Synthesis of some fused triazole derivatives containing 4-isobutylphenylethyl and 4-methylthiophenyl moieties

Article abstract of DOI:10.1515/znb-2010-1110

A series of substituted [1,3]thiazolo[3,2-b][1,2,4]triazole derivatives 4 were synthesized in good yield by condensing 2-substituted-1,2,4-triazole-5- thiols 3 with various N-aryl-maleimides in acetic acid media. All structures of the newly synthesized compounds were elucidated by elemental analyses and spectral data.

Full text of DOI:10.1515/znb-2010-1110

Synthesis of Some Fused Triazole Derivatives Containing
4-Isobutylphenylethyl and 4-Methylthiophenyl Moieties
Manjunatha Kumsia, Boja Poojarya, Prajwal L. Loboa, Jennifer Fernandesb,
and Chandrashekhar Chikkannac
a Department of Chemistry, Mangalore University, Mangalagangothri-574199, Karnataka, India
b Department of Pharmachemistry, NGSM College of Pharmacy, Panner, Deralakatte-574 160,
Karnataka, India
c Department of Medicinal Chemistry, SDM College, Ujire-574162, Karnataka, India
Reprint requests to Dr. Boja Poojary. Fax: +91-824-2287367. E-mail: bojapoojary@gmail.com
Z. Naturforsch. 2010, 65b, 1353 – 1358; received July 17, 2010
A series of substituted [1,3]thiazolo[3,2-b][1,2,4]triazole derivatives 4 were synthesized in good
yield by condensing 2-substituted-1,2,4-triazole-5-thiols 3 with various N-aryl-maleimides in acetic
acid media. All structures of the newly synthesized compounds were elucidated by elemental analyses
and spectral data.
Key words: 1,2,4-Triazole-5-thiol, N-Aryl-maleimides, [1,3]Thiazolo[3,2-b][1,2,4]triazoles
Introduction
1,2,4-Triazole derivatives due to their wide range
of biological activities such as antimicrobial, anti-
inflammatory [14], anticancer [15], antitubercular
[16] and antimycotic [17, 18] properties have received
considerable attention. 1,2,4-Triazole rings have
been incorporated into a variety of therapeutically
interesting drug candidates such as Triazolam [19],
Alprazolam [20], Etizolam [21], Furacyclin [22], and
Ribavirin [23].
On the other hand, thiazoles have attracted contin-
uing interest because of their varied biological activ-
ities [27– 32]. There are also some drugs containing
the thiazole moiety, for example: Fentiazac, Meloxi-
cam [24, 25] (both anti-inflammatory agents), Nizati-
dine [26] (antiulcerative agent), and Sulfathiazole [26]
(antimicrobial agent).
In view of these marked applications of [1,2,4]tri-
azoles and [1,3]thiazoles, it was envisaged that chemi-
cal entities containing both of these moieties would re-
sult in compounds of interesting biological activities. It
was considered to synthesize some substituted [1,3]thi-
azolo[3,2-b]-1,2,4-triazoles incorporating 2-(4-isobut-
ylphenyl)ethyl and 4-methylthiophenyl moieties.
Non-steroidal anti-inflammatory drugs (NSAIDs)
such as Ibuprofen are widely used for the treatment
of pain, fever and inflammation [1 – 3]. Prostaglandins
are important biological mediators of inflammation,
originating from biotransformation of arachidonic acid
catalyzed by cyclooxygenase [4]. In the early 1990s,
it was discovered that the enzyme exists as two iso-
forms, one constitutive (COX-1) and the other in-
ducible (COX-2) [5]. COX-1 is constitutively ex-
pressed and provides cytoprotection in the gastroin-
testinal (GI) tract, while COX-2 is inducible and me-
diates inflammation [4, 6]. Prolonged use of NSAIDs
like Ibuprofen has been associated with gastrointesti-
nal complications ranging from stomach irritation to
life-threatening gastrointestinal ulceration and bleed-
ing [7, 8]. Therefore the development of new NSAIDs
without these side effects has long been awaited. Se-
lective COX-2 inhibitors with better safety profile have
been marketed as a new generation of NSAIDs [9].
Thus, there remains a compelling need for effective
NSAIDs with an improved safety profile.
It has also been reported that the presence of the
4-methylthiophenyl moiety [10] is found to increase
the biological activity of the molecules. A few hetero-
cyclic analogs containing N-bridged heterocycles bear-
ing the 4-methylthiophenyl moiety possess good anti-
inflammatory [10, 11] and antimicrobial [12, 13] activ-
ities.
Results and Discussion
A synthetic approach to the title compounds is
outlined in Scheme 1. The acid hydrazides 2 were
prepared by the esterification of 2-(4-isobutylphen-
yl)propanoic acid and 4-methylthiophenyl acetic acid
c
0932–0776 / 10 / 1100–1353 $ 06.00 ꢀ 2010 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
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1354
M. Kumsi et al. · Fused Triazole Derivatives
R = CH2CH(CH3)2, SCH3; R1 = CH3, H; R2 = H, 3-Cl-4-F, 4-F, 4-Cl, 4-CH3, 4-OCH3, 4-Br
4a
4b
4c
4d
4e
4f
4g
R
CH2CH(CH3)2 CH2CH(CH3)2 CH2CH(CH3)2 CH2CH(CH3)2 CH2CH(CH3)2 CH2CH(CH3)2 CH2CH(CH3)2
R1 CH3
CH3
3-Cl-4-F
CH3
4-F
CH3
4-Cl
CH3
4-CH3
CH3
4-OCH3
CH3
4-Br
R2
H
4h
SCH3
H
4i
SCH3
H
4j
SCH3
H
4k
SCH3
H
4l
SCH3
H
4m
SCH3
H
4n
SCH3
H
R
R1
R2
H
3-Cl-4-F
4-F
4-Cl
4-CH3
4-OCH3
4-Br
Scheme 1.
followed by treatment with hydrazine hydrate in groups in the region 1710– 1725 cm−1 and 1585 –
absolute alcohol [33]. The resulting acid hydrazides 1610 cm−1, respectively, thus indicating their for-
on reaction with potassium thiocyanate in the presence mation from 3 through cyclocondenzation with N-
of conc. hydrochloric acid yielded the corresponding arylmaleimides.
1
thiosemicarbazides, which on cyclization with an
aqueous 5 % NaOH solution afforded 3-substituted-
[1,2,4]triazole-5-thiols 3. Condensation of these
triazoles with various substituted N-aryl-maleimides
in acetic acid media yielded 2-(2-substituted-6-oxo-
5,6-dihydro[1,3]thiazolo[3,2-b][1,2,4]triazol-5-yl)-N-
aryl-acetamides 4. The substituted N-aryl-maleimides
were prepared according to the literature procedures
[34]. The formation of fused thiazotriazoles 4a – n has
been confirmed by the elemental analyses and spectral
data of the products.
The H NMR spectrum of 1,2,4-triazole-5-thiol 3a
showed a downfield, broad singlet at δ = 12.64 ppm
for the D2O-exchangeable NH and SH protons. The
downfield shift of this signal indicates tautomerism in
the triazole ring. Two distinct doublets at δ = 0.85 (J =
8.0 Hz) and δ = 1.68 (J = 8.0 Hz) were observed for the
methyl protons. The isopropyl methyne proton was ob-
served as a multiplet in the range δ = 1.80 – 1.88 ppm,
and the other methyne proton was observed as a quar-
tet at δ = 4.14 ppm. The methylene protons resonated
as a doublet at δ = 2.45 ppm (J = 4.0 Hz). The aro-
In the IR spectra of 3a and 3b, absorption bands matic protons appeared as two doublets at δ = 6.97 and
due to an amide carbonyl function in the region 1760– 7.06 ppm with J = 8.0 Hz. Further, an LC-MS spectrum
1705 cm−1 and to the NH-NH2 moiety in the region of 3a showed the molecular ion peak at m/z = 261, in
3455 – 3203 cm−1 of their precursors were found to be conformity with its molecular formula, C14H19N3S.
The 1H NMR spectrum of 3b also showed a down-
absent. However, they showed a new absorption band
at 3114 cm−1of an NH group supporting their forma-
field broad singlet at δ = 13.30 ppm corresponding to
tion.
its D2O-exchangeable NH and SH protons. Two sin-
The IR spectra of thiazolotriazoles 4 showed the ab- glets at δ = 2.41 ppm and δ = 3.83 ppm have been
sorption bands corresponding to their C=O and C=N attributed to the SCH3 and CH2 protons. The four aro-
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M. Kumsi et al. · Fused Triazole Derivatives
1355
matic protons of the 4-methylthiophenyl moiety res- CH), 7.5 (br s, 5 H, C6H4 and NH). – LC-MS: m/z (%) = 220
(78) [M]+. – C13H20N2O (220.3): calcd. C 70.87, H 9.15,
N 12.72; found C 70.85, H 9.13, N 12.70.
onated as two doublets at δ = 7.18 and 7.20 ppm (J =
8.3 Hz), respectively. Further, an LC-MS spectrum of
3b showed the molecular ion peak at m/z = 237, in con-
formity with its molecular formula, C10H11N3S2.
2b: M. p. 136 ◦C; yield 86 %. – IR (KBr): ν = 3344 (NH,
NH2), 3203 (NH2), 2963 (C-H), 1622 (CO-NH) cm−1. – 1H
NMR (CDCl3): δ = 2.49 (s, 3 H, SCH3), 3.53 (s, 2 H, CH2),
3.82 (br s, 2 H, NH2), 6.67 (br s, 1 H, NH), 7.18 (d, J =
8.3 Hz, Ar-H), 7.26 (d, J = 8.3 Hz, Ar-H). – LC-MS: m/z
(%) = 196 (90) [M]+. – C9H12N2OS (196.2): calcd. C 55.09,
H 6.16, N 14.27, S 16.34; found C 55.06, H 6.15, N 10.25,
S 15.71.
1
In the H NMR spectra of compounds 4a – n, pro-
tons of a CH2-CH fragment showed the characteris-
tic pattern of an ABX system. The chemical shifts
of the protons HA, HB and HX are at δ ∼ 3.32 –
3.38, ∼ 2.81 – 2.95 and ∼ 4.55 – 4.65 ppm, respec-
tively. Large values of JAB = 12.0 – 18.0 Hz, JAX
=
General procedure for the preparation of 1,2,4-triazole-3-
thiols 3a, b
7.5– 9.0 Hz and JBX = 4.0 – 8.0 Hz were observed like
in the structurally related 2-thioxo-4-thiazolidinones,
referred to a “carbonyl effect” by Takahashi [35]. The
acetamide NH proton appeared as a sharp singlet at δ =
13.80– 14.10 ppm. In the 13C NMR spectra of 4 the
acetamide carbonyl carbon and the thiazolidinone car-
bonyl carbon atoms appeared in the region δ = 172.1–
174.2 and 176.2– 177.8 ppm, respectively, in addition
to other characteristic signals of the remaining carbon
atoms.
Aroyl hydrazide 2 (0.1 mol) was dissolved in wa-
ter (100 mL) containing concentrated hydrochloric acid
(10 mL). Potassium thiocyanate (0.2 mol) was added, and
the mixture was warmed on a water bath for 5 h. The reaction
mixture was cooled. The precipitated solid was filtered, dried
and recrystallized from ethanol to get the aroyl thiosemicarb-
azide. A mixture of aroyl thiosemicarbazide (0.01 mol) and
sodium hydroxide (5 %, 100 mL) was refluxed for 3 h. The
reaction mixture was poured on crushed ice and acidified
with dilute hydrochloric acid. The precipitate thus obtained
was filtered, dried and recrystallized from ethanol.
Experimental Section
Instruments and starting materials
3a: M. p. 198 ◦C; yield 85 %. – IR (KBr): ν = 3100 (Ar-H),
2972 (C-H), 1215 (C=S) cm−1. – 1H NMR (CDCl3): δ =
0.85 (d, J = 8 Hz, 6 H, 2 × CH3), 1.68 (d, J = 8 Hz,
3 H, CH3), 1.80 – 1.88 (m, 1 H, CH), 2.45 (d, J = 4.0 Hz,
2 H, CH2), 4.15 (q, J = 8.0 Hz, 1 H, CH), 697 (d, J =
8 Hz, 2 H, ArH), 706 (d, J = 8 Hz, 2 H, ArH), 12.64
(br s, 2 H, NH/SH). – 13C NMR ([D6]DMSO): δ = 18.34,
18.78, 22.42, 30.28, 37.48, 126.13, 126.32, 128.25, 128.43,
136.20, 139.05, 161.05, 167.15. – LC-MS: m/z (%) = 261
(86) [M]+. – C14H19N3S (261.3): calcd. C 64.31; H 7.33;
N 16.08; S 12.27; found C 64.30; H 7.33; N 16.09; S 12.27.
3b: M. p. 197 ◦C; yield 85 %. – IR (KBr): ν = 3154 (NH),
1206 (C=S) cm−1. – 1H NMR ([D6]DMSO): δ = 2.49 (s,
3 H, SCH3), 3.83 (s, 2 H, CH2), 7.18 (d, J = 8.36 Hz, Ar-H),
7.26 (d, J = 8.36 Hz, Ar-H), 13.30 (br s, 2 H, NH/SH). –
13C NMR ([D6] DMSO): δ = 16.12, 32.13, 127.51, 128.25,
131.99, 139.21, 152.16, 167.10. – LC-MS: m/z (%) = 237
(89) [M]+. – C10H11N3S2 (237.3): calcd. C 50.60, H 4.67,
N 17.70, S 27.02; found C 50.56, H 4.71, N 17.79, S 27.05.
The melting points were determined by an open capillary
method and are uncorrected. The IR spectra (from KBr pel-
lets) were recorded on a Shimadzu FT-IR 157 spectropho-
tometer. The 1H NMR and 13C NMR spectra were recorded
on a Brukar Avance II-400 (400 MHz) spectrometer using
TMS as an internal standard. Mass spectra were recorded in
an Agilent Technology LC-mass spectrometer. The acceler-
ating voltage was 10 kV, and spectra were recorded at r. t.
Elemental analyses (CHNS) were performed on the CHNS
analyzer. The progress of the reaction was monitored by thin-
layer chromatography (TLC) on silica gel plates.
General procedure for the preparation of acid hydrazides
2a, b
The mixture of ethyl esters of substituted aromatic acids 1
(0.1 mol) and hydrazine hydrate (0.2 mol) was refluxed in ab-
solute alcohol (50 mL) for 8 h. The excess solvent was then
distilled off under reduced pressure, and the concentrated so-
lution was quenched by its addition to ice cold water. The
solid separated was filtered, washed and dried. The crude
General procedure for the preparation of substituted
[1,3]thiazolo[3,2-b][1,2,4]triazole derivatives 4a – n
product was purified by recrystallization from ethanol.
A mixture of a 1,2,4-trizole-5-thiol (10 mmol) and the ap-
◦
2a: M. p. 71 C; yield 85 %. – IR (KBr): ν = 3449 (NH, propriate N-arylmaleimide (10 mmol) was refluxed for 2 h in
NH2), 3275 (NH2), 2972 (C-H), 1695 (CO-NH) cm−1. – 1H 10 mL of glacial acetic acid. After cooling to r. t., the reaction
NMR (CDCl3): δ = 0.85 (d, J = 8 Hz, 6 H, 2 × CH3), 1.68 mixture was poured into 50 mL of water. The precipitated
(d, J = 8 Hz, 3 H, CH3), 1.80 – 1.88 (m, 1 H, CH), 2.45 (d, colorless powder was filtered off, washed with methanol and
J = 4 Hz, 2 H, CH2), 4.0 (s, 2 H, NH2), 4.14 (q, J = 8 Hz, 1 H, recrystallized from ethanol.
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1356
M. Kumsi et al. · Fused Triazole Derivatives
4a: M. p. 157 ◦C; yield 85 %. – IR (KBr): ν = 3126 calcd. C 70.87, H 9.15, N 12.72; found C 70.85, H 9.13,
(NH), 3022 (Ar-H), 2954 (C-H), 1715 (C=O), 1596 (C=N) N 12.70.
cm−1. – 1H NMR ([D6]DMSO): δ = 0.83 (d, J = 8 Hz, 6 H,
2 × CH3), 1.51 (d, J = 8 Hz, 3 H, CH3), 1.74 – 1.81 (m, 1 H,
CH), 2.38 (d, J = 8 Hz, 2 H, CH2), 2.90 (dd, J = 16 Hz, 1 H),
3.37 (dd, J = 16, 8 Hz, 1 H), 4.19 (q, J = 4 Hz, 1 H, CH),
4.61 (dd, J = 8.7, 4 Hz, 1 H), 7.05 (d, J = 8 Hz, 2 H, Ar-H),
7.08 (d, J = 8 Hz, 2 H, Ar-H), 7.12 – 7.74 (m, 5 H, phenyl),
13.93 (s, 1 H, NH). – 13C NMR ([D6]DMSO): δ = 18.8,
19.2, 22.8, 30.6, 34.6, 37.7, 39.6, 127.4, 127.8, 129.8, 130.2,
139.0, 152.4, 169.5, 173.4, 179.7. – LC-MS: m/z (%) = 434
(55) [M]+. – C24H26N4O2S (434.5): calcd. C 70.87, H 9.15,
N 12.72; found C 70.85, H 9.13, N 12.70.
4b: M. p. 118 ◦C; yield 77 %. – IR (KBr): ν = 3126
(NH), 3050 (Ar-H), 2956 (C-H), 1713 (C=O), 1584 (C=N)
cm−1. – 1H NMR ([D6]DMSO): δ = 0.83 (d, J = 8 Hz,
6 H, 2 × CH3), 1.50 (d, J = 8 Hz, 3 H, CH3), 1.73 – 1.79
(m, 1 H, CH), 2.38 (d, J = 8 Hz, 2 H, CH2), 2.91 (dd, J =
16 Hz, 1 H), 3.34 (dd, J = 16, 8 Hz, 1 H), 4.19 (q, J = 4 Hz,
1 H, CH), 4.60 (dd, J = 8.7, 4 Hz, 1 H), 7.08 (d, J = 8 Hz,
2 H, Ar-H), 7.12 (d, J = 8 Hz, 2 H, Ar-H), 7.32 – 7.47 (m,
4 H, 3-chloro-4-fluorophenyl), 13.96 (s, 1 H, NH). – 13C
NMR ([D6]DMSO): δ = 18.7, 19.2, 22.8, 30.4, 34.5, 37.0,
39.8, 127.8, 128.5, 130.4, 132.0, 140.0, 153.1, 168.7, 173.2,
179.6. – LC-MS: m/z (%) = 486 (54) [M]+, 488 (18) [M]+. –
C24H24N4O2ClFS (486.9): calcd. C 70.87, H 9.15, N 12.72;
found C 70.85, H 9.13, N 12.70.
4c: M. p. 124 ◦C; yield 72 %. – IR (KBr): ν = 3128
(NH), 3058 (Ar-H), 2946 (C-H), 1703 (C=O), 1598 (C=N)
cm−1. – 1H NMR ([D6]DMSO): δ = 0.82 (d, J = 8 Hz,
6 H, 2 × CH3), 1.51 (d, J = 8 Hz, 3 H, CH3), 1.74 – 1.81
(m, 1 H, CH), 2.38 (d, J = 8 Hz, 2 H, CH2), 2.88 (dd, J =
16 Hz, 1 H), 3.39 (dd, J = 16, 8 Hz, 1 H), 4.18 (q, J = 4 Hz,
1 H, CH), 4.63 (dd, J = 8.7, 4 Hz, 1 H), 7.04 – 7.10 (m, 4 H,
Ar-H), 7.26 – 7.38 (m, 4 H, 4-fluorophenyl), 13.99 (s, 1 H,
NH). – 13C NMR ([D6]DMSO): δ = 18.7, 19.2, 22.8, 30.4,
34.6, 37.2, 39.0, 126.6, 127.8, 129.6, 130.4, 141.2, 152.9,
168.1, 173.1, 179.5. – LC-MS: m/z (%) = 452 (72) [M]+. –
C24H25N4O2FS (452.5): calcd. C 70.87, H 9.15, N 12.72;
found C 70.85, H 9.13, N 12.70.
4e: M. p. 142 ◦C; yield 88 %. – IR (KBr): ν = 3483
(NH), 3080 (Ar-H), 2958 (C-H), 1720 (C=O), 1607 (C=N)
cm−1. – 1H NMR ([D6]DMSO): δ = 0.82 (d, J = 8 Hz, 6 H,
2 × CH3), 1.51 (d, J = 8 Hz, 3 H, CH3), 1.74 – 1.81 (m, 1 H,
CH), 2.33 (s, 3 H, Ar-CH3), 2.38 (d, J = 8 Hz, 2 H, CH2),
2.93 (dd, J = 16 Hz, 1 H), 3.40 (dd, J = 16, 8 Hz, 1 H), 4.19
(q, J = 4 Hz, 1 H, CH), 4.61 (dd, J = 8.7, 4 Hz, 1 H), 7.04 –
7.08 (m, 4 H, Ar-H), 7.10 – 7.25 (m, 4 H, 4-methylphenyl),
13.93 (s, 1 H, NH). – 13C NMR ([D6]DMSO): δ = 18.7, 19.2,
20.4, 22.8, 30.5, 34.7, 38.2, 39.7, 126.4, 127.8, 129.2, 131.6,
141.2, 153.2, 168.6, 173.2, 179.6. – LC-MS: m/z (%) = 448
(58) [M]+. – C25H28N4O3S (448.5): calcd. C 70.87, H 9.15,
N 12.72; found C 70.85, H 9.13, N 12.70.
4f: M. p. 158 ◦C; yield 68 %. – IR (KBr): ν = 3249
(NH), 3062 (Ar-H), 2976 (C-H), 1710 (C=O), 1604 (C=N)
cm−1. – 1H NMR ([D6]DMSO): δ = 0.83 (d, J = 8 Hz, 6 H,
2 × CH3), 1.52 (d, J = 8 Hz, 3 H, CH3), 1.76 – 1.82 (m, 1 H,
CH), 2.38 (d, J = 8 Hz, 2 H, CH2), 2.92 (dd, J = 16 Hz, 1 H),
3.41 (dd, J = 16, 8 Hz, 1 H), 3.92 (s, 3 H, OCH3), 4.19 (q,
J = 4 Hz, 1 H, CH), 4.72 (dd, J = 8.7, 4 Hz, 1 H), 7.04 (d, J =
8 Hz, 2 H, Ar-H), 7.08 (d, J = 8 Hz, 2 H, Ar-H), 7.34 – 7.44
(m, 4 H, 4-methoxyphenyl), 13.93 (s, 1 H, NH). – 13C NMR
([D6]DMSO): δ = 18.7, 19.2, 22.8, 30.5, 35.3, 38.2, 39.7,
60.4, 126.2, 127.0, 128.8, 130.2, 140.0, 153.5, 168.4, 173.0,
179.6. – LC-MS: m/z (%) = 464 (63) [M]+. – C25H28N4O3S
(464.5): calcd. C 70.87, H 9.15, N 12.72; found C 70.85,
H 9.13, N 12.70.
4g: M. p. 152 ◦C; yield 83 %. – IR (KBr): ν = 3216 (NH),
3048 (Ar-H), 2964 (C-H), 1704 (C=O), 1607 (C=N) cm−1. –
1H NMR ([D6]DMSO): δ = 0.83 (d, J = 8 Hz, 6 H, 2 × CH3),
1.52 (d, J = 8 Hz, 3 H, CH3), 1.76 – 1.82 (m, 1 H, CH), 2.38
(d, J = 8 Hz, 2 H, CH2), 2.87 (dd, J = 16 Hz, 1 H), 3.39 (dd,
J = 16, 8 Hz, 1 H), 4.19 (q, J = 4 Hz, 1 H, CH), 4.66 (dd, J =
8.7, 4 Hz, 1 H), 7.04 (d, J = 8 Hz, 2 H, Ar-H), 7.08 (d, J =
8 Hz, 2 H, Ar-H), 7.34 – 7.44 (m, 4 H, 4-bromophenyl), 14.00
(s, 1 H, NH). – 13C NMR ([D6]DMSO): δ = 18.6, 19.3, 22.8,
30.4, 34.5, 37.6, 40.3, 126.2, 127.4, 129.4, 130.1, 140.2,
153.2, 168.8, 173.4, 179.5. – LC-MS: m/z (%) = 512 (62)
[M]+, 514 (62) [M]+. – C24H25N4O2BrS (513.4): calcd.
C 70.87, H 9.15, N 12.72; found C 70.85, H 9.13, N 12.70.
4d: M. p. 170 ◦C; yield 85 %. – IR (KBr): ν = 3130
(NH), 3068 (Ar-H), 2961 (C-H), 1710 (C=O), 1602 (C=N)
cm−1. – 1H NMR ([D6]DMSO): δ = 0.83 (d, J = 8 Hz,
4h: M. p. 157 ◦C; yield 78 %. – IR (KBr): ν
=
6 H, 2 × CH3), 1.52 (d, J = 8 Hz, 3 H, CH3), 1.76 – 3334 (NH), 3062 (Ar-H), 2924 (C-H), 1711 (C=O), 1599
1.82 (m, 1 H, CH), 2.38 (d, J = 8 Hz, 2 H, CH2), 2.86 (C=N) cm−1. – 1H NMR ([D6]DMSO): δ = 2.42 (s, 3 H,
(dd, J = 16 Hz, 1 H), 3.35 (dd, J = 16, 8 Hz, 1 H), SCH3), 2.89 (dd, J = 16 Hz, 1 H), 3.39 (dd, J = 16, 8 Hz,
4.19 (q, J = 4 Hz, 1 H, CH), 4.72 (dd, J = 8.7, 4 Hz, 1 H), 3.98 (s, 2 H, CH2), 4.62 (dd, J = 8.7, 4 Hz, 1 H),
1 H), 7.06 (d,J = 8 Hz, 2 H, Ar-H), 7.10 (d, J = 8 Hz, 7.12 – 7.23 (m, 5 H, Ar-H), 7.41 – 7.48 (m, 4 H, phenyl),
2 H, Ar-H), 7.32 – 7.48 (m, 4 H, 4-chlorophenyl), 13.98 14.00 (s, 1 H, NH). – 13C NMR ([D6]DMSO): δ = 16.1,
(s, 1 H, NH). – 13C NMR ([D6]DMSO): δ = 18.6, 19.3, 32.3, 35.2, 41.2, 124.3, 127.5, 128.5, 129.9, 139.9, 152.1,
22.8, 30.4, 34.5, 37.6, 40.3, 127.2, 128.4, 130.4, 132.1, 167.0, 172.7, 177.8. – LC-MS: m/z (%) = 410 (78) [M]+. –
141.2, 153.4, 169.1, 173.4, 179.8. – LC-MS: m/z (%) = C20H18N4O2S2 (410.5): calcd. C 70.87, H 9.15, N 12.72;
468 (60) [M]+, 470 (20) [M]+. – C24H25N4O2ClS (468.9): found C 70.85, H 9.13, N 12.70.
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4i: M. p. 160 ◦C; yield 72 %. – IR (KBr): ν = 3107 CH3), 2.41 (s, 3 H, SCH3), 2.86 (dd, J = 16 Hz, 1 H),
(NH), 3017 (Ar-H), 2920 (C-H), 1712 (C=O), 1596 (C=N) 3.38 (dd, J = 16, 8 Hz, 1 H), 3.98 (s, 2 H, CH2), 4.62 (dd,
cm−1. – 1H NMR ([D6]DMSO): δ = 2.41 (s, 3 H, SCH3), J = 8.7, 4 Hz, 1 H), 7.10 – 7.16 (m, 4 H, Ar-H), 7.29 – 7.33
2.85 (dd, J = 16 Hz, 1 H), 3.38 (dd, J = 16, 8 Hz, 1 H), 3.97 (s, (m, 4 H, 4-methylphenyl), 13.97 (s, 1 H, NH). – 13C NMR
2 H, CH2), 4.62 (dd, 1 H, J = 8.7, 4 Hz), 7.12 – 7.18 (m, 4 H, ([D6]DMSO): δ = 16.2, 21.6, 32.4, 35.2, 40.6, 126.8, 127.6,
Ar-H), 7.20 – 7.55 (m, 3 H, 3-chloro-4-fluorophenyl), 13.99 128.6, 129.4, 141.3, 151.4, 167.2, 172.2, 177.5. – LC-MS:
(s, 1 H, NH). – 13C NMR ([D6]DMSO): δ = 16.1, 32.3, 35.8, m/z (%) = 424 (61) [M]+. – C21H20N4O2S2 (424.5): calcd.
40.2, 127.6, 128.5, 128.7, 130.8, 139.2, 140.5, 152.1, 167.0, C 70.87, H 9.15, N 12.72; found C 70.85, H 9.13, N 12.70.
172.8, 177.7. – LC-MS: m/z (%) = 462 (69) [M]+, 464 (23)
4m: M. p. 138 ◦C; yield 79 %. – IR (KBr): ν = 3304
[M]+. – C20H16N4O2ClFS2 (462.9): calcd. C 70.87, H 9.15, (NH), 3086 (Ar-H), 2927 (C-H), 1715 (C=O), 1608 (C=N)
1
N 12.72; found C 70.85, H 9.13, N 12.70.
cm−1. – H NMR ([D6]DMSO): δ = 2.50 (s, 3 H, SCH3),
2.87 (dd, J = 16 Hz, 1 H), 3.38 (dd, J = 16, 8 Hz, 1 H),
3.85 (s, 3 H, OCH3), 4.02 (s, 2 H, CH2), 4.61 (dd, J =
8.7, 4 Hz, 1 H), 7.08 – 7.14 (m, 4 H, Ar-H), 7.36 – 7.42 (m,
4 H, 4-methoxyphenyl), 13.94 (s, 1 H, NH). – 13C NMR
([D6]DMSO): δ = 16.2, 32.3, 35.2, 40.8, 61.5, 127.2, 127.9,
129.2, 130.4, 140.6, 151.4, 168.1, 172.6, 177.9. – LC-MS:
4j: M. p. 182 ◦C; yield 68 %. – IR (KBr): ν = 3319
(NH), 3056 (Ar-H), 2923 (C-H), 1711 (C=O), 1603 (C=N)
cm−1. – 1H NMR ([D6]DMSO): δ = 2.43 (s, 3 H, SCH3),
2.86 (dd, J = 16 Hz, 1 H), 3.38 (dd, J = 16, 8 Hz, 1 H),
3.98 (s, 2 H, CH2), 4.60 (dd, J = 8.7, 4 Hz, 1 H), 7.14 –
7.24 (m, 4 H, Ar-H), 7.29 – 7.33 (m, 4 H, 4-fluorophenyl),
14.01 (s, 1 H, NH). – 13C NMR ([D6]DMSO): δ = 16.2, m/z (%) = 440 (68) [M]+. – C21H20N4O3S2 (440.5): calcd.
32.1, 35.3, 40.7, 127.5, 128.1, 129.1, 129.4, 140.4, 152.1, C 70.87, H 9.15, N 12.72; found C 70.85, H 9.13, N 12.70.
167.0, 172.7, 177.5. – LC-MS: m/z (%) = 428 (64) [M]+. –
4n: M. p. 170 ◦C; yield 68 %. – IR (KBr): ν = 3284
C20H17N4O2FS2 (428.5): calcd. C 70.87, H 9.15, N 12.72; (NH), 3042 (Ar-H), 2926 (C-H), 1705 (C=O), 1598 (C=N)
1
found C 70.85, H 9.13, N 12.70.
cm−1. – H NMR ([D6]DMSO): δ = 2.50 (s, 3 H, SCH3),
2.86 (dd, J = 16 Hz, 1 H), 3.38 (dd, J = 16, 8 Hz, 1 H), 4.02
(s, 2 H, CH2), 4.61 (dd, J = 8.7, 4 Hz, 1 H), 7.08 – 7.14 (m,
4 H, Ar-H), 7.36 – 7.42 (m, 4 H, 4-bromophenyl), 13.94 (s,
1 H, NH). – 13C NMR ([D6]DMSO): δ = 16.1, 32.2, 35.2,
41.1, 126.2, 127.1, 128.4, 129.8, 140.2, 151.4, 168.0, 172.4,
177.6. – LC-MS: m/z (%) = 488 (58) [M]+, 490 (58) [M]+. –
C20H17N4O2BrS2 (489.4): calcd. C 70.87, H 9.15, N 12.72;
found C 70.85, H 9.13, N 12.70.
4k: M. p. 171 ◦C; yield 80 %. – IR (KBr): ν
=
3248 (NH), 3084 (Ar-H), 2978 (C-H), 1713 (C=O), 1614
(C=N) cm−1. – 1H NMR ([D6]DMSO): δ = 2.48 (s, 3H,
SCH3), 2.85 (dd, J = 16 Hz, 1 H), 3.38 (dd, J = 16, 8 Hz, 1 H),
4.01 (s, 2 H, CH2), 4.61 (dd, J = 8.7, 4 Hz, 1 H), 7.12 – 7.16
(m, 4 H, Ar-H), 7.34 – 7.38 (m, 4 H, 4-chlorophenyl), 13.94
(s, 1 H, NH). – 13C NMR ([D6]DMSO): δ = 16.2, 32.3, 35.2,
40.9, 126.5, 127.2, 128.4, 129.2, 140.8, 151.2, 167.1, 172.9,
177.3. – LC-MS: m/z (%) = 444 (75) [M]+, 446 (25) [M]+. –
C20H17N4O2ClS2 (444.9): calcd. C 70.87, H 9.15, N 12.72;
found C 70.85, H 9.13, N 12.70.
Acknowledgements
The authors are thankful to the Director, IISE Bangalore
4l: M. p. 130 ◦C; yield 76 %. – IR (KBr): ν = 3308 and CDRI Lucknow for H NMR, 13C NMR, mass and IR
1
data. M. K. is grateful to UGC for providing financial assis-
tance under the UGC-RFSMS scheme.
(NH), 3067 (Ar-H), 2965 (C-H), 1709 (C=O), 1603 (C=N)
cm−1. – 1H NMR ([D6]DMSO): δ = 2.33 (s, 3 H, Ar-
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