Visible Light-Promoted Three-Component Tandem Annulation for the Synthesis of 2-Iminothiazolidin-4-ones

Article abstract of DOI:10.1021/acs.joc.7b02940

Described is a visible light-promoted three-component tandem annulation of amines, aryl/alkyl isothiocyanates, and α-bromoesters to form 2-iminothiazolidin-4-ones in the absence of metal and photocatalyst at room temperature. This [1 + 2 + 2] cyclization strategy involves visible light-promoted C-S/C-N bond formation and features a powerful approach to the synthesis of 2-iminothiazolidin-4-ones with broad substrate scope, excellent functional group tolerance, mild reaction conditions, step-economy, and simple operation, which also has potential applications in the pharmaceutical industry. UV-vis spectroscopy indicates that an in situ-generated H-bonding electron donor-acceptor (EDA) complex probably acts as the photocatalyst, facilitating the reaction process.

Full text of DOI:10.1021/acs.joc.7b02940

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Article
Visible Light-Promoted Three-Component Tandem
Annulation for Synthesis of 2-Iminothiazolidin-4-ones
Wei Guo, Mingming Zhao, Wen Tan, Lvyin Zheng, Kailiang
Tao, Lingxiu Liu, Xinyu Wang, Deliang Chen, and XiaoLin Fan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02940 • Publication Date (Web): 16 Jan 2018
Downloaded from http://pubs.acs.org on January 16, 2018
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Visible Light-Promoted Three-Component Tandem
Annulation for Synthesis of 2-Iminothiazolidin-4-ones
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Wei Guo,†* Mingming Zhao,† Wen Tan, Lvyin Zheng, Kailiang Tao, Lingxiu Liu,
Xinyu Wang, Deliang Chen,* Xiaolin Fan*
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Key Laboratory of Organoꢀpharmaceutical Chemistry of Jiangxi Province, Gannan Normal
University, Ganzhou 341000, China
Fax: (+86) 0797ꢀ8393536; *Eꢀmail: guoweigw@126.com; deliang2211@hotmail.com;
fanxl2008@gnnu.edu.cn
ABSTRACT: Described is a visible lightꢀpromoted threeꢀcomponent tandem
annulation of amines, aryl/alkyl isothiocyanates, and αꢀbromoesters to
2ꢀiminothiazolidinꢀ4ꢀones in the absence of metal and photocatalyst at room
temperature. This [1+2+2] cyclization strategy involves visible lightꢀpromoted
C−S/C−N bond formations and features a powerful approach to synthesis of
2ꢀiminothiazolidinꢀ4ꢀones with broad substrate scope, excellent functional group
tolerance, mild reaction conditions, stepꢀeconomy and simple operation, which also
has potential applications in the pharmaceutical industry. UV−vis spectroscopy test
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indicates that an in situ generated Hꢀbonding electron donorꢀacceptor (EDA) complex
probably acts as the photocatalyst facilitating the reaction process.
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INTRODUCTION
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The thiazolidines are ubiquitous molecular frameworks in various drug candidates
and natural products with immense biological potencies. In particular,
2ꢀiminothiazolidinꢀ4ꢀones and their derivatives feature broadꢀspectrum biological
activities.1 For example, compound I is a sphingosineꢀ1ꢀphosphate receptor agonist,2
II is a preferential hCA inhibitor,3 III has been determined to exhibit pronounced
anticonvulsant activity,4 IV is selective GSKꢀ3β inhibitor (Figure 1).5 Furthermore,
2ꢀiminothiazolidinꢀ4ꢀones (V and VI) have been described for their significant
antiꢀproliferative activity6. Therefore, the development of efficient and practical
methods for the acquisition of 2ꢀiminothiazolidinꢀ4ꢀones is an interesting research
area in organic and pharmaceutical chemistry.
Figure 1. Representative, Biologically Active Molecules Containing
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2-Iminothiazolidin-4-ones Motifs
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There is some general statement on the usefulness of multicomponent reaction with
literature examples to form biorelevant compounds and heterocycles (including
2ꢀiminothiazolidinꢀ4ꢀones ) under classical catalysis.7 Representative work of theses
methodologies include (i) condensation of thioureas, chloroacetic acid and aldehydes
under microwaveꢀirradiation (Scheme 1a);8 (ii) cyclization of thioureas with acyl
halides under basic conditions (Scheme 1b);9 (iii) regioselective cyclization of
unsymmetrical thioureas with αꢀbromoesters (Scheme 1c);10 (iv) oneꢀpot
regio/stereoselective threeꢀcomponent cyclization of isothiocycanates, amines, with
chloroacetic acid under solvent/scavengerꢀfree conditions (Scheme 1d).11 Although
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these
approaches
have
proven
valuable
for
the
preparation
of
2ꢀiminothiazolidinꢀ4ꢀones, they suffer from the disadvantages of requiring high
temperature, microwaveꢀirradiation, unavailable starting materials, or unstable,
moistureꢀsensitive reagents. Thus, the development of simple and efficient methods
for the synthesis of 2ꢀiminothiazolidinꢀ4ꢀones under milder conditions is still a
significant issue.
In the last few years, visible lightꢀinitiated organic transformations have attracted
increasing attention.12 Considering availability, safety, cost, and environmental
sustainability, the visible lightꢀpromoted/catalyzed reactions enable rapid and efficient
synthesis of fine chemicals.13 Inspired by the recent process of visible light
photocatalytic14 efficient synthesis strategy in organic chemistry,15 here, we develop a
visible lightꢀpromoted threeꢀcomponent tandem transformation16 to prepare the
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2ꢀiminothiazolidinꢀ4ꢀones scaffold via formal [1 + 2 + 2] cyclization of amines,
aryl/alkyl isothiocyanates, and αꢀbromoesters in the absent of metal and photocatalyst
(Scheme 1e).17 This is an efficient, visible lightꢀpromoted threeꢀcomponent tandem
strategy leading to 2ꢀiminothiazolidinꢀ4ꢀones.
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Scheme 1. Multicomponent Assembly of 2-Iminothiazolidin-4-ones Derivatives
RESULTS AND DISCUSSION
We initiated our study by exploring the condition optimization with the model
reaction of phenylmethanamine 1a, phenyl isothiocyanate 2a (1.1 equiv), and ethyl
2ꢀbromoacetate 3a (3 equiv) at room temperature in the presence of a base (4 equiv)
(Table 1). First, a variety of bases were investigated with the aim of
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2ꢀiminothiazolidinꢀ4ꢀones formation, and yields were obtained in the presence of
bases including K2CO3, KOH, tꢀBuOK, Cs2CO3, Na2CO3, NaOH, K3PO4, Et3N,
DABCO and DBU (entries 1ꢀ11). Fortunately, in the case of using NaOH as the base
in CH3CN, 2ꢀiminothiazolidinꢀ4ꢀone (4a) was obtained in 93% yield (entry 6). The
presence of Cs2CO3 and Na2CO3 were also effective, producing 4a in 90% and 87%
yields (entries 4 and 5). The amount of NaOH and reaction time were investigated,
however, the yield of 4a was not improved (see Tables S1, S2 and Table 1, entry 7).
For example, only 13% yield of 4a was obtained for 6 h (entry 7). Organic bases such
as Et3N, DABCO, and DBU afforded lower yields (entries 9ꢀ11). The yield was
decreased to 55% when the reaction was carried out in the absence of bases (entry 12).
Subsequently, during the screening of solvents, DMF, DMSO, CH2Cl2, toluene, EtOH
and THF were found to be inferior to CH3CN (entries 13ꢀ18). Notably, all of the
reactions were performed under blue light conditions. However, reactions carried out
in ambient light or in the dark led to obviously decreased yield (entries 19 and 20),
illustrating that visible light is helpful in promoting the reaction. In addition, the
reaction does not work under N2 atmosphere or vacuum atmosphere (entries 21 and
22), thus indicating that oxygen is necessary for the transformation.
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Table 1. Optimization of the Reaction Conditionsa
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Entry
Base
Solvent
Time(h) Yield (%)b
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K2CO3
KOH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
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tꢀBuOK
Cs2CO3
Na2CO3
NaOH
NaOH
K3PO4
Et3N
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19 c
20 d
21 e
22 f
DABCO
DBU
\
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
DMSO
CH2Cl2
toluene
EtOH
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62
36
0
THF
CH3CN
CH3CN
CH3CN
CH3CN
0
aReaction conditions: 1a (0.1 mmol), 2a (0.11 mmol), 3a (0.3 mmol) and base (4
equiv) in solvent (1 mL), open to air under a 5 W blue LED at room temperature.
bIsolated yield. In ambient light. In the dark. Reaction under N2 atmosphere.
c
d
e
fReaction under vacuum atmosphere.
Next, the scope and generality of this threeꢀcomponent cyclization reaction were
explored under the optimized conditions. Initially, we investigated a range of amines
(RCH2NH2) at room temperature in the open air conditions (Scheme 2). Generally,
benzylamines containing pꢀsubstituents (R = F, Cl, Br, CN, OCH3, CH3) with phenyl
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isothiocyanate 2a and ethyl 2ꢀbromoacetate 3a proceeded smoothly, affording the
corresponding 2ꢀiminothiazolidinꢀ4ꢀones 4bꢀ4g in good to excellent yields.
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mꢀSubstituted benzylamine (R
=
F, Cl, Br, OCH3, CH3) provided
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2ꢀiminothiazolidinꢀ4ꢀones 4hꢀ4l in moderate to good yields. Satisfactorily,
oꢀsubstituted benzylamine (R = F, Cl, OCH3) afforded the corresponding products
4mꢀ4o in moderate to good yields. Moreover, disubstituted and trisubstituted
benzylamines were applicable to this transformation, affording the desired products
4pꢀ4r in moderate to good yields. Naphthalenꢀ1ꢀylmethanamine also produced the
corresponding product 4s in 72% yield. Heterocyclic pyridinꢀ3ꢀylmethanamine,
thiophenꢀ2ꢀylmethanamine, and furanꢀ2ꢀylmethanamine could also be transformed
into the desired products 4tꢀ4v in moderate yields upon isolation. Interestingly, the
reactions of aliphatic amines were performed successfully under standard conditions.
For instance, cyclohexylmethanamine and hexanꢀ1ꢀamine were compatible in this
transformation (4w and 4x). Notably, 3ꢀphenylpropanꢀ1ꢀamine afforded product 4y in
89% yield. 3ꢀMorpholinopropanꢀ1ꢀamine was also transformed to the corresponding
2ꢀiminothiazolidinꢀ4ꢀones 4z in 23% yield, which provided potential applications in
the drug screening. Furthermore, aniline was tolerated within the reaction, producing
the corresponding products 5a11 in moderate yield (Scheme 3). Cyclohexanamine and
cyclopentanamine furnished the targeting products 5b and 5c in moderate yields.
However, pyridinꢀ2ꢀamine and pyridinꢀ3ꢀamine were explored and found to be
unsuitable substrates for the reaction under current conditions.
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a,b
Scheme 2. Scope of RCH2NH2
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aReaction conditions: 1 (0.1 mmol), 2a (0.11 mmol), 3a (0.3 mmol) and NaOH (4
equiv) in CH3CN (1 mL), open to air under a 5 W blue LED at room temperature.
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bYields of isolated products.
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a,b
Scheme 3. Scope of RNH2
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aReaction conditions: 1 (0.1 mmol), 2a (0.11 mmol), 3a (0.3 mmol) and NaOH (4
equiv) in CH3CN (1 mL), open to air under a 5 W blue LED at room temperature.
bYields of isolated products.
The scope of isothiocyanate derivatives is also crucial for the utility of the tandem
annulations under otherwise identical conditions (Scheme 4). As expected,
isothiocyanatobenzene containing pꢀsubstituents (R =F, Br, CF3, OCH3, CN, NO2, Et)
underwent the cyclization smoothly to afford the corresponding products 6aꢀ6g in
42ꢀ90%
yields.
1ꢀChloroꢀ2ꢀisothiocyanatobenzene
and
2ꢀtrifluoromethyl
isothiocyanatobenzene produced the targeting products 6h and 6i in moderate to good
yields. Meanwhile, 1ꢀchloroꢀ3ꢀisothiocyanatobenzene also afforded product 6j in 71%
yield. Furthermore, disubstituted and trisubstituted isothiocyanatobenzene were well
tolerated in this process to give desired products 6kꢀ6o. 1ꢀNapthyl isothiocyanate
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gave the target product 6p in 62% yield. Importantly, (isothiocyanatomethyl)benzene
furnished product 6q in 87% yield. Satisfactorily, the reactions of aliphatic
isothiocyanate were performed successfully under standard conditions. For instance,
isothiocyanatomethane provided the corresponding product 6r in 57% yield. However,
1ꢀisothiocyanatobutane and isothiocyanatocyclohexane led to the desired products
with poor yields (6s and 6t). Note that the 6u was successfully prepared in 57% yield
by the transformation of 1a, oꢀethyl carbonisothiocyanatidate 2u, and ethyl
2ꢀbromoacetate, which could be used as intermediate in the fields of organic synthesis
and pharmaceutical industries.
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Scheme 4. Scope of Isothiocyanate Compoundsa,b
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aReaction conditions: 1a (0.1 mmol), 2 (0.11 mmol), 3a (0.3 mmol) and NaOH (4
equiv) in CH3CN (1 mL), open to air under a 5 W blue LED at room temperature.
bYields of isolated products.
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Reactions of different αꢀbromoesters under the optimized reaction conditions were
also investgated (Scheme 5). Methyl 2ꢀbromobutanoate was able to undergo this
transformation, producing the desired product 7a in moderate yields. Gratifyingly,
ethyl 2ꢀbromopropanoate was successfully subjected to this reaction system providing
7b in good yields. In addition, methyl 2ꢀbromoꢀ2ꢀ(2ꢀchlorophenyl)acetate could be
transformed into the targeting product 7c in low yield because of a steric hindrance
effect.
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Scheme 5. Scope of α-Bromoestersa,b
aReaction conditions: 1a (0.1 mmol), 2a (0.11 mmol), 3 (0.3 mmol) and NaOH (4
equiv) in CH3CN (1 mL), open to air under a 5 W blue LED at room temperature.
bYields of isolated products.
Several control experiments were conducted to explore the reaction mechanism
(Scheme 6). In the presence of 2,2,6,6ꢀtetramethylpiperidineꢀNꢀoxyl (TEMPO), an
efficient free radical scavenger, the reaction was completely inhibited, suggesting that
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TEMPO has a significant effect on the tranformation. Similarly, when 3 equivalents of
1,1ꢀdiphenylethylene (DPE) or butylated hydroxytoluene (BHT), were added to the
reaction, no desired product 4a obtained (eq 2 or eq 3). When 3 equivalents of
2,2,6,6ꢀtetramethylpiperidylꢀ1ꢀoxyl (TEMPO) were added to the reaction of
propꢀ2ꢀenꢀ1ꢀamine, 2a with 3a, no desired product obtained. However, compound (8)
was detected by GCꢀMS (eq 4) (see the Supporting Information for details). Taken
together, these observations suggested that a possible radical mechanism should be
involved. Furthermore, 1ꢀbenzylꢀ3ꢀphenylthiourea 918 was used as the substrate under
the same conditions, and the desired product 4a was obtained in 77% isolated yield,
indicating that 9 might be a reasonable intermediate (eq 5). To provide a more critical
insight, the presence of 3 equiv of TEMPO significantly inhibited the reaction of 9
with 3a (eq 6).
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Scheme 6. Mechanistic Studies
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Figure 2. UV-vis Absorption Spectra for Mechaniam Study
To further gain insight into the mechanism, we performed UVꢀvis spectroscopic
measurement on combinations of 1a, 2a, 3a, and NaOH (Figure 2). An obvious red
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shift in absorption was observed when 3a (colorless) was added in the colorless
mixture of 1a, 2a, and NaOH. An in situ generated Hꢀbonding electron
donorꢀacceptor (EDA) complex from the association of the 1a, 2a and 3a, probably
leading to the red shift.19 The reaction solution containing the EDA complex is visibly
yellow and exhibits visibleꢀlight absorption at 400ꢀ600 nm. Therefore, an in situ
generated EDA complex probably acts as the photocatalyst to further promote the
transformation.
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Scheme 7. Possible Reaction Mechanism
On the basis of the above experimental results, we propose a plausible reaction
mechanism for the threeꢀcomponent reaction (Scheme 7). At first, a nucleophilic
attack of activated amine (1) on isothiocyanate (2) in situ forms a crucial active
intermediate A.10,20 Next, the intermediate A is coupling with 3a to form a Hꢀbonding
EDA complex B.21 Then the hemolytic dissociation of B releases radicals C and D.
Meanwhile, the intermediate A can also be transformed into the intermediate E by
isomerization.22 E is oxidized to intermediate F using B (EDA complex) as
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photocatalyst. Subsequently, the radicals coupling of the thioyl radical F with
intermediate D affords the intermediate G. Finally, the desired product 4 would be
produced from G through the ammonolysis/cyclization process under base conditions.
In the dark, ethylbromoaectate (3a) reacts with base to form the carbon ion H, which
further coupling with intermediate A to give the intermediate G and form the desired
product 4.
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CONCLUSION
In summary, we have developed an effective visible lightꢀpromoted
threeꢀcomponent tandem reaction for the convenient and practical synthesis of
2ꢀiminothiazolidinꢀ4ꢀones from readily accessible starting materials. The result of the
research provides highly efficient assembly of 2ꢀiminothiazolidinꢀ4ꢀones via formal
[1 + 2 + 2] annulation of the readily available amine compounds, aryl/alkyl
isothiocyanates, and αꢀbromoesters. A variety of amines and isothiocyanates
underwent
this
tandem
cyclization
with
αꢀbromoesters
to
afford
2ꢀiminothiazolidinꢀ4ꢀones in moderate to good yields. UVꢀvis spectroscop indicate
that an in stiu generated EDA complex serves as photocatalyst promoting the reaction
process. The present process provided a valuable new approach for the construction of
2ꢀiminothiazolidinꢀ4ꢀones scaffold via visible lightꢀpromoted C−S/C−N bond
formations, which will be useful in the synthesis of heterocyclics. Furthermore, these
easily available and highly functionalized 2ꢀiminothiazolidinꢀ4ꢀones would be of
great interest in medicinal screening and further synthetic application.
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EXPERIMENTAL SECTION
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General Information. Melting points were measured using a melting point
instrument and are uncorrected. 1H and 13CNMR spectra were recorded on a 400 MHz
NMR spectrometer (Bruker Avance DRXꢀ400 MHz). IR spectra were obtained with
an infrared spectrometer on either potassium bromide pellets or liquid films between
two potassium bromide pellets (Bruker Tensor 27). GCꢀMS (Thermo Trace 1300
GCꢀThermo ISO LT) data were obtained using electron ionization. HRMS (MAT
95XP, Thermo) was carried out on a highꢀresolution mass spectrometer
(LCMSꢀITꢀTOF). The photoreaction instrument (WPꢀTECꢀ1020L) was purchased
from WATTCAS, China. TLC was performed using commercially available 100−400
mesh silica gel plates (GF254). Unless otherwise noted, purchased chemicals were
used without further purification.
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General Procedure for Synthesis of 2-Iminothiazolidin-4-ones Derivatives.
A mixture of amines (0.10 mmol), isothiocyanates (0.11 mmol), αꢀbromoesters (0.30
mmol), NaOH (0.40 mmol, 4.0 equiv) was stirred in CH3CN (1.0 mL) under a 5 W
blue LEDs at room temperature for 12 h. After completion of the reaction (monitored
by TLC), water (10 mL) was added to the reaction mixture, and the resulting mixture
was extracted with ethyl acetate. The combined organic layers were then dried over
MgSO4, filtered, and then concentrated in vacuum. The residue was purified by flash
chromatography on silica gel to give the desired product (using the mixture of
petroleum ether and ethyl acetate (5:1) as eluents).
(Z)ꢀ3ꢀBenzylꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4a). Yellow liquid: 93% yield (26
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mg); IR (KBr, cmꢀ1) 3061, 3032, 2979, 2933, 1724, 1628, 1592, 1489, 1380, 1216,
1160, 756, 697; 1H NMR (400 MHz, d6ꢀDMSO, ppm) δ 7.39ꢀ7.36 (m, 3H), 7.34ꢀ7.32
(d, J = 8.0 Hz, 3H), 7.30ꢀ7.26 (m, 1H), 7.13ꢀ7.10 (m, 1H), 6.90ꢀ6.88 (m, 2H), 4.92 (s,
2H), 4.10 (s, 2H); 13C NMR (100 MHz, d6ꢀDMSO, ppm) δ 172.4, 155.5, 148.4, 136.6,
129.8, 128.9, 128.1, 127.9, 124.8, 121.3, 45.8, 33.1; MS (EI, 70 eV) m/z 282.1, 253.1,
240.1, 207.1, 148.1, 136.1; HRMS (ESI) calcd C16H15N2OS [M + H]+ m/z 283.0900,
found m/z 283.0892.
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(Z)ꢀ3ꢀ(4ꢀFluorobenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4b). Yellow liquid:
73% yield (22 mg); IR (KBr, cmꢀ1) 3057, 3035, 2980, 2933, 1724, 1627, 1592, 1487,
1
1381, 1221, 1157, 1098, 768, 697; H NMR (400 MHz, CDCl3, ppm) δ 7.55ꢀ7.50 (m,
2H), 7.37ꢀ7.33 (m, 2H), 7.17ꢀ7.13 (m, 1H), 7.04ꢀ6.99 (m, 2H), 6.96ꢀ6.93 (m, 2H),
4.99 (s, 2H), 3.81 (s, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 171.6, 162.6 (d, J =
249.0 Hz), 153.9, 147.8, 131.8 (d, J = 4.0 Hz), 131.2 (d, J = 8.0 Hz), 129.3, 124.7,
120.9, 115.3 (d, J = 21.0 Hz), 45.5, 32.7; MS (EI, 70 eV) m/z 300.1, 271.1, 258.1,
225.1, 166.1, 136.1; HRMS (ESI) calcd C16H14FN2OS [M + H]+ m/z 301.0805, found
m/z 301.0802.
(Z)ꢀ3ꢀ(4ꢀChlorobenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4c). Yellow liquid: 53%
yield (17 mg); IR (KBr, cmꢀ1) 3057, 3029, 2979, 2934, 1725, 1628, 1593, 1490, 1380,
1
1215, 1155, 1093, 768, 696; H NMR (400 MHz, CDCl3, ppm) δ 7.48ꢀ7.45 (m, 2H),
7.37ꢀ7.28 (m, 4H), 7.17ꢀ7.12 (m, 1H), 6.95ꢀ6.92 (m, 2H), 4.98 (s, 2H), 3.81 (s, 2H);
13C NMR (100 MHz, CDCl3, ppm) δ 171.6, 153.8, 147.8, 134.4, 133.9, 130.7, 129.3,
128.6, 124.7, 120.9, 45.6, 32.7; MS (EI, 70 eV) m/z 316.0, 287.0, 274.0, 242.1, 182.0,
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137.1; HRMS (ESI) calcd C16H14ClN2OS [M + H]+ m/z 317.0510, found m/z
317.0509.
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(Z)ꢀ3ꢀ(4ꢀBromobenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4d). Yellow solid: 94%
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o
yield (34 mg); mp 110ꢀ112 C; IR (KBr, cmꢀ1) 3063, 3030, 2971, 2934, 1718, 1638,
1593, 1487, 1380, 1158, 1070, 767, 694; H NMR (400 MHz, d6ꢀDMSO, ppm) δ
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7.55ꢀ7.53 (d, J = 8.0 Hz, 2H), 7.36ꢀ7.32 (t, J = 16.0 Hz, 4H), 7.13ꢀ7.09 (t, J = 16.0 Hz,
1H), 6.90ꢀ6.88 (d, J = 8.0 Hz, 2H), 4.88 (s, 2H), 4.09 (s, 2H); 13C NMR (100 MHz,
d6ꢀDMSO, ppm) δ 172.4, 155.5, 148.4, 136.0, 131.8, 130.5, 129.7, 124.8, 121.3,
121.1, 45.2, 33.0; MS (EI, 70 eV) m/z 360.0, 286.0, 260.0, 227.9, 207.1, 136.1;
HRMS (ESI) calcd C16H14BrN2OS [M + H]+ m/z 361.0005, found m/z 361.0001.
(Z)ꢀ4ꢀ((4ꢀOxoꢀ2ꢀ(phenylimino)thiazolidinꢀ3ꢀyl)methyl)benzonitrile (4e). Yellow
liquid: 85% yield (26 mg); IR (KBr, cmꢀ1) 3057, 2982, 2934, 2228, 1725, 1630, 1592,
1487, 1381, 1216, 1159, 896, 769, 697; H NMR (400 MHz, d6ꢀDMSO, ppm) δ
1
7.83ꢀ7.81 (d, J = 8.0 Hz, 2H), 7.55ꢀ7.53 (d, J = 8.0 Hz, 2H), 7.38ꢀ7.31 (m, 2H),
7.13ꢀ7.09 (m, 1H), 6.89ꢀ6.86 (t, J = 12.0 Hz, 2H), 5.02 (s, 2H), 4.12 (s, 2H); 13C NMR
(100 MHz, d6ꢀDMSO, ppm) δ 172.5, 155.4, 148.0, 142.2, 132.9, 129.8, 128.8, 124.9,
121.3, 119.1, 110.7, 45.5, 33.1; MS (EI, 70 eV) m/z 307.1, 278.1, 264.1, 232.1, 173.0,
136.1; HRMS (ESI) calcd C17H14N3OS [M + H]+ m/z 308.0852, found m/z 308.0851.
(Z)ꢀ3ꢀ(4ꢀMethoxybenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4f). White liquid:
63% yield (20 mg); IR (KBr, cmꢀ1) 3057, 3032, 2957, 2932, 1722, 1626, 1592, 1487,
1
1381, 1248, 1157, 1033, 769, 697; H NMR (400 MHz, CDCl3, ppm) δ 7.50ꢀ7.47 (m,
2H), 7.37ꢀ7.32 (m, 2H), 7.16ꢀ7.11 (m, 1H), 6.96ꢀ6.94 (m, 2H), 6.87ꢀ6.83 (m, 2H),
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4.96 (s, 2H), 3.79 (s, 3H), 3.77 (m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 171.6,
159.3, 154.0, 148.0, 130.8, 129.2, 128.3, 124.6, 121.0, 113.8, 55.3, 45.7, 32.7; MS (EI,
70 eV) m/z 312.1, 270.1, 238.1, 207.1, 178.1, 136.1; HRMS (ESI) calcd C17H17N2O2S
[M + H]+ m/z 313.1005, found m/z 313.1001.
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(Z)ꢀ3ꢀ(4ꢀMethylbenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4g). Yellow solid: 81%
yield (24 mg); mp 92ꢀ94 °C; IR (KBr, cmꢀ1) 3063, 3032, 2954, 2923, 1720, 1641,
1
1595, 1425, 1384, 1156, 1108, 769, 694; H NMR (400 MHz, CDCl3, ppm) δ
7.43ꢀ7.41 (d, J = 8.0 Hz, 2H), 7.34ꢀ7.30 (m, 2H), 7.13ꢀ7.12 (m, 3H), 6.95ꢀ6.93 (m,
2H), 4.97 (s, 2H), 3.73 (s, 2H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ
171.7, 154.0, 148.0, 137.7, 133.1, 129.3, 129.2, 129.2, 124.6, 121.0, 46.0, 32.8, 21.2;
MS (EI, 70 eV) m/z 296.1, 254.1, 222.1, 162.1, 137.1, 105.1; HRMS (ESI) calcd
C17H17N2OS [M + H]+ m/z 297.1056, found m/z 297.1050.
(Z)ꢀ3ꢀ(3ꢀFluorobenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4h). Yellow liquid:
73% yield (22 mg); IR (KBr, cmꢀ1) 3061, 3031, 2980, 2934, 1726, 1632, 1591, 1487,
1
1380, 1253, 1158, 1075, 769, 696; H NMR (400 MHz, CDCl3, ppm) δ 7.37ꢀ7.33 (m,
2H), 7.30ꢀ7.27 (m, 2H), 7.25ꢀ7.21 (m, 1H), 7.17ꢀ7.12 (m, 1H), 7.02ꢀ6.97 (m, 1H),
6.96ꢀ6.93 (m, 2H), 5.01 (s, 2H), 3.83 (s, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ
171.5, 162.8 (d, J = 245.0 Hz), 153.8, 147.8, 138.2 (d, J = 7.0 Hz), 130.0 (d, J = 8.0
Hz), 129.3, 124.7, 124.6 (d, J = 3.0 Hz), 121.0, 115.9 (d, J = 22.0 Hz), 114.9 (d, J =
21.0 Hz), 45.7 (d, J = 1.0 Hz), 32.7; MS (EI, 70 eV) m/z 300.1, 258.1, 225.1, 200.1,
166.0, 136.1; HRMS (ESI) calcd C16H14FN2OS [M + H]+ m/z 301.0805, found m/z
301.0803.
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(Z)ꢀ3ꢀ(3ꢀChlorobenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4i). White solid: 83%
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yield (26 mg); mp 72ꢀ74 °C; IR (KBr, cmꢀ1) 3060, 3030, 2925, 2853, 1718, 1631,
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9
1
1592, 1486, 1381, 1220, 1156, 1094, 767, 694; H NMR (400 MHz, CDCl3, ppm) δ
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7.55ꢀ7.51 (m, 2H), 7.38ꢀ7.33 (m, 2H), 7.17ꢀ7.13 (m, 1H), 7.04ꢀ6.99 (m, 2H),
6.98ꢀ6.93 (m, 2H), 4.99 (s, 2H), 3.81 (s, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ
171.6, 163.7, 161.3, 153.8, 147.8, 131.2, 131.1, 129.3, 124.7, 120.9, 115.4, 115.2,
45.5, 32.7; MS (EI, 70 eV) m/z 316.0, 287.0, 274.0, 216.1, 182.0, 137.1; HRMS (ESI)
calcd C16H14ClN2OS [M + H]+ m/z 317.0510, found m/z 317.0511.
(Z)ꢀ3ꢀ(3ꢀBromobenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4j). Yellow solid: 83%
yield (30 mg); mp 91ꢀ93 °C; IR (KBr, cmꢀ1) 3063, 3030, 2935, 2853, 1717, 1630,
1
1591, 1485, 1324, 1156, 1069, 767, 694; H NMR (400 MHz, CDCl3, ppm) δ
7.69ꢀ7.68 (t, J = 4.0 Hz, 1H), 7.44ꢀ7.42 (m, 2H), 7.37ꢀ7.32 (m, 2H), 7.22ꢀ7.17 (t, J =
20.0 Hz, 1H), 7.16ꢀ7.12 (m, 1H), 6.95ꢀ6.92 (m, 2H), 4.97 (s, 2H), 3.82 (s, 2H); 13C
NMR (100 MHz, CDCl3, ppm) δ 171.5, 153.7, 147.7, 138.0, 132.1, 131.1, 130.0,
129.3, 127.8, 124.8, 122.5, 120.9, 45.6, 32.7; MS (EI, 70 eV) m/z 360.0, 333.0, 287.0,
260.0, 207.1, 136.1; HRMS (ESI) calcd C16H14BrN2OS [M + H]+ m/z 361.0005,
found m/z 361.0009.
(Z)ꢀ3ꢀ(3ꢀMethoxybenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4k). Yellow solid:
66% yield (21 mg); mp 74ꢀ76 °C; IR (KBr, cmꢀ1) 3060, 3031, 2982, 2936, 1716, 1634,
1593, 1471, 1378, 1262, 1158, 1035, 766, 690; 1H NMR (400 MHz, d6ꢀDMSO, ppm)
δ 7.37ꢀ7.33 (m, 2H), 7.28ꢀ7.24 (m, 1H), 7.14ꢀ7.09 (m, 1H), 6.93ꢀ6.90 (d, J = 12.0 Hz,
2H), 6.88ꢀ6.84 (m, 3H), 4.89 (s, 2H), 4.10 (s, 2H), 3.75 (s, 3H); 13C NMR (100 MHz,
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d6ꢀDMSO, ppm) δ 172.4, 159.7, 155.5, 148.4, 138.1, 130.0, 129.8, 124.8, 121.3,
120.2, 113.9, 113.2, 55.4, 45.7, 33.0; MS (EI, 70 eV) m/z 312.1, 270.1, 238.1, 207.1,
178.1, 136.1; HRMS (ESI) calcd C17H17N2O2S [M + H]+ m/z 313.1005, found m/z
313.1002.
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(Z)ꢀ3ꢀ(3ꢀMethylbenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4l). Yellow liquid: 36%
yield (11 mg); IR (KBr, cmꢀ1) 3057, 3029, 2974, 2936, 1718, 1630, 1592, 1486, 1376,
1
1218, 1155, 1092, 768, 695; H NMR (400 MHz, CDCl3, ppm) δ 7.36ꢀ7.31 (m, 4H),
7.25ꢀ7.20 (m, 1H), 7.16ꢀ7.10 (m, 2H), 6.96ꢀ6.94 (m, 2H), 4.99 (s, 2H), 3.80 (s, 2H),
2.35 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 171.7, 154.0, 148.0, 138.1, 135.8,
129.8, 129.2, 128.7, 128.4, 126.1, 124.6, 121.0, 46.3, 32.7, 21.4; MS (EI, 70 eV) m/z
296.1, 254.1, 222.1, 162.1, 136.1, 105.1; HRMS (ESI) calcd C17H17N2OS [M + H]+
m/z 297.1056, found m/z 297.1055.
(Z)ꢀ3ꢀ(2ꢀFluorobenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4m). Yellow liquid:
33% yield (10 mg); IR (KBr, cmꢀ1) 3061, 3030, 2980, 2932, 1729, 1636, 1491, 1383,
1
1280, 1162, 1026, 758, 697; H NMR (400 MHz, CDCl3, ppm) δ 7.39ꢀ7.30 (m, 3H),
7.30ꢀ7.26 (m, 1H), 7.15ꢀ7.03 (m, 3H), 6.93ꢀ6.90 (m, 2H), 5.12 (s, 2H), 3.86 (s, 2H);
13C NMR (100 MHz, CDCl3, ppm) δ 171.4, 160.8 (d, J = 247.0 Hz), 153.4, 147.7,
129.7 (d, J = 4.0 Hz), 129.4 (d, J = 9.0 Hz), 129.2, 124.7, 124.0 (d, J = 3.0 Hz), 122.7
(d, J = 14.0 Hz), 120.9, 115.5 (d, J = 21.0 Hz), 40.3 (d, J = 5.0 Hz), 32.6; MS (EI, 70
eV) m/z 300.1, 281.1, 257.1, 225.1, 166.1, 136.1; HRMS (ESI) calcd C16H14FN2OS
[M + H]+ m/z 301.0805, found m/z 301.0804.
(Z)ꢀ3ꢀ(2ꢀChlorobenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4n). Yellow liquid:
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88% yield (28 mg); IR (KBr, cmꢀ1) 3061, 3032, 2979, 2932, 1726, 1629, 1592, 1485,
5
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7
1
1381, 1216, 1161, 1039, 751, 696; H NMR (400 MHz, CDCl3, ppm) δ 7.38ꢀ7.36 (m,
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9
1H), 7.33ꢀ7.29 (m, 2H), 7.25ꢀ7.20 (m, 2H), 7.19ꢀ7.15 (m, 1H), 7.14ꢀ7.09 (m, 1H),
6.91ꢀ6.88 (m, 2H), 5.16 (s, 2H), 3.90 (s, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ
171.5, 153.5, 147.8, 133.1, 132.9, 129.7, 129.2, 128.6, 127.6, 126.8, 124.7, 120.9,
44.2, 32.7; MS (EI, 70 eV) m/z 316.0, 281.1, 207.1, 165.1, 104.1, 77.1; HRMS (ESI)
calcd C16H14ClN2OS [M + H]+ m/z 317.0510, found m/z 317.0511.
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(Z)ꢀ3ꢀ(2ꢀMethoxybenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4o). Yellow solid:
69% yield (22 mg); mp 96ꢀ98 °C; IR (KBr, cmꢀ1) 3062, 3030, 2926, 1730, 1637, 1593,
1491, 1383, 1246, 1161, 1024, 750; 1H NMR (400 MHz, CDCl3, ppm) δ 7.35ꢀ7.25 (m,
3H), 7.16ꢀ7.11 (m, 2H), 6.96ꢀ6.88 (m, 4H), 5.11 (s, 2H), 3.87 (m, 5H); 13C NMR (100
MHz, CDCl3, ppm) δ 171.6, 157.2, 153.8, 148.0, 129.3, 128.4, 127.4, 124.5, 123.5,
121.0, 120.3, 110.5, 55.6, 41.9, 32.7; MS (EI, 70 eV) m/z 312.1, 281.1, 195.1, 121.1,
91.1, 77.1; HRMS (ESI) calcd C17H17N2O2S [M + H]+ m/z 313.1005, found m/z
313.1005.
(Z)ꢀ3ꢀ(3,5ꢀDichlorobenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4p). Yellow solid:
48% yield (17 mg); mp 106ꢀ108 °C; IR (KBr, cmꢀ1) 3060, 3032, 2951, 1725, 1648,
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1596, 1435, 1384, 1159, 1070, 759, 711; H NMR (400 MHz, CDCl3, ppm) δ
7.41ꢀ7.40 (d, J = 4.0 Hz, 2H), 7.38ꢀ7.34 (m, 2H), 7.31ꢀ7.30 (t, J = 4.0 Hz, 1H),
7.18ꢀ7.14 (m, 1H), 6.96ꢀ6.93 (dt, J = 8.0, 4.0 Hz, 2H), 4.94 (s, 2H), 3.83 (s, 2H); 13C
NMR (100 MHz, CDCl3, ppm) δ 171.4, 153.6, 147.5, 138.9, 135.0, 129.3, 128.2,
127.6, 124.9, 120.9, 45.2, 32.7; MS (EI, 70 eV) m/z 350.0, 307.0, 275.0, 216.0, 177.1,
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136.1; HRMS (ESI) calcd C16H13Cl2N2OS [M + H]+ m/z 351.0120, found m/z
351.0120.
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(Z)ꢀ3ꢀ(3ꢀChloroꢀ4ꢀfluorobenzyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4q). Yellow
solid: 87% yield (29 mg); mp 113ꢀ115 °C; IR (KBr, cmꢀ1) 3060, 3032, 2937, 1717,
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1636, 1590, 1499, 1379, 1249, 1158, 1061, 896, 769; H NMR (400 MHz, CDCl3,
ppm) δ 7.62ꢀ7.60 (dd, J = 4.0, 4.0 Hz, 1H), 7.43ꢀ7.39 (m, 1H), 7.38ꢀ7.33 (m, 2H),
7.17ꢀ7.13 (m, 1H), 7.11ꢀ7.06 (t, J = 20.0 Hz, 1H), 6.96ꢀ6.93 (m, 2H), 4.95 (s, 2H),
3.82 (s, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 171.5, 158.0 (d, J = 248.0 Hz),
153.7, 147.6, 132.9 (d, J = 4.0 Hz), 131.6, 129.3, 129.2, 124.8, 120.9, 120.9 (d, J =
17.0 Hz), 116.5 (d, J = 19.0 Hz), 45.1, 32.7; MS (EI, 70 eV) m/z 334.1, 292.0, 259.1,
234.1, 200.0, 143.1; HRMS (ESI) calcd C16H13ClFN2OS [M + H]+ m/z 335.0416,
found m/z 335.0417.
(Z)ꢀ2ꢀ(Phenylimino)ꢀ3ꢀ(3,4,5ꢀtrimethoxybenzyl)thiazolidinꢀ4ꢀone (4r). Yellow
liquid: 31% yield (12 mg); IR (KBr, cmꢀ1) 3058, 3030, 2934, 1720, 1628, 1591, 1459,
1
1379, 1236, 1154, 1007, 769, 697; H NMR (400 MHz, CDCl3, ppm) δ 7.38ꢀ7.33 (m,
2H), 7.18ꢀ7.13 (m, 1H), 6.96ꢀ6.93 (m, 2H), 6.84 (s, 2H), 4.95 (s, 2H), 3.85 (s, 6H),
3.85 (s, 3H), 3.81 (s, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 171.6, 154.3, 153.1,
148.0, 137.8, 131.5, 129.4, 124.7, 120.8, 106.7, 60.8, 56.1, 46.5, 32.7; MS (EI, 70 eV)
m/z 372.1, 357.1, 330.1, 238.1, 148.1, 136.1; HRMS (ESI) calcd C19H21N2O4S [M +
H]+ m/z 373.1217, found m/z 373.1214.
(Z)ꢀ3ꢀ(Naphthalenꢀ1ꢀylmethyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4s). Yellow
liquid: 72% yield (24 mg); IR (KBr, cmꢀ1) 3052, 3030, 2978, 2930, 1719, 1637, 1594,
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1487, 1381, 1215, 1152, 1072, 766, 697; H NMR (400 MHz, CDCl3, ppm) δ
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8.38ꢀ8.36 (d, J = 8.0 Hz, 1H), 7.85ꢀ7.77 (m, 2H), 7.56ꢀ7.40 (m, 4H), 7.33ꢀ7.29 (t, J =
16.0 Hz, 2H), 7.13ꢀ7.09 (t, J = 16.0 Hz, 1H), 6.93ꢀ6.90 (t, J = 12.0 Hz, 2H), 5.50 (s,
2H), 3.79 (s, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 171.8, 153.9, 147.9, 133.8,
131.5, 130.9, 129.3, 128.7, 128.5, 126.7, 126.4, 125.8, 125.2, 124.7, 123.9, 121.0,
44.3, 32.6; MS (EI, 70 eV) m/z 332.1, 290.1, 257.1, 215.1, 154.1, 141.1; HRMS (ESI)
calcd C20H17N2OS [M +H]+ m/z 333.1056, found m/z 333.1054.
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(Z)ꢀ2ꢀ(Phenylimino)ꢀ3ꢀ(pyridinꢀ3ꢀylmethyl)thiazolidinꢀ4ꢀone (4t). Yellow liquid:
34% yield (10 mg); IR (KBr, cmꢀ1) 3056, 3031, 2982, 2932, 1720, 1628, 1486, 1378,
1216, 1154, 1027, 769, 697; 1H NMR (400 MHz, CDCl3, ppm) δ 8.80ꢀ8.79 (d, J = 4.0
Hz, 1H), 8.57ꢀ8.55 (m, 1H), 7.88ꢀ7.85 (m, 1H), 7.36ꢀ7.25 (m, 3H), 7.16ꢀ7.12 (m, 1H),
6.95ꢀ6.93 (m, 2H), 5.03 (s, 2H), 3.82 (m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ
171.5, 153.6, 150.5, 149.2, 147.6, 137.1, 131.7, 129.3, 124.8, 123.5, 120.9, 43.8, 32.7;
MS (EI, 70 eV) m/z 283.1, 241.1, 208.1, 183.1, 149.1, 136.1; HRMS (ESI) calcd
C15H14N3OS [M + H]+ m/z 284.0852, found m/z 284.0850.
(Z)ꢀ2ꢀ(Phenylimino)ꢀ3ꢀ(thiophenꢀ2ꢀylmethyl)thiazolidinꢀ4ꢀone (4u). Yellow liquid:
71% yield (20 mg); IR (KBr, cmꢀ1) 3059, 3030, 2979, 2932, 1722, 1626, 1592, 1487,
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1381, 1215, 1181, 1026, 769, 696; H NMR (400 MHz, CDCl3, ppm) δ 7.39ꢀ7.34 (m,
2H), 7.25ꢀ7.24 (m, 1H), 7.22ꢀ7.21 (d, J = 4.0 Hz, 1H), 7.18ꢀ7.13 (m, 1H), 7.02ꢀ7.00
(m, 2H), 6.97ꢀ6.95 (m, 1H), 5.18 (s, 2H), 3.79 (s, 2H); 13C NMR (100 MHz, CDCl3,
ppm) δ 171.0, 153.3, 147.8, 137.1, 129.3, 128.5, 126.5, 126.2, 124.7, 121.0, 40.6, 32.8;
MS (EI, 70 eV) m/z 288.1, 246.0, 213.1, 154.0, 137.1, 110.1; HRMS (ESI) calcd
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C14H13N2OS2 [M + H]+ m/z 289.0464, found m/z 289.0457.
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(Z)ꢀ3ꢀ(Furanꢀ2ꢀylmethyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4v). Yellow solid:
73% yield (20 mg); mp 108ꢀ110 °C; IR (KBr, cmꢀ1) 3061, 3032, 2982, 1728, 1624,
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1591, 1379, 1155, 1073, 1011, 934, 776; H NMR (400 MHz, CDCl3, ppm) δ
7.36ꢀ7.31 (m, 3H), 7.15ꢀ7.11 (t, J = 16.0 Hz, 1H), 6.97ꢀ6.94 (dd, J = 8.0, 4.0 Hz, 2H),
6.41ꢀ6.40 (d, J = 4.0 Hz, 1H), 6.33ꢀ6.31 (dd, J = 4.0, 4.0 Hz, 1H), 5.02 (s, 2H), 3.80 (s,
2H); 13C NMR (100 MHz, CDCl3, ppm) δ 171.3, 153.4, 149.1, 147.8, 142.3, 129.2,
124.7, 121.0, 110.5, 109.5, 39.1, 32.6; MS (EI, 70 eV) m/z 272.1, 243.1, 230.1, 172.1,
138.1, 81.2; HRMS (ESI) calcd C14H13N2O2S [M + H]+ m/z 273.0692, found m/z
273.0691.
(Z)ꢀ3ꢀ(Cyclohexylmethyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4w). White solid:
49% yield (14 mg); mp 91ꢀ92 °C; IR (KBr, cmꢀ1) 3060, 3029, 2934, 1725, 1640, 1593,
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1383, 1169, 773, 700; H NMR (400 MHz, CDCl3, ppm) δ 7.36ꢀ7.32 (m, 2H),
7.15ꢀ7.11 (m, 1H), 6.95ꢀ6.93 (m, 2H), 3.79 (s, 2H), 3.72ꢀ3.70 (d, J = 8.0 Hz, 2H),
1.99ꢀ1.90 (m, 1H), 1.72ꢀ1.67 (t, J = 20.0 Hz, 4H), 1.31ꢀ0.94 (m, 6H); 13C NMR (100
MHz, CDCl3, ppm) δ 172.1, 154.6, 148.2, 129.2, 124.5, 120.9, 49.0, 35.8, 32.6, 30.7,
26.3, 25.7; MS (EI, 70 eV) m/z 288.2, 205.1, 193.2, 164.1, 145.1, 131.1; HRMS (ESI)
calcd C16H21N2OS [M + H]+ m/z 289.1369, found m/z 289.1363.
(Z)ꢀ3ꢀHexylꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4x). Yellow liquid: 59% yield (16
mg); IR (KBr, cmꢀ1) 3062, 3031, 2930, 2857, 1725, 1633, 1593, 1489, 1387, 1210,
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1165, 1075, 768, 696; H NMR (400 MHz, CDCl3, ppm) δ 7.37ꢀ7.32 (m, 2H),
7.16ꢀ7.11 (m, 1H), 6.96ꢀ6.93 (m, 2H), 3.86ꢀ3.82 (t, J = 16.0 Hz, 2H), 3.78 (s, 2H),
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1.75ꢀ1.68 (m, 2H), 1.38ꢀ1.29 (m, 6H), 0.91ꢀ0.87 (t, J = 16.0 Hz, 3H); 13C NMR (100
MHz, CDCl3, ppm) δ 171.8, 154.3, 148.2, 129.2, 124.5, 121.0, 43.3, 32.7, 31.4, 27.2,
26.5, 22.5, 14.0; MS (EI, 70 eV) m/z 276.2, 247.1, 233.1, 219.1, 205.1, 193.1; HRMS
(ESI) calcd C15H21N2OS [M +H]+ m/z 277.1369, found m/z 277.1368.
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(Z)ꢀ2ꢀ(Phenylimino)ꢀ3ꢀ(3ꢀphenylpropyl)thiazolidinꢀ4ꢀone (4y). Yellow liquid: 89%
yield (28 mg); IR (KBr, cmꢀ1) 3060, 3027, 2944, 1721, 1628, 1592, 1490, 1386, 1207,
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1148, 1090, 769, 697; H NMR (400 MHz, CDCl3, ppm) δ 7.36ꢀ7.31 (m, 2H),
7.29ꢀ7.25 (m, 2H), 7.23ꢀ7.20 (m, 2H), 7.19ꢀ7.10 (m, 2H), 6.96ꢀ6.93 (m, 2H),
3.93ꢀ3.89 (t, J = 16.0 Hz, 2H), 3.67 (s, 2H), 2.73ꢀ2.69 (t, J = 16.0 Hz, 2H), 2.13ꢀ2.05
(m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 171.8, 154.3, 148.1, 141.2, 129.3, 128.4,
128.3, 126.0, 124.6, 121.0, 43.1, 33.2, 32.7, 28.3; MS (EI, 70 eV) m/z 310.1, 218.1,
205.1, 193.1, 164.1, 145.1; HRMS (ESI) calcd C18H19N2OS [M + H]+ m/z 311.1213,
found m/z 311.1211.
(Z)ꢀ3ꢀ(3ꢀMorpholinopropyl)ꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (4z). Yellow liquid:
23% yield (7 mg); IR (KBr, cmꢀ1) 3061, 3031, 2954, 2853, 1723, 1630, 1592, 1488,
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1386, 1191, 1070, 769, 697; H NMR (400 MHz, CDCl3, ppm) δ 7.37ꢀ7.33 (m, 2H),
7.16ꢀ7.12 (m, 1H), 6.95ꢀ6.92 (m, 2H), 3.95ꢀ3.91 (t, J = 16.0 Hz, 2H), 3.80 (s, 2H),
3.73ꢀ3.71 (t, J = 8.0 Hz, 4H), 2.50ꢀ2.46 (t, J = 16.0 Hz, 6H), 1.98ꢀ1.91 (m, 2H); 13C
NMR (100 MHz, CDCl3, ppm) δ 171.8, 154.3, 148.0, 129.3, 124.6, 120.9, 66.9, 56.3,
53.5, 41.6, 32.8, 23.8; MS (EI, 70 eV) m/z 319.2, 289.2, 276.1, 232.1, 193.1, 127.2;
HRMS (ESI) calcd C16H22N3O2S [M + H]+ m/z 320.1427, found m/z 320.1423.
(Z)ꢀ3ꢀphenylꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (5a).11 Yellow solid: 12% yield (3
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mg); mp 166ꢀ168 °C; IR (KBr, cmꢀ1) 3060, 3029, 2965, 1725, 1632, 1589, 1493, 1364,
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1266, 1189, 692; H NMR (400 MHz, CDCl3, ppm) δ 7.55ꢀ7.50 (m, 2H), 7.46ꢀ7.38
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(m, 3H), 7.34ꢀ7.29 (m, 2H), 7.14ꢀ7.09 (m, 1H), 6.93ꢀ6.90 (m, 2H), 3.99 (s, 2H); 13C
NMR (100 MHz, CDCl3, ppm) δ 171.4, 154.9, 148.1, 134.7, 129.4, 129.2, 129.0,
128.0, 124.7, 120.9, 32.9; MS (EI, 70 eV) m/z 268, 194, 149, 123, 104, 77.
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(Z)ꢀ3ꢀcyclohexylꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (5b). White solid: 28% yield (8
mg); mp 110ꢀ111 °C; IR (KBr, cmꢀ1) 3058, 3032, 2929, 2856, 1722, 1629, 1591, 1334,
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1174, 1136, 1072, 772, 694; H NMR (400 MHz, CDCl3, ppm) δ 7.37ꢀ7.32 (m, 2H),
7.16ꢀ7.11 (m, 1H), 6.95ꢀ6.92 (m, 2H), 4.50ꢀ4.42 (m, 1H), 3.72 (s, 2H), 2.47ꢀ2.36 (m,
2H), 1.87ꢀ1.83 (m, 2H), 1.74ꢀ1.60 (m, 4H), 1.43ꢀ1.32 (m, 2H); 13C NMR (100 MHz,
CDCl3, ppm) δ 172.1, 154.5, 148.4, 129.3, 124.5, 120.9, 56.1, 32.5, 28.1, 26.1, 25.1;
MS (EI, 70 eV) m/z 274.2, 245.1, 203.1, 188.1, 151.2, 135.1; HRMS (ESI) calcd
C15H19N2OS [M + H]+ m/z 275.1213, found m/z 275.1211.
(Z)ꢀ3ꢀcyclopentylꢀ2ꢀ(phenylimino)thiazolidinꢀ4ꢀone (5c). Yellow liquid: 30% yield
(8 mg); IR (KBr, cmꢀ1) 3063, 3032, 2954, 2870, 1721, 1629, 1591, 1403, 1346, 1196,
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770, 695; H NMR (400 MHz, CDCl3, ppm) δ 7.37ꢀ7.32 (m, 2H), 7.15ꢀ7.11 (m, 1H),
6.96ꢀ6.93 (m, 2H), 5.01ꢀ4.93 (m, 1H), 3.74 (s, 2H), 2.32ꢀ2.22 (m, 2H), 1.98ꢀ1.84 (m,
4H), 1.64ꢀ1.58 (m, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 171.9, 154.3, 148.3,
129.3, 124.5, 120.9, 55.7, 32.5, 27.8, 25.4; MS (EI, 70 eV) m/z 260.2, 245.1, 231.1,
217.1, 193.1, 145.1; HRMS (ESI) calcd C14H17N2OS [M + H]+ m/z 261.1056, found
m/z 261.1049.
(Z)ꢀ3ꢀBenzylꢀ2ꢀ((4ꢀfluorophenyl)imino)thiazolidinꢀ4ꢀone (6a). Yellow liquid: 84%
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yield (25 mg); IR (KBr, cmꢀ1) 3066, 3038, 2985, 1724, 1627, 1501, 1426, 1381, 1210,
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1162, 1091, 766, 700; H NMR (400 MHz, CDCl3, ppm) δ 7.51ꢀ7.49 (m, 2H),
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7.35ꢀ7.26 (m, 3H), 7.05ꢀ6.99 (m, 2H), 6.92ꢀ6.87 (m, 2H), 5.00 (s, 2H), 3.78 (s, 2H);
13C NMR (100 MHz, CDCl3, ppm) δ 171.6, 160.0 (d, J = 242.0 Hz), 154.5, 144.0 (d,
J = 3.0 Hz), 135.9, 129.1, 128.5, 128.0, 122.4 (d, J = 8.0 Hz), 116.0 (d, J = 22.0 Hz),
46.3, 32.7; MS (EI, 70 eV) m/z 300.1, 271.1, 258.1, 225.1, 200.1, 148.1; HRMS (ESI)
calcd C16H14FN2OS [M + H]+ m/z 301.0805, found m/z 301.0806.
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(Z)ꢀ3ꢀBenzylꢀ2ꢀ((4ꢀbromophenyl)imino)thiazolidinꢀ4ꢀone (6b). White solid: 79%
yield (28 mg); mp 103ꢀ105 °C; IR (KBr, cmꢀ1) 3062, 3033, 2928, 1721, 1627, 1579,
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1482, 1385, 1150, 1067, 700; H NMR (400 MHz, CDCl3, ppm) δ 7.49ꢀ7.48 (d, J =
4.0 Hz, 2H), 7.44ꢀ7.43 (d, J = 4.0 Hz, 2H), 7.34ꢀ7.24 (m, 3H), 6.83ꢀ6.81 (d, J = 8.0
Hz, 2H), 4.99 (s, 2H), 3.79 (s, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 171.5, 154.6,
147.0, 135.8, 132.3, 129.1, 128.5, 128.0, 122.9, 117.7, 46.3, 32.7; MS (EI, 70 eV) m/z
360.0, 318.0, 286.0, 260.0, 214.9, 148.0; HRMS (ESI) calcd C16H14BrN2OS [M + H]+
m/z 361.0005, found m/z 360.9999.
(Z)ꢀ3ꢀBenzylꢀ2ꢀ((4ꢀ(trifluoromethyl)phenyl)imino)thiazolidinꢀ4ꢀone (6c). Yellow
solid: 76% yield (27 mg); mp 95ꢀ96 °C; IR (KBr, cmꢀ1) 3061, 3032, 2942, 1717, 1645,
1385, 1162, 1065, 844, 697; 1H NMR (400 MHz, CDCl3, ppm) δ 7.60ꢀ7.58 (d, J = 8.0
Hz, 2H), 7.51ꢀ7.48 (dt, J = 8.0, 4.0 Hz, 2H), 7.36ꢀ7.28 (m, 3H), 7.03ꢀ7.01 (d, J = 8.0
Hz, 2H), 5.02 (s, 2H), 3.84 (s, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 171.4, 155.0,
151.0 (d, J = 2.0 Hz), 135.7, 129.1, 128.6, 128.1, 126.8, 126.5 (q, J = 11.0 Hz), 124.3
(d, J = 270.0 Hz), 121.3, 46.4, 32.8; MS (EI, 70 eV) m/z 350.1, 331.1, 308.1, 275.1,
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