A convenient synthesis of some new thiazole and pyrimidine derivatives incorporating a naphthalene moiety

Article abstract of DOI:10.3184/174751912X13567137687630

The reaction of 2-[1-(naphthalen-2-yl)ethylidene]hydrazinecarbothioamide with hydrazonoyl halides afforded new thiazole derivatives, whilst reaction with compounds containing an activated double bond such as ethoxymethylenemalononitrile and benzylidenemalononitrile yielded the respective pyrimidine derivatives. A 4-thiazolidin-4-one was obtained by reaction of the hydrazinecarbothioamide with ethyl bromoacetate. Subsequent condensation of the thiazolidinone with aromatic aldehydes afforded the corresponding arylidene derivatives. Treatment of the hydrazinecarbothioamide with dimethyl acetylenedicarboxylate resulted in the formation of a (methoxycarbonylmethylidene) thiazolinone. Reaction of the hydrazinecarbothioamide with 2-chloro-1,3-dicarbonyl compounds gave the respective thiazole derivatives. The structures of the newly synthesised compounds were confirmed by their elemental analysis and spectral data.

Full text of DOI:10.3184/174751912X13567137687630

86 RESEARCH PAPER
FEBRUARY, 86–90
JOURNAL OF CHEMICAL RESEARCH 2013
A convenient synthesis of some new thiazole and pyrimidine derivatives
incorporating a naphthalene moiety
Sobhi M. Gomhaa* and Mohamed G. Badreyb
aDepartment of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt
bChemistry Department, Faculty of Science, Fayoum University, El-Fayoum, Egypt
The reaction of 2-[1-(naphthalen-2-yl)ethylidene]hydrazinecarbothioamide with hydrazonoyl halides afforded new
thiazole derivatives, whilst reaction with compounds containing an activated double bond such as ethoxymethylene-
malononitrile and benzylidenemalononitrile yielded the respective pyrimidine derivatives. A 4-thiazolidin-4-one was
obtained by reaction of the hydrazinecarbothioamide with ethyl bromoacetate. Subsequent condensation of the thia-
zolidinone with aromatic aldehydes afforded the corresponding arylidene derivatives. Treatment of the hydrazinecar-
bothioamide with dimethyl acetylenedicarboxylate resulted in the formation of a (methoxycarbonylmethylidene)
thiazolinone. Reaction of the hydrazinecarbothioamide with 2-chloro-1,3-dicarbonyl compounds gave the respective
thiazole derivatives. The structures of the newly synthesised compounds were confirmed by their elemental analysis
and spectral data.
Keywords: thiazoles, thiosemicarbazide, hydrazonoyl halides
Several heterocyclic compounds such as thiazoles and pyrimi-
dines have widespread applications especially in the field of
medicine and pharmacology. This has, in turn, attracted the
attention of many to develop the chemistry of this class of
compounds. Some drugs were found to possess antidiabetic
activities, however, most of them can cause problems such as
compliance and hypoglycaemia. Thiazolidinone derivatives
have been reported to possess antidiabetic activities,1–3 and
were also found to improve compliance and reduce side effects.
Furthermore, thiazolidinones have structural similarity with
clinically used thiazolidinediones.4 Also, biological activities
of substituted pyrimidines, in general, have received a great
deal of interest,5 and have been tested for their bactericidal and
fungicidal activities.6,7 In view of these observations and in
continuation of our previous work on the synthesis of hetero-
cyclic systems for biological evaluations,8–12 we report here a
facile route to various thiazole and pyrimidine derivatives,
incorporating a naphthalene moiety.
products obtained by direct reaction of compound 2 with
hydrazonyl halides. The azo derivatives of similar thiazoles
have found extensive applications in the dyeing of synthetic
fibres15,16 and the azo derivatives described in the present work
may find similar applications.
Next, we examined the reaction of 2 with compounds
containing an activated double bond. Thus, treatment of 2 with
ethoxymethylenemalononitrile 10 gave 4-imino-3-(1-(naph-
thalen-2-yl)ethylideneamino)-2-thioxo-1,2,3,4-tetrahydropy-
rimidine-5-carbonitrile (11) rather than its isomeric structure
12 (Scheme 2). The structure of 11 was confirmed by its
spectral data. For example, its 1H NMR spectrum revealed the
lack of the signals corresponding to amino and ethoxy groups
(hence excluding structure 12) and instead, exhibited the
presence of a signal for the pyrimidine H-6 proton which
absorbed at δ 8.29. The pyrimidine structure is in agreement
with literature reports.17–20 The reaction of ethoxymethylene-
malononitrile with thiosemicarbazones has not been reported
previously, though its reaction with thioureas is known to give
pyrimidines.17–20
Results and discussion
The mechanism of formation of 11 can be explained by a
nucleophilic addition of amino group of 2 to the double bond
of 10 followed by elimination of ethanol. Thereafter, the cycli-
sation occurs through addition of NH function to one cyano
group to afford the iminopyrimidine derivative 11 as shown in
Scheme 3.
Condensation of 2-acetylnaphthalene 1 with thiosemicarba-
zide in absolute ethanol in the presence of catalytic amount of
acetic acid afforded 2-[1-(naphthalen-2-yl)ethylidene]hydrazi
necarbothioamide 2 as previously reported.13 (Scheme 1).
The target compounds, namely 4-substituted-2-(2-(1-(naph-
thalen-2-yl)ethylidene)hydrazinyl)-5-(aryldiazenyl)thiazole
5a–i, were synthesised via a one-pot reaction of the thiosemi-
carbazone derivative 2 with hydrazonoyl halides 3 and 4 in
1,4-dioxane in the presence of triethylamine (TEA) (Scheme
1). The structural elucidation of compounds 5a–i was based on
spectral evidence and microanalyses. The mass spectra of
these products 5a–i showed the molecular ion peaks at the
expected m/z values. Their IR spectra showed the disappear-
ance of the amino group, and revealed, in each case, one
band at 1552–1559 cm−1 assignable to the N=N group (see
Experimental).
The thiazole derivatives 8 and 9 were synthesised in good
yields by treatment of thiosemicarbazone derivative 2 with
chloroacetone 6 or phenacyl bromide 7 in 1,4-dioxane under
reflux following the Hantzsch thiazole synthesis.14 Upon
coupling the thiazole derivatives 8 and 9 with the appropriate
diazonium salt in the presence of sodium acetate, the azo
derivatives 5a–i were obtained. All data obtained for the
latter compounds were in complete accord with those of the
In a similar manner, 2 reacted with benzylidenemalononitrile
13 in boiling methanol to give 6-amino-1-[1-(naphthalen-2-yl)-
ethylideneamino]-4-phenyl-2-thioxo-1,2-dihydropyrimidine-
5-carbonitrile (14) (Scheme 2). The mechanism of this reaction
resembles that depicted for compound 11, through a Michael-
type addition, except that no elimination occurs. The forma-
tion of compound 14 could be accounted for as follows: First,
nucleophilic attack of the amino group to the double bond
then addition of the NH group to a cyano function, thereafter,
imino–amine tautomerisation and finally dehydrogenation
through air-oxidation. The structure of 14 was confirmed on
the basis of spectroscopic data and elemental analyses.21–24 For
1
example, the H NMR spectrum showed the appearance of
D2O exchangeable amino group signals, and the aromatic
region was enriched by additional signals that integrated for
five protons (Ph group). Its IR spectrum revealed a band at
2225 cm−1 assignable to the CN group.
The 4-thiazolidinone 15 was obtained by reaction of 2 with
ethyl bromoacetate in ethanol in the presence of anhydrous
potassium carbonate. Reaction of the latter product 15 with
aromatic aldehydes afforded the corresponding 5-arylidene
* Correspondent. E-mail: s.m.gomha@hotmail.com

JOURNAL OF CHEMICAL RESEARCH 2013 87
Scheme 1 Synthesis of 5-arylazothiazole derivatives 5a–i.
Scheme 2 Reaction of 2 with activated unsaturated compounds 10 and 13.
derivatives 16a,b (Scheme 4). The 1H NMR spectral data were
basis of analytical and spectral data. Thus, the 1H NMR spec-
trum showed the presence of a singlet signal at δ 6.68 assigned
to the =CHCOOCH3 proton in the Z-configuration,27–30 and a
singlet at δ 3.29 for the ester methyl protons. Its mass spectrum
revealed a molecular ion peak at m/z 353.
Moreover, treatment of the title compound 2 with 2-
chloro-1,3-dicarbonyl compounds, namely, ethyl 2-chloro-3-
oxobutanoate 19a and 2-chloro-3-oxo-N-phenylbutanamide
19b in ethanol in the presence of TEA, gave the corresponding
also consistent with the assigned structures; thus the thiazolid-
inone CH2 protons of 15 appeared at δ 3.88. The arylidene
CH protons in 16a,b were observed at 8.3 ppm. These data
closely resemble those reported in literature on similar
compounds.25, 26
In addition, refluxing an equimolecular mixture of 2 and
dimethyl acetylenedicarboxylate 17 in methanol yielded com-
pound 18 (Scheme 4), whose structure was established on the

88 JOURNAL OF CHEMICAL RESEARCH 2013
Scheme 3 Mechanism for the reaction of 2 with ethoxymethylenemalononitrile 10.
Scheme 4 Synthesis of arylidenethiazolinone derivatives 16a,b and 18.
thiazole derivatives 20a and 20b, respectively (Scheme 5). The
structure of these products was elucidated by their microanaly-
sis and spectral data (mass, IR, H NMR). The H NMR data
showed singlet signals at δ 2.52 and 2.49 ppm assignable to the
thiazole-CH3, in addition to the characteristic signals for the
COOEt and CONHPh groups in compounds 20a and 20b,
respectively.
revealed a singlet signal at δ 3.98 due to the thiazoline–CH2
protons. The mass spectrum of 22 showed the molecular ion
peak at m/z 282. (see Experimental section).
1
1
Experimental
Melting points were measured on Electrothermal IA 9000 series digi-
tal melting point apparatus. The IR spectra were recorded in potas-
sium bromide discs on a Pye Unicam SP 3300 and Shimadzu FT IR
8101 PC IR spectrophotometers. 1H NMR and 13C NMR spectra were
recorded in deuterated dimethyl sulfoxide (DMSO-d6) using a Varian
Finally, the reaction of 2 with chloroacetonitrile 21 in
boiling ethanol containing a catalytic amount of TEA afforded
the aminothiazoline derivative 22 (Scheme 5). The structure
of compound 22 was elucidated on the basis of spectroscopic
1
Gemini 300 NMR spectrometer (300 MHz for H and 75 MHz for
1
13C). Mass spectra were recorded on a Shimadzu GCMS-QP1000 EX
data and microanalysis. For example, the H NMR spectrum
Scheme 5 Reaction of 2 with 2-chloro-1,3-dicarbonyl compounds 19a,b and 21.

JOURNAL OF CHEMICAL RESEARCH 2013 89
mass spectrometer at 70 eV. Elemental analysis was carried out at the
Microanalytical Centre of Cairo University, Giza, Egypt. All reactions
were followed by TLC (Silica gel, Merck).
exchangeable, NH);IR (KBr): vmax 1553 (N=N), 1634 (C=N), 3424
(NH) cm−1; MS m/z (%): 481 (M+, 75), 70(100). Anal. Calcd for
C27H20ClN5S (482.00): C, 67.28; H, 4.18; N, 14.53. Found C, 67.11;
H, 4.28; N, 14.32%.
2-[1-(Naphthalen-2-yl)ethylidene]hydrazinecarbothioamide 213 and
hydrazonoyl halides 3 and 431,32 were prepared as reported in the
literature.
2-[2-(1-(Naphthalen-2-yl)ethylidene)hydrazinyl]-5-[(4-nitrophenyl)-
diazenyl]-4-phenylthiazole (5i): Yield 72%; dark brown solid; m.p.
1
182 °C; H NMR (DMSO-d6): δ 2.68 (s, 3H, CH3), 7.35–8.31 (m,
Synthesis of 4-substituted-2-[2-(1-(naphthalen-2-yl)ethylidene)hydra-
zinyl]-5-(aryldiazenyl)thiazole (5a–i). General method A
15H, ArH), 8.47 (s, 1H, naphthalene-H1), 10.77 (s, 1H, D2O exchan-
geable, NH); IR (KBr): vmax 1559 (N=N), 1602 (C=N), 3444 (NH)
cm−1; MS m/z (%): 492 (M+, 5), 127(100).Anal. Calcd for C27H20N6O2S
(492.55): C, 65.84; H, 4.09; N, 17.06. Found C, 65.84; H, 4.09; N,
17.06%.
A mixture of 2-[1-(naphthalen-2-yl)ethylidene]hydrazinecarbothio-
amide 2 (0.486 g, 2 mmol) and the appropriate hydrazonoyl halides 3
or 4 (2 mmol) in 1,4-dioxane (30 mL) containing TEA (0.7 mL) was
refluxed for 3 h (monitored by TLC), allowed to cool and the solid
formed was filtered off, washed with EtOH, dried and recrystallised
from DMF to give 5a–i.
Synthesisof4-substituted-2-[(2-(1-(naphthalen-2-yl)ethylidene)hydra-
zinyl]thiazoles (8 and 9). General method B
4-Methyl-2-[2-(1-(naphthalen-2-yl)ethylidene)hydrazinyl]-5-(phen-
A mixture of 2 (0.243 g, 1 mmol) and chloroacetone 6 or phenacyl
bromide 7 (1 mmol) in absolute EtOH (30 mL) was refluxed for 1 h
(monitored by TLC). The product started to separate out during
the course of reaction. The crystalline solid was filtered, washed
with water, dried and recrystallised from DMF-EtOH to give the
corresponding compounds 8 and 9 respectively.
1
yldiazenyl)thiazole (5a): Yield 78%; dark red solid; m.p. 216 °C; H
NMR (DMSO-d6): δ 2.61 (s, 3H, CH3), 2.64 (s, 3H, CH3), 7.33–8.24
(m, 11H, ArH), 8.45 (s, 1H, naphthalene-H1), 10.63 (s, 1H, D2O
exchangeable, NH); 13C NMR (DMSO-d6): δ 11.8, 21.4, 114.5, 119.8,
124.6, 129.8, 130.5, 134.4, 134.9, 136.7, 138.9, 140.4, 144.6, 146.5,
149.6, 152.4, 164.3, 169.8; IR (KBr): vmax 1553 (N=N), 1591 (C=N),
3445 (NH) cm−1; MS m/z (%): 385 (M+, 26), 127 (100). Anal. Calcd
for C22H19N5S (385.48): C, 68.55; H, 4.97; N, 18.17. Found C, 68.45;
H, 4.64; N, 18.00%.
4-Methyl-2-[(2-(1-(naphthalen-2-yl)ethylidene)hydrazinyl]thiazole
1
(8): Yield 72%; yellow solid; m.p. 208 °C; H NMR (DMSO-d6):
δ 2.56 (s, 3H, CH3), 2.66 (s, 3H, CH3), 6.72 (s, 1H, 5-H), 7.15–8.23
(m, 6H, ArH), 8.44 (s, 1H, naphthalene-H1), 10.70 (s, 1H, D2O
exchangeable, NH); 13C NMR (DMSO-d6): δ 14.6, 21.4, 110.4, 117.4,
124.6, 128.6, 132.7, 136.2, 138.9, 140.3, 148.9, 151.6, 165.3, 171.5;
IR (KBr): vmax 1632 (C=N), 3442 (NH) cm−1; MS m/z (%): 281 (M+,
76), 57 (100). Anal. Calcd for C16H15N3S (281.38): C, 68.30; H, 5.37;
N, 14.93. Found C, 68.14; H, 5.19; N, 14.68%.
4-Methyl-2-[2-(1-(naphthalen-2-yl)ethylidene)hydrazinyl]-5-(p-
tolyldiazenyl)thiazole (5b): Yield 76%; dark red solid; m.p. 228 °C;
1H NMR (DMSO-d6): δ 2.21 (s, 3H, CH3), 2.61 (s, 3H, CH3), 2.64
(s, 3H, CH3), 7.30–8.24 (m, 10H, ArH), 8.46 (s, 1H, naphthalene-H1),
10.71 (s, 1H, D2O exchangeable, NH); IR (KBr): vmax 1553 (N=N),
1617 (C=N), 3478 (NH) cm−1; MS m/z (%): 399 (M+, 38), 127 (100).
Anal. Calcd for C23H21N5S (399.51): C, 69.15; H, 5.30; N, 17.53.
Found C, 69.32; H, 5.12; N, 17.29%.
5-[(4-Chlorophenyl)diazenyl]-4-methyl-2-[2-(1-(naphthalen-2-yl)-
ethylidene) hydrazinyl]thiazole (5c): Yield 81%; dark red solid; m.p.
242 °C; 1H NMR (DMSO-d6): δ 2.64 (s, 3H, CH3), 2.66 (s, 3H, CH3),
7.30–8.28 (m, 10H, ArH), 8.49 (s, 1H, naphthalene-H1), 10.76 (s, 1H,
D2O exchangeable, NH); IR (KBr): vmax 1556 (N=N), 1598 (C=N),
3441 (NH) cm−1; MS m/z (%): 419 (M+, 56), 127 (88), 57 (100). Anal.
Calcd for C22H18ClN5S (419.93): C, 62.92; H, 4.32; N, 16.68. Found
C, 62.76; H, 4.54; N, 16.34%.
4-Methyl-2-[2-(1-(naphthalen-2-yl)ethylidene)hydrazinyl]-5-[(4-
nitrophenyl)diazenyl]thiazole (5d): Yield 80%; dark red solid; m.p.
182 °C; 1H NMR (DMSO-d6): δ 2.63 (s, 3H, CH3), 2.69 (s, 3H, CH3),
7.30–8.318 (m, 10H, ArH), 8.49 (s, 1H, naphthalene-H1), 10.79 (s,
1H, D2O exchangeable, NH); IR (KBr): vmax 1558 (N=N), 1589 (C=N),
3432 (NH) cm−1; MS m/z (%): 430 (M+, 15), 127 (100). Anal. Calcd
for C22H18N6O2S (430.48): C, 61.38; H, 4.21; N, 19.52. Found C,
61.12; H, 4.11; N, 19.24%.
5-[(4-Bromophenyl)diazenyl]-4-methyl-2-[2-(1-(naphthalen-2-yl)-
ethylidene)hydrazinyl]thiazole (5e): Yield 76%; dark red solid; m.p.
232 °C; 1H NMR (DMSO-d6): δ 2.63 (s, 3H, CH3), 2.62 (s, 3H, CH3),
7.30–8.23 (m, 10H, ArH), 8.46 (s, 1H, naphthalene-H1), 10.72 (s, 1H,
D2O exchangeable, NH); IR (KBr): vmax 1552 (N=N), 1632 (C=N),
3439 (NH) cm−1; MS m/z (%): 463 (M+, 15), 154 (100). Anal. Calcd
for C22H18BrN5S (464.38): C, 56.90; H, 3.91; N, 15.08. Found C,
56.66; H, 3.71; N, 14.88%.
5-[(4-Methoxyphenyl)diazenyl]-4-methyl-2-[2-(1-(naphthalen-2-yl)-
ethylidene)hydrazinyl]thiazole (5f): Yield 74%; dark red solid; m.p.
228 °C; 1H NMR (DMSO-d6): δ 2.58 (s, 3H, CH3), 2.63 (s, 3H, CH3),
3.74 (s, 3H, OCH3), 6.96–7.60 (m, 10H, ArH), 8.43 (s, 1H, naphtha-
lene-H1), 10.56 (s, 1H, D2O exchangeable, NH); IR (KBr): vmax 1553
(N=N), 1610 (C=N), 3478 (NH) cm−1; MS m/z (%): 399 (M+, 38), 127
(100). Anal. Calcd for C23H21N5OS (415.51): C, 66.48; H, 5.09; N,
16.85. Found C, 66.31; H, 5.21; N, 16.55%.
2-[2-(1-(Naphthalen-2-yl)ethylidene)hydrazinyl]-4-phenyl-5-(phen-
yldiazenyl)thiazole (5g): Yield 73%; dark brown solid; m.p. 220 °C;
1H NMR (DMSO-d6): δ 2.68 (s, 3H, CH3), 7.35–8.31 (m, 16H, ArH),
8.47 (s, 1H, naphthalene-H1), 10.77 (s, 1H, D2O exchangeable, NH);
13C NMR (DMSO-d6): δ 20.8, 116.4, 119.4, 122.7, 128.6, 132.7,
133.6, 134.8, 135.3, 136.2, 137.4, 138.9, 140.4, 141.3, 144.6, 146.5,
147.3, 149.6, 151.4, 166.1, 174.8; IR (KBr): vmax 1556 (N=N), 1627
(C=N), 3448 (NH) cm−1; MS m/z (%): 477 (M+, 10), 105 (100). Anal.
Calcd for C27H21N5S (447.55): C, 72.46; H, 4.73; N, 15.65 Found C,
72.23; H, 4.54; N, 15.45%.
2-[2-(1-(Naphthalen-2-yl)ethylidene)hydrazinyl]-4-phenylthiazole
(9): m.p. 288 °C; lit.33 286 °C.
Coupling of (8 and 9) with arenediazonium chlorides: To a solution
of 8 or 9 (1 mmol) in EtOH (20 mL) was added sodium acetate trihy-
drate (0.138 g, 1 mmol), and the mixture was cooled to 0–5 °C in an
ice bath. To the resulting cold solution was added, portionwise, a cold
solution of an arenediazonium chloride [prepared by diazotising the
appropriate aniline derivative] (1 mmol) dissolved in hydrochloric
acid (6 M, 1 mL) with a solution of sodium nitrite (0.07 g, 1 mmol) in
water (2 mL)]. After complete addition of the diazonium salt, the reac-
tion mixture was stirred for a further 30 min in an ice bath. The solid
that separated was filtered off, washed with water and finally recryst-
allised from EtOH to give a product that proved to be identical in all
respects (m.p., mixed m.p. and IR spectra) with compounds 5a–i
obtained from method A.
Reaction of 2 with activated unsaturated compounds 10 and 13
4-Imino-3-[1-(naphthalen-2-yl)ethylideneamino]-2-thioxo-1,2,3,4-
tetrahydropyrimidine-5-carbonitrile (11): A mixture of 2 (0.243 g,
1 mmol) and ethoxymethylenemalononitrile 10 (0.122g, 1 mmol)
in MeOH (20 mL) was refluxed for 1 h (monitored by TLC). The
reaction mixture was cooled and the resulting precipitate was filtered
off and recrystallised from DMF/EtOH to give 11. Yield 70%;
yellow solid; m.p. 226 °C; 1H NMR (DMSO-d6): δ 2.42 (s, 3H, CH3),
7.50–8.02 (m, 6H, ArH), 8.29 (s, 1H, Pyrimidine-H6), 8.30 (s, 1H,
naphthalene-H1), 8.33 (s, 1H, D2O exchangeable, NH), 10.25 (s, 1H,
D2O exchangeable, NH); 13C NMR (DMSO-d6): δ 22.1, 104.2, 117.6,
119.8, 123.6, 126.6, 130.4, 132.7, 138.9, 141.3, 148.9, 152.6, 162.3,
168.7, 184.3; IR (KBr): vmax 1592 (C=N), 2220 (CN), 3234 (NH),
3400 (NH) cm−1;MS m/z (%): 319 (M+, 7), 127 (100). Anal. Calcd for
C17H13N5S (319.38): C, 63.93; H, 4.10; N, 21.93. Found C, 63.82; H,
4.00; N, 21.71%.
6-Amino-1-[1-(naphthalen-2-yl)ethylideneamino]-4-phenyl-2-
thioxo-1,2-dihydropyrimidine-5-carbonitrile (14): A mixture of 2
(0.243 g, 1 mmol) and benzylidenemalononitrile 13 (0.154g, 1 mmol)
in MeOH (20 mL) was refluxed for 1 h (monitored by TLC). The
reaction mixture was cooled and the resulting precipitate was filtered
off and recrystallised from DMF/EtOH to give 14. Yield 74%; yellow
solid; m.p. 189 °C; 1H NMR (DMSO-d6): δ 2.48 (s, 3H, CH3), 6.73 (s,
2H, D2O exchangeable, NH2), 7.53–8.12 (m, 11H, ArH), 8.41 (s, 1H,
naphthalene-H1); IR (KBr): vmax 1589 (C=N), 2225 (CN), 3227, 3585
(NH2) cm−1; MS m/z (%): 395 (M+, 2), 127(100). Anal. Calcd for
C23H17N5S (395.48): C, 69.85; H, 4.33; N, 17.71. Found C, 69.50; H,
4.82; N, 17.62%.
5-[(4-Chlorophenyl)diazenyl]-2-[2-(1-(naphthalen-2-yl)ethylidene)-
Synthesis of 5-arylidene-2-[2-(1-(naphthalen-2-yl)ethylidene)hydra-
zinyl]thiazol-4(5H)-ones (16a–d)
I. 2-[2-(1-(Naphthalen-2-yl)ethylidene)hydrazinyl]thiazol-4(5H)-one
(15): A mixture of 2 (0.243 g, 1 mmol) and ethyl bromoacetate
hydrazinyl]-4-phenylthiazole (5h): Yield 74%; dark brown solid;
1
m.p. 194 °C; H NMR (DMSO-d6): δ 2.68 (s, 3H, CH3), 7.35–8.31
(m, 15H, ArH), 8.47 (s, 1H, naphthalene-H1), 10.77 (s, 1H, D2O

90 JOURNAL OF CHEMICAL RESEARCH 2013
(0.167g, 1 mmol) in EtOH (20 mL) containing anhydrous potassium
carbonate (0.276 g, 2 mmol) was refluxed for 1 h (monitored by TLC).
The reaction mixture was cooled and poured into cold water; the
resulting precipitate was filtered off, washed with water, and recrystal-
lised from DMF to give 15. Yield 78%; yellow solid; m.p. 224 °C; 1H
NMR (DMSO-d6): δ 2.50 (s, 3H, CH3), 3.88 (s, 2H, CH2),7.53–8.13
(m, 6H, ArH), 8.30 (s, 1H, naphthalene-H1), 11.96 (s, 1H, D2O
exchangeable, NH); IR (KBr): vmax 1612 (C=N), 1704 (CO), 3443
(NH) cm−1; MS m/z (%): 283 (M+, 96), 154(100). Anal. Calcd for
C15H13N3OS (283.08): C, 63.58; H, 4.62; N, 14.83. Found C, 63.43; H,
4.54; N, 14.47%.
400 (M+, 27), 127 (100). Anal. Calcd for C23H20N4OS (400.50): C,
68.98; H, 5.03; N, 13.99. Found C, 68.77; H, 5.00; N, 13.76%.
4-Amino-2-[(1-(naphthalen-2-yl)ethylidene)hydrazono]-2,5-
dihydrothiazole (22): Yield 76%; yellow solid; m.p. 185 °C; 1H NMR
(DMSO-d6): δ 2.49 (s, 3H, CH3), 3.98 (s, 2H, CH2), 7.53–8.27 (m, 9H,
ArH and NH2; IR (KBr): vmax 1611 (C=N), 3270, 3451 (NH2) cm−1;
MS m/z (%): 282 (M+, 72), 127 (100). Anal. Calcd for C15H14N4S
(282.36): C, 63.80; H, 5.00; N, 19.84. Found C, 63.65; H, 5.23; N,
19.68%.
Conclusions
A series of novel 5-(aryldiazenyl)thiazole derivatives, 5-aryli-
dene-4-thiazolone derivatives, 6-amino-4-phenyl-2-thioxo-1,2-
dihydropyrimidine-5-carbonitrile derivatives and 4-imino-2-
thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives
have been synthesised readily and in a good yield from
2-(1-(naphthalen-2-yl)ethylidene) hydrazinecarbothioamide,
an easily available starting material, and characterised via IR,
NMR, MS and elemental analyses.
II. Reaction of (15) with aromatic aldehydes; general procedure
To a solution of 5-thiazolidinone 15 (0.283 g, 1 mmol) and benzalde-
hyde or 4-chlorobenzaldehyde (1 mmol) in glacial acetic acid
(20 mL), anhydrous sodium acetate (0.33 g, 4 mmol) was refluxed for
6 h (monitored by TLC). The reaction mixture was left to cool and the
formed solid was filtered off, washed with water, dried and recrystal-
lised from DMF to give 16a,b.
5-Benzylidene-2-[2-(1-(naphthalen-2-yl)ethylidene)hydrazinyl]-
1
thiazol-4(5H)-one (16a): Yield 72%; yellow solid; m.p. 254 °C; H
NMR (DMSO-d6): δ 2.52 (s, 3H, CH3), 7.33–8.11 (m, 11H, ArH),
8.26 (s, 1H, =CH), 8.44 (s, 1H, naphthalene-H1), 12.12 (s, 1H, D2O
exchangeable, NH); IR (KBr): vmax 1610 (C=N), 1669 (CO), 3423
(NH) cm−1; MS m/z (%): 371(M+, 26), 77(100). Anal.Calcd for
C22H17N3OS (371.45): C, 71.14; H, 4.61; N, 11.31. Found C, 71.10; H,
4.44; N, 11.01%.
5-(4-Chlorobenzylidene)-2-[2-(1-(naphthalen-2-yl)ethylidene)hydra-
zinyl]thiazol-4(5H)-one (16b): Yield 72%; yellow solid; m.p. 302 °C;
1H NMR (DMSO-d6): δ 2.53 (s, 3H, CH3), 7.43–8.26 (m, 10H, ArH),
8.30 (s, 1H, =CH), 8.46 (s, 1H, naphthalene-H1), 12.12 (s, 1H, D2O
exchangeable, NH); IR (KBr): vmax 1608 (C=N), 1662 (CO), 3427
(NH) cm−1; MS m/z (%): 405(M+, 18), 75(100). Anal. Calcd for
C22H16ClN3OS (405.90): C, 65.10; H, 3.97; N, 10.35. Found C, 65.18;
H, 3.72; N, 10.11%.
Received 14 September 2012; accepted 3 december 2012
Paper 1201520 doi: 10.3184/174751912X13567137687630
Published online: 13 February 2013
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(Z)-Methyl 2-[2-(1-(naphthalen-2-yl)ethylidene)hydrazono)-4-oxo-
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The formed solid was collected by filtration and recrystallised
from DMF to give compound 18. Yield 80%; canary yellow solid;
m.p. 278 °C; 1H NMR (DMSO-d6): δ 2.57 (s, 3H, CH3), 3.29 (s, 3H,
CH3), 6.68 (s, 1H, =CHCOOCH3), 7.55–8.03 (m, 6H, ArH), 8.38
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Reaction of (2) with 2-chloro-1,3-dicarbonyl compounds (19a,b and
21); general procedure
To a solution of 2 (0.243 g, 1 mmol) in EtOH was added TEA (0.7 mL)
and the mixture was stirred for 10 min at room temperature. To the
resulting clear solution was added the appropriate 2-chloro-1,3-dicar-
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Ethyl 4-methyl-2-[2-(1-(naphthalen-2-yl)ethylidene)hydrazinyl]thi
azole-5-carboxylate (20a): Yield 71%; yellow solid; m.p. 176 °C;
1H NMR (DMSO-d6): δ 1.27 (t, 3H, CH3), 2.52 (s, 3H, CH3), 2.60 (s,
3H, CH3), 4.11 (q, 2H, CH2), 7.55–8.01 (m, 6H, ArH), 8.39 (s, 1H,
naphthalene-H1), 10.40 (s, 1H, D2O exchangeable, NH); IR (KBr):
vmax 1540 (C=N), 1660 (C=O), 3417 (NH) cm−1. MS m/z (%): 353 (M+,
33), 127 (100). Anal. Calcd for C19H19N3O2S (353.44): C, 64.57; H,
5.42; N, 11.89. Found C, 64.24; H, 5.30; N, 11.77%.
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phenylthiazole-5-carboxamide (20b): Yield 74%; yellow solid; m.p.
160 °C; 1H NMR (DMSO-d6): δ 2.49 (s, 3H, CH3), 2.59 (s, 3H, CH3),
7.09–8.13 (m, 11H, ArH), 8.23 (s, 1H, naphthalene-H1), 9.65 (s, 1H,
D2O exchangeable, NH), 11.33 (s, 1H, D2O exchangeable, NH); IR
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