational
wavenumber for a stable isomer of the title com-
pound were calculated at Hartree-Fock (HF) and
B3LYP levels of theory with the 6-311þþG(d,p) basis
set. The results of the theoretical and spectroscopic
studies are reported herein. Detailed interpretations
of the vibrational spectra of methyl L-prolinate
hydrochloride have been made. The atomic charges
of methyl L-prolinate hydrochloride were investi-
gated using HF and B3LYP levels with the
6-311þþG(d,p) basis set. The calculated highest occu-
pied molecular orbital (HOMO) and lowest
unoccupied molecular orbital (LUMO) energy give
information on charge transfer behavior that takes
place within the molecule. Various thermodynamic
functions are also calculated by different temperatures.
region 4000–400 cmꢀ1 using a Perkin-Elmer spec-
trum RX1 spectrophotometer using the KBr pellet
technique. The signals were collected for 100 scans
with a scan interval of 1 cmꢀ1 and at an optical
resolution of 0.4 cmꢀ1. The FT-Raman spectrum
was also recorded in the region 3500–100 cmꢀ1 using
a Bruker-FRA 106=IFS100 spectrometer. The spec-
trometer consists of a quartz beam splitter and
a highly sensitive germanium diode detector cooled
to the liquid nitrogen temperature. The sample was
packed in a glass tube of about 5 mm diameter and
excited in the 180ꢁ geometry with a 1064-nm laser
line at 75 mW power from a diode-pumped air-
cooled-cw Nd:YAG laser as excitation wavelength
in the region of 3500–100 cmꢀ1. The signals were
collected for 300 scans at the interval of 1 cmꢀ1 and
optical resolution of 0.1 cmꢀ1.
Synthesis
Optically active L-proline amino acid was
purchased from LOBA Chemie and was commercial
grade and used without further purification for the
synthesis of methyl L-prolinate hydrochloride. About
1.0 g (6.0379 mmol) of L-proline was treated with
methanol in the presence of 0.7183 g (6.0379 mmol)
of SOCl2 to form this ester. It was synthetically an
effective and well-known acid-catalyzed method for
this esterification process.[11] Since the addition of
SOCl2 was an exothermic reaction, the entire reac-
tion system was maintained under ice bath for about
24 hr in a fume hood chamber. The completion of
the reaction and purity of the product were checked
during reasonable intervals using precoated Merck
graded thin layer chromatographic (TLC) plates in
the mixture of the hexane and ethyl acetate solvent
system. Finally, the formed ester was separated using
a Roto Vacuum Evaporator branded from Buche
Labortechnike AG with appropriate temperature
and pressure. The percentage of yield was >98%.
The scheme of the reaction is shown in Fig. 1.
Computational Methods
The molecular structure of methyl L-prolinate
hydrochloride and the corresponding vibrational
harmonic frequencies were calculated using HF
and B3LYP theory combined with 6-311þþG(d,p)
basis set model chemistries. All these calculations
EXPERIMENTAL
The FT-IR spectra of methyl L-prolinate hydro-
chloride were recorded at room temperature in the
Synthesis and Vibrational Spectra of Methyl L-Prolinate Hydrochloride
677

FIGURE 1 Synthesis scheme of methyl L-prolinate hydrochloride.
were performed using the GAUSSIAN09 W quantum
chemistry program package[12] on a Pentium IV
processor personal computer without constrained
geometry for the stable isomer, but the rest of the
other isomers were constrained. A close agreement
between observed and calculated frequencies was
achieved by means of the least square fit refinement
algorithm. In our present scenario, the frequencies of
the title molecule are scaled with four different scal-
ing factors. In the HF level, the frequencies above
1701 cmꢀ1 are scaled with 0.9287, and other frequ-
encies, which fall below 1700 cmꢀ1, are scaled with
0.9116. In the case of B3LYP, the scaling factors of
0.9731 and 0.9561 are used in between the above
said two different ranges of frequencies, respectively.
RESULTS AND DISCUSSION
Conformational Stability
An intensive study was carried out to identify the
most stable isomer out of eight possible isomers of
methyl L-prolinate hydrochloride. All the eight
possible isomers come to survive because of free
rotation of atoms in –COOCH3 group functionality.
The pictorial representations of all eight isomers
are shown in Fig. 2. The study on energy calculation
is performed with the Gaussian09 W program and
the results are viewed in GaussView 5.0.8 GUI.[13]
All the energies are tabulated in Table 1, and isomer
‘‘R5’’ is considered as the most stable isomer. There-
fore, further in this article, we focus on this particular
isomer and consider it the title molecule; also, all the
computational investigations are executed based on
this most stable isomer.
FIGURE 2 Possible rotational isomer geometry of methyl
L-prolinate hydrochloride.
optimization on the title molecule. The optimized
structural parameters are calculated by ab initio and
DFT methods listed in Table 2. After careful scrutiny,
we came to know that the crystallographic data of
methyl L-prolinate hydrochloride is not available
in the literature. Therefore, the optimized structure
can only be compared with the crystal structure
of other similar systems such as L-proline and DL-
proline.[14] The experimental geometric parameters
are much closer to the results of the B3LYP method
than the HF method. The optimized C(4)-C(5) bond
length shows good consistency between HF, B3LYP,
and experimental results. The experimental C(4)-C(5)
Molecular Geometry
The optimized geometry and labeling of atoms in
methyl L-prolinate hydrochloride are given in Fig. 3.
In our present work, we performed full geometry
678
V. Balachandran et al.

TABLE 1 Calculated Energies and Energy Difference for Eight Rotational Isomers of Methyl L-Prolinate Hydrochloride by HF/
6-311þþG(d,p) and B3LYP/6-311þþG(d,p) Methods
HF=6-311þþG(d,p)
Relative energya (Hartree)
B3LYP=6-311þþG(d,p)
Isomers
Energy (Hartree)
Energy (Hartree)
Relative energya (Hartree)
R1
R2
R3
R4
R5
R6
R7
R8
ꢀ897.8723
ꢀ897.8570
ꢀ897.8050
ꢀ897.8224
ꢀ897.9373ꢂ
ꢀ897.8511
ꢀ897.9267
ꢀ897.8861
0.0650
0.0803
0.1323
0.1149
0.0000
0.0862
0.0106
0.0512
ꢀ901.3174
ꢀ901.3049
ꢀ901.2579
ꢀ901.2740
ꢀ901.3742ꢂ
ꢀ901.3027
ꢀ901.3625
ꢀ901.3294
0.0568
0.0693
0.1163
0.1002
0.0000
0.0715
0.0117
0.0448
aEnergies of the other three isomers relative to the most stable ‘‘R5’’ isomers.
ꢂMinimum energy geometry.
bond length is 1.53 Aꢁ, which is identically produced
by HF and B3LYP results. Nevertheless, the computed
bond length in N(1)-C(5), N(1)-H(6), C(2)-C(3), C(3)-
C(4), C(3)-H(8), C(3)-H(9), C(4)-H(10), C(4)-H(11),
and C(5)-H(12) are varying by 0.01 Aꢁ against the
experimental bond length. The comparative and regres-
sive correlation graphs are plotted between experi-
mental and computed values of both bond length and
bond angle. The graphical presentation is given in
Figs. 4 and 5. The correlative regression value
for bond length shows the existence of a higher
degree of closeness between the computed and
experimental results. However, the bond angle
value is very poor due to the comparison between
stereochemically different DL-proline molecular
systems with the title molecule.
any literature. Therefore, we focused on this deriva-
tive of L-proline. The FT-IR and FT-Raman spectra of
the title compound are compared with the theoreti-
cally calculated vibrational spectra by the HF and
B3LYP methods with the 6-311þþG(d,p) basis set
and are shown in Figs. 6 and 7, respectively. The envi-
saged vibrational spectrum has no imaginary fre-
quency, implying that the optimized geometry is
located at the local minimum. Since the ab initio and
DFT potentials steadily overrate the vibrational wave-
number, the divergence can be minimized by imple-
menting an appropriate scaling procedure with a
suitable numerical scaling factor. Theoretical and
experimental frequencies are compared and tabulated
in Table 3. All calculated spectra are in good accord-
ance with experimental data. The calculated frequen-
cies are slightly higher than experimental frequencies
for the majority of the normal modes. Some factors
might be responsible for discrepancies between the
experimental and computed spectra of this title com-
pound. One is probably the interaction with the sur-
rounding molecules, and the other one is harmonic
oscillator approximation in theoretical calculations; it
should be noted that theoretical calculations neglect
the anharmonic effects. Besides, the errors in calcu-
lated frequencies result from the inadequate basis
set or from the lack of the electron correlation. A linear
relation was found between experimental and theor-
etical frequencies that are plotted in Fig. 8.
Vibrational Assignment
The vibrational spectra of methyl L-prolinate
hydrochloride have not been reported in detail in
N-H Vibrations
The title molecule methyl L-prolinate hydro-
chloride has a secondary amine group in which the
FIGURE 3 Optimized stable isomer geometry of methyl
L-prolinate hydrochloride.
Synthesis and Vibrational Spectra of Methyl L-Prolinate Hydrochloride
679

TABLE 2 Computed Optimized Geometrical Parameters of Methyl L-Prolinate Hydrochloride by HF/6-311þþG(d,p) and B3LYP/
6-311þþG(d,p) Methods
˚
Bond length (A)
Bond angle (degrees)
HF=6-311þþ
B3LYP=6-311þþ
HF=6-311þþ
B3LYP=6-311þþ
Parameters
G(d,p)
G(d,p)
Exp
Parameters
G(d,p)
G(d,p)
Exp
N1-C2
1.45
1.46
1.00
1.55
1.08
1.53
1.54
1.08
1.08
1.53
1.08
1.08
1.08
1.09
1.19
1.32
4.18
1.42
1.08
1.08
1.08
1.28
1.47
1.47
1.01
1.56
1.10
1.53
1.55
1.09
1.09
1.53
1.09
1.09
1.09
1.10
1.22
1.34
3.99
1.44
1.09
1.09
1.09
1.31
1.47
1.46
1.00
1.56
1.08
C2-N1-C5
106.60
111.89
112.51
104.75
111.91
114.56
108.71
113.59
103.39
104.61
109.30
112.59
111.80
111.88
106.74
103.91
112.43
110.66
112.49
109.73
107.63
102.66
110.72
112.09
113.16
110.25
107.97
119.11
122.55
154.15
118.32
35.06
106.44
111.64
112.68
104.54
112.01
114.12
108.55
114.37
103.35
104.85
109.07
112.64
111.77
111.86
106.72
103.97
112.35
110.63
112.41
109.78
107.71
102.43
110.50
112.46
113.23
110.24
108.01
119.33
122.78
157.90
117.88
39.00
110.1
115.5
116.0
104.2
111.7
113.0
111.8
108.7
107.5
104.3
109.0
111.4
109.2
113.1
109.0
101.4
112.9
109.8
113.0
109.2
109.8
101.0
110.4
112.5
112.9
110.4
109.6
N1-C5
C2-N1-H6
N1-H6
C5-N1-H6
C2-C3
N1-C2-C3
C2-H7
N1-C2-H7
C2-C14
C3-C4
N1-C2-C14
C3-C2-H7
1.54
1.08
1.08
1.53
1.08
1.08
1.08
1.08
1.20
C3-H8
C3-C2-C14
H7-C2-C14
C2-C3-C4
C3-H9
C4-C5
C4-H10
C4-H11
C5-H12
C5-H13
C14-O15
C14-O16
C14-Cl22
O16-C17
C17-H18
C17-H19
C17-H20
H21-Cl22
C2-C3-H8
C2-C3-H9
C4-C3-H8
C4-C3-H9
H8-C3-H9
C3-C4-C5
C3-C4-H10
C3-C4-H11
C5-C4-H10
C5-C4-H11
H10-C4-H11
N1-C5-C4
N1-C5-H12
N1-C5-H13
C4-C5-H12
C4-C5-H13
H12-C5-H13
C2-C14-O15
C2-C14-O16
C2-C14-Cl22
O15-C14-O16
O15-C14-Cl22
O16-C14-Cl22
C14-O16-C17
O16-C17-H18
O16-C17-H19
O16-C17-H20
H18-C17-H19
H18-C17-H20
H19-C17-H20
C14-Cl22-H21
83.26
79.03
127.26
110.85
111.80
104.64
109.60
110.49
109.37
10.18
125.11
110.87
109.97
104.64
110.76
111.26
109.17
11.76
nitrogen acts as an annular atom in the five-member
ring system. In general, the N-H stretching vibration
in the FT-IR spectrum is expected in the range
near 3400–3500 cmꢀ1.[10] The experimentally observed
spectrum shows 3473 cmꢀ1. This observation agrees
well with the theoretically calculated value. The
N-H in-plane bending vibrations usually occur in
the region of 1650–1580cmꢀ1. In the present title
molecule, the one medium FT Raman band is
observed at 1413 cmꢀ1
.
On considering the N-H out-of-plane bending
vibrations, one can expect the frequency around
680
V. Balachandran et al.

FIGURE 4 Comparison between experimental and computed bond length and bond angle in the HF and B3LYP approaches.
895 cmꢀ1.[15] It has good agreement with both the
observed and theoretical FT-IR and Raman values.
The observed frequencies are 838cmꢀ1 in Raman
and the theoretical frequencies are 854 and 840 cmꢀ1
in HF and B3LYP, respectively. From the observed
N-H vibrations, both stretching and bending vibrations
shows good agreement with expectations, except
with N-H in-plane bending, due to the impact of other
substitutions.
respective regions of frequency. An isolated C-H
bond has only one stretching frequency, but
the stretching vibrations of the C-H bond in the CH2
group combine together to produce two coupled
vibrations of different frequencies described as asym-
metric and symmetric frequencies, with the asymmet-
ric often being the higher frequency. It is noted while
the bonds are very close to each other in the CH2
system and have a similar frequency, they can easily
undergo vibrational coupling, or the fundamental
vibration may be coupled with an overtone of some
other vibration to show Fermi resonance behavior.
The vibrations of the CH2 group, the asymmetric
stretch tasCH2, the symmetric stretch tsCH2, the
scissoring vibrations of the dCH2, and the wagging
CH2 Vibrations
Methylene is involved in various modes of
vibrations such as asymmetry, symmetry stretching,
scissoring, wagging, twisting, and rocking in their
FIGURE 5 Correlation plot between experimental and computed bond length and bond angle in the HF and B3LYP approaches.
Synthesis and Vibrational Spectra of Methyl L-Prolinate Hydrochloride
681

FIGURE 6 FT-IR spectra of methyl L-prolinate hydrochloride: (a) observed, (b) calculated by HF=6-311þG(d,p) and scaled, and
(c) calculated by B3LY=6-311þG(d,p) and scaled.
vibration of the xCH2, appear in the regions
3000 ꢃ 50, 2965ꢃ 30, 1455 ꢃ 55, and 1350 ꢃ 85cmꢀ1,
respectively.[16,17] Methylene asymmetric and sym-
metric stretching bands of the pyrrolidine are usually
observed near 2953 and 2868 cmꢀ1, respectively.[18]
The HF and B3LYP calculations give three bands
for the asymmetric and symmetric stretching corre-
sponding to different methylene groups, C(1)-H(2)-
H(3), C(4)-H(5)-H(6), and C(7)-H(8)-H(9). Electronic
effects including back donation, mainly caused by
the presence of the nitrogen atom adjacent to the
methylene groups, can shift the position and alter
the intensity of CH stretching and bending modes.
The lowering of wavenumbers and the increasing
intensity of CH stretching modes of the CH2 of the
ring point to the influence of back donation in the
ring owing to the presence of the nitrogen atom.
For a molecule containing a methylene group, the
electronic charge is back donated from the lone pair
of nitrogen to the rꢂ orbital of the CH bonds, causing
a weakening of the CH bonds. This is followed by
the increase in C-H force constants and can result
in the enhancement of IR band intensity of C-H
stretching modes.[19,20] The asymmetric CH2 stretching
bands are observed at 3048, 3036, and 3024 cmꢀ1 in
the FT-Raman spectrum. The calculated values are
682
V. Balachandran et al.

FIGURE 7 FT-Raman spectra of methyl L-prolinate hydrochloride: (a) observed, (b) calculated by HF=6-311þG(d,p) and scaled, and
(c) calculated by B3LY=6-311þG(d,p) and scaled.
3072, 3048, and 3040 cmꢀ1 and 3054, 3035, and
3021 cmꢀ1 by HF and B3LYP levels, respectively.
The symmetrical CH2 stretching bands are observed
at 2975, 2950, and 2923 cmꢀ1 in the Raman spectra.
The bending vibrations of the C-H bonds in the
methylene group are identified in their respective
positions. The scissoring mode of the CH2 group
gives rise to a characteristic band observed near
1465 cmꢀ1 in the literature.[21] The twisting and rock-
ing vibrations of the CH2 group appear in the regions
1290 ꢃ 45 and 890 ꢃ 55 cmꢀ1, respectively.[15] The
twisting and rocking modes are also identified. For
proline oligomers and poly-L-proline,[22] the CH2
deformation bands are reported at 1446, 1261, and
1237 (dCH2); 1198, 1187, and 1172 (s=xCH2); and
781 and 662 cmꢀ1 (qCH2). For the title molecule, the
bands are observed at 1494, 1475, and 1450 cmꢀ1 in
the Raman spectrum, and the calculated frequencies
1502, 1479, and 1464 cmꢀ1 and 1496, 1483, and
1455 cmꢀ1 by HF and B3LYP, respectively, are ascribed
to the CH2 scissoring modes. The CH2 wagging modes
are observed at 1325, 1275, and 1250 cmꢀ1 in the
Raman spectrum, and the values 1308, 1295, and
1257 cmꢀ1 and 1324, 1302, and 1245 cmꢀ1 are theoreti-
cally calculated by HF=6-311þþG(d,p) and B3LYP=
6-311þþG(d,p), respectively. For the title molecule,
Synthesis and Vibrational Spectra of Methyl L-Prolinate Hydrochloride
683

TABLE 3 Calculated Vibrational Frequencies (cmꢀ1) Assignment of Methyl L-Prolinate Hydrochloride Based on HF/6-311þþG(d,p) and
B3LYP/6-311þþG(d,p) Methods
Observed frequencies
Calculated frequencies
HF=6-311þþG(d,p)
Unscaled Scaled
B3LYP=6-311þþG(d,p)
Unscaled Scaled
3537 3470
No
IR
Raman
Assignment
01.
02.
03.
04.
05.
06.
07.
08.
09.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
3473vs
3770
3322
3303
3255
3233
3227
3225
3212
3194
3194
3110
2579
1940
1655
1640
1527
1513
1508
1488
1465
1520
1495
1465
1451
1434
1431
1363
1334
1314
1291
1280
1239
1212
1192
1144
1071
1044
990
3458
3194
3157
3072
3048
3040
2982
2960
2925
2924
2847
2386
1731
1677
1633
1502
1479
1464
1449
1418
1357
1334
1308
1295
1280
1257
1216
1191
1173
1152
1142
1106
1082
1064
1021
956
tNH
3179 m
3167
3132
3114
3096
3077
3072
3055
3050
3015
2950
2573
1739
1630
1618
1512
1499
1493
1475
1443
1388
1362
1338
1316
1308
1299
1255
1219
1205
1178
1171
1110
1099
1088
1057
990
3171
3086
3054
3035
3021
2961
2949
2924
2891
2848
2384
1741
1614
1620
1496
1483
1455
1439
1415
1373
1345
1324
1302
1294
1245
1222
1190
1166
1138
1125
1098
1087
1077
1046
980
t
t
t
t
t
t
t
t
asymCH3
asymCH3
asymCH2
asymCH2
asymCH2
symCH2
symCH2
symCH3
3107 s
3048 m
3036 s
3024 m
2975 m
2950 m
2923 m
2900 m
tCH
symCH2
t
2378s
1737s
tHCl
tCO
1744w
1636s
dCH3
dCH3
qCH2
qCH2
qCH2
qCH3
dNH
1619w
1494w
1475 m
1465 m
1440 m
1387 m
1413 m
1375 m
1344 m
1325w
1275s
dCH
tCC
xCH2
xCH2
cCO
xCH2
tCH2
tCH2
tCH2
dCH3 rock
cCH3 rock
tCN
tCO
tCC
tCC
tCN
tCC
dRing
dCO
cNH
dCH2 rock
dCO
1247 m
1250 m
1225w
1188 m
1165w
1131w
1126 m
1073 m
932w
1100 m
1088 m
1050vs
988 m
925 m
900vs
868 m
838 m
813w
940
962
932
884
921
911
870w
871w
971
872
906
867
957
854
879
840
908
810
822
812
775 m
669 m
821
780
750
771
675 m
625w
808
684
697
666
dCO
dRing
dCC
dRing
cHCl
dHCl
704
628
649
625
608w
684
610
635
605
580w
544 m
494 m
623
556
583
578
595
551
556
545
532
506
500
490
(Continued )
684
V. Balachandran et al.

TABLE 3 Continued
Observed frequencies
Calculated frequencies
HF=6-311þþG(d,p)
Unscaled Scaled
B3LYP=6-311þþG(d,p)
Unscaled Scaled
438 400
No
IR
Raman
400 m
Assignment
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
453
355
294
235
206
176
127
98
404
317
284
210
184
157
122
87
cCO
cCO
cCC
306vw
281vw
213w
181 m
156 m
120 s
333
287
228
201
164
123
112
81
304
284
212
180
156
122
88
dCH2 rock
dCH2 rock
tCH3 twist
cCO
tO-HCl
dO-HCl
cRing
cHCl
85
76
80
69
62
70
60
22
20
34
21
18
16
20
16
cRing
vs, very strong; s, strong; m, medium; w, weak; vw, very weak; t, stretching; d, in-plane bending; c, out-of-plane bending; r, scissoring; x, wagging; t,
twisting.
the bands at 1225, 1188, and 1165 cmꢀ1 in the Raman
symmetrical stretching in CH3 (CH3 symmetric
stretch) and asymmetrical stretching (CH3 asymmet-
ric stretch); in-plane stretching modes (i.e., in-plane
hydrogen stretching mode); the symmetrical (CH3
symmetric deformation) and asymmetrical (CH3
asymmetric deformation) deformation modes; and
the in-plane rocking (CH3 ipr), out-of-plane rocking
(CH3 opr), and twisting (tCH3) modes. In general, the
methyl hydrogen atoms in the methyl group are sub-
jected to back-donation, which causes the decrease
of stretching wavenumbers and infrared intensities,
as reported in the literature.[23] The computed values
of two asymmetrical stretching vibrations of CH3
originate at 3194 and 3157 cmꢀ1 in the HF and 3171
spectrum and the calculated values 1222, 1190, and
1166 cmꢀ1 are assigned to the CH2 twisting modes,
whereas the bands at 813, 210, and 184 cmꢀ1 (HF)
and 812, 212, and 180 cmꢀ1 (B3LYP) are assigned to
the CH2 modes.
CH3 Group Vibrations
The title compound methyl L-prolinate hydro-
chloride under consideration holds one CH3 group.
For the assignments of CH3 group frequencies, one
can expect the following fundamental modes that
are associated to each CH3 group, namely, the
FIGURE 8 Graphic correlation between the experimental and the theoretical frequencies obtained at the (a) HF=HF=6-311þG(d,p)
level and (b) B3LY=6-311þG(d,p) level.
Synthesis and Vibrational Spectra of Methyl L-Prolinate Hydrochloride
685

and 3086 cmꢀ1 in the B3LYP methods, while experi-
mental values are reported at 3179 and 3107 cmꢀ1 in
the FT Raman spectrum. The theoretical CH3
symmetrical stretching frequency is found at 2925
and 2924 cmꢀ1 in the HF and B3LYP methods,
while the experimental value is at 2923 cmꢀ1. The
calculated symmetric bending vibration using HF
and B3LYP methods are 1449 and 1439 cmꢀ1. But
the experimental value contributes at 1440 cmꢀ1 in
FT-IR. On considering the other vibrational modes
of the CH3 group, in-plane rocking and out-of-plane
rocking are observed at 1152 and 1142 cmꢀ1 in the
HF and 1138 and 1125 cmꢀ1 in the B3LYP method,
but the experimental value of in-plane rocking in
FT-Raman is 1131 cmꢀ1, and that of out-of-plane
rocking is 1126 cmꢀ1 in FT-IR. Finally, CH3 twisting
frequency is calculated and found as very lower
frequency, that is, 157 and 156 cmꢀ1 in the above
said methods; obviously, the experimental value
is 156 cmꢀ1 under FT-Raman spectral data.
Ring Vibrations
L-Proline is
a
five-membered nonaromatic
N-heterocyclic chiral amino acid whose ring has
maximum similarity with the pyrrolidine ring while
excluding the carboxylic acid group. By comparing
the frequency behavior of pyrrolidine annular atoms
that form bonds in the ring such as C-C, C-N, we
can easily afford to interpret the ring vibrations of
the target molecule due to structural similarity. In
general, the stretching vibrations of pyrrolidine ring
regions are from 1100 to 800 cmꢀ1. It is acknowledged
with observed Raman values such as 1100, 988cmꢀ1
corresponding to C-N vibration and according to
the same, C-C vibration existence occurs at 1050,
925 cmꢀ1 equally 932 cmꢀ1 in FT-IR, finally at 900 cmꢀ1
in FT-Raman on the title molecule. The computed
values on C-C, C-N vibrations have a noteworthy
degree of closeness with the values of the B3LYP=
6-311þþGꢂꢂ basis sets than those of the HF approach.
This theoretical pattern is similar to ring in-plane-
bending too. The entire ring in-plane bending is
observed at 625 cmꢀ1 and 608 cmꢀ1 in FT-Raman
and FT-IR, respectively.
=
C O Vibrations
The stretching frequency of C¼O and C-O pro-
vides effective information on structural elucidation
of any esters. The C¼O stretching vibration of
saturated ester falls on 1730–1680 cmꢀ1. In general,
three factors have the foremost impact in determin-
ing the frequency of the carbonyl group: inductive,
resonance effects, and hydrogen bonding. Since
there is no aromatic ring or hyperconjugative system,
the frequency is not influenced by them. In addition,
it is witnessed in our present study that the C¼O
stretching vibration is assigned to 1744 cmꢀ1 in
FT-Raman and 1737 cmꢀ1 in FT-IR. The theoretical
investigation at B3LYP=6-311þþGꢂꢂ shows signi-
ficant agreement with real assignments. It lays
on 1741 cmꢀ1. Nevertheless, another theoretical
platform does not show considerable accordance with
the observed vibration whose value is 1731 cmꢀ1. The
C¼O in-plane bending vibration is found at 870 cmꢀ1
in FT-IR and 868 cmꢀ1 in FT-Raman spectra, and
the values 867 and 872cmꢀ1 are calculated by the
B3LYP and HF methods, respectively, under theoretical
consideration. Another fashion of C¼O out-of-plane
bending vibration is expected at 540 ꢃ 80 frequency,
but the observed value is 400 cmꢀ1 in FT-Raman
and the computed value lay on 404 and 400 cmꢀ1 by
HF and B3LYP consideration, respectively.
Mulliken Population Analysis:
Mulliken Atomic Charges
Mulliken atomic charge calculation[24] has an
important role in the application of quantum chemi-
cal calculation to the molecular system. Atomic
charges of the skeleton atom for the title compound
calculated at the HF=6-311þþG(d,p) and B3LYP=
6-311þþG(d,p) model chemistries are presented in
Table 4, because atomic charges affect dipole
moment, polarizability, electronic structure, and
more properties of molecular systems.
For the title compound the Mulliken atomic
charges of H6 and H7 atoms occupy the higher posi-
tive value and become highly acidic. The corre-
sponding Mulliken atomic charges of H6 and H7
are 0.2651e and 0.2625e, respectively, in B3LYP.
The C3 and C17 atoms have a high negative value.
The N1, O15, and O16 atoms have negative charges,
whereas all hydrogen atoms have positive charges.
The result suggests that the atoms N1, O15, and
O16 are electron acceptors, which indicates that the
charge shifts from H6 to N1, C17 to O16, and C14
to O15.
686
V. Balachandran et al.

TABLE 4 Mulliken Atomic Charges of Methyl L-Prolinate Hydrochloride Based on HF/6-311þþG(d,p) and B3LYP/
6-311þþG(d,p) Methods
Atom
HF
B3LYP
Atom
HF
B3LYP
N1
C2
ꢀ0.2508
ꢀ0.2394
ꢀ0.4698
ꢀ0.3136
ꢀ0.3006
0.2813
ꢀ0.2157
ꢀ0.0205
ꢀ0.3359
ꢀ0.3167
ꢀ0.3432
0.2651
H12
H13
C14
O15
O16
C17
H18
H19
H20
H21
Cl22
0.1581
0.1440
0.1676
0.1530
C3
ꢀ0.0232
ꢀ0.3297
ꢀ0.2532
ꢀ0.3271
0.0180
ꢀ0.0367
ꢀ0.2494
ꢀ0.1547
ꢀ0.3801
0.2264
C4
C5
H6
H7
H8
H9
H10
H11
0.2683
0.2625
0.1669
0.1647
0.1522
0.1575
0.1768
0.1572
0.1772
0.1871
0.1661
0.1735
0.2779
0.2471
0.1452
0.1466
ꢀ0.2658
ꢀ0.2555
enhancement of the molecular vibration as the
temperature increases.[26] The correlation equations
between these thermodynamic properties and tem-
peratures for the title compound are listed below.
The correlations between these thermodynamic
properties and temperatures T are shown in Fig. 10.
HOMO–LUMO Energy Gap
In general, a molecule can be characterized by a
highest occupied molecular orbital–lowest unoccu-
pied molecular orbital (HOMO–LUMO) separation,
which is the result of a significant degree of charge
transfer from the end–capping electron–donor to
the efficient electron acceptor group. This energy
gap offers extensive information on the wavelength
that a molecule can observe. The magnitude of
energy gap is largely influenced by nature of conju-
gation.[25] A less conjugated system has a higher
HOMO and LUMO gap. Therefore, a shorter wave-
length is required for electronic excitation. With
respect to methyl L-prolinate hydrochloride, the
HOMO–LUMO energy gap value was found as
4.1646 eV in B3LYP=6-311þþG(d,p) model chemis-
try. Since our target molecule does not have any pi
conjugation, the energy gap was found to be high.
Here, the charge transfer occurs from the
five-membered heterocyclic ring residue system to
the electron-withdrawing methyl ester fragment,
under a shorter wavelength of light. The pictorial
representation of HOMO and LUMO is given in Fig. 9.
Cp0;m ¼ 10:21 þ 0:122T ꢀ 3:0 ꢂ 10ꢀ5T 2ðR2 ¼ 0:998Þ
Hm0 ¼ 0:517 þ 0:157T ꢀ 5:0 ꢂ 10ꢀ5T 2ðR2 ¼ 0:999Þ
Gm0 ¼ ꢀ54:88 ꢀ 0:130T ꢀ 5:0 ꢂ 10ꢀ5T 2ðR2 ¼ 0:998Þ
Sm0 ¼ 55:4 þ 0:287T ꢀ 5:0 ꢂ 10ꢀ6T 2ðR2 ¼ 1:000Þ
Thermodynamic Function Analysis
On the basis of B3LYP=6-311þþG(d,p) vibrational
analyses and statistical thermodynamics, the standard
thermodynamic functions heat capacity (Cp0;m),
entropy (Hm0 ), Gibbs energy (Gm0 ), and enthalpy
(Sm0 ) of the title compound were obtained and are
listed in Table 5. As shown in Table 5, all the values
of Cp0;m, Hm0 , and Sm0 increase in temperature
from 100.0 to 700 K, which was attributed to the
FIGURE 9 Isodensity plots of the frontier molecular orbital of
methyl L-prolinate hydrochloride.
Synthesis and Vibrational Spectra of Methyl L-Prolinate Hydrochloride
687

TABLE 5 Thermodynamic Properties at Different Temperatures at the B3LYP/6-311þþG(d,p) Level for Methyl L-Prolinate Hydrochloride
T (K)
Cp0;m (cal molꢀ1 Kꢀ1
)
H0m (kcal molꢀ1
)
G0m (kcal molꢀ1
)
S0m(kcal molꢀ1Kꢀ1
)
100
200
300
400
500
600
700
23.0523
32.4560
43.2455
54.4163
64.3714
72.7202
79.6625
17.1012
33.3944
51.7263
71.1670
91.4112
112.3108
133.7659
ꢀ66.6160
ꢀ79.7347
ꢀ89.6414
ꢀ98.2168
ꢀ106.0840
ꢀ113.4740
ꢀ120.4840
83.7171
113.1292
141.3676
169.3839
197.4949
225.7845
254.2497
FIGURE 10 Correlation graphic of various thermodynamic parameters: (a) correlation graphic of heat capacity and temperature for
methyl L-prolinate hydrochloride; (b) correlation graphic of entropy and temperature for methyl L-prolinate hydrochloride; (c) correlation
graphic of enthalpy and temperature for methyl L-prolinate hydrochloride; and (d) correlation graphic of Gibb energy and temperature for
methyl L-prolinate hydrochloride.
chemistries. In this study, we have performed
energy calculation on possible rotational isomers.
Comparison between the theoretical and experi-
CONCLUSION
The derivative of L-proline called methyl L-
prolinate hydrochloride has been synthesized. The
mental structural parameters indicates that B3LYP is
optimized geometry and IR and Raman vibrational
spectra are computed for the synthesized mole-
cule using HF and B3LYP (6-311Gþþ(d,p)) model
in good agreement with experimental methods. It
is first time through this literature that the experi-
mental vibrational behavior of methyl-L-prolinate
688
V. Balachandran et al.

11. Li, J.; Sha, Y. A convenient synthesis of amino acid methyl esters.
Molecules 2008, 13(5), 1111–1119.
hydrochloride has been examined and reported
along with computational insight. The energy gap
and its significance between occupied and unoccu-
pied molecular orbitals have been clearly under-
stood. The isodensity surface contour map of the
frontier orbital of HOMO and LUMO indicates the
intramolecular charge transfer occurring within
the molecule. After the basis of vibrational analysis
of the title molecule, the thermodynamic proper-
ties of the methyl L-prolinate hydrochloride at dif-
ferent temperatures have been calculated, which
reveals the corrections between Cp0;m, Hm0 , Sm0 , and
various temperature T.
12. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.;
Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.;
Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, Jr., J. A.;
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin,
K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari,
K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.;
Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken,
V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev,
O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin,
R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;
¨
Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman,
J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision A.02;
Gaussian, Inc.: Wallingford, CT, 2009.
13. Frisch, M. J.; Nielsm, A. B.; Holder, A. J. Gaussview User Manual;
Gaussian 427: Pittsburgh, PA, 2008.
REFERENCES
14. Myung, S.; Pink, M.; Baik, M. H.; Clemmer, D. E. DL-proline. Acta
Cryst. C 2005, 61, 506–508.
1. Kotsuki, H.; Ikishima, H.; Okuyama, A. Organocatalytic asymmetric
synthesis using proline and related molecules. Heterocycles 2008,
75(4), 757–797.
2. List, B. Proline catalyzed asymmetric reactions. Tetrahedron 2002, 58,
5573–5590.
3. Srinivasan, M.; Perumal, S.; Selvaraj, S. (L)-Proline catalyzed efficient
synthesis of 3-substituted 2,6-diarylpiperidin-4-ones. Arkivoc 2005,
xi, 201–208.
4. Yang, X.; Wu, X.; Fang, M.; Yuan, Q.; Fu, E. Novel rigid chiral
macrocyclic dioxopolyamines derived from L-proline as chiral solvat-
ing agents for carboxylic acids. Tetrahedron Asymm. 2004, 15,
2491–2497.
5. Hajos, Z. G.; Parrish, D. R. Asymmetric synthesis of bicyclic
intermediates of natural product chemistry. J. Org. Chem. 1974,
39, 1615–1621.
6. Roomi, M. W.; Ivanov, V.; Kalinovsky, T.; Niedzwiecki, A.; Rath, M. In
vitro and in vivo antitumorigenic activity of a mixture of lysine, pro-
line, ascorbic acid, and green tea extract on human breast cancer
lines MDA-MB-231 and MCF-7. Med. Oncol. 2005, 22(2), 129–138.
7. Allemann, C.; Um, J. M.; Houk, K. N. Computational investigations of
the stereoselectivities of proline – related catalysts for aldol reactions.
J. Molec. Catal. A: Chem. 2010, 324, 31–38.
15. Socrates, G. Infrared and Raman Characteristic Group Wave
Numbers – Tables Charts, 3rd ed.; John Wiley & Sons, England, 2001.
16. Roeges, N. P. G. A Guide to the Complete Interpretation of Infrared
Spectra of Organic Structures; Wiley: New York, 1994.
17. Colthup, N. B.; Daly, L. H.; Wiberly, S. E. Introduction to Infrared and
Raman Spectroscopy; Academic Press: New York, 1975.
18. Evans, J. C.; Wahr, J. C. Thermodynamic and spectroscopic study of
pyrrolidine. II. Vibrational spectra and configuration. J. Chem. Phys.
1959, 31, 655.
19. Gussoni, M.; Castiglioni, C. Infrared intensities. Use of the
CH stretching band intensity as
a tool for evaluating the
acidity of hydrogen atoms in hydrocarbons. J. Mol. Struct. 2000,
521, 1–18.
20. Rumi, M.; Zerbi, G. Conformational dependence of vibrational and
molecular nonlinear optical properties in substituted benzenes: the
role of p-electron conjugation and back-donation. J. Mol. Struct.
1999, 509(1), 11–28.
21. Silverstein, R. M.; Webster, F. X. Spectrometric identification of
organic compounds, 6th ed; John Wiley: Daryaganj, New Delhi, 2003.
22. Rippon, W. B.; Koenig, J. L.; Walton, A. G. Raman spectroscopy of
proline oligomers and poly-L-proline. J. Am. Chem. Soc. 1970,
92(25), 7455–7459.
8. Wagner, C. C.; Torre, M. H.; Baran, E. J. Vibrational spectra of copper
(II) complexes of L-proline. Lat. Am. J. Pharm. 2008, 27(2), 197–202.
9. Mary, Y. S.; Ushakumari, L.; Harikumar, B.; Varghese, H. T.; Panicker,
C. Y. FT-IR, FT-Raman and SERS spectra of L-proline. J. Iran. Chem.
Soc. 2009, 6(1), 138–144.
10. Li, X.-J.; Zhong, Z.-J.; Wu, H.-Z. DFT and MP2 investigations of
L-proline and its hydrated complex. J. Mol. Model 2011, 17(10),
2623–2630.
23. Smith, B. Infrared Spectral Interpretation, A Systematic Approach;
CRC: Washington, DC, 1999.
24. Mulliken, R. S. Electronic Population Analysis on LCAO -MO Molecu-
lar Wave Functions. I. J. Chem. Phys. 1955, 23, 1833–1840.
25. Perepichka, D. F.; Bryce, M. R. Molecules with exceptionally small
HOMO–LUMO gaps. Angew. Chem. Int. Ed. 2005, 44, 5370–5373.
26. Bevan Ott, J.; Boerio-Goates, J. Chemical Thermodynamics: Principles
and Applications; Academic Press: San Diego, CA, 2000.
Synthesis and Vibrational Spectra of Methyl L-Prolinate Hydrochloride
689

Copyright of Spectroscopy Letters is the property of Taylor & Francis Ltd and its content may
not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.