Crystal structure, computational studies, and stereoselectivity in the synthesis of 2-aryl-thiazolidine-4-carboxylic acids via in situ imine intermediate

Article abstract of DOI:10.1080/17415993.2016.1156116

ABSTRACT: This article presents the synthesis of (2R/2S,4R)-2-aryl-thiazolidine-4-carboxylic acids via nucleophilic addition of L-Cysteine on aromatic aldehydes involving a yield and time-effective room temperature reaction in an aqueous DMSO medium in the presence of NaHCO₃ as a base. The synthesized diastereomers were spectroscopically characterized and quantified for diastereomeric excess by liquid chromatography-mass spectrometry analysis. The impact of the type and position of substituent in aromatic aldehydes on reaction time, % yield, ¹H NMR shift at newly formed chiral center [C(2)-H], and diastereomeric excess (de%) have been investigated. A plausible mechanism for stereoselectivity via an in situ imine intermediate is proposed using real-time IR monitoring of the synthetic reaction based on the significant signals at 1597, 1593 cm^?1 for imine (C=N) stretching. The imine mechanism for stereoselectivity was further supported by NMR studies of azomethine ¹³C NMR signals at 159, 160 δ ppm and by the single crystal structure of hitherto unknown (2S,4R)-3-(tert-butoxycarbonyl)-2-(2-hydroxyphenyl)thiazolidine-4-carboxylic acid (3a) obtained as a major diastereomer in the synthesis of the butyloxy carbonyl (BOC) derivative of (2R/2S,4R)-2-(2-hydroxyphenyl)thiazolidine-4-carboxylic acid. The significant ortho-OH effect of phenolic hydroxyl group leading to strong hydrogen bondings plays a vital role in the formation of 2S,4R BOC derivative stereoselectively. The frontier molecular orbitals, possible electronic excitations, IR band characterizations, and reactivity parameters of newly reported compound (3a) have been predicted using quantum chemical descriptors from density functional theory. The theoretical exploration of experimental spectra using time-dependent DFT indicated a (π–π*) transition between HOMO and LUMO in the ultraviolet region. (Figure presented.)

Full text of DOI:10.1080/17415993.2016.1156116

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Crystal structure, computational studies, and
stereoselectivity in the synthesis of 2-aryl-
thiazolidine-4-carboxylic acids via in situ imine
intermediate
Rohidas M. Jagtap, Masood A. Rizvi, Yuvraj B. Dangat & Satish K. Pardeshi
To cite this article: Rohidas M. Jagtap, Masood A. Rizvi, Yuvraj B. Dangat & Satish K. Pardeshi
(2016): Crystal structure, computational studies, and stereoselectivity in the synthesis of 2-aryl-
thiazolidine-4-carboxylic acids via in situ imine intermediate, Journal of Sulfur Chemistry, DOI:
10.1080/17415993.2016.1156116
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Date: 23 March 2016, At: 06:05

JOURNAL OF SULFUR CHEMISTRY, 2016
http://dx.doi.org/10.1080/17415993.2016.1156116
Crystal structure, computational studies, and stereoselectivity
in the synthesis of 2-aryl-thiazolidine-4-carboxylic acids via
in situ imine intermediate
Rohidas M. Jagtapa, Masood A. Rizvib, Yuvraj B. Dangatc and Satish K. Pardeshia
aDepartment of Chemistry, Savitribai Phule Pune University (formerly University of Pune), Pune, India;
bDepartment of Chemistry, University of Kashmir, Srinagar, India; cPhysical Chemistry Division, CSIR-National
Chemical Laboratory, Pune, India
ABSTRACT
ARTICLE HISTORY
Received 22 May 2014
Accepted 16 February 2016
This article presents the synthesis of (2R/2S,4R)-2-aryl-thiazolidine-
4-carboxylic acids via nucleophilic addition of L-Cysteine on aro-
matic aldehydes involving a yield and time-effective room temper-
ature reaction in an aqueous DMSO medium in the presence of
NaHCO3 as a base. The synthesized diastereomers were spectro-
scopically characterized and quantified for diastereomeric excess
by liquid chromatography-mass spectrometry analysis. The impact
of the type and position of substituent in aromatic aldehydes on
reaction time, % yield, 1H NMR shift at newly formed chiral cen-
ter [C(2)-H], and diastereomeric excess (de%) have been investi-
gated. A plausible mechanism for stereoselectivity via an in situ
imine intermediate is proposed using real-time IR monitoring of
the synthetic reaction based on the significant signals at 1597,
1593 cm−1 for imine (C = N) stretching. The imine mechanism for
stereoselectivity was further supported by NMR studies of azome-
KEYWORDS
2-aryl-thiazolidine-4-
carboxylic acids; imine
intermediate; X-ray crystal
structure; density function
theory; frontier molecular
orbitals
thine 13C NMR signals at 159, 160 δ ppm and by the single crys-
tal structure of hitherto unknown (2S,4R)-3-(tert-butoxycarbonyl)-
2-(2-hydroxyphenyl)thiazolidine-4-carboxylic acid (3a) obtained as
a major diastereomer in the synthesis of the butyloxy carbonyl
(BOC) derivative of (2R/2S,4R)-2-(2-hydroxyphenyl)thiazolidine-4-
carboxylic acid. The significant ortho-OH effect of phenolic hydroxyl
group leading to strong hydrogen bondings plays a vital role in
the formation of 2S,4R BOC derivative stereoselectively. The frontier
molecular orbitals, possible electronic excitations, IR band charac-
terizations, and reactivity parameters of newly reported compound
(3a) have been predicted using quantum chemical descriptors from
density functional theory. The theoretical exploration of experimen-
tal spectra using time-dependent DFT indicated a (π–π*) transition
between HOMO and LUMO in the ultraviolet region.
CONTACT Satish K. Pardeshi
skpar@chem.unipune.ac.in
Supplemental data for this article can be accessed here. http://dx.doi.org/10.1080/17415993.2016.1156116
© 2016 Informa UK Limited, trading as Taylor & Francis Group

2
R. M. JAGTAP ET AL.
1. Introduction
Researchers have focused on organosulfur compounds because of their huge biological
activities. Among these, thiazolidines have been revealed as a promising organosulfur
class with a wide range of medicinal values.[1–9] Thiazolidine moieties have also been
used as chiral heterocyclic ligands for transition metals and the crystal structures of some
mononuclear nickel, cobalt complexes have been reported.[10] Recently 2D, 3D-QSAR and
pharmacophore studies on thiazolidine-4-carboxylic acid derivatives as neuraminidase
inhibitors in H3N2 influenza virus have also been reported.[11] Considering the impor-
tance of this class (thiazolidines) of compounds, studies comparing substituent-dependent
reactivity of substrates and reagent specificity for their synthesis have been conducted.[12]
The (2R/2S,4R)-2-aryl-thiazolidine-4-carboxylic acid (2A-T4CA) moieties have been syn-
thesized from L-Cysteine hydrochloride by deploying several synthetic methods using
a variety of bases and solvents such as AcOK-EtOH,[13] AcONa-EtOH,[14] AcOK-
EtOH-Benzene,[15] NaOH-EtOH,[16] NaOH-H2O-Dioxane,[17] Et3N-EtOH,[18] Et3N-
NMP,[19] TiCl4-EtOH-NaOH,[20] NaHCO3-EtOH[04], Pyridine-H2O.[21] The natural
4R stereo center in 2A-T4CA can be also utilized to enhance stereoselectivity in L-proline-
based organo-catalytic synthesis.[22] In spite of the variety of synthetic methods for
thiazolidines, better protocols using non-volatile media, simple reagents, and time-efficient
reactions to give high-purity products is always desired. Besides, none of the synthetic
reports, mentioned above, focus on stereoselectivity of the products. In cognizance with
the concept of asymmetric induction, correlating impact of the stereochemistry of groups
present in a substrate with the control of chiral purity in the product, we report the
synthesis of 2A-T4CA through room temperature reaction in water-DMSO medium in
presence of NaHCO3 as a base. The complete characterization of diastereomeric prod-
ucts and stereoselectivity in terms of diastereomeric excess (de %) is reported. The impact
of aromatic aldehyde substituent on reaction time, and % yield is also reported. Real-
time IR and NMR monitoring of the reaction and the crystal structure of the unknown
(2S,4R)-3-(tert-butoxycarbonyl)-2-(2-hydroxyphenyl)thiazolidine-4-carboxylic acid (3a)

JOURNAL OF SULFUR CHEMISTRY
3
are used to propose an imine intermediate mechanism. The physicochemical properties
of this newly reported major diastereomer (3a) have been computationally explored with
density functional theory (DFT) at the recommended CAM-B3LYP/6-311G + (d,p) level
using Gaussian 09 software and compared with experimentally obtained values.
2. Results and discussion
2.1. Synthesis of (2R/2S,4R)-phenylthiazolidine-4 -carboxylic acid (2a) and role of
solvent
The synthesis of (2R/2S,4R)-phenylthiazolidine-4-carboxylic acid from L-Cysteine
=
hydrochloride and Benzaldehyde was used as a model reaction (Scheme 1, R H) for sol-
vent optimization of 2A-T4CA synthesis in different solvents using equimolar quantities
of substrate and reagents. The optimization results for compound 2a are shown in Table 1.
Among the ten solvents studied (Table 1), 20% aqueous DMSO was found optimum
for the synthesis of (2a) in terms of percent yield and reaction time, which is attributed
to appropriate polarity of the medium suitable for solubility and reactivity of the compo-
nents of the reaction. Furthermore, increasing water content after completion of reaction
in 20% aqueous DMSO resulted in product precipitation with excellent yields. Subsequent
to optimizing the reaction medium, the scope of NaHCO3 as a base in 20% aq. DMSO was
explored for several other aromatic aldehydes with different substituents at variable posi-
tions on the aromatic ring (Scheme 1). The nucleophilic addition underwent smoothly to
afford the respective diastereomers of 2A-T4CA with fair purity and yields (Table 2, Entries
1–18).
2.2. Setereochemical analysis and impact of substituents in synthesis
1
The presence of diastereomers was reflected in the signal replication pattern in H and
13C NMR spectra of 2A-T4CA, showing difference in chemical shifts as well as cou-
pling constants for similarly positioned protons. The diastereomers were quantified by
Scheme 1. Synthesis of 2A-T4CA.
Table 1. Optimization of the solvent medium for nucleophilic addition.
Entry
Solvent
Time (h)
Yield (%)
Entry
Solvent
Time (h)
Yield (%)
1
2
3
4
5
H2O
Dioxane
EtOH
MeOH
50% aq. EtOH
26.0
18.0
14.0
12.0
13.5
86
83
87
88
90
6
7
8
9
10
50% aq. MeOH
DMSO
10% aq. DMSO
20% aq. DMSO
30% aq. DMSO
13.0
09.0
10.5
12.0
10.0
91
89
92
94
91

4
R. M. JAGTAP ET AL.
Table 2. Stereochemical impact of substituent on synthesis of 2A-T4CA.
Entry
R
Product
Yielda (%)
Reaction timeb (h)
Chemical shift C(2)-H (δ ppm)c
ded (%)
1
2
3
4
5
6
7
8
H
2-OH
2-OCH3
2-NO2
3-NO2
4-CH3
4-OCH3
4-Br
4-Cl
4-N(CH3)2
4-COOH
4-OH
2-OH, 4-OCH3
2-OCH3, 4-OH
3-OCH3, 4-OH
2,3-OH
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2p
2q
2r
82
78
83
91
80
70
86
73
73
62
88
91
80
84
82
83
75
85
12.0
12.5
14.0
05.0
12.0
12.0
13.5
14.0
13.5
18.0
09.0
07.5
13.5
12.0
13.0
14.5
11.0
12.0
5.5, 5.7
5.7, 5.8
5.5, 5.6
6.3, 6.9
5.7, 5.9
5.4, 5.5
5.4, 5.5
5.5, 5.7
5.5, 5.7
5.1, 5.3
5.6, 5.8
6.1, 6.3
5.4, 5.6
5.3, 5.5
5.5,5.4
5.6, 5.8
5.3, 5.8
6.2
00
40
46
68
04
00
10
30
30
04
20
30
64
76
62
60
20
98
9
10
11
12
13
14
15
16
17
18
3,4-OH
2,6-Cl
2s
aOverall yields.
bObtained by TLC monitoring.
cObtained from 1H NMR spectra.
dObtained from LCMS analysis using commercial column.
Liquid chromatography-mass spectrometry (LCMS) analysis of the products (Supple-
mentary data, Figure S1). The stereochemical impact of different substituents and their
positions was studied in terms of reaction time, % yield, chemical shift at newly gener-
ated chiral center [C(2)-H] and quantified by diastereomeric excess (de %), as shown in
Table 2. It was observed that under our reaction conditions, the presence of electron-
withdrawing groups such as -NO2 reduced reaction time (5 h.), while electron-donating
groups such as -OH (12.5 h.) and -OCH3 (14 h.) increased reaction time in compari-
son to unsubstituted benzaldehyde (12 h.) (Table 2, Entry 1–4). In the case of aldehydes
with substituents at position-2, the reactivity of 2-nitrobenzaldehyde was the highest. The
substitution at position-3 of the aromatic ring does not have any significant impact on reac-
tivity of the aldehyde. The substitution at position -4 gave the following trend of reaction
time: -NO2 < -COOH < -CH3, <-OCH3, -Cl, <-Br, <-NMe2, which also indicated
that electron-withdrawing groups at position-4 increase rate of reaction. In case of disubsti-
tuted aromatic aldehydes, the time required for completion of reaction was in the range of
11.0–14.5 h. The 2-OH containing disubstituted aldehyde (Table 2, Entry-13) reacts slower
than 2-OCH3 (Table 2, Entry-14) possibly due to presence of intra molecular hydrogen
bonding. All the compounds (2a–2s) were obtained in good yields (>70%) under opti-
mized reaction conditions except, compound 2j (Table 2, Entry-10; 62%). This can be
attributed to strong + R effect of -NMe2 group, which diminishes the electrophilicity of
the aldehyde.
2.3. Substituent Effects on chemical shifts and diastereoselectivity
The diverse shielding and de-shielding effect of substituents on aromatic aldehy-
des generate different chemical shifts at C(2)-H. The overall trend in chemical shift
(δ ppm) values in case of electron-withdrawing substituents was 2-NO2 > 4-NO2 > 2,
6-Cl > 3-NO2 > 4-COOH. While in the case of electron-donating groups the trend

JOURNAL OF SULFUR CHEMISTRY
5
was 4-NMe2 < 2-OCH3, 4-OH < 3,4-OH < 2-OH, 2-OCH3 < 4-Me < 4-OMe < 2-
OMe < 4-Br = 4-Cl < 2-OH. The slight enhancement noted in δ ppm values in the case
of 2-OH (Table 2, Entry 2) in comparison to 2-OCH3 (Table 2, Entry 3) is likely due to a
significant field effect. Among all substituents, the 2-NO2 (Table 2, Entry 4) exhibited the
−
strongest deshielding (6.3, 6.9 δ ppm) due to synergism of R and field effect. While the
4-NMe2 substituent (Table 2, Entry 10) exerts a strong shielding due to a + R effect (5.1,
5.3 δ ppm). From an LCMS analysis, it is found that the substituent positions are more vital
to decide % de values than their electronegativity. The reaction of benzaldehyde gave both
isomers of 2a in nearly equal proportions but when we put substituents in the 2-position
the selectivity increased with their size (2-OH < 2-OMe < 2-NO2) to give high % de val-
ues. The 3-NO2 in 2e showed a minor role in selectivity. The % de values were higher
especially among electron-withdrawing groups at position-4, strongly implicating their
role in stabilization of reaction intermediates. The presence of electron-donating groups
at position-4 however showed lower % de values. For disubstituted aldehydes, the highest
de % was obtained with at least one of the substituent present at position-2 (Table 2, Entry
13, 14, 16, 18). Compound 2s gave the highest % de value, suggesting that both 2, 6 posi-
tioned substituent have a strong impact on holding the intermediate in one of the stable
conformations.
2.4. Proposed in situ imine intermediates mechanism
The stereoselectivity of the reaction can be explained on the basis of the plausible mech-
anism shown in Scheme 2. The reaction is proposed to proceed via diastereomeric E or
H2N
SH
NaHCO3
Cl
H3N
SH
(R)
CO2
H2O
HO
NaCl
O
(R)
HO
O
(C=O-1759 cm-1)
HO
OH
OH
H
H
N
(R)
H
N
(R)
2
(C=O - broad
at 1624 cm-1,
-OH 3098 cm-1)
2
(C=O - broad
at 1624 cm-1,
-OH 3098 cm-1)
H
H
(S)
S
(R)
S
O
4
4
HO
HO
O
O
(2S,4R)
Major
(2R,4R)
Minor
HO
H
OH
SH
H
H
OH
H
OH
S
S
N
N
N
H
(R)
(R)
(R)
HO
HO
HO
O
O
O
(Z)-imine
(E)-imine
(C=N-1573/1597 cm-1
,
(C=N-1573/1597 cm-1,
-OH 3098 cm-1)
-OH 3098 cm-1
Stable
)
Less Stable
Scheme 2. Plausible mechanism with diastereomeric imines for synthesis of 2b.

6
R. M. JAGTAP ET AL.
Z imine intermediates. The diastereomeric imines undergo cyclization by attack of thiol
to give the corresponding diastereomers. The enhanced thermodynamic stability of the E
isomer would result in the formation of 2S,4R diastereomer as the major product.
The proposed imine intermediate mechanism is based on the real-time IR reaction
monitoring for the synthesis of compound 2b. To ascertain the existence of imines, the
liquid fractions from reaction mixture (after addition of aldehyde) were quenched by ice at
−
an every 10 min time intervals and monitored by IR spectroscopy to identify the C=N
stretching frequency peaks of imines (azomethines) as shown in Figure 1. In the course of
reaction, the distinct, strongly hydrogen bonded C=O stretching band at 1759 cm−1 in
−
L-Cysteine hydrochloride disappeared due to generation of free amino acid by NaHCO3
in aqueous DMSO medium. More concentration of zwitter ion and high nucleophilicity
of S enable its initial attack on aldehyde, is not observed in this IR monitoring experi-
ment, which supports the initial attack by amine nitrogen. The elimination of water from
−
linear amino alcohols seems to be rapid as reflected in appearance of C=N peaks in
−1
−
the fraction isolated at 10 min. The appearance of acid C=O stretching at 1616 cm
along with two shoulder peaks at 1573 cm−1 and 1595 cm−1 attributed to C=N stretch-
−
ing emerged and progressively became prominent upto 180 min. After completion of the
−
reaction at about 12.5 h., the product showed broad distinct C=O stretching signal at
1624 cm−1, confirming that the imine intermediate has undergone cyclization to com-
pound 2b. This mechanism of stereoselectivity is in agreement with the proposed ring
opening imine intermediate mechanism [23] for selective inversion at C2 position in acety-
lation of Thiazolidine-4-carboxylic Acids. Recently the transformation of N-BOC T4CA
(2R/2S,4R) diastereomers into single diastereomer (2R,4R) by dynamic kinetic resolution
was proposed on the basis of imine (Schiff’s base) intermediates.[24] Our work is of more
Product
180 min
150 min
90 min
1624
20 min
10 min
1597
% T
L-Cysteine
1573
L-Cysteine.HCl
1582
1759
1800
1700
1600
1500
1400
1300
1200
-1
Frequency (cm )
Figure 1. Real-time IR monitoring for synthesis of 2b: investigation towards imine intermediates.

JOURNAL OF SULFUR CHEMISTRY
7
interest as it provides experimental support in favor of imine intermediate mechanism of
diastereoselectivity in synthesis of 2-aryl-thiazolidine-4-carboxylic acids not reported so
far.
Recently Ershov et al. [25] have reported the synthesis of 3-(3-mercapto-propionyl)
thiazolidine-4-carboxylic acids and the ring-chain tautomerism of 2-aryl-6-oxohexahydro
pyrimidine-4-carboxylic acid sodium salts in D2O on the basis of NMR signals of linear
azomethine intermediate.[26] In addition to real-time IR reaction monitoring, to ascer-
tain the existence of linear imine, we have monitored the reaction by NMR spectroscopy
to support the proposed mechanism for ring closure (Figure 2). The 0.2 mM (0.0350 g) of
L-Cysteine HCl was dissolved in 0.6 ml of 20% DMSO-d6 in D2O in a NMR tube. The 1H,
13C NMR spectra of this clear sample solution were recorded. After recording the data, to
the same tube 0.2 mM (0.0250 g) of Salicyldehyde was added and shaken for a minute. The
resultant reaction mixture was immediately used to record 1H NMR signals. From the 1H
NMR it is clear that, on addition of aldehyde the linear imine formation and its cycliza-
tion is rapid as H-5 singlet at 6.13, 6.34 δ ppm and azomethine proton signal at 9.19 δ ppm
could be identified in only 3 -min scan. At 10 min scan for the CMR signals of reaction mix-
ture, the appearance of signals at 159, 160 δ ppm represents azomethine carbons, whereas
the minor signal at 62.63 δ ppm of C-4 carbon reveals the coexistence of linear imine and
−
cyclized product 2b. The CH2SH carbon signal still found at 36.27 δ ppm indicates the
presence of unreacted amino acid. The minor downfield shifts in 1H NMR signals for H-
2 from 5.83, 5.64 δ ppm in pure 2b to 6.13, 6.34 δ ppm in experimental spectra might be
due the use of DMSO-d6–D2O solvent combination rather than only DMSO-d6 used to
record spectra of pure 2b. These NMR studies strongly support the proposed linear imine
intermediate mechanism.
Figure 2. NMR studies for existence linear imine intermediate.

8
R. M. JAGTAP ET AL.
2.5. Confirmation of major diastereomer
Encouraged by the results, we decided to confirm the major diastereomer through unam-
biguous and definitive conformations in the crystal state using the X ray crystallography
of the compound 2b or its derivative which could corroborate to the understanding of
stereochemical properties in solution. The tert-butoxycarbonyl (BOC) is known to be a
wonderful protecting group; besides this, it can also build up a variety of weak intermolec-
ular forces of attraction essential for packing of molecules during the crystal growth.[27]
Visualizing this concept the compound 2b was subjected for BOC protection of secondary
amine. The reaction products got separated as solid diastereomeric mixture 3. On solvent
evaporation, purification and separation over the silica column it gave white solids 3a with
25
25
[α]D + 10.7 (c 1.25, MeOH) and 3b with [α]D + 73.2 (c 1.25, MeOH), with individual
25
yields 85% and 15%, respectively, as shown in Scheme 3. The [α]D value of compound
3b having 2R,4R stereochemistry was in agreement with its structural analogs reported by
Ershov et al.[25] The major product 3a got crystallized by solvent diffusion method using
CHCl3-Hexane solvent system through slow evaporation of CHCl3 solvent.
2.6. X-ray crystallographic structure of 3a
The compound 3a is crystallized in monoclinic crystal system with P21 space group. A
perspective view of compound 3a through ORTEP diagram is shown in Figure 3 and the
detailed crystallographic characteristics are summarized in supplementary data (Table S5).
−
The asymmetric unit of 3a contains two molecules with ortho OH phenyl rings and
functionalized thiazolidine rings oriented orthogonal to each other.
The C6–C7, C21–C22 bond lengths in compound 3a are found as 1.501 Å,
1.503(1) Å, respectively. The torsion (dihedral) angles for S1–C7–C6–C1, N1–C7–C6–C5,
Scheme 3. Synthesis and separation of (2R/2S,4R)-3-(tert-butoxycarbonyl)-2-(2-hydroxyphenyl)
thiazolidine-4-carboxylic acid.

JOURNAL OF SULFUR CHEMISTRY
9
Figure 3. ORTEP view of the two molecules of compound (3a) in asymmetric unit with displacement
ellipsoids drawn at 50%.
S2–C22–C21–C16 and N2–C22–C21–C20 are obtained as −77.31, −18.28°, −80.19° and
−21.29°, respectively. The thiazolidine rings are functionalized with the carboxylic acid
and N-BOC ester on adjacent atoms. The five-member thiazolidine rings are in slightly
distorted cyclic conformation with S occupying endo position. The C8–S1 and C7–S1
bond length is 1.802(1) and 1.826(2) Å, respectively, along with C8-S1-C7 bond angle of
90.08(3)°. The X-ray structure of compound 3a indicates the 2S, 4R stereochemistry at the
chiral carbons C7 and C9 in one molecule and same stereochemistry is maintained at C22,
C24 of another molecule. The pendant carboxylic acid and carboxylate ester groups on the
thiazolidine ring undergo extensive intermolecular hydrogen bonding, leading to the for-
mation of a three-dimensional supramolecular assembly. Each molecule of 3a shows four
−
hydrogen bonding interactions with adjacent molecules, through two OH group donors
and two acceptor C=O groups (Figure 4). The various hydrogen bond parameters of
−
3a are given in Table 3. The supramolecular assembly of compound 3a through hydrogen
bonding interactions is shown in supplementary information (Figure S2).
Zhu et. al. [24] have recently reported the formation of exclusively single 2R,4R sim-
−
−
−
ilar N-BOC derivatives and their X-ray crystal structures having 2 Br, 2 OCH3, 4 Cl
substituents on aromatic ring The formation of major 2S,4R diastereomer in our case
distinguishes our work from this report. The preferred 2S stereochemistry in 3a may be
attributed to significant ortho-OH effect in which phenolic hydrogen extends the strong
H-bonding with carbonyl oxygen of carboxylate ester. This phenomenon may be playing
a vital role to prefer the 2S, 4R configuration in product, which ultimately results in the
formation of 3a as a major isomer.
2.7. DFT-optimized structure of 3a
DFT is a popular computational method of chemists for analysis of experimental prop-
erties. In this regard, we have performed DFT studies for perfect match of optimized
structure with the experimental crystal structure. In this studies, for assigning transitions

10
R. M. JAGTAP ET AL.
Figure 4. H-bonding pattern in 3a.
Table 3. Hydrogen bond distance and angle for 3a [Å and °].
D-H . . . A
d(D-H)
d(H . . . A)
d(D . . . A)
< (DHA)
O(1)-H(1Aꢀ) . . . O(9)#1
O(3)-H(3Aꢀ) . . . O(7)
O(6)-H(6Aꢀ) . . . O(4)#2
O(8)-H(8Aꢀ) . . . O(2)#3
0.82
0.82
0.82
0.82
1.97
1.93
1.94
1.87
2.767 (6)
2.665 (6)
2.758 (6)
2.674 (6)
164.3
149.0
172.4
164.3
Note: Symmetry transformations used to generate equivalent atoms: #1 −x + 1, y−1/2, −z + 1 #2 −x + 1, y + 1/2, −z + 2
#3 x−1, y, z.
we used the recommended [28] Coulomb-attenuating method (CAM-B3LYP) in conjunc-
tion with polarizable continuum model of solvation (PCM) together with a 6-31G (d,p)
basis set of DFT using Gaussian 09 software. The theoretical IR frequency bands assign-
ment was done by considering the major fragments of molecule as thiazolidine ring, BOC
ester, and hydroxyphenyl ring to generate theoretical IR spectra of compound 3a (sup-
plementary data, Table S6, Figure S3). Comparison of selected geometrical parameters of
the X-ray crystallographic structure and DFT-optimized structure of the compound 3a are
depicted (supplementary data, Table S7) to produce the DFT-optimized theoretical crystal
structure (A) as shown in Figure 5.
2.8. Optical behavior and stability of 3a
In order to explore any photovoltaic material property and to gain an insight of optical
behavior of newly reported compound 3a having two chiral centers, the absorption and
emission spectra were recorded in three solvents as shown in Figure 6.
From Figure 6 it can be seen that the absorption and emission spectra of compound 3a
show a slight bathochromic shift with increasing solvent polarity. The experimental stokes

JOURNAL OF SULFUR CHEMISTRY
11
(a)
(b)
Figure 5. DFT-optimized (A) and X-ray crystallographic structure (B) of 3a.
I
II
Figure 6. Absorption (I) and emission (II) spectra of compound 3a.

12
R. M. JAGTAP ET AL.
shift (difference in absorption and emission maxima) was also found to be increasing with
the increase in solvent polarity (26 and 22 nm respectively for methanol and THF). The
lowered fluorescence intensity in case of methanol compared to chloroform and THF can
be attributed to the solvent quenching.[29] In order to arrive at the nature of electronic
transition in the case of compound 3a, the HOMO–LUMO energies were computation-
ally worked out from single point energy calculation of crystal structure of compound
3a using CAM-B3LYP/6-31G (d,p) level of theory.[30] The computational analysis [31]
revealed the absorption spectrum involving a (π–π*) transition from HOMO to LUMO
as possible electronic excitation in compound 3a, which was also evident from the observed
solvatochromic behavior.[32] The time-dependent density functional theory (TDDFT)
calculation also indicate a (π–π*) transition between HOMO and LUMO in ultraviolet
region with an excitation energy of 4.60 eV corresponding to absorption wavelength of
269 nm(for CHCl3 solvent), which is fairly close to its experimental value of 279 nm. The
other theoretically possible transitions in ultraviolet region which are not experimentally
distinct can be a HOMO-1 to LUMO and HOMO to LUMO + 1 transitions. A perspective
view of frontier molecular orbitals of compound 3a is shown in Figure 7.
The molecular orbital plots indicate that the electron density in case of HOMO is con-
centrated on sulfur atom and phenyl ring, while in the case of LUMO the electron density
is predominantly on anti-bonding orbital of the phenyl ring. Quantum chemical descrip-
tors are good to predict such properties of compound [33–35] and hence calculating such
descriptors for a newly reported compound 3a is interesting. The global reactivity descrip-
tors such as electronegativity (χ = 3.54 eV), hardness (η = 5.38 eV), and electrophillicity
(ω = 1.16 eV) of compound 3a predict it to be a very stable compound, [36] which was
also corroborated from molecular electrostatic potential plot in which the higher electron
density is situated on more electronegative oxygen atoms (red) in comparison with very
Figure 7. Frontier molecular orbitals of compound 3a.

JOURNAL OF SULFUR CHEMISTRY
13
Figure 8. Electrostatic potential map and HOMO–LUMO orbital energy plots of compound 3a.
lower electron density on less electronegative carbon and hydrogen atoms (blue) Figure 8.
A band gap (HOMO–LUMO) of 5.38 eV, according to the frontier molecular orbital the-
ory, may not easily lead to the formation of a transition state between the frontier orbitals
of reactants.[37]
3. Conclusions
The present study demonstrated the efficient synthesis of 2A-T4CA in 20% aqueous
DMSO medium using NaHCO3 as a base. The formation of 2A-T4CA is proposed to occur
via in situ imine intermediate in which 2S, 4R diastereomer is the major isomer obtained
from E imine and 2R, 4R minor isomer obtained from Z imine. The plausible mechanism
is supported by real-time IR profiling of the reaction and NMR studies. The X-ray sin-
gle crystal structure of the N-BOC derivative 3a further validates the possibility of imine
intermediate in the synthesis of 2A-T4CA in 20% aqueous DMSO medium. The electron
density plot and other reactivity descriptors obtained from DFT study of newly reported
compound 3a predict it to be fairly stable. The quantum chemical calculations of 3a using
TDDFT indicate a (π–π*) transition between HOMO and LUMO in ultraviolet region.
4. Experimental
4.1. General information
The TLC monitoring was done on Merck DC precoated TLC plates with 0.25 mm Kieselgel
60 F254. Visualization was done using 254 nm UV lamp. All purified products were char-
acterized by 1H and 13C-NMR spectroscopy in δ ppm (300 and 500 MHz NMR, VARIAN
Mercury), IR spectroscopy in cm−1 (FTIR-8400 spectrometer, SHIMADZU), and elemen-
tal analysis was done using VARIAN EL-II instrument. The LCMS analysis was done using
Ultra Fast Mass Spectrometer (LCMS-8030, SHIMADZU) with Chiracel OD column and
isobutane as an eluting solvent. Super Nova Dual source X-ray Diffractometer System (Agi-
lent Technologies) equipped with a CCD area detector was used for X-ray crystal structure.

14
R. M. JAGTAP ET AL.
NMR mechanistic study was done by 1H and 13C-NMR spectroscopy in δ ppm (500 MHz
NMR, SHIMADZU) and specific rotation were taken using JASCO - P1020 polarimeter.
4.2. Solvent optimization for synthesis of (2R/2S,4R)-2- phenyl
thiazolidine-4-carboxylic acid (2a)
The 1.0 mM (0.175 g) of L-Cysteine hydrochloride(1), 1.0 mM (0.084 g) NaHCO3 and
0.95 mM (0.100 g) Benzaldehyde was stirred at R.T. in 40 ml of various solvents (Table 1,
entries 1–10) such as H2O, Dioxane, EtOH, MeOH, aq. EtOH, aq. MeOH, DMSO and
aqueous DMSO. After total consumption of aldehyde, the reaction (monitored by TLC)
mixture was poured on crushed ice, and precipitated white solid product was filtered and
dried to get the diastereomeric (2R/2S,4R)-2-phenyl thiazolidine-4-carboxylic acid (2a).
4.3. Real-time IR monitoring for synthesis of (2R/2S,4R)-2-(2-hydroxyphenyl)
thiazolidine-4-carboxylic acid (2b)
Initially the FT-IR spectrum for solid L-Cysteine hydrochloride was recorded as neat and
the same instrument as well as program was used to record subsequent spectra. For real-
time IR monitoring of the reaction, 1.0 mM (0.175 g) of L-Cysteine hydrochloride (1) and
1.0 mM (0.084 g) NaHCO3 was stirred in 40 ml of 25% aq. DMSO at R.T. to a homogenous
solution. After getting a clear solution, 0.25 ml solution fraction was collected, quenched
in ice (about 2–3 g), and filtered under vacuum to dryness using Whatmann 42 paper to
get a white solid examined for IR spectra of free amino acid (L-Cysteine). The zero time
was set while addition 0.95 mM (0.122 g) Salicylaldehyde and the sample fractions from
stirring reaction mixture were prepared by the above procedure and were monitored by IR
spectroscopy at an interval of 10 min up to 180 min. The final IR spectrum represents the
product precipitated at 12.5 h. as 2b.
4.4. Synthesis and separation of (2R/2S,4R)-3-(tert-butoxycarbonyl)-2-
(2-hydroxyphenyl) thiazolidine-4-carboxylic acid (3)
The 1.0 mM (0.225) of 2b and 2.5 mM (0.21 g) NaHCO3 were taken in a 100 ml two neck
flask and stirred in 25 ml 50% aqueous 1,4-dioxane at 0°C for 1.5 h., and 1.4 mM (0.305 g)
of di-t-butyloxy carbonyl was added to it drop wise, continuously stirred by natural heat-
ing to R.T. for 12 h. The reaction mixture was acidified up to pH 4.0 by cold 2N HCl and
extracted in ethyl acetate. The extract was washed by cold saturated NaHCO3 and the aque-
ous layer acidified up to pH 4.0 by cold 2N HCl. The acidic medium solution was extracted
in DCM, which on solvent evaporation gave an oily solid 3. The mixture 3 on purification
and separation by silica column chromatography using 40% ethyl acetate in hexane gave
white solids 3a (2S,4R diastereomer) and 3b (2R,4R diastereomer) with isolated yields 85%
and 15%, respectively.
4.5. Crystal structure determination of 3a and refinement
Single crystals of compound 3a were directly obtained by room temperature evapora-
tion of CHCl3 solution of reaction product purified from silica column. A colorless single

JOURNAL OF SULFUR CHEMISTRY
15
crystal (0.38×0.18×0.06 mm) of C15H19N1O5S1 was placed in 0.7 mm diameter nylon
CryoLoops (Hampton Research) with Paraton-N (Hampton Research). The loop was
mounted on a Super Nova Dual source X-ray Diffractometer system (Agilent Technolo-
gies) equipped with a CCD area detector and operated at 250 W power (50 kV, 0.8 mA)
to generate Mo Kα radiation (λ = 0.71073 Å) at 296(2) K. A total of 11580 reflections
were collected of which 4721 were unique. The range of θ was from 6.06 to 58.22°. Data
integration and indexing was carried out using Crystal clear, and structures were solved
using direct method SIR-92. The complete refinement calculations were carried using pro-
grams in WinGX module. The final refinement of structures was carried out using full least
square methods on F2 using SHELXL-97. The structure was solved in P21 space group, with
Z = 4. All non-hydrogen atoms were refined anisotropically with hydrogen atoms gener-
ated as spheres riding the coordinates of their parent atoms. Final full matrix least-squares
refinement on F2 converged to R1 = 0.0867 [I > 2σ (I)] and wR2 = 0.1924 (all data) with
GOF = 1.155.
4.6. Quantum chemical calculations
The DFT calculations performed in this work have been aimed to envisage the stabil-
ity of synthesized compound 3a through quantum chemical descriptors such as Frontier
molecular orbitals (FMO), HOMO–LUMO energy gap, and reactivity parameters such as
electronegativity, chemical hardness, electrophilicity index, and polarazability are depicted
as electrostatic potential map. Besides assigning the experimental IR bands and explor-
ing any possible photovoltaic material property, the TD-DFT calculations were performed
in solvent (methanol) to gain insight into the electronic states giving rise to the absorp-
tion spectra. During TD-DFT calculations, the 10 lowest singlet–singlet transitions were
considered. For the perfect match of optimized structure with the experimental crys-
tal structure and more importantly for assigning transitions, we used the recommended
Coulomb-attenuating method (CAM-B3LYP) in conjunction with PCM together with a
6-31G (d,p) basis set of DFT using Gaussian 09 software. In an MO framework, the chem-
ical reactivity can be compared or predicted in terms of Global reactivity parameters such
as electronegativity, chemical hardness and electrophilicity index.
4.6.1. Electronegativity
In Mullikan sense, electronegativity has been defined as the negative of the electronic
chemical potential
ꢀ
ꢁ
∂E
∂N
I + A
χ = −μ
= −
(1)
2
V
(r)
where χ is electronegativity, µ is chemical potential, E is the total electronic energy, N is
the no. of electrons, and V(r) is the external electrostatic potential an electron feels at r
due to the nuclei. Within the limitations of Koopmans’ theorem, the orbital energies of the
frontier orbitals are given by: −EHOMO = I; −ELUMO = A.
A very simple operational formula for µ, in terms of the one electron energies of HOMO
and LUMO, ꢀ and ꢀ , is given by [38]
H
L
ε + ε
H
L
μ ≈
.
(2)
2

16
R. M. JAGTAP ET AL.
4.6.2. Chemical hardness
The chemical hardness defines the resistance of the species to use electrons. The chemical
hardness was calculated using the equation [39]
η ≈ ELUMO − EHOMO
.
(3)
4.6.3. Electrophilicity index
The electrophilicity index tells us about the strength of electrophilicity of the species and
is calculated as [40]
μ2
ω =
.
(4)
2η
The electrophilicity index given in Eq. (4) encompasses both the propensity of the elec-
trophile to acquire an additional electronic charge driven by µ2 and the resistance of the
system to exchange electronic charge with the environment described by η simultaneously.
5. Physical and spectral data
5.1. (2R/2S,4R)-2- phenyl thiazolidine-4-carboxylic acid (2a)
White solid; yield: 0.17 g (82%). IR (KBr,υ,cm−1): 3431(COOH), 1577(C=O), 1435(aro-
matic C-C), 1381(C-S), 1305(C-N), 1236(C-O), 1024, 895, 808 (aromatic C-H) cm−1. 1H
NMR (300 MHz, DMSO-d6): δ = 7.35–7.50 (m, 5H, J = 8, 2 Hz, H-Ar), δ = 7.20–7.33
(m, 5H, J = 8, 2 Hz, H-Ar), δ = 5.64 (s, 1H, H-2), δ = 5.47 (s, 1H, H-2), δ = 4.22
(t, 1H, J = 6.9, H-4), δ = 3.90 (t, 1H, J = 7 Hz, H-4), δ = 3.39–3.31 (m, 2H, J = 6.9,
4.5 Hz, H-5), δ = 3.25–3.01 (m, 2H, J = 7, 4.7 Hz, H-5).13C NMR (75 MHz, DMSO-
d6): 172.92(C=O), 172.24(C=O), 141.25, 138.88, 128.42, 128.23, 128.15, 127.49, 127.20,
126.85 (C Ar), 71.72(C-2), 71.02(C-2), 65.57(C-4), 64.91(C-4), 38.98(C-5), 38.50(C-5).
GCMS (APCI): 210.0 (M+ + 1), 210.0 (M+ + 1). Anal. calcd for C10H11NO2S: C, 57.39;
H, 5.30; N, 6.69; S, 15.32%. Found: C, 57.34; H, 5.32; N, 6.76; S, 15.28%.
5.2. (2R/2S,4R)-2-(2-hydroxyphenyl) thiazolidine-4-carboxylic acid (2b)
White solid; yield: 0.17 g (78%). IR(KBr,υ,cm−1): 3097(COOH), 3010(N-H), 1627(C=O),
1383(C-S), 1332(C-N), 1280(C-O), 1238(C-O), 1097, 1093, 761 (aromatic C-H) cm−1. 1H
NMR (300 MHz, DMSO-d6): δ = 7.10–7.33 (m, 4H, J = 8, 2 Hz, H-Ar), δ = 6.73–6.82
(m, 4H, J = 8, 2 Hz, H-Ar), δ = 5.83 (s, 1H, H-2), δ = 5.64 (s, 1H, H-2), δ = 4.21 (t, 1H,
J = 6 Hz, H-4), δ = 3.83 (t, 1H, J = 8 Hz, H-4), δ = 3.4 (q, 2H, J = 8 Hz, H-5), δ = 3.33
(q, 1H, J = 8 Hz, H-5).
13C NMR (75 MHz, DMSO-d6): 172.92(C=O), 172.24(C=O), 155.13, 154.54, 128.99,
128.60, 127.84, 127.49, 126.04, 124.14, 118.99, 118.70, 115.62, 115.00(C Ar), 67.62(C-
2), 65.54(C-2), 65.13(C-4), 64.72(C-4), 38.00(C-5), 36.00(C-5). GCMS (APCI): 226.00
(M+ + 1), 226.00 (M+ + 1). Anal. calcd for C10H11NO3S: C, 53.32; H, 4.92; N, 6.22; S,
14.23%.Found: C, 53.39; H, 4.92; N, 6. 35; S, 14.25%.

JOURNAL OF SULFUR CHEMISTRY
17
5.3. (2R/2S,4R)-2-(2-methoxyphenyl) thiazolidine-4-carboxylic acid (2c)
White solid; yield: 0.19 g (83%). IR (KBr,υ,cm−1): 3500(broad) 1642(C=O), 1490(aro-
matic C-C), 1334(C-N), 1244(C-O) cm−1.1H NMR (300 MHz, DMSO-d6): δ = 7.51–7.20
(m, 4H, J = 8, 2 Hz, H-Ar), δ = 7.05–6.85 (m, 4H, J = 8, 2 Hz, H-Ar), δ = 5.82 (s, 1H,
H-2), δ = 5.62 (s, 1H, H-2), δ = 4.22 (t, 1H, J = 6 Hz, H-4), δ = 3.86 (t,1H, J = 3, 8 Hz,
H-4), δ = 3.82 (s, 3H, H CH3), δ = 3.72 (s, 3H, H CH3), δ = 3.18–3.05 (m, 2H, J = 6 Hz,
H-5), δ = 3.04–2.85(m, 2H, J = 8,3 Hz H-5).
13C NMR (75 MHz, DMSO-d6): 172.75(C=O), 172.24(C=O), 156.5, 156.1, 130.1,
129.2, 128.1, 127.2, 126.4, 125.2, 120.4, 120.1, 111.2, 110.70 (C Ar), 66.20 (C-2), 65.30 (C-
2), 64.98(C-4), 64.91(C-4), 55.43(C CH3), 55.39(C CH3), 37.50(C-5), 37.81(C-5). GCMS
(APCI): 239.90 (M+ + 1), 239.90 (M+ + 1). Anal calcd for C11H13NO3S: C, 55.21; H, 5.48;
N, 5.85; S, 13.40%. Found: C, 55.18; H, 4.64; N, 5.80; S, 13.36%. C11H13NO3S: C, 55.21; H,
5.48; N, 5.85; S, 13.40%. Found: C, 55.18; H, 4.64; N, 5.80; S, 13.36%.
5.4. (2R/2S,4R)-2-(2-nitrophenyl) thiazolidine-4-carboxylic acid (2d)
Yellow solid; yield: 0.23 g (91%). IR (KBr,υ,cm−1): 2797(broad, COOH), 1633(C=O),
1433(N-O), 1348(C-N), 1195(C-O) cm−1.1H NMR (300 MHz, DMSO-d6): δ = 8.10–8.03
(m, 2H, J = 8 Hz, H-Ar), δ = 7.97–7.91 (m, 2H, J = 10 Hz, H-Ar), δ = 7.85–7.81 (m, 2H,
J = 8 Hz, H-Ar), δ = 7.76–7.66 (m, 2H, J = 8 Hz, H-Ar), δ = 6.76 (s, 1H, H-2), δ = 6.33
(s, 1H, H-2), δ = 4.02 (t, 1H, J = 7 Hz, H-4), δ = 3.19 (q, 1H, J = 7, 3 Hz, H-4), δ = 3.03
(m, 2H, J = 7, 5 Hz, H-5), δ = 2.72(m, 2H, J = 7, 3 Hz, H-5).
13C NMR (100 MHz, DMSO-d6): 172.97(C=O), 172.80(C=O), 148.80, 147.90,
139.22, 135.86, 134.22, 133.79, 129.59, 128.92, 127.85, 125.77, 124.65(C Ar), 66.77(C-
2), 65.96(C-2), 65.67(C-4), 65.32(C-4), 37.31(C-5), 36.99(C-5). GCMS (APCI): 254.00
(M+ + 1), 254.00 (M+ + 1). Anal. calcd for C10H10N2O4S: C, 47.24; H, 3.96; N, 11.02;
S, 12.61%. Found: C, 47.24; H, 4.01; N, 11.08; S, 12.66%.
5.5. (2R/2S,4R)-2-(3-nitrophenyl) thiazolidine-4-carboxylic acid (2e)
Yellow solid; yield: 0.20 g (80%). IR (KBr,υ,cm−1): 3435 (broad, COOH), 3279(N-H),
1730(C=O), 1627(C=O), 1529(N-O), 1448(C-N), 1205(C-O), 1157, 835(aromatic C-
H) cm−1. 1H NMR (300 MHz, DMSO-d6): δ = 8.20 (dd, 2H J = 2 Hz, H-Ar), δ = 8.05
(m, 2H, J = 2,8 Hz, H-Ar), δ = 7.97 (dd, 2H, J = 8, 2 Hz, H-Ar), δ = 7.65 (dd, 2H,
J = 8 Hz, H-Ar), δ = 5.86 (s,1H,H-2), δ = 5.68 (s,1H, H-2), δ = 4.14 (t, 1H, J = 9 Hz,
H-4), δ = 3.93–3.98 (dd, 1H, J = 9, 3 Hz, H-4), δ = 3.36 (m, 2H, J = 9, 3 Hz, H-5), δ
3.12 (m, 2H, J = 9, 3 Hz, H-5).
13C NMR (75 MHz, DMSO-d6): 172.50(C=O), 171.80(C=O), 147.70, 147.60, 144.60,
141.9, 134.2, 133.70, 129.80, 122.90, 122.30, 122.10, 121.20, 111.00 (H Ar), 70.07(C-
2), 69.40 (C-2), 65.80(C-4), 64.70(C-4), 38.08(C-5), 38.20(C-5), GCMS (APCI): 254.00
(M+ + 1), 254.00 (M+ + 1). Anal. calcd for C10H10N2O4S: C, 47.24; H, 3.96; N, 11.02;
S, 12.61%. Found: C, 47.20; H, 3.99; N, 11.04; S, 12.65%.
5.6. (2R/2S,4R)-2-(4-methyl phenyl) thiazolidine-4-carboxylic acid (2f)
White solid; yield: 0.16 g (70%). IR (KBr,υ,cm−1): 3431(broad, COOH), 1577(C=O),
1435(C-N), 1381(C-S), 1305(C-N), 1236(C-O), 1024, 922, 895, 808, 765, 696 (aromatic

18
R. M. JAGTAP ET AL.
C-H) cm−1.1H NMR (300 MHz, DMSO-d6): δ = 7.35–7.50 (m, 4H, J = 2,8 Hz, H Ar),
δ = 7.20–7.33 (m, 4H, J = 2,8 Hz, H Ar), δ = 5.64 (s, 1H, H-2), δ = 5.47 (s, 1H, H-2),
δ = 4.22 (t, 1H, J = 6.9 Hz, H-4), δ = 3.90 (t, 1H, J = 7 Hz, H-4), δ = 3.39 (m, 2H, J = 7,
3 Hz, H-5), δ 3.25 (m,2H, J = 7, 3 Hz, H-4), 2.5 (s, 6H, H 2CH3).
13
=
C NMR (75 MHz, DMSO-d6): 172.92(C=O), 172.24 (C9 O), 141.25, 138.88, 128.42,
128.23, 128.15, 127.49, 127.20, 126.85(C Ar), 71.72(C-2),71.02 (C-2), 65.57(C-4), 64.91(C-
4), 38.98(C-5), 38.50 (C-5), 20.67 (C CH3), 20.62 (C CH3). GCMS (APCI): 224.00
(M+ + 1), 224.00 (M+ + 1). Anal. calcd for C11H13NO2S: C, 59.17; H, 5.87; N, 6.27; S,
14.36%. Found: C, 59.12; H, 5.865; N, 6.268; S, 14.37%.
5.7. (2R/2S,4R)-2-(4-methoxyphenyl) thiazolidine-4-carboxylic acid (2g)
White solid; yield: 0.20 g (86%). IR (KBr,υ,cm−1): 1797(C=O), 1579 (aromatic C=C),
1
1510(C-N), 1303 (C-S), 1204 (C-O), 1028, 835, 810 (aromatic CH) cm−1. H NMR
(300 MHz, DMSO-d6): δ = 7.4 (dd, 2H, J = 9 Hz, H Ar), δ = 6.90 (dd, 2H, J = 9 Hz, H
Ar), δ = 5.59 (s, 1H, H-2), δ = 5.45 (s, 1H, H-2), δ = 4.26 (t, 1H, J = 7 Hz, H-4), δ = 4.10
(t, 1H, J = 7 Hz, H-4), δ = 3.75 (s, 3H, H CH3), δ = 3.74 (s, 3H, H CH3), δ = 3.47–3.35
(m, 2H, J = 7, 3 Hz, H-5), δ = 3.32–3.15 (m, 2H, J = 7,4 Hz, H-5).
13C NMR (75 MHz, DMSO-d6): 172.98(C=O), 172.18(C=O), 159.15, 158.69, 132.65,
130.56, 128.53, 128.26, 113.71, 113.51(C Ar), 71.45 (C-2), 70.87 (C-2), 65.31 (C-4),
64.75(C-4), 55.05 (C 2CH3), 38.45(C-5), 37.81(C-5). GCMS (APCI): 240.00 (M+ + 1),
240.00 (M+ + 1).Anal. calcd for C11H13NO3S: C, 55.21; H, 5.48; N, 5.85; S, 13.40%. Found:
C, 55.18; H, 5.51; N, 5.88; S, 13.42%.
5.8. (2R/2S,4R)-2-(4-bromophenyl) thiazolidine-4-carboxylic acid (2h)
Pale yellow; yield: 0.21 g (73%). IR (KBr,υ,cm−1): 3431 (broad, COOH), 3014(N-H),1629
(C=O), 1491(C-N), 1375(C-S), 1257(C-N), 1288 (C-O), 1076, 1003, 875, 858, 823, 802
1
(aromatic C-H) cm−1. H NMR (300 MHz, DMSO-d6): δ = 7.57–7.37 (m, 8H, J = 8,
2 Hz, H Ar), δ = 5.68 (s, 1H, H-2), δ = 5.48 (s, 1H, H-2), δ = 4.15 (t, 1H, J = 7 Hz, H-4),
δ = 3.87 (t, 1H, J = 7 Hz, H-4), δ = 3.26–3.39 (m, 2H, J = 7, 3 Hz, H-5), δ = 2.82–2.98
(m, 2H, J = 7, 3 Hz, H-5).
13C NMR (75 MHz, DMSO-d6): 172.73(C=O), 171.98 (C=O), 141.15, 140.68, 138.57,
138.13, 132.58, 131.84, 131.25, 131.00, 129.51, 129.20, 129.05, 128.70 (C Ar), 70.70 (C-
2), 70.03 (C-2), 65.57(C-4), 64.79 (C-4), 38.28 (C-5), 37.90 (C-5). GCMS (APCI): 289.85
(M+ + 1), 289.85 (M+ + 1).Anal. calcd for C10H10BrNO2S: C, 41.68; H, 3.50; N, 4.86; S,
11.13%. Found: C, 41.64; H, 3.52; N, 4.82; S, 11.17%.
5.9. (2R/2S,4R)-2-(4-chlorophenyl) thiazolidine-4-carboxylic acid (2i)
White solid; yields: 0.18 g (73%). IR (KBr,υ,cm−1): 2962 (COOH), 1583(C=O), 1489 (C-
N), 1384(C-S), 1209(C-O), 1091, 1012, 862, 819 (aromatic C-H) cm−1.1H NMR (300 MHz,
DMSO-d6): δ = 7. 60–7.25 (m, 8H, J = 8, 2 Hz, H Ar), δ = 5.65 (s, 1H, H-2), δ = 5.45
(s, 1H, H-2), δ = 4.15 (t, 1H, J = 6 Hz, H-4), δ = 3.87 (t, 1H, J = 8 Hz, H-4), δ = 3.48
(s, broad, 1H, residual H2O from solvent), δ = 3.39–3.26 (m, 2H, J = 6, 3 Hz, H-5),
δ = 3.05–2.80 (m, 2H, J = 8, 3 Hz, H-5).

JOURNAL OF SULFUR CHEMISTRY
19
13C NMR (75 MHz, DMSO-d6): 172.79(C=O), 172.172.14(C=O), 140.82, 138.16,
132.58, 131.80, 129.17, 128.67, 128.35, 128.06, (C Ar), 70.78 (C-2), 70.03 (C-2), 65.80 (C-4),
64.91(C-4), 38.59 (C-5), 38.46 (C-5), GCMS (APCI): 243 (M+ + 1), 243 (M+ + 1). Anal.
calcd for C10H10ClNO2S:C, 49.28; H, 4.14; N, 5.75; S, 13.16%. Found: C, 49.32; H, 4.17; N,
5.72; S, 13.20%.
5.10. (2R/2S,4R)-2-(4-(dimethylamino)phenyl) thiazolidine-4-carboxylic acid (2j)
Pale brown solid; yields: 0.16 g (62%). IR (KBr,υ,cm−1): 3029 (broad, COOH), 1614
(C=O), 1520(C=C), 1338 (C-S) cm−1. 1H NMR (300 MHz, DMSO-d6): δ = 6.67 (d, 2H,
J = 8 Hz, H Ar), δ = 7.25 (q, 2H, J = 7 Hz, H Ar), δ = 6.76 (d, 2H, J = 8 Hz, H Ar),
δ = 6.66 (t, 2H, J = 8 Hz, H Ar), δ = 5.51 (s, 1H, H-2), δ = 5.38 (s, 1H, H-2), δ = 4.24
(dd, 1H, J = 5, 7 Hz, H-4), δ = 3.78–3.84 (t, 1H, J = 7 Hz, H-2), δ = 3.28–3.35 (m, 2H,
J = 7, 5 Hz, H-5), δ = 3.14–3.25 (m, 2H, J = 7, 5 Hz, H-2), δ = 2.87(s,6H, H 2NCH3).
13C NMR (75 MHz, DMSO-d6): 172.90(C=O), 172.12(C=O), 159.11, 158.55, 132.25,
130.36, 128.44, 128.13, 113.06, 113.00(C Ar), 71.37 (C-2), 70.07 (C-2), 65.24 (C-4),
64.71(C-4), 40.03 (C 2N-CH3), 38.22(C-5), 37.41(C-5). GCMS (APCI): 252.90 (M+ + 1),
252.90 (M+ + 1). Anal. calcd for C12H16N2O2S:C, 57.12; H, 6.39; N, 11.10; S, 12.71%.
Found: C, 57.14; H, 6.44; N, 11.08; S, 12.68%.
5.11. (2R/2S,4R)-2-(4-carboxyphenyl) thiazolidine-4-carboxylic acid (2k)
White solid; yields:0.22 g (88%). IR (KBr,υ,cm−1): 3410 (COOH), 3228 (broad, N-
H), 1710(C=O), 1629(C=O),1427(C=C), 1383(C-N), 1300(C-S), 1253(C-O) cm−1
.
1H NMR (300 MHz, DMSO-d6): δ = 7.93(d, 2H, J = 2, 8 Hz, H Ar), δ = 7.89 (d, 2H
J = 9 Hz, H Ar), δ = 7.63(d, 2H, J = 8 Hz, H Ar), δ = 7.53 (d, 2H, J = 8 Hz, H Ar),
δ = 5.77(s, 1H, H-2), δ = 5.58 (s,1H, H-2), δ = 4.17 (t, 1H, J = 6 Hz, H-4), δ = 3.92
(t, 1H, J = 9 Hz, H-4), δ = 3.31–3.27 (m, 2H, J = 6, 3 Hz, H-5), δ = 3.12–3.04 (dd, 2H,
J = 9, 3 Hz, H-5).
13C NMR(100 MHz, DMSO-d6): 173.28 (C=O), 172.61 (C=O), 167.56 (C=O),167.48,
147.22, 147.46, 131.02, 130.62, 129.96, 129.82, 127.93, 127.39 (C Ar),71.43(C-2), 70.74
(C-2), 66.07 (C-4), 65.42 (C-4), 38.54(2C-5). GCMS (APCI): 253.95 (M+ + 1), 253.95
(M+ + 1). Anal. calcd for C11H11NO4S: C, 52.16; H, 4.38; N, 5.53; S, 12.66%. Found: C,
52.20; H, 4.36; N, 5.55; S, 12.65%.
5.12. (2R/2S,4R)-2-(4-hydroxyphenyl) thiazolidine-4-carboxylic acid (2l)
White solid; yield 0.20 g (91%). IR (KBr,υ,cm−1): 1797(C=O), 1579(C=C), 1510(C=C),
1020, 838, 813 (aromatic C-H) cm−1. 1H NMR (300 MHz, DMSO-d6): δ = 7.38 (dd, 4H,
J = 9 Hz), δ = 6.90 (dd, 4H, J = 9 Hz), δ = 5.57 (s, 1H), δ = 5.40 (s, 1H), δ 4.23 = (t, 1H,
J = 7 Hz), δ 4.15 = (t, 1H, J = 7 Hz), δ = 3.45–3.33 (m, 2H, J = 7, 3 Hz),δ = 3.30–3.15
(m, 2H, J = 7, 4 Hz).
13C NMR (75 MHz, DMSO-d6): 172.08(C=O), 172.00(C=O), 159.05, 158.60, 132.62,
130.44, 128.03, 128.11, 113.61, 113.50 (C Ar), 71.40 (C-2), 70.27 (C-2), 65.26 (C-4),
64.65(C-4), 38.40(C-5), 37.51(C-5). GCMS (APCI): 225.95 (M+ + 1), 225.95 (M+ + 1).

20
R. M. JAGTAP ET AL.
Anal. calcd for C10H11NO3S: C, 53.32; H, 4.92; N, 6.22; S, 14.23%. Found: C, 53.30; H,
4.87; N, 6. 26; S, 14.21%.
5.13. (2R/2S,4R)-2-(2-hydroxy-4-methoxyphenyl) thiazolidine-4-carboxylic
acid (2m)
White solid; yield: 0.20 g (80%). IR (KBr,υ,cm−1): 3304(broad, COOH), 3037(N-H),
1629(C=O), 1591, 1518(C=C), 1375(C-N), 1289(C-S), 1236(C-O), 1060, 1020, 977, 910,
824, 798 (aromatic C-H) cm−1.1H NMR (300 MHz, DMSO-d6): δ = 6.94–6.8 (m, 6H,
J = 8, 2 Hz, H Ar), δ = 5.51 (s, 1H, H-2), δ = 5.37 (s, 1H, H-2), δ = 4.22 (q, 1H, J = 6 Hz,
H-4), δ = 3.85(dd, 1H, J = 6, 3 Hz, H-4), δ = 3.75 (s, 3H, H CH3), δ = 3.74 (s, 3H, H
CH3), δ = 3.47–3.35 (m, 2H, J = 6, 3 Hz, H-5), δ = 3.15–3.32 (m, 2H, J = 8, 4 Hz, H-5).
13C NMR (75 MHz, DMSO-d6): 173.05(C=O), 172.37(C=O), 147.68, 147.18, 146.99,
133.24, 131.65, 124.40, 118.11, 117.78,114.35,114.27,113.45,111.87, (C Ar), 71.71(C-2),
71.07(C-2), 65.08(C-4), 64.73(C-4), 55.61 (C 2CH3), 38.42(C-5), 37.76(C-5). GCMS
(APCI): 256.00 (M+ + 1), 256.00 (M+ + 1). Anal. calcd for C11H13NO3S:C, 51.75; H, 5.13;
N, 5.49; S, 12.56%. Found: C, 51.79; H, 5.11; N, 5.48; S, 12.52%.
5.14. (2R/2S,4R)-2-(2-methoxy-4-hydroxyphenyl) thiazolidine-4-carboxylic
acid (2n)
White solid; yield 0.21 g (84%). IR (KBr,υ,cm−1): 3452 (broad, COOH), 3111(N-H),
1614(C=O), 1516(C=C), 1381(C-N), 1244(C-O), 1051, 997, 831, 798 (aromatic C-
H) cm−1.1H NMR (300 MHz, DMSO-d6): δ = 7.26 (dd, 3H, J = 8 Hz, H Ar), δ = 6.73
(dd, 3H, J = 8, 2 Hz, H Ar), δ = 5.51 (s, 1H, H-2), δ = 5.37 (s, 1H, H-2), δ = 4.26(q, 1H,
J = 6 Hz, H-4), δ = 3.91(t, 1H, J = 8 Hz, H-4), δ = 3.86 (s, 6H, H 2CH3), δ = 3.2–3.0
(m, 2H, J = 6, 4 Hz, H-5), δ = 3.2–3.0 (m, 2H, J = 8, 4 Hz, H-5).
13C NMR (75 MHz, DMSO-d6): 173.50(C=O), 172.86(C=O), 157.86, 157.37, 131.22,
129.28, 128.98, 128.77, 116.30, 115.62, 115.36 (C Ar), 74.30 (C-2), 71.67 (C-2),
65.81(C-4),65.22(C-4), 40.73(C CH3), 40.45(C CH3), 38.26(2C-5). GCMS (APCI): 256.00
(M+ + 1), 256.00 (M+ + 1). Anal calcd for C11H13NO3S: C, 51.75; H, 5.13; N, 5.49; S,
12.56%. Found: C, 51.72; H, 5.18; N, 5.45; S, 12.58%.
5.15. (2R/2S,4R)-2-(2,3-dihydroxyphenyl) thiazolidine-4-carboxylic acid (2p)
White solid; yield: 0.20 g (82%). IR(KBr,υ,cm−1): 3339(COOH), 3352(N-H), 1624(C=O),
1685(C=O), 1475, 1440(C=C), 1383(C-N), 1332(C-S), 1190(C-O) cm−1.1H NMR
(300 MHz, DMSO-d6): δ = 9.37 (broad s, 1H, H OH), δ = 9. 25 (broad s, 1H, H OH),
δ = 6.71–6.79 (m, 3H, J = 8, 2 Hz, H Ar), δ = 6.55–6.68 (m, 3H, J = 7, 2 Hz, H Ar),
δ = 5.83 (s, 1H, H-2), δ = 5.64 (s, 1H, H-2), δ = 4.21 (t, 1H, J = 6 Hz, H-4), δ = 3.82 (t,
1H, J = 8 Hz, H-4), δ = 3.36–3.30 (q, 2H, J = 6 Hz, H-5), δ = 3.05–2.96 (m, 2H, J = 8,
4 Hz, H-5).
13C NMR (75 MHz, DMSO-d6): 172.10(C=O), 172.00(C=O), 145.00, 144.00, 143.00,
124.00, 127.00, 124.00, 118.80, 118.50, 118.00, 116.60, 114.90, 114.30 (C Ar), 67.75(C-
2), 65.80(C-2), 65.00(C-4), 64.75(C-4), 38.00(C-5), 36.50(C-5). GCMS (APCI): 241.95

JOURNAL OF SULFUR CHEMISTRY
21
(M+ + 1), 241.95 (M+ + 1). Anal. calcd for C10H11NO4S: C, 49.78; H, 4.60; N, 5.81; S,
13.29%. Found: C, 49.72; H, 4.61; N, 5.78; S, 13.28%.
5.16. (2R/2S,4R)-2-(3-methoxy-4-hydroxyphenyl) thiazolidine-4-carboxylic
acid (2q)
White solid; yield: 0.21 g (83%). IR (KBr,υ,cm−1): 3057 (broad), 1624(C=O), 1381(C-
N), 1278(C-S), 1159(C-O), 1136, 1028, 844, 796(aromatic C-H) cm−1.1H NMR (300 MHz,
DMSO-d6): δ = 7.11 (d, 2H, J = 8 Hz, H Ar), δ = 7.03 (dd, 2H, J = 8 Hz, H Ar), δ = 6.90
(d, 2H, J = 2 Hz, H Ar), δ = 5.52 (s, 1H, H-2), δ = 5.39 (s, 1H, H-2), δ = 4.30 (dd, 1H,
J = 7, 3 Hz, H-4), δ = 3.83 (q, 1H, J = 4, 7 Hz, H-4), δ = 3.76 (s, 3H, H CH3), δ = 3.75
(s, 3H, H CH3), δ = 3.25–3.36 (m, 2H, J = 7, 3 Hz, H-5), δ = 3.13–3.18 (m, 2H, J = 7,
4 Hz, H-5).
13C NMR (75 MHz, DMSO-d6):173.00(C=O), 172.72(C=O), 147.40, 14.30, 146.60,
146.20, 131.08, 129.20, 119.90, 119.60, 115.40, 115.10, 111.47, 111.28, (C Ar), 72.40 (C-
2), 72.10 (C-2), 65.43(C-4), 64.70 (C-4), 55.60(C 2CH3), 38.37(C-5), 37.72(C-5). GCMS
(APCI): 255.95 (M+ + 1), 255.95 (M+ + 1). Anal. calcd for C11H13NO3S: C, 51.75; H, 5.13;
N, 5.49; S, 12.56%. Found: C, 51.78; H, 5.13; N, 5.50; S, 12.53%.
5.17. (2R/2S,4R)-2-(3,4-dihydroxyphenyl) thiazolidine-4-carboxylic acid (2r)
White solid; yield: 1.8 g (75%). IR (KBr,υ,cm−1): 3327(COOH), 3173(N-H), 1627(C=O),
1599(C=O), 1454(C-N), 1338(C-S), 1294(C-O), 1114, 1058, 829, 796(aromatic C-
H) cm−1.1H NMR (300 MHz, DMSO-d6): δ = 9.05 (broad s, 1H, H OH), δ = 6.8
(m, 3H, J = 8, 2 Hz, H Ar), δ = 6.7 (m, 3H, J = 8, 2 Hz, H Ar), δ = 5.47 (s,
1H, H-2), δ = 5.32 (s, 1H, H-2), δ = 4.24 (t, 1H, J = 8 Hz, H-4), δ = 3.83 (t, 1H,
J = 8 Hz, H-4), δ = 3.37–3.25 (m, 2H, J = 8, 4 Hz, H-5), 3.22–2.98 (m, 2H, J = 8,
4 Hz, H-5).
13C NMR (75 MHz, DMSO-d6):173.00(C=O), 172.30(C=O), 145.78, 145.20, 143.00,
144.93, 131.23, 131.17, 129.18, 118.26, 118.04, 115.43, 115.20, 114.69 (C Ar), 71.29 (C-
2), 71.24 (C-2), 64.70(C-4), 65.04(C-4), 38.43(C-5), 37.64(C-5). GCMS (APCI): 241.95
(M+ + 1), 241.95 (M+ + 1). Anal. calcd for C10H11NO4S: C, 49.78; H, 4.60; N, 5.81; S,
13.29%. Found: C, 49.79; H, 4.64; N, 5.80; S, 13.32.
5.18. (2R/2S,4R)-2-(2,6-dichlorophenyl) thiazolidine-4-carboxylic acid (2s)
White solid; yield: 0.23 g (85%). [α]D25−101.1 (c 1.25, MeOH). IR (KBr,υ,cm−1):
3454(COOH), 3298(N-H), 1726(C=O), 1330(C-S), 1271(C-O), 912, 781(aromatic C-
H) cm−1
.
1H NMR (300 MHz, DMSO-d6): δ = 7.50 (dd, 1H, J = 8 Hz, H Ar), δ 7.42–7.37 (t, 2H,
J = 7,2 Hz, H Ar), δ 6.42(s, 1H, H-2), δ 3.88 (dd, 1H, J = 10,6 Hz, H-4), δ 3.46 (dd, 1H,
J = 10,6 Hz, H-5), δ 2.96 (t, 1H, J = 10 Hz, H-5).
13C NMR (75 MHz, DMSO-d6):173.00(C=O), 134.00, 131.00, 130.00, 129.00, 128.60,
128.00(C Ar), 70.00 (C-2), 63.41 (C-4), 38.58 (C-5). GCMS (APCI): 277.90 (M+ + 1).Anal.
calcd for C10H9Cl2NO2S: C, 43.18; H, 3.26; N, 5.04; S, 11.53%. Found: C, 43.14; H, 3.22;
N, 5.02; S, 11.57%.

22
R. M. JAGTAP ET AL.
HO
OH
O
OH
SH
O
O
DMSO-d6
S
N
O
N
O
O
N
SH
(R)
(R)
(R)
HO
HO
HO
O
O
O
3a / 3b
E (70 %)
Z (30 %)
Figure 9. Conformational isomers obtained from 3a and 3b in DMSO-d6.
5.19. (2S,4R)-3-(tert-butoxycarbonyl)-2-(2-hydroxyphenyl)
thiazolidine-4-carboxylic acid (3a)
25
C15H19NO5S, white solid, M.P 187°C (85%), [α]D +10.7 (c 1.25, MeOH). IR(KBr):
3097(COOH), 1627 (C=O), 13,831,332, (C-S), 1280, 1238 (C-O), 1097, 1093, 761
(aromatic C-H) cm−1, 1H- NMR (DMSO-d6): δ 10.3 (s, 1H,broad, H COOH), δ
7.83 (d, 1H, J = 8 Hz, H Ar), δ 7.17 (t, 1H, J = 8 Hz, H Ar), δ 6.83 (m, 2H,
J = 8 Hz, H Ar), δ 5.93 (s, 1H, H-2), δ 4.86 (q, 1H, J = 7.2 Hz, H-4), δ, δ 3.43 (dd,
1H, J = 7.2, 4.5 Hz, H-5), δ 2.73 (dd, 1H, J = 7.2, 4.5 Hz, H-5), δ 1.38 (s, 6H, H
CH3C(CH3)2), δ 1.25 (s, 3H, H CH3C(CH3)2). 13C NMR (DMSO-d6): 172.69 (C=O),
172.24 (C=O), 154.60, 130.29, 127.50, 120.47, 119.90, 115.13(C Ar), 83.35 (C C(CH3)3),
60.89 (C-2), 49.43 (C-4), (C-5, merged in DMSO-d6 signals), 28.10 (C C(CH3)3). MS:
326.00 (M + 1)
5.20. (2R,4R)-3-(tert-butoxycarbonyl)-2-(2-hydroxyphenyl)
thiazolidine-4-carboxylic acid (3b)
25
C15H19NO5S, White solid, M.P 145°C; (15%). [α]D +73.2 (c 1.25, MeOH).[25] IR
(KBr,υ,cm−1): 3389 (COOH), 1718 (C=O),1627, 1396 (C-S), 1282 (C-O), 908, 848
1
(aromatic C-H) cm−1. H NMR (DMSO-d6): δ 9.66 (s, 1H, H COOH), δ 7.81 (d, 1H,
J = 7.5 Hz, H Ar), 7.03 (m, J = 7.5, 1.5 Hz, 1H, H Ar), 6.73 (m, 2H, J = 7.5, 1.5 Hz, H
Ar), 6.11 (s, 1H, H-2), 4.46 (dd, J = 7, 4.3 Hz, 1H, H-4), 3.37 (m, J = 7, 4.3 Hz, 1H, H-
5), 3.07–2.90 (m, J = 7, 4.3 Hz, 1H, H-5), 1.32 (s, 6H, H CH3C(CH3)2), δ 1.10 (s, 3H,
H CH3C(CH3)2). 13C NMR (DMSO-d6):172.20 (C=O), 171.82 (C=O), 153.58, 152.52,
127.97, 118.43, 114.50 (C Ar), 80.42 (C C(CH3)3), 64.60 (C-2), 61.06 (C-4), (C-5, merged
in DMSO-d6 signals), 27.65(C C(CH3)3). MS: 324.00 (M-1).
Though the X-ray data in the crystalline state compound 3a have shown a trans-
conformation, the doubling of signals of t-butyl group at 1.25 and 1.38 δ ppm, as well as
1
the signals of Ar-OH at 10.25 and 10.37 δ ppm was found in the H NMR spectrum of
the compound 3a. This splitting of the signals for t-butyl group can be attributed to the
effect of the hindered rotation of the BOC-fragment relative to C-N bond (E-Z isomerism)
in DMSO-d6 represents the coexistence of a mixture of trans/cis isomers in the approx-
imate ratio of trans/cis as 7/3. The same situation is observed for compound 3b. This
tendency of cis/trans isomerism in solutions is in accordance with a general property of
N-acyl derivatives of thiazolidine-4-carboxylic acid [23] as shown in Figure 9.

JOURNAL OF SULFUR CHEMISTRY
23
Also, the melting point of compounds 3b (145°C) is found to be in good agreement to
its reported value (143–145°C).[41] However, compound 3a showed higher melting point
(187°C) than 3b, which is attributed to more intermolecular attractive interactions of trans-
oriented carboxylic acid group and 2-hydroxyphenyl ring substituent.
Acknowledgements
MAR thankfully acknowledges Dr Rahul Banerjee, CSIR-National Chemical Laboratory Pune, India
for the X-ray crystallography.
Disclosure statement
No potential conflict of interest was reported by the author.
Funding
YD thanks CSIR-India for an SRF grant.
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