Utilization of α-halocarbonyl compounds in the synthesis of thiazole, thiadiazole, and thiophene derivatives

Article abstract of DOI:10.1002/hc.20206

The behavior of ethyl 2-phenylthiocarbamoyl acetate 1 toward a variety of several α-halocarbonyl compounds was investigated. Thus, reaction of 1 with α-bromoketones, hydrazonoyl bromides, and 2-chloro-N-arylacetamides afforded the corresponding dihydrothi

Full text of DOI:10.1002/hc.20206

Heteroatom Chemistry
Volume 17, Number 4, 2006
Utilization of α-Halocarbonyl Compounds
in the Synthesis of Thiazole, Thiadiazole,
and Thiophene Derivatives
Ehab Abdel-latif and Samir Bondock
Faculty of Science, Chemistry Department, University of Mansoura, Mansoura 35516, Egypt
Received 20 July 2005; revised 29 October 2005
terial DNA gyrase B [13]. Also, thiazoles were used
ABSTRACT: The behavior of ethyl 2-phenylthiocarb-
as a building block of electrically and optically func-
amoyl acetate 1 toward a variety of several ꢀ-halo-
tional pi-conjugated polymers [14,15]. The demon-
carbonyl compounds was investigated. Thus, reaction
strated clinically effective antitumor activity of cer-
of 1 with ꢀ-bromoketones, hydrazonoyl bromides, and
tain substituted-thiazole analogs [16–19] prompted
2-chloro-N-arylacetamides afforded the correspond-
us to explore an efficient and easily synthesis of some
ing dihydrothiazole, 1,3,4-thiadiazole, and thiophene
thiazole derivatives.
derivatives, respectively. The synthesis of thiazolidin-4-
one 11, thiazolidin-5-one 12, and some azo derivatives
of thiazolidin-5-one were described. 5-Arylazothiazoles
17 and 19 were synthesized by condensation of hy-
RESULTS AND DISCUSSION
In continuation of our interest in the synthe-
sis of novel thiazole derivatives of industrial im-
portance [20,21], we report here a facile one-pot
synthesis of the title compounds via reaction
of various ꢀ-halocarbonyl compounds with the
thiocarbamoyl derivative 1. Thus, treatment of
ethyl 2-phenylthiocarbamoyl acetate 1 [22] with
ꢀ-bromoketones, e.g., bromoacetone and phenacyl
bromide in ethanol under reflux, afforded prod-
ucts identified as 2-(ethoxycarbonylmethylene)-2,3-
dihydro-3-phenylthiazole derivatives 2 (Scheme 1).
All of the isolated products 2a and 2b gave satis-
factory elemental analyses and spectroscopic data
(IR, 1H NMR, and MS) consistent with their assigned
structures. For example, the IR spectra of the prod-
ucts showed conjugated carbonyl absorption band
near 1652 cm−1 and the absence of NH absorption
drazonoyl bromides 3 with different thiourea deriva-
ꢀ
C
tives.
2006 Wiley Periodicals, Inc. Heteroatom Chem
17:299–305, 2006; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20206
INTRODUCTION
ꢀ-Halocarbonyl compounds are highly versatile in-
termediates for the synthesis of a variety of hetero-
cyclic compounds [1,2]. Thiazole derivatives have at-
tracted continuing interest over the years because of
their varied biological activities [3,4], recently found
application in drug development for the treatment
of allergies [5], hypertension [6], inflammation [7],
schizophrenia [8], bacterial [9] and HIV infections
[10], and very recently for the treatment of pain
[11], as fibrinogen receptor antagonists with anti-
thrombotic activity [12], as new inhibitors of bac-
1
band. The H NMR spectrum of 2a revealed ethyl
ester protons as triplet and quartet signals at ꢁ 1.40
and 4.40, a singlet signal at δ 1.75 due to methyl pro-
tons, olefinic CH singlet at δ 5.20, thiazole-5-CH pro-
ton at δ 6.60, in addition to a multiplet in the region
δ 7.30–7.70 corresponding to the aromatic protons.
Correspondence to: Ehab Abdel-latif; e-mail: ehabattia00@gmx.
net.
c
ꢀ
2006 Wiley Periodicals, Inc.
299

300 Abdel-latif and Bondock
SCHEME 2
SCHEME 1
On the other hand, treatment of 1 with hydra-
zonoyl bromides 3 in ethanol in the presence of tri-
ethylamine under reflux, afforded a single product in
each case, as evidenced by TLC. The structure of the
isolated products was established by analytical and
spectroscopic data (IR, 1H NMR, and MS) and identi-
fied as 2-(ethoxycarbonylmethylene)-5-benzoyl-2,3-
dihydro-3-aryl-1,3,4-thiadiazoles 5 instead of the
arylazothiazole derivatives 6. The formation of 1,3,4-
thiadiazole derivatives 5 from the reaction of 1 with 3
seems to follow the sequence outlined in Scheme 1.
It is suggested that the reaction starts with nucle-
ophilic substitution of the bromine atom in 3 by the
thiolate group of 1 to give the nonisolable interme-
diate 4 which cyclizes via elimination of aniline [23]
to give 5 as end product. The IR spectrum of 5a re-
vealed two carbonyl absorption bands at 1667 (CO
ester) and 1628 cm−1 (conjugated CO). The 1H NMR
spectrum of the same compound showed ethyl ester
protons as triplet and quartet signals at δ 1.20 and
4.10, olefinic CH singlet at δ 5.30, in addition to a
multiplet in the region δ 7.20–7.60 due to the aro-
matic protons. The mass spectra of the products 5a
and 5b exhibited in each case a molecular ion peak
with high intensity.
A different reaction path was observed when
the anilide 1 reacts with 2-chloro-N-arylacetamides
7. The reaction proceeds only in ethanolic sodium
ethoxide solution under reflux to afford the cor-
responding thiophene derivatives 9 through nucle-
ophilic attack of the thiolate group followed by ring
closure and ethanol elimination (Scheme 2). The
products were assigned the thiophene structure 9
and not the thiazole structure 10 on the basis of
their elemental analysis and spectral data. Thus,
e.g., the IR spectrum of 9a showed three absorp-
tion bands at 3303, 3235, and 3192 cm−1 due to OH
and two (NH) functions besides one carbonyl ab-
1
sorption band at 1671 cm−1. Its H NMR revealed
a singlet at δ 6.20 due to thiophene 4-CH, multiplet
at δ 6.90–7.60 corresponding to the aromatic pro-
tons, in addition to three exchangeable singlets at δ
9.20, 9.55, and 11.80 due to two NH and OH protons,
respectively.
Treatment of 1 with ethyl bromoacetate and with
chloroacetyl chloride afforded two different thiazo-
lidinones according to their TLC, melting points,
and spectral data. The structures of these thiazo-
lidinones were clearly differentiated and identified
as thiazolidin-4-one 11 and thiazolidin-5-one 12 on
1
the basis of their IR, H NMR, 13C NMR and MS
spectra. For example, in the IR spectra, there is a
pronouncing difference: the carbonyl absorption fre-
quency in the thiazolidin-4-one 11 appears at 1719
cm−1, while in the thiazolidin-5-one 12 this absorp-
tion is shifted to higher frequency at 1742 cm−1. The
1H NMR spectra showed a strong chemical shift dif-
ference of methylene protons of about 1.00 ppm,
thiazolidin-4-one 11 absorbs at lower chemical shift
δ 3.90. The 13C NMR spectra also showed a strong
chemical shift difference of carbonyl carbon of about
12.84 ppm, thiazolidin-4-one 11 absorbs at lower
chemical shift δ 171.72 (see Experimental).
The reactivity of thiazolidin-5-one derivative 12
toward the electrophilic substitution reaction by
aromatic diazonium salts was also examined. The
methylene group of the thiazolidine ring proved
to be more reactive toward the azo coupling with
diazonium salts than the olefinic methine group.
Thus, an equimolar amount of aryl diazonium chlo-
rides at 0–5◦C reacted with compound 12 to yield
the corresponding monohydrazono derivatives 13
Heteroatom Chemistry DOI 10.1002/hc

Utilization of ꢀ-Halocarbonyl Compounds in the Synthesis of Thiazole, Thiadiazole, and Thiophene Derivatives 301
of the dyes 19a–c exhibited, in all cases, the presence
of NH, carbonyl and azo stretching bands near 3284,
1656, and 1558 cm−1, respectively. The 1H NMR
spectrum of 19c (for example) revealed three singlet
signals at δ 2.40, 3.00, and 4.20 corresponding
to three CH3 and one CH2 protons in addition
to abroad signal at δ 6.90 and a multiplet in the
region δ 7.20–7.50 due to NH and aromatic protons,
respectively.
CONCLUSION
In conclusion, several thiazole derivatives were pre-
pared from the readily available thiocarbamoyl com-
pound 1 and a variety of ꢀ-halocarbonyl com-
pounds especially ꢀ-bromoketones, ethyl bromoac-
etate, and chloroacetyl chloride. The synthesis of
1,3,4-thiadiazoles was achieved by the reaction of 1
with hydrazonoyl bromides 3. While the interaction
of 1 with ꢀ-chloroacetamides furnished the corre-
sponding thiophene derivatives. A large number of
5-arylazothiazole derivatives have been synthesized
on useful paths. These highly functionalized deriva-
tives may be of interest for dyeing purposes, yet to
be explored.
SCHEME 3
instead of the azo compounds 14 (Scheme 3).
The azo compounds 14 were obtained in good
yields from the reaction of ethyl 2-arylhydrazono-
2-phenylthiocarbamoyl acetate derivatives 15 [24]
with chloroacetyl chloride by stirring in DMF con-
taining few drops of triethylamine as a catalyst. The
molecular structures of the compounds 13 and 14
were established by elemental analyses and spectro-
scopic data.
Condensation of hydrazonoyl bromides 3 with
thiosemicarbazone derivatives 16 by reflux in
ethanol containing a catalytic amount of triethyl-
amine afforded the corresponding 5-phenyl-
azothiazole derivatives 17. The chemical structures
of 17a–e were secured by their elemental analyses,
IR, NMR, and MS spectra (see Experimental).
Finally, the appropriate hydrazonoyl bromides 3
were reacted with 1-[(dimethylcarbamoyl)methyl]-
thiourea 18 to afford the corresponding 5-
arylazothiazole derivatives 19 (Scheme 4). The
structures of the highly functionalized thiazolyl
dyes 19a–c were assigned on the basis of their
elemental analyses and spectral data. The IR spectra
EXPERIMENTAL
Melting points were recorded on a Gallenkamp melt-
ing point apparatus and are uncorrected. IR spec-
tra (KBr) were determined on a Mattson 5000 FTIR
spectrometer (not all frequencies are reported). The
1H NMR and 13C NMR spectra were acquired us-
ing a Bruker WP 300 spectrometer at 300 MHz (1H)
or 75.5 MHz (13C; in broad band mode) using TMS
as an internal standard. Mass spectra were recorded
on a Finnigan MAT 212 instrument. Elemental anal-
yses were carried out at the microanalytical unit,
Faculty of Science, University of Mansoura, Egypt.
Due to the limited solubility of the products in com-
mon 13C NMR solvents, the 13C NMR spectra were
recorded for 9a, 11, 12, 14c, 17c, 17d, 19a, and
19b only as representative examples of the series
prepared.
Synthesis of 2,3-Dihydro-3-phenyl-1,3-thiazole
Derivatives 2a,b
A mixture of the thiocarbamoyl derivative 1 (5 mmol)
and the appropriate ꢀ-bromoketone, bromoacetone
or phenacyl bromide (5 mmol) in absolute ethanol
(25 mL) was refluxed for 2 h, then allowed to cool.
The precipitate that formed was filtered off, dried,
and recrystallized from ethanol to give the dihy-
drothiazoles 2a and 2b, respectively.
SCHEME 4
Heteroatom Chemistry DOI 10.1002/hc

302 Abdel-latif and Bondock
2-(Ethoxycarbonylmethylene)-2,3-dihydro-4-me-
thyl-3-phenyl-1,3-thiazole 2a. Yellow crystals; yield
88%; mp 171–172◦C; IR (ν/cm−1) = 1652 (CO ester),
1596 (C C); 1H NMR (DMSO): δ = 1.40 (t, 3H, CH3),
1.75 (s, 3H, CH3), 4.40 (q, 2H, CH2), 5.20 (s, 1H,
CH), 6.60 (s, 1H, thiazole 5-H), 7.30–7.70 (m, 5H,
Ar-H); MS (M+ + H; CI iso-butane) m/z (%): 262
(100). Calcd for C14H15NO2S (261.34): C, 64.34;
H, 5.79; N, 5.36%. Found: C, 64.23; H, 5.71; N,
5.44%.
Synthesis of 3-Hydroxy-5-(phenylamino)-
thiophene-2-carboxamide Derivatives 9a–c
General Procedure. To a solution of 1 (5 mmol)
in ethanolic sodium ethoxide (5 mmol) (prepared
by dissolving sodium metal (0.12 g) in abso-
lute ethanol (30 mL)), the appropriate 2-chloro-N-
arylacetamides 7a–c were added. The reaction mix-
ture was heated under reflux for 4 h. The reaction
mixture was poured into cold water, neutralized with
dilute HCl, and the solid product that formed was
filtered off and recrystallized from dioxane to afford
the corresponding thiophene derivatives 9a–c.
2-(Ethoxycarbonylmethylene)-2,3-dihydro-3,4-di-
phenyl-1,3-thiazole 2b. Yellow crystals; yield 68%;
mp 192–193◦C; IR (ν/cm−1) = 1646 (CO ester), 1598
(C C); 1H NMR (DMSO): δ = 1.40 (t, 3H, CH3), 4.40
(q, 2H, CH2), 5.20 (s, 1H, CH), 6.60 (s, 1H, thiazole
5-H), 7.10–7.70 (m, 10H, Ar-H); MS (M+ + H; CI iso-
butane) m/z (%): 324 (100). Calcd for C19H17NO2S
(323.41): C, 70.56; H, 5.30; N, 4.33%. Found: C,
70.38; H, 5.19; N, 4.28%.
3-Hydroxy-N-phenyl-5-(phenylamino)thiophene-
2-carboxamide 9a. White crystals; yield 68%; mp
196–197◦C; IR (ν/cm−1) = 3303 (OH), 3235 (NH),
3192 (NH), 1671 (CO amide); 1H NMR (DMSO):
δ = 6.20 (s, 1H, thiophene 4-H), 6.90–7.60 (m, 10H,
Ar-H), 9.20 (s, 1H, NH), 9.55 (s, 1H, NH), 11.80
(s, 1H, OH); 13C NMR (DMSO): δ = 96.05, 99.38,
116.89 (2C), 119.42 (2C), 121.40, 122.83, 128.72
(2C), 129.40 (2C), 138.86, 141.74, 151.41, 157.55,
161.14; MS (M+ + H; CI iso-butane) m/z (%): 311
(78). Calcd for C17H14N2O2S (310.37): C, 65.79; H,
4.55; N, 9.03%. Found: C, 65.62; H, 4.43; N, 8.86%.
Synthesis of 2,3-Dihydro-3-phenyl-1,3,4-
thiadiazole Derivatives 5a,b
To a mixture of the thiocarbamoyl derivative 1
(5 mmol) and the appropriate hydrazonoyl bromides
3a,b (5 mmol) in absolute ethanol (25 mL), few drops
of triethylamine was added as a catalyst. The mix-
ture was refluxed for 4 h, then left to cool at room
temperature. The solid that formed was collected by
flirtation, dried, and recrystallized form ethanol to
give the thiadiazoles 5a,b in 78 and 74% yield, re-
spectively.
3-Hydroxy-5-(phenylamino)-N-(4-phenylthiazol-
2-yl)thiophene-2-carboxamide 9b. White crystals;
yield 58%; mp 211–212◦C; IR (ν/cm−1) = 3294 (OH),
1
3244 (NH), 3146 (NH), 1677 (CO amide); H NMR
(DMSO): δ = 6.20 (s, 1H, thiophene 4-H), 6.90–7.80
(m, 11H, Ar-H, thiazole 5-H), 9.20 (s, 1H, NH),
9.70 (s, 1H, NH), 11.90 (s, 1H, OH). Calcd for
C20H15N3O2S2 (393.48): C, 61.05; H, 3.84; N, 10.68%.
Found: C, 61.22; H, 3.93; N, 10.77%.
2-(Ethoxycarbonylmethylene)-5-benzoyl-2,3-di-
hydro-3-phenyl-1,3,4-thiadiazole 5a. Red crystals;
yield 78%; mp 234–235◦C; IR (ν/cm−1) = 1667 (CO
ester), 1628 (CO conjugated); 1H NMR (DMSO):
δ = 1.20 (t, 3H, CH3), 4.10 (q, 2H, CH2), 5.30 (s, 1H,
CH), 7.20–7.60 (m, 10H, Ar-H); MS (M+ + H; CI
iso-butane) m/z (%): 353 (80). Calcd for C19H16N2O3S
(352.41): C, 64.76; H, 4.58; N, 7.95%. Found: C,
64.86; H, 4.67; N, 7.81%.
3-Hydroxy-5-(phenylamino)-N-(4-phenyl-5-phenyl-
azothiazol-2-yl)thiophene-2-carboxamide 9c. Red
crystals; yield 62%; mp 184–185◦C; IR (ν/cm−1) =
3303 (OH), 3235 (NH), 3182 (NH), 1671 (CO amide);
1H NMR (DMSO): δ = 6.20 (s, 1H, thiophene 4-H),
7.00–7.80 (m, 15H, Ar-H), 9.20 (s, 1H, NH), 9.60 (s,
1H, NH), 11.70 (s, 1H, OH). Calcd for C26H19N5O2S2
(497.59): C, 62.76; H, 3.85; N, 14.07%. Found: C,
62.58; H, 3.94; N, 14.18%.
2-(Ethoxycarbonylmethylene)-5-benzoyl-2,3-di-
hydro-3-(p-tolyl)-1,3,4-thiadiazole 5b. Red crystals;
yield 74%; mp 276–277◦C; IR (ν/cm−1) = 1662 (CO
ester), 1630 (CO conjugated); 1H NMR (CDCl3):
δ = 1.20 (t, 3H, CH3), 2.40 (s, 3H, CH3), 4.10 (q, 2H,
CH2), 5.30 (s, 1H, CH), 7.10–7.80 (m, 9H, Ar-H);
MS (M+ + H; CI iso-butane) m/z (%): 367 (67). Calcd
for C20H18N2O3S (366.43): C, 65.55; H, 4.95; N,
7.64%. Found: C, 65.73; H, 4.82; N, 7.76%.
Synthesis of 2-(Ethoxycarbonylmethylene)-3-
phenyl-1,3-thiazolidin-4-one 11
A mixture of 1 (5 mmol) and ethyl bromoacetate
(5 mmol) in ethanol (30 mL) containing fused
sodium acetate (0.40 g) was refluxed for 4 h. The
reaction mixture was left to cool to room tempera-
ture. The solid product was collected by filtration,
Heteroatom Chemistry DOI 10.1002/hc

Utilization of ꢀ-Halocarbonyl Compounds in the Synthesis of Thiazole, Thiadiazole, and Thiophene Derivatives 303
washed with water, and recrystallized from ethanol
to give 11 as follows.
2-(Ethoxycarbonylmethylene)-3-phenyl-4-(p-me-
thoxyphenylhydrazono)-1,3-thiazolidin-5-one 13b.
White crystals; yield 78%; mp 161–162◦C; IR
(ν/cm−1) = 1719 (CO ring), 1683 (CO ester); 1H NMR
(CDCl3/DMSO): δ = 1.20 (t, 3H, CH3), 3.90 (s, 2H,
CH2), 4.10 (q, 2H, CH2), 5.10 (s, 1H, CH), 7.15–7.55
(m, 5H, Ar-H); 13C NMR (CDCl3/DMSO): δ = 14.02,
31.79, 59.65, 92.36, 127.68 (2C), 129.45, 129.86 (2C),
134.61, 158.76, 167.21, 171.72; MS (M+ + H; CI iso-
butane) m/z (%): 264 (100). Calcd for C13H13NO3S
(263.06): C, 59.30; H, 4.98; N, 5.32%. Found: C, 59.13;
H, 4.85; N, 5.18%.
Reddish brown crystals; yield 66%; mp 231–232◦C;
IR (ν/cm−1) = 1709 (CO ring), 1682 (CO ester);
1H NMR (DMSO): δ = 1.10 (t, 3H, CH3), 3.85 (s,
3H, OCH3), 4.10 (q, 2H, CH2), 5.10 (s, 1H, CH),
6.90–7.60 (m, 9H, Ar-H), 8.80 (s, 1H, NH). MS
(M+ + H; CI iso-butane) m/z (%): 398 (100). Calcd for
C20H19N3O4S (397.45): C, 60.44; H, 4.82; N, 10.57%.
Found: C, 60.30; H, 4.88; N, 10.63%.
Synthesis of 2-[Ethoxycarbonyl(aryldiazenyl)-
methylene]-thiazolidin-5-ones 14a,b
Synthesis of 2-(Ethoxycarbonylmethylene)-3-
phenyl-1,3-thiazolidin-5-one 12
To a solution of 15 (5 mmol) in N,N-dimethyl-
formamide (20 mL) containing drops of triethy-
lamine, chloroacetyl chloride (10 mmol) was added
dropwise with stirring. After complete addition,
the reaction mixture was stirred for 2 h and then
poured into ice-cooled water. The solid product
was collected by filtration and recrystallized from
EtOH/DMF mixture (2:1) to give 14a,b.
To a solution of 1 (5 mmol) in N,N-dimethyl-
formamide (20 mL) containing drops of triethy-
lamine, chloroacetyl chloride (10 mmol) was added
dropwise with stirring. After complete addition, the
reaction mixture was stirred for 2 h and then poured
into ice-cooled water. The solid product was col-
lected by filtration and recrystallized from ethanol
to give 12 as follows.
2-[Ethoxycarbonyl(p-tolyldiazenyl)methylene]-3-
phenyl-1,3-thiazolidin-5-one 14a. Orange crystals;
yield 83%; mp 161–162◦C; IR (ν/cm−1) = 1731 (CO
Yellow crystals; yield 84%; mp 137–138◦C; IR
(ν/cm−1) = 1742 (CO ring), 1688 (CO ester); 1H
NMR (CDCl3/DMSO): δ = 1.20 (t, 3H, CH3), 4.10 (q,
2H, CH2), 4.90 (s, 2H, CH2), 5.10 (s, 1H, CH),
6.95–7.80 (m, 5H, Ar-H); 13C NMR (CDCl3/DMSO):
δ = 13.85, 43.14, 59.65, 106.74, 128.06 (2C), 129.11,
130.74 (2C), 137.42, 158.94, 168.36, 184.56. Calcd for
C13H13NO3S (263.06): C, 59.30; H, 4.98; N, 5.32%.
Found: C, 59.08; H, 4.79; N, 5.23%.
1
ring), 1706 (CO ester); H NMR (DMSO): δ = 1.10
(t, 3H, CH3), 2.40 (s, 3H, CH3), 3.50 (q, 2H, CH2),
5.10 (s, 2H, CH2), 7.10–7.70 (m, 9H, Ar-H). Calcd for
C20H19N3O3S (381.45): C, 62.97; H, 5.02; N, 11.02%.
Found: C, 63.17; H, 5.12; N, 10.94%.
2-[Ethoxycarbonyl(p-methoxyphenyldiazenyl)me-
thylene]-3-phenyl-1,3-thiazolidin-5-one
14b. Or-
ange crystals; yield 78%; mp 153–154◦C; IR
(ν/cm−1) = 1734 (CO ring), 1698 (CO ester); 1H
NMR (DMSO): δ = 1.00 (t, 3H, CH3), 3.45 (q, 2H,
CH2), 3.80 (s, 3H, OCH3), 5.25 (s, 2H, CH2), 6.95–
7.80 (m, 9H, Ar-H); 13C NMR (DMSO): δ = 13.15,
44.47, 55.51, 61.29, 113.99 (2C), 124.05 (2C), 126.82,
128.45, 128.74 (2C), 130.85 (2C), 138.55, 139.33,
159.94, 160.88, 169.11, 185.90; MS (M+ + H; CI
iso-butane) m/z (%): 398 (60). Calcd for C20H19N3O4S
(397.45): C, 60.44; H, 4.82; N, 10.57%. Found: C,
60.26; H, 4.71; N, 10.49%.
Synthesis of 3-Phenyl-4-(arylhydrazono)-1,3-
thiazolidin-5-ones 13a,b
An aqueous solution of the appropriate arenediazo-
nium chloride (5 mmol) was added portionwise to a
stirred solution of 12 (5 mmol) in pyridine (30 mL)
at 0–5◦C. The reaction mixture was stirred for 2 h,
the resulting solid was collected, washed with water,
and recrystallized from ethanol to give 13a,b in 71
and 66% yield, respectively.
2-(Ethoxycarbonylmethylene)-3-phenyl-4-(p-tolyl-
hydrazono)-1,3-thiazolidin-5-one 13a. Red crystals;
yield 71%; mp 253–254◦C; IR (ν/cm−1) = 1711 (CO
Synthesis of 5-Phenylazo-1,3-thiazole
Derivatives 17 and 19
1
ring), 1686 (CO ester); H NMR (DMSO): δ = 1.10
General Procedure. A mixture of hydrazonoyl
bromides 3 (2 mmol) and the appropriate thiosemi-
carbazones 16 or thiourea derivative 18 (2 mmol)
in absolute ethanol (20 mL), in the triethylamine
(0.2 mL), was refluxed for 2 h, then left to cool.
The precipitated product was filtered off, dried, and
(t, 3H, CH3), 2.40 (s, 3H, CH3), 4.10 (q, 2H, CH2),
5.10 (s, 1H, CH), 7.10–7.80 (m, 9H, Ar-H), 8.90 (s,
1H, NH). Calcd for C20H19N3O3S (381.45): C, 62.97;
H, 5.02; N, 11.02%. Found: C, 62.84; H, 5.09; N,
11.11%.
Heteroatom Chemistry DOI 10.1002/hc

304 Abdel-latif and Bondock
finally recrystallized from EtOH/DMF mixture (2:1)
to afford the corresponding thiazoles 17a–e and
19a–c.
(M+; EI) m/z (%): 417 (100). Calcd for C22H16ClN5S
(417.91): C, 63.23; H, 3.86; N, 16.76%. Found: C,
63.06; H, 3.74; N, 16.68%.
2-(Benzylidenehydrazino)-4-phenyl-5-phenylazo-
1,3-thiazole 17a. Red crystals; yield 60%; mp 217–
218◦C; IR (ν/cm−1) = 3153 (NH), 1601 (C N), 1561
(N N); 1H NMR (DMSO): δ = 7.05–7.55 (m, 12H,
Ar-H, NH), 7.80 (d, 2H, Ar-H), 8.30 (d, 2H, Ar-H),
8.40 (s, 1H, N CH); MS (M+; EI) m/z (%): 383 (100).
Calcd for C22H17N5S (383.47): C, 68.91; H, 4.47; N,
18.26%. Found: C, 69.02; H, 4.54; N, 18.34%.
2-(4-Phenyl-5-phenylazo-thiazol-2-ylamino)-N,N-
dimethylacetamide 19a. Red crystals; yield 91%;
mp 209–210◦C; IR (ν/cm−1) = 3284 (NH), 1656 (CO),
1558 (N N); 1H NMR (CDCl3): δ = 3.00 (s, 6H,
2CH3), 4.20 (s, 2H, CH2), 6.90 (s, 1H, NH), 7.30–7.50
(m, 6H, Ar-H), 7.70 (d, 2H, Ar-H), 8.25 (d, 2H, Ar-H);
13C NMR (CDCl3): δ = 35.75, 35.87, 45.38, 122.44
(2C), 128.22 (2C), 128.98 (2C), 129.14, 129.32,
130.38 (2C), 134.69, 141.44, 152.82, 154.52, 167.07,
167.37; MS (M+; EI) m/z (%): 365 (100). Calcd for
C19H19N5OS (365.45): C, 62.44; H, 5.24; N, 19.16%.
Found: C, 62.50; H, 5.28; N, 19.12%.
2-(p-Methylbenzylidenehydrazino)-4-phenyl-5-ph-
enylazo-1,3-thiazole 17b. Red crystals; yield 62%;
mp 204–205◦C; IR (ν/cm−1) = 3168 (NH), 1607
1
(C N), 1571 (N N); H NMR (CDCl3): δ = 2.40 (s,
3H, CH3), 7.10–7.70 (m, 15H, Ar-H, NH), 8.40 (s,
1H, N CH); MS (M+; EI) m/z (%): 397 (100). Calcd
for C23H19N5S (397.50): C, 69.50; H, 4.82; N, 17.62%.
Found: C, 69.58; H, 4.87; N, 17.71%.
2-(4-Phenyl-5-(p-tolylazo)thiazol-2-ylamino)-N,N-
dimethylacetamide 19b. Red crystals; yield 82%;
mp 220–221◦C; IR (ν/cm−1) = 3288 (NH), 1655 (CO),
1542 (N N); 1H NMR (CDCl3): δ = 2.40 (s, 3H, CH3),
3.00 (s, 6H, 2CH3), 4.20 (s, 2H, CH2), 6.90 (s, 1H,
NH), 7.20–7.50 (m, 9H, Ar-H); 13C NMR (CDCl3):
δ = 21.37, 35.73, 35.86, 45.35, 122.39 (2C), 128.20
(2C), 129.16, 129.67 (2C), 130.32 (2C), 134.20,
139.56, 141.56, 150.90, 153.70, 167.03, 167.14.
Calcd for C20H21N5OS (379.48): C, 63.30; H, 5.58; N,
18.46%. Found: C, 63.24; H, 5.52; N, 18.53%.
2-(p-Methoxybenzylidenehydrazino)-4-phenyl-5-
phenylazo-1,3-thiazole 17c. Red crystals; yield
82%; mp 215–216◦C; IR (ν/cm−1) = 3246 (NH), 1602
(C N), 1553 (N N); 1H NMR (CDCl3/CF3COOD):
δ = 3.85 (s, 3H, OCH3), 6.95 (d, 2H, Ar-H), 7.40–8.05
(m, 12H, Ar-H), 8.20 (s, 1H, N CH); 13C NMR
(CDCl3/CF3COOD): δ = 55.56, 114.79 (2C), 121.39
(2C), 121.96, 124.63, 127.95, 129.36 (2C), 129.79
(2C), 130.20 (2C), 130.57 (2C), 131.03, 133.00,
137.15, 147.49, 154.33, 163.17, 170.04; MS (M+; EI)
m/z (%): 413 (100). Calcd for C23H19N5OS (413.49):
C, 66.81; H, 4.63; N, 16.94%. Found: C, 66.86; H,
4.68; N, 16.87%.
2-(4-Phenyl-5-(p-methoxyphenylazo)-thiazol-2-
ylamino)-N,N-dimethylacetamide 19c. Red crystals;
yield 87%; mp 224–225◦C; IR (ν/cm−1) = 3238 (NH),
1651 (CO), 1581 (N N); 1H NMR (CDCl3/CF3COOD):
δ = 3.00 (s, 6H, 2CH3), 3.80 (s, 3H, OCH3), 4.35 (s,
2H, CH2), 6.90 (d, 2H, Ar-H), 7.40–7.90 (m, 7H,
Ar-H); MS (M+; EI) m/z (%): 395 (100). Calcd for
C20H21N5O2S (395.48): C, 60.74; H, 5.35; N, 17.71%.
Found: C, 60.68; H, 5.30; N, 17.78%.
2-(p-N,N-Dimethylaminobenzylidenehydrazino)-
4-phenyl-5-phenylazo-1,3-thiazole 17d. Red crys-
tals; yield 86%; mp 212–213◦C; IR (ν/cm−1) = 3164
1
(NH), 1599 (C N), 1578 (N N); H NMR (CDCl3):
δ = 3.05 (s, 6H, 2CH3), 6.65 (d, 2H, Ar-H), 7.00–7.75
(m, 13H, Ar-H, NH), 8.40 (s, 1H, N CH); 13C NMR
(CDCl3): δ = 40.05 (2C), 111.59 (2C), 114.21 (2C),
121.76, 122.70, 128.32 (2C), 129.51 (2C), 130.24,
130.66 (2C), 130.93 (2C), 131.91, 141.04, 142.82,
152.67, 161.42, 168.61, 172.02; MS (M+; EI) m/z (%):
426 (100). Calcd for C24H22N6S (426.54): C, 67.58;
H, 5.20; N, 19.70%. Found: C, 67.44; H, 5.12; N,
19.62%.
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