Carbodiimide mediated synthesis of new thiazolidin-4-ones and thiazinan-4-ones from thiosemicarbazone derivatives of 6,7-dihydro-1H-indazole- 4(5H )-ones

Article abstract of DOI:10.3184/174751914X13940194215183

5,5-Dimethyl-2-[(2-substitutedphenylhydrazinyl)methylene]cyclohexane-1, 3-dione, obtained from heating dimedone with N,N'-dimethylformamide dimethyl acetal (DMF-DMA) and phenyl hydrazines, on cyclisation in ethanol gave 6,7-dihydro- 1H-indazol-4(5H )-ones

Full text of DOI:10.3184/174751914X13940194215183

226 RESEARCH PAPER
VOL. 38 APRIL, 226–230
JOURNAL OF CHEMICAL RESEARCH 2014
Carbodiimide mediated synthesis of new thiazolidin-4-ones and
thiazinan-4-ones from thiosemicarbazone derivatives of
6,7-dihydro-1H-indazole-4(5H)-ones
Poonam Gautam and Ram P. Chaudhary*
Department of Chemistry, Sant Longowal Institute of Engineering & Technology, Longowal (Sangrur) Punjab-148106, India
5,5-Dimethyl-2-[(2-substitutedphenylhydrazinyl)methylene]cyclohexane-1,3-dione, obtained from heating dimedone with
N,N′-dimethylformamide dimethyl acetal (DMF–DMA) and phenyl hydrazines, on cyclisation in ethanol gave 6,7-dihydro-
1H-indazol-4(5H)-ones. The thiosemicarbazone derivative of 6,7-dihydro-1H-indazole-4(5H)-ones, on cyclocondensation
with α and β-haloacids in the presence of N,N′-dicyclohexylcarbodiimide afforded new thiazolidin-4-ones and 1,3-thiazinan-
4-ones respectively. Thiosemicarbazone of 6,7-dihydro-1H-indazol-4(5H)-ones on stirring with phenacyl bromides yields
2,4-disubstituted thiazoles. X-ray structure of the intermediate compound 5-dimethyl-2-[(2-phenylhydrazinyl)methylene]
cyclohexane-1,3-dione was determined.
Keywords: cyclocondensation, thiazolidin-4-ones, thiazinan-4-ones, thiazoles, indazole, N,N′-dicyclohexylcarbodiimide
The pyrazole scaffold, in general, has drawn a good deal of
attention due to its biological and pharmaceutical activities.1,2
Indazoles, in particular, have been reported to possess
antineoplastic activity. As examples, N2-(substituted benzyl)-
bidentate nucleophiles. Pyrazoles are generally prepared by
reaction of enaminoketones with substituted hydrazines. The
reaction is tandem addition–elimination/cyclodehydration,
which takes place by a Michael addition of the terminal amino
group of hydrazines to form acyclic intermediate 2 followed
by intramolecular cyclodehydration to pyrazole derivative 3.
The synthesis of pyrazole 3a has been reported by refluxing of
enaminoketonesinbutanoloraceticacid19 orthroughmicrowave
irradiations20 without isolation of the acyclic intermediate 2. In
the present investigations, it was found that heating of dimedone
with DMF–DMA and phenyl hydrazine at 70 °C just for 5 min
without any solvent yielded intermediate 2, which on refluxing
in ethanol for 2 h furnish pyrazoles 3. The cyclodehydration
of compound 2 to yield 3 also occurs during the synthesis of
thiosemicarbazone derivative of 2. The structure of 2a and 2b
was established by spectral data. The crystal structure of 2a
(Ar=C6H5) is reported in the crystallography section of this
paper. Pyrazoles 3a and 3b have been characterised by display
of characteristic CH peak of pyrazole ring in 1H NMR spectrum.
Thiosemicarbazone derivative of pyrazole 3, on condensation
with α-or β-halo acids in presence of DCC and tetrahydrofuran
(THF) furnished thiazolidin-4-ones 5 and thiazinan-4-ones 6
respectively (Schemes 1 and 2). Compounds 5 and 6 could also
be obtained by conventional refluxing of thiosemicarbazones
and haloacids in presence of sodium acetate and acetic acid
for 6–12 h. In the present investigation, compounds 5 and 6
were assembled from reactants by DCC, as coupling agent, at
0 °C in just 50 min. The reaction was also carried out at room
temperature in THF but the yield of products was less than at
0 °C. The 1H NMR spectra of 5a and 5c display singlet of two
protons each at δ 3.77 and δ 3.79, which is assigned to SCH2
group of thiazolidin-4-one ring. The IR spectrum of 5a and 5c
showed peaks at 1710 and 1715 cm–1 confirming the formation
3-(4-methylphenyl)-2H-indazoles
exhibit
antiangiogenic
activity,3 pyrimidol[1,2-b]indazoles are potential anticancer
agents and lonidamine, 1-(2,4-dichlorobenzyl)-1H-indazole-3-
carboxylic acid is a new anticancer drug that selectively inhibits
the metabolism of neoplastic cells. Thiazoles, 1,3-thiazinan-4-
ones and thiazolidin-4-ones are the heterocyclic compounds
with multiple applications and have long been known to be
biologically active.4,5 Thiazoles show very intensive antitumour
activity especially the phenyl substituted benzothiazoles,6
while 4-thiazolidinones and their derivatives exert antiviral
activity.7 These heterocycles have been reported to show a
broad spectrum of biological activities,8,9 and a wide range of
pharmacological activities such as analgesic,10 anticonvulsant,11
and antitubercular12 activities. Since the combination of
pharmacophores on the same scaffold is a well-established
approachtothesynthesisofbiologicallymorepotentcompounds,
we decided to incorporate thiazole, thiazolodin-4-one and
1,3-thiazinan-4-one rings in the indazole moiety in an effort to
synthesise new derivatives of indazoles. Various approaches for
the synthesis of thiazolidin-4-ones and 1,3-thiazinan-4-ones
are have been reported.13 Nevertheless, a common synthetic
strategy to construct thiazolidin-4-one and 1,3-thiazinan-4-
one ring is the cyclisation of thiosemicarbazide derivatives
with α-halo esters or acids and β-haloacids in presence of
inorganic base (i.e. NaOAc) in polar solvents using either a
conventional or microwave irradiation methods.14,15 However,
most of the reported procedures suffer from drawbacks of
longer reaction times, use of hazardous solvents and moderate
yields. In continuation of our research programme on synthesis
of thiazolidin-4-ones16,17 and 1,3-thiazinan-4-ones,18 we now
report the synthesis of new indazole derivatives containing
bioactive moieties, thiazoles, thiazolidin-4-ones and thiazinan-
4-ones, by using N,N′-dicyclohexylcarbodiimide (DCC) as the
coupling agent in 50 min at 0°C with excellent yields.
1
of thiazolidin-4-one ring. H NMR spectrum of 5b and 5d
display quartet of one proton at δ 4.03 and 4.04 and doublet
of methyl group at δ 1.51 and δ 1.56 corroborated by their
structures. IR, 13C NMR and mass spectra of these compounds
also supported the assigned structure. IR spectra of 6a and 6b
display peaks at 1690 cm–1 and 1685 cm–1 which are assigned to
carbonyl group of a six membered ring. 13C NMR spectrum and
mass support structure of 6a. Similarly the structure of 6b has
been established by spectral and mass data. Thiosemicarbazone
derivatives 4, on condensation with phenacyl bromides yielded
thiazoles 7 (Scheme 2). In compound 7a, the appearance of
Results and discussion
Enaminoketones, obtained by the reaction of active methylene
ketoneswithdimethylformamidedimethylacetal(DMF–DMA),
gave a vast array of heterocyclic compounds with appropriate
1
* Correspondent. E-mail: rpchaudhary65@gmail.com
a characteristic peak in H NMR spectrum at δ 7.22 showed
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JOURNAL OF CHEMICAL RESEARCH 2014 227
N
N
O
O
r
O
A
CHNHNHAr
O
ArNHNH2.HCl
EtOH
conc.
H
Cl
-
DMF DMA
O
3(a), Ar= C6H5
(b), Ar= C6H4-Cl-p
2
1
H
R
N
N
N
S
N
N
O
N
O
r
Ar
NNHCSNH2
A
r
N
A
N
NH2NHCSNH2
N
DCC
H
ClCH2COOH
or
CH3CH(Br)COOH
5 (a), R=H,
(b), R= CH , Ar C H
6
5
Ar C H
=
6
5
=
4
3
3
p
p
(c), R= H, Ar C H -Cl-
=
6
4
(d), R=CH , Ar C H -Cl-
=
3
6
4
Scheme 1 Synthesis of 6,7-dihydro-1H-indazole-4(5H)-ones 3 and thiazolidin-4-ones 5 containing indazole moiety.
N
S
N
N
S
Ar'
N
N
N
N
Ar
r
A
NNHCSNH2
N
Ar
N
N
N
N
H
Ar'COCH2Br
O
DCC
H
Cl(CH2)2COOH
4
(a), Ar=C H ;
Ar'= C6H5
7
6 a , Ar C H
( )
=
6
5
6
5
(b), Ar= C6H5;
(c), Ar= C6H5;
Ar'= C6H4-Cl-p
(b), Ar C H -Cl-p
=
6
4
Ar'= C H -NO -
p
(d), Ar= p-Cl-C6H4; Ar'= C66H54
2
(e), Ar= p-Cl-C6H4; Ar'= C6H4-Cl-p
(f), Ar= p-Cl-C H ; Ar'= C H -NO -
p
2
6
4
6
4
Scheme 2 Synthesis of 1,3-thiazinan-4-ones 6 and 2,4-disubstituted thiazoles 7 bearing 6,7-dihydro-1H-indazole moiety.
that thiazole ring has been formed. The structures of other
thiazole derivatives (7b–f) have been established in similar
fashion by analytical and spectral data.
Table 1 Crystal data and the structure refinement of 5,5-dimethyl-2-
[(2-phenylhydrazinyl)methylene]cyclohexane-1,3-dione (2a)
CCDC no.
Empirical formula
Formula weight
Temperature/K
Wavelength/Å
945437
C15H18N2O2
258.31
Crystallography
293 (2)
X-ray diffraction measurements were performed on X
Calibur EOS Oxford Diffractometer at 293 (2) K. The
intensity data were collected using graphite monochromated
Mo-Kα radiation (λ=0.71073 Å). The structure was solved by
direct method using the SHELX-97 software package21 and
refined by full-matrix least-squares procedures on F2. All
non-hydrogen atoms were refined with anisotropic thermal
parameters.
0.71073
Monoclinic
C2/c
Crystal system
Space group
Unit cell dimensions
a/Å
b/Å
26.986(10)
9.271(4)
c/Å
12.691(5)
α/˚
90.00
β/˚
116.66(5)
The compound 2a crystallises in the monoclinic space
group C2/c, with Z=8 and cell parameters a=26.986(10)
Å, b=9.271(4) Å, c=12.691(5) Å, αꢀ=ꢀ90.00˚, βꢀ= 116.66(5)˚,
γꢀ=ꢀ90.00˚. In the compound, O(1)–C(12) and C–C(7) bond
distances of 1.242(3) and 1.379(3) Å, respectively, indicate the
double character of these bonds. The bond angles N2CC7 and
O1C12C7 are 126.4˚ (2) and 122.1˚ (2) respectively, which is
consistent with the sp2 hybrid character of C and C12 atoms.
The crystallographic data and refinement parameters of 2a
are shown in Fig. 1, and Tables 1 and 2.
γ/˚
90.00
2837.5(19)
8
1.209
0.081
Volume/Å3
Z
Density (calculated)/Mg m–3
Absorption coefficient/mm–1
Crystal size/mm3
Theta range for data collection
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I>2σ(I)=2591 data]
R indices (all data)
Largest diff. peak and hole/eÅ–3
0.28×0.24×0.16
3.1818 to 28.8377
5,136
1,378
2868/0/173
1.011
R1 =0.0579, wR2 = 0.1475
R1 =0.1286, wR2 =0.1976
–0.326, 0.342
Crystallographic data for the structure reported in this paper
has been deposited with the Cambridge Crystallographic Data
Centre and its CCDC No is 945437.
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228 JOURNAL OF CHEMICAL RESEARCH 2014
Table 2 Selected bond parameters of 5,5-dimethyl-2-
[(2-phenylhydrazinyl)methylene]cyclohexane-1,3-dione (2a)
Bond
Length/Å
Bond
Angle/˚
O(1)–C(12)
N(2)–C
N(2)–N
O–C(8)
N–C(5)
C(5)–C(9)
C(5)–C(11)
C(7)–C(12)
1.242(3)
1.311(3)
1.396(3)
1.239(3)
1.414(3)
1.373(4)
1.394(3)
1.449(3)
C–N(2)–H(2)
119.5
119.5
116.4(2)
121.8
123.0(2)
126.4(2)
116.8
N–N(2)–H(2)
N(2)–N–C(5)
C(5)–N–H(0)
C(9)–C(5)–N
N(2)–C–C(7)
N(2)–C–H0(A)
C(7)–C(8)–C(15)
C(5)–C(9)–C(13)
C(7)–C–H0(A)
O(1)–C(12)–C(7)
118.9(2)
119.9(3)
C(7)–C(8)
C–C(7)
1.461(3)
1.379(3)
116.8
122.1(2)
Fig. 1 ORTEP drawing and atomic labelling of 5,5-dimethyl-2-[(2-
phenylhydrazinyl)methylene]cyclohexane-1,3-dione (2a) with displacement
ellipsoids plotted at 50% probability level.
Experimental
8.16 (s, 1H, CH of pyrazole ring). Anal. calcd for C15H15ClN2O: C,
65.57; H, 5.50; N, 10.20; found: C, 65.78; H, 5.12; N, 9.99%.
All the chemicals used were obtained from Sigma and used without
further purification. Melting points were determined in open
capillaries and are reported uncorrected. Elemental analysis was done
on a Euro EA 3000 elemental analyser. Mass spectra were recorded
Synthesis of 4; general procedure
on Waters, Q-TOF Micromass (LC-MS) instrument. 1H NMR and 13
C
A mixture of 3 (1.0 mmol), thiosemicarbazide (0.09 g, 1.0 mmol) and
0.4 mL conc. HCl in absolute ethanol (10 mL) was stirred at room
temperature for 3 h. The reaction mixture was poured into ice-cold
water. The solid thus obtained was filtered, dried and recrystallised
from ethanol.
NMR were recorded in CDCl3 and DMSO-d6 on a Bruker Avance II
400 NMR spectrometer using tetramethylsilane (TMS) as an internal
standard. The chemical shifts are reported in ppm. IR spectra were
recorded on ABB FTIR spectrometer and the results are reported in
cm–1. TLC was performed on silica gel G coated plates and using iodine
vapour as visualising agent. X-ray diffraction was performed on X
Calibur EOS Oxford diffractometer.
2-[6,6-dimethyl-1-phenyl-6,7-dihydro-1H-indazol-4(5H)-yliden]
hydrazinecarbothioamide (4a): White crystals, yield 90%, m.p. 180–
182 °C. IR (cm–1): 3433, 3256 (NH), 1582 (C=N), 1497 (C=C), 1288
1
(C=S); H NMR (400 MHz, DMSO-d6): δ 1.05 (s, 6H, 2CH3), 2.56 (s,
Synthesis of 2; general procedure
2H, CH2), 2.74 (s, 2H, CH2), 7.38–7.39 (m, 1H, C6H5), 7.50–7.53 (m,
4H, C6H5), 7.69 (br, 1H, NH), 7.95 (br, 1H, NH), 8.09 (s, 1H, CH), 10.10
(br, 1H, NH). Anal. calcd for C16H19N5S: C, 61.31; H, 6.11; N, 22.34; S,
10.23; found: C, 61.17; H, 5.96; N, 21.95; S, 10.31%.
A mixture of dimedone (0.7 g, 5 mmol) and DMF–DMA (1.19 mL,
10 mmol) was stirred at 70 °C for 2 min. Substituted hydrazine
(4 mmol)) was then added to the reaction mixture and stirring
continued for 5 min. The solid obtained was filtered, washed with
benzene and recrystallised from ethanol.
2-[1-(4-chlorophenyl)-6,6-dimethyl-6,7-dihydro-1H-indazol-4(5H)-
ylidene]hydrazinecarbothioamide (4b): White crystals yield 90%, m.p.
214–216 °C. IR (cm–1): 3433, 3256 (NH), 1582 (C=N), 1497 (C=C), 1288
5,5-Dimethyl-2-[(2-phenylhydrazinyl)methylene]cyclohexane-1,3-
dione (2a): White crystalline solid, yield 81%, m.p. 168–169 °C; IR
1
(C=S); H NMR (400 MHz, DMSO-d6): δ 1.03 (s, 6H, 2CH3), 2.75 (s,
1
(cm–1): 1690 (C=O); H NMR (400 MHz, DMSO-d6): δ 1.00 (s, 6H,
2H, CH2), 2.93 (s, 2H, CH2), 7.50–7.56 (m, 4H, C6H5), 7.79 (br, 1H, NH),
8.12 (br, 1H, NH), 8.17 (s, 1H, CH), 10.20 (br, 1H, NH). Anal. calcd for
C16H18ClN5S: C, 55.24; H, 5.22; N, 20.13; S, 9.22; found: C, 55.46; H,
5.27; N, 20.36; S, 9.43%.
2CH3), 2.28 (s, 2H, CH2), 2.38 (s, 2H, CH2), 6.72–6.74 (d, 2H, C6H5,
J=8.0 Hz), 6.85–6.88 (t, 1H, C6H5, J=7.2 Hz), 7.24 (m, 2H, C6H5), 8.0
(s, 1H, CH), 9.0 (s, 1H, NH), 12.01 (s, 1H, NH); mass m/z 259.1( M + H+,
100%). Anal. calcd for C15H18N2O2: C, 69.74; H, 7.02; N, 10.84; found:
C, 69.44; H, 6.65; N, 10.51%.
2-[{2-(4-Chlorophenyl)hydraziny}methylene]-5,5-dimethyl-
cyclohexane-1,3-dione (2b): Yellow crystalline solid, yield 71%, m.p.
162–164 °C. IR (cm–1): 1690 (C=O); 1H NMR (400 MHz, DMSO-d6): δ
1.03 (s, 6H, 2CH3), 2.28 (s, 2H, CH2), 2.39 (s, 2H, CH2), 6.73–6.77 (m,
2H, C6H5), 7.20–7.24 (m, 2H, C6H5), 8.03–8.05 (d, 1H, CH, J=8.0 Hz),
9.13 (s, 1H, NH), 12.08 (s, 1H, NH). Anal. calcd for C15H17ClN2O2: C,
61.54; H, 5.85; N, 9.57; found: C, 61.56; H, 5.78; N, 9.52%.
Syntheses of 5 and 6; general procedure
A mixture of thiosemicarbazone 4 (1.0 mmol), chloroacetic acid/2-
bromopropionic acid or 3-chloropropionic acid (2.5 mmol) in THF
(15 mL) was stirred at 0 °C for 5 min and then DCC (1.2 mmol) was
added to the reaction mixture at 0°C and reaction mixture was stirred
for additional 50 min at room temp. The progress of the reaction was
monitored by TLC. DCU was removed by filtration and the filtrate was
concentrated to dryness under reduced pressure and the residue was
taken up in ethyl acetate. The organic layer was successively washed
with 10% aq. citric acid, water, 10% aq. sodium hydrogen carbonate
and then finally with brine. The organic layer was dried over sodium
sulphate and solvent was removed under reduced pressure to get a
crude product, which was recrystallised from ethanol.
Synthesis of 3; general procedure
A mixture of 2 (0.625 mmol) in ethanol (5.0 mL) and 0.5 mL conc. HCl
was refluxed for 3 h. The reaction mixture was then cooled to room
temperature and poured in to ice cold water. The solid, obtained was
filtered, dried and recrystallised from ethanol.
(E)-2-[(E)-{6,6-dimethyl-1-phenyl-6,7-dihydro-1H-indazol-4(5H)-
ylidene}hydrazono]thiazolidin-4-one (5a): Yellow crystals, yield 72%,
m.p. 190–192 °C. IR (cm–1): 3742 (NH), 1710 (N–C=O), 1620 (C=N);
1H NMR (400 MHz, DMSO-d6): δ 1.05 (s, 6H, 2CH3), 2.14 (s, 2H, CH2),
2.47 (s, 2H, CH2), 3.77 (s, 2H, SCH2), 7.38–7.52 (m, 5H, C6H5), 8.57 (s,
1H, CH), 11.70 (br, 1H, NH); 13C NMR (100 MHz, DMSO-d6): δ 173.0
(C=O), 159.4 (C=N), 159.4 (C=N), 142.8, 142.4, 138.5, 128.8, 127.2,
123.2, 113.6 (C6H5), 44.8, 36.9, 33.4, 32.8, 27.4; mass m/z 354.1 (M+H+,
100%). Anal. calcd for C18H19N5OS: C, 61.17; H, 5.42; N, 19.81; S, 9.07;
found: C, 61.49; H, 5.29; N, 19.61; S, 9.31%.
6,6-Dimethyl-1-phenyl-6,7-dihydro-1H-indazol-4(5H)-one (3a):
White crystalline solid, yield 65%, m.p. 116–118 °C. IR (cm–1): 1690
(C=O); 1H NMR (400 MHz, CDCl3): δ 1.11 (s, 6H, 2CH3), 2.43 (s, 2H,
CH2), 2.83 (s, 2H, CH2), 7.42–7.46 (m, 1H, C6H5), 7.49–7.55 (m, 4H,
C6H5), 8.08 (s, 1H, CH of pyrazole ring). Anal. calcd for C15H16N2O: C,
74.97; H, 6.71; N, 11.66; found: C, 75.21; H, 6.82; N, 11.38%.
1-(4-Chlorophenyl)-6,6-dimethyl-6,7-dihydro-1H-indazol-4(5H)-
one (3b): White crystalline solid, yield 81%, m.p. 126–128 °C. IR
1
(cm–1): 1690 (C=O); H NMR (400 MHz, DMSO-d6): δ 1.07 (s, 6H,
2CH3), 2.37 (s, 2H, CH2), 2.91 (s, 2H, CH2), 7.55–7.62 (m, 4H, C6H5),
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JOURNAL OF CHEMICAL RESEARCH 2014 229
(E)-2-[(E)-{6,6-dimethyl-1-phenyl-6,7-dihydro-1H-indazol-4(5H)-
ylidene}hydrazono]-5-methylthiazolidin-4-one (5b): White crystals,
yield 75%, m.p. 208–210 °C. IR (cm–1): 3342 (NH), 1705 (N–C=O),
2.77 (s, 2H, CH2), 7.22 (s, 1H, CH of thiazole ring), 7.35–7.46 (m, 4H,
C6H5), 7.51–7.59 (m, 4H, C6H5), 7.79–7.81 (m, 2H, C6H5), 8.01 (s, 1H,
CH), 8.24–8.26 (d, 2H, C6H4, J=8.9 Hz); mass m/z 414.2 (M+H+,
100%). Anal. calcd for C24H23N5S: C, 69.71; H, 5.61; N, 16.94; S, 7.75;
found: C, 69.88; H, 5.78; N, 17.12; S, 7.92%.
1
1610 (C=N); H NMR (400 MHz, DMSO-d6): δ 0.99 (s, 6H, 2CH3),
1.51–1.53 (d, 3H, CH3, J=7.2 Hz), 2.41 (s, 2H, CH2), 2.73 (s, 2H, CH2),
4.04–4.09 (q, 1H, HA, J=7.0 Hz, 7.2 Hz), 7.47–7.51 (m, 4H, C6H5),
8.52 (s, 1H, CH), 11.69 (br, 1H, NH); 13C NMR(100 MHz, DMSO-d6):
δ 176.0 (C=O), 158.1 (C=N), 154.2 (C=N), 143.8, 142.4, 138.6, 129.8,
127.3, 123.3, 113.6 (C6H5), 44.8, 41.9, 36.8, 33.5, 27.4, 18.9; mass m/z
368.1 (M+H+, 100%). Anal. calcd for C19H21N5OS: C, 62.10; H, 5.76; N,
19.06; S, 8.73; found: C, 62.23; H, 5.81; N, 18.96; S, 8.83%.
(E)-2-[(E)-{1-(4-chlorophenyl)-6,6-dimethyl-6,7-dihydro-1H-
indazol-4(5H)-ylidene}hydrazono]thiazolidin-4-one (5c): Yellow
crystalline compound, yield 72%, m.p. 198–200 °C. IR (cm–1): 3742
(NH), 1715 (N–C=O), 1620 (C=N) 1H NMR (400 MHz, CDCl3):
δ 1.03 (s, 6H, 2CH3), 2.68 (s, 2H, CH2), 2.70 (s, 2H, CH2), 3.79 (s, 2H,
SCH2), 7.43–7.45 (m, 4H, C6H5), 8.03 (br, 1H, NH), 8.10 (s, 1H, NH);
13C NMR(100 MHz, CDCl3): δ 173.4 (C=O), 162.6, 160.8, 157.3 (C=N),
143.5, 142.7, 137.6, 137.3, 133.17, 129.4, 124.9, 117.6 (C6H5), 45.4, 39.4,
39.2, 37.6, 36.5, 34.0, 33.9, 31.4, 28.4, 27.9; mass m/z 388.1 (M+H+,
100%). Anal. calcd for C18H18ClN5OS: C, 55.74; H, 4.68; N, 18.06; S,
8.27; found: C, 55.61; H, 4.78; N, 18.21; S, 8.34%.
(E)-4-(4-chlorophenyl)-2-[2-{6,6-dimethyl-1-phenyl-6,7-dihydro-
1H-indazol-4(5H)-ylidene}hydrazinyl]thiazole (7b): Yellow solid,
yield 78%, m.p. 212–215 °C. IR (cm–1): 3112 (NH), 1601 (C=N), 1494
1
(C=C), 728 (C–Cl); H NMR (400 MHz, DMSO-d6): δ 1.08 (s, 6H,
2CH3), 2.60 (s, 2H, CH2), 2.77 (s, 2H, CH2), 7.13 (s, 1H, CH of thiazole
ring), 7.38–7.40 (m, 3H, C6H5), 7.52–7.53 (m, 4H, C6H5), 7.80–7.82
(m, 2H, C6H5), 7.94 (s, 1H, CH), 8.00 (br, 1H, NH). Anal. calcd for
C24H22ClN5S: C, 64.35; H, 4.95; N, 15.63; S, 7.16; found: C, 64.48; H,
5.19; N, 15.88; S, 7.02%.
(E)-2-[2-{6,6-dimethyl-1-phenyl-6,7-dihydro-1H-indazol-4(5H)-
ylidene}hydrazinyl]-4-(4-nitrophenyl)thiazole (7c): Orange solid, yield
72%, m.p. 210–212 °C. IR (cm–1): 3342 (NH), 1641 (C=N), 1494 (C=C),
1558, 1328 (NO2), 1509 (C=C); 1H NMR (400 MHz, DMSO-d6): δ 1.09
(s, 6H, 2CH3), 2.57 (s, 2H, CH2), 2.77 (s, 2H, CH2), 7.43 (s, 1H, C6H5),
7.52 (s, 1H, CH of thiazole ring), 7.53 (m, 4H, C6H5), 8.01 (s, 1H, CH),
8.08–8.09 (d, 2H, C6H4, J=6.9 Hz), 8.24–8.26 (d, 2H, C6H4, J=8.9 Hz).
Anal. calcd for C24H22N6O2S: C, 62.86; H, 4.84; N, 18.33; S, 6.99; found:
C, 62.57; H, 4.88; N, 18.42; S, 6.88%.
(E)-2-[(E)-{1-(4-chlorophenyl)-6,6-dimethyl-6,7-dihydro-1H-
indazol-4(5H)-ylidene}hydrazon]-5-methylthiazolidin-4-one (5d):
White crystals, yield 75%, m.p. 194–196 °C. IR (cm–1): 3342 (NH),
(E)-2-[2-{1-(4-chlorophenyl)-6,6-dimethyl-6,7-dihydro-1H-indazol-
4(5H)-ylidene}hydrazinyl]-4-phenylthiazole (7d): Black compound,
yield 80%, m.p. 190–192 °C. IR (cm–1): 3115 (NH), 1610 (C=N), 1501
(C=C); 1H NMR (400 MHz, DMSO-d6): δ 0.90 (s, 6H, 2CH3), 2.63 (s,
2H, CH2), 2.79 (s, 2H, CH2), 7.14 (s, 1H, CH of thiazole ring), 7.38–7.49
(m, 4H, C6H5), 7.50–7.54 (m, 4H, C6H5), 7.70–7.71 (m, 1H, C6H5), 8.02
(s, 1H, CH). Anal. calcd for C24H22ClN5S: C, 64.35; H, 4.95; N, 15.63; S,
7.16; found: C, 64.55; H, 5.13; N, 15.78; S, 7.32%.
1
1705 (N–C=O), 1610 (C=N); H NMR (400 MHz, DMSO-d6): δ 1.04
(s, 6H, 2CH3), 1.56–1.58 (d, 3H, CH3, J=6.9 Hz), 2.45 (s, 2H, CH2),
2.75 (s, 2H, CH2), 4.03–4.08 (q, 1H, HA, J=7.1 Hz, 6.9 Hz), 7.52–7.53
(d, 4H, C6H5, J=5.0 Hz), 8.57 (s, 1H, CH), 11.68 (br, 1H, NH); 13C
NMR (100 MHz, DMSO-d6): δ 176.0 (C=O), 158.1 (C=N), 154.2
(C=N), 143.8, 142.4, 138.6, 129.8, 127.3, 123.3, 113.6 (C6H5), 44.8, 41.9,
36.8, 33.5, 27.4, 18.9; mass m/z 402.1 (M+H+, 100%). Anal. calcd for
C19H20ClN5OS: C, 56.78; H, 5.02; N, 17.43; S, 7.98; found: C, 56.78; H,
4.88; N, 17.39; S, 7.92%.
(E)-2-[(E)-{6,6-dimethyl-1-phenyl-6,7-dihydro-1H-indazol-4(5H)-
ylidene}hydrazono]-1,3-thiazinan-4-one (6a): Light yellow crystals,
yield 55%, m.p. 218–220 °C. IR (cm–1): 3241 (NH), 1690 (N–C=O),
1595 (C=N); 1H NMR (400 MHz, DMSO-d6): δ 1.02 (s, 6H, 2CH3), 2.53
(m, 2H, CH2), 2.77 (m, 4H, CH2), 3.07 (s, 2H, CH2), 7.50 (s, 1H, C6H5),
7.52–7.57 (m, 4H, C6H5), 8.74 (s, 1H, CH), 11.13 (br, 1H, NH); 13C NMR
(100 MHz, DMSO-d6): δ 169.9 (C=O), 154.9 (C=N), 154.2 (C=N),
142.9, 142.9, 138.7, 129.0, 129.0, 127.3, 123.3, 122.7, 113.54 (C6H5), 44.9,
36.9, 33.9, 33.4, 28.0, 27.4, 21.9; mass m/z 368.1 (M+H+, 100%). Anal.
calcd for C19H21N5OS: C, 62.10; H, 5.76; N, 19.06; S, 8.73; found: C,
61.47; H, 5.41; N, 18.91; S, 8.43%.
(E)-4-(4-chlorophenyl)-2-[2-{1-(4-chlorophenyl)-6,6-dimethyl-6,7-
dihydro-1H-indazol-4(5H)-ylidene}hydrazinyl]thiazole (7e): Yellow
compound, yield 80%, m.p. 202–204 °C. IR (cm–1): 3118 (NH), 1615
1
(C=N), 1510 (C=C); H NMR (400 MHz, DMSO-d6): δ 1.03 (s, 6H,
2CH3), 2.49 (s, 2H, CH2), 2.69 (s, 2H, CH2), 7.20 (s, 1H, CH of thiazole
ring), 7.37–7.58 (m, 4H, C6H5), 7.83–7.90 (m, 4H, C6H5), 7.93 (s, 1H,
CH). Anal. calcd for C24H21Cl2N5S: C, 59.75; H, 4.39; N, 14.52; S, 6.65;
found: C, 59.71; H, 4.63; N, 14.69; S, 6.59%.
(E)-2-[2-{1-(4-chlorophenyl)-6,6-dimethyl-6,7-dihydro-1H-indazol-
4(5H)-ylidene}hydrazinyl]-4-(4-nitrophenyl)thiazole (7f): Yellow
compound, yield 80%, m.p.>240 °C. IR (cm–1): 3120 (NH), 1618
1
(C=N), 1512 (C=C); H NMR (400 MHz, DMSO-d6): δ 1.04 (s, 6H,
(E)-2-[(E)-{1-(4-chlorophenyl)-6,6-dimethyl-6,7-dihydro-1H-
indazol-4(5H)-ylidene}hydrazono]-1,3-thiazinan-4-one (6b): Light
yellow crystals, yield 55%, m.p. 210–212 °C. IR (cm–1): 3265 (NH),
2CH3), 2.49 (s, 2H, CH2), 2.71 (s, 2H, CH2), 7.25 (s, 1H, CH of thiazole
ring), 7.39–7.59 (m, 4H, C6H5), 7.84–7.91 (m, 4H, C6H5), 7.98 (s, 1H,
CH). Anal. calcd for C24H21ClN6O2S: C, 58.47; H, 4.29; N, 17.05; S,
6.50; found: C, 58.63; H, 4.41; N, 16.89; S, 6.38%.
1
1685 (N–C=O), 1605 (C=N); H NMR (400 MHz, DMSO-d6): δ 1.04
(s, 6H, 2CH3), 2.41 (m, 2H, CH2), 2.75–2.78 (m, 4H, CH2), 3.06 (s, 2H,
CH2), 7.51–7.58 (m, 4H, C6H5), 8.74 (s, 1H, CH), 11.11 (br, 1H, NH); 13C
NMR (100 MHz, DMSO-d6): δ 169.9 (C=O), 155.2 (C=N), 154.0 (C=N),
143.1, 143.1, 137.5, 132.0, 129.2, 129.1, 124.8, 113.8, (C6H5), 44.9, 36.8,
33.9, 33.4, 27.4, 21.9; mass m/z 402.1 (M+H+, 100%). Anal. calcd for
C19H20ClN5OS: C, 56.78; H, 5.02; N, 17.43; S, 7.98; found: C, 56.96; H,
5.12; N, 17.56; S, 8.26%.
Electronic supplementary information
NMR and mass spectra of the new compounds are available
through:
stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data.
The facilities provided by authorities of Sant Longowal Institute
of Engineering and Technology, Longowal are gratefully
acknowledged. We are thankful to Prof. S. Bhattacharya, BHU,
Varanasi for crystallographic studies.
Synthesis of 7; general procedure
A mixture of 4 (0.5 mmol) and phenacyl bromides (0.5 mmol) in 5.0 mL
ethanol was stirred at room temperature for 15 minutes. The separated
solid was filtered, dried and recrystallised from ethanol.
(E)-2-[2-{6,6-dimethyl-1-phenyl-6,7-dihydro-1H-indazol-4(5H)-
yliden}hydrazinyl]-4-phenylthiazole (7a): Orange crystals, yield 80%,
Received 18 December 2013; accepted 12 February 2014
Paper 1302355 doi: 10.3184/174751914X13940194215183
Published online: 2 April 2014
1
m.p. 208–210 °C. IR (cm–1): 3112 (NH), 1601 (C=N), 1494 (C=C); H
NMR (400 MHz, DMSO-d6): δ 1.09 (s, 6H, 2CH3), 2.63 (s, 2H, CH2),
JCR1302355_FINAL.indd 229
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