A convenient and efficient conversion of 4-aminobenzophenone into some new 1,2,3-triazole and benzothiazole derivatives

Article abstract of DOI:10.1002/jccs.200500023

Several heterocyclic systems such as 1,2,3-triazoles (5-9), pyrimidotriazoles (10-13), benzothiazole (16), thiazolo (17), andpyrimidinone derivative (18) was obtained from 4-aminobenzophenone (1) and the appropriatere agents.

Full text of DOI:10.1002/jccs.200500023

Journal of the Chinese Chemical Society, 2005, 52, 149-153
149
A Convenient and Efficient Conversion of 4-Aminobenzophenone into
some new 1,2,3-Triazole and Benzothiazole Derivatives
Eman M. Kamel,a Ragaa A. Ahmadb and Osama S. Moustafab*
aNational Research Center, Dokki, Cairo, Egypt
bChemistry Department, Faculty of Science, Assiut University, Assiut, 71516, Egypt
Several heterocyclic systems such as 1,2,3-triazoles (5-9), pyrimidotriazoles (10-13), benzothiazole (16),
thiazolo (17), and pyrimidinone derivative (18) was obtained from 4-aminobenzophenone (1) and the appro-
priate reagents.
Keywords: Synthesis; 1,2,3-Triazole; 1,3,4-Triazole and benzothiazole.
INTRODUCTION
A wide variety of benzothiazole and triazole deriva-
compound 5 was achieved with abs.ethanol and catalyzed by
conc. H2SO4 to afford the corresponding ethyl ester 6
(Scheme I).
tives have been developed as anticancer agents1-6 and flavone
(egquercetin) and isoflavone (genistien) isosteres to inhibit
PTK enzymes7 Tricyclazole is a well known fungicide for the
control of Piricularia oryzae in the prevention of rice blast8
furthermore, new 1,3,4-triazole derivatives have been re-
ported as potential anticonvulsants9 and anti-inflammatory
and analgesic agents.10 Taking all the above benefits into con-
sideration and in continuation of our work on the synthesis of
many fused heterocyclic systems11-17 we investigate the use
of 4-aminobenzophenone for the synthesis of these fused
heterocyclic systems with the aim of investigating their anti-
microbial activities.
Scheme I
Also, the azide 4 was reacted with active nitriles,
namely p-nitrobenzylcyanide and malonodinitrile in sodium
ethoxide to produce 4-amino-1-[4¢-benzophenone]-5-p-niro-
phenyl-1,2,3-triazole 7 and 4-amino-1-[4¢-benzophenone]-
5-cyano-1,2,3-triazole 8. Compound 8 was reacted with eth-
ylene diamine to give imidazoyl-1,2,3-triazole derivative 9
which was cyclized to 9-[4¢-benzophenone]-imidazopyr-
imidotriazole 10 through reaction with triethyl orthoformate.
The cyano compound 8 was cyclized to pyrimidotriazoles
11-13 on treatment with formamide, CS2 in alc. KOH and/or
phenyl isothiocyanate in pyridine, respectively (Scheme II).
4-Benzoyl-anilinehydrochloride 14 was prepared from
4-aminobenzophenone 1 by boiling with conc. HCl, and this
RESULTS AND DISCUSSION
Diazotization of 4-aminobenzophenone 1 by nitrous
acid at 0-5 °C led to the formation of 4-benzoylphenyldi-
azonium chloride 2, which when coupled with b-naphthol
yielded 4-benzoylphenylazo-b-naphthol 3. Reaction of the
diazonium salt 2 with sodium azide produced 4-azidobenzo-
phenone 4. It was reported that the azide compound can be
cyclized using ethyl acetoacetate to furnish 1,2,3-triazole de-
rivative.18,19 In a similar fashion azide compound 4 was
cyclized with ethyl acetoacetate in the presence of sodium
ethoxide to afford 5-methyl-1-[4¢-benzophenone]-1,2,3-tri-
azole-4-carboxylic acid 5. Esterification of the carboxylic
* Corresponding author. E-mail: oshmous@acc.aun.edu.eg

150 J. Chin. Chem. Soc., Vol. 52, No. 1, 2005
Kamel et al.
Scheme II
NH
NH2
N
N
N
N
N
N
Ph
NO2
N
N
N
N
S
7 R
N
R
N
R
N
H
NO2
N
13
HC(OEt )3
EOtNa
10
PhNCS
Pyr.
NH2
CH2CN
N3
NH2
N
N
NH2
N
NH2
CS2
CH2 (CN)2
EtONa
N
N
N
R
8
CN
N
R
N
H
COPh
9
CS2 / KOH
4
HCONH2
H
N
S
N
N
N
N
N
NH
N
N
R
N
R
S
NH2
12
11
COPh
R =
was reacted with potassium thiocyanate to give p-thioureido-
benzophenone 15. The latter compound in acetic acid solu-
tion was brominated and cyclized to 2-amino-6-benzoyl-
benzothiazole hydrobromide 16 on treatment with bromine
(Scheme III).
Scheme IV
O
O
NH
HN
S
ClCH2COOEt
CH3COONa
malonic acid
CH3COCl
O
S
15
N
N
Scheme III
COPh
18
COPh
17
S
NH2.HCl
NHCNH2
NH2
HCl conc.
KSCN
EXPERIMENTAL
Br2 / ACOH
COPh
1
COPh
14
COPh
15
Melting points were determined on a Gallen Kamp
melting point apparatus and were uncorrected. IR spectra
were recorded on a Pye-Unicam SP3-100 spectrophotometer
using KBr wafer technique. 1H NMR spectra were recorded
on a 90 MHz Varian EM-390 NMR spectrometer in a suitable
deutreated solvent (TMS) as the internal standard. Elemental
analyses were determined on a Perkin-Elmer 240 C micro-
analyzer, and all compounds gave results in an acceptable
range. Melting points, yields and spectroscopic data of com-
pounds 2-18 are listed in Tables 1 and 2.
N
NH2.HBr
S
PhOC
16
Thioureido compound 15 was cyclized to thiazolo de-
rivative 17 and/or to pyrimidinone derivative 18 through re-
actions with ethyl chloroacetate in the presence of fused so-
dium acetate and/or with malonic acid in the presence of
acetylchloride, respectively (Scheme IV).

4-Aminobenzophenone Coverts into Azole Derivatives
J. Chin. Chem. Soc., Vol. 52, No. 1, 2005 151
Table 1. Physical constants of compounds 2-18
Comp.
No
M.P °C
(Yield %)
Formula
Mol.Wt
Comp.
No
M.P °C
(Yield %)
Formula
Mol.Wt
2
-
C13H9N2OCl
244.5
C23H16N2O2
352
C13H9N3O
223
C17H13N3O3
307
C19H17N3O3
335
C21H15N5O3
385
C16H11N5O
289
C18H16N6O
332
11
12
13
14
15
16
17
18
> 300
(68-71)
> 310
(63-65)
165
(70-72)
182
(66-69)
120
(65-70)
161
(69-71)
202
(65-68)
210
(68-70)
C17H12N6O
316
C17H11N5OS2
365
C23H16N6OS
424
C13H12NOCl
233.5
C14H12N2OS
256
C14H11N2OSBr
335
C16H12N2O2S
296
C17H12N2O3S
324
3
230
(80-83)
135*
(83-85)
192
(76-80)
142
(75-76)
> 300
(84-88)
235
4
5
6
7
8
(90-92)
143
(77-78)
230
9
10
C19H14N6O
342
(61-65)
*: decomposition.
Table 2. Spectral data of compounds 3-18
Comp. No
IR (n cm -1) / 1HNMR (d ppm)
3
1670 (N=N), 1660 (C=O), 1590 (C=N); (DMSO-d6): d 7.2-8.0 (m, 15H, Ar-H), 10.2 (s,
1H, OH).
4
5
2230 (azide N3), 1660 (C=O); (DMSO-d6): d 7.2-8.1 (m, 9H, Ar-H).
3450-3500 (acid, OH), 2980 (CH-alph.), 1700, 1650 (C=O); (DMSO-d6): d 2.3 (s, 3H,
CH3), 7.4-8.00 (m, 9H, Ar-H), 10.5 (s, 1H, OH).
6
2980 (CH-alph.), 1720, 1650 (C=O); (CDCl3): d 1.35 (t, 3H, CH3), 2.45 (s, 3H, CH3
triazole), 4.2 (q, 2H, CH2), 7.4-8.2 (m, 9H, Ar-H).
7
3300, 3200 (NH2), 1650 (C=O); (DMSO-d6): d 7.22 (s, 2H, NH2 disappeared by D2O),
7.3-8.1 (m, 13H, Ar-H).
8
3300, 3200 (NH2), 2220 (CN), 1640 (C=O), 1590 (C=N); (DMSO-d6): d 7.2 (s, 2H,
NH2 disappeared by D2O), 7.4-8.0 (m, 13H, Ar-H).
9
3400, 3300, 3200 (NH, NH2), 1650 (C=O); (DMSO-d6): d 4.1 (s, 4H, 2CH2), 7.15 (s,
2H, NH2 disappeared by D2O), 7.2-7.9 (m, 9H, Ar-H), 10.1 (s, 1H, NH).
1695 (C=O), 1610 (C=N); (CF3COOD): d 4.24 (s, 4H, 2CH2), 7.3-8.1 (m, 9H, Ar-H),
10.1 (s, 1H, CH).
3340, 3240 (NH2), 1665 (C=O), 1600 (C=N); (DMSO-d6): d 7.1 (s, 2H, NH2 cancelled
by D2O), 7.5-8.4 (m, 9H, Ar-H), 9.9 (s, 1H, CH).
10
11
12
13
3200-3420 (NH), 1665 (C=O), 1210 (C=S); (CF3COOD): d 7.5-8.4 (m, 9H, Ar-H).
3200 (NH), 1665 (C=O), 1210 (C=S); (DMSO-d6): d 7.5-8.4 (m, 9H, Ar-H), 9.9 (s, 1H,
NH).
14
15
3450-3500 (b, acid, NH2), 1660 (C=O).
3400, 3200 (NH, NH2), 1660 (C=O), 1220 (C=S); (DMSO-d6): d 7.35-8.15 (m, 9H, Ar-
H), 9.55 (s, 1H, NH).
16
17
18
3450, 3310 (b, acid, NH2), 1645 (C=O), 1610 (C=N); (DMSO-d6): d 7.2-8.1 (m, 8H,
Ar-H).
3280-3120 (NH), 1720, 1650 (2C=O), 1620 (C=N); (DMSO-d6): d 4.15 (s, 2H, CH2),
7.1-8.1 (m, 9H, Ar-H), 10.2 (s, H, NH).
3220-3100 (NH), 1710, 1645 (C=O); (DMSO-d6): d 4.25 (s, 2H, CH2), 7.2-8.1 (m, 9H,
Ar-H), 9.75 (s, H, NH).

152 J. Chin. Chem. Soc., Vol. 52, No. 1, 2005
Kamel et al.
Synthesis of 4-Benzoyl-phenyldiazonium chloride (2) &
Synthesis of 4-benzoyl-phenylazo-b-naphthol (3)
Synthesis of 4-Amino-1-[4¢-benzophenone]-5-(amidazol-
2-yl)-4²,5²-dihydro-1,2,3-triazole (9)
The title compounds were prepared by treatment of
4-aminobenzophenone 1 (0.015 mol) with hydrochloric acid
(25 mL) while adding dropwise sodium nitrite solution at 0-5
°C and stirring for one hour (afforded the diazonium chloride
2); b-naphthol (0.015 mol) was added to the latter diazonium
salt. An orange solid product was collected.
To a mixture of 8 (0.01 mol) and ethylenediamine (10
mL) was added dropwise CS2 (1 mL). The resulting reaction
mixture was heated on a steam bath for 3 hr. The cold reaction
mixture was poured into cold water and left to stand for 2 hr.
The greenish needles solid precipitate was filtered and re-
crystallized from ethanol.
Synthesis of p-Azidobenzophenone (4)
Synthesis of 9-[4¢-Benzophenone]-imidazopyrimido-2,4,5-
trihydro-1,2,3-triazole (10)
To a cooled stirred solution of diazonium chloride 2
was added a solution of sodium azide (25 mL, 10%) for 30
min, and the resulting solid was filtered and recrystallized
from ethanol as yellow crystals.
To a mixture of 9 (0.01 mol) and triethyl orthoformate
(10 mL) a few drops of acetic acid were added. The reaction
mixture was heated under reflux for 4 hr. The solid product
thus formed on heating was filtered and recrystallized from
acetic acid as pale yellow crystals.
Synthesis of 5-Methyl-1-[4¢-benzophenone]-1,2,3-triazole-
4-carboxylic acid (5)
A mixture of azide 4 (0.1 mol), ethyl acetoacetate (0.1
mol) in absolute ethanol (40 mL), and sodium ethoxide solu-
tion (20 mL) was refluxed for 4 hr; the white solid which
formed on heating was filtered and recrystalized from etha-
nol.
Synthesis of 5-[4¢-Benzophenone]-4-amino-(2H)-
pyrimido[4,5-d]-1,2,3-triazole (11)
A solution of 8 (0.5 g) in formamide (10 mL) was
refluxed for 2 hr, then allowed to cool; the yellow precipitate
was filtered and recrystallized from ethanol.
Synthesis of Ethyl(5-methyl-1-[4¢-benzophenone]-1,2,3-
triazole)-4-carboxylate (6)
Synthesis of 5-[4¢-Benzophenone]-2,4-dimercapto-(1,3H)-
pyrimido[4,5-d]-1,2,3-triazole (12)
The esterification of 5 was achieved with abs ethanol. A
mixture of 5 (0.1 mol) in abs ethanol (40 mL) and concen-
trated sulfuric acid (5 mL) was refluxed gently for 3 hr, then
cooled to room temperature. A white solid was obtained and
filtered and recrystalized from ethanol.
A mixture of 8 (0.01 mol) and carbon disulfide (8 mL)
in KOH (30 mL, 20%) was refluxed on a steam bath for 5 hr,
then allowed to cool. The solid product thus formed on neu-
tralization by acetic acid was recrystallized from ethanol as
yellow crystals.
Synthesis of 4-Amino-1-[4¢-benzophenone]-5-p-niro-
phenyl-1,2,3-triazole (7)
Synthesis of 7-[4¢-Benzophenone]-3-mercapto-2-phenyl-
4-emino(1,3H)-pyrimido[4,5-d]-1,2,3-triazole (13)
To a solution of 8 (0.01 mol) in pyridine (20 mL) added
phenyl isothiocyanate (0.01 mol) and the mixture was re-
fluxed for 4 hr. After cooling, the solid product was recrystal-
lized from ethanol as buff crystals.
Sodium ethoxide solution (20 mL) was added dropwise
to a stirred solution from a mixture of azide 4 (0.1 mol) and
p-nitrobenzyl cyanide (0.1 mol) in absolute ethanol (20 mL)
over 10 min. at room temperature. The gray solid quickly pre-
cipitated and was filtered and recrystallized from ethanol.
Synthesis of 4-Benzoyl-anilinehydrochloride (14)
A solution of 4-aminobenzophenone 1 (1 g) in conc.
HCl (10 mL) was refluxed for one hour, then allowed to cool;
the white solid product was filtered and dried in air.
Synthesis of 4-Amino-1-[4¢-benzophenone]-5-cyano-1,2,3-
triazole (8)
Sodium ethoxide solution (20 mL) was added dropwise
to a stirred solution contaning azide 4 (0.1 mol) and
malonodinitrile (0.1 mol) in absolute ethanol (25 mL) over 10
min. at room temperature. The buff solid quickly precipitated
and was filtered and recrystallized from ethanol.
Synthesis of p-thioureidobenzophenone (15)
Potassium thiocyanate soultion (0.01 mol in 10 mL of
H2O) was added dropwise to a stirred solution of 14 (0.01

4-Aminobenzophenone Coverts into Azole Derivatives
J. Chin. Chem. Soc., Vol. 52, No. 1, 2005 153
Westwell, A. D.; Stevens, M. F. G. Bioorg. Med. Chem. Lett.
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mol) over 10 min. at room temperature. The deep yellow pre-
cipitate was filtered and recrystallized from ethanol.
2. Kashiyama, E.; Hutchinson, I.; Chua, M. S.; Stinson, S. F.;
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Synthesis of 2-Amino-6-benzoylbenzothiazole hydrobro-
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To a solution of thioureido 15 (0.01 mol) in acetic acid
(25 mL) was added dropwise bromine solution (0.01 mol) at
room temperature with stirring for half an hour. The resulting
solid was filtered and recrystallized from ethanol as yellow-
ish needles crystals.
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Synthesis of 2-[4¢-Aminobenzophenone]-(3,5H)-1,3-
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A mixture of 15 (0.01 mol) and ethyl chloroacetate
(0.01 mol) added (1 g) of fused sodium acetate; the resulting
reaction mixture was refluxed for 3 hr. The cold reaction mix-
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A mixture of thioureido 15 (0.015 mol) and malonic
acid (0.015 mol) in CH3COCl (15 mL) was refluxed for 3 hr.
The reaction mixture was cooled, poured into ice and neutral-
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