Synthesis and biological screening of novel thiadiazoles, selenadiazoles, and spirocyclic benzopyran by ultrasonic and microwave irradiation

Article abstract of DOI:10.1080/10426500903136913

We describe the synthesis of novel thiadiazole, selenadiazole, and spirocyclic benzopyrans via the semicarbazides 3 and thiosemicarbazides 3 of 2-ethyl-2-methyl-4H-chromen-4-ones 1 by conventional and nonconventional methods. The microwave and ultrasonic irradiation methods form the respective products in excellent yields in very short reaction time as compared to the conventional method. The synthesized compounds were tested for antimicrobial screening against bacteria and fungi show moderate activity. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903136913

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Synthesis and Biological Screening of
Novel Thiadiazoles, Selenadiazoles, and
Spirocyclic Benzopyran by Ultrasonic and
Microwave Irradiation
a
a
a
a
A. D. Shinde , S. S. Sonar , B. B. Shingate & M. S. Shingare
a
Department of Chemistry , Dr. Babasheb Ambedkar Marathwada
University , Aurangabad, India
Published online: 02 Aug 2010.
To cite this article: A. D. Shinde , S. S. Sonar , B. B. Shingate & M. S. Shingare (2010) Synthesis
and Biological Screening of Novel Thiadiazoles, Selenadiazoles, and Spirocyclic Benzopyran by
Ultrasonic and Microwave Irradiation, Phosphorus, Sulfur, and Silicon and the Related Elements,
185:8, 1594-1603, DOI: 10.1080/10426500903136913
To link to this article: http://dx.doi.org/10.1080/10426500903136913
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Phosphorus, Sulfur, and Silicon, 185:1594–1603, 2010
Copyright ꢀ
Taylor & Francis Group, LLC
C
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903136913
SYNTHESIS AND BIOLOGICAL SCREENING OF NOVEL
THIADIAZOLES, SELENADIAZOLES, AND SPIROCYCLIC
BENZOPYRAN BY ULTRASONIC AND MICROWAVE
IRRADIATION
A. D. Shinde, S. S. Sonar, B. B. Shingate, and M. S. Shingare
Department of Chemistry, Dr. Babasheb Ambedkar Marathwada University,
Aurangabad, India
We describe the synthesis of novel thiadiazole, selenadiazole, and spirocyclic benzopyrans
via the semicarbazides 3 and thiosemicarbazides 3 of 2-ethyl-2-methyl-4H-chromen-4-ones
1
by conventional and nonconventional methods. The microwave and ultrasonic irradiation
methods form the respective products in excellent yields in very short reaction time as com-
pared to the conventional method. The synthesized compounds were tested for antimicrobial
screening against bacteria and fungi show moderate activity.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Biological activities; microwave and ultrasonic irradiation; selenadiazole; spiro-
cyclic benzopyran; thiadiazole
INTRODUCTION
H-Chromen-4-ones, a class of two oxygen heterocyclic systems, have a widespread
4
1
existence among the plant kingdom. Many natural and synthetic 4H-chromen-4-ones
2
,3
2a
derivatives exhibit various types of biological activities such as antiallergenic, anti-
2
b
2c
2a
cancer, antifungal, and protein kinase C inhibitor, and are also used as substrates in
3
the preparation of a variety of rearranged products and new heterocyclic systems.
4
a
Thiadiazole derivatives are highly potent inhibitors of HIV-1 and useful as anti-
inflammatory and anti-arrhythmic agents. In addition, it is a common structural feature in
many biologically active molecules that are used clinically in the treatment of some forms of
epilepsy. The complexes of thiadiazole derivatives show antifungal and antibacterial, as
well as carbonic anhydrase inhibitory activities. In particular, 1,2,3-thiadiazoles are useful
4b
4c
4
d
5a
5c
5
b
6
pharmacophore and biologically active agents. The compounds with the 1,2,3-thiadiazole
nucleus are antibacterial, antipsychotic, platelet-activating factors and antagonistic agents.
7
Received 24 February 2009; accepted 18 June 2009.
Address correspondence to M. S. Shingare, Department of Chemistry, Dr. Babasheb Ambedkar Marathwada
University, Aurangabad- 431 004, MS, India. E-mail: prof msshingare@rediffmail.com
1
594

THIADIAZOLES, SELENADIAZOLES, SPIROCYCLIC BENZOPYRAN
1595
1
,2,4-Selenadiazole derivatives have potential biological activities and are important
8
intermediates in medicinal chemistry. The pair of sulfur and selenium are considered to
be isosteric, and the medicinal application of isosterism has been reviewed. Selenium
compounds have been found to be bactericides and their chemotherapeutic activities are
9
10
11
reported. Moreover, some bicyclic annelated 1,2,3-selenadiazoles are potent bioactive
1
2
agents. Recently, the synthesis of some fused selenadiazoles and thiodiazoles has been
13
reported.
Spirocyclic compounds have attracted considerable attention of organic chemists due
to their unique structural and reactivity patterns. The spiro-1,3,4-thiadiazolines exhibit a
broad spectrum of biological activities such as fungi-toxic, CNS stimulant, anticholinergic,
hypoglycemic, and anticonvulsant.14 They are used in industry as oxidation inhibitors,
coloring agents, and complexing agents with metals.
The resistance of pathogenic bacteria toward available antibiotics is rapidly becoming
a major worldwide problem, and it is known that antifungal drugs do not have selective
activity because of the biochemical similarity between human cell and fungi forms. There-
fore, the synthesis of new compounds to deal with antibacterial and antifungal activity is
of growing interest.15
The science of green chemistry was developed to meet the increasing demand for
16
17
environmentally benign chemical processes. Microwave and ultrasonic irradiation tech-
niques are important in the search for green synthesis because of their use as an efficient
alternative heating source for organic reactions. The main advantage of microwave and
ultrasonically assisted organic synthesis is the shorter reaction time, simple experimental
procedure, very high yields, and clean reaction of many microwave and ultrasonically in-
duced transformations, which offer additional convenience in the field of organic synthesis.
Thus, in this article, we describe syntheses of some new 4H-chromen-4-ones contain-
ing some 1,2,3-thiadiazole, 1,2,3-selenadiazole, and spiro-1,3,4-thiadiazoline moieties by
modern techniques and their antimicrobial activities.
RESULTS AND DISCUSSION
In continuation of our work in synthetic organic chemistry,18 a number of 2-ethyl-2-
methyl-4H-chromen-4-ones 1 were synthesized by reacting ortho hydroxy acetophenone
with 2-butanone in presence of pyrrolidine in 78–90% yield. Compound 1 was converted
into semicarbazones 2 and thiosemicarbazones 3 by the treatment of semicarbazide hy-
drochloride and thiosemicarbazides, respectively, in presence of sodium acetate in good
yields.
◦
Semicarbazones 2 upon treatment with SeO2 in acetic anhydride at 60 C for 2–3
h gave selenadiazoles 4 in 68–73% yield. The same selenadiazoles were obtained under
ultrasound and microwave irradiation with 78–84% and 86–95% yields, respectively. The
same semicarbazones 2 upon treatment with SOCl2 under conventional, ultrasonic, and
microwave irradiation afforded the 1,2,3-thiadiazoles 5 in 69–74%, 80–88%, and 89–97%
yields, respectively. Similarly, thiosemicarbazide 3, upon reaction with acetic anhydride at
◦
6
0 C for 6 h, resulted in thiadizolines 6 in 62–71% yield. The same compounds 6 were
obtained under ultrasound and microwave irradiation with 70–89% and 76–98% yields,
respectively. The formation of compounds 1–6 was confirmed by physical and spectroscopic
analysis (Tables I and II). In all cases, due to super heating, the time required to complete the
reaction under microwave irradiation is lower than the ultrasonic irradiation (cavitation) and
than conventional heating. Also, the formation of product using nonconventional energy

1596
A. D. SHINDE ET AL.
Table I Characterization data of the synthesized compounds
Yield (%)a
Mp ( C)
◦
Entry
Compound no.
R1
R2
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e
3a
3b
3c
3d
3e
H
F
Cl
H
H
Cl
F
H
H
H
Cl
F
H
H
H
Cl
F
90
89
85
78
81
91
88
92
87
89
93
90
88
86
91
56
40
39
56
40
120
145
140
155
160
139
148
144
137
140
F
OCH3
H
F
Cl
F
1
1
1
1
1
1
OCH3
H
F
Cl
F
OCH3
H
aIsolated yields.
(microwave and ultrasonic irradiation) takes place in greater percentage as compared with
the conventional heating.
All the synthesized compounds were screened for antibacterial activities against
Staphylococcus aureus and Escherichia coli and for antifungal activity against Candida
albicansa and A. fumigatus at two conc. (500 and 1000 µg/mL). The compounds tested are
compared against the standards (vancomycin and fluconazole) by measuring the diameter
of zone of inhibition. All the compounds tested exhibited moderate activity at 1000 µg/mL,
Table II Characterization data of the synthesized compounds
Conventional
Ultrasound
Microwave
Compound
No.
Mp/bp
◦
Entry
R1
R2 Time(h) Yield(%)a Time(min) Yield(%)a Time(min) Yield(%)a ( C)
b
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
4a
4b
4c
4d
4e
5a
5b
5c
5d
5e
6a
6b
6c
6d
6e
H
F
Cl
H
H
Cl
F
H
H
H
Cl
F
H
H
H
Cl
F
3
3
3
3
3
2
2
2
2
2
4
4
4
4
4
70
73
71
68
69
74
73
70
72
69
65
68
62
67
71
30
30
30
30
30
20
20
20
20
20
45
45
45
45
45
82
84
80
78
79
88
85
82
83
80
81
84
70
86
89
10
10
10
10
10
05
05
05
05
05
15
15
15
15
15
91
95
89
86
88
97
95
91
93
89
90
92
88
93
96
150
175
157
189
173
127
135
142
131
167
76
b
b
b
b
b
b
b
b
b
F
OCH3
H
F
Cl
F
1
1
1
1
1
1
OCH3
H
F
Cl
79
98
78
88
F
OCH3
H
a
b
Isolated yields.
Boiling point.

THIADIAZOLES, SELENADIAZOLES, SPIROCYCLIC BENZOPYRAN
1597
and very few compounds at 500 µg/mL conc. Were found to be active against the bacteria
and fungi. The results are described in Table S1 (Supplemental Materials, available online).
R
1
OH
O
O
R
1
O
R
1
2
O
Pyrrolidine
NH
2 2
NHCSNH
MeOH, reflux
NaOAc, HCl, EtOH
R
2
R
2
R
o
60
C
O
NNHCSNH
3a-e
2
1
a-e
NH
NaOAc, H
40-45 o
C
a: R
b: R
c: R
d: R
e: R
1
= R
2
= H
= H
NHCONH .
O-EtOH
2
2
HCl
1
= F, R
2
Ac
O
2
O
= R
= R
2
= Cl
= F
= OCH , R = H
3 2
2
1
1
2
1
R
1
2
O
R
1
R
R
2
S
NNHCONH
a-e
2
3
H COC
N
2
NHCOCH
3
6a-e
SeO
2
, Ac
2
O
SOCl2
O
R
1
O
R
1
2
R
2
Se
R
S
N
N
N
N
4
a-e
5a-e
Scheme 1 Synthesis of novel thiadiazoles, selenadiazoles, and spirocyclic benzopyran by ultrasonic and
microwave irradiation.
CONCLUSION
The experimental results show that the conventional methods are time-consuming
and gives less yield as compared to modern methods such as microwave and sonication.
We have synthesized a series of selenium and sulfur containing compounds, and among
them, some of compounds are promising and show significant in vitro antifungal activity.
The results suggest that selenium and sulfur are potent broad-spectrum antifungal agents
with low toxicity.
EXPERIMENTAL
All the melting points were taken in open capillaries and are uncorrected. Cem
Discover (Maximum current 6.3 A and 50/33 KHz frequency model No. 908010, USA)
microwave oven was used for microwave irradiation. Bandelin Sonorex (35 KHz frequency)
ultrasonic bath was used for ultrasonic irradiation. IR spectra were recorded in nujal on a
1
Perkin-Elmer 1420 spectrophotometer. H NMR spectra were recorded on a Varian (300
MHz) spectrometer in DMSO as a solvent with TMS as internal standards. Mass spectra
were recorded on a Kcatos MS-80 mass spectrometer.
Antibacterial Activity
All the compounds were screened for antibacterial activities against Staphylococcus
aureus (MRSAE 710) and Escherichia coli (ESS 2231) using vancomycin as a standard, and

1598
A. D. SHINDE ET AL.
for antifungal activity against Candida albicansa (TCC 14503) and A. fumigatus (ATCC
16424) using fluconazole as a standard.
General Procedure: Compounds 1a–e
To a well stirred solution of 2-hydroxy acetophenone (0.01 mol) and butan-2-one
(0.011 mol) in methanol (10 mL), pyrrolidine (0.012 mol) was added at room temperature.
The reaction mixture was refluxed for 2–3 h. The completion of the reaction was monitored
by TLC. The reaction mixture was quenched by crushed ice and extracted with ethyl acetate.
The organic layer was washed by brine (2 × 15 mL) and dried over anhydrous sodium
sulfate, and the solvent was removed under pressure to obtain the crude products. The
obtained residues were purified by column chromatography on silica gel 60 (by packing
wet column with silica gel 60, Merck, Darmstadt, Germany) by adsorbing residue on
silica gel, and methylenedichloride and methanol (9:1) elutes were used. After evaporation
of solvent, the pure desired compounds (1a–e) with high purity and 78–91% yield were
obtained.
Compounds 2a–e
Semicarbazide hydrochloride (0.012 mol) and sodium acetate (0.015 mol) were taken
in a conical flask and dissolved in distilled water (30 mL). To liberate a free base, the content
was warmed on a water bath until a clear solution was obtained. To this reaction mixture,
compound 1 (0.01 mol) was dissolved in ethanol (10 mL) and was added dropwise into the
◦
above reaction mass. Then the contents were warmed on a water bath for 3 h at 40–45 C,
and the progress of the reaction was monitored by TLC. After the complete conversion, the
contents were cooled. The white colored solid was separated out, which was filtered and
recrystallized from ethanol to get pure product 2.
Compounds 3a–e
To a well stirred solution of compound 1 (0.01 mol) in ethanol, a few drops of conc.
HCl and an ethanolic solution of thiosemicarbazide (0.01 mol) were added dropwise with
◦
constant stirring. The reaction mixture was maintained at 60 C for 2 h on a water bath.
After cooling, the solid product was filtered off and purified by column chromatography as
described for compounds 1a–e to yield 89–93% 3a–e.
Compounds 4a–e
Method (A) conventional method. Compound 2 (0.01 mol) was dissolved in
◦
acetic acid (15 mL) and warmed to 60 C with stirring. To this, selenium dioxide (0.05
◦
mol) was added portionwise. The stirring was continued at 60 C for 2–3 h until the
evolution of gas ceased. After completion of the reaction as monitored by TLC, the contents
were filtered to remove the deposited selenium. The filtrate was then poured over crushed
ice, and the solid obtained was filtered, washed thoroughly with cold water, then with
sodium carbonate solution, and again with water. The obtained compound was purified by
column chromatography on silica gel 60 (by packing wet column with silica gel 60 [Merck,

THIADIAZOLES, SELENADIAZOLES, SPIROCYCLIC BENZOPYRAN
1599
Darmstadt, Germany]) by elution with methylene chloride and methanol (9:1). Evaporation
of the solvent yielded 4a–e with high purity.
Method (B) ultrasound method. The solution of compound 2 (0.01 mol) and
acetic acid (15 mL) was irradiated under ultrasonic irradiation for 3 min. To this, selenium
dioxide (0.05 mol) was added portionwise, and the irradiation was continued until the
evolution of gas ceased. The progress of the reaction was monitored by TLC, and after
completion of the reaction, the contents were filtered to remove the deposited selenium.
The filtrate was then poured over crushed ice, and the obtained solid was filtered, washed
thoroughly with cold water, then with sodium carbonate solution, and again with water.
The same chromatographic workup was used to purify the products.
Method (C) microwave method. Compound 2 (0.01 mol) and selenium dioxide
(0.05 mol) were dissolved in acetic acid (15 mL) in a 50 mL borosilicate glass tube. The
reaction mixture was then irradiated inside a microwave oven for 10 min at an output of 500
Watts power, with short interruptions for 1 min. The progress of the reaction was monitored
by TLC. After completion, the contents were filtered to remove the deposited selenium.
The filtrate was then poured over crushed ice, and the obtained solid was filtered, washed
thoroughly with cold water, then with sodium carbonate solution, and again with water.
The obtained product 4 was purified by the column chromatographic technique described
above.
Compounds 5a–e
Method (A) conventional method. In a 50 mL round bottom flask, compound 2
◦
was dissolved (0.01 mol) in freshly distilled thionyl chloride (15 mL) at 0–5 C with constant
◦
stirring. The reaction was stirred for 4 h at 35–38 C. After completion of the reaction as
monitored by TLC, it was poured in to ice cold water. The product was extracted with
dichloromethane (50 mL), and the organic layer was washed with a 10% sodium bicarbonate
solution. The organic layer was separated and dried over sodium sulfate, and the solvent
was distilled out on a rotary evaporator until the compounds were purified by column
chromatographic technique as described in compound 1a–e to get compounds 5a–e.
Method (B) ultrasound method. In a 50 mL round bottom flask, compound
◦
2
(0.01 mol) was dissolved in freshly distilled thionyl chloride (15 mL) at 0–5 C with
constant stirring. The mixture was subjected for ultrasound irradiation for 20 min. Progress
of reaction was monitored with the help of TLC. After completion of the reaction, the
contents were poured onto crushed ice. The product was extracted with dichloromethane,
and the organic layer was washed with a 10% sodium bicarbonate solution. The organic
layer was separated and dried over sodium sulfate, and the solvent was distilled out on a
rotary evaporator to yield the desired product.
Method (C) microwave method. In a 50 mL borosilicate glass tube, compound
◦
2
(0.01 mol) was dissolved in freshly distilled thionyl chloride (15 mL) at 0–5 C with
constant stirring. The reaction mixture was irradiated inside a microwave oven for 10 min
at an output of 500 Watts power, with short interruptions of 1 min. The progress of the
reaction was monitored by TLC. After completion of the reaction, the contents were cooled
and poured into crushed ice. The product was extracted with dichloromethane, and the
organic layer was washed with 10% sodium bicarbonate solution. It was separated and
dried over sodium sulfate, and the solvent was removed by a rotary evaporator to get the
desired product.

1600
A. D. SHINDE ET AL.
Compounds 6a–e
Method (A) conventional method. The solution of compound 3 (0.01 mol) in
◦
freshly distilled acetic anhydride (20 mL) was heated on an oil bath at 60–70 C for 4 h.
After completion of reaction as monitored by TLC, the resulting contents were poured over
crushed ice with vigorous stirring to give a pale yellow product, which was purified by
the column chromatographic technique as described in compound 1a–e to get compounds
6a–e.
Method (B) ultrasound method. In a 100 mL round bottom flask, a solution of
compound 3 (0.01 mol) and freshly distilled acetic anhydride (15 mL) was subjected for
ultrasound irradiation for 45 min. The progress of the reaction was monitored with the help
of TLC. After completion of the reaction, the contents were poured into crushed ice with
vigorous stirring. The solid obtained was then filtered and recrystallized from ethanol.
Method (C) microwave method. A mixture of compound 3 (0.01 mol) and
freshly distilled acetic anhydride (15 mL) was taken in a 50 mL borosilicate glass beaker.
The reaction mixture was irradiated inside a microwave oven for 15 min at an output of 500
Watts power, with short interruptions of 1 min. The progress of the reaction was monitored
by TLC. After completion, the reaction mixture was cooled and poured into crushed ice
with vigorous stirring. The solid obtained was then filtered and recrystallized from ethanol.
Spectral Data of Principle Compounds
−1
1
1
a: IR (KBr, cm ): 2974, 1692, 1608, 1239. H NMR (DMSO-d6, δ ppm): 0.91
(3H, t, CH3); 1.32 (3H, s, CH3); 1.62–1.78 (2H, m, CH2); 2.79 (2H, q, CH2); 6.98 (2H, m,
Ar-H); 7.52 (1H, t, J = 7.5 Hz, Ar-H); 7.69 (1H, d, J = 7.8 Hz, Ar-H). MS: 191.33 (m + 1).
13
C NMR (CDCl3, δ ppm): 7.84, 23.24, 31.93, 46.88, 81.26, 118.20, 120.27, 120.46, 126.29,
1
36.03, 159.78, 182.68.
−1
1
1b: IR (KBr, cm ): 2987, 1677, 1611, 1245. H NMR (CDCl3, δ ppm): 0.92 (3H, t,
CH3); 1.35 (3H, s, CH3); 1.62–1.81 (2H, m, CH2); 2.90 (2H, q, CH2); 7.05 (2H, m, Ar-H);
1
3
7
4
.75 (1H, m, Ar-H); MS: 209.83 (m + 1). C NMR (DMSO-d6, δ ppm): 7.77, 24.27, 33.90,
9.48, 91.55, 129.28 130.34, 135.42, 146.32, 155.14, 169.77, 188.67.
−1
1
1
c: IR (KBr, cm ): 3077, 1677, 1610, 1167. H NMR (DMSO-d6, δ ppm): 1.0 (3H,
t, CH3); 1.43 (3H, s, CH3); 1.72–1.86 (2H, m, CH2); 2.73 (2H, q, CH2); 7.54 (1H, s, Ar-H);
1
3
7
4
.75 (1H, s, Ar-H); MS: 259.85 (m + 1). C NMR (DMSO-d6, δ ppm): 7.81, 23.18, 31.73,
6.84, 83.09, 121.87 124.28, 124.52, 125.32, 135.58, 159.70, 190.90.
−1
1
1
d: IR (KBr, cm ): 3145, 1665, 1600, 1152. H NMR (DMSO-d6, δ ppm): 1.0 (3H,
t, CH3); 1.43 (3H, s, CH3); 1.72–1.86 (2H, m, CH2); 2.73 (2H, q, CH2); 7.54 (1H, m,
13
Ar-H); 7.75 (1H, m, Ar-H); MS: 226.45 (m + 1). C NMR (DMSO-d6, δ ppm): 9.18,
2
4.10, 33.77, 47.82, 85.10, 122.77 125.38, 126.22, 128.65, 139.88, 165.70, 192.45.
−1
1
1
e: IR (KBr, cm ): 3014, 1669, 1605, 1167. H NMR (DMSO-d6, δ ppm): 1.0 (3H,
t, CH3); 1.72–1.86 (2H, m, CH2); 2.73 (2H, q, CH2); 3.47 (3H, OCH3), 7.54 (1H, d, J =
.6 Hz, Ar-H); 7.75 (1H, d, J = 7.2 Hz, Ar-H), 7.78 (1H, d, J = 3.5 Hz, Ar-H), MS: 220.56
8
13
(
1
m + 1). C NMR (DMSO-d6, δ ppm): 8.14, 24.26, 32.56, 47.45, 87.14, 122.57 126.54,
27.47, 126.25, 135.65, 160.70, 197.90
−1
1
2
a: IR (KBr, cm ): 3471, 1715, 1581, 1123. H NMR (DMSO-d6, δ ppm): 0.90
(3H, t, CH3); 1.21 (3H, s, CH3); 1.61 (2H, m, CH2); 2.71 (2H, q, CH2); 6.55 (2H, s, NH2);
6
.78 (1H, d, J = 7.0 Hz, Ar-H); 6.86 (1H, m, Ar-H); 7.19 (1H, t, J = 7.4 & 3 Hz, Ar-H);
13
8.07 (1H, d, J = 7.6 Hz, Ar-H); 9.40 (1H, s, NH). MS: 247.29 (m + 1). C NMR (CDCl3,

THIADIAZOLES, SELENADIAZOLES, SPIROCYCLIC BENZOPYRAN
1601
δ ppm): 8.20, 24.29, 32.70, 33.79, 39.40, 79.00, 123.45, 123.89, 124.77, 125.61, 129.13,
36.23, 148.20, 158.45.
1
−
1
1
2
b: IR (KBr, cm ): 3521, 17141, 1551, 1123. H NMR (DMSO-d6, δ ppm): 0.93
3H, t, CH3); 1.32 (3H, s, CH3); 1.77 (2H, m, CH2); 2.54 (2H, q, CH2); 6.52 (2H, s, NH2);
.70 (1H, d, J = 7.5 Hz, Ar-H); 7.23 (1H, m, Ar-H); 7.25 (1H, m, Ar-H); 9.40 (1H, s, NH).
(
6
1
3
MS: 265.29 (m + 1). C NMR (CDCl3, δ ppm): 9.14, 25.30, 35.21, 36.56, 49.45, 85.12,
125.44, 126.91, 127.87, 128.59, 132.11, 138.27, 155.20, 1654.45.
−1
1
2
c: IR (KBr, cm ): 3517, 1725, 1589, 1133. H NMR (DMSO-d6, δ ppm): 0.91 (3H,
t, CH3); 1.25 (3H, s, CH3); 1.56 (2H, m, CH2); 3.19 (2H, q, CH2); 7.60 (1H, s, Ar-H); 7.85
1
3
(
1H, s, Ar-H), 8.42 (2H, s, NH2); 10.42 (1H, s,). MS: 316.29 (m + 1). C NMR (CDCl3,
δ ppm): 8.22, 23.39, 31.79, 33.89, 39.37, 79.62, 123.00, 123.30, 123.71, 125.81, 129.83,
36.63, 148.90, 157.57.
1
−1
1
3
a: IR (KBr, cm ): 3668, 1686, 1574, 1230. H NMR (DMSO-d6, δ ppm): 0.90 (3H,
t, CH3); 1.21 (3H, s, CH3); 1.63 (2H, m, CH2); 2.91 (2H, q, CH2); 6.78 (1H, d, J = 7.2 Hz,
Ar-H); 6.86 (1H, t, J = 7.8 Hz, Ar-H); 8.02 (2H, s, NH2); 8.20 (2H, m, Ar-H); 10.34 (1H,
13
s, NH). MS: 263.35 (m + 1). C NMR (CDCl3, δ ppm): 9.45, 22.35, 30.77, 34.79, 40.47,
8
0.67, 124.52, 125.30, 126.52, 127.85, 130.74, 137.25, 150.90, 155.57
−1
1
3d: IR (KBr, cm ): 3674, 1696, 1564, 1245. H NMR (DMSO-d6, δ ppm): 0.95
(3H, t, CH3); 1.26 (3H, s, CH3); 1.58 (2H, m, CH2); 2.80- 2.91 (2H, q, CH2); 6.85–6.90
(
1H, m, Ar-H); 7.30 (1H, m, Ar-H); 8.22 (2H, s, NH2); 10.35 (1H, s, NH). MS: 2323.65 (m
1). C NMR (CDCl3, δ ppm): 9.12, 21.56, 31.32, 35.23, 41.52, 85.75, 127.55, 127.53,
13
+
1
29.45, 131.44, 133.77, 141.84, 158.74, 165.25.
−1
1
3e: IR (KBr, cm ): 3601, 1645, 1565, 1247. H NMR (DMSO-d6, δ ppm): 0.85 (3H,
t, CH3); 1.11 (3H, s, CH3); 1.40–1.62 (2H, m, CH2); 2.62–2.80 (2H, q, CH2); 3.78 (3H, s,
OCH3) 6.80 (1H, d, J = 8.5 Hz, Ar-H); 6.85 (2H, t, J = 7.0 & 3 Hz, Ar-H); 7.58 (2H, s,
NH2); 9.42 (1H, s, NH). MS: 293.75 (m+1).
−1
1
4
a: IR (KBr, cm ): 2973, 1679, 1614, 1228. H NMR (DMSO-d6, δ ppm): 0.92 (3H,
t, CH3); 1.79 (3H, s, CH3); 1.97–2.0 (2H, m, CH2); 7.08 (1H, d, J = 8 Hz, Ar-H); 7.31
(
2H, t, J = 7.3 & 2.8 Hz, Ar-H); 7.55 (1H, d, J = 7.8 Hz, Ar-H). MS: 279.26 (m + 1).
−1
1
4
c: IR (KBr, cm ): 3073, 1666, 1610, 1211. H NMR (DMSO-d6, δ ppm): 0.94 (3H,
t, CH3); 1.77 (3H, s, CH3); 1.67–2.0 (2H, m, CH2); 7.63 (1H, s, Ar-H); 7.99 (1H, s, Ar-H);
13
MS: 348.26 (m + 1). C NMR (DMSO-d6, δ ppm): 8.61, 28.32, 35.33, 86.05, 120.50,
1
22.92, 123.06,126.56, 130.21, 147.11, 151.98, 160.47.
−1
1
4
e: IR (KBr, cm ): 2985, 1691, 1625, 1218. H NMR (DMSO-d6, δ ppm): 0.92 (3H,
t, CH3); 1.65 (3H, s, CH3); 1.93–1.98 (2H, m, CH2); 3.80 (3H, s, OCH3) 6.88 (1H, d, J =
.85 Ar-H); 6.95 (1H, d, J = 7.21 Hz, Ar-H); 7.59 (1H, d, J = 3 Hz, Ar-H). MS: 309.22
m + 1).
a: IR (KBr, cm ): 2940, 1670, 1627, 1233. H NMR (DMSO-d6, δ ppm): 0.91 (3H,
t, CH3); 1.70 (3H, s, CH3); 2.00 (2H, m, CH2); 7.11 (2H, m, Ar-H,); 7.35 (1H, d, Ar-H, J =
8
(
−1
1
5
13
7
.3 Hz); 8.03 (1H, d, J = 7.5 Hz, Ar-H). MS: 233.19 (m + 1). 232.30. C NMR (DMSO-d6,
δ ppm): 9.31, 27.32, 36.32, 87.05, 122.70, 122.92, 125.45,127.47, 132.23, 150.11, 155.44,
1
65.54.
−1
1
5b: IR (KBr, cm ): 3025, 1741, 1710, 1125. H NMR (DMSO-d6, δ ppm): 0.91
(
3H, t, CH3); 1.67 (3H, s, CH3); 2.19 (2H, m, CH2); 6.90 -7.15 (2H, dd, J = 7.2 & 2 Hz,
13
Ar-H); 7.55 (1H, d, J = 7.1 Hz, Ar-H). MS: 250.49. C NMR (DMSO-d6, δ ppm): 10.22,
2
9.12, 37.78, 89.25, 127.77, 130.92, 135.45,139.47, 144.23, 151.56, 157.47, 169.59.
−1
1
5
e: IR (KBr, cm ): 2956, 1650, 1632, 1243. H NMR (DMSO-d6, δ ppm): 0.93 (3H,
t, CH3); 1.65 (3H, s, CH3); 2.10 (2H, m, CH2); 3.83 (3H, s, OCH3); 6.90 -7.15 (2H, d,

1602
A. D. SHINDE ET AL.
J = 8.5 Hz, Ar-H); 7.55 (1H, d, J = 7.9 Hz, Ar-H). MS: 263.39 (m + 1).262.32. 13C NMR
(DMSO-d6, δ ppm): 9.54, 21.57, 35.77, 85.55, 125.52, 133.25, 137.40,139.45, 148.25,
1
55.76, 159.49, 174.55.
−1
1
6a: IR (KBr, cm ): 2939, 1710, 1621, 1237. H NMR (DMSO-d6, δ ppm): 0.892
(3H, m, CH3), 1.19 (3H, s, CH3), 1.20 (3H, s, CH3), 1.91 (3H, s, CH3), 2.05 (2H, s, CH2),
6
1
.75 (1H, d, J = 7.2 Hz, Ar-H), 7.11 (1H, t, J = 7.3 & 3 Hz, Ar-H), 7.25 (2H, m, Ar-H)
1.71 (1H, s, NH). MS: 347.43 (m + 1).
−1
1
6
b: IR (KBr, cm ): 2949, 1700, 1611, 1245. H NMR (DMSO-d6, δ ppm): 0.89
(3H, m, CH3), 1.19 (3H, s, CH3), 1.25 (3H, s, CH3), 1.41 (3H, s, CH3), 1.95 (2H, t, CH2),
3.25 (2H, s, CH2), 6.95 (1H, m, Ar-H), 7.11 (2H, m, Ar-H), 11.91 (1H, s, NH). MS: 366.35
(
m + 16 ).
−1
1
c: IR (KBr, cm ): 2976, 1714, 1627, 1235. H NMR (DMSO-d6, δ ppm): 0.96 (3H,
m, CH3), 1.59 (2H, m, CH2), 1.62 (2H; m, CH2) 1.89 (3H, s, CH3); 1.91 (3H, s, CH3), 2.84
(2H, q, CH2), 3.74 (3H, s, CH3), 6.75 (1H, s, Ar-H), 7.50 (1H, bs), 7.64 (1H; s, Ar-H); 9.89
(
1H, s, NH). MS: 416.32 (m + 1).
−1
1
6
d: IR (KBr, cm ): 2970, 1710, 1615, 1225. H NMR (DMSO-d6, δ ppm): 0.91
(3H, m, CH3), 1.25 (3H, s, CH3), 1.35 (3H; s, CH3) 1.89 (2H, t, CH2); 2.01 (3H, s, CH3),
2
.24 (3H, s, CH3), 3.4 (2H, s, CH2), 7.15 (1H, dd, J = 7.8 & 2.9 Hz, Ar-H), 7.33 (1H, m),
11.79 (1H, s, NH). MS: 383.41 (m + 1).
−1
1
6
e: IR (KBr, cm ): 3016,1740, 1633, 1245. H NMR (DMSO-d6, δ ppm): 0.95 (3H,
m, CH3), 1.20 (3H, s, CH3), 1.80–1.97 (6H, 2×CH3) 2.8 (2H; m, CH2) 3.78 (3H, s, OCH3);
7
.45 (1H, d, J = 8.35 Hz, Ar-H), 8.10 (1H, d, J = 7.5 Hz, Ar-H), 8.25 (1H; d, J = 3 Hz,
Ar-H); 9.87 (1H, s, NH). MS: 457.55 (m + 1).
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1