Metal-Free One-Pot Four-Component Cascade Annulation in Ionic Liquids at Room Temperature: Convergent Access to Thiazoloquinolinone Derivatives

Article abstract of DOI:10.1021/acs.joc.8b00814

An efficient, eco-friendly, and highly convergent one-pot route to privileged thiazoloquinolinone derivatives has been developed via four-component cascade coupling (4CCC) of α-enolic dithioesters, cysteamine/2-aminothiophenols, aldehydes, and cyclic 1,3-diketones in recyclable [EMIM][EtSO₄] ionic liquid at room temperature for the first time. The reaction proceeds via a N,S-acetal formation, Knoevenagel condensation, aza-ene reaction, imine-enamine/keto-enol tautomerization, and intramolecular N-cyclization cascade sequence. The merit of the protocol is highlighted by its efficacy of forming consecutive five new bonds (two C-C, two C-N, and one C-S) and two rings with all reactants being efficiently utilized. The operational simplicity, sustainability, mild conditions, excellent yields, tolerance of wide functional groups, and avoidance of expensive/toxic reagents are additional attributes to this domino four-component protocol. Notably, the products were easily separated from the ionic liquid, and thus the ionic liquid obtained was reused four times without considerable loss of any activity.

Full text of DOI:10.1021/acs.joc.8b00814

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Article
Metal-Free One-Pot Four-Component Cascade Annulation in Ionic Liquids at
Room Temperature: Convergent Access to Thiazoloquinolinone Derivatives
Anshu Singh, Abhijeet Srivastava, and Maya Shankar Singh
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00814 • Publication Date (Web): 06 Jul 2018
Downloaded from http://pubs.acs.org on July 6, 2018
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Metal-Free One-Pot Four-Component Cascade Annulation in Ionic Liquids at Room
Temperature: Convergent Access to Thiazoloquinolinone Derivatives
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Anshu Singh, Abhijeet Srivastava, and Maya Shankar Singh*
Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India
ABSTRACT: An efficient, eco-friendly and highly convergent one-pot route to privileged
thiazoloquinolinone derivatives has been developed via four-component cascade coupling (4CCC) of α-
enolic dithioesters, cysteamine/2-aminothiophenols, aldehydes, and cyclic 1,3-diketones in recyclable
[
EMIM][EtSO ] ionic liquid at room temperature for the first time. The reaction proceeds via N,S-acetal
4
formation, Knoevenagel condensation, aza-ene reaction, imine-enamine/keto-enol tautomerization, and
intramolecular N-cyclization cascade sequence. The merit of the protocol is highlighted by its efficacy
of forming consecutive five new bonds (two CC, two CN and one CS) and two rings with all
reactants being efficiently utilized. The operational simplicity, sustainability, mild conditions, excellent
yields, tolerance of wide functional groups and avoidance of expensive/toxic reagents are additional
attributes to this domino four-component protocol. Notably, the products were easily separated from the
ionic liquid, and thus ionic liquid obtained was reused four times without considerable loss of any
activity.
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INTRODUCTION
Polycyclic molecules are important skeletal units that are widely distributed in a number of natural
1
products and biologically active compounds. Organic synthesis has recently experienced various
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innovative scientific breakthroughs accompanied by improved and efficient synthetic protocols that
avoid the use of toxic solvents and reagents. Over the years, chemists have devoted their efforts towards
the development of operationally simple and sustainable strategies to assemble heterocyclic systems,
which are frequently encountered scaffolds in numerous natural products, drugs and pharmaceutically
significant substances.2,3 Amongst polycyclic heterocycles, the thiazoloquinoline scaffold is a notable
4
template in medicinal chemistry, and its derivatives possess useful biological and pharmacological
5
properties. Some thiazoloquinoline derivatives have been described as potential anti-inflammatory,
6
antispasmodics, probes for fluorescent molecules and precursors of symmetrical cyanines. Moreover,
thiazoloquinoline is also found to be active in the production of polymethine dyes and as spectral
sensitizers of silver halide emulsions.7
Literature reports for the construction of thiazoloquinolinone derivatives involve
hydration/cyclodehydration of 3-substituted 2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl-thiocyanates via
8a
thiocarbamates and a palladium-catalyzed reaction of ethyl 2-bromo-5-chlorothiazole-4-carboxylate
with arylboronic acids.8b Sadeghzadeh and co-workers reported the synthesis of thiazoloquinoline
derivative by using magnetite polyoxometalate hybrid nanomaterials. Shaterian and co-workers9b
disclosed the synthesis of thiazoloquinoline derivative by using superparamagnetic silica-encapsulated
9a
10
γ-Fe
2
3
O supported L-leucine at 80 ˚C. However, aforementioned synthesis of thiazoloquinolinones has
been rather disappointing due to significant limitations such as harsh reaction conditions, use of catalysts
and additives, multiple solvent systems, excess of base and ligands, cumbersome workup procedures,
use of toxic solvents and reagents (Scheme 1). Inspite of tremendous applications, there are limited
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reports toward the synthesis of thiazoloquinoline scaffolds. Therefore, it is still challenging and highly
desirable to explore operationally simple, efficient and widely applicable general approach for the
construction of structurally diverse thiazoloquinolines that could be recognized as strategic issue.
Scheme 1. Brief Description of Strategies for the Synthesis of Thiazoloquinolines
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Ionic liquids (ILs)11,12 have attracted significant attention as highly efficient catalysts and innovative
greener solvents in organic reactions due to their unique physical properties such as non-volatility,
reaction rate acceleration effects, and high thermal stability. The use of room temperature ionic liquids
RTILs), which are generally accepted to be quite environmentally benign,12a,b allow a simplified
efficient synthesis, easy isolation of the products,12c,d and recycling.12e,f Multicomponent reactions
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(
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(
MCRs) have become powerful tools in modern organic synthesis because of their advantages over
conventional multistep procedures towards the construction of a diverse array of novel and complex
molecular structures. With this in mind, we envisioned to perform the multicomponent reactions in ILs
due to their operational simplicity, convergence, atom economy and high bond‐forming efficiency in
one-pot. The combination of synthetic potentialities of MCR with the dual properties of ionic liquid as
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promoter and greener solvent could lead to highly efficient and sustainable new strategies. To the best
of our knowledge, MCR involving α-enolic dithioester, cysteamine, aldehyde and cyclic 1,3-diketone as
reaction partners in ionic liquid for the synthesis of thiazoloquinoline scaffold to date is not known. On
the basis of the above advantages of ILs, multicomponent, metal-free and catalyst-free reactions, herein
we report a green, facile and efficient one-pot metal-free procedure for the synthesis of a wide range of
structurally diverse thiazoloquinoline derivatives via four-component cascade reaction.
RESULTS AND DISCUSSION
The demand for better synthetic methods towards bioactive heterocyclic scaffolds and their derivatives
is high and continuous. α-Enolic dithioester exert diverse and amazing reactivity as novel multi-role-
synthons, and have been widely utilized as a practical key intermediate for the construction of diverse
1
5
important heterocyclic frameworks. Recently, our group reported the synthesis of thiazoloquinoline in
16
water-PEG at reflux temperature. As part of our ongoing study towards the design and development of
operationally simple and efficient methodologies for the construction of valuable heterocycles utilizing
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α-enolic dithioesters, we envisioned to employ this novel precursor as one of the reaction partner
toward MCRs in ionic liquid with a view to make reaction conditions more efficient and milder. Thus,
upon treatment of α-enolic dithioesters 1 with cysteamine/2-aminothiophenols 2, aldehydes 3 and cyclic
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,3-diketones 4 in ionic liquid at room temperature corresponding thiazoloquinolinones 5 were obtained
in good to excellent yields (Scheme 2).
Scheme 2. Synthesis of Thiazoloquinolinones 5 in Ionic Liquid at Room Temperature
We started our investigations employing α-enolic dithioester 1a, cysteamine 2, benzaldehyde 3a and
dimedone 4a as model substrates. The four-component reaction was vehemently scrutinized under
varying conditions at room temperature, and the results are listed in Table 1. Initially, the model reaction
was carried out with equimolar amounts of above four partners without any solvent and catalyst at room
temperature. We did not observe the trace of the desired product 5aa, even after 24 h of stirring and the
starting materials remained completely unreacted (Table 1, entry 1). In an effort to trigger the reaction,
we carried out the model reaction in various polar protic and polar aprotic solvents such as H O, MeOH,
2
EtOH, DMF and DCM at room temperature (Table 1, entries 2-6). Reaction did not proceed at all in
water even after 24 h of stirring (Table 1, entry 2). Other solvents did trigger the reaction, but they gave
low yield of the desired product 5aa (15-20%) except DMF which provided 45% isolated yield in 24 h
(
Table 1, entries 3-6). In above all reactions, most of the reactants remained unconsumed. During the
recent past, ionic liquids have emerged as greener and clean solvent/catalyst that could be used to
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construct carbon-carbon and carbon-heteroatoms bonds at room temperature. Therefore, we carried out
the model reaction in ionic liquid at room temperature.
Table 1. Optimization of Reaction Conditions for the Synthesis of Thiazoloquinolinones 5aaa
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entry solvent (1 mL)
name
time (h)
yield (%)
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none
none
Water
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NR
NR
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15
45
20
92
93
93
94
94
2
H O
3
MeOH
EtOH
Methanol
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Ethanol
5
DMF
Dimethyl formamide
Dichloromethane
Pyrrolidinium formate
Pyrrolidinium nitrate
1-methylpiperazinium formate
1-ethylpiperidinium ethylsulphate
6
DCM
7
[Pyr][HCOO]
8
[Pyr][NO
[HMPy][HCOO]
[EtPip][EtSO
[EtMPy][EtSO
3
]
3.5
4
9
10
4
]
4
1
1
4
]
1-ethyl-4-methyl piperazinium
ethylsulphate
3.5
1
2
[EMIM][EtSO
4
]
1-ethyl-3-methylimidazolium
ethylsulphate
2.5
96
1
1
3
4
[BMIM][Br]
1-butyl-3-methylimidazolium bromide
1-ethylpyridinium ethylsulphate
5
3.5
4
85
95
91
[EtP][EtSO
4
]
15
[MeP][MeSO
4
]
1-methylpyridinium methylsulphate
aReaction conditions: 1a (0.5 mmol) was treated with 2 (0.5 mmol), followed by addition of 0.5 mmol of
3a and 0.5 mmol of 4a at room temperature under inert atmosphere.
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To our pleasure, non-aromatic protic ionic liquid [Pyr][HCOO] promoted the reaction well at room
temperature affording the desired thiazoloquinoline 5aa in 92% yield (Table 1, entry 7). Pyrrolidinium
formate [Pyr][HCOO] ionic liquid not only enabled green and clean reaction profile, but also diminished
the reaction time significantly to 4 h. Encouraged by the above result, we investigated some other non-
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aromatic protic ILs such as [Pyr][NO
, entries 8-11). All the above ILs promoted the reaction well producing the desired product 5aa in
excellent yield exhibiting significant improvement in the outcomes of the reaction. To check the
generality of the protocol, we also investigated aprotic aromatic ILs such as [EMIM][EtSO ],
BMIM][Br], [EtP][EtSO ], and [MeP][MeSO ] (Table 1, entries 12-15). It was observed that EtSO
anion based ionic liquid 1-ethyl-3-methylimidazolium ethylsulphate [EMIM][EtSO ] afforded maximum
conversion in minimum time providing the desired product 5aa in 96% yield within 2.5 h (Table 1, entry
2), thus showing better efficacy than other ILs. Thus, the optimum condition for the synthesis of 5aa
was achieved by employing 1a (0.5 mmol), 2 (0.5 mmol), 3a (0.5 mmol), 4a (0.5 mmol) in 1 mL of
EMIM][EtSO ] at room temperature (Table 1, entry 12).
It could be postulated that the enhanced rate of the reactions in ILs as compared to conventional
3
], [HMPy][HCOO], [EtPip][EtSO
4
], and [EtMPy][EtSO
4
] (Table
1
4
[
4
4
4
4
1
[
4
solvents may be due to decrease in the activation energy of rate-determining step as a result of ionic
liquid effect. In general, the highly polar or charged intermediates such as carbocations, carbanions, and
activated complexes are more stable and long-lived in ionic liquid. The extensive stability and
sustainability of the charged species in the ionic media results from the electrostatic interaction between
the cation and anion of ILs. The ionic morphology imparted by the asymmetry in the structure of cation
and anion of ILs and its moderate to high polarity offers wide solubility window. These attributes make
ionic liquid a universal green solvent with very few limitations.
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Solvent-Reactivity Relationship
Polarity of ILs can be determined by a multiparameter approach, Kamlet-Taft parameters and electronic
(30).18 One of the most comprehensive and extensively used multiparameter
transition energy E
T
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approach for explaining and interpreting solvent behavior in reaction dynamics is linear solvation energy
relationship (LSER). The use of solvatochromic probes for the characterization of molecular
environment of reactants by LSER is well accepted. The interaction of dyes with pure solvents or
mixtures is a resultant of various effects. The most established multivariate of LSER is that of Kamlet
19
and Taft given by the equation (XYZ) = (XYZ)
0
+ aα + bβ + cπ* where a, b, and c are coefficients,
which show the dependence of physical and chemical properties (XYZ) in a particular solvent on
various parameters of the solvent. Kamlet-Taft parameters α represents hydrogen bond donor acidity, β
denotes hydrogen bond acceptor basicity and π* symbolizes dipolarity/polarizability of ILs.
20
We have made attempts to correlate reaction yields with the β values of ILs. Our observations of
explicit enhancements in ethylsulphate anion based ILs can be explained on the basis of polarity data of
ILs. Although the data are not available for all the ILs, however the excellent conversions can be
correlated with the polarity of the media. Since the reaction involves various electrophilic and
nucleophilic centres, henceforth a polar media can facilitate the reaction by stabilization of the
intermediates and charged species. β value which denotes basicity of the anion of ILs is an important
parameter since higher β value denotes higher electron density. This in turn can provide momentum to
the course of reaction and can enhance yields. EtSO
4
based ionic liquid has a β value of 0.788 which is
higher as compared to NO
0.689).21
3
anion (0.53), water (0.50), methanol (0.61), DCM (0.059) and DMF
(
With the established optimal conditions in hand, we then set out to explore the generality and
robustness of the protocol by using structurally diverse α-enolic dithioesters 1, aldehydes 3, and cyclic
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,3-diketones 4. The results are summarized in Tables 2 and 3. To address the factors that determine the
1
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reaction outcome, the electronic and steric properties of the substituents R , R , and R at reaction
partners 1, 3 and 4 were systematically varied. A broad spectrum of α-enolic dithioesters 1, bearing R1
as phenyl and aryl (both with electron-donating and electron-withdrawing) substituents, regardless of
their positions, participated well in the reaction affording the corresponding thiazoloquinolinones 5 in
high yields, revealing no obvious electronic impact (Table 2, 5aa-5ar, 18 examples). Various aromatic
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aldehydes 3 bearing R as electron-donating as well as electron-withdrawing substituents, regardless of
3
their positions, and 1,3-cyclohexanediones 4 bearing R as methyl and hydrogen could be employed and
tolerated well under the standard conditions affording the desired products in excellent yields (Table 2).
1
The variants of the substituents like OCH
and OMe, NO , CF , Cl, CH
2
O, OMe, CF
3
, and Cl groups on the phenyl ring (R moiety),
2
2
3
3
, OH, Br and F groups on the phenyl ring (R moiety), regardless of their
positions, were found to be compatible under the standard conditions (Table 2, 5aa-5ar). Notably,
disubstituted aromatic aldehyde with opposite electronic effect also worked well furnishing the desired
product 5ar in 89% isolated yield. Halo-substituted derivatives could be potential precursors for further
synthetic manipulations.
After the successful utilization of aromatic dithioesters, we envisioned to investigate the efficacy of
heteroaromatic dithioesters derived from 2-acetylfuran and 2-acetylthiophene. Importantly, dithioesters
1
bearing electron excessive groups such as 2-furyl and 2-thienyl substituent at R moiety were also well
tolerated under standard conditions resulting the corresponding products in high yields (Table 3, 5as-
5ba). It is noteworthy that α-enolic dithioesters bearing not only aromatic and heteroaromatic groups at
1
R moiety, but extended aromatics such as biphenyl and 1-naphthyl groups were also found to be
1
compatible well under the optimized conditions (Table 3, 5bb-5be). Notably, when R was switched to
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4
4
4
4
4
4
4
4
4
4
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5
5
5
5
5
5
5
5
5
6
Table 2. Substrate Scope for Synthesis of Thiazoloquinolinones 5a
0
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aReaction conditions: 1 (1.0 mmol) was treated with 2 (1.0 mmol), after the formation of N, S-acetal, 1.0
mmol of 3 and 1.0 mmol of 4 was added and reaction mixture was stirred at room temperature under
inert atmosphere.
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methyl group (dithioester derived from acetone), also underwent the reaction smoothly affording the
corresponding thiazoloquinolinones 5bf, 5bg and 5bh in high yields (upto 84%). Remarkably,
disubstituted aromatic aldehyde bearing both electron-donating as well as electron-withdrawing groups
also worked well furnishing the desired product 5bh in 84% yield.To further enhance the scope of the
reaction and to introduce substituent diversity into the product, we envisioned to evaluate aliphatic
aldehyde. Thus, treatment of isopropyl aldehyde in place of aromatic aldehyde under standard reaction
conditions resulted only trace of the desired product even after 20 h of stirring at room temperature
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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3
3
3
3
3
3
3
4
4
4
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4
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4
4
4
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0
(Table 3, 5bi and 5bj). In order to extend the substrate scope, next we investigated acyclic diketone
acetylacetone. In this case also, we obtained only a trace amount of the product even after 24 h of
stirring at room temperature (Table 3, 5bk), thus limiting the scope of the reaction to some extent. The
feasibility of the reaction was also checked for variation in the aminothiol moiety. To increase the
diversity of the reaction, 2-aminothiophenol and 2-amino-4-chlorothiophenol were used as new aromatic
2-aminothiophenols instead of cysteamine (Table 3, 5bl and 5bm). However, the reaction resulted only
in 22% and 20% isolated yield for 5bl and 5bm, respectively. The one-pot cascade strategy reported
herein allows a novel entry to functionalized thiazoloquinolinones, which would otherwise be more
difficult to prepare by alternative routes. The structure of all the newly synthesized thiazoloquinolinones
1
13
5
are deduced by their satisfactory spectral ( H, C, IR and mass) studies.
Although the exact mechanism is still unclear, taking into account all of the above observations and
entire experimental outcomes into consideration, a plausible mechanistic pathway for the formation of
compound 5 is outlined in Scheme 3. The first step is believed to be the formation of cyclic N,S-acetal A
by the reaction of α-enolic dithioester 1 with cysteamine 2, which was isolated and fully characterized.22
Next, reaction of aromatic aldehyde 3 with cyclic 1,3-diketone 4 generated Knoevenagel product B, a
highly reactive ortho-quinonemethide intermediate that could not be isolated.
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4
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4
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4
4
4
4
4
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5
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5
5
6
Table 3. Substrate Scope for Synthesis of Thiazoloquinolinones 5a
0
1
2
3
4
5
6
7
8
9
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aReaction conditions: 1 (1.0 mmol) was treated with 2 (1.0 mmol), after the formation of N, S-acetal, 1.0 mmol of
3
and 1.0 mmol of 4 was added and reaction mixture was stirred at room temperature under inert atmosphere.
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Subsequently, the N,S-acetal A undergoes a conjugate addition with ortho-quinonemethide intermediate
B via aza-ene fashion to generate acyclic enol intermediate C. Intermediate C undergoes imine-enamine
and keto-enol tautomerization to give intermediate D, which rapidly undergoes intramolecular
dehydrative N-cyclization to give the desired triheterocyclic product 5. The separately synthesized
cyclic N,S-acetal A and Knoevenagel product B provided our desired product 5 under optimized
reaction conditions. It turns out that the intermediates A and B might be formed concomitantly and
reacts instantly to form the desired product and limiting the formation of byproducts.
4
5
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8
9
1
1
1
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9
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8
9
0
Scheme 3. Plausible Mechanism for the Synthesis of Thiazoloquinolinone 5
Next, we tried to check the ability of ILs to be used as a recyclable material for environmental
remediation. After each reaction, the recovered IL was dried and further checked for any contamination
1
13
by H and C NMR spectroscopy. No degradation was observed during the reaction (as evidenced by
the NMR spectra of the IL after each run, and the fact that there was no discolouration also). Further the
reusability of the IL [EMIM][EtSO ] was also examined in the model reaction for the synthesis of 5aa.
4
The results show that the IL can be reused for four consecutive runs without any significant loss of its
catalytic activity (Figure 1).
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6
Figure 1. Reusability of [EMIM][EtSO ] for Synthesis of 5aa
4
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The efficiency of IL was additionally checked by calculating the turn over number (TON) and turn
over frequency (TOF). The data is given in the Supporting Information file. To further evaluate the
thermal stability of employed ILs, TGA-DTA studies were conducted. [EMIM][EtSO
4
] and
[
BMIM][Br] were initially taken up for the analysis. The samples were heated from 30 °C to 710 °C
-1
under nitogen flow at heating rate of 20 °C min . Tonset for [BMIM][Br] ionic liquid was found to be
282.87 °C and for [EMIM][EtSO ] at 281.89 °C. The data signify the tremendous stability of the
4
catalyst. The TGA-DTA data are given in the Supporting Information file.
CONCLUSION
In summary, a practical and reliable one-pot four-component annulative coupling strategy has been
realized for the direct synthesis of diverse thiazoloquinolinone derivatives from α-enolic dithioesters,
cysteamine/2-aminothiophenols, aldehydes and cyclic 1,3-diketones in ionic liquid at room temperature.
The reaction proceeds via N,S-acetal formation/Knoevenagel condensation/aza-ene reaction/imine-
enamine/keto-enol tautomerization/intramolecular cyclization cascade sequence as key steps. The merit
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of the protocol is highlighted by its efficacy of forming consecutive five new bonds (two C-C, two C-N
and one C-S) and two rings with all reactants being efficiently utilized in a single operation. The
operational simplicity, clean reaction profile, sustainability, mild conditions, excellent yields, reusability
of the ionic liquid, tolerance of wide functional groups and avoidance of expensive/toxic reagents are
additional attributes to this novel one-pot transformation. Notably, the products have been easily
separated from the ionic liquid, which was reused four times without any considerable loss of activity.
Also, the presence of various functionality makes thiazoloquinolinones an excellent precursor, which
could pursue further synthetic renovations for significant practical applications. The modular character
of this multicomponent approach and the availability of the starting compounds make this process
potentially attractive for combinatorial chemistry and diversity-oriented synthesis (DOS).
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
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2
3
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5
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5
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5
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6
0
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9
0
EXPERIMENTAL SECTION
General Information
Unless otherwise noted, all reagents have been purchased from commercial suppliers and used without
further purification. α-Enolic dithioesters 1 are not commercially sourced and were synthesized in good
2
3
yields following the reported procedure. All the reactions were carried out in an oven-dried glass ware
under inert atmosphere. Chromatograms were visualized by fluorescence quenching with UV light at
-1
1
13
2
54 nm. IR spectra were recorded in KBr and wavelengths (ʋ) are reported in cm . H and C NMR
spectra were recorded on NMR spectrometer operating at 500 and 125 MHz, respectively. Chemical
1
13
shifts for H and C NMR spectra are reported as δ in units of parts per million (ppm) downfield from
SiMe (δ 0.0). Coupling constants (J) are given in Hz. Mass spectra were recorded under ESI/HRMS
4
using ion trap mass analyzer. Melting points have been determined with Büchi B-540 melting point
apparatus and are uncorrected. TGA-DTA data were recorded on a Perkin Elmer Simultaneous Thermal
Analyzer STA 6000.
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5
5
6
General Procedure for the Synthesis of 4,5-Disubstituted Thiazolo[3,2-a]quinolin-6(2H)-ones 5.
α-Enolic dithioester 1 (1.0 mmol), cysteamine 2 (1.0 mmol) were added to a round bottom flask
containing freshly prepared and dried 1.0 ml of ionic liquid21b under inert conditions. The reaction
mixture was stirred at room temperature for 1 h till the formation of cyclic N,S-acetal (monitored by
TLC), followed by addition of aldehyde 3 (1.0 mmol) and cyclic-1,3-diketone 4 (1.0 mmol). The
reaction mixture was further stirred for stipulated period of time (Table 1). After completion of the
reaction as shown by TLC, water (20 ml) was added to the reaction mixture. The product was extracted
with ethyl acetate (2 x 10 ml). Employed ionic liquid has affinity for water and hence easily separated
0
1
2
3
4
5
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7
8
9
0
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3
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2
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0
1
2
3
4
5
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8
9
0
from the product. The combined organic fraction is then dried with anhydrous Na
2
SO and dried under
4
vacuo. The crude product thus obtained was purified by column chromatography on silica gel using
ethyl acetate/hexane (10:90) as eluent to afford pure thiazoloquinolinones 5 in good to excellent yields.
The spectral and analytical data of all the compounds are given as follows:
4-Benzoyl-8,8-dimethyl-5-phenyl-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-one (5aa).
1
6
-1
(
0.37 g, 90%), Yellow solid; mp 210-211 °C (lit., 210-212 °C). IR (KBr) ʋ (cm ) 3059, 2925, 2854,
1
1
4
2
627, 1525, 1477, 1386, 1346. H NMR (500 MHz, CDCl
3
): δ (ppm) 7.42-7.35 (m, 1H), 7.30-7.24 (m,
H), 7.10-7.04 (m, 3H), 6.92 (d, J = 5 Hz, 2H), 5.22 (s, 1H), 4.08-3.98 (m, 2H), 3.21-3.16 (m, 2H), 2.52-
13
.39 (m, 2H), 2.26-2.16 (ABq, J
): δ (ppm) 195.1, 194.7, 155.1, 148.2, 145.8, 139.7, 130.0, 128.2, 128.1, 127.3, 127.2,
26.3, 115.6, 107.8, 50.1, 48.8, 40.8, 37.2, 32.4, 30.0, 28.3, 25.9.
1
= 35 Hz, J = 15 Hz, 2H), 1.08 (s, 3H), 0.87 (s, 3H). C NMR (125
2
MHz, CDCl
3
1
4-benzoyl-5-(4-methoxyphenyl)-8,8-dimethyl-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-
-1
one (5ab). (0.37 g, 84%), Yellow solid; mp 156.2-157.1˚C. IR (KBr) ʋ (cm ) 3060, 2924, 2856, 1628,
1
1
2
524, 1481, 1386, 1347. H NMR (500 MHz, CDCl
3
): δ (ppm) 7.32-7.16 (m, 5H), 6.76 (d, J = 10 Hz,
H), 6.58 (d, J = 5 Hz, 2H), 5.08 (s, 1H), 4.01-3.90 (m, 2H), 3.63 (s, 3H), 3.15-3.09 (m, 2H), 2.44-2.33
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(
ABq, J
1
= 40 Hz, J
2
= 20 Hz, 2H), 2.18-2.08 (ABq, J
1
= 35 Hz, J
2
= 15 Hz, 2H), 1.01 (s, 3H), 0.80 (s,
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
3
H). C NMR (125 MHz, CDCl
3
): δ (ppm) 195.4, 194.7, 157.9, 154.8, 148.1, 139.8, 138.4, 130.1,
128.4, 128.1, 127.2, 115.9, 113.6, 108.1, 55.1, 50.1, 49.8, 40.8, 36.4, 32.4, 30.0, 28.3, 26.9. HRMS
+
+
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
ESI ): calcd for C27
H
28NO S [M + H ], 446.1790; found, 446.1781.
3
4
-Benzoyl-5-(3-nitrophenyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-one (5ac). (0.37
-1
g, 86%), Yellow solid; mp 116.9-117.0 ˚C. IR (KBr) ʋ (cm ) 3060, 2925, 2855, 1628, 1525, 1480,
1
1387, 1348. H NMR (500 MHz, CDCl
3
): δ (ppm) 7.90 (d, J = 5 Hz, 1H), 7.68 (br, 1H), 7.43-7.40 (m,
1
2
H), 7.33-7.29 (m, 2H), 7.25-7.18 (m, 4H), 5.37 (s, 1H), 4.15-4.08 (m, 2H), 3.25-3.20 (m, 2H), 2.72-
1
3
.65 (m, 2H), 2.36-2.31 (m, 2H), 2.08-2.04 (m, 1H), 1.90-1.88 (m, 1H). C NMR (125 MHz, CDCl ): δ
3
(
ppm) 195.5, 194.5, 155.2, 150.8, 148.3, 139.5, 134.2, 130.5, 129.1, 128.5, 126.8, 122.5, 121.5, 115.5,
+
+
1
07.3, 49.9, 37.9, 36.4, 28.4, 27.2, 20.9. HRMS (ESI ): calcd for C24
H
21
N
2
O S [M + H ], 433.1222;
4
found, 433.1210.
4
-Benzoyl-5-(4-(trifluoromethyl)phenyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-one
-1
(5ad). (0.41 g, 92%), Yellow solid; mp 165.1-166.2 ˚C. IR (KBr) ʋ (cm ) 3061, 2924, 2854, 1628,
1
1
2
2
522, 1479, 1387, 1345. H NMR (500 MHz, CDCl
3
): δ (ppm) 7.31-7.19 (m, 5H), 7.13 (d, J = 10 Hz,
H), 6.91 (d, J = 10 Hz, 2H), 5.25 (s, 1H), 3.97-3.91 (m, 2H), 3.08-3.02 (m, 2H), 2.57-2.48 (m, 2H),
13
.28-2.14 (m, 2H), 1.92-1.88 (m, 1H), 1.77-1.72 (m, 1H). C NMR (125 MHz, CDCl ): δ (ppm) 195.6,
3
194.5, 155.2, 150.7, 150.1, 139.6, 130.4, 128.4, 128.3, 127.9, 127.0, 125.2, 125.1, 115.7, 107.2, 49.8,
+
+
3
4
7.5, 36.4, 28.3, 27.1, 20.8. HRMS (ESI ): calcd for C25
H
21
F
3
NO S [M + H] , 456.1245; found,
2
56.1235.
4
-Benzoyl-5-(2-chlorophenyl)-8,8-dimethyl-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-
-1
one (5ae). (0.37 g, 83%), Yellow solid; mp 208.6-209.1 ˚C. IR (KBr) ʋ (cm ) 3059, 2923, 2855, 1627,
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
1
7
523, 1480, 1385, 1347. H NMR (500 MHz, CDCl
.23 (d, J = 10.0 Hz, 2H), 7.10 (d, J = 5 Hz, 1H), 6.94-6.91 (m, 1H), 6.86-6.83 (m, 1H), 6.65 (d, J = 5
= 40 Hz, J = 15 Hz,
): δ (ppm) 195.2, 193.4,
53.9, 148.8, 142.0, 139.9, 133.7, 132.2, 130.2, 130.1, 128.4, 127.5, 127.0, 126.1, 113.5, 107.4, 49.9,
3
): δ (ppm) 7.40-7.39 (m, 1H), 7.33-7.30 (m, 2H),
Hz, 1H), 5.51 (s, 1H), 4.17-4.05 (m, 2H), 3.14-3.11 (m, 2H), 2.56-2.45 (ABq, J
1
2
1
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
1
4
H), 2.24-2.10 (m, 2H), 1.11 (s, 3H), 0.95 (s, 3H). C NMR (125 MHz, CDCl
3
+
+
9.7, 41.2, 38.7, 32.1, 30.1, 27.9, 27.0. HRMS (ESI ): calcd for C26
H
25ClNO S [M + H ], 450.1295;
2
found, 450.1291.
4
-(Benzo[d][1,3]dioxole-5-carbonyl)-8,8-dimethyl-5-(4-trifluoromethyl-phenyl)-5,7,8,9-tetrahydro-
1
H-thiazolo[3,2-a]quinolin-6(2H)-one (5af). (0.38 g, 90%), Yellow solid; mp 162.4-163.1 ˚C. IR (KBr)
-1
1
ʋ (cm ) 2953, 2925, 2851, 1627, 1509, 1473, 1455, 1388. H NMR (500 MHz, CDCl
J = 5 Hz, 2H), 7.12 (d, J = 5 Hz, 2H), 6.86-6.81 (m, 2H), 6.74 (d, J = 5 Hz, 1H), 5.99 (s, 2H), 5.40 (s,
H), 4.10-4.05 (m, 2H), 3.25-3.20 (m, 2H), 2.55-2.43 (ABq, J = 40 Hz, J = 15 Hz, 2H), 2.30-2.20
= 15 Hz, 2H), 1.13 (s, 3H), 0.90 (s, 3H). C NMR (125 MHz, CDCl ): δ (ppm)
3
): δ (ppm) 7.40 (d,
1
1
2
1
3
(ABq, J
1
= 30 Hz, J
2
3
195.3, 193.1, 154.7, 149.8, 149.5, 148.8, 147.6, 133.2, 127.6, 125.4, 125.3, 122.6, 114.6, 108.2, 108.0,
+
1
07.2, 101.5, 50.0, 49.9, 40.9, 37.5, 32.4, 30.1, 28.3, 26.8. HRMS (ESI ): calcd for C28
H
25
F
3
NO S [M +
4
+
H ], 528.1456; found, 528.1478.
5
-(4-Bromophenyl)-4-(3-methoxybenzoyl)-8,8-dimethyl-5,7,8,9
tetrahydro-1H-thiazolo[3,2-
-1
a]quinolin-6(2H)-one (5ag). (0.46 g, 87%), Yellow solid; mp 202.2-203.3 ˚C. IR (KBr) ʋ (cm ) 2900,
1
2
962, 2933, 1628, 1508, 1460, 1381, 1324. H NMR (500 MHz, CDCl
3
): δ (ppm) 7.33-7.24 (m, 4H),
6
.87-6.81 (m, 4H), 5.30 (s, 1H), 4.08-3.97 (m, 2H), 3.81 (s, 3H), 3.17-3.15 (m, 2H), 2.53-2.40 (ABq, J
1
1
3
= 50 Hz, J
2
= 20 Hz, 2H), 2.27-2.17 (ABq, J
1
= 30 Hz, J = 15 Hz, 2H), 1.09 (s, 3H), 0.88 (s, 3H). C
2
NMR (125 MHz, CDCl
3
): δ (ppm) 195.3, 193.5, 161.6, 154.3, 148.8, 144.9, 131.8, 131.3, 129.6, 129.1,
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2
3
+
1
20.1, 114.7, 113.5, 107.5, 55.4, 50.0, 49.8, 40.8, 37.1, 32.3, 30.1, 28.3, 26.8. HRMS (ESI ): calcd for
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
C
27
H
27BrNO
3
S [M + H ], 524.0895; found, 524.0879.
4
-(3-Methoxybenzoyl)-5-(4-methoxyphenyl)-8,8-dimethyl-5,7,8,9-tetrahydro-1H-thiazolo[3,2-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
-
1
a]quinolin-6(2H)-one (5ah). (0.39 g, 83%), Yellow solid; mp 146.0-147.2 ˚C. IR (KBr) ʋ (cm ) 2901,
1
2
2
960, 2932, 1627, 1509, 1459, 1382, 1324. H NMR (500 MHz, CDCl
3
): δ (ppm) 7.34 (d, J = 10 Hz,
H), 6.91 (d, J = 10 Hz, 2H), 6.81 (d, J = 10 Hz, 2H), 6.68 (d, J = 10 Hz, 2H), 5.27 (s, 1H), 4.04-3.97
(m, 2H), 3.80 (s, 3H), 3.71 (s, 3H), 3.18-3.13 (m, 2H), 2.51-2.39 (ABq, J
1
= 40 Hz, J
2
= 20 Hz, 2H),
): δ
13
2
.27-2.17 (ABq, J
1
= 30 Hz, J
2
= 15 Hz, 2H), 1.09 (s, 3H), 0.88 (s, 3H). C NMR (125 MHz, CDCl
3
(
ppm) 195.5, 193.6, 161.5, 157.9, 154.1, 148.4, 138.3, 132.0, 129.7, 128.3, 115.5, 113.7, 113.4, 108.2,
+
5
5.3, 55.1, 50.1, 49.8, 40.7, 36.5, 32.3, 30.1, 28.3, 26.8. HRMS (eESI ): calcd for C28
H
30NO S [M +
4
+
H ], 476.1896; found, 476.1933.
4
-(3-Methoxybenzoyl)-8,8-dimethyl-5-(4-(trifluoromethyl)phenyl)-5,7,8,9-tetrahydro-1H-
thiazolo[3,2-a]quinolin-6(2H)-one (5ai). (0.44 g, 93%), Yellow solid; mp 207.2-208.0 ˚C. IR (KBr) ʋ
-1
1
(cm ) 2900, 2962, 2934, 1627, 1509, 1460, 1383, 1325. H NMR (500 MHz, CDCl
m, 4H), 7.01 (d, J = 5 Hz, 2H), 6.75 (d, J = 10 Hz, 2H), 5.34 (s, 1H), 3.98-3.96 (m, 2H), 3.73 (s, 3H),
.09-3.06 (m, 2H), 2.47-2.34 (ABq, J = 45 Hz, J = 20 Hz, 2H), 2.21-2.10 (ABq, J = 40 Hz, J = 20
Hz, 2H), 1.02 (s, 3H), 0.80 (s, 3H). C NMR (125 MHz, CDCl ): δ (ppm) 195.3, 193.5, 161.6, 154.3,
149.7, 149.1, 131.7, 129.6, 127.6, 125.3, 125.2, 114.3, 113.6, 107.3, 55.4, 50.0, 49.8, 40.8, 37.6, 32.3,
3
): δ (ppm) 7.31-7.23
(
3
1
2
1
2
1
3
3
+
+
3
0.1, 28.3, 26.8. HRMS (ESI ): calcd for C28
H
27
3
F NO S [M + H ], 514.1664; found, 514.1696.
3
5
-(p-Tolyl)-4-(4-(trifluoromethyl)benzoyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-
-
1
one (5aj). (0.48 g, 87%), Yellow solid; mp 127.9-128.1 ˚C. IR (KBr) ʋ (cm ) 2957, 2922, 2850, 1630,
1
1
518, 1482, 1381, 1323. H NMR (500 MHz, CDCl
3
): δ (ppm) 7.45 (d, J = 10 Hz, 2H), 7.22 (d, J = 5
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2
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6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Hz, 2H), 6.85 (d, J = 10 Hz, 2H), 6.72 (d, J = 10 Hz, 2H), 5.01 (s, 1H), 4.02-3.89 (m, 2H), 3.16-3.08 (m,
H), 2.57-2.45 (m, 2H), 2.31-2.26 (m, 1H), 2.21-2.16 (m, 1H), 2.14 (s, 3H), 1.93-1.88 (m, 1H), 1.79-
2
1
3
1.74 (m, 1H). C NMR (125 MHz, CDCl
3
): δ (ppm) 195.6, 193.1, 156.2, 149.9, 143.3, 143.0, 136.0,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
29.1, 127.4, 127.3, 125.2, 125.1, 125.0, 117.0, 107.2, 49.8, 36.5, 36.4, 28.3, 27.0, 21.1, 20.7. HRMS
+
+
(
ESI ): calcd for C26
H
23
F
3
NO S [M + H ], 470.1402; found, 470.1399.
2
8
,8-Dimethyl-4-(4-(trifluoromethyl)benzoyl)-5-(4-(trifluoromethyl)phenyl)-5,7,8,9-tetrahydro-1H-
thiazolo[3,2-a]quinolin-6(2H)-one (5ak). (0.46 g, 91%), Yellow solid; mp 155.9-156.1˚C. IR (KBr) ʋ
-1
1
(
cm ) 2959, 2923, 2851, 1630, 1517, 1481, 1381, 1323. H NMR (500 MHz, CDCl
5 Hz, 2H), 7.38 (d, J = 10 Hz, 2 H), 7.29 (d, J = 10 Hz, 2H), 7.03 (d, J = 10 Hz, 2H), 5.19 (s, 1H),
.18-4.02 (m, 2H), 3.30-3.24 (m, 2H), 2.56-2.45 (ABq, J = 40 Hz, J = 15 Hz, 2H), 2.28-2.17 (ABq, J
= 20 Hz, 2H), 1.11 (s, 3H), 0.87 (s, 3H). C NMR (125 MHz, CDCl ): δ (ppm) 195.2, 192.9,
3
): δ (ppm) 7.57 (d, J
=
4
1
2
1
1
3
=
40 Hz, J
2
3
1
4
56.7, 149.4, 148.5, 143.1, 131.9, 131.6, 128.7, 128.4, 127.8, 127.2, 125.3, 124.9, 115.1, 106.6, 49.9,
+
+
0.7, 37.4, 32.3, 29.9, 29.7, 28.3, 26.8. HRMS (ESI ): calcd for C28
H
24
F
6
NO S [M + H ], 552.1432;
2
found, 552.1428.
5
-(4-Fluorophenyl)-8,8-dimethyl-4-(4-(trifluoromethyl)benzoyl)-5,7,8,9-tetrahydro-1H-
thiazolo[3,2-a]quinolin-6(2H)-one (5al). (0.43 g, 84%), Yellow solid; mp 170.5-171.2 ˚C. IR (KBr) ʋ
-1
1
(
cm ) 2959, 2924, 2851, 1629, 1518, 1482, 1380, 1325. H NMR (500 MHz, CDCl
3
): δ (ppm) 7.56 (d, J
= 5 Hz, 2H), 7.31-7.28 (m, 2H), 6.89-6.79 (m, 4H), 5.08 (s, 1H), 4.15-4.01 (m, 2H), 3.27-3.21 (m, 2H),
2
.54-2.43 (ABq, J
1
= 40 Hz, J
2
= 15 Hz, 2H), 2.25-2.15 (ABq, J
1
= 35 Hz, J
2
= 15 Hz, 2H), 1.08 (s, 3H),
1
3
0
.85 (s, 3H). C NMR (125 MHz, CDCl
3
): δ (ppm) 195.3, 193.0, 162.3, 160.4, 156.5, 148.1, 143.3,
141.5, 129.1, 127.2, 125.2, 115.7, 115.1, 114.9, 107.1, 49.9, 49.8, 40.7, 36.6, 32.3, 29.9, 28.3, 26.7.
+
+
HRMS (ESI ): calcd for C27
H
24
F
4
NO
2
S [M + H ], 502.1464; found, 502.1456.
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5
5
-(2-Chlorophenyl)-8,8-dimethyl-4-(4-(trifluoromethyl)benzoyl)-5,7,8,9-tetrahydro-1H-
thiazolo[3,2-a]quinolin-6(2H)-one (5am). (0.40 g, 83%), Yellow solid; mp 120.4-121.0 ˚C. IR (KBr) ʋ
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
-
1
1
(cm ) 2958, 2923, 2849, 1628, 1517, 1479, 1380, 1321. H NMR (500 MHz, CDCl
10 Hz, 2H), 7.30-7.27 (m, 2H), 7.09 (d, J = 10 Hz, 1H), 6.96-6.93 (m, 1H), 6.87-6.84 (m, 1H), 6.69-
.67 (m, 1H), 5.38 (s, 1H), 4.17-4.08 (m, 2H), 3.17-3.13 (m, 2H), 2.57-2.47 (ABq, J = 35 Hz, J = 15
): δ (ppm) 195.3,
93.6, 155.8, 148.7, 143.6, 142.0, 133.4, 132.0, 130.1, 127.7, 127.1, 126.2, 125.5, 125.4, 125.0, 113.7,
3
): δ (ppm) 7.58 (d, J
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
=
6
1
2
1
3
Hz, 2H), 2.23-2.10 (m, 2H), 1.09 (s, 3H), 0.92 (s, 3H). C NMR (125 MHz, CDCl
3
1
1
5
+
S [M + H+],
06.9, 49.8, 41.0, 38.0, 32.1, 29.9, 29.7, 27.9, 26.9. HRMS (ESI ): calcd for C27
H
24ClF
3
NO
2
18.1168; found, 518.1150.
8
,8-dimethyl-5-phenyl-4-(4-(trifluoromethyl)benzoyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-
1
6
1
a]quinolin-6(2H)-one (5an). (0.47 g, 92%), Brown solid; mp 140-143 °C (lit., 143-145 °C). H NMR
(
500 MHz, CDCl
3
): δ (ppm) 7.61-7.51 (m, 2H), 7.29-7.20 (m, 4H), 7.11-7.06 (m, 2H), 6.91 (d, J = 6.9
Hz, 1H), 5.01 (s, 1H), 4.16-3.92 (m, 2H), 3.27-3.14 (m, 2H), 2.59-2.40 (m, 2H), 2.23-2.12 (m, 2H), 1.06
1
3
(s, 3H), 0.83 (s, 3H). C NMR (125 MHz, CDCl
3
): δ (ppm) 195.0, 192.8, 162.2, 156.3, 146.9, 145.3,
43.0, 130.2, 128.1, 127.8, 127.1, 125.2, 125.4, 124.7, 114.5, 115.2, 106.7, 49.7, 49.6, 40.3, 35.8, 32.0,
9.6, 27.0, 26.3.
1
2
5
-(4-Methoxyphenyl)-8,8-dimethyl-4-(4-(trifluoromethyl)benzoyl)-5,7,8,9-tetrahydro-1H-
thiazolo[3,2-a]quinolin-6(2H)-one (5ao). (0.43 g, 82%), Yellow solid; mp 138.0-139.1 ˚C. IR (KBr) ʋ
-1
1
(
cm ) 2958, 2922, 2850, 1629, 1516, 1480, 1380, 1322. H NMR (500 MHz, CDCl
10 Hz, 2H), 7.31 (d, J = 5 Hz, 2H), 6.84 (d, J = 5 Hz, 2H), 6.67 (d, J = 5 Hz, 2H), 5.02 (s, 1H), 4.14-
3.96 (m, 2H), 3.69 (s, 3H), 3.24-3.16 (m, 2H), 2.52-2.42 (ABq, J = 35 Hz, J = 15 Hz, 2H), 2.24-2.14
= 15 Hz, 2H), 1.07 (s, 3H), 0.86 (s, 3H). C NMR (125 MHz, CDCl ): δ (ppm)
95.5, 193.1, 158.0, 156.3, 148.0, 143.5, 138.1, 128.4, 127.3, 127.2, 125.12, 125.10, 116.0, 113.6, 107.4,
3
): δ (ppm) 7.56 (d, J
=
1
2
13
(
ABq, J
1
= 35 Hz, J
2
3
1
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7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
S [M + H+],
5
5
5.1, 50.0, 49.8, 40.6, 36.3, 32.3, 29.8, 28.2, 26.8. HRMS (ESI ): calcd for C28
H
27
F
3
NO
3
14.1664; found, 514.1647.
8
,8-Dimethyl-5-(4-nitrophenyl)-4-(4-(trifluoromethyl)benzoyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
-1
a]quinolin-6(2H)-one (5ap). (0.39 g, 86%), Yellow solid; mp 116.6-117.0 ˚C. IR (KBr) ʋ (cm ) 2958,
1
2
7
921, 2849, 1631, 1516, 1480, 1380, 1322. H NMR (500 MHz, CDCl
3
): δ (ppm) 7.97-7.90 (m, 2H),
.60-7.53 (m, 2H), 7.30-7.23 (m, 2H), 7.09-7.02 (m, 2H), 5.19 (s, 1H), 4.15-4.03 (m, 2H), 3.31-3.23 (m,
1
3
2H), 2.51-2.47 (m, 2H), 2.19-2.14 (m, 2H), 1.06 (s, 3H), 0.80 (s, 3H). C NMR (125 MHz, CDCl
3
): δ
(
ppm) 195.2, 192.8, 157.0, 152.6, 148.8, 146.4, 142.9, 128.4, 127.2, 125.5, 125.4, 123.6, 114.5, 106.2,
+
O
S [M + H+],
4
9.9, 49.8, 40.8, 37.7, 32.4, 29.9, 29.7, 28.3, 26.8. HRMS (ESI ): calcd for C27
H
24
F
3
N
2
4
529.1410; found, 529.1408.
4-(2-chlorobenzoyl)-8,8-dimethyl-5-phenyl-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-
one (5aq). (0.40 g, 83%), Yellow solid; mp 109-111 °C (lit.,16 112-114 °C). H NMR (500 MHz,
1
CDCl
(m, 2H), 3.32-3.16 (m, 2H), 2.61-2.40 (m, 2H), 2.25-2.09 (m, 2H), 1.05 (s, 3H), 0.83 (s, 3H). C NMR
125 MHz, CDCl ): δ (ppm) 194.9, 191.1, 155.3, 146.5, 145.6, 138.2, 129.8, 129.3, 127.7, 126.2, 126.0,
16.0, 108.4, 49.8, 49.5, 41.0, 37.4, 31.1, 29.8, 28.1, 26.0.
3
): δ (ppm) 7.30-7.21 (m, 3H), 7.07-7.01 (m, 4H), 6.76 (d, J = 3.6 Hz, 2H), 4.84 (s, 1H), 4.16-3.94
1
3
(
3
1
5
-(2-Hydroxy-5-nitrophenyl)-4-(3-methoxybenzoyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-
-
1
6(2H)-one (5ar). (0.36 g, 89%), Yellow solid; mp 118.0-119.0 ˚C. IR (KBr) ʋ (cm ) 2900, 2961, 2934,
1
1
1
3
628, 1508, 1457, 1381, 1324. H NMR (500 MHz, CDCl
3
): δ (ppm) 10.48 (b, 1H), 7.92 (d, J = 10 Hz,
H), 7.76 (s, 1H), 7.15 (d, J = 5 Hz, 2 H), 6.85-6.76 (m, 3H), 5.21 (s, 1H), 4.24-4.10 (m, 2H), 3.79 (s,
H), 3.34-3.25 (m, 2H), 2.79-2.68 (m, 2H), 2.50-2.40 (m, 2H), 2.09-2.04 (m, 1H), 1.85-1.84 (m, 1H).
13C NMR (125 MHz, CDCl
): δ (ppm) 199.3, 192.9, 161.7, 159.9, 154.8, 154.3, 141.1, 133.0, 131.2,
3
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2
3
29.1, 125.0, 124.5, 118.4, 113.9, 113.6, 108.0, 55.4, 50.2, 35.6, 31.9, 28.7, 27.4, 20.2. HRMS (ESI+):
1
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
calcd for C25
H
23
N
2
O S [M + H ], 479.1277; found, 479.1264.
6
4
-(furan-2-carbonyl)-8,8-dimethyl-5-phenyl-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
6
1
one (5as). (0.38 g, 92%), Brown solid; mp 235-236 °C (lit., 237-238 °C). H NMR (500 MHz, CDCl
3
):
δ (ppm) 7.49 (s, 1H), 7.26-7.08 (m, 5H), 6.97 (d, J = 3.3 Hz, 1H), 6.37 (s, 1H), 5.90 (s, 1H), 4.13-3.88
1
3
(
m, 2H), 3.27-3.12 (m, 2H), 2.45-2.36 (m, 2H), 2.26-2.21 (m, 2H), 1.08 (s, 3H), 0.86 (s, 3H). C NMR
(125 MHz, CDCl ): δ (ppm) 195.4, 178.0, 157.2, 152.6, 148.4, 145.4, 145.0, 128.3, 127.0, 126.1, 117.3,
15.9, 111.6, 106.6, 50.0, 49.7, 40.4, 34.9, 32.2, 29.8, 28.3, 26.7.
3
1
4
-(furan-2-carbonyl)-8,8-dimethyl-5-p-tolyl-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-
one (5at). (0.39 g, 84%), Yellow solid; mp 219-221 °C (lit.,16 221-222 °C). H NMR (500 MHz,
1
CDCl
3
): δ (ppm) 7.47 (s, 1H), 7.10 (d, J = 7.8 Hz, 2H), 6.96 (d, J = 7.5 Hz, 3H), 6.36 (s, 1H), 5.80 (s,
H), 4.06-3.85 (m, 2H), 3.21-3.15 (m, 2H), 2.41 (ABq, J = 27.4 Hz, J = 17.1 Hz, 2H), 2.25-2.23 (m,
): δ (ppm) 195.3, 178.0, 157.1, 152.5, 148.0,
1
5
1
2
1
3
H), 1.07 (s, 3H), 0.82 (s, 3H). C NMR (125 MHz, CDCl
3
144.9, 142.2, 135.5, 128.9, 125.9, 117.3, 115.0, 111.7, 110.5, 106.7, 50.0, 49.7, 41.3, 34.4, 32.2, 29.7,
8.2, 25.7, 20.9.
2
4
-(Furan-2-carbonyl)-8,8-dimethyl-5-(4-(trifluoromethyl)phenyl)-5,7,8,9-tetrahydro-1H-
thiazolo[3,2-a]quinolin-6(2H)-one (5au). (0.41 g, 89%), Yellow solid; mp 157.7-158.1 ˚C. IR (KBr) ʋ
-1
(cm ) 2959, 2924, 2853, 1626, 1474, 1380, 1325. 1H NMR (500 MHz, CDCl
3
): δ (ppm) 7.50 (s, 1H),
.45 (d, J = 5 Hz, 2H), 7.36 (d, J = 10 Hz, 2H), 7.03 (d, J = 3.5 Hz, 1H), 6.42-6.41 (m, 1H), 6.02 (s, 1H),
.15-4.10 (m, 1H), 3.99-3.94 (m, 1H), 3.25-3.20 (m, 2H), 2.53-2.42 (ABq, J = 35 Hz, J = 15 Hz, 2H),
): δ (ppm) 195.4, 177.9, 157.6,
7
4
2
1
2
1
3
.32-2.24 (m, 2H), 1.11 (s, 3H), 0.87 (s, 3H). C NMR (125 MHz, CDCl
3
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52.9, 149.7, 149.0, 145.2, 127.6, 125.4, 125.3, 117.7, 115.4, 111.9, 106.3, 50.1, 49.8, 40.6, 35.3, 32.4,
+
+
9.9, 28.4, 26.8. HRMS (ESI ): calcd for C25
H
23
F
3
NO S [M + H ], 474.1351; found, 474.1349.
3
5-(4-bromophenyl)-4-(furan-2-carbonyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-one
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
6
1
(5av). (0.37 g, 80%), Yellow solid; mp 140-143 °C (lit., 143-145 °C). H NMR (500 MHz, CDCl
3
): δ
(ppm) 7.48 (s, 1H), 7.31-7.25 (m, 2H), 7.10 (d, J = 8.1 Hz, 2H), 7.00 (d, J = 3.3 Hz, 1H), 6.42 (s, 1H),
5
.91 (s, 1H), 4.12-3.92 (m, 2H), 3.20-3.18 (m, 2H), 2.67-2.24 (m, 3H), 2.00-1.86 (m, 1H), 1.74 (s, 2H).
): δ (ppm) 195.3, 177.8, 157.1, 152.7, 150.3, 145.1, 131.2, 129.1, 120.0,
17.5, 116.6, 111.8, 111.5, 106.3, 49.6, 36.4, 34.7, 27.3, 26.8, 20.0.
13C NMR (125 MHz, CDCl
3
1
5-(4-Chloro-3-fluorophenyl)-4-(furan-2-carbonyl)-8,8-dimethyl-5,7,8,9-tetrahydro-1H-
thiazolo[3,2-a]quinolin-6(2H)-one (5aw). (0.38 g, 84%), Yellow solid; mp 143.6-144 ˚C. IR (KBr) ʋ
-1
1
(cm ) 2959, 2923, 2854, 1625, 1471, 1379, 1324. H NMR (500 MHz, CDCl
3
): δ (ppm) 7.42 (s, 1H),
7
2
.12-7.10 (m, 1H), 6.96-6.92 (m, 3H), 6.35 (s, 1H), 5.84 (s, 1H), 4.05-3.87 (m, 2H), 3.15-3.11 (m, 2H),
1
3
.45-2.33 (ABq, J
1
= 45 Hz, J = 15 Hz, 2H), 2.22-2.14 (m, 2H), 1.01 (s, 3H), 0.79 (s, 3H). C NMR
2
(125 MHz, CDCl
3
): δ (ppm) 195.4, 177.7, 158.9, 157.8, 156.9, 152.9, 149.1, 147.0, 145.2, 130.3, 123.8,
+
1
17.7, 115.5, 115.3, 112.0, 106.0, 50.0, 49.9, 40.5, 34.9, 32.3, 29.9, 28.3, 26.7. HRMS (ESI ): calcd for
+
C
24
H
22ClFNO S [M + H ], 458.0993; found, 458.0986.
3
8
,8-dimethyl-5-phenyl-4-(thiophene-2-carbonyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-
1
6
1
6(2H)-one (5ax). (0.35 g, 83%), Yellow solid; mp 243-245 °C (lit., 247-248 °C). H NMR (500 MHz,
CDCl ): δ (ppm) 7.42 (d, J = 4.5 Hz, 1H), 7.34 (d, J = 3.6 Hz, 1H), 7.21-7.12 (m, 5H), 6.93-6.91 (m,
H), 5.66 (s, 1H), 4.10- 4.04 (m, 1H), 3.96-3.86 (m, 1H), 3.26-3.18 (m, 2H), 2.49-2.16 (m, 4H), 1.06 (s,
3
1
3
1
1
3
H), 0.83 (s, 3H). C NMR (125 MHz, CDCl ): δ (ppm) 195.2, 183.0, 157.0, 147.7, 144.7, 144.0,
3
31.1, 130.6, 128.3, 127.7, 127.3, 126.3, 115.6, 106.2, 50.0, 49.7, 43.2, 35.5, 32.2, 29.7, 28.3, 26.6.
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,8-dimethyl-4-(thiophene-2-carbonyl)-5-p-tolyl-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-
16
1
6
(2H)-one (5ay). (0.30 g, 70%), Yellow solid; mp 198-200 °C (lit., 200-203 °C). H NMR (500 MHz,
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
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3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
CDCl ): δ (ppm) 7.41-7.36 (m, 2H),7.11-6.92 (m, 5H), 5.59 (s, 1H), 4.11-3.87 (m, 2H), 3.20-3.13 (m,
3
1
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
1
3
H), 2.50-2.24 (m, 7H), 1.03 (s, 3H), 0.85 (s, 3H). C NMR (125 MHz, CDCl ): δ (ppm) 195.0, 182.3,
3
57.1, 148.4, 143.7, 141.2, 135.1, 131.0, 130.1, 128.1, 127.3, 126.1, 115.2, 105.9, 49.6, 49.5, 39.8, 35.8,
1.8, 29.1, 28.0, 25.2, 20.5.
8,8-dimethyl-5-(2-nitrophenyl)-4-(thiophene-2-carbonyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-
16
1
a]quinolin-6(2H)-one (5az). (0.39 g, 85%), Brown solid; mp 243-245 °C (lit., 245-247 °C). H NMR
(
500 MHz, CDCl
3
): δ (ppm) 7.49-7.46 (m, 3H), 7.33-7.26 (m, 2H), 7.15 (d, J = 7.8 Hz, 1H), 7.02 (s,
= 27 Hz, J = 17.1 Hz, 2H), 2.15
= 16.0 Hz, 2H), 1.03 (s, 3H), 0.87 (s, 3H). C NMR (125 MHz, CDCl ): δ (ppm)
1
H), 6.11 (s, 1H), 4.19-3.98 (m, 2H), 3.69-3.45 (m, 2H), 2.45 (ABq, J
1
2
1
3
(ABq, J
1
= 23.5 Hz, J
2
3
1
1
94.7, 185.7, 151.4, 149.1, 147.7, 141.5, 138.4, 131.7, 131.4, 131.2, 129.7, 127.3, 127.2, 123.1, 112.4,
07.2, 50.0, 49.3, 41.0, 35.4, 31.9, 29.7, 27.8, 25.8.
8,8-dimethyl-5-(4-nitrophenyl)-4-(thiophene-2-carbonyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-
1
6
1
a]quinolin-6(2H)-one (5ba). (0.42 g, 90%), Yellow solid; mp 200–201°C (lit., 201-203 °C). H NMR
500 MHz, CDCl ): δ (ppm) 8.00 (d, J = 8.4 Hz, 2H), 7.51-7.29 (m, 4H), 6.99-6.96 (m, 1H), 5.87 (s,
H), 4.20-4.13 (m, 1H), 4.01-3.95 (m, 1H), 3.31-3.23 (m, 2H), 2.46 (ABq, J = 36.3 Hz, J = 17.4 Hz,
2H), 2.28 (distorted ABq, 2H), 1.10 (s, 3H), 0.81 (s, 3H). C NMR (125 MHz, CDCl ): δ (ppm) 195.0,
82.7, 155.8, 152.0, 149.5, 146.2, 143.2, 131.6, 130.2, 127.9, 127.8, 123.8, 123.7, 113.0, 105.3, 49.8,
9.7, 40.1, 36.2, 32.0, 29.8, 28.2, 25.2.
(
3
1
1
2
1
3
3
1
4
4
-(biphenylcarbonyl)-8,8-dimethyl-5-phenyl-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-
one (5bb). (0.39 g, 80%), Yellow solid; mp 191-193 °C (lit.,16 194-195 °C). H NMR (500 MHz,
1
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4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
CDCl ): δ (ppm) 7.61-7.34 (m, 10 H), 7.21-6.97 (m, 4H), 5.30 (s, 1H), 4.06-3.95 (m, 2H), 3.25-3.18 (m,
3
2
H), 2.46 (ABq, J
1
= 26.1 Hz, J
2
= 17.1 Hz, 2H), 2.21 (distorted ABq, 2H), 1.07 (s, 3H), 0.85 (s, 3H).
13C NMR (125 MHz, CDCl
): δ (ppm) 195.2, 194.0, 155.0, 148.0, 145.6, 142.6, 140.3, 138.1, 128.7,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
28.0, 127.8, 127.5, 127.2, 127.0, 126.5, 126.2, 115.3, 107.0, 50.0, 49.3, 40.7, 36.1, 32.2, 29.7, 28.2,
6.2.
2
4-(biphenylcarbonyl)-8,8-dimethyl-5-p-tolyl-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-
16
1
one (5bc). (0.40 g, 80%), Yellow solid; mp 231-235 °C (lit., 236-238 °C). H NMR (500 MHz,
CDCl ): δ (ppm) 7.61-7.33 (m, 9H), 6.92-6.86 (m, 4H), 5.26 (s, 1H), 4.07-4.02 (m, 2H), 3.27-3.23 (m,
H), 2.54-2.39 (m, 2H), 2.30-2.20 (m, 5H), 1.11 (s, 3H), 0.90 (s, 3H). C NMR (125 MHz, CDCl
ppm) 195.1, 194.0, 154.6, 147.1, 142.9, 141.7, 140.4, 138.3, 135.5, 128.9, 128.7, 127.9, 127.6, 127.1,
26.8, 115.8, 107.8, 50.0, 49.4, 40.5, 36.5, 32.0, 29.9, 28.3, 25.8, 20.7.
3
1
3
2
3
): δ
(
1
4-(biphenylcarbonyl)-8,8-dimethyl-5-(4-nitrophenyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-
16
1
a]quinolin-6(2H)-one (5bd). (0.41 g, 76%), Yellow solid; mp 232-234 °C (lit., 235-236 °C). H NMR
(500 MHz, CDCl ): δ (ppm) 7.94 (d, J = 8.7 Hz, 2H), 7.60-7.29 (m, 9H), 7.10 (d, J = 8.4 Hz, 2H), 5.41
s, 1H), 4.14-4.02 (m, 2H), 3.30-3.23 (m, 2H), 2.50 (ABq, J = 29.7, J = 17.4, 2H), 2.24 (ABq, J
= 16.2, 2H), 1.11 (s, 3H), 0.87 (s, 3H). C NMR (125 MHz, CDCl ): δ (ppm) 195.1, 193.7,
55.3, 152.9, 147.8, 146.3, 142.2, 140.0, 138.0, 128.7, 128.3, 127.8, 127.3, 127.1, 125.9, 123.5, 113.2,
3
(
1
2
1
=
13
2
1
8.2, J
2
3
106.8, 49.3, 40.8, 37.8, 31.3, 29.9, 27.2, 26.6.
4
-(1-naphthoyl)-8,8-dimethyl-5-p-tolyl-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-one
16
1
(
5be). (0.35 g, 73%), Yellow solid; mp 220-222 °C (lit., 222-224 °C). H NMR (500 MHz, CDCl
3
): δ
(ppm) 7.81-7.76 (m, 2H), 7.49-7.20 (m, 4H), 7.00 (d, J = 6.3 Hz, 1H), 6.70 (d, J = 7.5 Hz, 2H), 6.52 (d,
J = 7.8 H, 2H), 4.80 (s, 1H), 4.13-3.95 (m, 2H), 3.26-3.21 (m, 2H), 2.52-2.36 (m, 2H), 2.20-2.06 (m,
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13
5
H), 1.07 (s, 3H), 0.87 (s, 3H). C NMR (125 MHz, CDCl
3
): δ (ppm) 195.2, 194.6, 163.9, 154.4, 146.3,
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
43.2, 138.9, 135.3, 134.5, 130.2, 129.1, 128.4, 127.6, 127.5, 126.1, 125.8, 125.0, 124.9, 124.0, 115.4,
110.1, 50.0, 48.6, 40.9, 38.3, 32.2, 29.8, 28.2, 26.0, 20.7.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4-Acetyl-5-(4-methoxyphenyl)-8,8-dimethyl-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-
-1
one (5bf). (0.31 g, 80%), Yellow solid; mp 190.2-191.1 ˚C. IR (KBr) ʋ (cm ) 2958, 2923, 2853, 1597,
1
1
524, 1471, 1379, 1339. H NMR (500 MHz, CDCl
3
): δ (ppm) 7.18-7.16 (m, 2H), 6.77-6.75 (m, 2H),
5.13 (s, 1H), 4.11-4.07 (m, 1H), 3.90-3.84 (m, 1H), 3.75 (s, 3H), 3.25-3.14 (m, 2H), 2.47-2.40 (m, 2H),
13
2
1
.27-2.18 (m, 2H), 2.11 (s, 3H), 1.09 (s, 3H), 0.87 (s, 3H). C NMR (125 MHz, CDCl
3
): δ (ppm) 196.4,
95.6, 158.1, 152.4, 148.1, 137.8, 128.9, 116.1, 113.7, 108.8, 55.2, 50.1, 49.5, 40.8, 36.5, 32.4, 29.8,
+
+
28.2, 27.1, 27.0. HRMS (ESI ): calcd for C22
H
26NO S [M + H ], 384.1633; found, 384.1647.
3
4-Acetyl-8,8-dimethyl-5-(3-nitrophenyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-6(2H)-one
-1
(5bg). (0.33 g, 84%), Yellow solid; mp 183.1-184.0 ˚C. IR (KBr) ʋ (cm ) 2959, 2921, 2852, 1598,
1
1
525, 1471, 1380, 1339. H NMR (500 MHz, CDCl
3
): δ (ppm) 8.06-8.01 (m, 2H), 7.71-7.66 (m, 1H),
7.44-7.40 (m, 1H), 5.31 (s, 1H), 4.19-4.14 (m, 1H), 3.94-3.88 (m, 1H), 3.34-3.19 (m, 2H), 2.49-2.44 (m,
1
3
2
1
3
H), 2.29-2.18 (m, 2H), 2.10 (s, 3H), 1.11 (s, 3H), 0.86 (s, 3H). C NMR (125 MHz, CDCl
3
): δ (ppm)
95.5, 195.3, 153.8, 149.0, 148.6, 147.4, 134.3, 129.2, 122.7, 121.8, 114.8, 107.6, 49.8, 49.6, 40.8, 37.6,
+
+
2.4, 29.7, 28.2, 27.1, 27.0. HRMS (ESI ): calcd for C21
H
23
N
2
O S [M + H ], 399.1379; found,
4
399.1371.
4
-Acetyl-8,8-dimethyl-5-(2-hydroxy-5-nitrophenyl)-5,7,8,9-tetrahydro-1H-thiazolo[3,2-a]quinolin-
-1
6
1
7
(2H)-one (5bh). (0.35 g, 84%), Yellow solid; mp 186.8-187.0 ˚C. IR (KBr) ʋ (cm ) 2959, 2924, 2854,
1
598, 1525, 1472, 1380, 1340. H NMR (500 MHz, CDCl
3
): δ (ppm) 10.66 (b, 1H), 8.01-7.99 (m, 1H),
.72-7.71 (m, 1H), 7.01-6.99 (m, 1H), 5.14 (s, 1H), 4.26-4.21 (m, 1H), 4.02-3.96 (m, 1H), 3.40-3.23 (m,
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2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
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4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
13
2
H), 2.56 (b, 2H), 2.42-2.30 (m, 2H), 1.92 (s, 3H), 1.15 (s, 3H). C NMR (125 MHz, CDCl
3
): δ (ppm)
1
98.8, 195.4, 159.7, 153.1, 152.7, 133.3, 125.1, 124.7, 119.0, 114.1, 113.4, 108.4, 49.8, 49.1, 41.1, 32.3,
+
+
31.9, 28.3, 26.9, 26.3, 22.7. HRMS (ESI ): calcd for C21
H
23
N
2
O S [M + H ], 415.1328; found,
5
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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7
8
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0
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4
15.1340.
5
-(4-methoxyphenyl)-2,2-dimethyl-6-(4-(trifluoromethyl)benzoyl)-2,3-dihydro-1H-
benzo[4,5]thiazolo[3,2-a]quinolin-4(5H)-one (5bl). (0.12 g, 22%), Yellow solid; mp 225.1-226.2 ˚C. H
NMR (500 MHz, CDCl ): δ (ppm) 7.95-7.89 (m, 4H), 7.79-7.78 (m, 2H), 7.71-7.62 (m, 4H), 7.26-7.23
1
3
(m, 1H), 6.94-6.92 (m, 1H), 6.34 (s, 1H), 3.81 (s, 3H), 2.40-2.38 (m, 2H), 2.34-2.31 (m, 2H), 1.18 (s,
13
6
1
H). C NMR (125 MHz, CDCl
3
): δ (ppm) 202.1, 201.3, 177.9, 171.7, 160.1, 146.1, 141.2, 138.5,
37.5, 137.0, 135.3, 134.6, 134.0, 133.4, 131.3, 130.5, 128.8, 100.7, 52.5, 50.9, 38.1, 28.5, 28.4, 27.5.
+
+
HRMS (ESI ): calcd for C32
H
27
F
3
NO S [M + H ], 562.1664; found, 562.1672.
3
10-chloro-5-(4-methoxyphenyl)-2,2-dimethyl-6-(4-(trifluoromethyl)benzoyl)-2,3-dihydro-1H-
benzo[4,5]thiazolo[3,2-a]quinolin-4(5H)-one (5bm) (0.11 g, 20%), Yellow solid; mp 215.1-216.2 ˚C.
1H NMR (500 MHz, CDCl
H), 6.34 (s, 1H), 4.76 (s, 3H), 2.61 (b, 2H), 2.02 (b, 2H), 1.18 (s, 6H). C NMR (125 MHz, CDCl ): δ
): δ (ppm) 7.92-7.89 (m, 5H ), 7.79 (b, 2H), 7.65-7.62 (m, 3H), 7.25-7.19 (m,
3
1
3
1
3
(
ppm) 195.0, 193.8, 154.5, 150.1, 149.5, 139.0, 129.7, 128.0, 127.7, 127.7, 127.5, 127.2, 126.4, 124.8,
+
1
24.6, 124.5, 115.1, 106.6, 49.2, 36.9, 35.8, 27.6, 26.5, 20.1. HRMS (ESI ): calcd for C32
H26ClF
3
NO S
3
+
[
M + H ], 596.1274; found, 596.1281.
ASSOCIATED CONTENT
Supporting Information
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The Journal of Organic Chemistry
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Copies of H and C NMR spectra of all new compounds, TON and TOF of ionic liquids, TGA-DTA
data, structure of ionic liquids and dithioesters. The Supporting Information is available free of charge
on the ACS Publications website.
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AUTHOR INFORMATION
Corresponding Author
*
E-mail: mayashankarbhu@gmail.com; mssingh@bhu.ac.in Fax: +91-542-2368127
ORCID ID:
Anshu Singh: 0000-0002-6370-2531
Abhijeet Srivastava: 0000-0001-5118-7539
Maya Shankar Singh: 0000-0002-3199-0823
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We acknowledge the financial support from the Science and Engineering Research Board
(
SERB/EMR/2015/002482), New Delhi and the Council of Scientific and Industrial Research
02(0263)/16/EMR-II), New Delhi, India. A. Singh and A. Srivastava gratefully acknowledge the UGC
(
(DSKPDF) and CSIR, New Delhi for research fellowship, respectively.
REFERENCES
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