One PotTwo Step Synthesis of 2-Arylidenehydrazinyl-4-arylthiazole

Article abstract of DOI:10.13005/ojc/340360

An efficient, simple one pot, two step procedure has been developed for the synthesis of 2-arylidenehydrazinyl-4-arylthiazole. The reaction of aromatic aldehyde, thiosemicarbazide and phenacyl bromide gave the desired products in good yield. The first reaction product thiosemicarbazone was obtained on reaction with aromatic aldehyde and thiosemicarbazide; without isolating this directly treated with phenacyl bromide in presence of acidic buffer at room temperature desired product was obtained with simple workup procedure.

Full text of DOI:10.13005/ojc/340360

ISSN: 0970-020 X
CODEN: OJCHEG
2018, Vol. 34, No.(3):
Pg. 1646-1652
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
One PotTwo Step Synthesis of 2-Arylidenehydrazinyl-4-arylthiazole
PRAVIN TATYARAM TRYAMBAKE*
Department of Chemistry, S.N. Arts, D. J. M. Commerce and B. N. S. Science College,
Sangamner, Tal-Sangamner, Dist- Ahmednagar- 422 605 (MS), India.
*Corresponding author E-mail: pravintryambake21@rediffmail.com
http://dx.doi.org/10.13005/ojc/340360
(Received: October 23, 2017; Accepted: January 19, 2018)
ABSTRACT
An efficient, simple one pot, two step procedure has been developed for the synthesis
of 2-arylidenehydrazinyl-4-arylthiazole. The reaction of aromatic aldehyde, thiosemicarbazide
and phenacyl bromide gave the desired products in good yield. The first reaction product
thiosemicarbazone was obtained on reaction with aromatic aldehyde and thiosemicarbazide;without
isolating this directly treated with phenacyl bromide in presence of acidic buffer at room temperature
desired product was obtained with simple workup procedure.
Keywords: Thiosemicarbazone, Phenacyl bromide, Thiazole, Synthesis, One pot.
INTROdUCTION
for organic compounds by considering the minimum
steps. One of the aspect of method development is
one pot two step reaction15-18, which involves the
isolation of final product and not the intermediate
products. So this is less time consuming aspect.
By keeping in mind, in this procedure, the reaction
of aromatic aldehyde with thiosemicarbazide in
presence of sulphamic acid as catalyst (10 mmol)19
in ethanol was stirred at room temperature gave
thiosemicarbazone of corresponding aldehyde.
Without isolation of thiosemicarbazone the same
flask charged with phenacyl bromide and acidic
buffer (scheme 1).The reaction mixture was further
stirred till completion of reaction. The synthesized
molecules were supported by IR, 1H-NMR, 13C-NMR
and mass spectral data.
Thiazoles are nitrogen and sulphur
containing heterocyclic compound. Thiazoles and
their derivatives are found to be associated with
various biological activities such as antifungal,
anti-inflammatory activities1-3, antibacterial4-6
anti HIV7, pesticidal8, antiprotozoal9 anticancer10,11
antitumor12, hypertension13. The synthesis of
thiazole derivatives is important for their wide
range of pharmaceutical and biological properties.
Regarding the synthesis of hydrazinyl-thiazoles,
general procedure has been reported in the
literature.The cyclization of thiosemicarbazones with
α-halocarbonyl compounds in alcohol under reflux
resulted in hydrazinyl-thiazoles derivatives14. Now
people are working on development of new methods
,
,
This is an
Open Access article licensed under a Creative Commons Attribution-Non Commercial-Share Alike
4.0 International License (https://creativecommons.org/licenses/by-nc-sa/4.0/), which permits unrestricted
Non Commercial use, distribution and reproduction in any medium, provided the original work is properly cited.

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TRYAMBAKE., Orient. J. Chem., Vol. 34(3), 1646-1652 (2018)
MATERIAL ANd METHOdS
ethanol in a round bottomed flask, the mixture
was stirred at room temperature for 10-20 min.,
the completion of reaction was monitored by TLC.
Further sodium acetate (3 mmol) and acetic acid
(0.5 ml) and 4-methoxy phenacyl bromide (1 mmol)
was added to the above reaction mixture and stirred
till completion of reaction, monitored by TLC. Then
reaction mixture was poured into ice cold water.
Separated solid was filtered, dried and purified by
recrystallization.
Melting points were determined in open
capillary tubes and are uncorrected.IR spectra (KBr)
were recorded on a Shimadzu IR-408 spectrometer.
1H and 13C NMR spectra were determined
in DMSO-d6 solution on a Bruker Avance II
(400 MHz) NMR Spectrometer and TMS was used
as an internal standard.Mass spectra were recorded
on a Waters, Q-Tof Micromass (LC-MS).
General procedure for the synthesis of
2-Arylidenehydrazinyl-4-(4-methoxy phenyl)
thiazole 2(a-j)
The mixture of thiosemicarbazide
(1 mmole), aromatic aldehyde (1 mole) and
sulphamic acid (10 mole %) was taken in 10 ml
Reagents and Conditions: (a) Sulphamic
acid (10 mol %), EtOH, Stir at room temperature
(b) 4-methoxy phenacyl bromide (1 mmole), sodium
acetate(3mmol), glacial acetic acid (0.5 ml), stir at
room temperature.
Scheme 1
Spectroscopic data for synthesized compounds
2-(2-(3-chlorobenzylidene)hydrazinyl)-4-
(4-methoxyphenyl)thiazole (2a)
DMSO-d6):δ 54.9, 101.4, 113.7, 126.1, 126.7, 127.1,
127.4, 129.6, 130.0, 131.7, 132.2, 136.6, 150.4,
158.7, 167.7; MS: M+1= 344.2.
(KBr, mmax cm-1): 3300 (-NH), 1570 (C=N
azomethine), 1487 (C=N thiazole), 1442, 1342,
1251; 1141(-Cl); 1H NMR (DMSO-d6, 400 MHz) d
(ppm): 3.80 (s, 3H, –OCH3), 6.92 (d, J=7.24 2H,
p-anisyl Ar-H), 6.90 (s, 1H, Ar-H), 7.32 (d, 1H, Ar-H),
7.37 (t, 1H, Ar-H), 7.54 (d, 1H, Ar-H), 7.64 (s, 1H,
thiazole H), 7.76 (d, J=8.68, 2H, p-anisyl Ar-H), 7.96
(s, 1H, -N=CH); 12.07 (s, 1H, –NH–); 13C NMR (400
MHz, DMSO-d6):δ 54.8, 101.1, 113.6, 124.6, 125.2,
126.6, 127.4, 128.3, 130.0, 133.7, 138.9, 136.5,
150.4, 158.6, 167.9; MS: M+1= 344.1
2-(2-(4-chlorobenzylidene)hydrazinyl)-4-
(4-methoxyphenyl)thiazole ( 2c):
IR (KBr, mmax cm-1): 3142 (-NH), 1566
(C=N azomethine), 1491 (C=N thiazole), 1435, 1361,
1
1249; 1134(-Cl); H NMR (DMSO-d6, 400 MHz)
d (ppm): 3.78(s, 3H, –OCH3), 6.98 (d,J=2.8, 2H,
p-anisyl Ar-H), 7.15 (s, 1H, thiazole H), 7.49 (m, 2H,
Ar-H), 7.68 (d, 2H, Ar-H), 7.79 (d,J=2.8, 2H, p-anisyl
Ar-H), 8.02 (s, 1H, -N=CH);12.23 (s, 1H, –NH–); 13C
NMR (400 MHz, DMSO-d6): δ 55.0, 101.6, 113.9,
126.8, 127.4, 127.7, 128.8, 133.3, 133.5, 139.7,
150.3, 158.7, 167.9; MS: M+1= 344.2.
2-(2-(2-chlorobenzylidene)hydrazinyl)-4-
(4-methoxyphenyl)thiazole (2b):
IR (KBr, mmax cm-1): 3064 (-NH), 1597
(C=N azomethine), 1491 (C=N thiazole), 1473,
4-(4-methoxyphenyl)-2-(2-(2-nitrobenzylidene)
hydrazinyl)thiazole (2d)
1
1365, 1246; 1139(-Cl); H NMR (DMSO-d6, 400
IR (KBr, mmax cm-1): 3319 (-NH), 1577,
1521(C=N azomethine), 1492 (C=N thiazole), 1437,
1340, 1249;1H NMR (DMSO-d6, 400 MHz) d (ppm):
3.79(s, 3H, –OCH3), 6.97 (d,J=8.7, 2H, p-anisyl
Ar-H), 7.12 (s, 1H, thiazole H), 7.67 (t, 1H, Ar-H),
MHz) d (ppm): 3.78(s, 3H, –OCH3), 6.98 (d,J=8.7,
2H, p-anisyl Ar-H), 7.17 (s, 1H, thiazole H), 7.40
(m, 2H, Ar-H), 7.50 (d, 1H, Ar-H), 7.80 (d,J=8.7,
2H, p-anisyl Ar-H),7.94 (d, 1H, Ar-H), 8.39 (s, 1H,
-N=CH); 12.40 (s, 1H, –NH–); 13C NMR (400 MHz,

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TRYAMBAKE., Orient. J. Chem., Vol. 34(3), 1646-1652 (2018)
7.79 (d,J=8.7, 2H, p-anisyl Ar-H), 8.07 (d, 1H, 12.49 (br. s, 1H, -NH-); MS: M+1= 325.
Ar-H), 8.16 (s, 1H, -N=CH); 8.19 (d, 1H, Ar-H), 8.45
(s, 1H, Ar-H), 12.38 (s, 1H, –NH–); 13C NMR (400
MHz, DMSO-d6):δ 54.9, 101.8, 113.9, 124.2, 124.4,
126.7, 128.4, 128.8, 133.0, 135.6, 147.2, 158.7,
167.6, 178.5; MS: M+1= 355.29.
2-(2-(4-bromobenzylidene)hydrazinyl)-4-
(4-methoxyphenyl)thiazole (2h)
IR (KBr, mmax cm-1): 3140 (-NH), 1564,
(C=N azomethine), 1491 (C=N thiazole), 1456, 1361,
1249;1H NMR (DMSO-d6, 400 MHz) d (ppm):3.78(s,
3H, –OCH3), 6.98 (d, J=8.8, 2H, p-anisyl Ar-H), 7.15
(s, 1H, thiazole H), 7.59 (d, 1H, J=6.56, Ar-H), 7.63
(d, J=6.48, 2H, Ar-H), 7.79 (d, J=8.8, 2H, p-anisyl
Ar-H), 8.00 (s, 1H, -N=CH); 12.22 (br. s, 1H, –NH–);
13C NMR (400 MHz, DMSO-d6):δ 55.0, 101.6, 113.9,
122.2, 126.8, 127.4, 128.0, 131.7, 133.7, 139.7,
158.7, 167.9.
4-(4-methoxyphenyl)-2-(2-(3-nitrobenzylidene)
hydrazinyl)thiazole (2e)
IR (KBr, mmax cm-1): 3064 (-NH), 1583,
1527(C=N azomethine), 1492 (C=N thiazole), 1435,
1348, 1249;1H NMR (DMSO-d6, 400 MHz) d (ppm):
3.79(s, 3H, –OCH3), 6.97 (d,J=8.7, 2H, p-anisyl
Ar-H), 7.14 (s, 1H, thiazole H), 7.57 (t, 1H, Ar-H),
7.72 (s, 1H, Ar-H), 8.07 (q, 2H, Ar-H), 7.78 (d,J=8.7,
2H, p-anisyl Ar-H),7.94 (d, 1H, Ar-H), 8.44 (s, 1H,
-N=CH); 12.49 (s, 1H, –NH–); 13C NMR (400 MHz,
DMSO-d6):δ 54.9, 101.5, 113.7, 120.1, 122.9, 126.7,
127.4, 129.9, 131.9, 136.4, 138.2, 148.16, 158.7,
167.7; MS: M+1= 355.29.
4-((2-(4-(4-methoxyphenyl)thiazol-2-yl)
hydrazono)methyl)phenol (2i)
IR (KBr, mmax cm-1): 3329(-OH, -NH),
1535, 1512(C=N azomethine), 1492 (C=N thiazole),
1
, 1323, 1247; H NMR (DMSO-d6, 400 MHz) d
(ppm): 3.77(s, 3H, –OCH3), 6.80-6.83 (d, J=8.56,
2H, Ar-H), 6.91-6.93 (d,J=8.76, 2H, p-anisyl Ar-H),
6.98 (s, 1H, thiazole H), 7.48 (d, J=8.6, 2H, Ar-H),
7.77 (d,J=8.72, 2H, p-anisyl Ar-H), 7.93 (s, 1H, -N=CH);
9.75 (br.s, 1H, Ar–OH), 11.82 (br.s, 1H, –NH–);13CNMR
(400MHz, DMSO-d6):δ54.9, 100.6, 113.6, 115.5, 125.5,
126.6, 127.6, 127.7, 141.4, 150.2, 158.6, 168.3.
4-(4-methoxyphenyl)-2-(2-(4-nitrobenzylidene)
hydrazinyl)thiazole (2f)
IR (KBr, mmax cm-1): 3313 (-NH), 1556,
1527(C=N azomethine), 1489 (C=N thiazole),
1458, 1334, 1240; 1H NMR (DMSO-d6, 400 MHz)
d (ppm): 3.79(s, 3H, –OCH3), 6.96 (d,J=7.12, 2H,
p-anisyl Ar-H), 7.14 (s, 1H, thiazole H), 7.77 (d,
2H, J=6.96, Ar-H), 7.89 (d, 2H, J=8.88, Ar-H), 8.20
(s, 1H, -N=CH); 8.26 (d, 2H, J=8.84, Ar-H), 12.43
(s, 1H, -NH-): MS: M+1= 355.29.
2-(2-(4-methoxybenzylidene)hydrazinyl)-4-(4-
methoxyphenyl)thiazole (2j)
IR (KBr, mmax cm-1): 3151 (-NH), 1566,
1512(C=N azomethine), 1492 (C=N thiazole), 1361,
1246; 1H NMR (DMSO-d6, 400 MHz) d (ppm): 3.77
(s, 3H, –OCH3), 3.79 (s, 3H, –OCH3), 6.90-6.96
(m, 5H, Ar-H), 7.58 (d, J=8.72, 2H, p-anisyl Ar-H),
7.76 (d, J=8.72, 2H, p-anisyl Ar-H), 7.95 (s, 1H,
thiazole H), 11.86 (br. s, 1H, –NH–); 13C NMR
(400 MHz, DMSO-d6): δ 54.9, 55.1, 100.9, 113.7,
114.1, 126.7, 127.1, 127.6, 140.9, 150.3, 158.6,
160.1, 168.2.
3-((2-(4-(4-methoxyphenyl)thiazol-2-yl)hydrazono)
methyl)phenol ( 2g)
1H NMR (DMSO-d6, 400 MHz) d (ppm):
3.55(s, 3H, –OCH3), 6.79 (s, 1H, Ar-H), 6.96
(d, J=8.8, 2H, p-anisyl Ar-H), 7.04 (s, 1H, Ar-H),
7.08 (s, 1H, thiazole H), 7.10 (s, 1H, Ar-H),
7.23 (t, 1H, Ar-H), 7.78 (d,J=8.8, 2H, p-anisyl
Ar-H), 7.93 (s, 1H, -N=CH); 9.55 (br. s, 1H, Ar–OH),
Table 1: Physical data of newly synthesized compounds 2a-i
Entry
R-CHO
Yield (%)
m.p.(oC)
Comp. no.
1
2
3
4
5
6
7
8
9
3-Cl C6H4
2- Cl C H
91
90
92
88
90
87
92
85
83
88
168-170
164-166
234-236
174-176
218-220
228-230
216-218
236-238
220-222
208-210
2a
2b
2c
2d
2e
2f
2g
2h
2i
4- Cl C66H44
2-NO C6H4
3-NO2 C H
4-NO22 C6H4
3-OH C6H4
4-Br C66H44
4-OH C6H4
4-OCH3 C6H4
10
2j
a:Yield of isolated products

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TRYAMBAKE., Orient. J. Chem., Vol. 34(3), 1646-1652 (2018)
RESULT ANd dISCUSSION
1487 cm-1 region resulting from C=N (azomethine)
and C=N (thiazole) respectively. Fig. 1 showed IR
spectra for compound 2d. In the 1HNMR spectra,
of compounds 2(a-h) showed a singlet proton at
12.00-12.50 ppm for the -NH- and a singlet around at
7.90-8.45 ppm for the -CH-N= proton the presence
of a singlet proton at 7.15 for the thiazole. Peak
near 3.70-3.80 ppm in spectra of all synthesized
compounds is due to -OCH3 group of aromatic ring.
1-arylidene-2-(5-(4-methoxyphenyl)thiazol-
2-yl)hydrazine (2a-h, Table-1) were synthesized
according to scheme 1. Thiazole derivatives 2(a-h)
were prepared by one pot two step condensation of
aromatic aldehydes, thiosemicarbazide and phenacyl
bromide. In first step aromatic aldehydes 1a-h
(1 mmol), thiosemicarbazide(1 mmol) were reacted in
ethanol at room temperature catalyzed by 10 mol %
sulphamic acid.It was resulted in thiosemicarbazone
of corresponding aromatic aldehyde. Further same
flask was charged with phenacyl bromide (1 mmol)
and acidic buffer, stirred till completion of reaction.
Completion of reaction was monitored by thin
layer chromatography technique. After completion
of reaction mixture was treated with cold water,
separated solid was filtered, dried and recrystallized.
The products were obtained in moderate to good
yield. The structures of compounds 2(a-h) were
confirmed by spectroscopic methods such as IR,
1HNMR,13CNMRandmassspectroscopy.IRspectrum
of 1-arylidene-2-(5-(4-methoxyphenyl)thiazol-2-yl)
hydrazine 2(a-h) showed an absorption band around
the 3000-3242 cm-1 regions resulting from the
-NH- group.The absorption bands around 1570 and
1
Fig. 2 showed H NMR spectra for compound 2d.
The 13C NMR studies indicate azomethine, aromatic
and thiazole ring carbon in between δ 136-139,
101-160 and around 167 respectively.Fig.3 showed
13CNMR spectra for compound 2d.The compounds
were finally confirmed by mass analysis. Fig. 4
showed mass spectra for compound 2d.
From the above study it can be concluded
that, the one pot two step protocol for the synthesis
of 1-arylidene-2-(5-(4-methoxyphenyl)thiazol-2-yl)
hydrazine 2(a-h) has been developed. It involves
formation of thiosemicarbazone in first step and then
cyclization with phenacyl bromide in second step. It
has certain advantages such as facile, mild reaction
condition, efficient, runs at room temperature, simple
work-up and results in good yields.
Fig. 1. IR Spectra of 4-(4-methoxyphenyl)-2-(2-(2-nitrobenzylidene)hydrazinyl)thiazole(2d)

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TRYAMBAKE., Orient. J. Chem., Vol. 34(3), 1646-1652 (2018)
Fig. 2. 1H-NMR of 4-(4-methoxyphenyl)-2-(2-(2-nitrobenzylidene)
hydrazinyl)thiazole(2d)
Fig. 3. 13C NMR of 4-(4-methoxyphenyl)-2-(2-(2-nitrobenzylidene)
hydrazinyl)thiazole(2d)

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TRYAMBAKE., Orient. J. Chem., Vol. 34(3), 1646-1652 (2018)
Fig. 4. Mass spectra of 4-(4-methoxyphenyl)-2-(2-(2nitrobenzylidene)
hydrazinyl)thiazole(2d)
ACKNOwLEdGEMENT
Delhi (Grant No. 47-1986/11 (WRO)) for financial
assistant & Director, SAIF, Panjab University,
Chandigarh for providing spectral analysis facility.
Author is thankful to UGC (WRO), New
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