Synthesis of novel bis- and poly(hydrazinylthiazole) linked to benzofuran or benzothiazole as new hybrid molecules

Article abstract of DOI:10.24820/ark.5550190.p010.810

A novel series of bis- and poly(thiazoles) substituted with benzofuran and benzothiazole moieties were prepared in good yields by the reaction of the appropriate bis(α-bromoketones) with the corresponding bis- and poly(hydrazinecarbothioamide) in refluxing EtOH in the presence of TEA. The structures of the new compounds were confirmed based on elemental analyses as well as spectral data.

Full text of DOI:10.24820/ark.5550190.p010.810

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Synthesis of novel bis- and poly(hydrazinylthiazole) linked to benzofuran or
benzothiazole as new hybrid molecules
Mostafa E. Salem, Ahmed F. Darweesh, Mohamed R. Shaaban, and Ahmed H. M. Elwahy*
Chemistry Department, Faculty of Science, Cairo University, Giza-Egypt
E-mail: aelwahy@hotmail.com
Received 11-11-2018
Accepted 01-19-2019
Published on line 02-17-2019
Abstract
A novel series of bis- and poly(thiazoles) substituted with benzofuran and benzothiazole moieties were
prepared in good yields by the reaction of the appropriate bis(α-bromoketones) with the corresponding bis-
and poly(hydrazinecarbothioamide) in refluxing EtOH in the presence of TEA. The structures of the new
compounds were confirmed based on elemental analyses as well as spectral data.
Keywords: Bisaldehydes, poly(aldehydes), bis(thiazoles), poly(thiazoles), bromoacetylbenzofuran,
bromoacetylbenzothiazole, hybrid molecules
DOI: https://doi.org/10.24820/ark.5550190.p010.810
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Introduction
Thiazoles are promising scaffolds in the area of medicinal and pharmaceutical chemistry and have accounted
to show different biological activities, such as anti-HIV, anti-inflammatory, antimicrobial, antihypertensive,
1–10
antifungal, anticonvulsant, antiviral, anticancer, antimalarial, and anti-hypolipidemic activities.
thiazole containing compounds are well established as medicines (Figure 1).
Some
11–16
Moreover, among different heterocyclic compounds, benzofuran constitutes the most important class of
fused ring heterocyclic. They are considered the core of several interesting pharmacologically active natural
1
7–20
products.
Recently, benzofuran derivatives attracted natural product researchers due to their valuable
21,22
21
23,24
25
biological activities including antifungal,
anticonvulsant, anticancer, antiHIV, analgesic,29 antiparasitic,30 antihyperlipidemic,31 antioxidant,
antiplasmodial and anti-Alzheimer's. Several clinically approved drugs based on benzofuran moiety are
outlined in Figure 1.
antiprotozoal,
antitubercular,
antiinflammatory,
2
6
27
28
32
3
3
34
35–38
Furthermore, benzothiazole core is an important scaffold for drug development, because it has
demonstrated a wide spectrum of pharmacological activities and therapeutic functions including
3
9,40
41,42
43,44
45
46
47
antitumor,
anthelmintic,
recently reviewed.
antimicrobial,
anti-tubercular,
anti-HIV,
anti-malarial,
anti-convulsant,
48,49
50
anti-oxidant and analgesic. Synthesis and biological activities of benzothiazoles have been
51–55
Some important and clinically used drugs having benzothiazole ring in their structures
including; Riluzole, Pramipexole, Dimazole and Ethoxzolamide are shown in Figure 1.
Figure 1
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In addition, molecular hybridization have attracted much attention in the last decades in drug design and
development as it can lead to compounds with superior efficacy via integration of pharmacophoric moieties
from different bioactive substances.5
6–63
Motivated by these findings and in conjunction with our ongoing research work on bis- as well as
64–71
poly(heterocycles)
we report herein on the synthesis of novel scaffolds based on thiazole linked with
benzofuran or benzothiazole moieties as new hybrid molecules with enhanced biological potentials.
Results and Discussion
The desired starting building blocks; bromoacetylbenzofuran (3) and bromoacetylbenzothiazole (4) were
obtained in good yields by bromination of the corresponding acetyl derivatives 1 and 2 with bromine in acetic
72–75
acid (Scheme 1).
Scheme 1
The preparation of bis(thiazole) 8a-c, in which the (benzofuran-2-yl)-hydrazinyl)thiazole is linked to
benzene core via phenoxymethyl group, is depicted in Scheme 2. Thus, reaction of the appropriate
bis(aldehydes) 5a-c with thiosemicarbazide (6) in refluxing EtOH containing few drops of AcOH, gave the
corresponding alkylenebis(oxy)bis(2,1-phenylene)bis(methan-1-yl-1-ylidene))bis-(hydrazinecarbothioamide)
65
7
a-c. Reaction of the latter compounds with 1-(benzofuran-2-yl)-2-bromoethanone (3) in refluxing ethanol
in the presence of TEA, gave 8a-c in 75–85% yields (Scheme 2).
The same methodology was extended to the preparation of bis(thiazole) 9a-c in which hydrazinyl)thiazol-4-
yl)benzo[d]thiazole is linked to benzene core via phenoxymethyl group. Thus, reaction of 7a-c with 1-
(
benzo[d]thiazol-2-yl)-2-bromoethanone (4) in refluxing ethanol in the presence of TEA, gave 9a-c in 71–82%
yields (Scheme 2).
The novel isomeric bis(thiazoles) 11a,b and 12a,b in which the thiazoles are linked to thieno[2,3-
b]thiophene core could also prepared using a similar approach. Thus, reaction of bis(thiosemicarbazones)
10a,b with 1-(benzofuran-2-yl)-2-bromoethanone (3) and 1-(benzo[d]thiazol-2-yl)-2-bromoethanone (4),
respectively, in refluxing ethanol in the presence of TEA afforded 11a,b and 12a,b in 69-83% and 73-78%
yields, respectively (Scheme 3). Compounds 10a,b was obtained by the reaction of the appropriate
76
bis(aldehyde) with thiosemicarbazide (6) in refluxing EtOH containing few drops of AcOH.
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Scheme 2
All of the isolated compounds were characterized by elemental analyses, as well as their spectral data
which agree with the proposed structures. The structure of bis(thiazole) 8a as a representative example was
-
confirmed by IR, 1H-NMR and mass spectra. Thus, the IR spectrum of 8a showed absorption bands at 3428 cm
1
1
because of NH group. Moreover, the H NMR spectra of compound 8a showed a D
2
O-exchangeable signal at
group and C-5
δ 12.26 because of NH protons and sharp singlet signals at δ 5.24 and 7.35 attributed to OCH
2
proton of the thiazole ring, respectively. All other protons appeared at the expected chemical shifts and
integral values. Mass spectrum of compound 8a showed an intense molecular ion peak at m/z 772 in
agreement with its respective molecular formula.
Our study was extended to include the synthesis of novel tris-, tetrakis-, and hexakis(thiazoles), in which
the thiazolylhydrazone is linked to benzene core via phenoxymethyl group. For this purpose the required
aldehydes, tris(formylphenoxymethyl)benzenes (13), tetrakis(formylphenoxymethyl)benzenes (14) and
hexakis(formylphenoxymethyl)benzenes (15) were firstly synthesized as recently described by our group via
the reaction of 4-hydroxybenzaldehyde with the appropriate poly(bromomethyl)benzene in basic medium
77
(
Figure 2).
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Scheme 3
Figure 2
Acid catalyzed condensation of tris(aldehyde) 13 with thiosemicarbazide (6) afforded the corresponding
66
tris(aldehyde thiosemicarbazones) 16 . Reaction of the latter compound with each of 1-(benzofuran-2-yl)-2-
bromoethanone (3) and 1-(benzo[d]thiazol-2-yl)-2-bromoethanone (4), respectively, in refluxing ethanol in the
presence of TEA afforded 17 and 18 in 70% and 67% yields, respectively (Scheme 4).
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Scheme 4
The same methodology was extended to the preparation of tetrakis(thiazoles) 20 and 21. Thus, reaction of
4 with thiosemicarbazide (6) in refluxing EtOH containing few drops of AcOH gave tetrakis(aldehyde
thiosemicarbazone) 19 in good yield. Reaction of the latter compound with the appropriate bromoacetyl
compounds 3 and 4 in refluxing ethanol in the presence of TEA afforded the corresponding tetrakis(thiazoles)
1
6
6
20 and 21 in 68 and 64% yields, respectively (Scheme 5).
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Scheme 5
The hexakis(thiazoles) 23 and 24 were similarly prepared, starting from 15 by firstly reaction with
thiosemicarbazide (6) in refluxing EtOH containing few drops of AcOH to give hexakis(aldehyde
66
thiosemicarbazones) 22 followed by reaction with the appropriate bromoacetyl derivatives 3 and 4 under
similar conditions (Scheme 6).
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Scheme 6
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The structures of the new synthesized compounds were confirmed by IR, NMR, and mass spectra as well as
elementary analyses. The IR spectrum of tris (thiazolylhydrazone) 17 as a representative example of this class
-
1
1
of compounds revealed an absorption band at 3427 cm because of (NH). Its H NMR spectra showed the
presence of singlet signals at δ 5.20 and δ 8.00 ppm characteristic for the OCH group and the methine proton
―N=CH―), respectively. The presence of a single set of signals characteristic of the equivalent groups in the
2
(
1
H-NMR spectra of these compounds demonstrated their symmetry. The spectra of the poly(thiazoles) 18, 20,
1, 23 and 24 showed similar spectral data which are listed in the experimental part.
2
Conclusions
We have developed an efficient approach for the synthesis of bis(thiazoles) which are linked to arene or
heteroarene core via phenoxymethyl group. We used a similar strategy for the synthesis of novel
poly(thiazoles) which are linked to a benzene core via phenoxymethyl spacers. Full characterization of these
compounds is reported. The mild reaction conditions, good yields and easily accessible starting material are
the advantages of this methodology. The successful synthesis of these compounds opens a new access to
novel hybrid molecules with interesting inclusion properties as well as broad range biological activities.
Experimental Section
General. Melting points were determined in open glass capillaries with a Gallenkamp apparatus. The infrared
spectra were recorded in potassium bromide disks on a Pye Unicam SP 3-300 and Shimaduz FTIR 8101 PC
infrared spectrophotometer. NMR spectra were recorded using a Varian Mercury VXR-300 NMR spectrometer
at 300 MHz (1H NMR) and at 75 MHz (13C NMR) using DMSO-d
performed with a Shimadzu GC-14A or GC-14B, a Shimadzu C-R6A Integrator, and a HP 5 column (25 m length,
.25 mm i.d., 0.25 μm film) or recorded with an Agilent GC 6890N. Mass spectra (EI) were obtained at 70 eV
6
as solvent. Capillary GC analyses were
0
74
75
65
76
66
66
66
using a type Shimadzu GCMQP 1000 EX Spectrometer. Compounds 3, 4, 7a-c, 10a,b, 16, 19 and 22
were prepared according to literature.
Synthesis of bis((4-((2-(4-(benzofuran-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzenes (8a-c)
and bis((4-((2-(4-(benzo[d]thiazol-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzenes (9a-c).
General Procedure. To a solution of alkylenebis(oxy)bis(2,1-phenylene)bis(methan-1-yl-1-ylidene))bis
(
(
hydrazinecarbothioamide) 7a-c (1 mmol) in ethanol (15 mL) containing TEA (0.1 ml, 1 mmol), a solution of 1-
benzofuran-2-yl)-2-bromoethanone (3) (2 mmol) or 1-(benzo[d]thiazol-2-yl)-2-bromoethanone (4) (2 mmol) in
ethanol (10 mL) was added. The reaction mixture was heated at reflux for 5h. The solvent was then
evaporated in vacuo and the solid residue was collected and recrystallized from ethanol/DMF to give the
corresponding bis((4-((2-(4-(benzofuran-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzenes 8a-c
and
respectively.
,2-Bis((4-((2-(4-(benzofuran-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene (8a). Brown
bis((4-((2-(4-(benzo[d]thiazol-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzenes
9a-c,
1
-
1 1
crystals (75%); mp 232-234 ºC; IR (KBr)  3428, 3298, 1602, 1557, 1245, 1048 cm ; H NMR (300 MHz, DMSO-
) δ 5.24 (s, 4H, CH O), 7.01-7.22 (m, 6H, ArH), 7.35 (s, 2H, thiazole-5-H), 7.37-7.56 (m, 14H, ArH), 7.80 (s, 2H,
benzofuran-3-H), 8.50 (s, 2H, CH=N), 12.26 (br. s, 2H, NH); C NMR (75 MHz, DMSO-d
d
6
2
13
6
) δ 69.3, 101.7, 106.9,
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1
12.8, 113.1, 115.4, 121.0, 122.6, 123.5, 125.0, 126.9, 127.6, 130.7, 136.4, 137.5, 141.4, 152.8, 153.1, 156.1,
+
168.8; MS m/z (%) 772 (M ). Anal. Calcd for C44
H
32
N
6
O
4
S : C, 68.38; H, 4.17; N, 10.87; S, 8.30. Found: C, 68.51;
2
H, 4.48; N, 10.95; S, 8.60%.
,3-Bis((4-((2-(4-(benzofuran-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene (8b). Brown
1
-
1 1
crystals (82%); mp 260-262 ºC; IR (KBr)  3423, 3294, 1602, 1568, 1245, 1047 cm ; H NMR (300 MHz, DMSO-
) δ 5.18 (s, 4H, CH O), 7.03-7.10 (m, 6H, ArH), 7.35 (s, 2H, thiazole-5-H), 7.43-7.62 (m, 14H, ArH), 7.86 (s, 2H,
benzofuran-3-H), 7.99 (s, 2H, CH=N), 12.13 (s, 2H, NH); C NMR (75 MHz, DMSO-d
d
6
2
13
6
) δ 69.1, 101.6, 106.8,
12.9, 115.2, 115.4, 123.6, 125.0, 127.0, 127.3, 127.8, 130.7, 131.8, 137.0, 141.1, 141.8, 153.2, 154.1, 159.3,
69.0; MS m/z (%) 772 (M ). Anal. Calcd for C44
1
1
+
H
32
N
6
O
4
S : C, 68.38; H, 4.17; N, 10.87; S, 8.30. Found: C, 68.65;
2
H, 4.32; N, 10.55; S, 8.60%.
,4-Bis((4-((2-(4-(benzofuran-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene (8c). Brown
1
-
1 1
crystals (85%); mp > 300 ºC; IR (KBr)  3415, 3289, 1602, 1569, 1245, 1046 cm ; H NMR (300 MHz, DMSO-d
δ 5.16 (s, 4H, CH O), 7.02-7.09 (m, 6H, ArH), 7.36 (s, 2H, thiazole-5-H), 7.42-7.62 (m, 14H, ArH), 7.85 (s, 2H,
benzofuran-3-H), 7.99 (s, 2H, CH=N), 12.13 (s, 2H, NH); C NMR (75 MHz, DMSO-d
6
)
2
13
6
) δ 69.0, 101.7, 106.8,
12.8, 115.1, 115.4, 116.6, 123.6, 127.0, 127.7, 127.8, 128.8, 130.7, 131.7, 136.4, 141.3, 141.8, 152.8, 159.3,
69.0; MS m/z (%) 772 (M ). Anal. Calcd for C44
1
1
+
H
32
N
6
O
4
S : C, 68.38; H, 4.17; N, 10.87; S, 8.30. Found: C, 68.55;
2
H, 4.34; N, 10.60; S, 8.41%.
,2-Bis((4-((2-(4-(benzo[d]thiazol-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene (9a). Brown
1
-
1 1
crystals (71%); mp 205-207 ºC; IR (KBr)  3416, 1564, 1240, 1092 cm ; H NMR (300 MHz, DMSO-d
6
) δ 5.25 (s,
4
5
H, CH
-H), 7.83 (d, 2H, J 6.9 Hz, ArH), 8.00 (t, 2H, J 8.7 Hz, ArH), 8.52 (s, 2H, CH=N), 12.43 (s, 2H, NH); C NMR (75
) δ 69.2, 109.0, 113.1, 121.0, 122.1, 122.3, 122.5, 124.9, 126.3, 127.4, 130.7, 134.3, 136.3,
2
O), 7.05 (t, 2H, J 7.5 Hz, ArH), 7.21 (d, 2H, J 8.4 Hz, ArH), 7.36-7.57 (m, 12H, ArH), 7.75 (s, 2H, thiazole-
13
MHz, DMSO-d
37.8, 144.5, 153.4, 156.1, 162.4, 168.5; MS m/z (%) 807 (M ). Anal. Calcd for C42
N, 13.89; S, 15.89. Found: C, 62.86; H, 3.94; N, 14.03; S, 16.01%.
,3-Bis((4-((2-(4-(benzo[d]thiazol-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene (9b). Green
6
+
1
H
30
N
8
O
2
S : C, 62.51; H, 3.75;
4
1
-
1 1
crystals (74%); mp 270-272 ºC; IR (KBr)  3429, 1571, 1505, 1240, 1049 cm ; H NMR (300 MHz, DMSO-d
.18 (s, 4H, CH O), 7.09 (d, 4H, J 8.7 Hz, ArH), 7.43-7.56 (m, 8H, ArH), 7.62 (d, 4H, J 8.4 Hz, ArH), 7.74 (s, 2H,
thiazole-5-H), 7.99-8.01 (m, 4H, CH=N & ArH), 8.09 (d, 2H, J 8.1 Hz, ArH), 12.30 (s, 2H, NH); C NMR (75 MHz,
6
) δ
5
2
13
DMSO-d
6
) δ 69.1, 94.2, 108.9, 115.1, 122.2, 122.4, 125.0, 126.3, 126.9, 127.2, 127.9, 128.5, 134.5, 136.9,
+
142.1, 144.6, 153.5, 159.4, 162.6, 168.7; MS m/z (%) 807 (M ). Anal. Calcd for C42
H
30
N
8
O
2
S : C, 62.51; H, 3.75;
4
N, 13.89; S, 15.89. Found: C, 62.69; H, 3.43; N, 13.57; S, 15.75%.
,4-Bis((4-((2-(4-(benzo[d]thiazol-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene (9c). Green
1
-
1 1
crystals (82%); mp 265-267 ºC; IR (KBr)  3423, 1569, 1508, 1245 cm ; H NMR (300 MHz, DMSO-d
H, CH O), 7.09 (d, 4H, J 8.7 Hz, ArH), 7.43-7.53 (m, 8H, ArH), 7.62 (d, 4H, J 9.0 Hz, ArH), 7.74 (s, 2H, thiazole-5-
H), 8.00-8.02 (m, 4H, CH=N & ArH), 8.10 (d, 2H, J 8.1 Hz, ArH), 12.29 (s, 2H, NH); C NMR (75 MHz, DMSO-d
6
) δ 5.17 (s,
4
2
13
6
) δ
6
1
6
9.5, 109.5, 115.6, 122.7, 123.0, 125.6, 126.9, 127.4, 128.3, 128.4, 135.0, 136.9, 142.6, 145.1, 154.0, 159.9,
+
63.1, 169.2; MS m/z (%) 807 (M ). Anal. Calcd for C42
H
30
N
8
O
2
S : C, 62.51; H, 3.75; N, 13.89; S, 15.89. Found: C,
4
2.23; H, 3.47; N, 13.62; S, 15.60%.
Synthesis of diethyl 3,4-bis(((2-(4-(benzofuran-2-yl)thiazol-2-yl)hydrazono)methylphenoxy)-
methyl)thieno[2,3-b]-thiophene-2,5-dicarboxylates (11a,b) and diethyl 3,4-bis(((2-(4-(benzo[d]-thiazol-2-
yl)thiazol-2-yl)-hydrazono)methylphenoxy)methyl)thieno[2,3-b]thiophene-2,5-dicarboxylates (12a,b).
General Procedure. To a solution of diethyl thieno[2,3-b]thiophene-2,5-dicarboxylate derivatives 10a or 10b
(
1 mmol) in ethanol (15 mL) containing TEA (0.1 ml, 1 mmol), a solution of 1-(benzofuran-2-yl)-2-
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bromoethanone (3) (2 mmol) or 1-(benzo[d]thiazol-2-yl)-2-bromoethanone (4) (2 mmol) in ethanol (10 mL)
was added. The reaction mixture was heated at reflux for 5h. The solvent was then evaporated in vacuo and
the solid residue was collected and recrystallized from ethanol/DMF to give the corresponding pure products
1
1a,b and 12a,b, respectively.
Diethyl 3,4-bis((2-((2-(4-(benzofuran-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)thieno[2,3-b]-
thiophene-2,5-dicarboxylate (11a). Brown crystals (69%); mp > 300 ºC; IR (KBr)  3429, 1707, 1602, 1562,
-
1 1
1
7
2
439, 1248, 1094 cm ; H NMR (300 MHz, DMSO-d ) δ 1.23 (t, 6H, CH3CH2-, J 7.2 Hz), 4.30 (q, 4H, CH3CH2-, J
.2 Hz), 5.62 (s, 4H, CH
H, benzofuran-3-H), 8.17 (s, 2H, CH=N), 11.96 (s, 2H, NH); MS m/z (%) 979 (M ). Anal. Calcd for C50
6
2
O), 6.88-6.94 (m, 6H, ArH), 7.24 (s, 2H, thiazole-5-H), 7.39-7.51 (m, 10H, ArH), 7.73 (s,
+
H
38
N
6
O
8 4
S :
C, 61.33; H, 3.91; N, 8.58; S, 13.10. Found: C, 61.49; H, 3.69; N, 8.35; S, 13.30%.
Diethyl 3,4-bis((4-((2-(4-(benzofuran-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)thieno[2,3-b]-
thiophene-2,5-dicarboxylate (11b). Brown crystals (83%); mp > 300 ºC; IR (KBr)  3423, 1708, 1604, 1565,
-
1 1
1
6
2
439, 1246, 1101 cm ; H NMR (300 MHz, DMSO-d ) δ 1.28 (t, 6H, CH3CH2-, J 6.9 Hz), 4.33 (q, 4H, CH3CH2-, J
6
.9 Hz), 5.59 (s, 4H, CH
2
O), 6.84-6.88 (m, 6H, ArH), 7.19 (s, 2H, thiazole-5-H), 7.35-7.44 (m, 10H, ArH), 7.70 (s,
+
H, benzofuran-3-H), 7.91 (s, 2H, CH=N), 12.04 (s, 2H, NH); MS m/z (%) 979 (M ). Anal. Calcd for C50
H
38
N
6
O
8 4
S :
C, 61.33; H, 3.91; N, 8.58; S, 13.10. Found: C, 61.30; H, 3.70; N, 8.79; S, 12.77%.
Diethyl 3,4-bis((2-((2-(4-(benzo[d]thiazol-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)thieno[2,3-
b]thiophene-2,5-dicarboxylate (12a). Green crystals (73%); mp 270-272 ºC; IR (KBr)  3430, 1708, 1564, 1438,
-
1 1
1
244, 1091 cm ; H NMR (300 MHz, DMSO-d
6
) δ 1.23 (t, 6H, CH3CH2-, J 7.2 Hz), 4.30 (q, 4H, CH3CH2-, J 7.2
Hz), 5.64 (s, 4H, CH O), 6.89-6.96 (m, 4H, ArH), 7.19-7.47 (m, 6H, ArH), 7.64 (s, 2H, thiazole-5-H), 7.69-8.00 (m,
2
1
3
6
1
1
1
H, ArH), 8.20 (s, 2H, CH=N), 12.17 (s, 2H, NH); C NMR (75 MHz, DMSO-d
6
) δ 13.8, 55.9, 61.6, 109.1, 112.5,
20.5, 121.2, 122.0, 122.4, 125.1, 126.2, 130.5, 134.4, 135.1, 135.6, 137.5, 144.5, 145.9, 153.4, 155.6, 161.1,
62.5, 168.4. Anal. Calcd for C48
H
36
N
8
O
6
S : C, 56.90; H, 3.58; N, 11.06; S, 18.99. Found: C, 56.67; H, 3.43; N,
6
0.77; S, 18.70%.
Diethyl
3,4-bis((4-((2-(4-(benzo[d]thiazol-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)thieno[2,3-
b]thiophene-2,5-dicarboxylate (12b). Green crystals (78%); mp 267-269 ºC; IR (KBr)  3433, 1701, 1570, 1503,
-
1 1
1
242, 1105 cm ; H NMR (300 MHz, DMSO-d
Hz), 5.60 (s, 4H, CH O), 6.87 (d, 4H, J 8.4 Hz, ArH), 7.33-7.40 (m, 4H, ArH), 7.43 (d, 4H, J 8.4 Hz, ArH), 7.62 (s,
H, thiazole-5-H), 7.81-7.92 (m, 4H, ArH), 7.94 (s, 2H, CH=N), 12.21 (s, 2H, NH). Anal. Calcd for C48 : C,
6.90; H, 3.58; N, 11.06; S, 18.99. Found: C, 56.60; H, 3.66; N, 11.37; S, 19.29%.
6
) δ 1.27 (t, 6H, CH3CH2-, J 6.9 Hz), 4.32 (q, 4H, CH3CH2-, J 6.9
2
2
5
H
36 8
N O
S
6 6
Synthesis.of. poly(hydrazinylthiazole) derivatives 17, 18, 20, 21, 23 and 24.
General Procedure. To a solution of poly(thiosemicarbazones) 16 or 19 or 22 (1 mmol) in absolute ethanol (25
mL) containing TEA (0.1 ml, 1 mmol), a solution of 1-(benzofuran-2-yl)-2-bromoethanone (3) or 1-
(
benzo[d]thiazol-2-yl)-2-bromoethanone (4) (3 or 4 or 6 mmol) in ethanol (10 mL) was added. The reaction
mixture was heated at reflux for 3-5 h. The solid product formed upon cooling was collected and recrystallized
from ethanol/DMF to give the corresponding poly(hydrazinylthiazoles) 17, 18, 20, 21, 23 and 24.
1
,3,5-Tris((4-((2-(4-(benzofuran-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene (17). Brown
-
1 1
crystals (70%); mp > 300 ºC; IR (KBr)  3427, 2916, 1604, 1568, 1439, 1240, 1050 cm ; H NMR (300 MHz,
DMSO-d ) δ 5.20 (s, 6H, CH O), 7.02-7.10 (m, 9H, ArH), 7.34 (s, 3H, thiazole-5-H), 7.42-7.62 (m, 18H, ArH), 7.85
s, 3H, benzofuran-3-H), 8.00 (s, 3H, CH=N), 12.13 (br. s, 3H, NH). Anal. Calcd for C63 : C, 67.54; H,
6
2
(
H
45
N
9
O
S
6 3
4
1
.05; N, 11.25; S, 8.59. Found: C, 67.68; H, 4.33; N, 11.52; S, 8.84%.
,3,5-Tris((4-((2-(4-(benzo[d]thiazol-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene
(18).
-
1 1
Green crystals (67%); mp > 300 ºC; IR (KBr)  3419, 1568, 1506, 1235, 1017 cm ; H NMR (300 MHz, DMSO-d )
6
©ARKAT USA, Inc

Arkivoc 2019, v, 0-0
Salem, M. E. et al.
δ 5.21 (s, 6H, CH
2
O), 7.10 (d, 6H, J 9.0 Hz, ArH), 7.43-7.55 (m, 9H, ArH), 7.63 (d, 6H, J 8.7 Hz, ArH), 7.74 (s, 3H §,
thiazole-5-H), 7.98-8.10 (m, 9H, CH=N & ArH), 12.30 (s, 3H, NH). Anal. Calcd for C60
H
42
N
12
O
3
S : C, 61.52; H,
6
3.61; N, 14.35; S, 16.42. Found: C, 61.77; H, 3.44; N, 14.70; S, 16.38%.
1
,2,4,5-Tetrakis((4-((2-(4-(benzofuran-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene
(20).
-
1 1
Brown crystals (68%); mp > 300 ºC; IR (KBr)  3425, 2922, 1602, 1507, 1437, 1239, 1046 cm ; H NMR (300
MHz, DMSO-d ) δ 5.32 (s, 8H, CH O), 6.99-7.09 (m, 12H, ArH), 7.30 (s, 4H, thiazole-5-H), 7.34-7.81 (m, 22H,
ArH), 7.82 (s, 4H, benzofuran-3-H), 7.98 (s, 4H, CH=N), 12.11 (br. s, 4H, NH). Anal. Calcd for C82 : C,
6
2
H
58
N
12
O
S
8 4
67.10; H, 3.98; N, 11.45; S, 8.74. Found: C, 67.32; H, 3.61; N, 11.22; S, 8.53%.
1
,2,4,5-Tetrakis((4-((2-(4-(benzo[d]thiazol-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene
-
1 1
(
21). Brown crystals (64%); mp 270-273 ºC; IR (KBr)  3408, 1570, 1507, 1231, 1021 cm ; H NMR (300 MHz,
DMSO-d ) δ 5.32 (s, 8H, CH O), 7.09 (d, 8H, J 8.4 Hz, ArH), 7.41-7.50 (m, 8H, ArH), 7.61 (d, 8H, J 8.4 Hz, ArH),
.72 (s, 4H, thiazole-5-H), 7.73 (s, 2H, ArH), 7.96 (d, 4H, J 7.8 Hz, ArH), 8.00 (s, 4H, CH=N), 8.06 (d, 4H, J 7.8 Hz,
ArH), 12.29 (s, 4H, NH). Anal. Calcd for C78 : C, 61.00; H, 3.54; N, 14.59; S, 16.70. Found: C, 61.33; H,
6
2
7
H
54
N
16
O
S
4 8
3.65; N, 14.86; S, 16.93%.
1
,2,3,4,5,6-Hexakis((4-((2-(4-(benzofuran-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene (23).
-
1 1
Brown crystals (65%); mp > 300 ºC; IR (KBr)  3427, 2921, 1600, 1566, 1506, 1436, 1230, 1162 cm ; H NMR
300 MHz, DMSO-d ) δ 5.32 (s, 12H, CH O), 6.96-7.09 (m, 18H, ArH), 7.25 (s, 6H, thiazole-5-H), 7.37-7.71 (m,
0H, ArH), 7.78 (s, 6H, benzofuran-3-H), 7.94 (s, 6H, CH=N), 12.08 (br. s, 6H, NH). Anal. Calcd for
: C, 66.65; H, 3.92; N, 11.66; S, 8.90. Found: C, 66.50; H, 3.78; N, 11.52; S, 8.63%.
,2,3,4,5,6-Hexakis((4-((2-(4-(benzo[d]thiazol-2-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene
(
3
C
1
6
2
120
H
84
N
18
O
S
12 6
-
1 1
(
24). Green crystals (61%); mp > 300 ºC; IR (KBr)  3411, 1571, 1503, 1227, 1004 cm ; H NMR (300 MHz,
DMSO-d ) δ 5.35 (s, 12H, CH O), 6.99-7.01 (m, 12H, ArH), 7.39-7.51 (m, 24H, ArH), 7.67 (s, 6H, thiazole-5-H),
.89-7.95 (m, 12H, CH=N & ArH), 8.02 (d, 6H, J 7.5 Hz, ArH), 12.26 (s, 6H, NH). Anal. Calcd for C114
6
2
7
H
78
N
24
O
S :
6 12
C, 60.46; H, 3.47; N, 14.84; S, 16.99. Found: C, 60.24; H, 3.19; N, 14.77; S, 16.69%.
Supplementary Material
1
13
Supplementary material related to this article, including Nuclear Magnetic Resonance ( H and C NMR) figures
for compounds 8a-c; 9a-c; 11a,b; 12a,b; 17; 18; 20; 21 and 23 are available in the online version of the text.
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