The synthesis of some new sulfur-bearing various heterocyclic systems derived from asymmetrical N,N′-disubstituted thiourea derivatives

Article abstract of DOI:10.1080/10426500500366301

The heterocyclization of an asymmetrical N,N′-disubstituted thiourea (1a-d) in ring closure reactions with Br₂/AcOH, ethyl chloroacetate, diethyl oxalate, diethyl malonate, and hydrazine hydrate led to the direct formation of sulfur-bearing var

Full text of DOI:10.1080/10426500500366301

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Phosphorus, Sulfur, and Silicon
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The Synthesis of Some
New Sulfur-Bearing Various
Heterocyclic Systems Derived
from Asymmetrical N,N′-
Disubstituted Thiourea
Derivatives
Hosam Saad a
a Chemistry Department, Faculty of Science ,
Zagazig University , Zagazig, Egypt
Published online: 01 Feb 2007.
To cite this article: Hosam Saad (2006) The Synthesis of Some New Sulfur-Bearing
Various Heterocyclic Systems Derived from Asymmetrical N,N′-Disubstituted Thiourea
Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 181:7,
1557-1567, DOI: 10.1080/10426500500366301
To link to this article: http://dx.doi.org/10.1080/10426500500366301
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Phosphorus, Sulfur, and Silicon, 181:1557–1567, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500366301
The Synthesis of Some New Sulfur-Bearing Various
Heterocyclic Systems Derived from Asymmetrical
N,Nꢀ-Disubstituted Thiourea Derivatives
Hosam Saad
Chemistry Department, Faculty of Science, Zagazig University,
Zagazig, Egypt
The heterocyclization of an asymmetrical N,Nꢀ-disubstituted thiourea (1a–d) in
ring closure reactions with Br /AcOH, ethyl chloroacetate, diethyl oxalate, diethyl
2
malonate, and hydrazine hydrate led to the direct formation of sulfur-bearing vari-
ous heterocyclic systems (2–8) in which the thiaenolization is toward the aryl group.
The synthetic work and reactivity investigations have been well supported by stan-
1
13
dard modern spectroscopic techniques (IR, H NMR, C NMR, mass spectrum,
and microanalysis).
Keywords Asymmetrical N,Nꢀ-disubstituted thiourea; benzo[d]thiazole; thiazolidin-4-
one; thioxoimidazol-4,5-dione
INTRODUCTION
One of the major interests of sulfur-bearing asymmetrical disubstituted
thioureas is the design, synthesis, and biocidal evaluation of various
heterocyclic systems.1−4 In extension of our work in this area,5−7 the
principal objective of the present work is to propose further analogues of
disubstituted thioureas followed by ring closure reactions via treatment
with some reagents, which may enhance biocidal effects.
CHEMISTRY
Thioureas and substituted thiourea play an important role in the for-
mation of sulfur-containing and bearing various heterocyclic systems,
which have been a broad spectrum as biocidal effects for the treatment
of some diseases.8 Thus, the addition of the nitrogen nucleophile of p-
toluidine, α-naphthylamine, anthranilic acid, and 4-aminoantipyrine
Received June 20, 2005; accepted August 10, 2005.
Address correspondence to Hosam Saad, Zagazig University, Chemistry Department,
Faculty of Science, Zagazig, Egypt. E-mail: h saadzag@yahoo.com
1557

1558
H. Saad
to an electrophilic carbon of cyclohexyl isothiocyanate in dry dioxane
afforded the starting materials N,Nꢀ-disubstituted thioureas (1a–d).
The oxidation of compounds 1a–c via refluxing with Br2 in
acetic acid produced 2-cyclohexylamino-6-methylbenzo[d]thiazole (2),
2-cyclohexylaminonaphtho[2,1-d][1,3]thiazole (3), and 2-(cyclohexyla-
mino)-1,3-benzothiazole-4-carboxylic acid (4), respectively (Scheme 1).
SCHEME 1
On the other hand, ring closure reactions of asymmetrical N,Nꢀ-
disubstituted thiourea 1 were deduced from refluxing with oxygen
and nitrogen reagents.1 Thus, warming compound 1b with ethyl
chloroacetate and/or diethyl oxalate in basic media yielded 3-cyclohexyl-
2-(1-naphthylimino)-1,3-thiazolidin-4-one (5) and 1,3-disubstituted-2-
thioxoimidazol-4,5-dione (6), respectively.
Thiobarbituric acid derivatives and related compounds have been re-
ported for the treatment of some diseases.9,10 This encouraged us to syn-
thesize more of their derivatives via refluxing compound 1b with diethyl

Synthesis from N,Nꢀ-Disubstituted Thiorea Derivatives
1559
malonate in sodium ethoxide to furnish 1-cyclohexyl-3-(1-naphthyl)-2-
thioxodihydropyrimidine-4,6(1H,5H)-dione (7).
Among the full heterocyclization of compound 1d, on refluxing
with hydrazine hydrate (99%) in abs. ethanol resulted in cycliza-
tion affording 5-cyclohexylamino-2,3-dimethyl-1-phenyl-2,4-dihydro-
1H-pyrazolo[4,3-e][1,2,4]triazine (8) (Scheme 1). The formation of com-
pound 8 may be proceeded via the initial formation of a hydrazono
derivative followed by the loss of H2S, affording the final pyrazolotri-
azine derivative (Scheme 2).
SCHEME 2
The reactivity of the carboxylic group in the ortho position to
the thiourea moiety prompted us to synthesize 2-thioxoquinazolin-4-
one.11 Thus, refluxing compound 1c with sodium ethoxide produced 3-
cyclohexyl-2-mercaptoquinazolin-4(3H)-one (9). Compound 9 was used
as starting material for further functionalization and heterocyclization;
thus, the oxidation with I2 solution produced the disulphide 10. Also,
compound 9 was reacted with Br2 in glacial acetic acid to give 2-bromo-
3-cyclohexylquinazolin-4(3H)-one (11). The bromination of compound 9
may proceed through the formation of qunazoline-2-sulphonyl bromide,
which liberates SO2 to give the final product (Scheme 3).
The full fused heterocyclic system tetrazoloquinazoline 13 and/or 3-
thioxotriazoloquinazolinone 14 have been obtained from the hydrazi-
nolysis of compound 9 using hydrazine hydrate-ethanol to give the
hydrazono derivative 12 followed by diazodization using NaNO2/HCl
and/or worming with CS2-sodium ethoxide.
The cyclocondensation of the 2-hydrazino derivative 12 with ethyl
pyruvate afforded triazinoquinazoline 15 (Scheme 3).

1560
H. Saad
SCHEME 3
EXPERIMENTAL
All experiments were carried out using anhydrous solvents. M.p.s are
uncorrected. IR (KBr) was carried out on perkin–Elmer FTIR1600 spec-
trometer. 1H and 13C NMR (295K, internal reference TMS), was carried
out on Brucker AC–250 spectrometer, and mass spectra were recorded
on a gas chromatographic GCMSqp 1000ex Schimadzu instrument at
70 eV.
The Preparation of Asymmetrical N,Nꢀ-Disubstituted
Thioureas 1a–d: General Procedure
A mixture of cyclohexyl isothiocyanate (10 mmol) and appropriate pri-
mary amines, such as p-toluidine, α-naphthylamine, anthranilic acid,
and 4-aminoantipyrine (10 mmol), in dry dioxane (20 mL) were refluxed
for 2 h, cooled, and evaporated under vacuum. The solid obtained was
filtered off and crystallized from a suitable solvent.

Synthesis from N,Nꢀ-Disubstituted Thiorea Derivatives
1561
N-Cyclohexyl-Nꢀ-p-tolylthiourea (1a)
Crystallized with ethanol to give colorless crystals (86% yield); m.p. =
100–102◦C. IR (KBr): 1237 (NCSN), 1610 (C N), and (br) 3270 cm−1
1
(NH). H NMR: (DMSO-d6) δ = 1.07–2.05 (m, 10 H, cyclohexyl), 2.35
(s, 3H, CH3), 4.26 (m, 1H, N CH ), 5.92 (br, 1H, NH-cyclohexyl), 7.08
(d, J = 8.2 Hz, 2H, Ar-H), 7.22 (d, J = 8.2 Hz, 2H, Ar-H), 8.40 (s, 1H,
HN-aryl), 13C NMR (DMSO-d6): δ = 21.0, 24.7, 25.4, 32.5, 53.7 (CH3
and cyclohexyl), 125.1, 130.6, 133.6, 137.0 (Ar-C) and 178.9 (C S).
Calcd. for C14H20N2S (248.39): C, 67.70; H, 8.12; N, 11.28; S, 12.91.
Found: C, 67.64; H, 8.05; N, 11.24; S, 12.88.
N-Cyclohexyl-Nꢀ-1-naphthylthiourea (1b)
Crystallized with ethanol to give colorless crystals (80% yield);
m.p. = 136–138◦C. M+ = 284, base peak m/e = 143, IR (KBr): 1266
(NCSN), 1625 (C N), 3297 and 3367 cm−1 (2NH). 1H NMR: (DMSO-d6)
δ = 0.90–1.92 (m, 10 H, cyclohexyl), 4.24 (m, 1H, N CH ), 5.53 (br,
1H, NH-cyclohexyl), 7.28–8.01 (m, 7H, Ar-H), 8.50 (s, 1H, HN-aryl), 13
C
NMR (DMSO-d6): δ = 24.6, 25.2, 32.4, 53.9 (cyclohexyl), 122.7, 124.9,
125.8, 127.0, 127.2, 128.4, 128.7, 129.7, 131.8, 134.6 (Ar-C) and 179.8
(C S).
Calcd. for C17H20N2S (284.42): C, 71.79; H, 7.09; N, 9.85; S, 11.27.
Found: C, 71.68; H, 7.05; N, 9.84; S, 11.28.
N-Cyclohexyl-Nꢀ-(2-carboxyphenyl)-thiourea (1c)
Crystallized from ethanol to give colorless crystals (60% yield); m.p.
= 189–191◦C. IR (KBr): 1258 (NCSN), 1611 (C N), 1672 (C O) 3100,
3234 (2NH) and 3303 cm−1 (OH). 1H NMR: (DMSO-d6) δ = 1.12–1.92 (m,
10 H, cyclohexyl), 3.45 (m, 1H, N CH ), 6.48–8.41 (m, 4H, Ar-H), 8.63
(s, 1H, HN-cyclohexyl), 9.81 (s, 1H, HN-aryl), 13.70 (br, 1H, OH acid),
13C NMR: (DMSO-d6): δ = 24.6, 25.2, 30.4, 49.2 (cyclohexyl), 120.4,
120.9, 131.2, 131.7, 131.8, 140.5 (Ar-C), 167.6, 170.2 (C O and C S).
Calcd. for C14H18N2O2S (278.37): C, 60.41; H, 6.52; N, 10.06; S, 11.52.
Found: C, 60.37; H, 6.50; N, 10.00; S, 11.46.
N-Cyclohexyl-Nꢀ-(2,5-dihydro-2,3-dimethyl-5-oxo-1-phenyl-
1H-pyrazol-4-yl)thiourea (1d)
Crystallized from ethanol to give colorless crystals (70% yield); m.p. =
130–132◦C. M+ = 344, base peak m/e = 56, IR (KBr): 1248 (NCSN), 1615
1
(C N), 1715 (C O), 3103 and 3282 cm−1 (2NH). H NMR: (DMSO-d6)
δ = 1.13–1.91 (m, 10 H, cyclohexyl), 2.15 (s, 3H, CH3), 2.97 (s, 1H,

1562
H. Saad
NH-cyclohexyl), 3.06 (s, 3H, N CH3), 4.08 (m, 1H, N CH cyclohexyl),
7.29–7.49 (m, 5H, Ar-H), 8.12 (s, 1H, NH-aryl). 13C NMR: (DMSO-d6):
δ = 10.9, 24.4, 25.2, 32.0, 35.7, 52.9 (cyclohexyl, CH3, N-CH3), 109.0,
124.1, 126.4, 128.9, 135.4, 152.3 (Ar-C), 162.1, 181.8 (C O and C S).
Calcd. for C18H24N4OS (344.47): C, 62.76; H, 7.02; N, 16.26; S, 9.31.
Found: C, 62.70; H, 7.00; N, 16.22; S, 9.28.
The Cyclization of Asymmetrical N,Nꢀ-Disubstituted
Thioureas 2, 3, and 4: General Procedure
Appropriate asymmetrical N,Nꢀ-disubstituted thioureas (10 mmol)
were dissolved in glacial acetic acid (20 mL); and Br2 was added
(10 mmol) and the mixture was stirred for 3 h. The color of Br2 dis-
appeared, and a colorless precipitate was formed, which was filtered off
and crystallized from a proper solvent.
2-Cyclohexylamino-6-methylbenzo[d]thiazole (2)
Crystallized from DMF to give colorless crystals (85% yield); m.p. =
173–175◦C. M+ = 246, base peak m/e = 164, IR (KBr): 3172 cm−1 (NH).
1H NMR: (DMSO-d6) δ = 1.23–2.09 (m, 10 H, cyclohexyl), 2.10 (s, 3H,
CH3), 4.43 (m, 1H, N CH), 7.31 (d, J = 8.2 Hz, 1H, Ar-H), 7.44 (s, 1H,
Ar-H), 7.50 (d, J = 8.4 Hz, 1H, Ar-H), 9.90 (br, 1H, NH). 13C NMR:
(DMSO-d6): δ = 21.0, 21.3, 24.8, 31.9, 56.1 (cyclohexyl, CH3), 114.7,
121.6, 122.5, 128.4, 129.6, 135.2, 176.5 (Ar-C and C N).
Calcd. for C14H18N2S (246.37): C, 68.25; H, 7.36; N, 11.37; S, 13.01.
Found: C, 68.21; H, 7.35; N, 11.33; S, 12.95.
2-Cyclohexylaminonaphtho[2,1-d][1,3]thiazole (3)
Crystallized from DMF to give colorless crystals (88% yield); m.p. =
165–167◦C. IR (KBr): 3218 cm−1 (NH). 1H NMR: (DMSO-d6) δ = 1.34–
2.13 (m, 10H, cyclohexyl), 3.85 (m, 1H, N CH), 7.61–8.26 (m, 6H, Ar-
H), 8.47 (br, 1H, NH). 13C NMR: (DMSO-d6): δ = 23.9, 24.7, 31.6, 57.1,
(cyclohexyl), 118.4, 121.8, 122.4, 122.9, 127.8, 128.2, 128.4, 130.4, 131.8,
133.6, 172.7 (Ar-C and C N).
Calcd. for C17H18N2S (282.40): C, 72.30; H, 6.42; N, 9.92; S, 11.35
Found: C, 72.26; H, 6.38; N, 9.88; S, 11.31.
2-(Cyclohexylamino)-1,3-benzothiazole-4-carboxylic Acid (4)
Crystallized from DMF to give colorless crystals (83% yield); m.p. =
220–222◦C. IR (KBr): 1698 (C O), 3359 (NH), 3468 cm−1 (OH). 1H

Synthesis from N,Nꢀ-Disubstituted Thiorea Derivatives
1563
NMR: (DMSO-d6) δ = 1.26–1.95 (m, 10 H, cyclohexyl), 3.58 (m, 1H,
N CH), 7.03 (d, J = 8.9, 1H, Ar-H), 7.49 (d, J = 8.9, 1H, Ar-H), 7.70 (m,
1H, ArH), 7.89 (s, 1H, NH), 12.10 (s, 1H, OH), 13C NMR: (DMSO-d6): δ
= 23.9, 24.7, 31.6, 57.1, (cyclohexyl), 104.8, 110.5, 113.2, 132.9, 138.2,
146.9 (Ar-C), 167.8, 171.7 (C N and C O).
Calcd. for C14H16N2O2S (276.35): C, 60.85; H, 5.84; N, 10.14; S, 11.60.
Found: C, 60.81; H, 5.80; N, 10.12; S, 11.53.
3-Cyclohexyl-2-(1-naphthylimino)-1,3-thiazolidin-4-one (5)
To a mixture of 1b (10 mmol) and sodium ethoxide (prepared by dissolv-
ing 0.23 g of sodium metal in 20 mL of abs. ethanol), ethyl chloroacetate
(10 mmol) was added, and the reaction mixture was refluxed for 4 h,
diluted with water, and acidified. The solid thus separated was filtered
and crystallized from ethanol to give colorless crystals (76% yield); m.p.
= 210–212◦C. M+ = 324, base peak m/e = 163, IR (KBr): 1676 cm−1
1
(CO). H NMR: (DMSO-d6) δ = 1.15–1.93 (m, 10 H, cyclohexyl), 4.15
(m, 1H, N CH cyclohexyl), 4.39 (s, 2H, CH2), 6.99–7.91 (m, 7H, Ar-
H), 13C NMR: (DMSO-d6): δ = 24.2, 24.4, 31.9, 52.5, 61.9, (cyclohexyl,
CH2), 117.7, 121.4, 122.7, 122.9, 124.7, 125.4, 128.0, 128.4, 133.8, 134.9,
(Ar-C), 179.5, 181.1 (C N and C O).
Calcd. for C19H20N2OS (324.44): C, 70.34; H, 6.21; N, 8.63; S, 9.88.
Found: C, 70.29; H, 6.18; N, 8.58; S, 9.84.
1-Cyclohexyl-3-(1-naphthyl)-2-thioxoimidazolidin-4,5-dione (6)
To a mixture of 1b (10 mmol) and sodium ethoxide (prepared by dis-
solving 0.23 g of sodium metal in 20 mL of abs. ethanol), diethyl oxalate
(10 mmol) was added, and the reaction mixture was refluxed for 4 h,
diluted with water, and acidified with hydrochloric acid (3 mL, 60%).
The solid thus separated was filtered and crystallized from ethanol to
give colorless crystals (76% yield); m.p. = 115–117◦C. IR (KBr): 1447
(C S), 1660, 1670 cm−1 (2CO). 1H NMR: (DMSO-d6)δ = 1.06–1.88 (m,
10 H, cyclohexyl), 3.56 (m, 1H, N CH cyclohexyl), 7.34–8.54 (m, 7H,
Ar H), 13C NMR: (DMSO-d6): δ = 24.2, 25.2, 32.9, 47.6, (cyclohexyl),
115.7, 121.2, 121.6, 125.2, 125.3, 125.6, 125.8, 125.9, 126.0, 133.6, 153.3,
154.6, 181.8 (Ar C, 2C O, and C S).
Calcd. for C19H18N2O2S (338.42): C, 67.43; H, 5.36; N, 8.28; S, 9.47.
Found: C, 67.38; H, 5.35; N, 8.26; S, 9.46.
1-Cyclohexyl-3-(1-naphthyl)-2-thioxodihydropyrimidine-
4,6(1H,5H)-dione (7)
To a mixture of 1b (10 mmol) and sodium ethoxide (prepared by dissolv-
ing 0.23 g of sodium metal in 20 mL of abs. ethanol), diethyl malonate

1564
H. Saad
(10 mmol) was added, and the reaction mixture was refluxed for 4 h,
diluted with water, and acidified with hydrochloric acid (3 mL, 60%).
The solid thus separated was filtered and crystallized from ethanol
to give colorless crystals (76% yield); m.p. = 138–140◦C. IR (KBr):
1
1490 (C S), 1660, 1670 cm−1 (2CO). H NMR: (DMSO-d6): δ = 0.90–
1.96 (m, 10 H, cyclohexyl), 4.26 (m, 1H, N CH cyclohexyl), 5.53 (s, 2H,
CH2), 7.27–8.33 (m, 7H, Ar H), 13C NMR: (DMSO-d6): δ = 24.6, 24.7,
25.2, 32.4, 32.6, (cyclohexyl, CH2), 122.7, 125.0, 125.7, 127.0, 127.3,
128.4, 128.5, 128.8, 129.7, 131.7, 134.6, 179.7, 179.8 (Ar C, 2C O, and
C S).
Calcd. for C20H20N2O2S (352.45): C, 68.16; H, 5.72; N, 7.95; S, 9.10.
Found: C, 68.14; H, 5.70; N, 7.95; S, 9.07.
5-Cyclohexylamino-2,3-dimethyl-1-phenyl-2,4-dihydro-
1H-pyrazolo[4,3-e][1,2,4]triazine (8)
A mixture of 1d (10 mmol) and hydrazine hydrate (15 mmol) in ethanol
(20 mL) was refluxed for 2 h. The precipitate obtained upon cooling
was collected and crystallized from ethanol to give colorless crystals
(63% yield); m.p. = 240–242◦C. IR (KBr): 3103 and 3281 cm−1 (2NH).
1H NMR: (DMSO-d6) δ = 1.12–1.98 (m, 10 H, cyclohexyl), 2.15 (s, 3H,
CH3), 3.06 (s, 3H, N CH3), 4.09 (m, 1H, NH CH), 7.15–7.67 (m, 5H,
Ar H), 8.12 (br, 2H, 2NH). 13C NMR: (DMSO-d6): δ = 10.9, 24.4, 25.2,
32.0, 35.7, 52.9 (cyclohexyl, CH3, N CH3), 109.1, 124.1, 126.4, 128.9,
135.4, 152.3, 162.1, 181.8 (Ar C and 2C N).
Calcd. for C18H24N6 (324.42): C, 66.64; H, 7.46; N, 25.90. Found: C,
66.59; H, 7.44; N, 25.87.
3-Cyclohexyl-2-mercaptoquinazolin-4(3H)-one (9)
A mixture of appropriate 1c (10 mmol) and (10 mmol) sodium ethox-
ide (prepared by dissolving 0.23 g of sodium metal in 20 mL of abs.
ethanol) was heated under reflux for 30 min. The precipitate formed
after cooling and acidification with hydrochloric acid (3 mL, 60%)
was collected and crystallized from ethanol to give colorless crys-
tals (72% yield); m.p. = 220–222◦C. IR (KBr): 1670 (CO), 2580 cm−1
1
(SH). H NMR: (DMSO-d6) δ = 1.08–2.46 (m, 10H, cyclohexyl), 3.50
(s, 1H, SH), 4.75 (m, 1H, N CH of cyclohexyl), 7.15–7.90 (m, 4H,
Ar H), 13C NMR (DMSO-d6): δ = 25.1, 26.0, 28.5, 52.9 (cyclohexyl),
114.3, 114.7, 122.2, 127.4, 134.6, 139.5, 150.2, 162.3 (Ar C, C N, and
C O).
Calcd. for C14H16N2OS (260.35): C, 64.58; H, 6.19; N, 10.76; S, 12.32.
Found: C, 64.55; H, 6.18; N, 10.73; S, 12.30.

Synthesis from N,Nꢀ-Disubstituted Thiorea Derivatives
1565
Bis[3-cyclohexylquinazolin-4(3H)-one]-2-disulphide (10)
To a solution of 9 (10 mmol) in acetic acid (20 mL), iodine (10 mmol,
0.25 g in 10 mL of acetic acid) was added portionwise with stirring; the
solid formed was collected by filtration and crystallized from ethanol
to give yellow crystals (66% yield); m.p. = 263–265◦C. M+ = 518, base
peak m/e = 280, IR (KBr): 1638 (N C), 1680, 1690 cm−1 (2CO). 1H NMR:
(DMSO-d6) δ = 1.09–2.46 (m, 20H, 2cyclohexyl), 4.74 (m, 2H, N CH of
cyclohexyls), 7.14–7.90 (m, 8H, of 2Ar H).
Calcd. for C28H30N4O2S2 (518.69): C, 64.84; H, 5.83; N, 10.80; S,
12.36. Found: C, 64.82; H, 5.81; N, 10.79; S, 12.35.
2-Bromo-3-cyclohexylquinazolin-4(3H)-one (11)
To a solution of 9 (10 mmol) in acetic acid (20 mL), bromine (10 mmol,
0.16 g in 10 mL of acetic acid) was added portionwise with stirring; the
solid formed was collected by filtration and crystallized from ethanol
to give colorless crystals (83% yield); m.p. = 248–250◦C. M+2 = 309,
base peak m/e = 163, IR (KBr): 1643 (N C), 1718 cm−1 (CO). 1H NMR
(DMSO-d6): δ = 1.28–2.11 (m, 10H, cyclohexyl), 3.38 (m, H, N CH of
cyclohexyl), 7.14–7.90 (m, 4H, Ar H).
Calcd. for C14H15BrN2O (307.19): C, 54.74; H, 4.92; Br, 26.01; N, 9.12.
Found: C, 54.72; H, 4.90; Br, 26.00; N, 9.09.
3-Cyclohexyl-2-hydrazono-2,3-dihydroquinazolin-4(1H)-one
(12)
A mixture of 9 (10 mmol) and hydrazine hydrate 99% (10 mmol) in
ethanol (30 mL) was refluxed for 3 h. The solid thus separated after
cooling was collected by filtration and crystallized from ethanol to give
colorless crystals (64% yield); m.p. = 268–270◦C. IR (KBr): 1639 (C N),
1
1715 (CO), 3132, 3220, 3286 cm−1 (NH and NH2). H NMR: (DMSO-
d6) δ = 1.10–2.51 (m, 10H, cyclohexyl), 3.38 (s, 2H, NH2), 4.74 (m, 1H,
N CH of cyclohexyl), 7.15–7.88 (m, 4H, Ar H), 11.31 (br, 1H, NH).
Calcd. for C14H18N4O (258.32): C, 65.09; H, 7.02; N, 21.69. Found: C,
65.05; H, 7.00; N, 21.65.
4-Cyclohexyltetrazolo[1,5-a]quinazolin-5(4H)-one (13)
An aqueous solution of sodium nitrite (0.19 g, 2.79 mmol) in dis-
tilled water (2 mL) was added to a solution of 12 (10 mmol) in dis-
tilled water (5 mL) with stirring in an ice bath. On addition of glacial
acetic acid (0.29 mL, 5.16 mmol) the solution turned dark red, and the

1566
H. Saad
solid started to precipitate. Another molar equivalent of sodium nitrite
(0.19 g, 2.79 mmol in 3 mL water) was added. The solid was filtered off,
washed with water, and dried under vacuum to give a light orange solid,
which crystallized from ethanol (10 mL), (60% yield); m.p. = 255–257◦C.
M+ = 269, base peak m/e = 143, IR (KBr): 1639 (C N), 1685 cm−1 (CO).
1H NMR: (DMSO-d6) δ = 1.16–2.52 (m, 10H, cyclohexyl), 4.73 (m, 1H,
N CH of cyclohexyl), 7.15–7.88 (m, 4H, Ar H).
Calcd. for C14H15N5O (269.30): C, 62.44; H, 5.61; N, 26.01. Found: C,
62.40; H, 5.58; N, 25.97.
4-Cyclohexyl-1,2-dihydro-1-thioxo-[1,2,4]triazolo
[4,3-a]quinazolin-5(4H)-one (14)
To a solution of potassium hydroxide (10%, 30 mL in ethanol), compound
12 (10 mmol) and carbon disulphide (10 mL) were added, and the re-
action mixture was refluxed for 4 h, cooled, and poured into crushed
ice-HCl (3 mL, 60%). The solid obtained was filtered off and crystal-
lized from ethanol to give 14 (64% yield); m.p. = 234–236◦C. IR (KBr):
1
1540 (C S), 1638 (C N), 1685 (CO), and 3220 cm−1 (NH). H NMR:
(DMSO-d6) δ = 1.09–2.46 (m, 10H, cyclohexyl), 3.27 (s, 2H, NH2), 4.74
(m, 1H, N CH of cyclohexyl), 7.15–7.88 (m, 4H, Ar-H), 11.32 (br, 1H,
NH).
Calcd. for C15H16N4OS (300.38): C, 59.98; H, 5.37; N, 18.65; S, 10.67.
Found: C, 59.96; H, 5.35; N, 18.61; S, 10.62.
5-Cyclohexyl-2-methyl-1H-[1,2,4]triazino[4,3-a]
quinazoline-1,6(5H)-dione (15)
A mixture of 12 (10 mmol) and ethyl pyruvate (10 mmol) in sodium
ethoxide (20 mmol Na in 50 mL of abs. ethanol) was heated under reflux
for 2 h, cooled, and poured into crushed ice. The solid obtained was
filtered off and crystallized from ethanol (10 mL), (60 % yield); m.p. =
265–267◦C. M+ = 310, base peak m/e = 275, IR (KBr): 1638 (C N),
1685 and 1699 cm−1 (2CO). 1H NMR: (DMSO-d6)δ = 1.16–2.51 (m, 10H,
cyclohexyl), 3.39 (s, 3H, CH3), 4.73 (m, 1H, N CH of cyclohexyl), 7.14–
7.90 (m, 4H, Ar H).
Calcd. for C17H18N4O2 (310.35): C, 65.79; H, 5.85; N, 18.05. Found:
C, 65.74; H, 5.80; N, 18.02.
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Synthesis from N,Nꢀ-Disubstituted Thiorea Derivatives
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