Novel betaines/mesoionic compounds via a simple and convenient MCR in aqueous micellar system: Synthesis of thiazolo[2,3-a]isoquinolin-4-ium derivatives

Article abstract of DOI:10.1016/j.tetlet.2014.03.122

An inexpensive one-pot green methodology has been developed for the synthesis of thiazolo[2,3-a]isoquinolin-4-ium derivatives by the reaction of different derivatives of isoquinoline and 2-bromoacetophenone/bromoacetonitrile with benzoyl isothiocyanate in aqueous micellar medium.

Full text of DOI:10.1016/j.tetlet.2014.03.122

Accepted Manuscript
Novel betaines/mesoionic compounds via a simple and convenient MCR in
aqueous micellar system: Synthesis of thiazolo[2,3-a]isoquinolin-4-ium deriv-
atives
Arindam Maity, Debanjana Chakraborty, Abhijit Hazra, Yogesh P. Bharitkar,
Sandip Kundu, Prakas R. Maulik, Nirup B. Mondal
PII:
S0040-4039(14)00554-1
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.03.122
TETL 44444
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
8 February 2014
27 March 2014
28 March 2014
Please cite this article as: Maity, A., Chakraborty, D., Hazra, A., Bharitkar, Y.P., Kundu, S., Maulik, P.R., Mondal,
N.B., Novel betaines/mesoionic compounds via a simple and convenient MCR in aqueous micellar system: Synthesis
of thiazolo[2,3-a]isoquinolin-4-ium derivatives, Tetrahedron Letters (2014), doi: http://dx.doi.org/10.1016/j.tetlet.
2014.03.122
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical abstract
Novel betaines/mesoionic compounds via a simple and convenient
MCR in aqueous micellar system: Synthesis of thiazolo[2,3-
a]isoquinolin-4-ium derivatives
Arindam Maity, Debanjana Chakraborty, Abhijit Hazra, Yogesh P. Bharitkar, Sandip Kundu,
Prakas R. Maulik, Nirup B. Mondal*
R3
R2
O
O
R3
N
Br
O
Amberlite IRA 402(OH)
CTAB, Water, 1.5h
N
+
+
N
O
R1
N C S
R2
S
R1
1 (a-c)
2 (a-f)
3
4 (a-p)
1

Novel betaines/mesoionic compounds via a simple and convenient
MCR in aqueous micellar system: Synthesis of thiazolo[2,3-
a]isoquinolin-4-ium derivatives
Arindam Maity, Debanjana Chakraborty, Abhijit Hazra, Yogesh P. Bharitkar, Sandip Kundu,
Prakas R. Maulik, Nirup B. Mondal*
Department of Chemistry, Indian Institute of Chemical Biology, Council of Scientific and
Industrial Research, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, India.
Abstract: An inexpensive one-pot green methodology has been developed for the synthesis of
thiazolo[2,3-a]isoquinolin-4-ium derivatives by the reaction of different derivatives of
isoquinoline and 2-bromoacetophenone/ bromoacetonitrile with benzoyl isothiocyanate in
aqueous micellar medium.
Keywords: Multicomponent reaction; 1,3-dipolar cycloaddition; thiazolo[2,3-a]isoquinolin-4-
ium; benzoyl isothiocyanate; mesoionic; aqueous micellar system.
Mesoionic compounds (MICs) are mesomeric betaines in which both positive and negative
charges are delocalized and have been known for more than a century.1,2 MICs have always
remained the centre of attraction to the chemists because of the bonding aspects associated with
their unusual structure. These are also regarded as mesomeric heterocyclic betaines, strongly
stabilized by π-electron delocalization and having large dipole moments.3 Among the various
synthetic approaches to mesoionic heterocycles, the 1,3 dipolar cycloaddition reactions were
widely employed and most of those are concerned with the formation of münchnones (1,3-
*Corresponding author. Dr. Nirup B. Mondal,
Indian Institute of Chemical Biology,
4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, India.
FAX: +91-33-2473-5197; Tel+91-33-2473-3491: E.Mail: nirup@iicb.res.in
2

oxazolium-5-olates) and the newer isomünchnones (1,3-oxazolium-4-olates). Some research
involving the mesoionic sydnones (1,2,3-oxadiazolium-5-olates), thiomünchnones (1,3-
oxathiolium-5-olates), and thioisomünchnones (1,3-thiazolium-4-olates) have also appeared in
the literature.4 In recent years, the related fused ring system of thiazolo[2,3-a]isoquinolin-4-ium
has received much attention, as the derivatives display various applications,5 but surprisingly,
work concerning the synthesis of this ring system exists scantily.6 However, preparative methods
involving cyclo-condensation reactions of 3,4-dihydroisoquinoline
/
3,4-dihydroiso-
thiocarbostyril or N-thioacylated phenyl ethylamine derivatives with α-mercapto-acids / esters,7
β-mercaptoacid halides,8 ethylene sulfide9,10 or α-haloacids / acid halides11-13 respectively have
been reported for partially hydrogenated racemic compounds. Kroehnke and coworkers have
prepared similar ring system by treatment of N-arylmethyl- and N-acylmethyl isoquinolinium
salts with carbon disulfide and alkali.14 An asymmetric synthesis of thiazolo[2,3-a]isoquinoline
derivatives involving the reaction of 6,7-dimethoxy-3,4-dihydroisoquinoline and (−)-methyl
thioglycolate also appeared in the literature.15
We felt that an eco- friendly, flexible and efficient synthetic protocol needed to be established for
this type of compounds as the current trend in organic chemistry is to establish methods of ring
formation from simple starting materials in fewer steps and using environmentally benign
conditions. In this regard, water16 is being preferred as solvent because it is abundant in nature,
has virtually no cost, and is safest among all available solvents, thus leading to environmentally
benign chemical processes.17 But the solubility of organic compounds in water is very poor
because of its hydrophobicity. Through the introduction of micelles18 as the reaction media,
which work both by solubilization due to hydrophobic effect and by counter ion binding due to
3

electrostatic forces, this problem of hydrophobicity has been minimized. The solubilization of
water-insoluble reactants and products inside the micelles results not only in high concentration
due to the small volume, but also in different orientations of the soluble molecules that influence
the reaction mechanism, resulting in remarkable differences in reaction rate and selectivity than
would be observed in a homogeneous system.19 It has also been established that chemical
reaction in aqueous micellar condition rather than in organic solvents results in better yield
because the insolubility of the final product in water allows easy isolation of the compound in
most of the cases. In continuation of our search in the area of 1,3-dipolar cycloaddition mostly
exploiting this approach,20 we herein report an efficient and environment-friendly methodology
for the synthesis of 3-benzoyl-2-(benzoylamido)-thiazolo[2,3-a]isoquinolin-4-ium [4a] (Figure
1) employing an isoquinolinium ylide (generated in situ from isoquinoline and phenacyl
bromide) and an activated dienophile (benzoyl isothiocyanate) in micellar solution at ambient
temperature (Scheme 1).
O
N
N
S
O
Figure 1. 3-benzoyl-2-(benzoylamido)-thiazolo[2,3-a]isoquinolin-4-ium [4a].
R3
R2
O
O
R3
N
Br
O
Amberlite IRA 402(OH)
CTAB, Water, 1.5h
N
+
+
N
O
R1
N C S
R2
S
R1
1 (a-c)
2 (a-f)
3
4 (a-p)
Scheme1. Synthesis of 4(a-p) in aqueous micellar medium
4

At the outset, we chose isoquinoline (1a), phenacyl bromide (2a) and benzoyl isothiocyanate (3)
as model reactants in presence of a base, Amberlite IRA 402(OH), for the synthesis of the
thiazolo[2,3-a]isoquinolin-4-ium 4a. These were reacted in water at room temperature for
different time periods to evaluate the effect of various conditions. We also investigated the
reactions systematically in aqueous solutions of cationic, anionic, and nonionic surfactants well
above their critical micellar concentrations (CMC) in order to study the effect of surfactant
solutions (Table-1).
The results revealed that reactions carried out without a surfactant were ineffective (Table 1,
entry 1); no reaction occurred even after prolonged time period. Gratifyingly, adding the
surfactant cetyl trimethyl ammonium bromide (CTAB: cmc value 0.92 mM) 21 to the system at a
concentration of 40 mM furnished 20% (entry 2) of the desired product 4a after 1.5 h of reaction.
Raising the concentration of CTAB to 60 mM further enhanced the yield to 55% (entry 3), but
the best result (yield 90%) was obtained when the concentration was raised to 80 mM (entry 4).
Table 1. Reaction monitored by using different surfactants
Entrya
Surfactant
Concentrationb (mM)
Yieldc of 4a
1
2
3
4
5
6
7
8
9
10
None
-
NRd
20
55
90
90
90
40
75
55
50
CTAB
CTAB
CTAB
CTAB
CTAB
TTAB
TTAB
Triton X-114
SDS
40
60
80
90
100
50
80
80
80
aReaction performed using 1a, 2a, and 3 in water at room temperature for 1.5 h in presence of
Amberlite IRA 402(OH)
bConcentrations of different surfactants (CTAB, SDS, TTAB and Triton-X).
cYield of isolated product.
dNo reaction.
5

No significant improvement in the yield was observed on further increase in the concentration to
90 mM (entry 5) or 100 mM (entry 6). We also used another surfactant tetradecyltrimethyl-
ammonium bromide (TTAB: cmc value 3.8 mM) 22 at concentrations of 50 mM and 80 mM, but
the yields that resulted were not satisfactory enough (40% for entry 7, 75% for entry 8). Use of
23
the nonionic surfactant Triton X-114 (cmc 0.28 mM)
and the anionic surfactant sodium
dodecylsulfate (SDS: cmc value 8.1 mM) 24 at 80 mM concentration also proved unsatisfactory,
furnishing the product to the extent of 55% (Table 1, entry 9) and 50% (Table 1, entry 10).
Using CTAB, reactions were then performed in the presence of different bases like DBU, NEt3,
DABCO, DMAP, piperidine, K2CO3, and Amberlite IRA-402(OH) resin. The Amberlite IRA-
402(OH) resin (Table 2, entries 1–8) was found to be the most effective base. It produced no side
reaction, gave maximum yield of the product repeatedly even when reused, and was cost
effective. But for other bases there were different side reactions and various colour formations
which also affected in lowering the yield of the product.
Table 2. Reaction monitored by using different bases
Entrya
Base
Time (h)
Yieldb of 4a
1
2
3
4
5
6
7
8
DBU
NEt3
DABCO
DMAP
Piperidine
K2CO3
Amberlite IRA-402(OH)
Amberlite IRA-402(OH)
4
4
3
3
9
5
4
1.5
65
70
65
60
70
50
90
90
aReaction performed using 1a, 2a, and 3 in water in presence of CTAB at room temperature.
bYield refers to pure products after crystallization.
After work-up of the reaction, the resin was recovered by filtration and thoroughly washed with
ethanol followed by alkaline water. It was then dried at 80 °C under reduced pressure for 2 h and
6

reused for subsequent runs. It was observed that after five-time use of the resin, there is a slight
decrease in the yield (91–67%) of the fused quinolinium products (Figure 2). Though the
mechanism is not yet established, the plausible pathway of the reaction is depicted in Scheme 2.
Figure 2. Reusability of the Amberlite IRA 402 (OH) resin. The reactions were performed with
1a (1 mmol), 2a (1 mmol) and 3 (1 mmol) successively using 350 mg Amberlite IRA 402 (OH)
resin at room temperature for 1.5 h.
To establish the generality and scope of this green MCR, we employed different derivatives of
isoquinoline and phenacyl bromide to carry out reactions with benzoyl isothiocyanate under the
optimized condition. We extend the number of derivatives by replacing phenacyl bromide to
bromo acetonitrile in two derivatives. The results are summarized in Table 3.
O
N
N
O
1a
CTAB, Water
[3+2]
N
O
N
+
O
S C N
cycloaddition
Amberlite IRA
402(OH)
S
O
Br
3
4a
2a
Scheme 2. Mechanistic pathway for Amberlite IRA 402 (OH) mediated 3-benzoyl
2(benzoylamido)-thiazolo[2,3-a]isoquinolin-4-ium [4a] formation.
7

1
13
The structures of compounds 4(a–r) were deduced from their mass, H NMR and C NMR
spectral data.25 The mass spectra of these compounds displayed molecular ion peaks at the
expected m/z values. Finally, the crystal structure of one of the products (4i) was conclusively
proved through X-ray diffraction analysis (Figure 3).
Table 3: Synthesis of thiazolo[2,3-a]isoquinolin-4-ium derivatives
Entrya N heterocycle
Phenacyl bromide benzoyl isothiocyanate
Yieldb(%)
R3
O
R2
N
O
N
R3
R2
Br
R1
R1
S
O
N
C
S
O
N
1
1a (R1 = H)
2a (R2=R3= H)
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
4a (R1=R2=R3=H)
85
90
87
91
90
82
86
90
83
80
90
84
85
87
82
86
2
1a
1a
1a
1a
1a
2b (R2 = CH3, R3= H)
2c (R2 = F, R3= H)
2d (R2 = Cl, R3= H)
2e (R2 = R3= Cl)
4b (R1=R3=H, R2=CH3)
4c (R1=R3=H, R2=F)
3
4
4d (R1=R3=H, R2=Cl)
5
4e (R1=H, R2= R3= Cl)
4f (R1= R3= H, R2=NO2)
4g (R1=Br, R2=R3=H)
6
2f (R2 = NO2, R3= H)
7
1b (R1 = 4-Br) 2a
8
1b
2b
4h (R1=Br, R2=CH3, R3=H)
4i (R1=Br, R2= F, R3=H)
4j (R1=Br, R2=Cl, R3= H)
4k (R1=Br, R2=R3=Cl)
4l (R1=Br, R2=NO2, R3= H)
4m (R1=Br, R2=R3=H)
4n (R1=Br, R2=CH3, R3=H)
4o (R1=Br, R2= F, R3=H)
4p (R1=Br, R2=Cl, R3= H)
9
1b
2c
10
11
12
13
14
15
16
1b
2d
1b
2e
1b
2f (R2 = NO2, R3= H)
1c (R1 = 5-Br)
2a
2b
2c
2d
1c
1c
1c
8

N
N
N
R1
S
Br
O
N
17
18
1a
1b
2g
2g
3
3
4q (R1=H)
4r (R1=Br)
85
80
aReaction condition: isoquinoline (1 mmol), phenacyl bromide (1 mmol), benzoyl isothiocyanate (1 mmol), CTAB
(4 mmol) and water (50 ml), in air for 1.5 h at room temperature.
bYield of isolated pure product.
Figure 3. ORTEP diagram showing the molecular structure of 4i at 30% probability level with
atomic numbering scheme of the non-hydrogen atoms
In summary, we have demonstrated a simple, convenient, and efficient one step methodology for
an environment friendly synthesis of thiazolo[2,3-a]isoquinolin-4-ium, a new group of mesoionic
compounds. The notable features are moderate reaction conditions, greater selectivity, and
operational simplicity that make it an attractive and useful process for the synthesis of newer
heteroaromatics of various applications.
Acknowledgments
The authors express their gratitude to the Director, IICB for laboratory facilities, the Council of
Scientific and Industrial Research (CSIR) for providing fellowships (to A.M., Y.B., and A.H.)
and an Emeritus Scientist scheme (to Dr Nirup Bikash Mondal and Dr. Prakas R. Maulik) and
Indian Council of Medical research(ICMR) for providing fellowships to D.C. We are indebted to
9

Dr. T. Sarkar and Mr. K. Sarkar for recording the spectra and Dr. B. Achari, former Emeritus
Scientist, CSIR, for his valuable suggestions.
Supplementary data
13
1H and CNMR spectra of all new compounds associated with this article can be found in the
online version. Crystallographic data in CIF format are available free of charge via the Internet at
CCDC 952393 contains the supplementary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033;
or deposit@ccdc.cam.ac.uk).
Reference
1. (a) Fischer, E.; Besthorn, E. Über die Hydrazinverbindungen. Ann, 1882, 212, 316-339. (b)
IUPAC. Compendium of Chemical Terminology (the ‘Gold Book’). 2nd ed. Compiled by
McKnight AD, Wilkinson A. Oxford: Blackwell Scientific Publications 1997.
2. (a) Schönberg, A. J. Chem. Soc. 1938, 824-825.; (b) Baker, W.; Ollis, W.D. Mesoionic
Compounds. Quart. Rev. 1957, 11, 15-29; (c) Ollis, W. D.; Ramsden, C. A. Mesoionic
Compounds. Adv. Heterocycl. Chem. 1976, 19, 3-122.
3. De Athayde, P. F.; Miller, J.; Simas, A. M. Synthesis 2000, 11, 1565-1568.
4. (a) Potts, K. T. 1, 3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley-Interscience:
New York, NY, 1984; Vol. 2, Chapter 8; (b) Padwa, A. 1, 3-Dipolar Cycloaddition
Chemistry; Wiley-Interscience: New York, NY, 1984; Vols. 1 and 2; (c) Gingrich, H. L.;
Baum, J. S. The Chemistry of Heterocyclic Compounds, Oxazoles; Turchi, I. J., Ed.; Wiley:
10

New York, NY, 1986; Vol. 45, p 731; (d) Schoffstall, A. M.; Padwa, A. Advances in
Cycloaddition; (Ed.: D. P. Curran), Jai, Press Inc: Greenwich, CT, 1990; Vol. 2, p 1.
5. Lee, S. K.; Kang, I. N.; Lee, J.C.; Shin, W. S.; So,W. W.; Moon S.J. J. Poly. Sci. Part A:
Poly. Chem. 2011, 49, 3129–3137.
6. Shahrekipour , F.; Heydari , R.; Tahamipour , B.; Saravani, H.; Graiff, C. Phosphorus,
Sulfur, and Silicon, 2014, 189:2, 263-273, DOI: 10.1080/10426507.2013.819866.
7. (a) Schneider, W.; Kammerer, E. Arch. Pharm. 1966, 299, 847–857; (b) Nair, M. D.;
Malik, S. R.; Mehta, S. R. Indian J. Chem. 1967, 5, 221–223; (c) Menendez, J. C.; Delgado-
Iribarren, A.; Sollhuber, M. M. An. Real Acad. Farm. 1987, 53, 238–248; (d) Menendez, J.
C.; Sollhuber, M. M. Heterocycles 1990, 31, 2065–2071.
8. Wimmer, T. L.; Day, F. H.; Bradsher, C. K. J. Org. Chem. 1974, 40, 1198–1201.
9. Potekhim, A. A.; Sokolov, W. W.; Ogloblin, K. A.; Esacov, S. M. Khim. Geterocycl.
Soedin. 1983, 6, 776–785.
10. Sokolov, W. W.; Salfetnikova, N.; Potekhin, A. A. Zh. Org. Khim. 1996, 32, 870–878.
11. Rozwadowska, M. D.; Sulima, A. Tetrahedron 2001, 57, 3499–3506.
12. Sheehan, S. M.; Beall, L. S.; Padwa, A. Tetrahedron Lett. 1998, 39, 4761–4764.
13. Padwa, A.; Beall, L. S.; Heidelbaugh, T. M.; Liu, B.; Sheehan, S. M. J. Org. Chem. 2000,
65, 2684–2695.
14. (a) Huisgen, R; Funke, F.; Scnaerer C. F.; Gotthardt, H.; and Brunn, E. Tetrahedron Lett.
1967, 1809-1814; (b) Sato, S.; Ohta, R. Bulletin of the Chem Soc of Japan. 1967, 4261; (c)
Baldwin, E. J.; McDaniel, C. M.; Newton, M.; Paul, C. I. Tetrahedron Lett. 1966, 35, 4239-
4241; (d) Kroehnke, F.; and Steuernagel, H. Angew. Chem. 1961, 73, 36; Chem. Ber. 1964,
11

97, 1118-11126; (e) Sato, S. and Ohta, R. Bulletin of the Chem Soc of Japan. 1969, 2054-
2056.
15. Kagan, H. B. Catalytic Asymmetric Synthesis; 2nd ed.; Wiley-VCH, 2000; 6C, 329–356.
16. (a) Manabe, K. S.; Iimura, S.; Sun, X.-M.; Kobayashi, S. J. Am. Chem. Soc. 2002, 124,
11971-11978; (b) Li, C. J.; Chan, T. H. Organic Reactions in Aqueous Media; John Wiley:
New York, 1997; (c) Li, C.-J.; Chen, L. Chem. Soc. Rev. 2006, 35, 68-82.
17. (a) Anastas, P.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford University
Press: Oxford, 1998; (b) Dallinger, D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563-2591; (c)
Polshettiwar, V.; Varma, R. S. J. Org. Chem. 2007, 72, 7420-7422.
18. Dwars, T.; Paetzold, E.; Oehme, G. Angew. Chem., Int. Ed. 2005, 44, 7174-7199.
19. Fendler, J. H.; Fendler, E. J. Catalysis in Micellar and Macromolecular Systems; Academic
Press: New York, 1975.
20. (a) Hazra, A.; Paira, P.; Sahu, K. B.; Naskar, S.; Saha, P.; Paira, R.; Mondal, S.; Maity, A.;
Luger, P.; Weber, M.; Mondal, N. B.; Banerjee, S. Tetrahedron Lett. 2010, 51, 1585-1588;
(b) Naskar, S.; Banerjee, M.; Hazra, A.; Mondal, S.; Maity, A.; Paira, R.; Sahu, K. B.; Saha,
P.; Banerjee, S.; Mondal, N. B. Tetrahedron Lett. 2011, 52, 1527-1531; (c) Hazra, A.;
Mondal, S.; Maity, A.; Naskar, S.; Saha, P.; Paira, R.; Sahu, K. B.; Paira, P.; Ghosh, S.;
Sinha, C.; Samanta, A.; Banerjee, S.; Mondal, N. B. Eur. J. Med. Chem. 2011, 46, 2132-
2140; (d) Mondal, S.; Maity, A.; Paira, R.; Banerjee, M.; Bharitkar, Y; Hazra, A.; Banerjee,
S.; Mondal, N. B. Tetrahedron Lett. 2012, 53, 6288-6291;
21. Kalyanasundaram, K. Photochemistry in Microheterogeneous Systems; Academic Press:
San Diego, 1987.
22. Evans, D. F.; Allen, M.; Ninham, B. W.; Fouda, A. J. Solution Chem. 1984, 13, 87-101.
12

23. McCarroll, M.; Toerne, K.; Wandruszka, R. V. Langmuir 1998, 14, 2965-2969.
24. Israelachvili, J. Intermolecular and Surface Forces; Academic Press: San Diego, 1997.
25. General reaction procedure for the synthesis of thiazolo[2,3-a]isoquinolin-4-ium
derivatives (4a–r).
One mmol each of the isoquinolines (1a–c), phenacyl bromide (2a–f)/ bromoacetonitrile
(2g), and benzoyl isothiocyanate (3) were taken in a 100 ml RB flask. Then water (50 ml),
CTAB (4 mmol) and Amberlite-IRA-402 (OH) ion exchange resin (300mg) were added and
the mixture was stirred continuously for 1.5 h at room temperature. After completion of the
reaction (monitored by TLC), the solid was filtered off, washed thoroughly with water (until
free from CTAB). Then the solid was dried, and dissolved in chloroform and again filtered
to separate the Amberlite resin from solution. The compound was further purified by
recrystallization from chloroform to yield the thiazolo[2,3-a]isoquinolin-4-ium derivatives
(4a–r).
1
Spectral data of Compound 4a: Yield: 85% ; H-NMR (600 MHz, CDCl3) δ 7.24 (m, 3H),
7.37 (m, 1H), 7.51 (m, 1H), 7.63 (m, 3H), 7.78 (d, 1H, J =7.2 Hz), 7.86 (m, 2H), 7.95 (m,
3H), 8.38 (d, 1H, J =7.8 Hz), 9.75 (d, 1H, J =6.6 Hz) ; 13C-NMR (150 MHz, CDCl3) δ
120.2 (CH), 120.5 (C) 125.0 (C), 125.7 (CH), 127.1 (CH), 127.7 (2xCH), 127.8 (CH), 128.1
(2xCH), 129.1 (2xCH), 129.7 (2xCH), 130.4 (CH), 131.2 (CH), 131.7 (CH), 132.2 (CH)
136.6 (C), 139.3 (C), 140.3 (C), 147.5 (C), 158.2 (C), 173.6(C), 187.4 (C); MS (ESI) m/z:
409 [M+H]+, 408[M]+.
Spectral data of Compound 4g:
Yield: 85% ; 1H-NMR (600 MHz, CDCl3) δ 7.24 (m, 3H), 7.53 (m, 2H), 7.64 (m, 3H), 7.90
(m, 3H), 7.96 (m, 1H), 8.29 (d, 1H, J = 8.4 Hz), 8.38 (d, 1H, J = 8.4 Hz), 10.08 (s,1H); 13C-
13

NMR (150 MHz, CDCl3) δ 117.5 (C), 120.1 (C), 124.8 (C), 125.9 (CH), 127.6 (CH), 127.7
(CH), 127.9 (2xCH), 128.1 (2xCH), 128.1 (C), 129.2 (2xCH) 129.7 (2xCH), 131.2 (CH),
131.4 (CH), 131.9 (CH), 133.1 (CH), 136.4 (C), 140.0 (C) 146.5 (C), 158.0 (C), 173.7 (C),
187.2 (C); MS (ESI) m/z: 487 [M+H]+, 489[M+H+2]+.
Spectral data of Compound 4q:
Yield: 82% ; 1H-NMR (600 MHz, CDCl3) δ 7.50 (m, 2H), 7.81 (d, 1H, J =7.8 Hz), 7.89 (m,
3H), 7.98 (m, 1H), 8.31 (m, 1H), 8.42 (m, 2H), 8.55 (d, 1H, J =7.2 Hz); 13C-NMR (150
MHz, CDCl3) δ 96.7 (C), 106.9 (C), 111.9 (C), 121.6 (CH), 124.1 (CH), 125.1 (C), 128.2
(2xCH), 129.5 (2xCH), 130.0 (C), 131.4 (CH), 131.8 (CH), 132.4 (CH), 136.1 (CH), 139.3
(CH), 145.8 (C), 159.3 (C), 175.0 (C); MS (ESI) m/z: 330 [M+H]+, 352[M+Na]+.
Spectral data of Compound 4r:
Yield: 82% ; 1H-NMR (600 MHz, CDCl3) δ 7.50 (m, 2H), 7.73 (m, 1H), 7.87 (m, 1H), 8.10
(m, 1H), 8.27 (m, 2H), 8.40 (m, 2H), 8.61 (d, 1H, J =7.2 Hz); 13C-NMR (150 MHz, CDCl3)
δ 105.4 (CH), 111.6 (C), 120.8 (CH), 123.4 (C), 124.3(CH), 124.9 (CH), 126.4 (C), 128.2
(CH), 128.2 (C), 129.5 (CH), 131.8 (CH), 132.0 (CH), 135.8 CH), 136.6 (CH), 137.3 (C),
140.9 (C), 145.1 (C), 159.5 (C), 175.3 (C); MS (ESI) m/z:408 [M+H]+, 410 [M+H+2]+.
14