Terephthalaldehyde: An Effecient Key Precursor for Novel Synthesis of Some Interesting Bis-thiazoles and Bis-triazolopyrimidinones

Article abstract of DOI:10.1002/jhet.3100

Novel bis-thiazoles were synthesized in high and efficient yields from the reaction of thiosemicarbazones with halogenated compounds. Also, new bis-triazolopyrimidines were prepared from the reaction of hydrazonoyl chlorides with bis-thione derivative. All prepared compounds were fully characterized by spectral methods. The synthesized bis-compounds will be attractive species for the medicinal researchers to investigate their biological activity.

Full text of DOI:10.1002/jhet.3100

Month 2018
Terephthalaldehyde: An Effecient Key Precursor for Novel Synthesis of
Some Interesting Bis-thiazoles and Bis-triazolopyrimidinones
Sobhi M. Gomha,a
Thoraya A. Farghaly,a,b
Eman M. H. Abbas,c and Nadia T. Alqurashib
*
aDepartment of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt
bDepartment of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukkarramah, Saudi Arabia
cDepartment of Chemistry of National and Microbial Products, National Research Center, Dokki, Cairo, Egypt
*
E-mail: thoraya-f@hotmail.com
Received July 26, 2017
DOI 10.1002/jhet.3100
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
Novel bis-thiazoles were synthesized in high and efficient yields from the reaction of thiosemicarbazones
with halogenated compounds. Also, new bis-triazolopyrimidines were prepared from the reaction of
hydrazonoyl chlorides with bis-thione derivative. All prepared compounds were fully characterized by
spectral methods. The synthesized bis-compounds will be attractive species for the medicinal researchers
to investigate their biological activity.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
RESULTS AND DISCUSSION
The researchers have recently focused on the design of
bis-heterocyclic compounds because of its biological
activity remarkably [1–5]. Bis-heterocyclic categories
that having 1,4-phenylene linker showed wide range of
biological activities including antimicrobial, antitumor,
anti-inflammatory, and analgesic activity [6–10]. Bis-
thiazoles have been determined as the potential entity in
the largely rising chemical scientist of heterocyclic
compounds possessing promising pharmacological
characteristics [11,12]. An extensive variety of
therapeutic applications of thiazole derivatives was
displayed in literature survey [13–18]. Another active
The thiosemicarbazones 2a,b were considered to be
useful intermediates for further synthesis of different
heterocyclic compounds. These starting compounds were
prepared from the condensation of terephthalaldehyde
with thiosemicarbazide 1a or ethyl thiosemicarbazide 1b
in absolute ethanol acidified with concentrated
hydrochloric acid under reflux for 6 h (Scheme 1).
Reaction of each derivative of thiosemicarbazone 2a,b
with α-keto-hydrazonoyl chlorides 3 in refluxing dioxane
in the presence of Et3N as a basic catalyst gave thiazole
derivatives 4a–f and 5a–f, respectively as depicted in
Scheme 1. All available spectral information was used to
elucidate the actual structure of the synthesized
compounds 4a–f and 5a–f. As for example, the IR
spectra of derivatives 5a–f were free from any absorption
bands due to NH groups, while IR spectra of compounds
heterocyclic
ring
system
is
triazolopyrimidine
derivatives, which are known by their activities as
antimicrobial [19], antitumor [20] and analgesic, and
anti-inflammatory [21,22]. Encouraged by all these
findings and in continuation of our program focusing on
the synthesis of bis-heterocyclic compounds that
expected to be biologically active [23–32], we reported
in the present work an efficient and rapid method for the
4a–f showed one absorption band at 3441–3218 cmꢀ1
.
Also, the mass spectra of all derivatives 4a–f and 5a–f
revealed the expected molecular ion peaks, which proved
the formation of the thiazole rings. Moreover, the 1H
NMR spectra of 4a–f had D2O exchangeable signals
attributed to one NH proton at 11.46–10.47 ppm.
Thiazole ring can also be prepared via the cyclization of
the thiosemicarbazone derivatives with various
haloketones. As depicted in Scheme 2, bis-thiazole
synthesis of
a
series of bis-thiazole and bis-
triazolopyrimidine derivatives from the titled aldehyde.
The synthesized bis-compounds will be attractive species
for the medicinal researchers to investigate their
biological activity.
© 2018 Wiley Periodicals, Inc.

S. M. Gomha, T. A. Farghaly, E. M. H. Abbas, and N. T. Alqurashi
Vol 000
Scheme 1. Synthesis of thiazole derivatives 4a–f and 5a–c.
Scheme 3. Synthesis of bis-triazolopyrimidines 9a–f.
synthesis of ethyl cyanoacetate, terephthalaldehyde, and
thiourea in absolute ethanol led to formation of
compound 8. The structure of compound
8 was
confirmed by elemental analyses and spectral data
(Experimental part). Refluxing equimolar quantities of
each
of
hydrazonoyl
chlorides
3
with
tetrahydropyrimidine-carbonitrile 8 in dioxane in the
presence of triethylamine gave in each case a single
product as indicated by TLC analysis of the crude
product. The structure of the product 9 was identified as
triazolo-pyrimidine-carbonitrile (Scheme 2) based on its
derivatives 6a–c and 7a,b were prepared from the reaction
of phenacyl bromide derivatives and chloroacetic acid with
thiaosemicarbazones 2a,b. The 1H NMR spectra of
thiazoles 6a–c showed the characteristic signal of CH2 of
the thiazole ring at δ = 3.63–3.56 ppm. However, IR
of compound 7b presented absorption band for carbonyl
1
elemental analysis and spectral (IR, H NMR, and MS)
1
data. For example, the H NMR spectra of the isolated
group at 1711 cmꢀ1
.
products 9e,f showed in each case a triplet and quartet
signals near the region δH 1.17 and 4.50 ppm with
coupling constant J = 7 Hz, assigned to the CH3CH2 group.
The required bis-tetrahydropyrimidine-carbonitrile 8
was prepared as outlined in Scheme 3. Thus, one pot
Scheme 2. Synthesis of compounds 6a–c and 7a,b.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Synthesis of Some Interesting Bis-thiazoles and Bis-triazolopyrimidinones
CONCLUSION
triethylamine (0.7 mL), and the mixture was refluxed for
4–6 h (monitored by TLC), allowed to cool, and the solid
formed was filtered off, washed with ethanol, dried, and
recrystallized from DMF to give 4a–f and 5a–c.
1,4-Bis((2-(4-methyl-5-(phenyldiazenyl)thiazol-2-yl)
In this context, we have synthesized bis-thiazoles and
bis-triazolopyrimidine derivatives by simple and efficient
method. The structure of all the novel products was
characterized by their spectral information. Such
synthesized bis-heterocyclic compounds will be attractive
for the pharmaceutical researchers because the thiazoles
and triazolopyrimidines are well known with their wide
range of biological activity.
hydrazono)methyl)benzene (4a).
Yield 68%; red solid;
mp = 237–239°C; IR (KBr): v 3242 (NH), 3057, 2956,
2906 (C─H), 1599, 1549 (C═N), 1495, 1373, 1296,
1244, 1171, 1111, 1071 cmꢀ1;1H NMR (DMSO-d6): δ
2.62 (6H, s, 2CH3), 7.01–7.37 (10H, m, Ar─H), 8.0 (4H,
s, Ar─H), 8.73 (2H, s, 2 = CH), 10.72 (2H, brs, 2NH);
MS m/z (%): 564 (M+, 2), 346 (13), 218 (12), 190 (19),
147 (9), 128 (10), 104 (13), 92 (18), 77 (100). Anal.
Calcd for C28H24N10S2 (564.69): C, 59.56; H, 4.28; N,
24.80. Found C, 59.37; H, 4.14; N, 24.67%.
EXPERIMENTAL
Melting points were determined on a Gallenkamp
apparatus and are uncorrected. IR spectra were recorded in
a Pye-Unicam SP300 instrument in potassium bromide
discs. 1H NMR spectra were recorded in a Varian Mercury
VXR-300 spectrometer 300 MHz in DMSO-d6 and the
chemical shifts were related to TMS as standard solvent.
Mass spectra were recorded in a GCMS-QP 1000 EX
Shimadzu spectrometer, the ionizing voltage was 70 eV.
Elemental analyses were carried out at the Microanalytical
Laboratory of Cairo University, Giza, Egypt. 2,20-(1,4-
Phenylenebis(methanylylidene))bis(hydrazinecarbothioamide)
(2a) [33], hydrazonoyl halides 3 [34] and 2,20-(1,4-
Phenylenebis(methanylylidene))bis(hydrazine-2,1-diylidene)
bis(thiazolidin-4-one) (7a) [35] were prepared as reported in
the literature.
1,4-Bis((2-(4-methyl-5-(p-tolyldiazenyl)thiazol-2-yl)
hydrazono)methyl)benzene (4b).
Yield 70%; red solid;
mp = 208–210°C; IR (KBr): v 3435 (NH), 3065, 2913
(C─H), 1604, 1552 (C═N), 1491, 1424, 1364, 1311,
1244, 1178, 1118, 1024 cmꢀ1;1H NMR (DMSO-d6): δ
2.28 (6H, s, 2CH3), 2.59 (6H, s, 2CH3), 7.16 (4H, d,
J = 8.4 Hz, Ar–H), 7.33 (4H, d, J = 8.4 Hz, Ar─H), 7.93
(4H, s, Ar─H), 8.58 (2H, s, 2 = CH), 10.85 (2H, brs,
2NH); MS m/z (%): 592 (M+, 2), 346 (13), 218 (12), 190
(19), 147 (9), 128 (10), 104 (13), 92 (18), 77 (100). Anal.
Calcd for C30H28N10S2 (592.74): C, 60.79; H, 4.76; N,
23.63. Found C, 60.67; H, 4.51; N, 23.49%.
1,4-Bis((2-(5-((4-chlorophenyl)diazenyl)-4-methylthiazol-2-
yl)hydrazono)methyl)benzene (4c).
Yield 71%; red solid;
mp = 244–246°C; IR (KBr): v 3218 (NH), 3053, 2956,
2910 (C─H), 1602, 1551 (C═N), 1484, 1424, 1362,
1298, 1244, 1173, 1111, 1017 cmꢀ1;1H NMR (DMSO-
d6): δ 2.60 (6H, s, 2CH3), 7.02–7.40 (8H, m, Ar─H),
7.97 (4H, s, Ar─H), 8.64 (2H, s, 2 = CH), 10.82 (2H,
brs, 2NH); MS m/z (%): 635 (M++2, 5), 633 (M+, 16),
354 (63), 252 (30), 224 (75), 127 (83), 128 (10), 111
(100), 77 (55). Anal. Calcd for C28H22Cl2N10S2 (633.58):
C, 53.08; H, 3.50; N, 22.11. Found C, 54.92; H, 3.38; N,
22.01%.
Reaction of terephthalaldehyde with thiosemicarbazide
derivatives.
A thiosemicarbazide derivative (2 mmol.)
was added to a solution of the terephthalaldehyde
(1.34 g, 1 mmol) in absolute ethanol (30 ml) containing a
few drops of conc HCl, the resulting mixture was
refluxed for 6 h. The solids formed after cooling were
collected by filtration, washed with ethanol, and
crystallized from dioxane.
2,20-(1,4-Phenylenebis(methanylylidene))bis(N-
ethylhydrazinecarbothioamide) (2b).
Yield 70%; yellow
1,4-Bis((2-(5-((4-bromophenyl)diazenyl)-4-methylthiazol-2-
solid; mp = 179–181°C; IR (KBr): v 3432, 3159 (2NH),
3022, 2935 (C─H), 1581 (C═N), 1407, 1326, 1294,
yl)hydrazono)methyl)benzene (4d).
Yield 69%; yellow
solid; mp = 225–227°C; IR (KBr): v 3441 (NH), 3056,
2956, 2911 (C─H), 1602, 1550 (C═N), 1485, 1430,
1362, 1297, 1243, 1173, 1114, 1072 cmꢀ1;1H NMR
(DMSO-d6): δ 2.49 (6H, s, 2CH3), 7.35–7.53 (8H, m,
Ar─H), 7.96 (4H, s, Ar─H), 8.69 (2H, s, 2 = CH), 10.80
(2H, brs, 2NH); MS m/z (%): 724 (M++2, 9), 722 (M+,
11), 412 (50), 270 (62), 171 (52), 128 (72), 128 (79), 75
(100). Anal. Calcd for C28H22Br2N10S2 (722.48): C,
46.55; H, 3.07; N, 19.39. Found C, 46.39; H, 3.01; N,
1
1243, 1096, 1041 cmꢀ1; H NMR (DMSO-d6): δ 1.25
(6H, t, J = 7.5 Hz, 2CH3), 4.30 (4H, q, J = 7.5 Hz,
2CH2), 8.03 (4H, s, Ar─H), 8.59 (2H, s, 2 = CH), 10.06
(2H, brs, 2NH), 10.70 (2H, brs, 2NH); MS m/z (%): 336
(M+, 8), 244 (53), 177 (26), 128 (19), 102 (36), 76 (50),
59 (100). Anal. Calcd for C14H20N6S2 (336.48): C,
49.97; H, 5.99; N, 24.98. Found C, 49.69; H, 5.75; N,
24.79%.
19.18%.
Synthesis of 1,4-bis((2-(4-methyl-5-(aryldiazenyl)thiazol-2-
yl)hydrazono)methyl)benzene derivatives (4a–f and 5a–c).
General procedure. To a mixture of thiosemicarbazides
1,4-Bis((2-(4-methyl-5-((4-nitrophenyl)diazenyl)thiazol-2-yl)
hydrazono)methyl)benzene (4e). Yield 74%; Brown solid;
2a or 2b (1 mmol) and the appropriate hydrazonoyl
halides (2 mmol) in dioxane (20 mL) was added
mp = 201–203°C; IR (KBr): v 3402 (NH), 3053, 2958,
2913 (C─H), 1594, 1554 (C═N), 1496, 1429, 1333,
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S. M. Gomha, T. A. Farghaly, E. M. H. Abbas, and N. T. Alqurashi
Vol 000
1294, 1255, 1157, 1105, 1016 cmꢀ1;1H NMR (DMSO-d6):
δ 2.62 (6H, s, 2CH3), 7.39–8.05 (8H, m, Ar─H), 8.21 (4H,
s, Ar─H), 8.67 (2H, s, 2 = CH), 11.46 (2H, brs, 2NH); MS
m/z (%): 654 (M+, 25), 345 (62), 230 (37), 189 (61), 138
(39), 65 (100). Anal. Calcd for C28H22N12O4S2 (654.68):
C, 51.37; H, 3.39; N, 25.67. Found C, 51.63; H, 3.32; N,
compounds (2 mmol), and the mixture was refluxed for
4 h (monitored by TLC). The solid that precipitated was
filtered off, washed with H2O, dried, and finally
crystallized from ethanol to give the respective 6a–c.
1-(((4-Phenylthiazol-2(5H)-ylidene)hydrazono)methyl)-4-((4-
phenylthiazol-2(5H)-ylidene)
(6a).
hydrazono)methyl)benzene
Yield 76%; yellow solid; mp = 172–174°C; IR
25.49%.
(KBr): v 3059, 2949, 2909 (C─H), 1557 (C═N), 1434,
1358, 1269, 1223, 1123, 1049 cmꢀ1;1H NMR (DMSO-
d6): δ 3.56 (4H, s, 2CH2), 7.27–7.43, 7.85–7.87 (10H, m,
Ar─H), 7.70 (4H, s, Ar─H), 8.05 (2H, s, 2 = CH); MS
m/z (%): 480 (M+, 6), 304 (9), 176 (100), 134 (83), 128
(13), 104 (13), 91 (14), 77 (30), 63 (18). Anal. Calcd for
C26H20N6S2 (480.61): C, 64.98; H, 4.19; N, 17.49.
1,4-Bis((2-(5-((4-methoxyphenyl)diazenyl)-4-methylthiazol-
2-yl)hydrazono)methyl)benzene (4f). Yield 66%; red solid;
mp = 239–241°C; IR (KBr): v 3406 (NH), 3053, 2911
(C─H), 1590, 1568 (C═N), 1490, 1426, 1362, 1305,
1239, 1173, 1121, 1025 cmꢀ1;1H NMR (DMSO-d6): δ
2.58 (6H, s, 2CH3), 3.88 (6H, s, 2OCH3), 6.98–8.05 (8H,
m, Ar─H), 8.21 (4H, s, Ar─H), 8.51 (2H, s, 2 = CH),
11.47 (2H, brs, 2NH); MS m/z (%): 624 (M+, 25), 486
(25), 316 (25), 285 (100), 167 (9), 128 (40), 114 (75),
108 (45), 78 (45), 51 (75). Anal. Calcd for
C30H28N10O2S2 (624.74): C, 57.68; H, 4.52; N, 22.42.
Found C, 64.74; H, 4.05; N, 17.38%.
1-(((4-(4-Nitrophenyl)thiazol-2(5H)-ylidene)hydrazono)
methyl)-4-(((4-(4-nitrophenyl) thiazol-2(5H)-ylidene)hydrazono)
methyl)benzene (6b). Yield 72%; yellow solid; mp = 163–
165°C; IR (KBr): v 2976, 2918 (C─H), 1573 (C═N), 1446,
Found C, 57.73; H, 4.59; N, 22.31%.
1,4-Bis((3-ethyl-(4-methyl-(5-(phenyldiazenyl)thiazol)-2(3H)-
1
1334, 1275, 1105, 1045 cmꢀ1; H NMR (DMSO-d6): δ
ylidene)hydrazono)methyl) benzene (5a).
Yield 68%; red
3.63 (4H, s, 2CH2), 7.72–8.13 (8H, m, Ar─H), 8.26 (4H,
s, Ar─H), 8.29 (2H, s, 2 = CH); MS m/z (%): 570 (M+,
23), 425 (4), 349 (19), 221 (100), 175 (41), 129 (24), 104
(24), 89 (68), 77 (20), 51 (39). Anal. Calcd for
C26H18N8O4S2 (570.60): C, 54.73; H, 3.18; N, 19.64.
Found C, 54.54; H, 3.03; N, 19.48%.
3-(2-((4-(((4-(2-oxo-2H-chromen-3-yl)thiazol-2(5H)-ylidene)
hydrazono)methyl)benzylidene) hydrazono)-2,5-dihydrothiazol-
solid; mp = 221–223°C; IR (KBr): v 2925, 2912 (C─H),
1599, 1522 (C═N), 1453, 1349, 1280, 1238, 1137,
1053 cmꢀ1;1H NMR (DMSO-d6): δ 1.21 (6H, t,
J = 7.5 Hz, 2CH3), 2.02 (6H, s, 2CH3), 4.13 (4H, q,
J = 7.5 Hz, 2CH2), 6.59–8.23 (10H, m, Ar─H), 8.23
(4H, s, Ar─H), 8.80 (2H, s, 2 = CH); MS m/z (%): 620
(M+, 19). Anal. Calcd for C32H32N10S2 (620.79): C,
61.91; H, 5.20; N, 22.56. Found C, 61.77; H, 5.14; N,
4-yl)-2H–chromen-2-one (6c).
Yield 73%; yellow solid;
mp = 218–220°C; IR (KBr): v 2934, 2909 (C─H), 1711
(C═O), 1579, 1516 (C═N), 1363, 1278, 1170, 1090,
1036 cmꢀ1;1H NMR (DMSO-d6): δ 3.56 (4H, s, 2CH2),
7.38–8.09 (10H, m, Ar─H), 8.19 (4H, s, Ar─H), 8.55
(2H, s, 2 = CH); MS m/z (%): 616 (M+, 40), 432 (30),
274 (90), 187 (89), 150 (100), 104 (60), 89 (60), 77 (40),
51 (90). Anal. Calcd for C32H20N6O4S2 (616.67): C,
62.33; H, 3.27; N, 13.63. Found C, 62.45; H, 3.20; N,
13.42%.
22.39%.
1,4-Bis((3-ethyl-(4-methyl-(5-(p-tolyldiazenyl)thiazol)-2(3H)-
ylidene)hydrazono)methyl) benzene (5b).
Yield 70%; red
solid; mp = 190–192°C; IR (KBr): v 3025, 2972, 2925
(C─H), 1597, 1519 (C═N), 1455, 1348, 1280, 1240,
1140, 1051 cmꢀ1;1H NMR (DMSO-d6): δ 1.35 (6H, t,
J = 7.5 Hz, 2CH3), 2.36 (6H, s, 2CH3), 2.73 (6H, s,
2CH3), 4.13 (4H, q, J = 7.5 Hz, 2CH2), 7.23–8.01 (8H,
m, Ar─H), 8.44 (4H, s, Ar─H), 8.75 (2H, s, 2 = CH);
MS m/z (%): 648 (M+, 28). Anal. Calcd for C34H36N10S2
(648.85): C, 62.94; H, 5.59; N, 21.59. Found C, 62.99;
Reaction of thiosemicarbazides 3a and 3b with chloroacetic
acid. A mixture of thiosemicarbazide 2a or 2b (1 mmol)
H, 5.39; N, 21.40%.
1,4-Bis((5-((4-chlorophenyl)diazenyl)-3-ethyl-4-
methylthiazol-2(3H)-ylidene)hydrazono) methyl)benzene (5c).
and chloroacetic acid (0.2 g, 2 mmol) in glacial acetic acid
(30 mL) containing anhydrous sodium acetate (0.33 g,
4 mmol) was refluxed for 6 h. (monitored by TLC). The
reaction mixture was cooled and the resulting precipitate
was filtered off and recrystallized from ethanol to give
Yield 69%; red solid; mp = 206–208°C; IR (KBr): v 2973,
2929 (C─H), 1595, 1525 (C═N), 1410, 1343, 1279, 1237,
1143, 1088, 1051 cmꢀ1;1H NMR (DMSO-d6): δ 1.27 (6H,
t, J = 7.5 Hz, 2CH3), 2.43 (6H, s, 2CH3), 4.39 (4H, q,
J = 7.5 Hz, 2CH2), 7.27–8.03 (8H, m, Ar─H), 8.14 (4H, s,
Ar─H), 8.69 (2H, s, 2 = CH); MS m/z (%): 691 (M++2, 8),
689 (M+, 37). Anal. Calcd for C32H30Cl2N10S2 (689.68): C,
55.73; H, 4.38; N, 20.31. Found C, 55.83; H, 4.31; N,
20.19%.
the respective 7a or 7b.
2,20-(1,4-Phenylenebis(methanylylidene))bis(hydrazine-2,1-
diylidene)bis(thiazolidin-4-one) (7a). [35]
2,20-((1,4-Phenylenebis(methanylylidene))bis(hydrazine-2,1-
diylidene))bis(3-ethyl thiazolidin-4-one) (7b).
Yield 69%;
yellow solid; mp = 252–254°C; IR (KBr): v 3022, 2935,
2909 (C─H), 1711 (C═O), 1581 (C═N), 1407, 1326,
1294, 1243, 1096, 1041 cmꢀ1;1H NMR (DMSO-d6): δ
1.21 (6H, t, J = 7.5 Hz, 2CH3), 3.78 (4H, s, 2CH2), 3.95
(4H, q, J = 7.5 Hz, 2CH2), 7.99 (4H, s, Ar─H), 8.54 (2H,
Reaction of 3 with α-bromoacetyl compounds. General
procedures.
To a solution of thiosemicarbazide 2a or
2b (1 mmol) in ethanol was added α-bromoacetyl
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Synthesis of Some Interesting Bis-thiazoles and Bis-triazolopyrimidinones
s, 2 = CH); MS m/z (%): 416 (M+, 31). Anal. Calcd for
C18H20N6O2S2 (416.52): C, 51.90; H, 4.84; N, 20.18.
Found C, 51.74; H, 4.72; N, 20.04%.
(632.59): C, 64.55; H, 3.19; N, 22.14. Found C, 64.42;
H, 3.06; N, 22.01%.
3-Acetyl-5-(4-(3-acetyl-6-cyano-5-oxo-1-(p-tolyl)-1,5-
dihydro-[1,2,4]triazolo[4,3-a] pyrimidin-7-yl)phenyl)-7-oxo-1-
(p-tolyl)-1,7-dihydro-[1,2,4]triazolo[4,3-a]pyrimidine-6-
carbonitrile (9d). Yield 74%; yellow solid; mp = 253–
255°C; IR (KBr): v 3020, 2921 (C─H), 2219 (C☰N),
1698, 1647 (2C═O), 1591, 1558 (C═N), 1462, 1392,
1224, 1017 cmꢀ1;1H NMR (DMSO-d6): δ 2.29 (6H, s,
2CH3), 2.44 (6H, s, 2CH3), 7.21–8.15 (12H, m, Ar─H);
MS m/z (%): 660 (M+, 30), 579 (26), 447 (25), 311 (25),
238 (33), 219 (40), 118 (34), 106 (100), 91 (51), 77 (85).
Anal. Calcd for C36H24N10O4 (660.64): C, 65.45; H,
3.66; N, 21.20. Found C, 65.36; H, 3.48; N, 21.03%.
Synthesis of 6,60-(1,4-phenylene)bis(4-oxo-2-thioxo-1,2,3,4-
tetrahydropyrimidine-5-carbonitrile) (8).
A mixture of
ethyl cyanoacetate (2.26 g, 2 mmol), terephthalaldehyde
(1.34 g, 1 mmol), and thiourea (1.52 g, 2 mmol) in
ethanol (30 mL) was heated under reflux for 8 h. After
cooling, the solid precipitated was collected and
crystallized from dioxane to give 8. Yield 74%; yellow
solid; mp = 189°C [36].
Reaction of
8
with hydrazonoyl halides. General
procedures. Equimolecular mixture of thione 8 (0.32 g,
1 mmol) and the appropriate hydrazonoyl halides 3
(1 mmol) in dioxane (20 mL) was added triethylamine
(0.7 mL), and the mixture was refluxed for 6 h
(monitored by TLC). The formed solid was collected by
filtration and recrystallized from DMF to give the
Ethyl
6-cyano-5-(4-(6-cyano-3-(ethoxycarbonyl)-5-oxo-1-
phenyl-1,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidin-7-yl)
phenyl)-7-oxo-1-phenyl-1,7-dihydro-[1,2,4]triazolo[4,3-a]
pyrimidine-3-carboxylate (9e). Yield 73%; yellowish-white
solid; mp = 270–272°C; IR (KBr): v 3063, 2977 (C─H),
2219 (C☰N), 1747, 1704 (2C═O), 1598, 1565 (C═N),
1474, 1397, 1288, 1152, 1074 cmꢀ1;1H NMR (DMSO-
d6): δ 1.17 (6H, t, J = 7.2 Hz, 2CH3), 4.56 (4H, q,
J = 7.2 Hz, 2CH2), 7.52–8.12 (10H, m, Ar─H), 8.14 (4H,
s, Ar─H); MS m/z (%): 692 (M+, 8), 666 (14), 444 (12),
401 (24), 119 (24), 104 (83), 92 (59), 77 (100). Anal.
Calcd for C36H24N10O6 (692.64): C, 62.43; H, 3.49; N,
respective compounds 9a–f.
5-(4-(6-Cyano-5-oxo-1,3-diphenyl-1,5-dihydro-[1,2,4]
triazolo[4,3-a]pyrimidin-7-yl)phenyl)-7-oxo-1,3-diphenyl-1,7-
dihydro-[1,2,4]triazolo[4,3-a]pyrimidine-6-carbonitrile (9a).
Yield 70%; yellow solid; mp = 230–232°C; IR (KBr): v
3060, 2928 (C─H), 2216 (C☰N), 1706 (C═O), 1593,
1563 (C═N), 1468, 1390, 1258, 1216, 1118,
1072 cmꢀ1;1H NMR (DMSO-d6): δ 7.52–8.19 (24H, m,
Ar─H); MS m/z (%): 701 (M++1, 53), 700 (M+, 100),
684 (63), 572 (67), 462 (62), 410 (62), 398 (85), 335
(76), 279 (67), 223 (67), 157 (71), 77 (73). Anal. Calcd
for C42H24N10O2 (700.71): C, 71.99; H, 3.45; N, 19.99.
20.22. Found C, 62.41; H, 3.36; N, 20.03%.
Ethyl 6-cyano-5-(4-(6-cyano-3-(ethoxycarbonyl)-5-oxo-1-(p-
tolyl)-1,5-dihydro-[1,2,4] triazolo[4,3-a]pyrimidin-7-yl)phenyl)-
7-oxo-1-(p-tolyl)-1,7-dihydro-[1,2,4]triazolo[4,3-a]pyrimidine-
3-carboxylate (9f).
Yield 72%; yellowish-white solid;
mp = 243–245°C; IR (KBr): v 3057, 2963 (C─H), 2219
(C☰N), 1747, 1692 (2C═O), 1595, 1560 (C═N), 1470,
1372, 1282, 1149, 1064 cmꢀ1;1H NMR (DMSO-d6): δ
1.18 (6H, t, J = 7.0 Hz, 2CH3), 2.43 (6H, s, 2CH3), 4.39
(4H, q, J = 7.0 Hz, 2CH2), 6.92–7.94 (12H, m, Ar─H);
MS m/z (%): 720 (M+, 46), 696 (50), 683 (82), 615 (86),
533 (82), 488 (91), 371 (89), 270 (90), 233 (100), 107
(98), 91 (76). Anal. Calcd for C38H28N10O6 (720.69): C,
63.33; H, 3.92; N, 19.44. Found C, 63.24; H, 3.73; N,
19.31%.
Found C, 71.75; H, 3.36; N, 19.73%.
6-Cyano-5-(4-(6-cyano-5-oxo-1-phenyl-3-
(phenylcarbamoyl)-1,5-dihydro-[1,2,4]triazolo [4,3-a]pyrimidin-
7-yl)phenyl)-7-oxo-N,1-diphenyl-1,7-dihydro-[1,2,4]
triazolo[4,3-a] pyrimidine-3-carboxamide(9b).
brown solid; mp = 244–246°C; IR (KBr): v 3381 (NH),
3105, 3021, 2952 (C─H), 2218 (C☰N), 1698, 1645
(2C═O), 1599, 1530 (C═N), 1483, 1441, 1398, 1265,
1228, 11838, 1077 cmꢀ1;1H NMR (DMSO-d6): δ 7.01–
8.15 (20H, m, Ar─H), 8.20 (4H, s, Ar─H), 10.18 (2H,
brs, 2NH); MS m/z (%): 786 (M+, 38), 720 (41), 704
(55), 536 (45), 525 (49), 477 (44), 339 (42), 213 (39),
187 (34), 157 (48), 118 (47), 91 (100), 77 (55). Anal.
Calcd for C44H26N12O4 (786.76): C, 67.17; H, 3.33; N,
Yield 71%;
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Yield 70%; brown solid; mp = 257–259°C; IR
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet