A convenient synthesis of novel 1,3-phenylene bridged bis-heterocyclic compounds

Article abstract of DOI:10.1080/17415993.2015.1126592

Reactions of bis-hydrazonoyl bromide 1 with each of phenyl-5-arylidene-2-thioxo-thiazol-4-one, triazinethiones and 4,6-dimethyl-2,6-dioxocyclohexane-1-thiocarboxanilide as sulfur dipolarophilic reagents led to the formation of the hitherto unreported 1,3-

Full text of DOI:10.1080/17415993.2015.1126592

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
A convenient synthesis of novel 1,3-phenylene
bridged bis-heterocyclic compounds
Hamdi M. Hassaneen, Ahmad S. Shawali & Fatma M. Saleh
To cite this article: Hamdi M. Hassaneen, Ahmad S. Shawali & Fatma M. Saleh (2016): A
convenient synthesis of novel 1,3-phenylene bridged bis-heterocyclic compounds, Journal of
Sulfur Chemistry, DOI: 10.1080/17415993.2015.1126592
To link to this article: http://dx.doi.org/10.1080/17415993.2015.1126592
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Date: 12 January 2016, At: 05:20

JOURNAL OF SULFUR CHEMISTRY, 2016
http://dx.doi.org/10.1080/17415993.2015.1126592
A convenient synthesis of novel 1,3-phenylene bridged
bis-heterocyclic compounds
Hamdi M. Hassaneen, Ahmad S. Shawali and Fatma M. Saleh
Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt
ABSTRACT
ARTICLE HISTORY
Received 8 August 2015
Accepted 27 November 2015
Reactions of bis-hydrazonoyl bromide 1 with each of phenyl-5-
arylidene-2-thioxo-thiazol-4-one, triazinethiones and 4,6-dimethyl-
2,6-dioxocyclohexane-1-thiocarboxanilide as sulfur dipolarophilic
reagents led to the formation of the hitherto unreported 1,3-
phenylene bis-heterocycles 4, 8 and 10, respectively. The structures
of the isolated products were established on the basis of their ele-
mental and spectral analyses. The mechanism and the site selectivity
in the studied reactions are discussed.
KEYWORDS
Cycloaddition;
bis-nitrilimines; heterocycles;
bis-hydrazonoyl halides;
spirocycloadducts
1. Introduction
In continuation of our interest in chemistry of hydrazonoyl halides I [1–13] and the
bis-hydrazonoyl halides II (Figure 1),[14–16] we thought it is interesting to explore the
utility of Nꢀ1,Nꢀ3-diphenyl-1,3-benzene-bis-carbohydrazonoyl bromide 2 as useful precur-
sor in synthesis of new 1,3-phenylene bridged bis-heterocycles that have not been reported
hitherto. Contrary to 1,4-phenylene bridged bis-heterocycles,[17] the target 1,3-phenylene
bridged bis-heterocycles have received little, if there is any, attention. The interest in syn-
thesis of such new 1,3-phenylene bridged bis-heterocycles is due to the fact that several
literature reports indicate that some bis-heterocyclic compounds exhibit various biological
activities, including antibacterial, fungicidal, tuberculostatic, antiamoebic, anthelmintic
and plant growth regulative properties.[17–19]
CONTACT Hamdi M. Hassaneen
hamdi_251@yahoo.com
© 2016 Taylor & Francis

2
H. M. HASSANEEN ET AL.
Figure 1. General structure of mono- and bis-hydrazonoyl halides.
2. Results and discussion
The target new bis-hydrazonoyl bromide 2 was prepared in this study, as depicted in
Scheme 1, by stirring a mixture of carbon tetrabromide, triphenylphosphine and N,Nꢀ-
diphenyl isophthalic hydrazide 1 in acetonitrile at room temperature.[20] Its structure
was determined from its elemental and spectroscopic (IR, 1H NMR, 13C NMR and MS)
analyses (see Section 3).
Reaction of bis-nitrilimine I, generated in situ by treatment of the bis-hydrazonoyl
bromide 2 with triethylamine in refluxing chloroform, with two molar equivalents of
each 3-phenyl-5-arylidene-2-thioxo-thiazol-4-ones 3 afforded, in each case, a single prod-
1
uct as evidenced by TLC analysis. Both the spectral (MS, IR, H and 13C NMR) and
elemental analysis data (see Section 3) indicated that the isolated products are the
corresponding derivatives of 3,3ꢀ-(1,3-pheneylene)bis-(1,6-diphenyl-7-oxo-8-substituted-
spiro(5H-thiazolo[2,2ꢀ]-3H-1,3,4-thiadiazole)) 4 (Scheme 2). Such products resulted via
=
cycloaddition of the generated nitrilimines I to the C S in compounds 2. On the basis
of such a finding, the spirocycloadducts of type 5 and 6, that result via cycloaddition of
=
=
the generated nitrilimine intermediate I to exocyclic C C and C O, respectively, were
=
discarded (Scheme 2). This finding indicates that the C S is more dipolarophilic than
=
=
both the exocyclic C C and C O groups. This observed site selectivity is also consistent
with literature reports on reactions of 3-phenyl-5-arylidene-2-thioxo-thiazol-4-one with
mono-nitrilimines.[21,22]
Next, the reaction of 2 with two molar equivalents of each of 6-arylmethylene-2,3-
dihydro-3-thioxo-1,2,4-triazin-5(4H)-ones 7a–g in refluxing chloroform in the presence
of triethylamine gave, in each case, a single product as evidenced by TLC analysis of the
crude products. Both mass spectra and elemental analyses of the isolated products indi-
cated that they are free of sulfur. The IR spectra of the products, while they are free of NH
bands, they revealed two amide-I absorption bands in the region 1670–1660 cm−1. On
the basis of these data, the isolated compounds were assigned the structure 8 (Scheme 3).
Scheme 1. Synthesis of bis-hydrazonoyl bromide.

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3
Scheme 2. Synthesis of bis-spiro compounds.
To account for the formation of latter, it is suggested as depicted in Scheme 3, that the
=
reaction involves an initial cycloaddition of the bis-nitrilimine to C S of 7 to give the bis-
cycloadduct A which undergo in situ tandem ring opening, recyclization and elimination
of H2S to give 8 as end products.
The differences recorded between reactions of 2 with each of 3 and 7 is due to the
absence of NH in the former 3 that facilitates ring opening of the initially formed thiadi-
azole cycloadduct. This rationalization is evidenced by the following result of the reaction
of 2 with the thioanilide 9.
Treatment of bis-hydrazonoyl bromide 2 with 4,4-dimethyl-2,6-dioxocyclohexane-
thiocarboxanilide 9 in refluxing chloroform in the presence of triethylamine gave a
single product that proved to be 5,5ꢀ-(1,3-phenylene)bis[2-(5,5-dimethylcyclohexane-1,3-
dione)-3-phenyl-3H-[1,3,4]thiadiazole] 10 (Scheme 4). The structure of product 10 was
established on the basis of its spectra (MS, IR, 1H and 13C NMR) and elemental analyses
data. Thus, its IR spectrum displayed an absorption band at ν 1645 (CO) cm−1 and its 1H
NMR spectrum exhibited, in addition to aromatic proton multiplet, a characteristic two
singlet signals at δ 1.07 and 2.38 assignable to the 4CH3 and 4CH2 groups, respectively.
The formation of the latter product 10 seems to result also via initial cycloaddition of the
=
nitrilimine I to the C S bond to the corresponding cycloadduct which in turn undergoes
in situ tandem ring opening, recyclization and elimination of H2NPh to give 10 as end

4
H. M. HASSANEEN ET AL.
Scheme 3. Synthesis of bis-1,2,4-triazolo-[4,3-b]-triazine derivatives.
products. Such a sequence is consistent with literature reports on reactions of thioanilides
with hydrazonoyl halides.[23,24]
3. Experimental section
Melting points were determined on a Stuart melting point apparatus and are uncor-
rected. The IR spectra were measured as KBr pellets on a FTIR Bruker-Vector 22
spectrophotometer. The 1H NMR and 13C NMR spectra were recorded in CDCl3 or [d6]
DMSO on a Varian Mercury VXR 300 spectrometer (300 MHz for 1H NMR and 75 MHz

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5
Scheme 4. Synthesis of bis-5,5-dimethylcyclohexane-[1,3,4]-thiadiazole.
for 13C NMR) using TMS as internal standard. Mass spectra were measured on a Shimadzu
GCMS-Q-1000 EX mass spectrometer at 70 eV. The elemental analyses were carried out at
the Microanalytical Center, Cairo University using Automated analyzer CHNS, Vario EL
III, Elementar, Germany.
3.1. Synthesis of Nꢀ1,Nꢀ3-diphenylisophthalohydrazide (1)
To a solution of phenylhydrazine (108.0 g, 1.0 mol) in cold ether (400 mL), the solution
of isophthaloyl dichloride (100 g, 0.5 mol) in cold ether (50 mL) was added dropwise
with stirring. The addition took 30 min. The reaction mixture was stirred for further
1 h and the precipitated solid was collected, washed with water and crystallized from
DMF to give Nꢀ1,Nꢀ3-diphenylisophthalohydrazide in 70% yield; m.p. 280–282°C [Lit. m.p.
260–262°C].[20]
3.2. Synthesis of Nꢀ1,Nꢀ3-diphenyl-1,3-benzene-bis-carbohydrazonoyl bromide (2)
To a solution of Nꢀ1,Nꢀ3-diphenylisophthalohydrazide 1 (3.5 g, 10.0 mmol) in acetonitrile
(40 mL), the triphenylphosphine (6.4 g) and carbon tetrabromide (6.8 g) were added. The
reaction mixture was stirred overnight at room temperature. The solid product was col-
lected, washed with ethanol and crystallized from acetonitrile to give product 2 as white
crystals, m.p. 240°C, yield (4.02 g, 84%). IR (KBr) ν 3280 (NH), 1595 (C N) cm−1. 1H
=
NMR (300 MHz, CDCl3): δ 6.90–8.40 (m, 14H) and 8.60 (s, 2H, 2NH). 13C NMR (75 MHz,
CDCl3): δ 113.9, 122.4, 128.4, 128.9, 129.5, 131.3, 131.5, 143.0, 155.2. GC/MS (m/z): 472

6
H. M. HASSANEEN ET AL.
(M+). Anal. Calcd. for C20H16Br2N4 (472.21): C, 50.87; H, 3.42; Br, 33.85; N, 11.87. Found:
C, 50.76; H, 3.30; Br, 33.87; N, 11.89.
3.3. Synthesis of 3,3ꢀ-(1,3-pheneylene)bis-(1,6-diphenyl-7-oxo-8-substituted-
spiro(5H-thiazolo[2,2ꢀ]-3H-1,3,4-thiadiazole)) derivatives (4a–j)
To a mixture of N,Nꢀ-biphenyl-1,3-benzene-bis-carbohydrazonoyl bromide 2 (1.15 g,
3.0 mmol) and the appropriate 3-phenyl-5-arylidene-2-thioxo-thiazol-4-ones3 (6.0 mmol)
in chloroform (20 mL), triethylamine (0.6 mL, 6.0 mmol) was added at room temperature.
The reaction mixture was refluxed for 6 h and then cooled, the excess chloroform was
removed under reduced pressure and the residue was treated with ethanol (10 mL). The
solid that precipitated was collected and crystallized from acetonitrile to give the corre-
sponding product 4. The compounds 4a–j prepared together with their physical properties
are listed below.
3.3.1. 3,3ꢀ-(1,3-Phenylene)bis(1,6-diphenyl-7-oxo-8-(4-methoxybenzylidene)-
spiro(5H-thiazolo[2,2ꢀ]-3H-1,3,4-thiazole) (4a)
Yellow crystals, m.p. 188–190°C, yield (2.49 g, 90%); IR (KBr) ν 1692 (CO) cm−1. 1H NMR
(300 MHz, CDCl3): δ 3.85 (s, 6H, 2CH3O), 7.09–7.50 (m, 32H) and 7.79 (s, 2H, 2CH). 13
C
NMR (75 MHz, CDCl3): δ 55.8, 101.2, 114.2, 116.7, 120.8, 121.0, 124.1, 127.5, 128.0, 128.9,
129.5, 130.2, 130.7, 131.5, 138.8, 139.1, 141.8, 143.8, 159.8, 162.3. GC/MS (m/z): 964 (M+).
Anal. Calcd. for C54H40N6O4S4 (964.95): C, 67.20; H, 4.18; N, 8.71; S, 13.29. Found: C,
67.28; H, 4.10; N, 8.69; S, 13.26.
3.3.2. 3,3ꢀ-(1,3-Phenylene)bis(1,6-diphenyl-7-oxo-8-(4-chlorobenzylidene)-spiro(5H-
thiazolo[2,2ꢀ]-3H-1,3,4-thiazole (4b)
1
Yellow crystals, m.p. 194–196°C, yield (2.48 g, 89%). H NMR (300 MHz, CDCl3): δ
6.99–7.50 (m, 32H) and 7.60 (s, 2H, 2CH). GC/MS (m/z): 973 (M+). Anal. Calcd. for
C52H34Cl2N6O2S4 (973.80): C, 64.12; H, 3.52; Cl, 7.28; N, 8.63; S, 13.17. Found: C, 64.21;
H, 3.53; Cl, 7.25; N, 8.61; S, 13.20.
3.3.3. 3,3ꢀ-(1,3-Phenylene)bis(1,6-diphenyl-7-oxo-8-(2-thienylmethylene)-spiro(5H-
thiazolo[2,2ꢀ]-3H-1,3,4-thiazole) (4c)
1
Yellow crystals, m.p. 182–184°C, yield (2.45 g, 93%). H NMR (300 MHz, CDCl3): δ
6.90–8.20 (m, 32H). GC/MS (m/z): 916 (M+). Anal. Calcd. for C48H32N6O2S6 (916.82):
C, 62.86; H, 3.52; N, 9.16; S, 20.98. Found: C, 62.91; H, 3.49; N, 9.19; S, 20.95.
3.3.4. 3,3ꢀ-(1,3-Phenylene)bis(1,6-diphenyl-7-oxo-8-(2,4-dichlorobenzylidene)-spiro
(5H-thiazolo[2,2ꢀ]-3H-1,3,4-thiazole) (4d)
1
Yellow crystals, m.p. 192–194°C, yield (2.83 g, 95%). H NMR (300 MHz, CDCl3): δ
7.00–7.76 (m, 30H) and 7.80 (s, 2H, 2CH). GC/MS (m/z): 1042 (M+). Anal. Calcd. for
C52H32Cl4N6O2S4 (1042.70): C, 59.89; H, 3.09; Cl, 13.60; N, 8.06; S 12.30. Found: C, 59.96;
H, 3.03; Cl, 13.61; N, 8.02; S 12.32.

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3.3.5. 3,3ꢀ-(1,3-Phenylene)bis(1,6-diphenyl-7-oxo-8-(benzylidene-spiro(5H-
thiazolo[2,2ꢀ]-3H-1,3,4-thiazole) (4e)
1
Yellow crystals, m.p. 168–170°C, yield (2.44 g, 94%). H NMR (300 MHz, CDCl3): δ
7.13–7.52 (m, 34H) and 7.84 (s, 2H, 2CH). GC/MS (m/z): 904 (M+). Anal. Calcd. for
C52H36N6O2S4 (904.90): C, 69.00; H, 4.01; N, 9.28; S, 14.17. Found: C, 69.05; H, 3.98; N,
9.22; S, 14.20.
3.3.6. 3,3ꢀ-(1,3-Phenylene)bis(1,6-diphenyl-7-oxo-8-(4-methylbenzylidene)-spiro(5H-
thiazolo[2,2ꢀ]-3H-1,3,4-thiazole) (4f)
Yellow crystals, m.p. 180–182°C, yield (2.44 g, 91%). 1H NMR (300 MHz, CDCl3): δ 2.40
(s, 6H, 2CH3), 6.71–7.40 (m, 32H) and 7.80 (s, 2H, 2CH). 13C NMR (75 MHz, CDCl3): δ
23.6, 101.2, 116.7, 120.8, 121.0, 124.1, 127.5, 128.0, 128.5, 128.7, 128.9, 129.2, 129.5, 130.7,
131.5, 132.2, 137.6, 138.8, 139.1, 141.8, 162.3. GC/MS (m/z): 932 (M+). Anal. Calcd. for
C54H40N6O2S4 (932.94): C, 69.50; H, 4.32; N, 9.01; S, 13.74. Found: C, 69.53; H, 4.35; N,
8.98; S, 13.76.
3.3.7. 3,3ꢀ-(1,3-Phenylene)bis(1,6-diphenyl-7-oxo-8-((cinnamylmethylene)-spiro(5H-
thiazolo[2,2ꢀ]-3H-1,3,4-thiazole) (4g)
Yellow crystals, m.p. 190–192°C, yield (2.44 g, 89%). 1H NMR (300 MHz, CDCl3): δ 6.70
(d, 2H, 2CH), 7.02 (d, 2H, 2CH) and 6.90–7.50 (m, 36H). 13C NMR (75 MHz, CDCl3) δ
101.3, 116.7, 118.5, 120.8, 121.0, 125.2, 127.5, 127.9, 128.0, 128.5, 128.6, 128.9, 129.5, 130.7,
131.5, 125.2, 138.4, 139.1, 141.8, 142.8, 143.8, 162.3. GC/MS (m/z): 956 (M+). Anal. Calcd.
for C56H40N6O2S4 (956.98): C, 70.27; H, 4.21; N, 8.78; S, 13.40. Found: C, 70.30; H, 4.19;
N, 8.76; S, 13.43.
3.3.8. 3,3ꢀ-(1,3-Phenylene)bis(1,6-diphenyl-7-oxo-8-(2-furylmethylene)-spiro(5H-
thiazolo[2,2ꢀ]-3H-1,3,4-thiazole) (4h)
1
Yellow crystals, m.p. 176–178°C, yield (2.23 g, 88%). H NMR (300 MHz, CDCl3): δ
6.8–8.10 (m, 32H). GC/MS (m/z): 884 (M+). Anal. Calcd. for C48H32N6O4S4 (884.82):
C, 65.14; H, 3.64; N, 9.50; S, 14.49. Found: C, 65.19; H, 3.61; N, 9.48; S, 14.43.
3.3.9. 3,3ꢀ-(1,3-Phenylene)bis(1,6-diphenyl-7-oxo-8-(4-dimethylamino-benzylidene)-
spiro(5H-thiazolo[2,2ꢀ]-3H-1,3,4-thiazole) (4i)
1
Orange crystals, m.p. 196–198°C, yield (2.62 g, 92%); IR (KBr) ν 1665 (CO) cm−1. H
NMR (300 MHz, CDCl3): δ 3.10 (s, 12H, 4CH3), 6.71–8.23 (m, 32H, ArH) and 8.49 (s, 2H,
2CH). 13C NMR (75 MHz, CDCl3) δ 41.3, 101.2, 111.7, 116.7, 121.0, 120.8, 124.1, 124.7,
127.5, 128.0, 128.9, 129.5, 129.7, 138.8, 139.1, 141.8, 143.8, 150.3. GC/MS (m/z): 991 (M+).
Anal. Calcd. for C56H46N8O2S4 (991.04): C, 67.85; H, 4.68; N, 11.30; S, 12.94. Found: C,
67.89; H, 4.63; N, 11.28; S, 12.90.
3.3.10. 3,3ꢀ-(1,3-Phenylene)bis(1,6-diphenyl-7-oxo-8-((4-florobenzylidene)-spiro(5H-
thiazolo[2,2ꢀ]-3H-1,3,4-thiazole) (4j)
Yellow crystals, m.p. 188–190°C, yield (2.53 g, 94%). GC/MS (m/z): 940 (M+). Anal. Calcd.
for C52H34F2N6O2S4 (940.88): C, 66.36; H, 3.64; F, 4.04; N, 8.93; S, 13.63. Found: C, 66.41;
H, 3.60; F, 3.99; N, 8.90; S, 13.65.

8
H. M. HASSANEEN ET AL.
3.4. Synthesis of 3,3ꢀ-(1,3-phenylene)bis(1-phenyl-6-(aryl)-7-oxo-1,2,4-triazolo-
[4,3-b]-triazine) derivatives (8a–g)
To a mixture of N,Nꢀ-biphenyl-1,3-benzene-bis-carbohydrazonoyl bromide 2 (1.15 g,
3.0 mmol) and the appropriate 6-benzyl-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-ones 7
(6.0 mmol) in chloroform (20 mL), triethylamine (0.6 mL, 6.0 mmol) was added at room
temperature. The reaction mixture was refluxed for 6 h and then cooled, the excess chlo-
roform was removed under reduced pressure and the residue was treated with ethanol
(10 mL). The solid that precipitated was collected and crystallized from a suitable solvent
to give the corresponding product 8. The compounds 8a–g prepared together with their
physical properties are listed below:
3.4.1. 3,3ꢀ-(1,3-Phenylene)bis(1-phenyl-6-benzyl-7-oxo-1,2,4-triazolo[4,3-b]triazine)
(8a)
Orange crystals, m.p. 278–280°C (DMF), yield (1.56 g, 80%). IR (KBr) ν 1660 (CO) cm−1
.
1H NMR (300 MHz, CDCl3): δ 4.07 (s, 4H, 2CH2) and 7.09–8.37 (m, 24H). GC/MS (m/z):
680 (M+). Anal. Calcd. for C40H28N10O2 (680.73): C, 70.58; H, 4.15; N, 20.58. Found: C,
70.61; H, 4.10; N, 20.55.
3.4.2. 3,3ꢀ-(1,3-Phenylene)bis(1-phenyl-6-(p-methoxybenzyl)-7-oxo-1,2,4-
triazolo[4,3-b]triazine) (8b)
Beige crystals, m.p. 270–272°C (DMF), yield (1.89 g, 87%). IR (KBr) ν 1656 (CO) cm−1
.
1H NMR (300 MHz, DMSO): δ 3.30 (s, 6H, 2CH3O), 3.99 (s, 4H, 2CH2) and 7.21–8.40
(m, 22H). 13C NMR (75 MHz, CDCl3): δ 24.4, 56.7, 122.3, 123.2, 127.1, 127.3, 128.1, 128.9,
129.1, 130.9, 133.8, 134.6, 135.8, 140.4, 148.9, 152.4, 164.8. GC/MS (m/z): 740 (M+). Anal.
Calcd. for C42H32N10O4 (740.78): C, 68.10; H, 4.35; N, 18.91. Found: C, 68.16; H, 4.31; N,
18.94.
3.4.3. 3,3ꢀ-(1,3-Phenylene)bis(1-phenyl-6-(p-chlorobenzyl-7-oxo-1,2,4-triazolo[4,3-
b]triazine) (8c)
Beige crystals, m.p. 296–298°C (DMF), yield (1.80 g, 84%). 1H NMR (300 MHz, CDCl3):
δ 3.90 (s, 4H, 2CH2) and 7.40–8.26 (m, 22H). GC/MS (m/z): 749 (M+). Anal. Calcd. for
C40H26Cl2N10O2 (749.63): C, 64.09; H, 3.50; Cl, 9.46; N, 18.69. Found: C, 64.13; H, 3.52;
Cl, 9.42; N, 18.66.
3.4.4. 3,3ꢀ-(1,3-Phenylene)bis(1-phenyl-6-(p-methylbenzyl)-7-oxo-1,2,4-triazolo[4,3-
b]triazine) (8d)
Beige crystals, m.p. 268–270°C (DMF), yield (1.61 g, 79%). 1H NMR (300 MHz, CDCl3):
δ 2.22 (s, 6H, 2CH3), 4.17 (s, 4H, 2CH2) and 6.99–9.07 (m, 22H).13C NMR (75 MHz,
CDCl3): δ 22.3, 25.4, 122.3, 123.1, 127.0, 127.3, 128.3, 128.9, 129.2, 130.4, 131.3, 133.7,
134.8, 135.4, 141.3, 149.9, 153.4, 164.6. GC/MS (m/z): 708 (M+). Anal. Calcd. for
C42H32N10O2 (708.79): C, 71.17; H, 4.55; N, 19.76. Found: C, 71.21; H, 4.52; N, 19.79.

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3.4.5. 3,3ꢀ-(1,3-Phenylene)bis(1-phenyl-6-(3,4-dimethoxybenzyl)-7-oxo-1,2,4-triazolo
[4,3-b]triazine) (8e)
Beige crystals, m.p. 258–260°C (CH3CN), yield (2.02 g, 82%). IR (KBr) ν 1667 (CO) cm−1
1H NMR (300 MHz, CDCl3): δ 3.67 (s, 6H, 2CH3O), 3.73 (s, 4H, 2CH2), 4.12 (s, 4H, 2CH2)
and 6.67–9.11 (m, 22H). GC/MS (m/z): 800 (M+). Anal. Calcd. for C44H36N10O6 (800.84):
C, 65.99; H, 4.53; N, 17.49. Found: C, 66.02; H, 4.50; N, 17.46.
.
3.4.6. 3,3ꢀ-(1,3-Phenylene)bis(1-phenyl-6-(p-bromobenzyl)-7-oxo-1,2,4-
triazolo[4,3-b] triazine) (8f)
Beige crystals, m.p. 300–302°C (DMF), yield (1.95 g, 81%). 1H NMR (300 MHz, CDCl3):
δ 3.80 (s, 4H, 2CH2) and 7.30–8.20 (m, 22H). 13C NMR (75 MHz, CDCl3): δ 25.3, 120.1,
122.2, 122.4, 126.8, 128.7, 128.9, 129.5, 129.6, 129.9, 131.1, 131.5, 140.4, 146.0, 148.9, 152.0,
161.1. GC/MS (m/z): 838 (M+). Anal. Calcd. for C40H26Br2N10O2 (838.55): C, 57.30; H,
3.13; Br, 19.06; N, 16.70. Found: C, 57.36; H, 3.10; Br, 19.02; N, 16.72.
3.4.7. 3,3ꢀ-(1,3-Phenylene)bis(1-phenyl-6-(2,4-dichlorobenzyl)-7-oxo-1,2,4-
triazolo[4,3-b]triazine) (8g)
Beige crystals, m.p. 284–286°C (DMF), yield (2.02 g, 86%). 1H NMR (300 MHz, CDCl3):
δ 3.90 (s, 4H, 2CH2) and 7.23–8.26 (m, 20H). GC/MS (m/z): 818 (M+). Anal. Calcd. for
C40H24Cl4N10O2 (818.53): C, 58.70; H, 2.96; Cl, 17.33; N, 17.11. Found: C, 58.78; H, 2.92;
Cl, 17.30; N, 17.18.
3.5. Synthesis of 5,5ꢀ-(1,3-phenylene)bis[2-(5,5-dimethylcyclohexane-1,3-dione)-
3-phenyl-3H-[1,3,4]thiadiazole] (10)
To a solution of hydrazonoyl bromide 2 (1.15 g, 3.0 mmol) and N-phenyl 4,4-dimethyl-2,6-
dioxocyclohexane-thiocarboxamide 9 (1.7 g, 6.0 mmol) in chloroform (50 mL), triethyl
amine (2 mL) was added. The reaction mixture was refluxed for 6 h. The excess chloroform
was removed under reduced pressure and the residue was treated with ethanol (10 mL). The
resulting solid product was collected, washed with ethanol and crystallized from DMF to
give compound 10, as yellow crystals, m.p. 334–336°C, yield (1.94 g, 84%). IR (KBr) ν 1645
(CO) cm−1. 1H NMR (300 MHz, CDCl3): δ 1.07 (s, 12H, 4CH3), 2.38 (s, 8H, 4CH2) and
7.27–8.46 (m, 14H). 13C NMR (75 MHz, CDCl3): δ 26.9, 31.5, 53.2, 106.2, 120.4, 122.5,
122.6, 126.9, 128.2, 130.4, 131.5, 148.4, 155.2, 166.4, 191.3. GC/MS (m/z): 674 (M+). Anal.
Calcd. for C38H34N4O4S2 (674.71): C, 67.63; H, 5.08; N, 8.30; S, 9.50. Found: C, 67.69; H,
5.07; N, 8.28; S, 9.47.
Disclosure statement
No potential conflict of interest was reported by the authors.
References
[1] Shawali AS, Parkanyi C. Hydrazidoyl halides in the synthesis of heterocycles. J Heterocycl
Chem. 1980;17(5):833–854.
[2] Shawali AS. Reactions of hydrazidoyl halides with sulfer compounds. Heterocycles. 1983;
20(11):2239–2285.

10
H. M. HASSANEEN ET AL.
[3] Shawali AS. Reactions of heterocyclic compounds with nitrilimines and their precursors. Chem
Rev. 1993;93(8):2731–2777.
[4] Shawali AS, Abdallah, MA. The chemistry of heterocyclic hydrazonoyl halides. Adv Heterocycl
Chem. 1995;63:277–338.
[5] Shawali AS, Elsheikh SM. Annelated[1,2,4,5]tetrazines. J Heterocycl Chem. 2001;38(3):541–559.
[6] Shawali AS, Mosselhi MAN. Hydrazonoyl halides: useful building blocks for the synthesis of
arylazoheterocycles. J Heterocycl Chem. 2003;40(5):725–746.
[7] Shawali AS, Mosselhi MAN. The chemistry of thiohydrazonates and their utility in organic
synthesis. J Sulfur Chem. 2005;26(3):267–303.
[8] Shawali AS, Edrees MM. Reactions of nitrilimines with heterocyclic amines and enam-
ines. Convenient methodology for synthesis and annulation of heterocycles. Arkivoc.
2006;(ix):292–365.
[9] Shawali AS, Sherif MS. The chemistry of hydrazonates. Curr Org Chem. 2007;11:773–799.
[10] Shawali AS, Farghaly TA. Reactions of hydrazonoyl halides with heterocyclic thiones. Conve-
nient methodology for heteroannulation, synthesis of spiroheterocycles and heterocyclic ring
transformation. Arkivoc. 2008;(i):18–64.
[11] Shawali AS, Nevien AS. Hydrazonoyl halides: their versatile biological activities. Open Bioact
Compd J. 2009;2:8–16.
[12] Shawali AS. Tandem in situ generation and 1,5-electrocyclization of N-hetaryl nitrilimines. A
facile methodology for synthesis of annulated 1,2,4-triazoles and their acyclo C-nucleosides.
Arkivoc. 2010;(i):33–97.
[13] Shawali AS, Abdelhamid AO. Synthesis of spiro-heterocycles via 1,3-dipolar cycloadditions of
nitrilimines to exoheterocyclic enones. Site-, regio- and stereo-selectivities overview. Curr Org
Chem. 2012;16:2623–2651.
[14] Farag AM, Shawali AS, Algharib MS, et al. One-step synthesis of novel 2,2ꢀ-bi(4,5-
dihydro-1,3,4-thiadiazole) and 2,3-disubstituted 1,4-benzo-thiazine derivatives. Tetrahedron.
1994;50:5091–5098.
[15] Shawali AS, Farag AM, Albar HA, et al. Facile syntheses of bi-1,2,4-triazoles via hydrazonyl
halides. Tetrahedron. 1993;49:2761–2766.
[16] Shawali AS, Abed Nosrat M, Dawood KM, et al. 1,3-dipolar cycloaddition syntheses
of 3,3ꢀ-bi(2-pyrazolives), 3,3ꢀ-bipyrazoles and 3,3ꢀ-bi(1,2,4-triazoles). Gazzetta Chim Ital.
1993;123(8):467–470.
[17] Raafat M Shaker. Synthesis of 1,4-phenylene bridged bis-heterocyclic compounds. Arkivoc.
2012;(i):1–44.
[18] Kudari SM, Beede SM, Munera W. Synthesis and biological studies of bis-heterocycles. Asian J
Chem. 1997;9:20–26.
[19] Shawali AS, Sherif SM, El-Merzabani MM, Darwish MA. Synthesis and antitumor activity
of novel pyrazolylenaminone and bis(pyrazolyl)ketones via hydrazonoyl halides. J Heterocycl
Chem. 2009;46:548–551.
[20] Stille JK, Harris FW, Bedford MA. Phenyl substituted dipyrazoles: 1,3-dipole addition reactions
of sydnones and nitrilimines. J Heterocyclic Chem. 1966;3:155–157.
[21] Shawali AS. Chemoselectivity in 1,3-dipolar cycloaddition reactions of nitrilimines with
multifunctionalized dipolarophiles. Curr Org Chem. 2014;18:598–614.
[22] Hassaneen HM, Daboun HA, Abd El-hadi HA, et al. Site selectivity and rgiochem-
istry of nitrilimines. Cycloadditions to 1,3-diphenyl-2-thiono-4-imidazolidinone and its 5-
phenylmethylene derivatives. Phos Sulf Silicon. 1995;107:269–273.
[23] Dawood KM, Elwan N M. Synthesis of 3,3ꢀ-bipyrazole, 5,5ꢀ-bi-1,3,4-thia-diazole and fused
azole systems via bis-hydrazonoyl chlorides. J Chem Res. 2004;4:264–266.
[24] Abd-El-Rahman N M, Saleh TS, Mady MF. Ultrasound assisted synthesis of some new 1,3,4-
thiadiazole and bi(1,3,4-thiadiazole) derivatives incorporating pyrazolone moiety. Ultrason
Sonochem 2009;18:70–74.