Synthesis and Structures of Novel Multi-armed Molecules Involving Benzene as a Core and 4-Phenylthiazole, 4-Pyrazolylthiazole, or Thiadiazole Units as Arms

Article abstract of DOI:10.1002/jhet.2629

A synthesis of novel three-, four-, and sixfold branched 4-phenylthiazolylhydrazones, 4-pyrazolylthiazolyl hydrazones, and thiadiazoles which are linked to a benzene core via phenoxymethyl spacers was reported. The synthetic methodology includes initially formation of poly(aldehyde thiosemicarbazones) 9, 14, and 15 by acid catalyzed condensation of thiosemicarbazide (8) with the appropriate poly(aldehydes) 3, 5, and 7, respectively. Subsequent reaction of 9, 14, and 15 with each of 2-bromo-1-phenylethanone (10a) and 2-bromo-1-(4-chlorophenyl)ethanone (10b) in refluxing ethanol in the presence of few drops of TEA afforded 11, 16, and 18, respectively, in good yields. On the other hand, the synthesis of the novel poly(4,5-dihydro-1,3,4-thiadiazolyl) derivatives 20, 21a,21b, and 22 was performed by cyclization of 9b, 14a,14b, and 15a, respectively, in refluxing acetic anhydride.

Full text of DOI:10.1002/jhet.2629

Month 2016
Synthesis and Structures of Novel Multi-armed Molecules Involving
Benzene as a Core and 4-Phenylthiazole, 4-Pyrazolylthiazole, or
Thiadiazole Units as Arms
*
Mostafa E. Salem, Ahmed F. Darweesh, Ahmad M. Farag, and Ahmed H. M. Elwahy
Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt
*
E-mail: aelwahy@hotmail.com
Received December 4, 2015
DOI 10.1002/jhet.2629
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
A synthesis of novel three-, four-, and sixfold branched 4-phenylthiazolylhydrazones, 4-pyrazolylthiazolyl
hydrazones, and thiadiazoles which are linked to a benzene core via phenoxymethyl spacers was reported. The syn-
thetic methodology includes initially formation of poly(aldehyde thiosemicarbazones) 9, 14, and 15 by acid cata-
lyzed condensation of thiosemicarbazide (8) with the appropriate poly(aldehydes) 3, 5, and 7, respectively.
Subsequent reaction of 9, 14, and 15 with each of 2-bromo-1-phenylethanone (10a) and 2-bromo-1-(4-
chlorophenyl)ethanone (10b) in refluxing ethanol in the presence of few drops of TEA afforded 11, 16, and 18,
respectively, in good yields. On the other hand, the synthesis of the novel poly(4,5-dihydro-1,3,4-thiadiazolyl)
derivatives 20, 21a,b, and 22 was performed by cyclization of 9b, 14a,b, and 15a, respectively, in refluxing acetic
anhydride.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
reported to exhibit numerous pharmacological and biological
applications, such as anti-HIV, anti-inflammatory, antimicro-
bial, antihypertensive, analgesic, and herbicidal activity [15].
Moreover, pyrazole system is also considered as an impor-
tant class of heterocyclic compounds not only for being the
core unit in a variety of drugs such as celecobix (Celebrex)
[16], sildenafil (Viagra) [17], and rimonabant (Acomplia)
[18], but also for possessing a wide range of activities such
as antifungal [19], anti-inflammatory [20], antimicrobial
[21], antidepressant [22], antiparasitic [23], antiviral [24],
and antitumor activities [25].
Since the pioneering work of Vögtle and Weber [1] as
well as that of MacNicol et al. [2] on multi-armed molecules,
much attention have been paid to the synthesis of such com-
pounds for their wide range of applications [3–8]. This class
of compounds is considered important hosts for constructing
microporous networks possessing selective inclusion proper-
ties and their applications in supramolecular host–guest
chemistry have been recently reported [9]. Some related
compounds have also been used for the formation of discotic
mesogens [10], organic electronic and optoelectronic mate-
rials [11–13]. They have also been used as building units
for dendrimers [14]. Furthermore, thiazole derivatives were
In addition, 1,3,4-thiadiazole derivatives have also
attracted much attention in the last decades for their wide
spectrum of biological activities including anti-inflammatory
© 2016 Wiley Periodicals, Inc.

M. E. Salem, A. F. Darweesh, A. M. Farag, and A. H. M. Elwahy
Vol 000
[26], antimicrobial [27], antituberculosis [28], anticancer [29],
antidepressant and anxiolytic [30], antihypertensive [31], anti-
oxidant [32], anticonvulsants [33], and antifungal activities [34].
In connection with these findings, we report herein on the
synthesis of novel three-, four-, and sixfold branched 4-
phenylthiazolylhydrazones, 4-pyrazolylthiazolylhydrazones,
Scheme 1. Synthesis of tris-(formylphenoxymethyl)benzenes 3a,b.
Figure 1. Tetrakis- and hexakis(formylphenoxymethyl)benzenes 5a,b and 7a,b.
Scheme 2. Synthesis of tris(aldehyde thiosemicarbazones) 9a and 9b.
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Synthesis and Structures of Novel Multi-armed Molecules
and thiadiazoles which are linked to a benzene core via
phenoxymethyl spacers.
group or after modification of literature procedure described
by other groups. Thus, tris(formylphenoxymethyl)benzenes
3a,b were prepared by reacting the potassium salt of 4-
hydroxybenzaldehyde (2a) or salicylaldehyde (2b) with tris
(bromomethyl)benzene (1) in refluxing DMF (Scheme 1) [35].
Similarly, the tetrakis(formylphenoxymethyl)benzenes 5a
and 5b were prepared, by fourfold substitution of tetrakis
RESULTS AND DISCUSSION
We first synthesized the required aldehydes 3a,b, 5a,b,
and 7a,b following reported methods, described by our
Scheme 3. Reaction of compounds 9a,b with the appropriate 2-bromo-Ethanone derivatives.
Figure 2. Tetrakis- and hexakis (aldehyde thiosemicarbazones) 14a,b and 15a,b.
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M. E. Salem, A. F. Darweesh, A. M. Farag, and A. H. M. Elwahy
Vol 000
(bromomethyl)benzenes (4) with four equivalents of the potas-
sium salt of 4-hydroxybenzaldehyde (2a) or salicylaldehyde
(2b), respectively. With the same reaction sequence, the
hexakis(formylphenoxymethyl)benzenes 7a and 7b were pre-
pared, by sixfold substitution of hexakis(bromomethyl)
benzenes (6) with six equivalents of the potassium salt of
4-hydroxybenzaldehyde or salicylaldehyde, respectively
(Fig. 1) [35].
The synthetic utility of aldehydes 3, 5, and 7 as building
blocks for novel tris-, tetrakis-, and hexakis(thiazoles), in
which the 4-phenylthiazolylhydrazone or 4-pyrazolylthia-
zolylhydrazone is linked to benzene core via phenoxy-
methyl group, was investigated. Thus, the tris(aldehyde
thiosemicarbazones) 9a and 9b were first synthesized in
77 and 72% yields, respectively, by acid catalyzed conden-
sation of thiosemicarbazide (8) with the appropriate tris
(aldehydes) 3a and 3b, respectively (Scheme 2).
Reaction of the latter compounds with each of 2-bromo-
1-phenylethanone (10a) and 2-bromo-1-(4-chlorophenyl)
ethanone (10b) in refluxing ethanol in the presence of
few drops of TEA afforded 11a and 11b in 67 and 69%
yields, respectively (Scheme 3). In analogy, reaction of
compounds 9a,b with 2-bromo-1-(5-methyl-1-phenyl-1H-
pyrazol-4-yl)ethanone (12) in refluxing ethanol in the pres-
ence of few drops of TEA afforded 13a and 13b in 70 and
64% yields, respectively (Scheme 3). Compound 12 was
Figure 3. Tetrakis- and hexakis(thiazoles) 16a,b, 17a,b, 18a,b and 19a,b.
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Synthesis and Structures of Novel Multi-armed Molecules
synthesized by the reaction of phenylhydrazine with
((dimethylamino)methylene)pentane-2,4-dione, obtained
upon treatment of acetylacetone with dimethylformamide
dimethylacetal (DMFDMA), followed by bromination
upon treatment with Br2 in AcOH [36].
tris(aldehyde thiosemicarbazone) 9b in refluxing acetic
anhydride (Scheme 4).
Encouraged by the above results, we expanded the
scope of this reaction to prepare novel fourfold branched
(4,5-dihydro-1,3,4-thiadiazolyl) derivatives 21a and 21b
and sixfold branched (4,5-dihydro-1,3,4-thiadiazolyl) de-
rivative 22 (Fig. 4) by cyclization of the appropriate
tetrakis(aldehyde thiosemicarbazones) 14a and 14b and
hexakis(aldehyde thiosemicarbazone) 15a, respectively,
with acetic anhydride.
The same methodology was extended to the preparation
of tetrakis- and hexakis(thiazoles) 16–19. Thus, compounds
16–19 were successfully prepared, from 5a,b and 7a,b
firstly by reaction with thiosemicarbazide (8) in refluxing
EtOH containing few drops of AcOH to give 14a,b and
15a,b in 70, 73 and 68, 64% yields, respectively (Fig. 2).
Subsequent reaction of the latter compounds with the
appropriate bromoacetyl compounds 10a,b and 12 in refluxing
ethanol in the presence of few drops of TEA afforded the corre-
sponding tetrakis(thiazoles) 16a,b and 17a,b in 65, 69 and 66,
68% yields, respectively, as well as hexakis(thiazoles) 18a,b
and 19a,b in 63, 65 and 66, 67% yields, respectively (Fig. 3).
Our study was extended to include the synthesis of the
novel tris(4,5-dihydro-1,3,4-thiadiazolyl) derivative 20 in
which the thiadiazolyl moiety is linked to the benzene core
via phenoxymethyl group, in good yield, by cyclization of
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) 11a as a representative example of
these class of compounds revealed an absorption band at
1
3431 cm-1 because of (NH). Its H NMR spectra showed
the presence of a characteristic singlet signal at 7.99ppm
because of one methine proton (―N¼CH―). Mass spec-
trum of compound 11a showed the molecular ion peaks at
m/z 999 (M+) in agreement with its respective molecular
formula. The spectra of other bis(thiazoles) 11b, 16a,b,
Scheme 4. Synthesis of tris(4,5-dihydro-1,3,4-thiadiazolyl) derivative 20 from 9b.
Figure 4. Tetrakis- and hexakis (4,5-dihydro-1,3,4-thiadiazolyl) derivatives 21a,b and 22.
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M. E. Salem, A. F. Darweesh, A. M. Farag, and A. H. M. Elwahy
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1
and 18a,b showed similar spectral data which are listed in
the experimental part.
3367 (NH2), 3254 (NH), 1601 (C¼N) cm-1; H-NMR: δ
5.19 (s, 6H, 3 CH2O), 7.03–7.99 (m, 21H, ArH + 3 NH2),
8.07 (s, 3H, 3 CH¼N), 11.26 (s, 3H, 2 NH); ms: m/z (%)
699 (9.5, M+) 389 (54.2), 151 (100), 135 (29.3), 57
(93.5), 43 (82.6). Anal. Calcd. for C33H33N9O3S3: C,
56.63; H, 4.75; N, 18.01; S, 13.74. Found: C, 56.55; H,
4.66; N, 17.91; S, 13.68.
The symmetry of compounds 19a,b is manifested by a
single set of signals characteristic of the six equivalent
OCH2 and six methyl groups in the 1H-NMR spectra. Sim-
ilarly, compounds 21a,b are characterized by a single set of
signals characteristic of the four equivalent OCH2, four
acetyl (CH3CO), four acetamido (NHCOCH3), and four
methine (CH) groups.
2,2′,2′′-(2,2′,2′′-(Benzene-1,3,5-triyltris(methylene))tris(oxy)
tris(benzene-2,1-diyl))tris(methan-1-yl-1-ylidene)tris
(hydrazinecarbothioamide) 9b. Pale yellow powder, (72%
yield), mp. 200–202°C; IR: (potassium bromide) 3421,
CONCLUSIONS
1
3366 (NH2), 3251 (NH), 1595 (C¼N) cm-1; H-NMR: δ
5.26 (s, 6H, 3 CH2O), 6.96–8.13 (m, 21H, ArH + 3
NH2), 8.51 (s, 3 CH¼N), 11.39 (s, 3H, 3 NH); ms: m/z
(%) 699 (10.2, M+), 630 (60.2), 321 (100), 310 (47.2),
55 (40.3). Anal. Calcd. for C33H33N9O3S3: C, 56.63; H,
4.75; N, 18.01; S, 13.74. Found: C, 56.52; H, 4.69; N,
17.95; S, 13.66.
We developed a simple method for the preparation of
novel three-, four-, and sixfold branched 4-phenylthia-
zolylhydrazones, 4-pyrazolylthiazolylhydrazones, and thiadi-
azoles which are linked to a benzene core via phenoxymethyl
spacers. Full characterization of these compounds is re-
ported. The new synthesized compounds are interesting both
in their own right as unusual molecules and for their promis-
ing pharmacological and biological activities as well as for
their expected inclusion properties. The extension of the
scope of this method to cover additional multi-armed hetero-
cyclic compounds is now under study.
2,2′,2′′,2′′′-(4,4′,4′′,4′′′-(Benzene-1,2,4,5-tetrayltetrakis(methylene))
tetrakis (oxy)-tetrakis(benzene-4,1-diyl))tetrakis(methan-1-yl-1-ylidene)
tetrakis (hydrazinecarbo-thioamide) 14a.
Pale yellow powder,
(73% yield), mp. 246–248°C; IR: (potassium bromide) 3425,
3364 (NH2), 3254 (NH), 1594 (C¼N) cm-1; 1H-NMR: δ 5.29
(s, 8H, 4 CH2O), 7.03–7.98 (m, 26H, ArH +4 NH2), 8.07 (s,
4H, 4 CH¼N), 11.29 (s, 4H, 4 NH); ms: m/z (%) 906 (24.9,
M+), 815 (100), 801 (31.3), 481 (21.9), 249 (12.2), 57 (11.8).
Anal. Calcd. for C42H42N12O4S4: C, 55.61; H, 4.67; N, 18.53;
S, 14.14. Found: C, 55.51; H, 4.53; N, 18.39; S, 14.01.
EXPERIMENTAL
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 Shimadzu FTIR 8101 PC infrared spectro
photometer. NMR spectra were recorded in deuterated
dimethyl sulfoxide (DMSO-d6) with a Varian Mercury
VXR-300 NMR spectrometer at 300MHz (1H NMR) and
at 75 MHz (13C NMR). Mass spectra (EI) were obtained at
70eV with a type Shimadzu GCMQP 1000 EX spec
trometer. Analytical thin-layer chromatography was per
formed using pre-coated silica gel 60778 plates (Fluka),
and the spots were visualized with UV light at 254nm. The
elemental analyses were performed at the Micro analytical
center, Cairo University.
2,2′,2′′,2′′′-(2,2′,2′′,2′′′-(Benzene-1,2,4,5-tetrayltetrakis
(methylene))tetrakis (oxy)tetrakis(benzene-2,1-diyl))tetrakis(methan-
1-yl-1-ylidene)tetrakis (hydrazine-carbothioamide) 14b.
Pale
yellow powder, (70% yield), mp. 203–205°C; IR:
(potassium bromide) 3430, 3275 (NH2), 3150 (NH), 1595
(C¼N) cm-1; 1H-NMR: δ 5.41 (s, 8H, 4 CH2O), 6.93–8.11
(m, 26H, ArH+4 NH2), 8.51 (s, 4H, CH¼N), 11.42 (s,
4H, 4 NH); ms: m/z (%) 906 (14.9, M+), 816 (47.6), 814
(100), 801 (31.3), 481 (21.9), 250 (12.2), 59 (12.8). Anal.
Calcd. for C42H42N12O4S4: C, 55.61; H, 4.67; N, 18.53; S,
14.14. Found: C, 55.44; H, 4.45; N, 18.41; S, 13.88.
2,2′,2′′,2′′′,2′′′′,2′′′′′-(4,4′,4′′,4′′′,4′′′′,4′′′′′-(Benzene-1,2,3,4,5,6-
hexaylhexakis (methylene))hexakis(oxy)hexakis(benzene-4,1-diyl))
hexakis(methan-1-yl-1-ylidene)hexakis(hydrazinecarbothioamide)
15a. Pale yellow powder, (68% yield), mp. > 300°C; IR:
(potassium bromide) 3423, 3271 (NH2), 3159 (NH), 1601
Synthesis of poly(thiosemicarbazones) 9a,b, 14a,b, and 15a,b.
General procedure.
To a solution of poly(aldehydes)
3a,b or 5a,b or 7a,b (1mmol) in absolute ethanol (25mL)
containing few drops of acetic acid, thiosemicarbazide (8)
(3 or 4 or 6 mmol) was added. The reaction mixture was
heated under reflux for 3 h. The solid formed upon cooling
was collected and recrystallized from ethanol/DMF to give
the corresponding.poly(thiosemicarbazones) 9a,b, 14a,b,
and 15a,b.
2,2′,2′′-(4,4′,4′′-(Benzene-1,3,5-triyltris(methylene))tris(oxy)
tris(benzene-4,1-diyl))-tris(methan-1-yl-1-ylidene)tris
(hydrazinecarbothioamide) 9a. Pale yellow powder, (77%
yield), mp. 204–205°C; IR: (potassium bromide) 3421,
1
(C¼N) cm-1; H-NMR: δ 5.32 (s, 12H, 6 CH2O), 6.93–7.94
(m, 36H, ArH+6 NH2), 8.05 (s, 6H, CH¼N), 11.26 (s, 6H,
6 NH). Anal. Calcd. for C60H60N18O6S6: C, 54.53; H,
4.58; N, 19.08; S, 14.56. Found: C, 54.40; H, 4.43; N,
18.91; S, 14.44.
2,2′,2′′,2′′′,2′′′′,2′′′′′-(2,2′,2′′,2′′′,2′′′′,2′′′′′-(Benzene-1,2,3,4,5,6-
hexaylhexakis (methylene))hexakis(oxy)hexakis(benzene-2,1-diyl))
hexakis(methan-1-yl-1-ylidene)hexakis(hydrazinecarbothioamide)
15b. Pale yellow powder, (64% yield), mp. 240–242°C; IR:
(potassium bromide) 3418, 3260 (NH2), 3145 (NH), 1600
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1
(C¼N) cm-1; H-NMR: δ 5.52 (s, 12H, 6 CH2O), 6.95–8.11
(m, 36H, ArH+6 NH2), 8.39 (s, 6H, 6 CH¼N), 11.31 (s,
6H, 6 NH). Anal. Calcd. for C60H60N18O6S6: C, 54.53; H,
4.58; N, 19.08; S, 14.56. Found: C, 54.40; H, 4.42; N, 19.19;
S, 14.72.
1,2,3,4,5,6-Hexakis((4-((2-(4-phenylthiazol-2-yl)hydrazono)
methyl)phenoxy) methyl)benzene 18a.
Orange powder,
(63% yield), mp. > 300°C; IR: (potassium bromide)
3428 (NH), 1602 (C¼N) cm-1; 1H-NMR: δ 5.32 (s,
12H, 6 CH2O), 7.01–7.80 (m, 60H, ArH + 6 thiazole-
H), 7.95 (s, 6H, 6 CH¼N), 11.96 (s, 6H, 6 NH). Anal.
Calcd. for C108H84N18O6S6: C, 67.48; H, 4.40; N,
13.12; S, 10.01. Found: C, 67.28; H, 4.18; N, 12.90;
S, 9.87.
Synthesis of poly(thiazoles) 11a,b, 16a,b, and 18a,b.
General procedure. To a solution of poly(thiosemicarbazones)
9a,b or 14a,b or 15a,b (1 mmol) in absolute ethanol
(25 mL) containing few drops of TEA, 2-bromo-1-
phenylethanone (10a) or 2-bromo-1-(4-chlorophenyl)
ethanone (10b) (3 or 4 or 6mmol) was added. The reaction
mixture was heated under reflux for 5 h. The solid product
formed upon cooling was collected and recrystallized
from ethanol/DMF to give the corresponding poly
(thiazoles) 11a,b, 16a,b, and 18a,b.
1,2,3,4,5,6-Hexakis((2-((2-(4-(4-chlorophenyl)thiazol-2-yl)
hydrazono) methyl)phenoxy)methyl)benzene 18b.
Yellow
powder, (65% yield), mp. 208–210°C; IR: (potassium
1
bromide) 3433 (NH), 1599 (C¼N) cm-1; H-NMR: δ 5.55
(s, 12H, 6 CH2O), 6.94–7.77 (m, 54H, ArH+ 6 thiazole-H),
8.35 (s, 6H, 6 CH¼N), 11.88 (s, 6H, NH); 13C-NMR: δ
64.3, 104.2, 112.8, 120.5, 120.7, 123.0, 127.0, 128.3, 129.3,
130.3, 131.7, 133.4, 149.2, 155.8, 162.2, 168.0. Anal.
Calcd. For C108H78Cl6N18O6S6: C, 60.93; H, 3.69; N,
11.84; S, 9.04. Found: C, 60.67; H, 3.52; N, 11.71; S, 8.89.
1,3,5-Tris((4-(2-(4-phenylthiazol-2-yl)hydrazono)methyl)
phenoxy)methyl)benzene 11a.
Orange powder, (67%
yield), mp. 210–212°C; IR: (potassium bromide) 3431 (NH),
1603 (C¼N) cm-1; 1H-NMR: δ 5.20 (s, 6H, 3 CH2O), 7.01–
7.85 (m, 33H, ArH +3 thiazole-H), 7.99 (s, 3H, 3 CH¼N),
11.98 (s, 3H, 3 NH); ms: m/z (%) 999 (4.5, M+), 992 (100),
815 (67.1), 481 (21.9), 249 (12.2), 57 (11.8). Anal. Calcd.
for C57H45N9O3S3: C, 68.45; H, 4.53; N, 12.60; S, 9.62.
Found: C, 68.29; H, 4.38; N, 12.45; S, 9.44.
Synthesis of Poly(pyrazolylthiazoles) 13a,b, 17a,b and
19a,b.
General procedure.
To a solution of poly
(thiosemicarbazones) 9a,b or 14a,b or 15a,b (1mmol) in
absolute ethanol (25 mL) containing few drops of TEA, 2-
bromo-1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethanone (12)
(3 or 4 or 6mmol) was added. The reaction mixture was
heated under reflux for 5 h. The solid product formed upon
cooling was collected and recrystallized from ethanol/DMF
to give the corresponding poly(pyrazolylthiazoles) 13a,b,
17a,b, and 19a,b.
1,3,5-Tris((4-((2-(4-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thiazol-
2-yl)hydrazono) methyl)phenoxy)methyl)benzene 13a. Orange
powder, (70% yield), mp. 220–222°C; IR: (potassium
bromide) 3424 (NH), 1601 (C¼N) cm-1; 1H-NMR: δ
2.49 (s, 9H, 3 CH3), 5.20 (s, 6H, 3 CH2O), 6.84 (s, 3H, 3
thiazole-H), 7.08–7.61 (m, 30H, ArH), 7.91 (s, 3H,
CH¼N), 7.98 (s, 3H, 3 pyrazole-H), 11.95 (s, 3H, 3 NH);
13C-NMR: δ 11.9, 69.1, 101.4, 115.2, 116.7, 120.2,
124.8, 125.2, 126.4, 127.4, 129.3, 135.4, 137.4, 138.7,
139.2, 141.0, 144.3, 159.1, 168.1; ms: m/z (%) 1239 (9.5,
M+), 992 (100), 815 (67.1), 481 (21.9), 249 (12.2), 57
(11.8). Anal. Calcd. for C69H57N15O3S3: C, 66.81; H,
4.63; N, 16.94; S, 7.75. Found: C, 66.69; H, 4.52; N,
16.85; S, 7.58.
1,3,5-Tris((2-((2-(4-(4-chlorophenyl)thiazol-2-yl)hydrazono)
methyl)phenoxy)-methyl)benzene 11b.
Yellow powder,
(69% yield), mp. 180–182°C; IR: (potassium bromide) 3436
(NH), 1599 (C¼N) cm-1; 1H-NMR: δ 5.30 (s, 6H, 3 CH2O),
7.01–7.95 (m, 30H, ArH +3 thiazole-H), 8.47 (s, 3H, 3
CH¼N), 12.11 (s, 3H, 3 NH); ms: m/z (%) 1101 (5.6, M+),
1067 (9.1), 603 (100), 339 (59.4), 264 (62.6), 55 (64.5).
Anal. Calcd. for C57H42Cl3N9O3S3: C, 62.04; H, 3.84; N,
11.42; S, 8.72. Found: C, 61.95; H, 3.79; N, 11.31; S, 8.62.
1,2,4,5-Tetrakis((4-((2-(4-phenylthiazol-2-yl)hydrazono)
methyl)phenoxy)methyl)-benzene 16a.
Orange powder,
(65% yield), mp. > 300°C; IR: (potassium bromide)
3433 (NH), 1602 (C¼N) cm-1; H-NMR: δ 5.32 (s, 8H, 4
1
CH2O), 7.08–7.84 (m, 42H, ArH + 4 thiazole-H), 7.98 (s,
4H, 4 CH¼N), 11.99 (s, 4H, 4 NH). 13C-NMR: δ 66.9,
104.5, 115.1, 127.9, 128.4, 129.2, 129.3, 130.6, 131.3,
131.6, 134.6, 135.0, 135.3, 155.7, 159.4. Anal. Calcd. for
C74H58N12O4S4: C, 67.97; H, 4.47; N, 12.85; S, 9.81.
Found: C, 67.83; H, 4.31; N, 12.67; S, 9.69.
1,2,4,5-Tetrakis((2-((2-(4-(4-chlorophenyl)thiazol-2-yl)
hydrazono)methyl) phenoxy)methyl)benzene 16b.
1,3,5-Tris((2-(2-(4-(5-methyl-1-phenyl-1H-pyrazol-4-yl)
thiazol-2-yl)hydrazono)-methyl)phenoxy)methyl)benzene 13b.
Orange powder, (64% yield), mp. > 300°C; IR: (potassium
Yellow
powder, (69% yield), mp. 190–192°C; IR: (potassium
bromide) 3438 (NH), 1598 (C¼N) cm-1; 1H-NMR: δ
5.45 (s, 8H, 4 CH2O), 7.00–7.86 (m, 38H, ArH + 4
thiazole-H), 8.46 (s, 4H, 4 CH¼N), 12.10 (s, 4H, 4 NH).
13C-NMR: δ 67.5, 104.2, 112.8, 121.1, 122.7, 125.1,
127.1, 128.0, 130.5, 131.8, 133.4, 135.1, 136.8, 149.2,
155.9, 162.2, 168.2. Anal. Calcd. for C74H54Cl4N12O4S4:
C, 61.49; H, 3.77; N, 11.63; S, 8.87. Found: C, 61.36; H,
3.65; N, 11.44; S, 8.73.
1
bromide) 3433 (NH), 1597 (C¼N) cm-1; H-NMR: δ 2.50
(s, 9H, 3 CH3), 5.30 (s, 6H, 3 CH2O), 6.86 (s, 3H, 3
thiazole-H), 7.01–7.83 (m, 30H, ArH), 7.90 (s, 3H, 3
CH¼N), 8.46 (s, 3H, 3 pyrazole-H), 12.08 (s, 3 NH); ms:
m/z (%) 1239 (11.4, M+), 992 (100), 874 (10.7), 249
(12.2), 57 (11.8). Anal. Calcd. for C69H57N15O3S3: C,
66.81; H, 4.63; N, 16.94; S, 7.75. Found: C, 66.71; H,
4.51; N, 16.79; S, 7.93.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. E. Salem, A. F. Darweesh, A. M. Farag, and A. H. M. Elwahy
Vol 000
1,2,4,5-Tetrakis((4-((2-(4-(5-methyl-1-phenyl-1H-pyrazol-4-yl)
thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene 17a.
Orange powder, (66% yield), mp. > 300°C; IR: (potassium
CH2O), 6.77 (s, 3H, 3 thiadiazole-H), 6.96–7.47 (m, 15H,
ArH), 11.69 (s, 3H, 3 NH); ms: m/z (%) 951 (11, M+), 920
(66.4), 800 (100), 400 (24.6), 232 (19), 139 (7.6). Anal. Calcd.
for C45H45N9O9S3: C, 56.77; H, 4.76; N, 13.24; S, 10.10.
Found: C, 56.65; H, 4.52; N, 13.09; S, 9.87.
1
bromide) 3447 (NH), 1588 (C¼N) cm-1; H-NMR: δ 2.49
(s, 12H, 4 CH3), 5.32 (s, 8H, 4 CH2O), 6.83 (s, 4H, 4
thiazole-H), 7.08–7.61 (m, 38H, ArH), 7.90 (s, 4H, 4
CH¼N), 7.98 (s, 4H, 4 pyrazole-H), 11.95 (s, 4H, 4 NH).
13C-NMR: δ 11.9, 66.8, 101.4, 115.2, 116.7, 124.8, 127.5,
127.7, 129.1, 134.8, 135.4, 138.7, 139.2, 140.9, 144.3,
159.0, 168.1. Anal. Calcd. for C90H74N20O4S4: C, 66.40;
H, 4.58; N, 17.21; S, 7.88. Found: C, 66.55; H, 4.66; N,
17.07; S, 8.01.
N,N′,N′′,N′′′-(5,5′,5′′,5′′′-(4,4′,4′′,4′′′-(Benzene-1,2,4,5-
tetrayltetrakis-(methylene))tetrakis(oxy)tetrakis(benzene-4,1-
diyl))tetrakis(4-acetyl-4,5-dihydro-1,3,4-thiadiazole-5,2-diyl))
tetraacetamide 21a. Colorless powder, (68% yield), mp.
242–245°C; IR: (potassium bromide) 3448 (NH), 1705
1
(C¼O), 1644 (C¼O), 1605 (C¼N) cm-1; H-NMR: δ 1.98,
2.24 (2s, 24H, 8 CH3CO), 5.43 (s, 8H, 4 CH2O), 6.92 (s,
4H, 4 thiadiazole-H), 7.26–7.94 (m, 18H, ArH), 11.62 (s,
4H, 4 NH); 13C-NMR: δ 21.7, 22.4, 61.6, 67.2, 112.6, 120.8,
124.1, 128.5, 129.3, 146.6, 153.7, 167.3, 169.1; ms: m/z (%)
1242 (10.4, M+), 1148 (7.5), 991 (100), 815 (67.1), 249
(12.2), 58 (12.8). Anal. Calcd. for C58H58N12O12S4: C,
56.02; H, 4.70; N, 13.52; S, 10.32. Found: C, 55.88; H, 4.57;
N, 13.28; S, 10.19.
1,2,4,5-Tetrakis((2-((2-(4-(5-methyl-1-phenyl-1H-pyrazol-
4-yl)thiazol-2-yl)hydrazono)methyl)phenoxy) methyl)benzene
17b. Orange powder, (68% yield), mp. > 300°C; IR:
(potassium bromide) 3434 (NH), 1599 (C¼N) cm-1; 1H-
NMR: δ 2.49 (s, 12H, 4 CH3), 5.45 (s, 8H, 4 CH2O), 6.84
(s, 4H, 4 thiazole-H), 7.00–7.80 (m, 38H, ArH), 7.88 (s, 4H,
4 CH¼N), 8.46 (s, 4H, 4 pyrazole-H), 12.06 (s, 4H, 4 NH).
Anal. Calcd. for C90H74N20O4S4: C, 66.40; H, 4.58; N,
17.21; S, 7.88. Found: C, 66.17; H, 4.34; N, 17.39; S, 7.65.
1,2,3,4,5,6-Hexakis((4-((2-(4-(5-methyl-1-phenyl-1H-pyrazol-4-
yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene 19a.
Orange powder, (66% yield), mp. > 300°C; IR: (potassium
N,N′,N′′,N′′′-(5,5′,5′′,5′′′-(2,2′,2′′,2′′′-(Benzene-1,2,4,5-
tetrayltetrakis-(methylene))tetrakis(oxy)tetrakis(benzene-2,1-
diyl))tetrakis(4-acetyl-4,5-dihydro-1,3,4-thiadiazole-5,2-diyl))
tetraacetamide 21b. Colorless powder, (66% yield), mp.
203–205°C; IR: (potassium bromide) 3444 (NH), 1728
(C¼O), 1669 (C¼O), 1607 (C¼N) cm-1; 1H-NMR: δ
2.17, 2.38 (2 s, 24H, 8 CH3CO), 5.20 (s, 8H, 4 CH2O),
6.77 (s, 4H, 4 thiadiazole), 6.95–7.66 (m, 18H, ArH),
11.69 (s, 4H, NH); ms: m/z (%) 1242 (23.4, M+), 1127
(9.8), 991 (100), 815 (60.9), 297 (11.2), 60 (4.3). Anal.
Calcd. for C58H58N12O12S4: C, 56.02; H, 4.70; N,
13.52; S, 10.32. Found: C, 55.97; H, 4.66; N, 13.44; S,
10.27.
1
bromide) 3432 (NH), 1600 (C¼N) cm-1; H-NMR: δ 2.49
(s, 18H, 6 CH3), 5.35 (s, 12H, 6 CH2O), 6.78 (s, 6H, 6
thiazole-H), 7.01–7.53 (m, 54H, ArH), 7.89 (s, 6H, 6
CH¼N), 7.94 (s, 6H, 6 pyrazole-H), 11.93 (s, 6H, 6 NH).
Anal. Calcd. for C132H108N30O6S6: C, 65.98; H, 4.53; N,
17.49; S, 8.01. Found: C, 65.80; H, 4.69; N, 17.25; S, 7.78.
1,2,3,4,5,6-Hexakis((2-((2-(4-(5-methyl-1-phenyl-1H-pyrazol-
4-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)methyl)benzene
19b. Orange powder, (67% yield), mp. 286–288°C; IR:
(potassium bromide) 3431 (NH), 1597 (C¼N) cm-1;
1H-NMR: δ 2.39 (s, 18H, 6 CH3), 5.57 (s, 12H, 6
CH2O), 6.76 (s, 6H, 6 thiazole-H), 6.79–7.80 (m, 54H,
ArH), 7.95 (s, 6H, 6 CH¼N), 8.35 (s, 6H, 6 pyrazole-H),
11.89 (s, 6H, NH). Anal. Calcd. for C132H108N30O6S6: C,
65.98; H, 4.53; N, 17.49; S, 8.01. Found: C, 66.21; H,
4.76; N, 17.64; S, 8.26.
N,N′,N′′,N′′′,N′′′′,N′′′′′-(5,5′,5′′,5′′′,5′′′′,5′′′′′-(4,4′,4′′,4′′′,4′′′′,
4′′′′′-(Benzene-1,2,3,4,5,6-hexaylhexakis(methylene))hexakis(oxy)
hexakis(benzene-4,1-diyl))hexakis(4-acetyl-4,5-dihydro-1,3,4-
thiadiazole-5,2-diyl))hexa-acetamide 22.
Colorless powder,
(67% yield), mp. 230–232°C; IR: (potassium bromide)
3433 (NH), 1702 (C¼O), 1662 (C¼O), 1607 (C¼N) cm-1;
1H-NMR: δ 2.02, 2.16 (2 s, 36H, 12 CH3CO), 5.17 (s,
12H, 6 CH2O), 6.72 (s, 6H, 6 thiadiazole-H), 6.85–7.11
(m, 24H, ArH), 11.67 (s, 6H, 6 NH); 13C-NMR: δ 21.8,
22.5, 63.6, 65.4, 114.6, 126.6, 134.0, 137.3, 145.9,
157.9, 167.2, 169.2. Anal. Calcd. For C84H84N18O18S6:
C, 55.25; H, 4.64; N, 13.81; S, 10.54. Found: C, 55.18;
H, 4.75; N, 13.72; S, 10.43.
Synthesis of poly(4,5-dihydro-1,3,4-thiadiazolyl) derivatives
20b, 21a,b, and 22a.
General procedure.
A solution of
each of poly(thiosemicarbazones) 9b, 14a,b, or 15a in acetic
anhydride (20mL) was heated under reflux for 7–10 h. The
reaction mixture was then cooled and poured into crushed
ice. The solid residue was collected and recrystallized from
ethanol/ethylacetate to give poly(4,5-dihydro-1,3,4-thiadi
azolyl) derivatives 20, 21a,b, and 22.
Acknowledgments. Professor A. H. M. Elwahy and Dr. A. F.
Darweesh gratefully acknowledge the Alexander von Humboldt
Foundation for a research fellowship.
N,N′,N′′-(5,5′,5′′-(2,2′,2′′-(Benzene-1,3,5-triyltris(methylene)
tris(oxy)tris-(benzene-2,1-diyl))tris(4-acetyl-4,5-dihydro-1,3,4-
thiadiazole-5,2-diyl))-triacetamide 20.
Colorless crystal,
REFERENCES AND NOTES
(64% yield), mp. 198–200°C; IR: (potassium bromide)
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1H-NMR: δ 2.03, 2.38 (2 s, 18H, 6 CH3CO), 5.14 (s, 6H, 3
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Synthesis and Structures of Novel Multi-armed Molecules
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