Intermolecular cyclization of cinnamoyl isothiocyanate: A new synthetic entry for pyrimidine, triazine, and triazole candidates

Article abstract of DOI:10.1080/00397911.2017.1422522

An efficient and facile protocol for the synthesis of azine and azole ring systems was reported. Whereas, reaction of cinnamoyl isothiocyanate with N-nucleophile containing compounds (namely, p-aminophenol (2), N¹-phenylbenzene-1,4-diamine (5)

Full text of DOI:10.1080/00397911.2017.1422522

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Intermolecular cyclization of cinnamoyl
isothiocyanate: A new synthetic entry for
pyrimidine, triazine, and triazole candidates
Hassan A. El-Sayed, Atef M. Abdel Hamid, Mohamed G. Assy & Tahani S. Faraj
To cite this article: Hassan A. El-Sayed, Atef M. Abdel Hamid, Mohamed G. Assy & Tahani
S. Faraj (2018): Intermolecular cyclization of cinnamoyl isothiocyanate: A new synthetic
entry for pyrimidine, triazine, and triazole candidates, Synthetic Communications, DOI:
10.1080/00397911.2017.1422522
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https://doi.org/10.1080/00397911.2017.1422522
Intermolecular cyclization of cinnamoyl isothiocyanate: A new
synthetic entry for pyrimidine, triazine, and triazole
candidates
Hassan A. El-Sayeda, Atef M. Abdel Hamida, Mohamed G. Assya, and Tahani S. Farajb
aDepartment of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt; bDepartment of Chemistry,
Faculty of Science, Omar El-Mukhtar University, Al Bayda, Libya
ABSTRACT
ARTICLE HISTORY
Received 2 December 2017
An efficient and facile protocol for the synthesis of azine and azole
ring systems was reported. Whereas, reaction of cinnamoyl
isothiocyanate with N-nucleophile containing compounds (namely,
p-aminophenol (2), N1-phenylbenzene-1,4-diamine (5) and
p-aminoacetophenone (8)) tolerated thiourea derivatives 3, 6, and 9,
respectively. The later compounds underwent intramolecular cycliza-
tion upon treatment with EtONa to give pyrimidinethiones 4, 7, and
10, respectively, in moderate yield (74–79%). Compound 9 underwent
intramolecular cyclization and condensation upon reaction with NaOH
and benzaldehyde to give pyrimidinethione 12. Thiosemicarbazides
14 and 19 were obtained through reaction of heteroallen 1 with
2,4-dinitrophenylhydrazine 13 and hydrazone 18, respectively.
Compound 14 was cyclized to pyrimidinethione 15 and triazine
derivatives 17 through its reaction with EtONa at room temperature
and refluxing temperature, respectively. Finally, base mediated and
oxidative cyclization of thiourea derivative 19 with EtONa, Br2/AcOH,
and Pb(OAc)2 afforded thiadiazole 20, benzothiazolotriazole 21, and
triazolethione 22 derivatives, respectively.
KEYWORDS
Heterocyclizaton;
isothiocyanate;
pyrimidinethione; triazine;
triazole
GRAPHICAL ABSTRACT
CONTACT Atef M. Abdel Hamid
atefmohamed40@yahoo.com
Department of Chemistry, Faculty of Science,
Zagazig University, Zagazig 44519, Egypt.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data (Full experimental detail on syntheses of compounds 4, 7, 9, 10, 12, 14, 15, 17, 19-22, IR, mass, 1H-NMR,
and 13C-NMR spectra) can be accessed on the publisher’s website.
© 2018 Taylor & Francis

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H. A. EL-SAYED ET AL.
Introduction
Nitrogen containing heterocyclic compounds have promising pharmaceutical interests
which have drawn the attention of scientists in recent years. One of such compounds is
Figure 1. Reactivity profile of cinnamoyl isothiocyanate.
Scheme 1. Synthetic approaches of pyrimidines 4, 7, 10, and 12.

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pyrimidine which acts as the main unit in a wide range of industrially and biologically
important compounds. For example, many pyrimidine derivatives act as anti-
inflammatory,[1] antihypertensive,[2] antifungal,[3] antiviral,[4] antioxidant,[5] antitumor,[6]
and anti-HIV agents.[7] Similarly, triazine ring is an interest six-membered heterocycle
component for designing new biologically active compounds. Therefore, triazine contain-
ing compounds have anticancer,[8] antitumor,[9] antimicrobial,[10] antibacterial,[11]
antimalarial,[12] herbicidal,[13] and anti-HIV activities.[14] In addition, some new triazoles
are also an important group of heterocyclic derivatives of important biological activities.
They have been investigated as anticonvulsant,[15] antibacterial, anticancer,[16] anti-
inflammatory,[17] antitubercular[18] agents. In addition, the core moiety of 1,2,4-triazole
is present in a variety of medically used drugs such as tricyclazole (5-methyl-1,2,4-
triazolo[3,4-b]benzothiazole), fluconazole,[19] and ribavirin[20] as antifungal and antiviral
drugs, respectively. Acyl isothiocyanates, well-known as very important synthons in
synthetic organic chemistry, particularly in the construction of heterocyclic ring systems
such as functionalized pyrimidines, triazines, triazoles, pyridines, pyrazoles, isothiazoles,
pyrans, and pyridazines.[21,22] In particularly, cinnamoyl isothiocyanate is an example for
the reactive intermediates in organic chemistry, thus it contains several active centers
(three electrophilic and two nucleophilic centers, in addition to Michael addition center)
(Fig. 1), this reactivity was the reason for synthesize some biologically active heterocyclic
systems through its reaction with simply available reagents. Completing to our
Scheme 2. Synthetic routes for compounds 14–17 and 19–22.

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H. A. EL-SAYED ET AL.
experience[23–26] in design and synthesis of heterocyclic compounds of interesting
biological activity from simply available reagents, we wish herein to use an efficient and
a facile approach to synthesize novel heterocyclic compounds utilizing cinnamoyl
isothiocyanate as a synthon (Schemes 1 and 2).
Results and discussion
A good example of the reactivity of cinnamoyl isothiocyanate 1 (prepared through reaction
of cinnamoyl chloride with amm.thiocyanate in acetone)[27] can be found in the synthesis
of benzoxazine with pyrimidine moiety 4. The reaction sequence started with treating of
heteroallen 1 with p-aminophenol (2) to yield the isolable thiourea derivative 3 (Scheme 1),
then undergo double pyrimidine oxazine cyclization affording pyrimidine derivative 4
1
(Scheme 1). H NMR spectrum of compound 3 displayed four singlets at δ 9.60, 11.50,
and 12.36 ppm indicating the presence of phenolic OH and 3NH protons, respectively,
in addition multiplet at δ 6.67–7.87 ppm corresponding to olefinic and aromatic protons.
=
=
Its IR bands confirm the presence of OH, NH, C O, and C S functional groups at 3423,
1672, and 1258 cm−1, respectively. 1H NMR spectrum of compound 4 provided two
3
doublets at δ 6.54 and 7.57 ppm with coupling constant J ¼ 16.0 Hz for the trans olefinic
protons, two singlets at δ 6.90 and 12.36 ppm for pyrimidine ring and NH protons, respect-
ively, in addition two multiplet signals at δ 7.41 and 7.68 ppm for aromatic protons. Its
13C NMR spectral parameter confirm the presence of carbonyl and two thiocarbonyl
signals at δ 167.5, 177.4, and 178.0 ppm, respectively, which were approved from the IR
analysis. Compound 7 was obtained when cinnamoylisothiocyanate derivative 1 was
treated with aniline derivative 5 presumably through the nonisolable thiourea derivative
6 [followed by intramolecular cycloaddition and dehydrogenation] (Scheme 2). The key
1
signal of this compound in its H NMR spectrum is the singlet at 12.58 ppm due to the
NH proton of the pyrimidine ring, the spectrum also showed the other NH at
11.48 ppm and aromatic protons. The 13C NMR of pyrimidine derivative 7 illustrated
=
=
=
signals at 166.2, 178.2 ppm for C O and C S, respectively, while C N and aromatic carbon
appeared at the expected chemical shift. IR bands of 7 showed a sharp medium peak at
3392, 3235, and 1668 cm−1 for 2NH and C O function also strong absorption for C C
=
=
was observed at 1599 cm−1 in addition to C S absorption frequency that was detected at
=
1266 cm−1. Upon using electron deficient amine derivative 8 (namely, p-aminoacetophe-
none) to react with isothiocyanate 1, the thiourea 9 was obtained in good yield (80%)
(Scheme 2), its structure was confirmed by the spectral analysis, which were agreement
with the structure (see the “Experimental” section). When compound 9 was left to cyclize
intramoleculary at room temperature the reactant 9 was recovered completely unchanged.
While refluxing of thiourea derivative 9 in the presence of base led to pyrimidine 10
(Scheme 1). 1H NMR spectrum of pyrimidine derivative 10 showed the equilibrium
mixture of thion-form 10A and thiol form 10B, the thiol form can be detected by singlet
at δ 11.64 ppm due to SH group, while the singlet at δ 10.07 ppm result from the NH
proton of the thione-tautomer (Scheme 1). In addition the multiplet in the region δ
7.22–7.94 ppm is due to the absorption of aromatic protons, while H-5 and H-6 of pyrim-
idine ring appeared as doublet and triplets at δ 5.34 and 3.70 ppm with coupling constant
3J ¼ 4.0 Hz, respectively, finally COCH3 protons signal was observed as a singlet at δ
13
=
2.5 ppm. Its C-NMR data showed signals at 165.9 and 181.1 ppm for the C O and

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2
3
=
C S SP carbon, in addition aliphatic SP carbon of C-6, C-5, and CH3 were observed at
δ 26.56, 26.84, and 62.39 ppm.
Thiourea derivative 9 underwent condensation beside the intramolecular cyclization
when treated with benzaldehyde in basic medium to furnish cinnamoyl pyrimidine deriva-
tive 12 (Scheme 1). The presence of the thiol-thione tautomerizatin of 12 was indicated by
two signals at δ 11.67 ppm and δ 11.71 ppm for NH and SH. Its 13C NMR data illustrate
=
=
signals at δ 182.0, 187.5, and 193.2 ppm for electronic different 2 C O and C S, also the
signal for aromatic and styryl moiety appeared at the expected chemical shift.
In the same manner, the thiosemicarbazide derivative 14 was obtained as a result of
addition of NH2 of 13 to isothiocyanate electrophilic carbon of 1 (Scheme 2). The structure
of thiosemicarbazide derivative 14 was established from the spectral data and the elemental
analysis and was agreed with its structure (see the “Experimental” section). Introduction of a
second nucleophilic group besides the amino functionality, offers the possibility to form sev-
eral products depending on the reaction condition, thus 6-phenylpyrimidine derivative 15
was produced by base-induced intramolecular conjugate addition reaction at room
temperature (Scheme 2). Refluxing of base mediated solution of 14 resulted in triazine cycli-
zation leading to formation of triazine intermediate 16 followed by intramolecular conjugate
addition reaction to produce 8-nitro-3-phenylbenzo[e][1,3]thiazino[2,3-c][1,2,4]triazin-1
1
(6H)-one (17) in moderate yield (59%) (Scheme 2). The H NMR spectrum of compound
15 exhibited down field two singlets arising from 2NH (δ 10.78 and 12.38 ppm) and multiplet
at δ 7.40–8.35 ppm representing the aromatic protons, in addition singlet at δ 6.53 ppm char-
acterizes pyrimidine-H-5. Its 13C NMR potentiated the pyrimidine structure 15. The IR spec-
trum 15 showed absorption bands at 1681 and 1617 cm−1 which are attributed to C O and
=
C C stretching. 1H NMR spectrum of the benzotriazine 17 showed two singlets, at δ
=
11.62 ppm corresponding to NH proton, the multiplet of aromatic protons was observed
at δ 7.40–7.58 ppm. The ring olefinic proton (thiazine-H-2) appeared as singlet at δ
5.13 ppm. The 13C NMR of compound 17 revealed SP2 carbons at δ 115.8, 119.1, 120.6,
120.8, 122.9, 127.5, 128.5, 128.7, 129.8, 130.0, 136.5, 144.5, 157.4, 168.3 ppm.
Finally, when Schiff base 18 was allowed to react with heteroallene 1 yielded thiosemi-
carbzide derivative 19, which gave different heterocyclic systems through its reaction with
strong base or different oxidizing agents, thus refluxing of 19 in sod.ethoxide solution
afforded 2-imino-1,3,4-thiadiazole derivative 20[28] in good yield (≈70%). While, treating
of compound 19 with bromine or lead acetate in acetic acid tolerated triazole derivatives 21[29]
and 22[30] in 60 and 80% yields, respectively (Scheme 2). The structure of thiadiazole and
triazole derivatives 20–22 were proved from their spectral parameter and elemental analysis.
Thus, 1H NMR of 20 showed a deshielded NH signal at δ 10.33 ppm and aromatic protons at
δ 6.73–7.87 ppm. The 13C NMR of compound 20 clarified two C N carbons at 145.2 ppm and
=
159.3 ppm beside aromatic SP2 carbon. Its IR data showed two absorption bands at 3321 and
1
1601 cm−1 for NH and C N, respectively. The H NMR parameter of 2-phenylbenzo[4,5]
=
thiazolo[3,2-b][1,2,4]triazole (21) showed aromatic multiplet in the region δ 7.48–7.92 ppm.
The 13C NMR of compound 21 gives 12 signals for SP2 carbons at δ 108.2, 112.5, 116.9,
122.9, 127.6, 128.8, 129.0, 130.2, 131.9, 134.1, 139.3, 147.6 ppm. The structure of triazole
thione derivative 22 was established from the spectral data and the elemental analysis and
was agreement with its structure (see the “Experimental” section).
Scheme 3 illustrates the mechanistic route for formation of thiadiazole 20, where the
=
reaction started with nucleophilic attack of thiolate anion to the electrophilic C N carbon,

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H. A. EL-SAYED ET AL.
Scheme 3. Mechanistic route of thiadiazole 20.
Scheme 4. Mechanistic route of thiadiazole 21.
Scheme 5. Mechanistic route of triazole 22.
followed by dehydrogenation and subsequent hydrolysis with the extrusion of cinnamic
acid (Scheme 3).
While the formation of compound 21 proceeds through oxidation thiazole cyclization,
=
hydrolysis, imino attack to C N electrophilic carbon and finally aromatization producing
polyheterocyclic derivative 21 (Scheme 4).
In Scheme 5, lead acetate reacted with thiosemicarbazone 19 to achieve oxidation
triazole cyclization with losing of cinnamic acid molecule and aromatization forming 22.
Experimental
General
The elemental analyses were obtained on a PerkinElmer 240. The mass spectra (Ms) were
measured with Shimadzu GCMS-QP 1000 EX mass spectrometer. The IR spectra were

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1
acquired in KBr on a Pye Unicam Sp-3–300 infrared spectrophotometer. The H NMR
spectra were measured on a Bruker Avance 400 spectrometer at 400.0 MHz. The chemical
shifts were measured relative to DMSO-d6 proton signal. The melting points were
determined on an Electro thermal IA 9100 apparatus and are uncorrected.
N-((3-(Cinnamoylcarbamothioyl)-4-hydroxyphenyl)carbamothioyl)cinnamamide (3)
A mixture of cinnamoyl isothiocyanate (0.02 mol, 3.78 g) and 4-aminophenol 2 (0.02 mol,
2.18 g) in acetone (30 mL) was stirred at room temperature for 2 h, then poured onto cold
water, the solid formed was heated with sodium bicarbonate, filtered and recrystallized
from ethanol to give 3. Yield: 7.89 g (81%); brown crystals; m.p. > 340 °C. IR (KBr):
−1
3423 (NH, OH) 1672, 1623 (C O), 1258 (C S) cm . 1H NMR (DMSO-d6, ppm) δ
6.67–7.78 (m, 17H, olefinic-H and Ar-H), 9.60 (s, 1H, OH), 11.50 (s, 1H, 2NH), 12.49
(s, 1H, NH). 13C NMR (100 MHz, DMSO-d6, ppm): 89.7, 97.3, 114.1, 115.9, 120.5,
120.8, 120.9, 124.8, 126.6, 127.4, 128.2, 128.9, 129.1, 129.96, 131.6, 134.0, 143.8, 144.8,
155.6, 166.1, 175.5, 178.7. Anal: C26H21N3O3S2 (487.59); Calcd: C, 64.04; H, 4.34;
N, 8.62. Found: C, 64.11; H, 4.38; N, 8.57.
=
=
Conclusion
In summary, we report an efficient and facile synthetic approaches for some pyrimidine
thiones, triazines, triazoles, and thiadiazole. Cinnamoyl isothiocyanate was treated with a
variety of N-nucleophilic reagents affording thiourea or thiosemicarbazide derivatives,
the later intermediates were underwent intramolecular cyclization to give the target
compounds.
References
[1] Tozkoparan, B.; Ertan, M.; Kelicen, P.; Demirdamar, R. Synthesis and Anti-Inflammatory
Activities of Some Thiazolo[3,2-a]Pyrimidine Derivatives. Farmaco 1999, 54, 588–593. DOI:
10.1016/s0014-827x(99)00068-3.
[2] Jeanneau-Nicolle, E.; Benoit-Guyod, M.; Namil, A.; Leclerc, G. New Thiazolo[3,2-a]Pyrimidine
Derivatives, Synthesis and Structure-Activity Relationships. Eur. J. Med. Chem. 1992, 27,
115–120.
[3] Pan, B.; Huang, R.; Zheng, L.; Chen, C.; Han, S.; Qu, D.; Zhu, M.; Wei, P. Thiazolidione
Derivatives as Novel Antibiofilm Agents: Design, Synthesis, Biological Evaluation, and
Structure - Activity Relationships. Eur. J. Med. Chem. 2011, 46, 819–824.
[4] Mohamed, S. F.; Flefel, E. M.; Amr, A. E. G. E.; El-Shafy, D. N. Anti-HSV-1 Activity and
Mechanism of Action of Some New Synthesized Substituted Pyrimidine, Thiopyrimidine
and Thiazolopyrimidine Derivatives. Eur. J. Med. Chem. 2010, 45, 1494–1501.
[5] Maddila, S.; Damu, G.; Oseghe, E.; Abafe, O.; Rao, C. V.; Lavanya, P. Synthesis and Biological
Studies of Novel Biphenyl-3,5-dihydro-2H-Thiazolopyrimidines Derivatives. J. Korean Chem.
Soc. 2012, 56, 334–340.
[6] Flefel, E.; Salama, M.; El-Shahat, M.; El-Hashash, M.; El-Farargy, A. A Novel Synthesis of Some
New Pyrimidine and Thiazolopyrimidine Derivatives for Anticancer Evaluation. Phosphorus
Sulfur Silicon Relat. Elem. 2007, 182, 1739–1756.
[7] Danel, K.; Pedersen, E. B.; Nielsen, C. Synthesis and Anti-HIV-1 Activity of Novel 2,3-Dihydro-
7H-thiazolo[3,2-a]pyrimidin-7-ones. J. Med. Chem. 1998, 41, 191–198. DOI: 10.1002/chin.
199820192.
[8] Alterman, M.; Samulsson, B. J.; Danielson, H. Design and Synthesis of New Potent
C2-Symmetric HIV-1 Protease Inhibitors. Use of l-Mannaric Acid as a Peptidomimetic
Scaffold. J. Med. Chem. 1998, 41, 3782–3792.

8
H. A. EL-SAYED ET AL.
[9] Dhainaunt, A.; Regnier, G.; Tizot, A.; Berthier, L. K. New Purines and Purine Analogs as
Modulators of Multidrug Resistance. J. Med. Chem. 1996, 39, 4099–4108. DOI: 10.1021/
jm960361i.
[10] Brzozowski, Z.; Saczewski, F.; Gdaniec, M. Synthesis, Structural Characterization and
Antitumor Activity of Novel 2,4-Diamino-1,3,5-Triazine Derivatives. Eur. J. Med. Chem.
2000, 35, 1053–1064. DOI: 10.1002/chin.200116161.
[11] Gahtori, P.; Ghosh, S. K.; Singh, B.; Singh, U. B.; Bhat, H. R.; Uppal, A. Synthesis, SAR
and Antibacterial Activity of Hybrid Chloro, Dichloro-Phenylthiazolyl-s-triazines. Saudi
Pharmaceutical J. 2012, 20, 35–43. DOI: 10.1016/j.jsps.2011.05.003.
[12] Dutta, M. M.; Goswami, B. N.; Kataky, J. C. S. Studies on biologically active heterocycles. Part I.
Synthesis and antifungal activity of some new aroyl hydrazones and 2,5-disubstituted-1,3,4-
oxadiazoles. J. Heterocyclic Chem. 1986, 23, 793–795. DOI: 10.1002/jhet.5570230328.
[13] Srinivas, K.; Bhanuprakash, K.; Murtly, U. S. N. Synthesis and Antibacterial Activity of 2,4,6-
Trisubstituted s-Triazines. Bioorg. Med. Chem. Lett. 2005, 15, 1121–1129. DOI: 10.1002/chin.
200710176.
[14] Klenke, B.; Stewart, M.; Barrett, M. P. Synthesis and Biological Evaluation of s-Triazine
Substituted Polyamines as Potential New Anti-Trypanosomal Drugs. J. Med. Chem. 2001, 44,
3440–3452. DOI: 10.1021/jm010854þ.
[15] Botros, S.; Khalil, N. A.; Naguib, B. H.; El-Dash. Y. Synthesis and Anticonvulsant Activity of
New Phenytoin Derivatives. Eur. J. Med. Chem. 2013, 60, 57–63 DOI: 10.1016/j.ejmech.2012.
11.025.
[16] Al-Soud, Y. A.; Al-Masoudi, N. A.; Ferwanah, A. E. S. Synthesis and Properties of
New Substituted 1,2,4-triazoles: Potential Antitumor Agents. Bioorg. Med. Chem. 2003, 11,
1701–1708. DOI: 10.1016/s0968-0896(03)00043-9.
[17] Tozkoparan, B.; Gokhan, N.; Aktay, G.; Yesilada, E.; Ertan, M. 6-Bnzyllidenethiazolo[3,2-b]-
1,2,4-triazole-5(6H)-one substituted with Ibuprofen: Synthesis, Characterization and
Evaluation of Anti-Inflammatory Activity. Eur. J. Med. Chem. 2000, 35, 743–750. DOI:
10.1016/s0223-5234(00)00157-4.
[18] Varvaressou, A.; Siatra-Papastaikoudi, T.; Tsotinis, A.; Tsantili-Kakoulidou, A.; Vamvakides, A.
Synthesis, Lipophilicity and Biological Evaluation of Indole-Containing Derivatives of 1,3,4-
thiadiazole and 1,2,4-triazole. Farmaco 1998, 53, 320–326. DOI: 10.1016/s0014-827x(98)
00024-x.
[19] Tsukuda, T.; Shiratori, Y.; Watanabe, M.; Ohtsuka, H.; Hattori, K.; Shirai, M.; Shimma, N.
Modeling, Synthesis and Biological Activity of Novel Antifungal Agents (1). Bioorg. Med.
Chem. Lett. 1998, 8, 1819–1827. DOI: 10.1016/s0960-894x(98)00316-3.
[20] Witoaski, J. T.; Robins, R. K.; Sidwel, R. W.; Simon, L. N. Design, Synthesis, and Broad
Spectrum Antiviral Activity of 1-.beta.-D-ribofuranosyl-1,2,4-triazole-3-carboxamide and
Related Nucleosides. J. Med. Chem. 1972, 15, 1150–1154. DOI: 10.1021/jm00281a014.
[21] Sherif, M.; Assy, M.; Yousif, N.; Galahom, M. Studies on Heterocyclization of Acetoacetanilide.
J. Iran. Chem. Soc. 2013, 10, 85–91. DOI: 10.1007/s13738-012-0128-x.
[22] Sayed, H. A.; Moustafa, A. H.; Yousif, N. M.; Assy, M. G.; Abd El-Halim, M. A. Synthesis
and Reactions of Some Novel Mercaptopyrimidine Derivatives for Biological Evaluation.
Phosphorus Sulfur Silicon Relat. Elem. 2008, 183, 2318–2329.
[23] El-Sayed, H. A. Design and Synthesis of Some Tricyclic Pyrimidines and Triazines via
Cycloaddition and Intermolecular Cyclization of Cyclic Amidine. J. Iran. Chem. Soc. 2017,
14, 2239–2246. DOI: 10.1007/s13738-017-1160-7.
[24] El-Sayed, H. A.; Said, S. A.; Amr, A. E. Synthesis of Some Fused Heterocyclic Systems and Their
Nucleoside Candidates. Res. Chem. Intermed. 2014, 40, 833–845. DOI: 10.1007/s11164-012-
1006-y.
[25] Abdelghani, E.; Said, A. S.; Assy, M. G.; Abdel Hamid, A. M. Heterocyclization of Thiouracil
Derivative: Synthesis of Thiazolopyrimidines, Tetrazolopyrimidines and Triazolopyrimidines
of Potential Biological Activity. J. Iran. Chem. Soc. 2015, 12, 1809–1817. DOI: 10.1007/
s13738-015-0656-2.

SYNTHETIC COMMUNICATIONS®
9
[26] Abdelghani, E.; Said, A. S.; Assy, M. G.; Abdel Hamid, A. M. Synthesis and Antimicrobial
Evaluation of Some New Pyrimidines and Condensed Pyrimidines. Arab. J. Chem. 2017, 10,
S2926–S2933. DOI: 10.1016/j.arabjc.2013.11.025.
[27] Assy, M. G. Some Reactions with ethyl 2-aryl-4-mercapto-6-methylpyrimidine-5-carboxylates.
Sulfur Lett. 1990, 11, 75–82.
[28] Wolkoff, P.; Nemeth, S. T.; Gibson, M. S. Reaction of Hydrazonyl Halides with Derivatives of
Thiourea and Thiosemicarbazide; A New Source of C- amino- and C-hydrazino- l,2,4-triazoles.
Can. J. Chem. 1975, 53, 3211–3215.
[29] Deshmukh, M. B.; Patil, S. S.; Jadhav, S. D.; Shejwal, R. V. Synthesis of New Triazolo and
Pyrazolo Benzothiazoles. Indian J. Heterocycl. Chem. 2010, 20, 163–166.
[30] y Barnikow, G.; Ebeling, H. Isothiocyanates. XXXVII. Reactions of Imidoyl Isothiocyanates
with Substituted Hydrazines. Zeitschrift fuer Chemie 1980, 20, 55–56.