Rhodium(II)-Catalyzed Annulative Coupling of β-Ketothioamides with α-Diazo Compounds: Access to Highly Functionalized Thiazolidin-4-ones and Thiazolines

Article abstract of DOI:10.1021/acs.joc.0c00378

An operationally simple and efficient one-pot protocol for the synthesis of highly functionalized thiazolidin-4-ones and thiazolines has been devised via Rh(OAc)2-catalyzed annulative coupling of β-ketothioamides with diazo compounds under mild reaction conditions for the first time. This double functionalization of diazo compounds proceeds via selective S-alkylation followed by intramolecular N-cyclization enabling the formation of C-S and C-N bonds at moderate temperature. Notably, the products possess Z-stereochemistry with regard to the exocyclic C═C double bond at the 2-position of the ring. Further, the synthetic utility of the strategy has been revealed to access 2,3-dihydrobenzo[d]thiazoles. Remarkably, atom economy and tolerance of a wide range of functional groups are added characteristics to this strategy.

Full text of DOI:10.1021/acs.joc.0c00378

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Article
Rhodium(II)-Catalyzed Annulative Coupling of #-
Ketothioamides with #-Diazo compounds: Access to
Highly Functionalized Thiazolidin-4-ones and Thiazolines
Monish A Ansari, Dhananjay Yadav, and Maya Shankar Singh
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00378 • Publication Date (Web): 05 Jun 2020
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Rhodium(II)-Catalyzed Annulative Coupling of β-Ketothioamides with -Diazo
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compounds: Access to Highly Functionalized Thiazolidin-4-ones and Thiazolines
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Monish Arbaz Ansari, Dhananjay Yadav, and Maya Shankar Singh*
Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India
E-mail address: mayashankarbhu@gmail.com; mssingh@bhu.ac.in
ABSTRACT: An operationally simple and efficient one-pot protocol for the synthesis of highly func-
tionalized thiazolidin-4-ones and thiazolines has been devised via Rh(OAc)2-catalyzed annulative cou-
pling of β-ketothioamides with diazo compounds under mild reaction conditions for the first time. This
double functionalization of diazo compounds proceeds via selective S-alkylation followed by intramo-
lecular N-cyclization enabling the formation of CS and CN bonds at moderate temperature. Notably,
the products possess Z-stereochemistry with regard to the exocyclic C=C double bond at the 2-position
of the ring. Further, the synthetic utility of the strategy has been revealed to access 2,3-
dihydrobenzo[d]thiazoles. Remarkably, atom-economy and tolerance of a wide range of functional
groups are added characteristics to this strategy.
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INTRODUCTION
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The utility of nitrogen/sulfur heterocycles has become prevalent in medicinal and agricultural industries.
Thiazolidine-4-one/thiazoline derivatives represent an important class of heterocycles, which are ubiqui-
tous core structural motifs in many natural products, pharmaceuticals and functional materials.1 The thi-
azolidine derivatives exhibit extensive pharmacological property such as anticancer,2a antihistaminic,2b
anti-HIV2c activities, and selective COX-2 inhibitors.2d Thiazolidin-4-one scaffold has been considered
as a magic moiety because it possesses almost all types of biological properties such as antifungal, an-
titubercular, antimicrobial, antioxidant, antibacterial, cytotoxic, anti-inflammatory, analgesic and anti-
YFV (yellow fever virus) activities.3 Among the various available reports for the synthesis of thiazoli-
dine-4-ones, the most common and general approach involves the reaction between aldehyde, amine (or
Schiff’s base) and mercaptoacetic acid.4a Bolognese and co-workers4b synthesized the thiazolidine 4-
ones via microwave technique, while Lingampalle et al.4c constructed thiazolidines utilizing ionic liq-
uid. Jagodzinski et al.5a and our group5b,c synthesized the thiazolidin-4-ones by the reaction of β-
ketothioamides with different coupling partners. Despite the aforesaid approaches for the synthesis of
thiazolidin-4-ones, most of them suffer from one or more limitations such as use of excess base, lack of
generality, pre-functionalization of starting materials, limited functional group tolerability, and poor
yield. Therefore, it is still challenging and highly desirable to explore an operationally simple, efficient
and widely applicable general approach for the synthesis of thiazolidin-4-one derivatives.
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Over the past several decades, the decomposition of diazo compounds generating carbenes or metal-
stabilized carbenoids provided synthetic chemist a valuable tool for the selective construction of both
C−C and C−heteroatom bonds.6 Diazo compounds are amphiphilic, and the negatively polarized diazo
carbon atom is nucleophilic, while the metal carbene species generated from a diazo compound has an
electron-deficient carbene center.7 The utility of α-diazocarbonyl compounds as versatile synthon has
been established in various areas of organic synthesis such as Wolff rearrangements,8 cyclopropanation
reactions,9a-c benzannulation,9d cycloaddition chemistry,10 and C−H/heteroatom−H inser-
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tion/functionalization reactions.11 Furthermore, diazo compounds are widely used for the synthesis of
heterocyclic frameworks.12 Very recently, Wang et al.13a reported sulfhydryl-directed iridium-catalyzed
C−H/diazo coupling with naphthalene-1-thiols to construct naphtho fused thiopyrans. Koenigs et al.13b
reported iron-catalysed S-alkylation of thioether with diazoalkane. Rh(OAc)2 introduced by Teyssie and
co-workers14 in the early 1970s, is still the catalyst of choice for metal carbenoid formation.15
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In contrast, the coupling reactions involved metal carbenes and thiocarbonyl (CS) group are not of-
ten explored. In this regard, Zeng16a and Moody16b developed Rh-catalyzed intermolecular coupling re-
action of carbonyl group (CO) with diazo compounds, in which nucleophilic attack of carbonyl oxygen
of amide to Rh-carbenes generated carbonyl ylides, which upon further intramolecular cyclization af-
forded oxazole derivatives. In addition to above approaches the reaction of diazo compounds with thio-
amides for the synthesis of heterocyclic motifs have been reported but most of them suffer from general-
ity, poor yield of desired products and vigorous conditions.16c,d To date, the intermolecular coupling re-
action between diazo compounds and thiocarbonyl C=S of -ketothioamides has not been explored,
while this type of transformation could provide an alternative approach for the gathering of structurally
diverse molecules.
The success of carbenoid insertion/annulation strategy relies on the judicious choice of starting mate-
rial, which requires two orthogonal reactivity types: a site for insertion and a compatible electrophile,
which will not undergo reaction with the metal carbenoid. One such simple substrate is β-ketothioamide
that has been well-documented as an intriguing synthon to access valuable heterocyclic scaffolds.17 Site-
selectivity in -ketothioamide functionalizations has been achieved by leveraging several factors.18
Against this background and our experience towards the chemistry of -ketothioamides,18 it was envi-
sioned that the marriage of the carbenoid insertion/annulation with -ketothioamides would provide ac-
cess to interesting and potentially useful heterocyclic frameworks. To this end, herein we disclose the
Rh(OAc)2-catalyzed annulative coupling of -ketothioamides with diazo compounds for the synthesis of
highly functionalized thiazolidinones and thiazolines (Scheme 1).
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Scheme 1. Synthesis of Thiazolidinones and Thiazolines
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RESULTS AND DISCUSSION
In general, most of the reactions in organic chemistry are reagent/catalyst-controlled, and their regio-
and stereoselectivity are directed by the inherent nature of the reagent or catalyst. While in substrate-
directed reactions, the selectivity is determined by the functional group on the substrate. In this perspec-
tive, one of the simple substrate is β-ketothioamide, which exerts amazing reactivity and emerged as
novel multi-role-synthon for the construction of various heterocyclic motifs.17,18 In continuation of our
ongoing research toward the development of powerful synthetic strategies to assemble different hetero-
cyclic scaffolds employing β-ketothioamide as a reaction partner, we turned our attention to react β-
ketothioamide with diazoalkane, which could generate hitherto unknown heterocyclic motif via one-pot
cascade annulation. To validate our hypothesis, we commenced our study employing β-ketothioamide
1a and diazoalkane 2a as model substrates to examine various reaction parameters to optimize the reac-
tion conditions. The results are summarized in Table 1.
Initially, the reaction of 1a and 2a in equimolar ratio in the presence of 2 mol % of Rh(OAc)2 in di-
chloromethane (DCM) at room temperature under inert atmosphere could provide only a trace of the
desired product 3a after 24 h (Table 1, entry 1). The above result encouraged us to continue our investi-
gations for the formation of desired product 3a in good yield. To this end, the test reaction was carried
out at 50 oC, which afforded the desired product 3a in 82% isolated yield (Table 1, entry 2). Further in-
creasing the temperature not only decreased the yield, but also made the reaction messy (Table 1, entry
3).
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Table 1. Optimization of Reaction Conditionsa
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entry conditions
solvent temp yield (%)b
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(oC)
3a
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as shown
as shown
as shown
as shown
as shown
as shown
as shown
as shown
DCM
DCM
DCM
DCE
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50
Trace
82
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3
65c
NR
NR
NR
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NR
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CH3CN 50
DMSO 50
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Dioxane 50
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[Rh(COD)Cl]2 DCM
[RhCl(PPh3)]3 DCM
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CuCl
DCM
DCM
DCM
DCM
DCM
65
CuBr
65
Cu(OAc)2
AgSbF6
No catalyst
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NR
NR
aUnless otherwise noted all the reaction were carried out using 0.5 mmol of each 1a and 2a in the pres-
ence of 2 mol % of catalyst in 5 mL of solvent. bIsolated yields. cComplex TLC pattern. NR = No reac-
tion.
Inspired by the above result, we intended to see the effect of some other solvents. Thus, the test reac-
tion is performed in various solvents such as dichloroethane (DCE), CH3CN, DMSO, DMF and diox-
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ane, but none of them did trigger the reaction (Table 1, entries 4-8). After optimizing DCM as a choice
of solvent, next we screened some other rhodium catalysts such as Rh(COD)Cl]2 and RhCl(PPh3)3. No-
tably, Rh(COD)Cl]2 did not trigger the reaction, while RhCl(PPh3)3 triggered the reaction producing the
desired product 3a albeit in lower yield (Table 1, entries 9 & 10). Keeping in mind the use of relatively
inexpensive and less toxic copper salts, we screened some copper catalysts such as CuCl, CuBr, and
Cu(OAc)2, which also could not provide better result than rhodium (Table 1, entries 11-13). To check
the generality of the protocol, we also screened AgSbF6, which did not trigger the reaction (Table 1, en-
try 14). In the absence of a catalyst, the reaction did not occur at all revealing the significance of catalyst
to the success of the reaction (Table 1, entry 15). Thus, the optimum condition for the synthesis of 3a
was achieved by employing 1a (0.5 mmol), 2a (0.5 mmol), Rh(OAc)2 (2 mol %), in 5 mL of DCM at 50
°C under inert atmosphere (Table 1, entry 2).
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With the established optimal conditions in hand, we explored the scope and generality of the proto-
col. A wide range of β-ketothioamides (KTAs) with diverse substituents at R1 moiety irrespective of
their substitution pattern (ortho, meta, or para) are found to be compatible well under the optimized
conditions showing no obvious electronic/steric hindrance (Table 2). The KTAs bearing substituents like
Cl, Br, OMe, Me, CF3, and -OCH2O- at phenyl group of R1 moiety participated well with neutral, elec-
tron-donating and electron-withdrawing diazoalkanes affording the corresponding thiazolidinones in
good to excellent yields (Table 2). The introduction of halogen (e.g., chloro and bromo) substituents into
target product is attractive because of their potential for further synthetic elaborations. Different thioam-
ides (1a-1f, SI Table S4) were well tolerated with ethyl 2-diazo-2-phenylacetate furnishing the desired
thiazolidinones up to 82% yield (Table 2, entries 3a-3f). After effective implementation of the neutral
diazoalkane, next we employed the electron-rich diazoalkane, which was found to be viable participant
with different thioamides (1g-1l, SI Table S4) and afforded the corresponding products in good yields
(Table 2, entries 3g-3l). Further, we examined the scope of this transformation with electron-poor diazo-
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alkanes with diverse KTAs (1m-1x, SI Table S4), which also delivered the corresponding thiazoli-
dinones in excellent yield (Table 2, entries 3m-3x).
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Table 2. Scope of -Ketothioamides and α-Diazoacetates to Access Diverse Thiazolidinonesa
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aAll the reaction were performed with 0.5 mmol of each thioamides (1) and diazo compounds (2).
Remarkably, KTAs bearing not only aromatic, extended aromatic, and heteroaromatic entrants at R1
moiety were found to be highly amenable to this protocol, but also alicyclic and aliphatic groups like
cyclopropyl and iso-butyl at R1 moiety were also tolerated well under the standard conditions affording
the corresponding thiazolidinones in good yields (Table 2, entries 3r and 3w). Interestingly, thioamides
bearing three strong electron-donating methoxy groups and strong electron-withdrawing CF3 group at
R1 moiety were also coupled well with electron-poor diazoalkane furnishing the desired products in
good yields (Table 2, entries 3u and 3v). After successful utilization of β-ketothioamides containing ar-
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omatic moiety at nitrogen atom, next we employed the thioamides bearing alkyl substituents at nitrogen
like ethyl group and found to be compatible well affording the corresponding thiazolidinones in good
yield (Table 2, entries 3f and 3x).
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Next, the protocol generality was investigated by carrying out the reaction of thioamides 1 with dif-
ferent diazo compounds with a view to add further diversity to thiazolidinone ring (Table 3). Notably,
the -diazocarbonyl (2b) and -diazo 1,3-diketone (2c) also underwent the reaction smoothly with di-
verse β-ketothioamides bearing R1 moiety as phenyl and aryl (substituted with both electron-
withdrawing and electron-donating groups) substituents under optimized conditions affording the corre-
sponding thiazolidinones and thiazolines in good yields (Table 3, entries 3y-3ec).
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Table 3. Scope of ethyl diazoacetate (2b) and -diazo 1,3-diketone (2c)a
aAll the reaction were performed with 0.5 mmol of each thioamides (1) and diazocompounds (2).
Importantly, thioamide bearing -electron excessive group like 2-thienyl substituent at R1 moiety was
also well tolerated under standard conditions affording the corresponding thiazolidinone and thiazoline
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in good yields (Table 3, 3eb and 3ec). It has been observed that thioamides with -diazocarbonyl as
coupling partner provided the desired products up to 78% yield, while with -diazo 1,3-diketone as
coupling partner afforded slightly decreased yield (up to 65%).
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To validate the further synthetic utility of the present protocol, and in order to extend the substrate
scope, we intended to employ 2-aminothiophenol instead of β-ketothioamide with different diazo com-
pounds under above optimized conditions. It has been observed that only -diazo 1,3-diketone gave the
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expected product with 2-amino thiophenol, while -diazocarbonyl and -diazoalkane could not provide
even a trace of the anticipated product under standard conditions. In this regard, we employed 2-
aminothiophenols, which underwent reaction efficiently with -diazo 1,3-diketone under standard con-
ditions providing the desired 2,3-dihydrobenzo[d]thiazoles in satisfactory yield (Scheme 2, 4a and 4b).
As one of the most important exponents, 2-substituted benzothiazoles are of huge interest since they
have been used as antimicrobial, antitumor, anticonvulsant, and neuroprotective agents.19
Scheme 2. Application towards Benzo[d]thiazoles
The structural determination of all the newly synthesized compounds was achieved by their satisfac-
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tory spectral (1H, H decoupled C NMR, and HRMS) studies. The structure of one of the representa-
tive compound (Z)-2-(2-oxo-2-(thiophen-2-yl)ethylidene)-3,5-diphenylthiazolidin-4-one (3e) was fur-
ther unambiguously established by the single crystal X-ray crystallography (see Supporting Information
Figure S1 for details).20
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Further to check the practical efficacy of this protocol, we performed the large scale reaction em-
ploying -ketothioamide 1a (5 mmol) and α-diazoacetate 2a (5 mmol) under optimized reaction condi-
tions (Scheme 3). The desired thiazolidinone 3a was obtained in 77% yield (1.43 g), which was found to
be comparable to the small scale reaction. This observation indicated that the present method could be
easily implemented for a large scale preparation of thiazolidinones.
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Scheme 3. Gram-scale Synthesis of Compound 3a
Based on our experimental observation, a plausible mechanism is proposed in Scheme 4. The first
step is believed to be the reaction between Rh(OAc)2 and diazo compound to generate rhodium carbe-
noid species A via the extrusion of nitrogen. Next, the rhodium carbenoid species A reacts with thioam-
ide sulfur to form the sulphonium ylide B, which in turn follows proton transfer to form N,S-acetal in-
termediate C by the regeneration of rhodium catalyst. Finally, in situ generated N,S-acetal intermediate
C undergoes intramolecular N-cyclization by elimination of ethanol to give the desired thiazolidinones
and thiazolines, respectively. To validate the proposed reaction mechanism, we recorded the mass spec-
trum of the reaction mixture, which shows the existence of intermediate C (See SI, Figure S2). The
above observation supported that reaction proceeds via intermediate C.
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Scheme 4. Proposed Mechanism for the Reaction
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CONCLUSION
In summary, we have developed a concise and efficient protocol for the synthesis of diverse thiazoli-
dinones and thiazolines via Rh(II)-catalyzed annulative coupling of β-ketothioamides with diazo com-
pounds for the first time. Moreover, the described methodology is not limited to only β-ketothioamides
but was also applicable to 2-amino thiophenols, which enabled direct approach to substituted ben-
zo[d]thiazoles. The clean reaction profile, flexible structural modification, broad substrate scope, good
functional group tolerance, and alcohol being the only byproduct are additional attributes to this one-pot
strategy. Our method enables the synthesis of a broad range of highly functionalized thiazolidinones and
thiazolines in good to excellent yield under mild reaction conditions.
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EXPERIMENTAL SECTION
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Commercially available chemicals used in this manuscript were used without further purification and
were purchased from TCI, Sigma-Aldrich and Alfa Aesar. Solvents used for reactions were p.A. grade,
and solvents for column chromatography were technical grade and distilled before use; solvent mixtures
are understood as volume/volume. All the reactions were carried out in a flame or oven dried glass
wares with freshly distilled dry solvents under anhydrous conditions. All the reactions were monitored
by analytical thin layer chromatography (TLC) using Merck precoated aluminium sheets and visualized
by UV lamp. Column chromatography using silica gel (100-200 mesh) was performed for the purifica-
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tion of products. The H and C NMR spectra were recorded on JEOL 500 FT-NMR spectrometer op-
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erating at 500 and 125 MHz, respectively. Chemical shifts (δ) for H and C{1H} NMR are given in
parts per million (ppm) using the residual solvent peaks as reference relative to tetramethylsilane
(TMS). Coupling constant (J) values are reported in Hz. Mass spectra were recorded on Sciex X500R
Q-TOF instruments. Melting points are uncorrected.
Materials: All solvents were distilled under argon and dried before use. Catalysts used in this protocol
Rh(OAc)2, [Rh(COD)Cl]2, RhCl(PPh3)3, CuCl, CuBr, Cu(OAc)2 and AgSbF6 were purchased from
Sigma-Aldrich Chemicals Pvt. Ltd. The -ketothioamides21a and diazocompounds21b,c were synthesized
by reported procedures.
Important Safety Note. Diazo compounds should only be handled in a well-ventilated fume cupboard.
An additional blast shield is recommended. Although we did not realise any problem in the handling of
diazo compounds, extreme care should be taken when manipulating them due to their potentially explo-
sive nature. However, the reader should be aware of hazards of the diazo compounds. Safety precautions
should be followed and strict risk assessment and proper safety precautions are recommended.
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General Procedures for the Synthesis of Thiazolidinones and Thiazolines. In a two neck round bot-
tom flask 0.5 mmol of -ketothioamides 1, 0.5 mmol of diazo compounds (2a/2b/2c) and 2 mol % of
Rh(OAc)2 were taken and sealed with double channel balloon adopter and flushed with argon for 5 to 6
times with the help of vacuum pump. Thereafter dichloromethane (5 mL) was added with the help of
syringe. Now, the whole reaction mixture was put into pre-heated oil bath at 50 °C and stirred for stipu-
lated period of time till completion. After the completion of the reaction (monitored by TLC), aqueous
work up of reaction mixture was performed using ethyl acetate as organic phase. Organic phase was
separated and dried over anhydrous Na2SO4 and solvent was evaporated under vacuum. Thus crude re-
action mixture obtained was purified by column chromatography using hexane-ethyl acetate (8:2) as
eluent to afford the pure final product.
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The spectral and analytical data of all the compounds are given as follows:
(Z)-2-(2-oxo-2-phenylethylidene)-3,5-diphenylthiazolidin-4-one (3a): The product was obtained as
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brown solid (82%, 152 mg); mp 205-206 C; H NMR (500 MHz, CDCl3) δ 7.74 (d, J = 5.0 Hz, 2H),
7.61-7.53 (m, 3H), 7.51-7.46 (m, 3H), 7.43-7.34 (m, 7H), 6.40 (s, 1H), 5.16 (s, 1H); 13C{1H} NMR (125
MHz, CDCl3) δ 188.9, 173.4, 160.7, 138.2, 135.6, 135.3, 132.3, 130.3, 130.0, 129.2, 128.8, 128.5,
128.4, 128.0, 127.6, 97.5, 50.3; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H18NO2S 372.1053;
Found 372.1031.
(Z)-2-(2-oxo-2-(o-tolyl)ethylidene)-3,5-diphenylthiazolidin-4-one (3b): The product was obtained as
o
brown solid (80%, 154 mg); mp 144-145 C; 1H NMR (500 MHz, CDCl3) δ 7.54 (t, J = 7.5 Hz, 2H),
7.49 (d, J = 5.0 Hz, 2H), 7.43-7.41 (m, 2H), 7.36 (d, J = 5.0 Hz, 1H), 7.31-7.26 (m, 4H), 7.18-7.13 (m,
3H), 6.07 (s, 1H), 5.16 (s, 1H), 2.44 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 193.1, 173.4, 159.7,
139.7, 137.2, 135.6, 135.3, 131.5, 130.8, 130.6, 130.3,129.9, 129.3, 128.8, 128.5, 128.0, 127.8, 126.9,
125.7, 101.5, 101.2, 50.3, 31.7, 22.7, 20.7, 14.2; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C24H20NO2S 386.1209; Found 386.1183.
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(Z)-2-(2-(2-chlorophenyl)-2-oxoethylidene)-3,5-diphenylthiazolidin-4-one (3c): The product was ob-
tained as white solid (78%, 158 mg); mp 149-150 oC; 1H NMR (500 MHz, CDCl3) δ 7.55 (t, J = 7.5 Hz,
2H), 7.51-7.47 (m, 5H), 7.39-7.36 (m, 1H), 7.32-7.31 (m, 2H), 7.29-7.28 (m, 2H), 7.29-7.18 (m, 2H),
6.19 (s, 1H), 5.18 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 189.9, 173.4, 160.1, 139.5, 135.4, 135.1,
131.5, 131.3, 130.8, 130.4, 130.2, 130.0, 129.9, 129.3, 128.9, 128.5, 128.0, 127.0, 101.8, 50.5; HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C23H17ClNO2S 406.0663; Found 406.0645.
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(Z)-2-(2-oxo-2-(4-(trifluoromethyl)phenyl)ethylidene)-3,5-diphenylthiazolidin-4-one (3d): The prod-
uct was obtained as white solid (75%, 165 mg); mp 198-199 oC; 1H NMR (500 MHz, CDCl3) δ 7.72 (d,
J = 5.0 Hz, 2H), 7.55-7.45 (m, 5H), 7.39 (d, J = 10.0 Hz, 2H), 7.33-7.25 (m, 5H+1H of CDCl3), 6.26 (s,
1H), 5.08 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.5, 173.3, 162.2, 141.1, 135.3, 135.1, 133.5
(q, 2JCF3 = 32.5 Hz), 130.4, 130.1, 129.5, 129.3, 128.9, 128.6, 128.4, 128.0, 127.9, 126.6, 125.6, 125.6,
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123.7 (q, JCF3 = 271.2 Hz), 97.2, 50.3; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H17F3NO2S
440.0927; Found 440.0897.
(Z)-2-(2-oxo-2-(thiophen-2-yl)ethylidene)-3,5-diphenylthiazolidin-4-one (3e): The product was ob-
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tained as yellow solid (70%, 132 mg); mp 204-205 C; H NMR (500 MHz, CDCl3) δ 7.50-7.39 (m,
6H), 7.33-7.17 (m, 6H+1H of CDCl3), 6.93 (t, J = 5.0, 1H), 6.13 (s, 1H), 5.06 (s, 1H); 13C{1H} NMR
(125 MHz, CDCl3) δ 181.5, 173.2, 159.9, 145.5, 135.6, 135.2, 132.7, 130.3, 130.0, 129.9, 129.2, 128.8,
128.4, 128.1, 128.0, 97.6, 50.4; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H16NO2S2 378.0617;
Found 378.0593.
(Z)-3-ethyl-2-(2-(4-methoxyphenyl)-2-oxoethylidene)-5-phenylthiazolidin-4-one (3f): The product
was obtained as white solid (67%, 118 mg); mp 142-143 oC; 1H NMR (500 MHz, CDCl3) δ 7.87 (d, J =
10.0 Hz, 2H), 7.28-7.24 (m, 5H+1H of CDCl3), 6.88 (d, J = 10.0 Hz, 2H), 6.66 (s, 1H), 4.86 (s, 1H),
3.81 (q, J = 6.6 Hz, 2H), 3.78 (s, 3H), 1.24 (t, J = 5.0 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
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187.6, 173.5, 163.0, 158.6, 135.7, 131.3, 131.1, 129.7, 129.1, 128.6, 128.4, 114.0, 113.8, 95.1, 55.5,
50.1, 39.1, 12.1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H20NO3S 354.1158; Found 354.1132.
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(Z -)-5-(3-methoxyphenyl)-2-(2-oxo-2-(o-tolyl)ethylidene)-3-phenylthiazolidin 4-one (3g): The prod-
uct was obtained as yellow solid (75%, 156 mg); mp 134-135 oC; 1H NMR (500 MHz, CDCl3) δ 7.53 (t,
J = 7.5 Hz, 2H), 7.47 (t, J = 7.5 Hz, 1H), 7.33-7.24 (m, 5H+1H of CDCl3), 7.17-7.12 (m, 2H), 7.07 (d, J
= 5.0 Hz, 1H), 7.02 (s, 1H), 6.90-6.88 (m, 1H), 6.06 (s, 1H), 5.12 (s, 1H), 3.81 (s, 3H), 2.44 (s,3H); 13C
{1H} NMR (125 MHz, CDCl3) δ 193.0, 173.1, 160.1, 159.6, 139.6, 137.1, 137.0, 135.2, 131.5, 130.5,
130.2, 130.2, 129.9, 127.9, 127.8, 125.6, 120.6, 114.3, 114.1, 101.2, 55.4, 50.1, 20.6; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C25H22NO3S 416.1315; Found 416.1287.
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(Z)-5-(3-methoxyphenyl)-2-(2-(3-methoxyphenyl)-2-oxoethylidene)-3-phenylthiazolidin-4-one (3h):
The product was obtained as yellow solid (76%, 164 mg); mp 166-167 oC; 1H NMR (500 MHz, CDCl3)
δ 7.58-7.52 (m, 3H), 7.37 (s, 1H), 7.33-7.21 (m, 5H+1H of CDCl3), 7.07 (d, J = 5.0 Hz, 1H), 7.02 (s,
2H), 6.90-6.88 (m, 1H), 6.36 (s, 1H), 5.11 (s, 1H), 3.81 (s, 3H), 3.80 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 188.6, 173.2, 160.8, 160.2, 159.8, 139.7, 137.0, 135.3, 130.3, 130.3, 130.0, 129.5, 128.0,
120.6, 119.9, 118.7, 114.3, 114.2, 112.2, 97.7, 55.4, 50.2; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C25H22NO4S 432.1264; Found 432.1235.
(Z)-2-(2-(benzo[d][1,3]dioxol-5-yl)-2-oxoethylidene)-5-(3-methoxyphenyl)-3-phenylthiazolidin-4-one
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(3i): The product was obtained as brown solid (70%, 156 mg); mp 194-195 C; H NMR (500 MHz,
CDCl3) δ 7.59-7.52 (m, 3H), 7.33-7.25 (m, 5H+1H of CDCl3), 7.07 (d, J = 10.0 Hz, 1H), 7.01 (s, 1H),
6.89-6.88 (m, 1H), 6.75 (d, J = 5.0 Hz, 1H), 6.28 (s, 1H), 5.99 (s, 2H), 5.10 (s, 1H), 3.81 (s, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 187.1, 173.2, 160.2, 160.1, 151.2, 148.1, 137.1, 135.3, 133.0,
130.3, 130.3, 130.0, 128.1, 123.3, 120.7, 114.3, 114.2, 107.9, 107.8, 101.8, 97.4, 55.4, 50.2; HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C25H20NO5S 446.1057; Found 446.1057.
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(Z)-2-(2-(4-bromophenyl)-2-oxoethylidene)-5-(3-methoxyphenyl)-3-phenylthiazolidin-4-one (3j): The
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product was obtained as yellow solid (78%, 187 mg); mp 182-183 C;1H NMR (500 MHz, CDCl3) δ
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7.59-7.50 (m, 7H), 7.32 (t, J = 7.5 Hz, 3H), 7.0 (d, J = 5.0 Hz, 1H), 7.0 (s, 1H), 6.90-6.88 (m, 1H), 6.30
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(s, 1H), 5.11 (s, 1H), 3.81 (s, 3H); C{1H} NMR (125 MHz, CDCl3) δ 187.6, 173.2, 161.4, 160.2,
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137.0, 136.8, 135.2, 131.8, 130.4, 130.3, 130.1, 129.1, 128.0, 127.2, 120.6, 114.3, 114.2, 97.1, 55.4,
50.2; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H19BrNO3S 480.0264; Found 480.0258.
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(Z)-5-(3-methoxyphenyl)-2-(2-(naphthalen-2-yl)-2-oxoethylidene)-3-phenylthiazolidin-4-one (3k):
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The product was obtained as light brown solid (69%, 156 mg); mp 194-195 C; H NMR (500 MHz,
CDCl3) δ 8.19 (s, 1H), 7.87-7.82 (m, 4H), 7.62-7.47 (m, 5H), 7.36-7.31 (m, 3H), 7.08 (d, J = 10.0 Hz,
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1H), 7.04 (s, 1H), 6.89 (d, J = 5.0 Hz, 1H), 6.53 (s, 1H), 5.13 (s, 1H), 3.82 (s, 3H); C{1H} NMR (125
MHz, CDCl3) δ 188.8, 173.3, 160.7, 160.2, 137.0, 135.6, 135.4, 135.2, 132.6, 130.4, 130.3, 130.0,
129.5, 128.6, 128.4, 128.1, 127.8, 126.7, 123.9, 120.7, 114.3, 114.2, 97.8, 55.4, 50.3; HRMS (ESI-TOF)
m/z: [M + H]+Calcd for C28H22NO3S 452.1315; Found 452.1302.
(Z)-2-(2-(furan-2-yl)-2-oxoethylidene)-5-(3-methoxyphenyl)-3-phenylthiazolidin-4-one (3l): The
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product was obtained as yellow solid (67%, 131 mg); mp 177-178 C; H NMR (500 MHz, CDCl3) δ
7.59-7.52 (m, 3H), 7.43 (s, 1H), 7.31 (t, J = 10.0 Hz, 3H), 7.07-06 (m, 2H), 7.01 (s, 1H), 6.89-6.88(m,
1H), 6.45 (d, J = 5.0 Hz, 1H), 6.27 (s, 1H), 5.11 (s, 1H), 3.81 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3)
δ 177.8, 173.1, 160.2, 160.0, 153.5, 145.4, 137.0, 135.2, 130.3, 129.9, 128.1, 120.6, 115.5, 114.2, 112.4,
97.4, 55.4, 50.3; HRMS (ESI-TOF) m/z: [M + H]+Calcd for C22H18NO4S 392.0951; Found 392.0923.
(Z)-5-(2-chlorophenyl)-2-(2-oxo-2-(p-tolyl)ethylidene)-3-phenylthiazolidin-4-one (3m): The product
was obtained as yellow solid (72%, 151 mg); mp 203-204 oC; 1H NMR (500 MHz, CDCl3) δ 7.61 (t, J =
10.0 Hz, 4H), 7.56 (t, J = 7.5 Hz, 1H), 7.45-7.43 (m, 1H), 7.41-7.36 (m, 3H), 7.31-7.28 (m, 2H), 7.16
(d, J = 10.0 Hz, 2H), 6.36 (s, 1H), 5.53 (s, 1H), 2.36 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 188.6,
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172.7, 160.4, 143.0, 135.6, 135.4, 134.5, 133.7, 130.5, 130.3, 130.1, 130.0, 129.2, 128.0, 127.7, 127.6,
97.6, 48.6, 21.6; HRMS (ESI-TOF) m/z: [M + H]+Calcd for C24H19ClNO2S 420.0820; Found 420.0801.
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product was obtained as white solid (75%, 165 mg); mp 209-210 C; H NMR (500 MHz, CDCl3) δ
7.65 (d, J = 10.0 Hz, 2H), 7.61 (d, J = 10.0 Hz, 2H), 7.58-7.55 (m, 1H), 7.46-7.44 (m, 1H), 7.40-7.36
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(m, 3H), 7.34-7.32 (m, 2H), 7.31-7.29 (m, 2H), 6.30 (s, 1H), 5.53 (s, 1H); C{1H} NMR (125 MHz,
CDCl3) δ 187.4, 172.6, 161.6, 138.6, 136.5, 135.2, 134.5, 133.5, 130.6, 130.5, 130.4, 130.2, 130.1,
129.0, 128.8, 127.9, 127.6, 97.1, 48.6; HRMS (ESI-TOF) m/z: [M + H]+Calcd for C23H16Cl2NO2S
440.0273; Found 440.0255.
(Z)-2-(2-(3-bromophenyl)-2-oxoethylidene)-5-(2-chlorophenyl)-3-phenylthiazolidin-4-one (3o): The
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product was obtained as yellow solid (76%, 184 mg); mp 166-167 C; H NMR (500 MHz, CDCl3) δ
7.86 (s, 1H), 7.63-7.56 (m, 5H), 7.45-7.43 (m, 1H), 7.40-7.36 (m, 3H), 7.31-7.29 (m, 2H), 7.22 (t, J =
7.5 Hz, 1H), 6.28 (s, 1H), 5.33 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.1, 172.6, 161.9, 140.0,
135.1, 135.0, 134.4, 133.4, 130.6, 130.5, 130.4, 130.2, 130.2, 130.1, 127.8, 127.6, 126.0, 122.9, 97.0,
48.6; HRMS (ESI-TOF) m/z: [M + H]+Calcd for C23H16BrClNO2S 483.9768; Found 483.9757.
(Z)-2-(2-([1,1'-biphenyl]-4-yl)-2-oxoethylidene)-5-(2-chlorophenyl)-3-phenylthiazolidin-4-one (3p):
The product was obtained as yellow solid (70%, 169 mg); mp 207-208 oC; 1H NMR (500 MHz, CDCl3)
δ 7.79 (d, J = 10.0 Hz, 2H), 7.64-7.56 (m, 7H), 7.46-7.44 (m, 3H), 7.43-7.36 (m, 4H), 7.32-7.30 (m,
2H), 6.40 (s, 1H), 5.55 (s, 1H); C{1H} NMR (125 MHz, CDCl3) δ 188.4, 172.7, 160.9, 145.0, 140.0,
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136.9, 135.4, 134.5, 133.7, 130.5, 130.4, 130.2, 130.1, 129.0, 128.4, 128.2, 128.2, 128.0, 127.6, 127.4,
127.3, 127.2, 97.6, 48.6; HRMS (ESI-TOF) m/z: [M + H]+Calcd for C29H21ClNO2S 482.0976; Found
482.0975.
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(Z)-5-(2-chlorophenyl)-3-(4-methoxyphenyl)-2-(2-oxo-2-(p-tolyl)ethylidene)thiazolidin-4-one (3q):
The product was obtained as yellow solid (68%, 153 mg); mp 176-177 oC; 1H NMR (500 MHz, CDCl3)
δ 7.63 (d, J = 5.0 Hz, 2H), 7.45-7.43 (m, 1H), 7.40-7.38 (m, 1H), 7.31-7.27 (m, 4H), 7.17 (d, J = 5.0 Hz,
2H), 7.11-7.09 (m, 2H), 6.37 (s, 1H), 5.52 (s, 1H), 3.90 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 188.6, 172.9, 160.8, 160.5, 143.0, 135.7, 134.5, 133.9, 130.5, 130.1, 129.2, 127.8, 127.7,
127.6, 115.6, 97.6, 55.7, 48.5, 21.7; HRMS (ESI-TOF) m/z: [M + H]+Calcd for C25H21ClNO3S
450.0925; Found 450.0896.
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(Z)-5-(2-chlorophenyl)-2-(2-cyclopropyl-2-oxoethylidene)-3-phenylthiazolidin-4-one (3r): The prod-
uct was obtained as yellow solid (66%, 122 mg); mp 156-157 oC; 1H NMR (500 MHz, CDCl3) δ 6.69 (t,
J = 7.5 Hz, 2H), 7.64 (t, J = 7.5 Hz, 1H), 7.54 (t, J = 5.0 Hz, 1H), 7.48-7.46 (m, 1H), 7.43 (d, J = 10.0
Hz, 2H), 7.40-7.38 (m, 2H), 5.40 (s, 1H), 5.60 (s, 1H), 1.84-1.80 (m, 1H), 1.05 (t, J = 5.0 Hz, 2H), 0.81
(t, J = 5.0 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 198.4, 172.7, 157.4, 135.3, 134.5, 133.9, 130.4,
130.3, 130.1, 129.9, 128.0, 127.6, 101.1, 48.5, 21.5, 10.9, 10.9; HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C20H17ClNO2S 370.0663; Found 370.0638.
(Z)-5-(4-nitrophenyl)-2-(2-oxo-2-phenylethylidene)-3-phenylthiazolidin-4-one (3s): The product was
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obtained as brown solid (70%, 146 mg); mp 178-179 C; H NMR (500 MHz, CDCl3) δ 8.27 (d, J =
10.0 Hz, 2H), 7.74-7.70 (m, 4H), 7.62-7.57 (m, 4H), 7.50 (t, J = 7.5 Hz, 1H), 7.40 (t, J = 7.5 Hz, 3H),
6.43 (s, 1H), 5.25 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 189.1, 172.2, 159.5, 148.1, 142.6, 137.9,
135.0, 132.6, 130.5, 130.3, 129.6, 128.7, 127.9, 127.7, 124.4, 98.3, 49.6; HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C23H17N2O4S 417.0904; Found 417.0887.
(Z)-5-(4-nitrophenyl)-2-(2-oxo-2-(m-tolyl)ethylidene)-3-phenylthiazolidin-4-one (3t): The product
was obtained as brown solid (72%, 155 mg); mp 139-140 oC; 1H NMR (500 MHz, CDCl3) δ 8.28 (d, J =
10.0 Hz, 2H), 7.71 (d, J = 5.0 Hz, 2H), 7.66-7.56 (m, 5H), 7.47 (d, J = 5.0 Hz, 1H), 7.32-7.27 (m, 3H),
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6.41 (s, 1H), 5.25 (s, 1H), 2.36 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 189.3, 172.2, 159.3, 148.2,
142.7, 138.6, 138.0, 135.0, 133.5, 130.5, 130.3, 129.6, 128.5, 128.3, 128.0, 124.8, 124.4, 98.5, 49.6,
21.5; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H19N2O4S 431.1060; Found 431.1033.
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(3u): The product was obtained as brown solid (66%, 167 mg); mp 141-142 C; H NMR (500 MHz,
CDCl3) δ 8.28 (d, J = 10.0 Hz, 2H), 7.72 (d, J = 10.0Hz, 2H ), 7.61-7.42 (m, 5H), 6.98 (s, 2H), 6.35 (s,
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1H), 5.26 (s, 1H), 3.88 (s, 3H), 3.82 (s, 6H); C{1H} NMR (125 MHz, CDCl3) δ 188.0, 172.1, 159.4,
153.2, 148.2, 142.5, 142.4, 135.0, 133.3, 130.4, 130.3, 129.6, 128.0, 124.4, 105.4, 98.1, 61.0, 56.4, 56.2,
49.7; HRMS (ESI-TOF) m/z: [M + H]+Calcd for C26H23N2O7S 507.1220; Found 507.1192.
(Z)-5-(4-nitrophenyl)-2-(2-oxo-2-(4-(trifluoromethyl)phenyl)ethylidene)-3-phenylthiazolidin-4-one
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(3v): The product was obtained as brown solid (65%, 157 mg); mp 171-172 C; H NMR (500 MHz,
CDCl3) δ 8.28 (d, J = 10.0 Hz, 2H), 7.82 (d, J = 5.0 Hz, 2H), 7.71 (d, J = 5.0 Hz, 2H), 7.67-7.59 (m,
5H), 7.36-7.31 (m, 2H), 6.40 (s, 1H), 5.28 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.84, 172.18,
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161.00, 148.23, 142.28, 140.81, 138.12, 134.82, 133.8 (q, JCF3 J = 32.5), 131.72, 130.62, 130.49,
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130.40, 129.65, 128.02, 127.91, 125.78, 125.76, 124.49, 123.7 (q, JCF3 J = 270.8 Hz), 97.90, 49.65;
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H16F3N2O4S 485.0777; Found 485.0767.
(Z)-2-(4-methyl-2-oxopentylidene)-5-(4-nitrophenyl)-3-phenylthiazolidin-4-one (3w): The product
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was obtained as dark brown solid (60%, 119 mg); mp 135-136 C; H NMR (500 MHz, CDCl3) δ 8.27
(d, J = 10.0 Hz, 2H), 7.68 (d, J = 10.0 Hz, 2H), 7.58-7.55 (m, 1H), 7.41 (t, J = 7.5 Hz, 3H), 7.29 (t, J =
7.5 Hz, 1H), 5.67 (s, 1H), 5.19 (s, 1H), 2.24 (d, J = 5.0 Hz, 2H), 2.11-2.04 (m, 1H), 0.89 (d, J = 5.0 Hz,
6H) ; 13C{1H} NMR (125 MHz, CDCl3) δ 172.2, 156.6, 142.7, 134.9, 130.4, 129.7, 129.6, 127.9, 127.3,
125.4, 124.4, 101.7, 52.3, 49.5, 25.5, 22.7; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H21N2O4S
397.1217; Found 397.1204.
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(Z)-3-ethyl-2-(2-(4-methoxyphenyl)-2-oxoethylidene)-5-(4-nitrophenyl)thiazolidin-4-one (3x): The
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product was obtained as white solid (63%, 125 mg); mp 183-184 C; H NMR (500 MHz, CDCl3) δ
8.23 (d, J =5.0 Hz, 2H), 7.96 (d, J = 5.0 Hz, 2H), 7.59 (d, J = 5.0 Hz, 2H), 6.98 (d, J = 7.5 Hz, 2H), 6.79
(s, 1H), 5.06 (s, 1H), 3.93 (d, J = 3.33, 2H), 3.89 (s, 3H), 1.36 (t, J = 5.0 Hz, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 187.8, 172.3, 163.3, 157.4, 148.0, 142.9, 131.0, 129.9, 129.6, 124.3, 114.0, 95.8, 55.6,
49.5, 39.5, 12.2; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H19N2O5S 399.1009; Found 399.0997.
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(Z)-2-(2-oxo-2-phenylethylidene)-3-phenylthiazolidin-4-one (3y): The product was obtained as brown
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solid (78%, 115 mg); mp 190-191 C; H NMR (500 MHz, CDCl3) δ 7.72-7.70 (m, 2H), 7.62-7.56 (m,
3H), 7.45 (d, J = 5.0 Hz, 1H), 7.37 (t, J = 7.5 Hz, 2H), 7.32-7.30 (m, 2H), 6.32 (s, 1H), 3.90 (s, 2H);
13C{1H} NMR (125 MHz, CDCl3) δ 188.9, 172.6, 162.3, 138.3, 135.2, 132.3, 130.4, 130.1, 128.6,
128.0, 127.6, 97.8, 32.2; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H14NO2S 296.0740; Found
296.0725.
(Z)-2-(2-oxo-2-(p-tolyl)ethylidene)-3-phenylthiazolidin-4-one (3z): The product was obtained as
brown solid (75%, 116 mg); mp 215-216 oC; 1H NMR (500 MHz, CDCl3) δ 7.62-7.56 (m, 5H), 7.30 (d,
J = 5.0 Hz, 2H), 7.17 (d, J = 10.0 Hz, 2H), 6.30 (s, 1H), 3.90 (s, 2H), 2.36 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 188.6, 172.7, 161.9, 143.0, 135.7, 135.2, 130.4, 130.0, 129.3, 128.0, 127.7, 97.9, 32.2,
21.7; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H16NO2S 310.0896; Found 310.0883.
(Z)-2-(2-(4-chlorophenyl)-2-oxoethylidene)-3-phenylthiazolidin-4-one (3nb): The product was ob-
tained as brown solid (72%, 119 mg); mp 160-161 oC; 1H NMR (500 MHz, CDCl3) δ 7.69 (s, 1H), 7.63-
7.54 (m, 4H), 7.43 (d, J = 10.0 Hz, 1H), 7.32-7.29 (m, 3H), 6.24 (s, 1H), 3.91 (s, 2H); 13C{1H} NMR
(125 MHz, CDCl3) δ 169.2, 153.1, 139.3, 128.93, 128.6, 125.4, 123.2, 122.1, 121.3, 121.3, 121.2, 119.7,
119.7, 119.7, 119.7, 29.8, 20.4; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H13ClNO2S 330.0350;
Found 330.0330.
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(Z)-3-(4-methoxyphenyl)-2-(2-oxo-2-(p-tolyl)ethylidene)thiazolidin-4-one (3mb): The product was
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obtained as brown solid (69%, 117 mg); mp 194-195 C; H NMR (500 MHz, CDCl3) δ 7.63 (d, J =
10.0 Hz, 2H), 7.22-7.17 (m, 4H), 7.08 (d, J = 5.0 Hz, 2H), 6.32 (s, 1H), 3.89 (s, 3H), 3.87 (s, 2H), 2.36
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(s, 3H); C{1H} NMR (125 MHz, CDCl3) δ 188.6, 172.9, 162.2, 160.5, 143.0, 135.8, 129.2, 129.1,
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127.7, 127.6, 115.6, 97.8, 55.7, 32.1, 29.8, 21.7; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C19H18NO3S 340.1002; Found 340.0985.
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(Z)-2-(2-oxo-2-(thiophen-2-yl)ethylidene)-3-phenylthiazolidin-4-one (3eb): The product was obtained
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as dark brown solid (65%, 98 mg); mp 139-140 C; H NMR (500 MHz, CDCl3) δ 7.62-7.54 (m, 3H),
7.52 (d, J = 5.0 Hz, 1H), 7.35 (d, J = 5.0 Hz, 1H), 7.29 (d, J = 5.0 Hz, 2H), 7.01 (t, J = 5.0 Hz, 1H), 6.15
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(s, 1H), 3.90 (s, 2H); C{1H} NMR (125 MHz, CDCl3) δ 181.5, 172.5, 161.6, 145.5, 135.1, 132.7,
130.4, 130.1, 129.8, 128.0, 128.0, 97.8, 32.3; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H12NO2S2
302.0304; Found 302.0296.
(Z)-2-(5-acetyl-4-methyl-3-phenylthiazol-2(3H)-ylidene)-1-phenylethanone (3ac): The product was
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obtained as yellow solid (63%, 106 mg); mp 229-230 C; H NMR (500 MHz, CDCl3) δ 7.73 (d, J =
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10.0 Hz, 2H), 7.67-7.61 (m, 3H), 7.40-7.29 (m, 5H), 6.07 (s, 1H), 2.51 (s, 3H), 2.31 (s, 3H); C{1H}
NMR (125 MHz, CDCl3) δ 191.0, 184.3, 162.3, 145.6, 139.1, 136.7, 130.9, 130.9, 130.6, 128.3, 128.1,
127.1, 116.7, 90.1, 30.4, 14.5; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H18NO2S 336.1053;
Found 336.1053.
(Z)-2-(5-acetyl-4-methyl-3-phenylthiazol-2(3H)-ylidene)-1-(m-tolyl)ethanone (3tc): The product was
obtained as pale yellow solid (65%, 113 mg); mp 174-175 oC; 1H NMR (500 MHz, CDCl3) δ 7.68-7.63
(m, 3H), 7.59 (s, 1H), 7.48-7.46 (m, 1H), 7.31-7.30 (m, 2H), 7.22 (t, J = 7.5 Hz, 2H), 6.06 (s, 1H), 2.52
(s, 3H), 2.34 (s, 3H), 2.31 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 191.1, 184.5, 162.2, 145.6,
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139.1, 138.0, 136.7, 131.7, 130.9, 130.5, 128.1, 128.1, 127.8, 124.1, 116.6, 90.2, 30.4, 21.5, 14.5;
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H20NO2S 350.1209; Found 350.1186.
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(Z)-2-(5-acetyl-4-methyl-3-phenylthiazol-2(3H)-ylidene)-1-(4-bromophenyl)ethanone (3jc): The
product was obtained as pale yellow solid (62%, 128 mg); mp 215-216 oC; 1H NMR (500 MHz, CDCl3)
δ 7.68-764 (m, 3H), 7.59 (d, J = 10.0 Hz, 2H), 7.46 (d, J = 10.0 Hz, 2H), 7.30 (d, J = 5.0 Hz, 2H), 6.0 (s,
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1H), 2.52 (s, 3H), 2.32 (s, 3H); C{1H} NMR (125 MHz, CDCl3) δ 190.9, 182.8, 162.6, 145.7, 137.9,
136.5, 131.5, 130.9, 130.7, 128.7, 128.0, 125.5, 116.9, 89.7, 30.4, 14.5; HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C20H17BrNO2S 414.0158; Found 414.0159.
(Z)-2-(5-acetyl-4-methyl-3-(p-tolyl)thiazol-2(3H)-ylidene)-1-(4-methoxyphenyl)ethanone (3fc): The
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product was obtained as yellow solid (60%, 104 mg); mp 205-206 C; H NMR (500 MHz, CDCl3) δ
7.66 (d, J = 5.0 Hz, 2H), 7.22-7.19 (m, 2H), 7.16-7.11 (m, 4H), 6.08 (s, 1H), 3.93 (s, 3H), 2.51 (s, 3H),
2.36 (s, 3H), 2.31 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 191.1, 184.2, 162.4, 160.8, 146.2, 141.3,
136.5, 129.2, 129.1, 129.0, 127.2, 115.9, 90.0, 55.8, 30.4, 21.6, 14.5; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C22H22NO3S 380.1315; Found 380.1303.
(Z)-2-(5-acetyl-4-methyl-3-phenylthiazol-2(3H)-ylidene)-1-(thiophen-2-yl)ethanone (3ec): The prod-
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uct was obtained as yellow solid (59%, 101 mg); mp 218-219 C; H NMR (500 MHz, CDCl3) δ 7.68-
7.63 (m, 3H), 7.40 (d, J = 5.0 Hz, 1H), 7.32-7.29 (m, 3H), 6.98 (t, J = 5.0 Hz, 1H), 5.90 (s, 1H), 2.50 (s,
3H), 2.31 (s, 3H); C{1H} NMR (125 MHz, CDCl3) δ 190.9, 177.6, 161.8, 145.6, 136.6, 130.9, 130.6,
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130.3, 128.1, 127.7, 127.6, 117.1, 89.9, 30.4, 14.5; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C18H16NO2S2 342.0617; Found 342.0617.
1-(3-methyl-4H-benzo[b][1,4]thiazin-2-yl)ethanone (4a): The product was obtained as brown sticky
solid (60%, 66 mg); 1H NMR (500 MHz, CDCl3) δ 8.02 (d, J = 10.0 Hz, 1H), 7.88 (d, J = 5.0 Hz, 1H),
7.49 (t, J = 7.5 Hz, 1H), 7.39 (t, J = 7.5 Hz, 1H), 5.19 (s, 1H), 2.49 (s, 3H), 1.96 (s, 3H); 13C{1H} NMR
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(125 MHz, CDCl3) δ 206.7, 174.0, 153.8, 135.7, 132.0, 129.9, 127.8, 127.1, 126.2, 125.5, 125.3, 123.2,
122.5, 121.9, 81.3, 25.9, 23.5; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C11H12NO2S 222.0583;
Found 222.0559.
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1-(6-chloro-3-methyl-4H-benzo[b][1,4]thiazin-2-yl)ethanone (4b): The product was obtained as
white solid (58%, 74 mg); mp 134-135 oC; 1H NMR (500 MHz, CDCl3) δ 8.01 (s,1H), 7.80 (d, J = 10.0
Hz, 1H), 7.37 (dd, J = 10.0 Hz, 5.0 Hz, 1H), 5.17 (s, 1H), 2.50 (s, 3H), 1.93 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 206.4, 176.2, 154.7, 134.0, 132.3, 125.9, 123.1, 122.7, 81.4, 26.0, 23.5; HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C11H11ClNO2S 256.0194; Found 256.0181.
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ASSOCIATED CONTENT
Supporting Information
1
Experimental procedure, full characterization of products, copies of H, 13C NMR, HRMS spectra
(PDF), and CIF information. The Supporting Information is available free of charge on the ACS Publi-
cations website.
AUTHOR INFORMATION
Corresponding Author
* E-mail: mayashankarbhu@gmail.com; mssingh@bhu.ac.in
ORCID
Maya Shankar Singh: 0000-0002-3199-0823
Monish Arbaz Ansari: 0000-0003-2706-8649
Dhananjay Yadav: 0000-0003-1649-8926
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGEMENTS
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We acknowledge the financial support from the Science and Engineering Research Board
(SERB/EMR/2015/002482), the Council of Scientific and Industrial Research (02(0263)/16/EMR-II),
and DST-PURSE programme, New Delhi. The authors acknowledge to SAIF IIT, Patna for providing
single crystal X-Ray facility. The authors (M.A.A. & D.Y.) are thankful to University Grants Commis-
sion (UGC), New Delhi for fellowship.
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REFERENCES
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