One-Pot Synthesis of Benzothiazole-Tethered Chromanones/Coumarins via Claisen Rearrangement Using the Solid State Melt Reaction

Article abstract of DOI:10.1021/acs.joc.5b02920

A novel protocol has been successfully established for the efficient synthesis of benzothiazole-tethered chromanone/coumarin scaffolds via Claisen rearrangement using a solid state melt reaction in a one-pot manner. Benzothiazole formation and Claisen rearrangement involve the cleavage of S-S and C-O bonds and formation of C-S, C=N, and C-C bonds in a single operation without using a catalyst or solvent.

Full text of DOI:10.1021/acs.joc.5b02920

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Note
One Pot Synthesis of Benzothiazole Tethered Chromanones /
Coumarins via Claisen Rearrangement Using Solid State Melt Reaction
Manickam Bakthadoss, and RAMAN SELVAKUMAR
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02920 • Publication Date (Web): 18 Mar 2016
Downloaded from http://pubs.acs.org on March 19, 2016
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One Pot Synthesis of Benzothiazole Tethered Chromanones / Coumarins via Claisen
Rearrangement Using Solid State Melt Reaction
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Manickam Bakthadossa* and Raman Selvakumarb
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aDepartment of Chemistry, Pondicherry University, Pondicherry ꢀ 605 014, India
bDepartment of Organic Chemistry, University of Madras, Guindy Campus, Chennaiꢀ600 025,
Tamilnadu, India
ABSTRACT
A novel protocol has been successfully established for the efficient synthesis of
benzothiazole tethered chromanone / coumarin scaffolds via Claisen rearrangement using a solid
state melt reaction (SSMR) in one pot manner. Benzothiazole formation and Claisen
rearrangement involves the cleavage of S–S and C–O bonds, formation of C–S, C=N and C–C
bonds in a single operation without using catalyst and solvent.
The rapid synthesis of functionalized organic molecular building blocks, intermediates
and bioactive molecular entities represents an important endeavor in organic synthesis,1aꢀd
particularly in targetꢀoriented synthesis. Among pericyclic reactions, [3,3]ꢀsigmatropic
rearrangements are the most powerful and straightforward synthetic tool utilized for the atomꢀ
economical synthesis of many natural and bioactive molecules.1e,1f For instance, the Claisen
rearrangement is a very important and useful synthetic tool widely exploited for the synthesis of
library of natural products and bioactive scaffolds through C–C bond formation.1g It is well clear
from the literature that the Claisen rearrangement is found to be one of the prominent reaction in
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synthetic chemistry since its introduction in 19721e and known to delineate widespread
applications in preparative chemistry.2
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Benzothiazole derivatives are known to be the integral part of a wide variety of natural
products, bioactive compounds and industrial chemicals. They are widely used in many
industries, for example, 2ꢀmercaptobenzothiazole, cambendazole, and thiabendazole3 are
effectively utilized as rubber vulcanization accelerators and as slimicides in paper and pulp
industry.3
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Chromanone and coumarin units belong to privileged scaffold of various natural
products. Most of these compounds are well screened for their biological properties and found to
be useful in cancer treatment,4a antibacterial,4b antifungal,4b autoimmune,4b inflammatory
diseases,5 estrogenic,5 antilipoperoxidant,5 antiplatelet,5 antiviral,5 antihemolytic5 and
antiallergic.5
Claisen rearrangement is one of the key reactions available for the synthesis of numerous
natural products1f such as acorone, homogynolide B and pancratistatin. Benzothiazole,
chromanone and coumarin moieties are identified as the core unit of several natural products and
bioactive molecules particularly, Geiparvarin (I),6a 1ꢀisopropylꢀ2ꢀmethyleneꢀ1,2ꢀdihydroꢀ3Hꢀ
benzo[f]chromenꢀ3ꢀone (II) [antiꢀtumor agent],6b isodispar B (III),6c 3ꢀ(benzo[d]thiazolꢀ2ꢀyl)ꢀ7ꢀ
hydroxycoumarin (IV) [antiꢀproliferative agent],6d Dꢀluciferin (V)6e and CJM 126 (VI) [antiꢀ
cancer agent]6f are shown in Figure 1 as representatives. Due to the significance of these
interesting bioactivities, several research groups have been interested towards the syntheses of
chromanones,6g coumarins6h and benzothiazole based heterocycles.6i
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Figure 1. Natural products and bioactive molecules containing chromanone, coumarin and
benzothiazole units.
Since the Claisen rearrangement is widely exploited for the synthesis of variety of
heterocyclic compounds with various biological applications,1e,1f we envisaged that the Baylisꢀ
Hillman derivatives8cꢀe,9 can be utilized for the synthesis of chromanone / coumarin frameworks
through Claisen rearrangement. As a part of our continual effort in the field of solidꢀstate melt
reaction (SSMR)7 and heterocyclic chemistry,8 here in, we describe a simple and novel method
for the synthesis of benzothiazole tethered chromanone / coumarin scaffolds using Solid State
Melt Reaction (SSMR). This new protocol involves benzothiazole formation, Claisen
rearrangement and intramolecular lactonization for the formation of benzothiazole tethered
chromanone / coumarin scaffolds via SSMR in one pot manner for the first time. We envisaged
that the BaylisꢀHillman8cꢀe,9 derivative 1a and disulfide 2 will be the suitable substrates for
making an array of benzothiazole tethered chromanone / coumarin scaffolds.
To execute our idea, we have prepared disulfide 2 from aminothiophenol under aerobic
oxidation10 and melted with BaylisꢀHillman9 derivative 1a at different temperature levels, the
best result was obtained when we carried out the reaction without catalyst and solvent at 180oC
for 1 h which successfully led to the formation of Claisen rearrangement product (4a). The
reaction probably proceeded via benzothiazole formation and Claisen rearrangement.
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Interestingly, the benzothiazole formation and Claisen rearrangement carried out by the
cleavage of disulfide S–S, Oꢀallyl C–O bonds and formation of thiazole C–S, C=N and arylꢀ
allylic C–C bonds in a single step process. After the formation of compound 4a, the crude
reaction mixture was further treated with Con. H2SO4 (1 mmol) in DCM as a solvent at room
temperature for 1 h in oneꢀpot manner which successfully afforded the desired benzothiazole
tethered chromanone (5a) in 79% yield (Table 1) along with minor benzothiazole product (6a) in
9% yield. This type of domino benzothiazole formation and Claisen rearrangement followed by
lactonization in one pot is new and not known so far in the literature. It is surprising to note that
this novel protocol provides a single product even though multiple reaction sites are present in
the reactants with comparable reactivities. Interestingly, the first two parts of the protocol does
not involve any solvent and catalyst even though both the reactants (1a and 2) are solid in nature.
Delighted by this result, we have employed various Baylis–Hillman derivatives8cꢀe,9 (1b-
p) under the optimized reaction conditions which smoothly provided the desired functionalized
chromanones (5b-p) in very good yields (73–78%) along with minor benzothiazoles (6a and 6b)
in 9ꢀ12% yields. The results are summarized in Table 1. Based on the results, electron donating
and withdrawing group in the aryl moiety does not have any remarkable difference in the
reactivities on Claisen rearrangement. Further, the structure of compound 5b was confirmed by
singleꢀcrystal Xꢀray11 analysis (see the Supporting Information ꢀ Figure S1).
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Table 1. Synthesis of Benzothiazole Tethered Chromanones (5a-p)a,b,c
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aAll reactions were carried out on 1 mmol of BꢀH derivative (1a-p) with 0.5 mmol of compound
b
2 at 180 °C for 1 h. Further, 1 mmol of Con. H2SO4 was added. Isolated yields of the pure
products. cAll the new compounds were fully characterized (see the Supporting Information).
Based on this successful result, we have employed several Baylis–Hillman derivatives8cꢀ
e,9
(7a-i), possessing nitrile functionality. Accordingly, we melted BꢀH derivatives (7a-i) with
disulfide (2) in the round bottom flask at 180oC for 1 h which successfully led to the Claisen
rearrangement products tethered with benzothiazole moiety (9). In the same round bottom flask,
potassium tertꢀbutoxide (2 equiv.) was added in THF as a solvent and stirred at room
temperature for 2 h which successfully afforded the benzothiazole tethered coumarin scaffolds
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10a-i in 74ꢀ78% yields (Table 2) along with minor benzothiazole (6a) in 9ꢀ11% yields. It is
interesting to note that, the olefinic double bond in the Claisen rearrangement product (9) got
isomerized and formed coumarin moiety 10. The structure of 10d was confirmed by singleꢀ
crystal Xꢀray11 analysis (see the Supporting Information ꢀ Figure S2).
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Table 2. Synthesis of Benzothiazole Tethered Coumarins (10a-i)a,b,c
NH2
N
O
S
CHO
O
S
S
CN
H2
N
CN
2 (solid)
R2
8a-i
melt, 180oC, 1h
R2
7a-i (solid)
N
S
N
t-BuO- K+
,
S
N
S
+
O
THF, 2h, rt
OH
CN
O
R2
OH
R2
9a-i
6a (9-11%)
10a-i (74-78%)
aAll reactions were carried out on 1 mmol of BꢀH derivative (7a-i) with 0.5 mmol of compound
2 at 180 °C for 1 h. Further, 2 mmol of potassium tertꢀbutoxide was added. bIsolated yields of the
c
pure products. All the new compounds were fully characterized (see the Supporting
Information).
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To understand the reaction pathway, we have isolated Claisen rearrangement product 4a
and treated with Con. H2SO4 (1 mmol) which efficiently led to anticipated chromanone
derivative (5a) in excellent yield (95%). Subsequently, we also treated Claisen product 9a
containing nitrile functionality with 2 equivalent potassium tertiary butoxide smoothly provided
the coumarin derivative (10a) in excellent yield (92%) as shown in Scheme 1. It is remarkable, to
note that the Claisen rearrangement products on BꢀH derivatives with ester functionality led to
chromanone derivative (5a) with exo methylene double bond, whereas the Claisen rearrangement
on BꢀH derivatives with nitrile functionality led to the formation of coumarin derivative (10a) in
which the double bond migrated to the lactone ring system.
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Scheme 1. Synthesis of Chromanone and Coumarin Derivatives (5a and 10a) from Claisen
Rearrangement Products (4a and 9a)
After the successful synthesis of orthoꢀmigrated Claisen rearrangement products from
BaylisꢀHillman derivatives, we turned our attention towards the para migrated Claisen
rearrangement product which can be achieved from the ortho substituted BaylisꢀHillman
derivatives8cꢀe,9 via Claisen rearrangement using SSMR.
To accomplish this idea, we treated ortho substituted BaylisꢀHillman derivative 1q with
disulfide (2) at 180oC for 1 h which successfully afforded the desired para migrated Claisen
rearrangement product tethered with benzothiazole (13a) in 75% yield along with minor product
6c (benzothiazole) in 12% yield. Encouraged by this result, we have treated couple of ortho
substituted BaylisꢀHillman derivatives (1r and 1s) with disulfide (2) at 180oC for 1 h, which
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smoothly afforded the anticipated para migrated Claisen rearrangement products (13b and 13c)
in 74 and 76% yields (Table 3) along with minor product 6c (benzothiazole) in 10ꢀ14% yields.
Table 3. para Claisen Rearrangement Products (13a-c)a,b via Solid State Melt Reaction
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aAll
reactions
were
carried
out
on
1
mmol
of
BꢀH
derivative
(1q-s ) with 0.5 mmol of compound (2) at 180 °C for 1 h. bIsolated yields of the pure products.
To further expand the generality of the para migration in the Claisen rearrangement, we
have decided to engage the ortho substituted Baylis–Hillman derivatives8cꢀe,9 bearing nitrile
functionality. Accordingly, we subjected the ortho substituted Baylis–Hillman derivatives (7j-l)
with disulfide (2) at 180oC for 1 h which smoothly led to the desired para migrated Claisen
rearrangement products (16a-c) in 70ꢀ76% yields (Table 4) along with minor benzothiazole (6c)
product in 10ꢀ15% yields. The structure of 16c was confirmed by singleꢀcrystal Xꢀray11 analysis
(see the Supporting Information ꢀ Figure S3).
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Table 4. para Claisen Rearrangement Products (16a-c)a,b via Solid State Melt Reaction
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OH
N
OH
N
OH
N
EtO
EtO
EtO
S
S
S
CN
CN
CN
Me
Cl
16b, 75%
16a, 76%
16c, 70%
aAll reactions were carried out on 1 mmol of BꢀH derivative (7j-l) with 0.5 mmol of compound
(2) at 180 °C for 1 h. bIsolated yields of the pure products.
Finally, we also examined the BaylisꢀHillman derivative (1a) for the Claisen
rearrangement without disulfide (2). Accordingly, the BꢀH derivative 1a melted at 220oC for 1 h
which led to the desired diaryl vinyl methane derivative (17a) in 63% yield via Claisen
rearrangement as shown in Scheme 2.
Scheme 2. Claisen Rearrangement in B-H Derivative 1a.
In conclusion, we have developed a novel and efficient protocol for the facile
construction of benzothiazole tethered chromanone and coumarin frameworks via benzothiazole
formation, Claisen rearrangement and lactonization reaction sequence in one pot fashion utilizing
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BaylisꢀHillman derivatives (BꢀH) for the first time. Notably, the first two steps of the protocol
carried out through a solid state melt reaction which does not require catalyst and solvent even
though all the starting materials are solids. We also utilized ortho substituted BaylisꢀHillman
derivatives for the para Claisen rearrangement products (para migration) with diverse
functionalities in good yields. It is surprising to note that this new protocol provides a single
product even though various reactive functionalities are present in the reactants with comparable
reactivities. This novel protocol also opens new avenues for making a library of wide variety of
diversified chromanone/coumarin scaffolds for biological screening.
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EXPERIMENTAL SECTION
General Information. All reagents were procured from commercial sources and utilized without
further purification. Solvents were distilled prior to use. Silica gel used for Column
chromatography purification as stationary phase. FTIRꢀ spectrophotometer was used for IR
1
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spectral studies. H NMR (300 and 400 MHz) and C NMR (75 and 100 MHz) were recorded
using CDCl3 as solvent and TMS as an internal standard; chemical shifts are reported in δ (ppm).
Mass spectra were recorded on a QTOF mass spectrometer using the electrospray ionization
(ESI) mode. Melting points were uncorrected. Thinꢀlayer chromatography (TLC) was performed
using glass plates coated with silica gel (254F). Spots were visualized using UV lamp and iodine
vapour. The single crystal Xꢀray diffraction measurements were carried on a graphite
monochromatic MoKα radiation and CCD detector.
Typical Experimental Procedure for the Synthesis of Compound 5a
A mixture of (E)ꢀmethylꢀ2ꢀ((2ꢀformylphenoxy)methyl)ꢀ3ꢀphenylacrylate (1a, 1mmol), and 2ꢀ(2ꢀ
(2ꢀminophenyl)disulfanyl)benzenamine (2, 0.5 mmol) was placed in a round bottom flask and
melted at 180 ºC for 1 h. After formation of the Claisen rearrangement product as indicated by
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TLC, the crude product was further treated with Con.H2SO4 in DCM at room temperature for 1
h. After completion of the reaction as indicated by TLC, the reaction mixture was concentrated
and the resulting crude mass was diluted with water (10 mL) and extracted with ethyl acetate (3
x 10 mL). The combined organic layers were washed with brine (2 x 10 mL) and dried over
anhydrous Na2SO4. The crude reaction mass was purified by column chromatography on silica
gel (Acme 60ꢀ120 mesh), using ethyl acetate : hexanes (1 : 9) to afford 5a as a colourless solid in
79% yield.
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Methyl 2ꢀ((3ꢀ(benzo[d]thiazolꢀ2ꢀyl)ꢀ2ꢀhydroxyphenyl)(phenyl)methyl)acrylate (4a).
White solid: (84%, 0.337g); mp: 143ꢀ145 °C; Reaction time: 1h; 1H NMR (300 MHz, CDCl3): δ
13
3.70 (s, 3H), 5.28 (s, 1H), 5.93 (s, 1H), 6.45 (s, 1H), 6.84 – 7.90 (m, 12H), 13.00 (s, 1H) ; C
NMR (75 MHz, CDCl3) : δ 45.6, 52.0, 116.5, 118.9, 121.5, 122.0, 125.5, 126.6, 126.7, 127.0,
127.1, 128.4, 129.1, 130.9, 132.4, 132.6, 140.8, 142.8, 151.6, 155.5, 167.3, 169.4; IR (KBr):
1623, 1712, 3415 cmꢀ1; HRMS calculated for C24H20NO3S [M+H]+ 402.1164, found 402.1174.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ3ꢀmethyleneꢀ4ꢀphenylchromanꢀ2ꢀone (5a).
1
White solid: (79%, 0.29g); mp: 137ꢀ139 °C; Reaction time: 2h; H NMR (300 MHz, CDCl3): δ
13
5.03 (s, 1H), 5.82 (s, 1H), 6.55 (s, 1H), 7.17 – 8.52 (m, 12H) ; C NMR (75 MHz, CDCl3) : δ
48.3, 121.5, 122.5. 123.1, 124.9, 125.2, 125.7, 126.2, 127.8, 127.8, 129.2, 130.1, 130.7, 135.8,
136.4, 139.7, 148.1, 152.1, 161.4, 161.6; IR (KBr): 1631, 1724, 3015 cmꢀ1; HRMS calculated for
C23H16NO2S [M+H]+ 370.0902, found 370.0894.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ3ꢀmethyleneꢀ4ꢀoꢀtolylchromanꢀ2ꢀone (5b).
White solid : (73%, 0.27g); mp : 148ꢀ150 °C; Reaction time : 2h; 1H NMR (300 MHz, CDCl3) :
δ 2.28 (s, 3H), 5.29 (s, 1H), 5.55 (s, 1H), 6.58 (s, 1H), 6.95 – 8.48 (m, 11H); 13C NMR (75 MHz,
CDCl3): δ 20.3, 45.1, 121.5, 122.3, 123.1, 124.8, 125.2, 125.7, 126.2, 126.9, 128.0, 129.0, 129.9,
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130.1, 130.3, 131.5, 135.0, 136.4, 136.5, 137.4, 148.1, 152.2, 161.3, 161.5; IR (KBr) : 1632,
1720, 3026 cmꢀ1; HRMS calculated for C24H18NO2S [M+H]+ 384.1058, found 384.1052.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ3ꢀmethyleneꢀ4ꢀpꢀtolylchromanꢀ2ꢀone (5c).
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White solid : (76%, 0.29g); mp : 147ꢀ149 °C; Reaction time : 2h; 1H NMR (400 MHz, CDCl3) :
δ 2.36 (s, 3H), 5.03 (s, 1H), 5.84 (s, 1H), 6.57 (s, 1H), 7.08 ꢀ8.53 (m, 11H); 13C NMR (100 MHz,
CDCl3) : δ 21.1, 48.0, 121.6, 122.6, 123.2, 125.0, 125.3, 126.1, 126.3, 127.8, 129.2, 130.0, 130.1,
130.8, 136.1, 136.5, 136.8, 137.7, 148.2, 152.3, 161.5, 161.9; IR (KBr) : 1636, 1794, 3018 cmꢀ1;
HRMS calculated for C24H18NO2S [M+H]+ 384.1058, found 384.1048.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(4ꢀethylphenyl)ꢀ3ꢀmethylenechromanꢀ2ꢀone (5d).
White solid : (74%, 0.29g); mp : 146ꢀ148°C; Reaction time : 2h; 1H NMR (300 MHz, CDCl3) :
δ 1.21 (t, J = 7.5 Hz, 3H), 2.62 (q, J = 7.5 Hz, 2H), 4.99 (s, 1H), 5.81 (s, 1H), 6.53 (s, 1H), 7.06 ꢀ
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8.51 (m, 11H); C NMR (75 MHz, CDCl3) : δ 15.4, 28.4, 48.0, 121.5, 123.1, 124.8, 125.2,
126.0, 126.2, 126.7, 127.7, 128.6, 129.1, 129.9, 130.7, 136.0, 136.4, 136.9, 143.9, 148.1, 152.1,
161.4, 161.7; IR (KBr) : 1635, 1728, 3025 cmꢀ1; HRMS calculated for C25H20NO2S [M+H]+
398.1215, found 398.1216.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(4ꢀisopropylphenyl)ꢀ3ꢀmethylenechromanꢀ2ꢀone (5e).
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White solid: (76%, 0.31g); mp: 145ꢀ147 °C; Reaction time: 2h; H NMR (400 MHz, CDCl3): δ
1.15 (d, J = 6.4 Hz, 6H), 2.80 (sep, J = 6.8 Hz, 1H), 4.93 (s, 1H), 5.75 (s, 1H), 6.43 (s, 1H), 7.00
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– 8.42 (m, 11H). C NMR (100 MHz, CDCl3) : δ 24.0, 33.8, 48.1, 121.6, 122.6, 123.2, 125.0,
125.3, 126.1, 126.3, 127.3, 127.8, 129.2, 130.0, 130.8, 136.1, 136.5, 137.0, 148.2, 148.6, 152.3,
161.6, 162.0; IR (KBr): 1625, 1738, 3030 cmꢀ1; HRMS calculated for C26H22NO2S [M+H]+
412.1371, found 412.1382.
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8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ3ꢀmethyleneꢀ4ꢀ(naphthalenꢀ2ꢀyl)chromanꢀ2ꢀone (5f).
White solid : (73%, 0.30g); mp : 136ꢀ138 °C; Reaction time : 2h; 1H NMR (400 MHz, CDCl3) :
δ 5.55 (d, J = 1.5 Hz, 1H), 5.76 (s, 1H), 6.57 (d, J = 1.8 Hz, 1H), 6.91ꢀ8.48 (m, 14H); 13C NMR
(100 MHz, CDCl3) : δ 45.9, 121.7, 122.5, 123.3, 125.0, 125.0, 125.4, 125.8, 125.8, 126.0, 126.3,
126.4, 128.8, 129.2, 129.3, 129.5, 130.4, 130.5, 131.1, 134.6, 134.8, 134.9, 136.6, 148.0, 152.4,
161.6, 161.7; IR (KBr) : 1635, 1730, 3026 cmꢀ1; HRMS calculated for C27H18NO2S [M+H]+
420.1058, found 420.1062.
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8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(4ꢀfluorophenyl)ꢀ3ꢀmethylenechromanꢀ2ꢀone (5g).
White solid : (76%, 0.29g); mp : 139ꢀ141 °C; Reaction time : 2h; 1H NMR (400 MHz, CDCl3) :
δ 5.02 (s, 1H), 5.81 (s, 1H), 6.55 (s, 1H), 7.02 ꢀ 8.51 (m, 11H); 13C NMR (100 MHz, CDCl3) : δ
47.6, 116.2 (d, 2JCꢀF = 21 Hz), 121.7, 122.8, 123.3, 125.1, 125.6, 126.3, 127.6, 129.2, 129.5,
129.6, 129.7, 130.3, 130.6, 135.4, 135.9, 136.5, 148.2, 152.3, 161.7, 161.7, 162.6 (d, 1JCꢀF =
223 Hz); IR (KBr) : 1630, 1740, 3033 cmꢀ1; HRMS calculated for C23H15FNO2S [M+H]+
388.0808, found 388.0825.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(2ꢀchlorophenyl)ꢀ3ꢀmethylenechromanꢀ2ꢀone (5h).
White solid : (75%, 0.30g); mp : 143ꢀ145 °C; Reaction time : 2h; 1H NMR (300 MHz, CDCl3) :
δ 5.66 (s, 1H), 5.90 (s, 1H), 6.61 (s, 1H), 7.12 ꢀ8.51 (11H); 13C NMR (75 MHz, CDCl3) : δ 44.5,
121.5, 122.4, 123.1, 124.8, 125.0, 125.2, 126.2, 127.8, 129.1, 129.3, 130.0, 130.4, 131.2, 133.5,
134.1, 136.4, 138.1, 148.3, 152.2, 161.0, 161.4; IR (KBr): 1645, 1730, 3026 cmꢀ1; HRMS
calculated for C23H15ClNO2S [M+H]+ 404.0512, found 404.0500.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(3ꢀchlorophenyl)ꢀ3ꢀmethylenechromanꢀ2ꢀone (5i).
White solid : (77%, 0.31g); mp : 142ꢀ144 °C; Reaction time : 2h; 1H NMR (300 MHz, CDCl3) :
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δ 5.00 (s, 1H), 5.85 (s, 1H), 6.58 (s, 1H), 7.04 ꢀ8.54 (m, 11H); C NMR (75 MHz, CDCl3) : δ
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47.9, 121.5, 122.7, 123.1, 124.9, 125.0, 125.3, 125.9, 126.2, 128.0, 128.1, 129.5, 130.49, 130.6,
130.7, 135.1, 135.2, 136.4, 141.7, 148.1, 152.1, 161.2, 161.3; IR (KBr) : 1645, 1740, 3031 cmꢀ1;
HRMS calculated for C23H15ClNO2S [M+H]+ 404.0512, found 404.0503.
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8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(4ꢀchlorophenyl)ꢀ3ꢀmethylenechromanꢀ2ꢀone (5j).
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White solid : (75%, 0.30g); mp : 141ꢀ143 °C, Reaction time : 2h; H NMR (300 MHz, CDCl3) :
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δ 5.00 (s, 1H), 5.82 (s, 1H), 6.56 (s, 1H), 7.09 ꢀ8.53 (m, 11H); C NMR (75 MHz, CDCl3) : δ
47.7, 121.5, 122.7, 123.2, 125.0, 125.2, 125.3, 126.2, 129.2, 129.4, 129.4, 130.3, 130.5, 133.8,
135.5, 136.4, 138.1, 148.1, 152.2, 161.2, 161.3; IR (KBr) : 1647, 1741, 3031 cmꢀ1; HRMS
calculated for C23H15ClNO2S [M+H]+ 404.0512, found 404.0504.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(2,4ꢀdichlorophenyl)ꢀ3ꢀmethylenechromanꢀ2ꢀone (5k).
White solid : (75%, 0.32g); mp : 140ꢀ142 °C; Reaction time : 2h; 1H NMR (300 MHz, CDCl3) :
δ 5.61 (s, 1H), 5.89 (s, 1H), 6.61 (s, 1H), 7.02 – 8.52 (m, 10 H); 13C NMR (75 MHz, CDCl3) : δ
44.1, 121.5, 122.6, 123.2, 124.3, 125.1, 125.3, 126.3, 128.2, 129.6, 130.2, 130.2, 130.8, 131.5,
133.7, 134.2, 134.4, 136.4, 136.7, 148.2, 152.1, 160.8, 161.2; IR (KBr) : 1650, 1743, 3036 cmꢀ1;
HRMS calculated for C23H14Cl2NO2S [M+H]+ 438.0122, found 438.0123.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(3ꢀbromophenyl)ꢀ3ꢀmethylenechromanꢀ2ꢀone (5l).
White solid : (74%, 0.33g); mp : 152ꢀ156 °C; Reaction time : 2h; 1H NMR (300 MHz, CDCl3) :
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δ 4.99 (s, 1H), 5.85 (s, 1H), 6.58 (s, 1H), 7.07 – 8.54 (m, 11H); C NMR (75 MHz, CDCl3) : δ
47.8, 121.5, 122.7, 123.2, 123.2, 124.8, 125.0, 125.3, 126.2, 126.4, 129.5, 130.6, 130.7, 130.9,
131.0, 135.2, 136.4, 142.0, 148.0, 152.2, 161.2, 161.3; IR (KBr) : 1625, 1730, 3026 cmꢀ1; HRMS
calculated for C23H15BrNO2S [M+H]+ 448.0007, found 448.0012.
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8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ3ꢀmethyleneꢀ4ꢀ(4ꢀnitrophenyl)chromanꢀ2ꢀone (5m).
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White solid : (78%, 0.32g); mp : 156ꢀ158 °C; Reaction time : 2h; 1H NMR (300 MHz, CDCl3) :
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δ 5.16 (s, 1H), 5.92 (s, 1H), 6.63 (s, 1H), 7.22ꢀ8.57 (m, 11H); C NMR (75 MHz, CDCl3) : δ
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48.0, 121.5, 123.0, 123.2, 124.2, 124.4, 125.2, 125.4, 126.3, 128.7, 129.9, 130.4, 131.2, 134.6,
136.4, 146.9, 147.5, 148.0, 152.2, 160.9; IR (KBr) : 1635, 1720, 3029 cmꢀ1; HRMS calculated
for C23H15N2O4S [M+H]+ 415.0753, found 415.0754.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ6ꢀbromoꢀ3ꢀmethyleneꢀ4ꢀphenylchromanꢀ2ꢀone (5n).
White solid: (76%, 0.33g); mp: 151ꢀ153 °C; Reaction time: 2h; 1H NMR (300 MHz, CDCl3) : δ
5.00 (s, 1H), 5.82 (s, 1H), 6.57 (s, 1H), 7.16 – 8.68 (11H); 13C NMR (75 MHz, CDCl3) : δ 48.1,
117.8, 121.6, 123.3, 124.2, 125.5, 126.4, 127.7, 127.8, 128.1, 129.4, 130.9, 131.5, 132.9, 135.1,
136.5, 139.0, 147.1, 152.0, 159.7, 161.0; IR (KBr): 1635, 1737, 3026 cmꢀ1; HRMS calculated
for C23H15BrNO2S [M+H]+ 448.0007, found 448.0005.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ6ꢀbromoꢀ4ꢀ(4ꢀethylphenyl)ꢀ3ꢀmethylenechromanꢀ2ꢀone (5o).
White solid: (77%, 0.36g); mp: 150ꢀ152 °C; Reaction time: 2h; 1H NMR (300 MHz, CDCl3) : δ
1.35 (t, J = 7.5 Hz, 3H), 2.78 (q, J = 7.5 Hz, 2H), 4.97 (s, 1H), 5.82 (s, 1H), 6.55 (s, 1H), 7.06 –
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8.15 (9H), 8.79 (s, 1H); C NMR (75 MHz, CDCl3) : δ 15.0, 28.7, 47.8, 117.1, 121.5, 121.6,
123.2, 123.3, 124.4, 125.6, 126.5, 127.7, 128.2, 128.6, 128.8, 131.3, 131.4, 132.8, 132.9, 136.5,
145.3, 152.1, 159.4; IR (KBr) : 1625, 1734, 3026 cmꢀ1; HRMS calculated for C25H19BrNO2S
[M+H]+ 476.0320, found 476.0323.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ6ꢀbromoꢀ4ꢀ(4ꢀchlorophenyl)ꢀ3ꢀmethylenechromanꢀ2ꢀone (5p).
White solid : (78%, 0.37g); mp : 149ꢀ151 °C; Reaction time : 2h; 1H NMR (300 MHz, CDCl3) :
δ 4.98 (s, 1H), 5.82 (s, 1H), 6.59 (s, 1H), 7.10 – 8.15 (m, 9H), 8.69 (s, 1H); 13C NMR (75 MHz,
CDCl3): δ 47.5, 117.9, 121.6, 122.2, 123.3, 125.6, 126.0, 126.5, 127.0, 128.8, 129.2, 129.6,
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130.4, 131.8, 132.8, 134.7, 137.4, 147.0, 151.9, 159.6, 160.7; IR (KBr) : 1628, 1740, 3029 cmꢀ1;
HRMS calculated for C23H14BrClNO2S [M+H]+ 481.9617, found 481.9612.
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Typical Experimental Procedure for the Synthesis of Compound 10a.
A mixture of (E)ꢀ2ꢀ((2ꢀformylphenoxy)methyl)ꢀ3ꢀphenylacrylonitrile (7a, 1mmol), 2ꢀ(2ꢀ(2ꢀ
minophenyl)disulfanyl)benzenamine (2, 0.5 mmol) was placed in a round bottom flask and
melted at 180 ºC for 1 h. After formation of the Claisen product as indicated by TLC, the crude
product was further treated with potassium tertiary butoxide in THF at room temperature for 2 h.
After the completion of the reaction as showed by TLC, the reaction mixture was concentrated
and the resulting crude mass was diluted with water (10 mL) and extracted with ethyl acetate (3
x 10 mL). The combined organic layers were washed with brine (2 x 10 mL) and dried over
anhydrous Na2SO4. The crude reaction mass was purified by column chromatography on silica
gel (Acme 60ꢀ120 mesh), using ethyl acetate : hexanes (1 : 9) to afford 10a as a colourless solid
in 78% (0.28 g) yield.
2ꢀ((3ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ2ꢀhydroxyphenyl)(phenyl)methyl)acrylonitrile (9a).
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White solid: (86%, 0.31g); mp : 140ꢀ142 °C, Reaction time : 1h; H NMR (300 MHz, CDCl3) :
δ 5.58 (s, 1H), 5.62 (d, J = 1.5Hz, 1H), 6.14 (d, J = 0.9Hz, 1H), 6.92 – 7.94 (12H), 13.06 (s, 1H);
13C NMR (75 MHz, CDCl3) : δ 48.2, 116.8, 118.8, 119.3, 121.5, 122.1, 125.2, 125.7, 126.8,
127.4, 127.8, 128.1, 128.8, 128.9, 132.4, 132.4, 132.6, 138.5, 151.6, 155.6, 169.2; IR (KBr) :
1625, 2230, 3421 cmꢀ1; HRMS calculated for C23H17N2OS [M+H]+ 369.1062, found 369.1069.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ3ꢀmethylꢀ4ꢀphenylꢀ2Hꢀchromenꢀ2ꢀone (10a).
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White solid : (78%, 0.28g); mp : 161ꢀ163 °C, Reaction time : 3h; H NMR (300 MHz, CDCl3) :
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δ 2.03 (s, 3H), 7.08 – 8.63 (12H); C NMR (75 MHz, CDCl3) : δ 14.8, 121.3, 121.6, 123.1,
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123.2, 123.9, 125.2, 126.2, 128.2, 128.3, 128.8, 129.0, 129.3, 130.7, 134.8, 136.4, 149.7, 150.6,
152.1, 160.7, 160.8; IR (KBr) : 1625, 1740, 3036 cmꢀ1; HRMS calculated for C23H16NO2S
[M+H]+ 370.0902, found 370.0907.
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8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ3ꢀmethylꢀ4ꢀpꢀtolylꢀ2Hꢀchromenꢀ2ꢀone (10b).
White solid: (78%, 0.29g); mp: 160ꢀ162 °C; Reaction time: 3h; 1H NMR (300 MHz, CDCl3): δ
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2.03 (s, 3H), 2.46 (s, 3H), 6.98 – 8.49 (m, 11H) ; C NMR (75 MHz, CDCl3) : δ 15.6, 21.3,
120.4, 121.4, 122.1, 122.9, 123.1, 124.2, 125.2, 126.2, 128.7, 129.0, 129.5, 129.6, 132.5, 136.0,
138.2, 143.3, 149.5, 152.2, 159.5, 161.2; IR (KBr) : 1624, 1728, 3026 cmꢀ1; HRMS calculated
for C24H18NO2S [M+H]+ 384.1058, found 384.1048.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(4ꢀethylphenyl)ꢀ3ꢀmethylꢀ2Hꢀchromenꢀ2ꢀone (10c).
White solid : (76%, 0.30g); mp : 159ꢀ161 °C; Reaction time : 3h; 1H NMR (300 MHz, CDCl3) :
δ 1.34 (t, J = 7.5 Hz, 3H), 2.06 (s, 3H), 2.77 (q, J = 7.5 Hz, 2H), 7.17 – 8.66 (m, 11H); 13C NMR
(75 MHz, CDCl3) : δ 14.8, 15.3, 28.7, 121.5, 121.6, 123.1, 123.2, 123.8, 125.2, 126.2, 128.3,
128.4, 129.4, 130.6, 132.0, 136.4, 145.0, 149.7, 150.9, 152.2, 160.8, 161.0; IR (KBr) : 1621,
1720, 3016 cmꢀ1; HRMS calculated for C25H20NO2S [M+H]+ 398.1215, found 398.1221.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(4ꢀisopropylphenyl)ꢀ3ꢀmethylꢀ2Hꢀchromenꢀ2ꢀone (10d).
White solid : (75%, 0.30g); mp : 156ꢀ158 °C; Reaction time : 3h; 1H NMR (400 MHz, CDCl3) :
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δ 1.34 (d, J = 6.8 Hz, 6H), 2.07 (s, 3H), 3.02 (sep, J = 6.8 Hz, 1H), 7.15 – 8.65 (m, 11H); C
NMR (100 MHz, CDCl3) : δ 15.1, 24.1, 34.1, 121.6, 121.8, 123.3, 123.4, 124.0, 125.4, 126.4,
127.0, 127.1, 128.5, 128.9, 129.6, 130.8, 132.2, 136.6, 149.8, 151.1, 152.3, 161.1, 161.1; IR
(KBr) : 1631, 1731, 3027 cmꢀ1; HRMS calculated for C26H22NO2S [M+H]+ 412.1371, found
412.1395.
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8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(2ꢀmethoxyphenyl)ꢀ3ꢀmethylꢀ2Hꢀchromenꢀ2ꢀone (10e).
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White solid: (74%, 0.29g); mp : 166ꢀ168 °C; Reaction time : 3h; 1H NMR (300 MHz, CDCl3) : δ
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2.02 (s, 3H), 3.79 (s, 3H), 6.91 – 7.96 (m, 11H); C NMR (75 MHz, CDCl3) : δ 18.6, 55.6,
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111.0, 111.3, 111.5, 117.0, 118.9, 120.5, 121.0, 121.5, 122.2, 123.1, 125.7, 126.8, 127.7, 128.6,
129.1, 129.7, 130.1, 130.6, 132.6., 133.1, 154.6, 156.6; IR (KBr) : 1641, 1730, 3041 cmꢀ1;
HRMS calculated for C24H18NO3S [M+H]+ 400.1007, found 400.1016.
4ꢀ(Benzo[d][1,3]dioxolꢀ5ꢀyl)ꢀ8ꢀ(benzo[d]thiazolꢀ2ꢀyl)ꢀ3ꢀmethylꢀ2Hꢀchromenꢀ2ꢀone (10f).
White solid: (74%, 0.30g); mp : 168ꢀ170 °C; Reaction time : 3h; 1H NMR (400 MHz, CDCl3) :
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δ 2.09 (s, 3H), 6.09 (s, 2H), 6.72 – 8.64 (m, 10H); C NMR (100 MHz, CDCl3) : δ 15.0, 101.7,
109.0, 121.6, 121.8, 121.8, 122.2, 123.3, 123.7, 124.1, 125.4, 126.4, 128.3, 129.4, 130.9, 136.9,
140.6, 148.1, 148.3, 152.3, 160.9, 160.9; IR (KBr) : 1631, 1739, 3046 cmꢀ1; HRMS calculated
for C24H16NO4S [M+H]+ 414.0800, found 414.0795.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(2ꢀchlorophenyl)ꢀ3ꢀmethylꢀ2Hꢀchromenꢀ2ꢀone (10g).
White solid : (75%, 0.30g); mp : 163ꢀ165 °C; Reaction time : 3h; 1H NMR (400 MHz, CDCl3) :
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δ 2.05 (s, 3H), 7.09 – 8.68 (m, 11H); C NMR (100 MHz, CDCl3) : δ 15.0, 121.2, 121.8, 123.3,
123.4, 123.8, 124.2, 125.5, 126.4, 129.1, 129.5, 129.9, 130.0, 131.0, 131.1, 133.4, 135.2, 136.7,
138.7, 138.9, 149.9, 160.7, 160.9; IR (KBr) : 1634, 1747, 3031 cmꢀ1; HRMS calculated for
C23H15ClNO2S [M+H]+ 404.0512, found 404.0515.
8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(3ꢀchlorophenyl)ꢀ3ꢀmethylꢀ2Hꢀchromenꢀ2ꢀone (10h).
White solid : (76%, 0.30g); mp : 162ꢀ164 °C; Reaction time : 3h; 1H NMR (300 MHz, CDCl3) :
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δ 2.00 (s, 3H), 6.88 – 8.49 (m, 11H); C NMR (75 MHz, CDCl3) : δ 15.6, 120.6, 121.4, 121.5,
122.2, 123.1, 123.2, 125.2, 126.3, 127.0, 128.6, 128.7, 128.8, 129.9, 130.3, 132.9, 135.0, 136.0,
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137.3, 141.7, 149.4, 152.1, 161.0; IR (KBr) : 1639, 1740, 3036 cmꢀ1; HRMS calculated for
C23H15ClNO2S [M+H]+ 404.0512, found 404.0538.
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8ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ4ꢀ(4ꢀchlorophenyl)ꢀ3ꢀmethylꢀ2Hꢀchromenꢀ2ꢀone (10i).
White solid : (75%, 0.30g); mp : 163ꢀ165 °C; Reaction time : 3h; 1H NMR (300 MHz, CDCl3) :
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δ 2.01 (s, 3H), 6.97 – 7.95 (m, 11H); C NMR (75 MHz, CDCl3) : δ 14.8, 121.6, 122.2, 123.2,
124.0, 125.3, 125.9, 126.9, 128.6, 129.4, 129.8, 130.0, 130.9, 133.0, 135.0, 137.6, 149.4, 151.5,
154.7, 160.5, 160.7 ; IR (KBr) : 1639, 1740, 3036 cmꢀ1; HRMS calculated for C23H15ClNO2S
[M+H]+ 404.0512, found 404.0548.
Typical Experimental Procedure for the Synthesis of Compound 13a.
A mixture of (E)ꢀmethyl 2ꢀ((3ꢀethoxyꢀ2ꢀformylphenoxy)methyl)ꢀ3ꢀphenylacrylate (1r, 1mmol),
and 2ꢀ(2ꢀ(2ꢀminophenyl)disulfanyl)benzenamine (0.5 mmol) was placed in a round bottom flask
and melted at 180 ºC for 1 h. After completion of the reaction as indicated by TLC, The crude
reaction mass was purified by column chromatography on silica gel (Acme 60ꢀ120 mesh), using
ethylacetate : hexanes (0.5 : 9.5) to afford 13a as a colourless solid in 75% (0.33 g) yield.
(E)ꢀMethyl 2ꢀ(3ꢀ(benzo[d]thiazolꢀ2ꢀyl)ꢀ5ꢀethoxyꢀ4ꢀhydroxybenzyl)ꢀ3ꢀphenylacrylate (13a).
White solid: (75%, 0.33g); mp : 147ꢀ149 °C; Reaction time : 1h; 1H NMR (300 MHz, CDCl3) : δ
1.48 (t, J = 6.9 Hz, 3H), 3.80 (s, 3H), 3.92 (s, 2H), 4.10 (q, J = 6.9 Hz, 2H), 6.81 – 7.97 (m,
13
12H), 12.64 (br s, 1H); C NMR (75 MHz, CDCl3) : δ 14.8, 32.5, 52.2, 64.7, 115.9, 116.6,
118.9, 121.4, 122.1, 125.4, 126.6, 128.7, 128.8, 129.1, 130.1, 130.8, 132.7, 135.3, 141.1, 146.9,
148.2, 151.8, 168.5, 169.4; IR (KBr) : 1625, 1715, 3426 cmꢀ1; HRMS calculated for C26H24NO4S
[M+H]+ 446.1426, found 446.1437.
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(E)ꢀMethyl 2ꢀ(3ꢀ(benzo[d]thiazolꢀ2ꢀyl)ꢀ5ꢀethoxyꢀ4ꢀhydroxybenzyl)ꢀ3ꢀoꢀtolylacrylate (13b).
White solid : (74%, 0.33g); mp : 144ꢀ146 °C; Reaction time : 1h; 1H NMR (300 MHz, CDCl3) :
δ 1.47 (t, J = 6.9 Hz, 3H), 2.30 (s, 3H), 3.71 (s, 3H), 3.80 (s, 2H), 4.07 (q, J = 6.9 Hz, 2H), 6.46 –
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7.94 (m, 11H), 12.61 (br s, 1H); C NMR (75 MHz, CDCl3) : δ 14.8, 20.0, 32.4, 52.1, 64.7,
116.5, 119.2, 121.4, 122.1, 125.4, 125.9, 126.6, 128.1, 128.6, 130.2, 130.6, 132.6, 134.9, 136.6,
140.3, 143.2, 146.8, 148.0, 148.3, 151.8, 168.3, 169.4; IR (KBr) : 1625, 1720, 3421 cmꢀ1; HRMS
calculated for C27H26NO4S [M+H]+ 460.1583, found 460.1585.
(E)ꢀMethyl 2ꢀ(3ꢀ(benzo[d]thiazolꢀ2ꢀyl)ꢀ5ꢀethoxyꢀ4ꢀhydroxybenzyl)ꢀ3ꢀpꢀtolylacrylate (13c).
White solid : (76%, 0.34g); mp : 142ꢀ144 °C; Reaction time : 1h; 1H NMR (300 MHz, CDCl3) :
δ 1.47 (t, J = 6.6 Hz, 3H), 2.35 (s, 3H), 3.79 (s, 3H), 3.93 (s, 2H), 4.09 (q, J = 6.6 Hz, 2H), 6.83 –
13
7.94 (m, 11H), 12.53 (br s, 1H); C NMR (75 MHz, CDCl3) : δ 14.8, 21.3, 32.5, 52.1, 64.7,
116.0, 116.7, 118.9, 121.4, 122.1, 125.4, 126.6, 129.2, 129.4, 129.8, 130.2, 132.5 132.7, 139.1,
141.3, 147.0, 148.2, 151.8, 168.7, 169.5; IR (KBr) : 1619, 1710, 3410 cmꢀ1; HRMS calculated for
C27H26NO4S [M+H]+ 460.1583, found 460.1596.
Typical Experimental Procedure for the Synthesis of Compound 16a.
A mixture of (E)ꢀ2ꢀ((2ꢀethoxyꢀ6ꢀformylphenoxy)methyl)ꢀ3ꢀphenylacrylonitrile (7j, 1mmol), and
2ꢀ(2ꢀ(2ꢀminophenyl)disulfanyl)benzenamine (0.5 mmol) was placed in a round bottom flask and
melted at 180 ºC for 1 h. After completion of the reaction as indicated by TLC, The crude
reaction mass was purified by column chromatography on silica gel (Acme 60ꢀ120 mesh), using
ethylacetate : hexanes (0.5 : 9.5) to afford 16a as a colourless solid in 76% (0.31 g) yield.
(Z)ꢀ2ꢀ(3ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ5ꢀethoxyꢀ4ꢀhydroxybenzyl)ꢀ3ꢀphenylacrylonitrile (16a).
White solid : (76%, 0.31g); mp : 139ꢀ141°C; Reaction time : 1h; 1H NMR (400 MHz, CDCl3) : δ
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1.57 (t, J = 6.8 Hz, 3H), 3.75 (s, 2H), 4.22 (q, J = 6.8 Hz, 2H), 6.94 – 8.04 (m, 12H); C NMR
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(100 MHz, CDCl3) : δ 14.9, 41.8, 65.0, 110.7, 116.3, 116.9, 120.1, 121.6, 122.3, 125.7, 126.8,
127.2, 128.8, 129.0, 130.3, 132.8, 133.5, 144.1, 148.0, 148.7, 151.8, 169.1; IR (KBr) : 1635,
2239, 3426 cmꢀ1 ; HRMS calculated for C25H21N2O2S [M+H]+ 413.1324, found 413.1322.
(Z)ꢀ2ꢀ(3ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ5ꢀethoxyꢀ4ꢀhydroxybenzyl)ꢀ3ꢀpꢀtolylacrylonitrile (16b).
White solid : (75%, 0.31g); mp : 138ꢀ140 °C; Reaction time : 1h; 1H NMR (400 MHz, CDCl3) :
δ 1.51 (t, J = 6.8 Hz, 3H), 2.37 (s, 3H), 3.68 (s, 2H), 4.17 (q, J = 6.8 Hz, 2H), 6.87 – 8.00 (m,
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11H), 12.76 (brs, 1H); C NMR (100 MHz, CDCl3) : δ 14.9, 21.6, 41.8, 65.0, 109.4, 116.3,
117.0, 120.2, 121.6, 122.4, 125.7, 126.9, 127.4, 128.9, 129.7, 130.9, 132.8, 140.8, 144.2, 148.0,
151.8, 169.1; IR (KBr) : 1632, 2231, 3410 cmꢀ1; HRMS calculated for C26H23N2O2S [M+H]+
427.1480, found 427.1493.
(Z)ꢀ2ꢀ(3ꢀ(Benzo[d]thiazolꢀ2ꢀyl)ꢀ5ꢀethoxyꢀ4ꢀhydroxybenzyl)ꢀ3ꢀ(4ꢀchlorophenyl)acrylonitrile
(16c).
White solid : (70%, 0.31g); mp : 138ꢀ140 °C; Reaction time : 1h; 1H NMR (300 MHz, CDCl3) :
δ 1.50 (t, J = 6.9 Hz, 3H), 3.66 (s, 2H), 4.13 (q, J = 6.9 Hz, 2H), 6.86 – 7.97 (m, 11H), 12.77 (br
s, 1H); 13C NMR (75 MHz, CDCl3) : δ 14.8, 41.6, 64.9, 111.3, 116.9, 120.0, 121.5, 122.2, 125.6,
125.7, 126.7, 126.9, 129.1, 129.2, 129.9, 130.0, 131.9, 132.6, 136.1, 142.6, 148.6, 151.6, 168.8;
IR (KBr) : 1633, 2246, 3424 cmꢀ1; HRMS calculated for C25H20ClN2O2S [M+H]+ 447.0934,
found 447.0937.
Typical Experimental Procedure for the Synthesis of Compound 17a.
(E)ꢀMethylꢀ2ꢀ((2ꢀformylphenoxy)methyl)ꢀ3ꢀphenylacrylate (1a, 1mmol), was placed in a round
bottom flask and melted at 220 ºC for 1 h. After completion of the reaction as indicated by TLC,
The crude reaction mass was purified by column chromatography on silica gel (Acme 60ꢀ120
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mesh), using ethylacetate : hexanes (0.5 : 9.5) to afford 17a as a semiꢀsolid in 63% (0.18 g)
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yield.
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Methyl 2ꢀ((3ꢀformylꢀ2ꢀhydroxyphenyl)(phenyl)methyl)acrylate (17a).
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White semiꢀsolid: (63%, 0.18g); Reaction time: 1h; H NMR (300 MHz, CDCl3): δ 3.69 (s, 3H),
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5.23 (s, 1H), 5.79 (s, 1H), 6.44 (s, 1H), 6.93 – 7.48 (m, 8H), 9.89 (s, 1H), 11.41 (s, 1H). C
NMR (75 MHz, CDCl3): δ 44.8, 52.0, 119.3, 120.4, 126.8, 127.4, 128.5, 129.0, 130.8, 132.3,
136.4, 140.2, 142.3, 159.1, 167.0, 196.5; IR (KBr): 1613, 1710, 3411 cmꢀ1; HRMS calculated for
C18H17O4 [M+H]+ 297.1127, found 297.1111.
ASSOCIATED CONTENT
The Supporting Information is available free of charge on the ACS Publications website at DOI:.
1H NMR, 13C NMR and mass spectra of all new compounds.
Xꢀray crystallographic data (CIF files) for compounds 5b, 10d and 16c
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: bhakthadoss@yahoo.com
ACKNOWLEDGMENT
We thank DST, New Delhi for the financial support. We also thank DSTꢀFIST for the
NMR facility. R.S thanks CSIR for his SRF fellowship.
REFERENCES
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(11) Structures were confirmed by singleꢀcrystal Xꢀray data. CCDC numbers for 5b, 10d and
16c are 1036725, 1036724 and 1036726 respectively.
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