European

Journal of Chemistry 3 (3) (2012) 322‐331

European Journal of Chemistry

Journal homepage: www.eurjchem.com

Synthesis of 5‐arylazothiazoles, pyridines and

thieno[2,3‐b]pyridines derivatives containing 1,2,3‐triazole moiety

Abdou Osman Abdelhamid*, Nadia Abdelhamid Abdel‐Riheem,

Tamer Tawhid El‐Idreesy and Huda Refat Mahmoud Rashdan
Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt

*Corresponding author at: Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt. Tel.: +20.2.1005205750;
fax: +20.2.35676573. E‐mail address: abdelhamid45@gmail.com (A.O. Abdelhamid).

ARTICLE INFORMATION ABSTRACT
Received: 04 May 2012
Received in revised form: 25 June 2012 1‐(2‐(4,5‐Dihydro‐3‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐5‐phenylpyrazol‐1‐yl)‐4‐subs‐
tituted‐thiazol‐5‐yl)‐2‐phenyldiazene (4) and substituted pyridines (5‐12) were synthesized
Accepted: 25 June 2012 via reaction of 1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐3‐phenylprop‐2‐en‐1‐one with
Online: 30 September 2012
hydrazonoyl halides and active methylene compounds. Also, thieno[2,3‐b]pyridines (14a‐e)
were prepared through reactions of 2‐mercapto‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐
KEYWORDS 4‐phenyl‐pyridine‐3‐carbonitrile with halo ester and halo ketones, respectively. The newly
synthesized derivetived were elucidated by elemental analysis, spectral data and alternative
Urea
Pyridines synthetic routes wherever possobile.
Quinazoline
Carbamates
5‐Arylthiazoles
Thieno[2,3‐b]pyridines

1. Introduction were recorded on a GC‐MS QP1000 EX Shimadzu. Elemental
analyses were carried out at the Microanalytical Center of Cairo
The pharmaceutical importance of pyrazolines lies in the University. Hydrazonoyl halides [42,43] and 1‐(5‐methyl‐1‐
fact that they can be effectively utilized as antibacterial, phenyl‐1H‐1,2,3‐triazol‐4‐yl)ethanone [44] were prepared as
antifungal, antiviral, antiparasitic, antitubercular and previously reported.
insecticidal agents [1‐6]. Some of these compounds have also
anti‐inflammatory, antidiabetic, anaesthetic and analgesic 2.2. Synthesis
properties [7‐9]. In addition, pyrazolines have played a crucial
part in the development of theory in heterocyclic chemistry and 2.2.1. 1‐(5‐Methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐3‐
also been used extensively in organic synthesis [10‐14]. On the phenylprop‐2‐en‐1‐one (1)
other hand, thienopyrimidine derivatives are characterized by
a very broad spectrum of biological activities such as Sodium hydroxide (10 mL, 10%) was added dropwise to a
antiallergic [15], antiatherosclerotic [16], antibacterial [17‐19], mixture of 1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl) ethan‐
anticancer [20], antiviral [21,22], antihypertensive [23,24], one (2 g, 10 mmol) and benzaldehyde (1 g, 10 mmol) in ethanol
antidepressant [25], antihistaminic [26], antimicrobial [27‐31] (20 mL) while stirring at 0‐5 oC. The reaction mixture was left
and neurotropic [32] activities. As an extension of our study for 2 h then the resulting solid was collected and recrystallized
[33‐41] and as a part of our program aiming at the synthesis of from ethanol to give 1 (Scheme 1). Color: White. Yield: 87%.
different heterocyclic derivatives, we report herein the M.p.: 126‐128 °C (M.p.: 123‐125 oC [45]). FT‐IR (KBr, , cm‐1):
convenient synthesis of 5‐arylazothiazoles, synthesis of 3064 (CH), 1665 (CO), 1604 (C=N), 1574 (C=C). 1H NMR (300
pyridines and thienopyridine derivatives containing 1,2,3‐ MHz, DMSO‐d6, δ, ppm): 2.60 (s, 3H, CH3), 7.42‐7.44 (m, 3H,
triazole moiety ArH's), 7.47‐7.50 (m, 2H, ArH's), 7.75‐7.60 (m, 3H, ArH's), 7.72‐
7.75 (m, 2H, ArH's), 7.90‐7.96 (d, 1H, J = 16 Hz, CH=C), 8.10‐
2. Experimental 8.15 (d, 1H, J = 16 Hz, CH=C). MS (EI, m/z (%)): 289 (M+, 3), 233
(60), 217 (11), 180 (25), 140 (6), 130 (53), 118 (66), 115 (25),
2.1. Instrumentation 103 (50), 77 (100), 51 (70). Anal calcd. for C18H15N3O: (289.33)
C, 74.72; H, 5.23; N, 14.52.. Found: C, 74.79; H, 5.18; N, 14.61%.
All melting points were determined on an electrothermal
apparatus and are uncorrected. IR spectra were recorded (KBr 2.2.2. 3‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐5‐phenyl‐
discs) on a Shimadzu FT‐IR 8201 PC spectrophotometer. 1H and 4,5‐dihydro‐1H‐pyrazole‐1‐carbothioamide (2)
13C NMR spectra were recorded in CDCl3 and (CD3)2SO
solutions on a Varian Gemini 300 MHz and JNM‐LA 400 FT‐ A mixture of 1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐3‐
NMR system spectrometer and chemical shifts are expressed in phenylprop‐2‐en‐1‐one (1) (1.45 g, 5 mmol), thiosemicarbazide
 ppm units using TMS as an internal reference. Mass spectra

European Journal of Chemistry
ISSN 2153‐2249 (Print) / ISSN 2153‐2257 (Online)  2012 EURJCHEM
DOI:10.5155/eurjchem.3.3.322‐331.629
 Abdelhamid et al. / European Journal of Chemistry 3 (3) (2012) 322‐331 323

R'
O Ph
NH2
S S
N
N N Ph
i ii N Ph
R= N N
N N
Ph R
2 R
1 3
R' = CH3, C6H5 iii

i = NH2NHCSNH2 Ph
ii = CH3COCH2Cl, N N
C6H5COCH2Br R'
iii = CH3COC(Cl):NNHPh,
C6H5COC(Br):NNHPh S PhN2Cl
N

N Ph
N
4a, R' = CH3
R b, R' = C6H5

Scheme 1


(0.46 g, 5 mmol) and sodium hydroxide (0.5 g, 10 mmol) in 70.11; H, 4.79; N, 18.17; S, 6.93. Found: C, 70.23; H, 4.92; N,
ethanol (20 mL) was refluxed for 3 h. The resulting solid was 17.88; S, 7.13%.
collected and recrystallized from ethanol to give 2 (Scheme 1).
Color: White. Yield: 82%. M.p.: 184‐186 °C. FT‐IR (KBr, , cm‐1): 2.2.4. 1‐(2‐(4,5‐Dihydro‐3‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐
3475, 3355(NH2), 3035 (CH), 1600 (C=N), 1562 (C=C). 1H NMR triazol‐4‐yl)‐5‐phenylpyrazol‐1‐yl)‐4‐substituted thiazol‐5‐
(300 MHz, DMSO‐d6, δ, ppm): 2.54 (s, 3H, CH3), 3.66 (dd, 1H, J = yl)‐2‐phenyldiazene (4a, b)
18.1, 5.8 Hz, CH2 (pyraz)), 4.01 (dd, 1H, J = 18.1, 12 Hz, CH2
(pyraz)), 5.33 (dd, 1H, J = 12.2, 5.8 Hz , CH (pyraz)), 7.25‐7.72 Method A: A mixture of 4,5‐dihydro‐3‐(5‐methyl‐1‐phenyl‐
(m, 10H, ArH’s), 9.11 (s. br., 2H, NH2). 13C NMR (75 MHz, DMSO‐ 1H‐1,2,3‐triazol‐4‐yl)‐5‐phenyl‐pyazole‐1‐carbothioamide (2)
d6, δ, ppm): 7.90 (CH3), 39.52 (CH2), 60.12 (CH), 118.35, 127.22, (1.81 g, 5 mmol), the appropriate of hydrazonoyl halides (5
127.41, 127.80, 129.31, 129.67, 131.47, 138.36, 139.45, 142.67, mmol) and triethylamine (0.75 mL, 0.5 g, 5 mmol) in ethanol
144.44, 178.24. MS (EI, m/z (%)): 359 (M‐3, 0.1), 358 (M‐4, (20 mL) refluxes 4 h. The resulting solid was collected and
0.2), 93 (4.4), 91 (100), 60 (59), 59 (27), 58 (8). Anal. calcd. for recrystallized to give 4a and 4b, respectively (Scheme 1).
C19H18N6S: C, 62.96; H, 5.01; N, 23.19; S, 8.85. Found: C, 63.10; Method B: Benzenediazonium chloride (5 mmol), which
H, 4.88; N, 23.00; S, 8.78%. prepared from aniline (0.45 mL, 5 mmol), hydrochloric acid (6
N, 6 mL), and sodium nitrite (0.35 g, 5 mmol), was added
2.2.3. 4‐(4,5‐Dihydro‐1‐(4‐substituted thiazol‐2‐yl)‐5‐phenyl‐ dropwise with stirring to a cold solution (0‐5 oC ) of a mixture
1H‐pyrazol‐3‐yl)‐5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazole (3a, b) of the appropriate 3a or 3b (5 mmol) and sodium acetate
trihydrate (1.3 g, 10 mmol) in ethanol (50 ml). The resulting
A mixture of 4,5‐dihydro‐3‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐ solid was collected and recrystallized to afford products
triazol‐4‐yl)‐5‐phenyl‐pyazole‐1‐carbothioamide (2) (1.81 g, 5 identical with 4a and 4b.
mmol), the appropriate of chloroacetone or ω‐bromo 1‐(2‐(4,5‐Dihydro‐3‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐
acetophenone (5 mmol) in ethanol (20 mL) refluxes for 3 h. The yl)‐5‐phenylpyrazol‐1‐yl)‐4‐methylthiazol‐5‐yl)‐2‐phenyldiazene
resulting solid, after cooling was collected and recrystallized to (4a): Color: Orange crystals from acetic acid. Yield: 82%. M.p.:
give 3a and 3b, respectively (Scheme 1). 218‐220 °C. FT‐IR (KBr, , cm‐1): 3023 (CH), 1597 (C=C). 1H
4‐(4,5‐Dihydro‐1‐(4‐methylthiazol‐2‐yl)‐5‐phenyl‐1H‐ NMR (300 MHz, DMSO‐d6, δ, ppm): 2.44 (s, 3H, CH3), 2.56 (s,
pyrazol‐3‐yl)‐5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazole (3a): Color: 3H, CH3), 3.61 (dd, 1H, J = 18.1, 5.8 Hz, CH2(pyraz)), 4.01 (dd,
Grey crystals from acetic acid. Yield: 81%. M.p.: 198‐200 °C. FT‐ 1H, J = 18.1, 12 Hz, CH2(pyraz)), 5.32 (dd, 1H, J = 12.2, 5.8 Hz ,
IR (KBr, , cm‐1): 3058 (CH), 1595 (C=C). 1H NMR (300 MHz, CH(pyraz)), 7.21‐7.89 (m, 15H, ArH’s). MS (EI, m/z (%)): 505
DMSO‐d6, δ, ppm): 2.10 (s, 3H, CH3), 2.54 (s, 3H, CH3), 3.66 (dd, (M+1, 2.8), 504 (M+, 15), 169 (5), 155 (9), 143 (6), 130 (21),
1H, J = 18.1, 5.8 Hz, CH2(pyraz)), 4.01 (dd, 1H, J = 18.1, 12.0 Hz, 112 (14), 104 (15), 91 (13), 77 (100), 66 (11). Anal. calcd. for
CH2(pyraz)), 5.33 (dd, 1H, J = 12.2, 5.8 Hz , CH(pyraz)), 6.10 (s, C28H24N8S: C, 66.65; H, 4.79; N, 22.21; S, 6.35. Found: C, 66.55;
1H, thiazole H‐5), 7.25‐7.66 (m, 10H, ArH’s). MS (EI, m/z (%)): H, 4.87; N, 22.00; S, 6.51%.
400 (M+, 19), 399 (19), 389 (16), 385 (22), 374 (21), 362 (26), 1‐(2‐(4,5‐Dihydro‐3‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐
341 (24), 322 (18), 302 (26), 279 (25), 256 (23), 244 (21), 222 yl)‐5‐phenylpyrazol‐1‐yl)‐4‐phenylthiazol‐5‐yl)‐2‐phenyldiazene
(28), 212 (48), 206 (18), 167 (27), 149 (91), 139 (19), 125 (42), (4b): Color: Red crystals from acetic acid. Yield: 81%. M.p.: 246‐
110 (63), 95 (58). Anal. calcd. for C22H20N6S: C, 65.98; H, 5.03; 248 °C. FT‐IR (KBr, , cm‐1): 3062 (CH), 1601 (C=C). 1H NMR
N, 20.98; S, 8.01. Found: C, 66.12; H, 4.97; N, 21.20; S, 7.89%. (300 MHz, DMSO‐d6, δ, ppm): 2.56 (s, 3H, CH3), 3.61 (dd, 1H, J =
4‐(4,5‐Dihydro‐5‐phenyl‐1‐(4‐phenylthiazol‐2‐yl)‐1H‐ 18.1, 5.8 Hz, CH2(pyraz)), 4.01 (dd, 1H, J = 18.1, 12 Hz,
pyrazol‐3‐yl)‐5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazole (3b): Color: CH2(pyraz)), 5.32 (dd, 1H, J = 12.2, 5.8 Hz , CH(pyraz)), 7.09‐
Yellow crystals from dioxane. Yield: 79%. M.p.: 250‐252 °C. FT‐ 8.19 (m, 20H, ArH’s). MS (EI, m/z (%)): 566 (M+, 0.4), 174 (31),
IR (KBr, , cm‐1): 3058 (CH), 1597 (C=C). 1H NMR (300 MHz, 102 (38), 80 (100), 74 (38), 73 (13). Anal. calcd. for C33H26N8S
DMSO‐d6, δ, ppm): 2.54 (s, 3H, CH3), 3.66 (dd, 1H, J = 18.1, 5.8 (566.68) C, 69.94; H, 4.62; N, 19.77; S, 5.66. Found: C, 70.12; H,
Hz, CH2(pyraz)), 4.01 (dd, 1H, J = 18.1, 12 Hz, CH2(pyraz)), 5.33 4.75; N, 19.62; S, 5.81%.
(dd, 1H, J = 12.2, 5.8 Hz , CH(pyraz)), 6.58 (s, 1H, thiazole H‐5),
7.21‐7.69 (m, 15H, ArH’s). MS (EI, m/z (%)): 462 (M+, 0.06),
400 (46), 242 (6), 240 (8), 156 (14), 130 (26), 113 (15), 103
(20), 91 (15), 77 (100), 67 (11). Anal. calcd. for C27H22N6S: C,
324 Abdelhamid et al. / European Journal of Chemistry 3 (3) (2012) 322‐331

Scheme 2


2.2.5. 6‐(5‐Methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐phenyl calcd. for C24H22N4O2: C, 72.34; H, 5.57; N, 14.06. Found: C,
pyridine derivatives (5‐10) and pyrazolo[3,4‐b]pyridine 72.41; H, 5.70; N, 13.8%.
(11a, b) 2‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐
phenylpyridine‐3‐carbonitrile (6): Color: Yellow crystals from
Method A: A mixture of 1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐ ethanol. Yield: 73%. M.p.: 224‐226 °C [45]. FT‐IR (KBr, , cm‐1):
triazol‐4‐yl)‐3‐phenylprop‐2‐en‐1‐one (1) (1.45 g, 5 mmol), the 3465, 3502 (NH2), 2202 (CN), 1589 (C=C). 1H NMR (400 MHz,
appropriate ethyl acetoacetate, malononitrile, ethylcyano‐ DMSO‐d6, δ, ppm): 2.49 (s, 3H, CH3), 7.02 (s. br., 2H, NH2), 7.41‐
acetate, cyanoacetamide, benzoylacetonitrile, cyanothio‐ 7.61 (m, 11H, ArH’s). MS (EI, m/z (%)): 353 (M+1, 3.3), 351
acetamide, 3‐methyl‐1H‐pyrazol‐5(4H)‐one or 3‐methyl‐1‐ (M+, 29), 324 (93), 281 (11), 247 (13), 220 (48), 194 (11),
phenyl‐1H‐pyrazol‐5(4H)‐one (5 mmol) and ammonium 17614), 149 (13), 130 (85), 77 (92), 51 (63). Anal. calcd. for
acetate (0.38 g, 5 mmol), was heated in acetic acid (10 mL) C21H16N6: C, 71.58; H, 4.58; N, 23.85. Found: C, 71.62; H, 4.74; N,
under reflux for 3 h. on cooling, the separated solid was filtered, 23.69%.
washed with water and crystallized from the proper solvent to 1,2‐Dihydro‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐2‐
afford 5‐11a and 11b (Scheme 2). oxo‐4‐phenylpyridine‐3‐carbonitrile (7): Color: White crystals
Method B: A mixture of 1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐ from acetic acid. Yield: 87%. M.p.: 250‐252 °C. FT‐IR (KBr, ,
triazol‐4‐yl)ethanone (1 g, 5 mmol), benzaldehyde (0.51 g, (5 cm‐1): 3344 (NH), 3062 (CH), 2218 (CN), 1701 (CO), 1616
mmol)) and the appropriate ethyl acetoacetate, malononitrile, (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.45 (s, 3H, CH3),
ethyl cyanoacetate, cyanoacetamide, benzoylacetonitrile, 7.02 ‐7.61 (m, 11H, ArH’s and pyridine H‐5), 11.65 (s. br., 1H,
cyanothioacetamide, 3‐methyl‐1H‐pyrazol‐5(4H)‐one or 3‐ NH). MS (EI, m/z (%)): 353 (M+, 27.8), 352 (M‐1, 32), 327 (91),
methyl‐1‐phenyl‐1H‐pyrazol‐5(4H)‐one (5 mmol) and 269 (12), 254 (16), 221 (37), 194 (10), 176 (15), 152 (15), 130
ammonium acetate (4.0 g), was heated in n‐butanol (10 mL) (69), 77 (100), 51 (55). Anal. calcd. for C21H15N5O: C, 71.38; H,
under reflux for 4 h. on cooling, the separated yellow solid was 4.28; N, 19.82. Found: C, 71.41; H, 4.15; N, 20.00%.
filtered, washed with water and recrystallized from the proper 1,2‐Dihydro‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐2‐
solvent to give corresponding products which obtained in oxo‐4‐phenylpyridine‐3‐carboxamide (8): Color: White crystals
method A. from ethanol. Yield: 72%. M.p.: 230‐232 °C. FT‐IR (KBr, , cm‐1):
Ethyl 2‐methyl‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐ 3440, 3394 (NH2), 3062 (CH), 1693 (CO), 1601 (C=C). 1H NMR
4‐phenylpyridine‐3‐carboxylate (5): Color: Yellow. Crystals from (400 MHz, DMSO‐d6, δ, ppm): 2.48 (s, 3H, CH3), 7.10‐7.62 (m,
ethanol. Yield: 69%. M.p.: 188‐190 °C. FT‐IR (KBr, , cm‐1): 13H, ArH’s and pyridine H‐5), 14.86 (s. br., 1H, NH). MS (EI, m/z
2923, 2854 (CH), 1681 (CO), 1612 (C=N), 1570 (C=C). 1H NMR (%)): 373 (M+, 1.6), 233 (3.3), 188 (1.7), 130 (29), 117 (52),
(400 MHz, DMSO‐d6, δ, ppm): 1.03 (t, 3H, J = 7, 12 Hz, CH2CH3), 103 (7), 77 (100), 51 (50). Anal. calcd. for C21H17N5O2: C, 67.91;
2.22 (s, 3H, CH3), 2.49 (s, 3H, CH3), 4.57 (q, 2H, J = 7 Hz, H, 4.61; N, 18.86. Found: C, 68.11; H, 4.52; N, 18.79%.
CH2CH3), 7.11‐7.60 (m, 10H, ArH’s), 8.35 (s, 1H, pyridine H‐5). 6‐(5‐Methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐2,4‐diphenyl‐
MS (EI, m/z (%)): 398 M+, (4)), 343 (13), 295 (14), 267 (98), pyridine‐3‐carbonitrile (9): Color: White crystals from acetic
164 (11), 130 (24), 118 (19), 115 914), 77 (100), 65 (11). Anal. acid. Yield: 87%. M.p.: 244‐246 °C. FT‐IR (KBr, , cm‐1): 3062
 Abdelhamid et al. / European Journal of Chemistry 3 (3) (2012) 322‐331 325

(CH), 2218 (CN), 1589 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, Yield: 87%. M.p.: 170‐172 °C. FT‐IR (KBr, , cm‐1): 3026 (CH),
ppm): 2.55 (s, 3H, CH3), 7.17‐8.42 (m, 16H, ArH’s and pyridine 2914 (CH), 1601 (C=N), 1549 (C=C). 1H NMR (400 MHz, DMSO‐
H‐5). MS (EI, m/z (%)): 414 (M+1, 8), 413 (M+, 27), 385 (100), d6, δ, ppm): 2.64 (s, 3H, CH3), 7.32‐8.22 (m, 15H, ArH’s and
308 (15), 281 (39), 191 (17), 171 (14), 130 (45), 77 (80), 51 pyridine H‐3, H‐5, furan H‐3, H‐4, H‐5). MS (EI, m/z (%)): 378
(56). Anal. calcd. for C27H19N5: C, 78.43; H, 4.63; N, 16.94. (M+, 0.02), 360 (100), 289 (5), 283 (15), 256 (34), 179 (15),
Found: C, 78.43; H, 4.63; N, 16.94%. 202 (8), 180 (15), 130 (25), 118 (23), 103 (16), 77 (69), 64 (6).
1,2‐Dihydro‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐ Anal. calcd. for C24H18N4O: C, 76.17; H, 4.79; N, 14.81. Found: C,
phenyl‐2‐thioxopyridine‐3‐carbonitrile (10): Color: Orange 76.24; H, 4.61; N, 14.97%.
crystals from dioxane. Yield: 87%. M.p.: 244‐246 °C. FT‐IR (KBr, 2‐(Benzofuran‐2‐yl)‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐
, cm‐1): 3310 (NH), 3066 (CH), 2218 (CN), 1616 (C=N), 1589 4‐yl)‐4‐phenylpyridine (12d): Color: Brown crystals from acetic
(C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.45 (s, 3H, CH3), acid. Yield: 87%. M.p.: 208‐210 °C. FT‐IR (KBr, , cm‐1): 3082
7.10‐7.69 (m, 11H, ArH’s and pyridine H‐5), 15.45 (s. br., 1H, (CH), 2920 (CH), 1604 (C=N), 1562 (C=C). 1H NMR (400 MHz,
NH). MS (EI, m/z (%)): 371 (M+2, 2.6), 370 (M+1, 6), 369 (M+, DMSO‐d6, δ, ppm): 2.62 (s, 3H, CH3), 7.21‐7.59 (m,17H, ArH’s
22), 341 (95), 340 (82), 339 (12), 307 (12), 237 (34), 130 (56), and pyridine H‐3, H‐5, furan H‐3)).
77 (100), 51 (79). Anal. calcd. for C21H15N5S: C, 68.27; H, 4.09; MS (EI, m/z (%)): 428 (M+, 5), 426 (M‐2, 9), 394 (7), 382 (6),
N, 18.96; S, 8.68. Found: C, 68.34; H, 4.21; N, 18.82; S, 8.54%. 361 (6), 334 (9), 306 (7), 279 (8), 262 (6), 233 (9), 212 (16),
3‐Methyl‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐ 190 (12), 185 (11), 181 (14), 175 (9), 167 (6), 155 (16), 149
phenyl‐1H‐pyrazolo[3,4‐b]pyridine (11a): Color: Brown crystals (10), 123 (13), 111 (10), 105 (9), 95 (16), 93 (21), 81 (34), 75
from benzene. Yield: 91%. M.p.: 168‐170 °C. FT‐IR (KBr, , cm‐ (16), 71 (74), 69 (43), 67 (25). Anal. calcd. for C28H20N4O: C,
1): 3379 (NH), 3062 (CH), 1635 (C=N), 1596 (C=C). 1H NMR 78.49; H, 4.70; N, 13.08. Found: C, 78.53; H, 4.64; N, 13.16%.
(400 MHz, DMSO‐d6, δ, ppm): 2.56 (s, 3H, CH3), 2.65 (s, 3H, 2‐(5‐Bromobenzofuran‐2‐yl)‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐
CH3), 7.10‐7.75 (m, 11H, ArH’s and pyridine H‐5), 11.23 (s. br., triazol‐4‐yl)‐4‐phenylpyridine (12e): Color: White crystals from
1H, NH). MS (EI, m/z (%)): 366 (M+, 100), 365 (M‐1, 48), 250 acetic acid. Yield: 87%. M.p.: 196‐198 °C. FT‐IR (KBr, , cm‐1):
(11), 234 (13), 221 (20), 220 (14), 219 (14), 206 (15), 145 (14), 3060 (CH), 2915 (CH), 1610 (C=N), 1576 (C=C). 1H NMR (400
130 (19), 118 (13),103 (15), 77 (24). Anal. calcd. for C22H18N6: MHz, DMSO‐d6, δ, ppm): 2.67 (s, 3H, CH3), 7.12‐7.89 (m, 16H,
C, 72.11; H, 4.95; N, 22.94. Found: C, 72.24; H, 5.11; N, 22.76%. ArH’s and pyridine H‐3, H‐5 and furan H‐3). MS (EI, m/z (%)):
3‐Methyl‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐1,4‐ 509 (M+, 20), 507 (M+, 22), 480 (87), 479 (100), 375 (19), 373
diphenyl‐1H‐pyrazolo[3,4‐b]pyridine (11b): Color: Brown (26), 293 (13), 212 (11), 200 (29), 199 (22), 164 (13), 130 (63),
crystals from ethanol. Yield: 89%. M.p.: 118‐120 °C. FT‐IR (KBr, 77 (63), 51 (48). Anal. calcd. for C28H19BrN4O: C, 66.28; H, 3.77;
, cm‐1): 3476 (NH), 3070 (CH), 1632 (C=N), 1603 (C=C). 1H Br, 15.75; N, 11.04. Found: C, 66.35; H, 3.65; Br, 15.56; N,
NMR (400 MHz, DMSO‐d6, δ, ppm): 2.65 (s, 3H, CH3), 2.78 (s, 11.13%.
3H, CH3), 7.00‐7.82 (m, 16H, ArH’s and pyridine H‐5). MS (EI, 3‐(6‐(5‐Methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐phenyl‐
m/z (%)): 443 (M+1, 29), 442 (M+, 100), 413 (15), 346 (16), pyridin‐2‐yl)‐2H‐chromen‐2‐one (12f): Color: Beige crystals
345 (41), 316 (10), 264 (24), 248 (10), 228 (58), 214 (45), 200 from dioxane. Yield: 72%. M.p.: 264‐266 °C. FT‐IR (KBr, , cm‐
(12), 196 (17),148 (16), 174 (14), 158 (14), 146 (18), 144 (18), 1): 3055 (CH), 2920 (CH), 1602 (C=N), 1700 (CO), 1550 (C=C).

131 (20), 115 (11), 77 (6), 54 (14). Anal. calcd. for C28H22N6: C, 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.63 (s, 3H, CH3), 7.12‐

76.00; H, 5.01; N, 18.99. Found: C, 76.12; H, 5.14; N, 18.78%. 7.82 (m, 15H, ArH’s and pyridine H‐3), 7.95 (s, 1H, pyridine H‐
5), 8.78 (s, 1H, pyrane H‐4). MS (EI, m/z (%)): 456 (M‐2, 30),
2.2.6. 2‐(5‐Methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐phenyl‐ 428 (58), 267 (20), 164 (18), 125 (15), 119 (15), 103 (22), 82
6‐substituted pyridine (12a‐f) (27), 67 (22). Anal. calcd. for C29H20N4O2: C, 76.30; H, 4.42; N,
12.27. Found: C, 76.42; H, 4.34; N, 12.10%.
A mixture of 1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐3‐
phenylprop‐2‐en‐1‐one (1) (1.45 g, 5 mmol), the appropriate 1‐ 2.2.7. 2‐(Substituted thio)‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐
(2‐oxo‐2‐substituted ethyl)‐pyridinium bromides (5 mmol) and triazol‐4‐yl)‐4‐phenylpyridine‐3‐carbonitrile (13a‐f)
ammonium acetate (0.38 g, 5 mmol) in acetic acid (10 mL)
refluxes for 4 h. The resulting solid, which formed after cooling, A mixture of 1,2‐dihydro‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐
was filtered, washed with water and crystallized from the triazol‐4‐yl)‐4‐phenyl‐2‐thioxopyridine‐3‐carbonitrile (10)
proper solvent to give 12a‐f (Scheme 2). (1.84 g, 5 mmol), potassium hydroxide (0.28 g, 5 mmol) in N,N‐
2‐(5‐Methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,6‐diphenyl‐ dimethylformamide (10 mL) was stirred for 2h at room
pyridine (12a): Color: White crystals from acetic acid. Yield: temperature. The appropriate of ethyl chloroacetate,
84%. M.p.: 186‐188 °C. FT‐IR (KBr, , cm‐1): 3058 (CH), 2931 chloroacetone, 2‐bromo‐1‐phenylethanone, 2‐bromo‐1‐p‐
(CH), 1602 (C=N), 1550 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, tolylethanone, chloroacetonitrile or iodomethane (5 mmol) was
ppm): 2.76 (s, 3H, CH3), 7.30‐8.12 (m, 17H, ArH’s and pyridine added while stirring. Stirred was continued for 2h. The
H‐3 & H‐5). MS (EI, m/z (%)): 388 (M+, 33), 387 (M‐1, 33), 361 resulting solid was collected and crystallized to afford 13a‐f,
(33), 373 (47), 360 (88), 359 (100), 256 (47), 227 (17), 158 respectively, (Scheme 3).
(17), 130 (50), 129 (67), 85 (133), 77 (33), 69 (33), 61 (36). Ethyl 2‐(3‐cyano‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐
Anal. calcd. for C26H20N4: C, 80.39; H, 5.19; N, 14.42. Found: C, yl)‐4‐phenylpyridin‐2‐ylthio)acetate (13a): Color: Brown
80.39; H, 5.19; N, 14.42%. crystals from ethanol. Yield: 77%. M.p.: 138‐140 °C. FT‐IR (KBr,
2‐(5‐Methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐phenyl‐6‐p‐ , cm‐1): 3065 (CH), 2977, 2929 (CH), 2114 (CN), 1742 (CO),
tolylpyridine (12b): Color: White crystals from acetic acid. 1587 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 1.09 (t, 3H,
Yield: 87%. M.p.: 170‐172 °C. FT‐IR (KBr, , cm‐1): 3026 (CH), CH2CH3), 2.62 (s, 3H, CH3), 4.05 (q, 2H, CH2CH3), 4.29 (s, 2H,
2914 (CH), 1601 (C=N), 1549 (C=C). 1H NMR (400 MHz, DMSO‐ SCH2), 7.59‐7.97 (m, 11H, ArH’s and pyridine H‐5). MS (EI, m/z
d6, δ, ppm): 2.34 (s, 3H, CH3), 2.76 (s, 3H, CH3), 7.30‐8.28 (m, (%)): 456 (M+1, 5), 455 (M+, 18), 426 (11), 352 (33), 351 (23),
16H, ArH’s and pyridine H‐3 & H‐5). MS (EI, m/z (%)): 403 339 (10), 250 (10), 130 (13), 77 (100), 51 (58). Anal. calcd. for
(M+1, 9), 402 (M+, 26), 401 (M‐1, 25), 375 (24), 374 (89), 373 C25H21N5O2S: C, 65.92; H, 4.65; N, 15.37; S, 7.04. Found: C, 66.12;
(100), 270 (30), 130 (22), 91(11), 77 (60), 51 (39). Anal. calcd. H, 4.54; N, 15.52; S, 7.17%.
for C27H22N4: C, 80.57; H, 5.51; N, 13.92. Found: C, 80.71; H, 2‐(2‐Oxopropylthio)‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐
5.36; N, 14.00%. 4‐yl)‐4‐phenylpyridine‐3‐carbonitrile (13b): Color: Brown
2‐(Furan‐2‐yl)‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐ crystals from ethanol. Yield: 87%. M.p.: 154‐156 °C.
4‐phenylpyridine (12c): Color: White crystals from acetic acid.

326 Abdelhamid et al. / European Journal of Chemistry 3 (3) (2012) 322‐331

Scheme 3


FT‐IR (KBr, , cm‐1): 3058 (CH), 2916 (CH), 2211 (CN), 1720 H, 4.62; N, 13.96; S, 6.39. Found: C, 71.95; H, 4.57; N, 14.15; S,
(CO), 1581 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.32 (s, 6.28%.
3H, CH3), 2.62 (s, 3H, CH3), 4.42 (s, 2H, SCH2), 7.27‐7.95 (m, 2‐(Cyanomethylthio)‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐
11H, ArH’s and pyridine H‐5). MS (EI, m/z (%)): 426 (M+1, 5), 4‐yl)‐4‐phenylpyridine‐3‐carbonitrile (13e): Color: Gray crystals
425 (M+, 25), 424 (20), 396 (14), 382 (19), 353 (49), 251 (10), from ethanol. Yield: 78%. M.p.: 198‐200 °C. FT‐IR (KBr, , cm‐1):
129 (19), 77 (100), 51 (69). Anal. calcd. for C24H19N5OS: C, 3062 (CH), 2970, 2924 (CH), 2214 (CN), 1647(C=N), 1585
67.74; H, 4.50; N, 16.46; S, 7.54. Found: C, 67.91; H, 4.48; N, (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.72 (s, 3H, CH3),
16.64; S, 7.41%. 4.42 (s, 2H, SCH2), 7.58‐8.06 (m, 11H, ArH’s and pyridine H‐5).
6‐(5‐Methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐2‐(2‐oxo‐2‐ Anal. calcd. for C23H16N6S: C, 67.63; H, 3.95; N, 20.57; S, 7.85.
phenyl‐ethylsulfanyl)‐4‐phenyl‐nicotinonitrile (13c): Color: Found: C, 67.81; H, 4.11; N, 20.68; S, 7.98%.
White crystals from acetic acid. Yield: 88%. M.p.: 158‐160 °C. 6‐(5‐Methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐2‐(methylthio)‐
FT‐IR (KBr, , cm‐1): 3061 (CH), 2908 (CH), 2213 (CN), 1679 4‐phenylpyridine‐3‐carbonitrile (13f): Color: White crystals
(CO), 1585 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.62 (s, from acetic acid. Yield: 78%. M.p.: 210‐212 °C. FT‐IR (KBr, ,
3H, CH3), 4.52 (s, 2H, SCH2), 7.27‐7.82 (m, 16H, ArH’s and cm‐1): 3062 (CH), 2923, 2854 (CH), 2210 (CN), 1627(C=N),
pyridine H‐5). MS (EI, m/z (%)): 489 (M+1, 2), 488 (M+, 8), 487 1595 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.62 (s, 6H,
(19), 457 (28), 353 (17), 130 (12.4), 77 (100), 76 (13), 51 (29). 2CH3), 7.24‐7.89 (m, 11H, ArH’s and pyridine H‐5). MS (EI, m/z
Anal. calcd. for C29H21N5OS: C, 71.44; H, 4.34; N, 14.36; S, 6.58. (%)): 384 (M+1, 23), 383 (M‐1, 100), 171 (14), 170 (100), 168
Found: C, 71.23; H, 4.45; N, 14.61; S, 6.72%. (20), 154 (15), 149 (18), 127 (10). Anal. calcd. for C22H17N5S: C,
6‐(5‐Methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐2‐(2‐oxo‐2‐p‐ 68.91; H, 4.47; N, 18.26; S, 8.36. Found: C, 69.10; H, 4.54; N,
tolyl‐ethylsulfanyl)‐4‐phenyl‐nicotinonitrile (13d): Color: White 18.43; S, 8.18%.
crystals from acetic acid. Yield: 88%. M.p.: 208‐210 °C. FT‐IR
(KBr, , cm‐1): 3050 (CH), 2914 (CH), 2210 (CN), 1678 (CO), 2.2.8. 3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐
1588 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.37 (s, 3H, 4‐phenyl‐2‐substituted thieno[2,3‐b]pyridine derivatives
CH3), 2.70 (s, 3H, CH3), 4.62 (s, 2H, SCH2), 7.27‐7.95 (m, 15H, (14a‐e)
ArH’s and pyridine H‐5). Anal. calcd. for C30H23N5OS: C, 71.83;
 Abdelhamid et al. / European Journal of Chemistry 3 (3) (2012) 322‐331 327

A mixture of the appropriate 13a‐e (5 mmol) and catalytic , cm‐1): 3452 (NH), 3047 (CH), 2920, 2850 (CH), 1686 (CO),
amount of piperidine (5 drops) in ethanol (20 mL) refluxes for 1577 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.67 (s, 3H,
1h. The resulting solid was collected and recrystallized from CH3), 7.51‐8.35 (m, 12H, ArH’s), 12.85 (s. br., 1H, NH). MS (EI,
acetic acid to give thieno[2,3‐b]pyridines 14a‐e, respectively, m/z (%)): 436 (M+, 18), 355 (10), 318 (15), 317 (64), 265 (11),
(Scheme 3). 264 (55), 257 (25), 235 (10), 222 (14), 221 (61), 209 (12), 194
Ethyl 3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐ (54), 193 (100), 153 (14), 98 (19), 83 (16), 67 (15), 55 (34).
phenylthieno[2,3‐b]pyridine‐2‐carboxylate (14a): Color: Yellow. Anal. calcd. for C24H16N6OS: C, 66.04; H, 3.69; N, 19.25; S, 7.35.
Yield: 92%. M.p.: 214‐216 °C. FT‐IR (KBr, , cm‐1): 3474, 3355 Found: C, 66.15; H, 3.75; N, 19.37; S, 7.22%.
(NH2), 3060 (CH), 2972, 2917 (CH), 1672 (CO), 1600 (C=C). 1H 2‐(5‐Methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐phenyl‐9‐thia‐
NMR (400 MHz, DMSO‐d6, δ, ppm): 1.04 (t, 3H, CH2CH3), 2.71 (s, 1,5,7‐triaza‐fluoren‐8‐ylamine (16): Color: Brown crystals from
3H, CH3), 4.22 (q, 2H, CH2CH3), 5.81 (s. br., 2H, NH2), 7.59‐7.89 dioxane. Yield: 92%. M.p.: >300 °C. FT‐IR (KBr, , cm‐1): 3309,
(m, 11H, ArH’s and pyridine H‐5). MS (EI, m/z (%)): 455 (M+, 3120 (NH2), 3062 (CH), 2923, 2854 (CH), 1647 (C=N), 1570
16), 454 (M‐1, 63), 380 (27), 379 (31), 353 (18), 317 (14), 258 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.63 (s, 3H, CH3),
(12), 148 (14), 139 (28), 107 (20), 76 (100), 57 (18), 51 (65). 6.68 (s. br., 2H, NH2), 7.51‐8.11 (m, 12H, ArH’s and pyridine H‐
Anal. calcd. for C25H21N5O2S: C, 65.92; H, 4.65; N, 15.37; S, 7.04. 5). MS (EI, m/z (%)): 435 (M+, 3), 285 (9), 241 (11), 240 (38),
Found: C, 66.12; H, 4.56; N, 15.42; S, 7.17%. 151 (40), 150 (13), 91 (100), 65 (6). Anal. calcd. for C24H17N7S:
1‐(3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐ C, 66.19; H, 3.93; N, 22.51; S, 7.36. Found: C, 66.25; H, 4.12; N,
phenylthieno[2,3‐b]pyridin‐2‐yl)ethanone (14b): Color: Orange. 22.37; S, 7.43%.
Yield: 71%. M.p.: 226‐228 °C. FT‐IR (KBr, , cm‐1): 3476, 3314
(NH2), 3056 (CH), 2918, 2885 (CH), 1720 (CO), 1590 (C=C). 1H 2.2.10. Ethyl N‐[2‐cyano‐6‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]
NMR (400 MHz, DMSO‐d6, δ, ppm): 2.35 (s, 3H, CH3), 2.68 (s, triazol‐4‐yl)‐4‐phenyl‐thieno[2,3‐b]pyridin‐3‐yl]‐
3H, CH3), 5.80 (s. br., 2H, NH2), 7.39‐7.69 (m, 11H, ArH’s and formimidate (17)
pyridine H‐5). MS (EI, m/z (%)): 452 (M+, 100), 424 (M‐1, 95),
395 (47), 391 (47), 353 (30), 292 (23), 248 (11), 198 (29), 196 A mixture of 14e (2 g, 5 mmol) and triethyl ortho‐formate
(13), 177 (16), 130 (64), 77 (92), 51 (67). Anal. calcd. for (1.48 g, 10 mmol) in acetic anhydride (20 mL) refluxes for 6 h.
C24H19N5OS: C, 67.74; H, 4.50; N, 16.46; S, 7.54. Found: C, 67.64; The reaction mixture was poured onto ice (30 g). The resulting
H, 4.36; N, 16.54; S, 7.35%. solid was collected and recrystallized from ethanol to give 17
(3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐ (Scheme 3). Color: Brown. Yield: 88%. M.p.: 180‐182 °C. FT‐IR
phenylthieno[2,3‐b]pyridin‐2‐yl)(phenyl)methanone (14c): (KBr, , cm‐1): 3062 (CH), 2854 (CH), 2206 (CN), 1639 (C=N),
Color: Yellow. Yield: 86%. M.p.: 260‐262 °C. FT‐IR (KBr, , cm‐ 1582 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 1.37 (t, 3H,
1): 3471, 3275 (NH2), 3052 (CH), 2919, 2851 (CH), 1712 (CO), CH2CH3), 2.58 (s, 3H, CH3), 4.21 (q, 2H, CH2CH3), 7.15‐7.48 (m,
1591 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.64 (s, 3H, 11H, ArH’s and pyridine H‐5), 8.15 (s, 1H, CH=N). MS (EI, m/z
CH3), 6.22 (s. br., 2H, NH2), 7.21‐7.79 (m, 16H, ArH’s and (%)): 464 (M+, 0.3), 297 (10), 256 (8), 150 (100), 130 (7), 120
pyridine H‐5). MS (EI, m/z (%)): 487 (M+, 55), 486 (M‐1, 49), (6), 105 (13), 104 (15), 76 (6). Anal. calcd. for C26H20N6OS: C,
458 (92), 229 (20), 130 (19), 77 (100), 51 (27). Anal. calcd. for 67.22; H, 4.34; N, 18.09; S, 6.90. Found: C, 67.41; H, 4.43; N,
C29H21N5OS: C, 71.44; H, 4.34; N, 14.36; S, 6.58. Found: C, 71.52; 17.79; S, 6.82%.
H, 4.41; N, 14.54; S, 6.66%.
(3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐ 2.2.11. 8‐Chloro‐2‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐
phenylthieno[2,3‐b]pyridin‐2‐yl)(4‐methylphenyl)methanone yl)‐4‐phenyl‐9‐thia‐1,5,7‐triaza‐fluorene (18)
(14d): Color: Yellow. Yield: 80%. M.p.: 262‐264 °C. FT‐IR (KBr,
, cm‐1): 3478, 3292 (NH2), 3031 (CH), 2918, 2852 (CH), 1709 A mixture of 15 (2.18 g, 5 mmol) and phosphorus
(CO), 1590 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.26 (s, oxychloride (20 mL) refluxes for 5 h. The reaction mixture was
3H, CH3), 2.48 (s, 3H, CH3), 5.09 (s. br., 2H, NH2), 7.31‐7.94 (m, cooled and poured onto ice (50 g). The resulting solid was
15H, ArH’s and pyridine H‐5). MS (EI, m/z (%)): 501 (M+, 52), collected and recrystallized from acetic acid to afford 18
500 (M‐1, 41), 472 (100), 235 (17), 190 (11), 130 (14), 77 (35), (Scheme 3). Color: Yellow. Yield: 96%. M.p.: 240‐242 °C. FT‐IR
65 (19), 51 (14). Anal. calcd. for C30H23N5OS (501.6) C, 71.83; H, (KBr, , cm‐1): 3056 (CH), 2920, 2850 (CH), 1647 (C=N), 1585
4.62; N, 13.96; S, 6.39. Found: C, 71.92; H, 4.51; N, 14.15; S, (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.62 (s, 3H, CH3),
6.52%. 7.15‐7.77 (m, 11H, ArH’s and pyridine H‐5), 8.68 (s, 1H,
3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐ pyrimidine H‐2). MS (EI, m/z (%)): 456 (M+2, 0.03), 454 (M+,
phenylthieno[2,3‐b]pyridine‐2‐carbonitrile (14e): Color: Yellow. 0.1), 370 (10), 369 (36), 354 (100), 353 (54), 263 (31), 262 (8),
Yield: 87%. M.p.: 246‐248 °C. FT‐IR (KBr, , cm‐1): 3467, 3328 248 (11), 247 (7.6), 236 (27), 233 (23), 221 (13), 177 (11), 118
(NH2), 2923, 2854 (CH), 2191 (CN), 1631 (C=N), 1585 (C=C). 1H (21), 106 (12), 77 (31), 51 (5). Anal. calcd. for C24H15ClN6S: C,
NMR (400 MHz, DMSO‐d6, δ, ppm): 2.65 (s, 3H, CH3), 5.60 (s. br., 63.36; H, 3.32; Cl, 7.79; N, 18.47; S, 7.05. Found: C, 63.12; H,
2H, NH2), 7.51‐7.90 (m, 11H, ArH’s and pyridine H‐5). MS (EI, 3.23; Cl, 7.87; N, 18.37; S, 7.11%.
m/z (%)): 409 (M+1, 13), 408 (M+, 54), 407 (45), 380 (91), 379
(100), 277 (13), 190 (16), 169 (14), 130 (83), 77 (77), 51 (65). 2.2.12. 8‐Azido‐2‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐
Anal. calcd. for C23H16N6S: C, 67.63; H, 3.95; N, 20.57; S, 7.85. 4‐phenyl‐9‐thia‐1,5,7‐triaza‐fluorene (19)
Found: C, 67.75; H, 4.12; N, 20.42; S, 7.96%.
A mixture of 18 (2.77 g, 5 mmol) and sodium azide (0.65 g,
2.2.9. 2‐(5‐Methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐phenyl‐ 19 mmol) in N,N‐dimethylformamide was stirred at room
9‐thia‐1,5,7‐triaza‐fluorene derivatives (15 and 16) temperature for 2h. Then, poured onto ice‐cold water (50 mL).
The resulting solid was collected and recrystallized from
A mixture of 14e (2 g, 5 mmol) and the appropriate of ethanol to give 19 (Scheme 3). Color: Brown. Yield: 96%. M.p.:
formic acid (99%) or formamide (5 mL) in N,N,‐ >300 °C. FT‐IR (KBr, , cm‐1): 3055 (CH), 2920, 2854 (CH), 2044
dimethylformamide refluxes for 7 h. The reaction mixture was (N3) [46], 1658 (C=N), 1543 (C=C). 1H NMR (400 MHz, DMSO‐
poured onto ice (50 g). The resulting solid was collected and d6, δ, ppm): 2.62 (s, 3H, CH3), 7.15‐7.82 (m, 11H, ArH’s and
recrystallized from from the proper solvent to give 15 and 16, pyridine H‐5), 8.68 (s, 1H, pyrimidine H‐2). Anal. calcd. for
respectively, (Scheme 3). C24H15ClN6S: C, 62.46; H, 3.28; N, 27.32; S, 6.95. Found: C, 62.52;
2‐(5‐Methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐phenyl‐7H‐9‐ H, 3.31; N, 27.46; S, 7.17%.
thia‐1,5,7‐triaza‐fluoren‐8‐one (15): Color: White crystals from
N,N‐dimethylformamide. Yield: 90%. M.p.: >300 °C. FT‐IR (KBr,
328 Abdelhamid et al. / European Journal of Chemistry 3 (3) (2012) 322‐331


Ph NH2
Ph Ph NH2
NH2 O
HN NH2
O X
R N S N
O R N S O
R N S N
23
14a 22
CH3

Ph NH2
Ph NH2 Ph O
O NH2
N3 X
N R' S N
H N R N N
S H O N Ph
R N R N S N
27 26 CH3
24

Ph NH2 O
+ 22
N
R N S NH
O O
28 Y
Ph NH2 H3C
O
N
NH
N R''
H O Ph
R N S
25
29

R = 5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl
23, 24a, X = OH 25a, Y = CO2C2H5 27a, R' = C6H5 29a, R'' = C6H5
23, 24b, X = CH3 25b, Y = COCH3 b, R' = 4-CH3C6H4 29b, R'' = 4-O2NC6H4
c, R' = 4-CH3OC6H4 29c, R'' = 2,4,6- (O2N)3C6H2
d, R' = 5-phenylpyrazol-3-yl

Scheme 4


2.2.13. [2‐(5‐Methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐ (s, 3H, CH3), 7.15‐7.68 (m, 11H, ArH’s and pyridine H‐5), 8.48
phenyl‐9‐thia‐1,5,7‐triaza‐fluoren‐8‐yl]‐hydrazine (20) (s, 1H, pyrimidine H‐2). MS (EI, m/z (%)): 461 (M+, 6), 360
(100), 289 (23), 260 (39), 248 (23), 232 (81), 220 (15), 202
A mixture of 18 (2.18 g, 5 mmol) and hydrazine hydrate (1 (20), 189 (75), 178 (10), 174 (55), 155 (29), 148 (45), 136 (51),
g, 20 mmol) in ethanol (20 mL) refluxes for 3 h. The resulting 97 (12), 91 (77), 43 (19). Anal. calcd. for C24H15N9S: C, 62.46; H,
solid was collected and recrystallized from acetic acid to give 3.28; N, 27.32; S, 6.95. Found: C, 62.61; H, 3.37; N, 27.28; S,
20 (Scheme 3). Color: Yellow. Yield: 96%. M.p.: 240‐242 °C. FT‐ 7.11%.
IR (KBr, , cm‐1): 3388, 3337, 3217 (NH, NH2), 3062 (CH), 2920,
2851 (CH), 1645 (C=N), 1551 (C=C). 1H NMR (400 MHz, DMSO‐ 2.2.15. 3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐
d6, δ, ppm): 2.62 (s, 3H, CH3), 6.25 (s. br., 3H, NH, NH2), 7.15‐ 4‐phenylthieno[2,3‐b]pyridine‐2‐carbohydrazide (22)
7.77 (m, 11H, ArH’s and pyridine H‐5), 8.68 (s, 1H, pyrimidine
H‐2). MS (EI, m/z (%)): 450 (M+, 4), 332 (20), 331 (100), 238 A mixture of ethyl 3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐
(54), 174 (12), 160 (64), 155 (62), 94 (12), 93 (35), 91 (54), 84 triazol‐4‐yl)‐4‐phenylthieno[2,3‐b]pyridine‐2‐carboxylate
(17), 65 (8), 56 (9). Anal. calcd. for C24H18N8S: C, 63.98; H, 4.03; (14a) (2.27 g, 5 mmol) and hydrazine hydrate (1g, 1 mL, 10
N, 24.87; S, 7.12. Found: C, 64.12; H, 4.11; N, 24.94; S, 7.23%. mmol) in ethanol (20 mL) refluxes for 1h. The solid formed was
collected and recrystallized from ethanol afforded 22 (Scheme
2.2.14. 8‐(5‐Methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐6‐ 4). Color: Yellow. Yield: 82%. M.p.: 230‐232 °C. FT‐IR (KBr, ,
phenyl‐10‐thia‐1,2,3,3a,5,9‐hexaaza‐cyclopenta[a]fluorene cm‐1): 3483, 3359, 3267 (NH, NH2), 3062(CH), 2920, 2854 (CH),
(21) 1659 (CO), 1593 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm):
2.56 (s, 3H, CH3), 5.88 (s. br., 5H, NH, 2NH2), 7.10‐7.60 (m, 11H,
Saturated solution of sodium nitrite (10 mL) was added ArH’s and pyridine H‐5). MS (EI, m/z (%)): 441 (M+, 49), 426
while stirring to a cold solution at 0 oC of 20 (2.25 g, 5 mmol) in (24), 289 (23), 260 (39), 248 (23), 232 (81), 220 (15), 202 (20),
acetic acid (30 mL). The reaction was stirred for 1h. The 189 (75), 178 (10), 174 (55), 155 (29), 148 (45), 380 (29), 353
resulting solution was collected and recrystallized from acetic (36), 312 (24), 249 (22), 191 (38), 149 (76), 77 (100), 51 (76).
acid gave 21 (Scheme 3). Color: Brown. Yield: 89%. M.p.: >300 Anal. calcd. for C23H19N7OS: C, 62.57; H, 4.34; N, 22.21; S, 7.26.
°C. FT‐IR (KBr, , cm‐1): 3070 (CH), 2920, 2850 (CH), 1625 Found: C, 62.75; H, 4.24; N, 22.141; S, 7.356%.
(C=N), 1585 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.64
 Abdelhamid et al. / European Journal of Chemistry 3 (3) (2012) 322‐331 329

2.2.16. (3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐ calcd. for C33H25N9O2S: C, 64.80; H, 4.12; N, 20.61; S, 5.24.

yl)‐4‐phenylthieno[2,3‐b]pyridin‐2‐yl)(5‐substituted 3‐ Found: C, 64.92; H, 4.00; N, 20.75; S, 5.35%.
methyl‐1H‐pyrazol‐1‐yl)methanone dervatives (23a and b) (3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐
phenylthieno[2,3‐b]pyridin‐2‐yl)(3,5‐dimethyl‐4‐(phenyldiazen‐
A mixture of 3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐ yl)‐1H‐pyrazol‐1‐yl)methanone (24b): Color: Brown. Yield:
triazol‐4‐yl)‐4‐phenylthieno[2,3‐b]pyridine‐2‐carbohydrazide 88%. M.p.: 240‐242 °C. FT‐IR (KBr, , cm‐1): 3614, 3568 (NH2),
(22) (2.2 g, 5 mmol), ethyl acetoacetate or acetylacetone in 3058 (CH), 2916, 2850 (CH), 1693 (CO), 1608 (C=N), 1550
ethanol (20 mL) and acetic acid (5 drops) refluxes for 3 h. on (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.18 (s, 3H, CH3),
cooling, the separated yellow solid was filtered, washed with 2.28 (s, 3H, CH3), 2.61 (s, 3H, CH3), 6.78 (s. br., 2H, NH2), 7.12‐
water and crystallized from acetic acid to afford 23a and 23b 7.99 (m, 16H, ArH’s and pyridine H‐5). MS (EI, m/z (%)): 609
(Scheme 4). (M+, 35), 608 (100), 607 (45), 593 (11), 397 (29), 396 (29), 381
2‐[3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐ (25), 365 (12), 214 (11), 212 (20), 195 (20). Anal. calcd. for
phenyl‐thieno[2,3‐b]pyridine‐2‐carbonyl]‐5‐methyl‐2,4‐dihydro‐ C34H27N9OS: C, 66.98; H, 4.46; N, 20.68; S, 5.26. Found: C, 67.11;
pyrazol‐3‐one (23a ): Color: Brown. Yield: 89%. M.p.: 180‐182 H, 4.34; N, 20.88; S, 5.14%.
°C. FT‐IR (KBr, , cm‐1): 3479, 3325 (NH2), 3062 (CH), 2924,
2855 (CH), 1724, 1674 (CO), 1593 (C=C). 1H NMR (400 MHz, 2.2.18. (3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐
DMSO‐d6, δ, ppm): 2.12 (s, 3H, CH3), 2.57 (s, 3H, CH3), 4.31 (dd, yl)‐4‐phenylthieno[2,3‐b]pyridin‐2‐yl)azidomethanone (26)
1H, CH2, , pyrazolole), 3.56 (dd, 1H, CH2, pyrazole), 6.77 (s. br.,
2H, NH2), 7.12‐7.74 (m, 11H, ArH’s and pyridine H‐5). MS (EI, A stirred solution of 22 (2.2 g, 5 mmol) in hydrochloric acid
m/z (%)): 507 (M+, 10), 450 (18), 449 (28), 448 (100), 390 (15 mL, 6 M) at 0‐5 °C, sodium nitrite was added portionwise
(13), 274 (16). Anal. calcd. for C27H21N7O2S: C, 63.89; H, 4.17; N, tell effervescence ended. The reaction mixture was stirred for 1
19.32; S, 6.32. Found: C, 64.00; H, 4.05; N, 19.45; S, 6.48%. h. The resulting solid, was collected, filtered, washed with
3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐ water and recrystallized from acetic acid to give 26 (Scheme 4).
phenyl‐thieno[2,3‐b]pyridin‐2‐yl]‐(3,5‐dimethyl‐pyrazol‐1‐yl)‐ Color: Beige. Yield: 88%. M.p.: 190‐192 °C. FT‐IR (KBr, , cm‐1):
methanone (23b): Color: Brown. Yield: 89%. M.p.: 218‐220 °C. 3479, 3325 (NH2), 3031 (CH), 2920 (CH), 2124 (Azide), 1678
FT‐IR (KBr, , cm‐1): 3479, 3325 (NH2), 3062 (CH), 2923, 2855 (CO), 1596 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.61 (s,
(CH), 1670 (CO), 1627 (C=N), 1593 (C=C). 1H NMR (400 MHz, 3H, CH3), 6.65 (s. br., 2H, NH2), 7.12‐7.85 (m, 11H, ArH’s and
DMSO‐d6, δ, ppm): 2.28 (s, 3H, CH3), 2.38 (s, 3H, CH3), 2.59 (s, pyridine H‐5). MS (EI, m/z (%)): 455 (M+1, 18), 454 (16), 440
3H, CH3), 5.52 (s, 1H, pyrazole H‐4), 6.55 (s. br., 2H, NH2), 7.12‐ (41), 380 (38), 354 (22), 324 (19), 286 (19), 265 (45), 239 (25),
7.79 (m, 11H, ArH’s and pyridine H‐5). MS (EI, m/z (%)): 505 220 (41), 205 (38), 189 (31), 161 (34), 134 (44), 128 (47), 98
(M+, 3.6), 503 (14), 465 (9), 448 (41), 406 (21), 331 (39), 220 (53), 91 (16), 82 (100), 77 (41), 64 (25), 51 (28). Anal. calcd.
(7), 206 (10), 178 (27), 169 (78), 136 (23), 135 (23), 127 (14), for C23H16N8OS: C, 61.05; H, 3.56; N, 24.76; S, 7.09. Found: C,
109 (24), 43 (100). Anal. calcd. for C28H23N7OS: C, 66.52; H, 61.12; H, 3.42; N, 24.61; S, 7.00%.
4.59; N, 19.39; S, 6.34. Found: C, 66.45; H, 4.48; N, 19.28; S,
6.52%. 2.2.19. Urea derivatives (27a‐d)

2.2.17. 2‐[3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐ A mixture of appropriate aniline, p‐toluidine, p‐anisidine or
yl)‐4‐phenyl‐thieno[2,3‐b]pyridine‐2‐carbonyl]‐5‐methyl‐4‐ 3‐amino‐5‐phenylpyrazole (5 mmol) and azido compound 26
(phenyl‐hydrazono)‐2,4‐dihydro‐pyrazol‐3‐one (24a) and (2.26 g, 5 mmol) in dry dioxane (20 mL) refluxes for 4 h. The
[3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐ resulting solid, so formed, was collected and recrystallized to
phenyl‐thieno[2,3‐b]pyridin‐2‐yl]‐(3,5‐dimethyl‐4phenylazo‐ give 27a‐d, respectively, (Scheme 4).
pyrazol‐1‐yl)‐methanone (24b) 1‐(3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐
4‐phenylthieno[2,3‐b]pyridin‐2‐yl)‐3‐phenylurea (27a): Color:
Method A: Benzenediazonium chloride (5 mmol), which Brown crystals from ethanol. Yield: 78%. M.p.: 240‐242 °C. FT‐
was prepared via reaction of aniline (0.46 g. 5 mmol), IR (KBr, , cm‐1): 3614, 3568 (NH2), 3031 (CH), 2920(CH), 1678
hydrochloric acid (3 mL, 6 M) and sodium nitrite (0.37 gm, 5 (CO), 1596 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.54 (s,
mmole) at 0‐5 °C, was added to a mixture of the appropriate 3H, CH3), 7.12‐7.66 (m, 20H, ArH’s, pyridine H‐5, 2NH, NH2). MS
23a or 32b (5 mmole) and sodium acetate (0.41 g, 5 mmole) in (EI, m/z (%)): 517 (M+, 0.2), 309 (100), 280 (18), 231 (7), 208
ethanol (30 mL) at 0‐5 °C, while stirring. The reaction mixture (18), 204 (14), 206 (24), 128 (15), 105 (41), 77 (19). Anal.
was stirred for 3 h. The resulting solid, was collected, washed calcd. for C29H23N7OS: C, 67.29; H, 4.48; N, 18.94; S, 6.19. Found:
with water and recrystallized from acetic acid to give 24a and C, 67.29; H, 4.48; N, 18.94; S, 6.19%.
24b, respectively, (Scheme 4). 1‐(3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐
Method B: A mixture of 22a (2.2 g, 5 mmol) and the 4‐phenylthieno[2,3‐b]pyridin‐2‐yl)‐3‐p‐tolylurea (27b): Color:
appropriate of ethyl 2‐(2‐phenylhydrazono)‐3‐oxobutanoate or Brown crystals from ethanol. Yield: 87%. M.p.: 208‐210 °C. FT‐
3‐(2‐phenyl‐hydrazono)pentane‐2,4‐dione (5 mmol) in ethanol IR (KBr, , cm‐1): 3429, 3568 (NH2), 3066 (CH), 2924, 2823
(20 mL) and catalytic amount of acetic acid (2 drops) was (CH), 1685 (CO), 1604 (C=N), 1551 (C=C). 1H NMR (400 MHz,
refluxed for 2 h. The resulting solid, so formed, was collected DMSO‐d6, δ, ppm): 2.25 (s, 3H, CH3), 2.58 (s, 3H, CH3), 7.12‐7.99
and recrystallized from acetic acid to give products identical in (m, 19H, ArH’s and pyridine H‐5, 2H, NH2). MS (EI, m/z (%)):
all aspects to those obtained from method A. 531 (M+, 38), 530 (100), 516 (18), 515 (49), 219 (31), 203 (12),
2‐[3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐ 189 (10), 147 (15), 67 (13), 83 (15), 71 (12), 69 (18), 57 (57),
phenyl‐thieno[2,3‐b]pyridine‐2‐carbonyl]‐5‐methyl‐4‐(phenyl‐ 43 (22). Anal. calcd. for C30H25N7OS: C, 67.78; H, 4.74; N, 18.44;
hydrazono)‐2,4‐dihydro‐pyrazol‐3‐one (24a): Color: Brown. S, 6.03. Found: C, 67.87; H, 4.7456; N, 18.22; S, 6. 14%.
Yield: 92%. M.p.: 208‐210 °C. FT‐IR (KBr, , cm‐1): 3479, 3359, 1‐(3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐
3325 (NH, NH2), 3066 (CH), 2920 (CH), 1678, 1647 (CO), 1605 4‐phenylthieno[2,3‐b]pyridin‐2‐yl)‐3‐(4‐methoxyphenyl)urea
(C=N), 1550 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.10 (27c): Color: Beige crystals from acetic acid. Yield: 89%. M.p.:
(s, 3H, CH3), 2.62 (s, 3H, CH3), 6.89‐7.72 (m, 16H, ArH’s and 140‐142 °C. FT‐IR (KBr, , cm‐1): 3614, 3568 (NH2), 2923, 2854
pyridine H‐5), 9.42 (s. br., 3H, NH, NH2). MS (EI, m/z (%)): 611 (CH), 1653 (CO), 1600 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ,
(M+, 0.2), 373 (6), 355 (100), 313 (9), 256 (10), 240 (17), 239 ppm): 2.61 (s, 3H, CH3), 3.65 (s, 3H, OCH3), 7.12‐7.99 (m, 19H,
(96), 227 (12), 171 (47), 159 (14), 158 (23), 117 (26), 112 (14), ArH’s and pyridine H‐5), NH2, 2NH). MS (EI, m/z (%)): 547 (M+,
98 (34), 95 (13), 83 (24), 73 (13), 69 (26)57 (55), 43 (57). Anal. 2.7), 305 (5), 304 (33), 303 (100), 273 (6), 195 (6), 117 (9), 81
330 Abdelhamid et al. / European Journal of Chemistry 3 (3) (2012) 322‐331

(6). Anal. calcd. for C30H25N7O2S: C, 65.80; H, 4.60; N, 17.90; S, (9), 216 (5), 122 (7), 105 (100), 77 (24). Anal. calcd. for
5.86. Found: C, 65.98; H, 4.51; N, 18.12; S, 5.64%. C29H19N9O8S: C, 53.29; H, 2.93; N, 19.29; S, 4.91. Found: C,
1‐(3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐ 53.42; H, 3.12; N, 19.419; S, 5.00%.
4‐phenylthieno[2,3‐b]pyridin‐2‐yl)‐3‐(3‐phenyl‐1H‐pyrazol‐5‐
yl)urea (27d): Color: Brown crystals from acetic acid. Yield: 3. Results and discussion
88%. M.p.: 240‐242 °C. FT‐IR (KBr, , cm‐1): 3433, 3394 (NH2),
2974, 2939 (CH), 1647 (CO), 1550 (C=C). 1H NMR (400 MHz, Treatment of 1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐
DMSO‐d6, δ, ppm): 2.61 (s, 3H, CH3), 5.23 (s, 1H, pyrazole H‐4), 3‐phenyl‐prop‐2‐en‐1‐one (1) with thiosemicarbazide in
7.12‐7.99 (m, 16H, ArH’s and pyridine H‐5), 9.26 (s. br., 5H, boiling ethanolic sodium hydroxide gave 4,5‐dihydro‐3‐(5‐
3NH, NH2). MS (EI, m/z (%)): 583 (M+, 65), 300 (34), 299 (100), methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐5‐phenyl‐pyazole‐1‐
288 (12), 287 (17), 286 (78), 241 (11), 239 (15.19), 211 (18), carbothioamide (2). Compound 2 reacted with the appropriate
197 (7), 106 (6), 79 (4), 44 (31). Anal. calcd. for C32H25N9OS: C, hydrazonoyl halides in boiling ethanol containing catalytic
65.85; H, 4.32; N, 21.60; S, 5.49. Found: C, 65.99; H, 4.16; N, amount of triethylamine gave 1‐(2‐(4,5‐dihydro‐3‐(5‐methyl‐1‐
21.72; S, 5.55%. phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐5‐phenylpyrazol‐1‐yl)‐4‐methyl‐
thiazol‐5‐yl)‐2‐phenyldiazene (4a) and 1‐(2‐(4,5‐dihydro‐3‐(5‐
2.2.20. 3‐(3‐Amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐ methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐5‐phenylpyrazol‐1‐yl)‐
yl)‐4‐phenylthieno[2,3‐b]pyridin‐2‐yl)quinazoline‐ 4‐phenylthiazol‐5‐yl)‐2‐phenyldiazene (4b), respectively
2,4(1H,3H)‐dione (28) (Scheme 1).
Structures 4a and 4b were confirmed by elemental
A mixture of appropriate methyl anthranilate or anthranilic analyses, spectral data, and alternative synthetic routes. Thus,
acid (5 mmol) and azido compound 26 (2.26 g, 5 mmol) in dry benzenediazonium chloride reacted with each of 4‐(4,5‐
dioxane (20 mL) refluxes for 4 h. The resulting solid, so formed, dihydro‐1‐(4‐methylthiazol‐2‐yl)‐5‐phenyl‐1H‐pyrazol‐3‐yl)‐5‐
was collected and recrystallized from ethanol to give 28 methyl‐1‐phenyl‐1H‐1,2,3‐triazole (3a) and 4‐(4,5‐dihydro‐5‐
(Scheme 4). Color: Brown. Yield: 93.6%. M.p.: >300 °C. FT‐IR phenyl‐1‐(4‐phenylthiazol‐2‐yl)‐1H‐pyrazol‐3‐yl)‐5‐methyl‐1‐
(KBr, , cm‐1): 3433, 3394, 3179 (NH, NH2), 3062 (CH), 2923 phenyl‐1H‐1,2,3‐triazole (3b), which prepared via reaction of 2
(CH), 1681 (CO), 1600 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, with the appropriate chloroacetone or ‐bromoacetophenone,
ppm): 2.62 (s, 3H, CH3), 926 (s. br., 2H, NH2), 7.14‐7.99 (m, 15H, in pyridine to give a product identical in all aspects (m.p., mixed
ArH’s and pyridine H‐5), 10.55 (s. br., 1H, NH). MS (EI, m/z m.p., and spectra) with 4a and 4b, respectively (Scheme 1).
(%)): 544 (M+, 2.7), 305 (5), 303 (100), 227 (8), 126 (9), 117 Condensation of compound 1 with ethyl acetoacetate in
(9), 81 (6). Anal. calcd. for C30H21N7O2S: C, 66.28; H, 3.89; N, presence of ammonium acetate in acetic acid afforded the
18.04; S, 5.90. Found: C, 66.12; H, 3.979; N, 1800; S, 6.10%. corresponding ethyl 2‐methyl‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐
triazol‐4‐yl)‐4‐phenylpyridine‐3‐carboxylate (5) (Scheme 2).
2.2.21. Aryl carbamates (29a‐c) Similarly, the reaction of compound 1 with malononitrile, ethyl
cyanoacetate, cyanoacetamide, benzoylacetonitrile, 2‐
A mixture of 26 (2.26 g, 5 mmol) and the appropriate cyanothioacetamide, 3‐methyl‐1H‐pyrazol‐4‐one or 1‐phenyl‐
phenol, 4‐nitrophenol or picric acid (5 mmol) in dry benzene 3‐methyl‐1H‐pyrazol‐4‐one yielded the corresponding pyridine
(20 mL) refluxes for 4 h. The resulting solid, so formed, was derivatives 6‐10, 3‐methyl‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐
collected and recrystallized from ethanol to give 29a‐c, triazol‐4‐yl)‐4‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine (11a) and 3‐
respectively, (Scheme 4). methyl‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐1,4‐di‐
Phenyl 3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐ phenyl‐1H‐pyrazolo‐[3,4‐b]pyridine (11b) in good yields,
4‐phenylthieno[2,3‐b]pyridin‐2‐ylcarbamate (29a): Color: respectively (Scheme 2). The structures of the synthesized
Brown. Yield: 73%. M.p.: 226‐228 °C. FT‐IR (KBr, , cm‐1): 3271, compounds were confirmed on the basis of their elemental
3190 (NH2), 3062 (CH), 2974, 2939 (CH), 1700 (CO), 1627 analysis and alternative synthetic route. Thus, one pot reaction
(C=N), 1593 (C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.62 of 1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)ethanone, benz‐
(s, 3H, CH3), 5.23 (s, 1H, pyrazole H‐4), 6.88‐7.89 (m, 18H, aldehyde, appropriate ethyl acetoacetate, malononitrile, ethyl
ArH’s, pyridine H‐5, NH, NH2). MS (EI, m/z (%)): 518 (M+, 0.1), cyanoacetate, cyanoacetamide, benzoylacetonitrile, cyano‐
310 (31), 308 (100), 280 (18), 265 (5), 208 (18), 204 (14), 203 thioacetamide, 3‐methyl‐1H‐pyrazol‐4‐one or 1‐phenyl‐3‐
(24), 202 (20), 154 (9), 128 (15), 105 (41), 77 (18). Anal. calcd. methyl‐1H‐pyrazol‐4‐one and excess ammonium acetate in n‐
for C29H22N6O2S: C, 67.17; H, 4.28; N, 16.21; S, 6.18. Found: C, butanol gave identical product in all aspects (mp., mixed mp.
67.17; H, 4.28; N, 16.21; S, 6.18%. and spectra) with corresponding compounds 5‐11 (Scheme 2).
4‐Nitrophenyl 3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐ 2‐(5‐Methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐phenyl‐6‐
triazol‐4‐yl)‐4‐phenylthieno[2,3‐b]pyridin‐2‐ylcarbamate (29b): substituted pyridine 12a‐f were also prepared in good yield by
Color: Yellow. Yield: 79%. M.p.: >300 °C. FT‐IR (KBr, , cm‐1): Krohnke reaction via tratment of 1 with 1‐(2‐oxo‐2‐substituted
3352 (NH), 3059 (NH2), 2922, 2854 (CH), 1667 (CO), 1594 ethyl)‐pyridinium bromides in glacial acetic acid.
(C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.63 (s, 3H, CH3), 2‐Mercapto‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐
7.15‐7.66 (m, 16H, ArH’s, pyridine H‐5, NH, NH2), 8.30‐8.32 (d, phenyl‐pyridine‐3‐carbonitrile (10) was reacted with each of
2H, J = 8 Hz, ArH's). MS (EI, m/z (%)): 564 (M+1, 7), 551 (16), ethyl chloroacetate, chloroacetone, ω‐bromoacetophenone,
548 (6), 533 (9), 494 (7), 478 (10), 463 (10), 419 (7), 400 (5), chloroacetonitrile or iodomethane gave corresponding S‐
382 (7), 363 (11), 323 (12), 273 (12), 239 (13), 218 (10), 197 alkylated derivatives 13a‐f, respectively. Structures 13a‐f were
(10), 179 (11), 155 (13), 138 (20), 123 (22), 113 (19), 111 (38), elucidated by elemental analysis, spectral data and chemical
97 (15), 93 (31), 86 (14), 62 (33). Anal. calcd. for C29H21N7O4S: transformation. Thus, boiling pyridine derivatives in ethanol in
C, 61.80; H, 3.76; N, 17.40; S, 5.69. Found: C, 61.80; H, 3.76; N, presence of catalytic amount of piperidine afforded 2‐
17.40; S, 5.69%. substituted 6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐
2,4,6‐Trinitrophenyl 3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐ phenylthieno[2,3‐b]pyridin‐3‐amine derivatives 14a‐c,
triazol‐4‐yl)‐4‐phenylthieno[2,3‐b]pyridin‐2‐ylcarbamate (29c): respectively (Scheme 3).
Color: Yellow. Yield: 74%. M.p.: >300 °C. FT‐IR (KBr, , cm‐1): Structures 14e was converted to 2‐(5‐methyl‐1‐phenyl‐1H‐
3352 (NH), 3059 (NH2), 2922, 2854 (CH), 1667 (CO), 1594 [1,2,3]triazol‐4‐yl)‐4‐phenyl‐7H‐9‐thia‐1,5,7‐triaza‐fluoren‐8‐
(C=C). 1H NMR (400 MHz, DMSO‐d6, δ, ppm): 2.62 (s, 3H, CH3), one (15) and 2‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐
7.15‐7.89 (m, 14H, ArH’s, pyridine H‐5, NH, NH2), 9.14 (s, 2H, phenyl‐9‐thia‐1,5,7‐triaza‐fluoren‐8‐ylamine (16) by its boiling
ArH's). MS (EI, m/z (%)): 653 (M+, 0.1), 460 (10), 445 (13), 255 in formic acid and formamide, respectively. Also, compound
14e reacted with triethyl orthoformate in acetic anhydride
 Abdelhamid et al. / European Journal of Chemistry 3 (3) (2012) 322‐331 331

gave ethyl N‐[2‐cyano‐6‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐ Chem. Ther. 1980, 15, 567‐569.

4‐yl)‐4‐phenyl‐thieno[2,3‐b]pyridin‐3‐yl]‐formimidate (17), [9]. Husain, M. I.; Shukla, S. Indian J. Chem. 1985, 24B, 761‐764.
[10]. Tomilovi, Y. V.; Okonnishnikova, G. P.; Shulishov, E. V.; Nefedov, O. M.
which was converted to 16 with ammonia (Scheme 3). Russ. Chem. Bull. 1995, 44, 2114‐2117.
Also, compound 15 was converted to 8‐chloro‐2‐(5‐methyl‐ [11]. Klimova, E. I.; Garcia; M. M.; Berestneva, T. K.; Toledano, C. A.;
1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐phenyl‐9‐thia‐1,5,7‐triaza‐ Toskano, R. A.; Ramierz, L. R. J. Organomet. Chem. 1999, 585, 106‐114.
fluorene (18) by reaction with phosphrous oxychloride. The [12]. Azarifar, D.; Ghasemnejad, H. Molecules 2003, 8, 642‐648.
[13]. Padmavathi, V.; Sumathi, R. P.; Babu, N. C.; Bhaskar, D. J. Chem. Res.
chloro derivative 18 was reacted with sodium azide and
1999, 10, 610‐611.
hydrazine hydrate gave 8‐azido‐2‐(5‐methyl‐1‐phenyl‐1H‐ [14]. Reddy, D. B.; Babu, N. C.; Padmavathi, V.; Sumathi, R. P. Synthesis
[1,2,3]triazol‐4‐yl)‐4‐phenyl‐9‐thia‐1,5,7‐triazafluorene (19) 1998, 3, 491‐494.
and [2‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐phenyl‐9‐ [15]. Gillespie, E.; Dungan, K. W.; Gomol, A. W.; Seidehamel, R. Int. J.
thia‐1,5,7‐triaza‐fluoren‐8‐yl]‐hydrazine (20) in a good yield. Immunopharmacol. 1985, 7, 655‐660.
[16]. Bol’but, A. V.; Vovk, M. V. Abstracts of International Confeerence on
The later was converted to 8‐(5‐methyl‐1‐phenyl‐1H‐ the Chemistry of Nitrogen Containing Heterocycles, CNH‐2003,
[1,2,3]triazol‐4‐yl)‐6‐phenyl‐10‐thia‐1,2,3,3a,5,9‐hexaaza‐ Kharkiv (Ukraine), 2003, pp. 68.
cyclopenta[a]fluorene (21) by reaction with nitrous acid at 0 [17]. Allan, J. D.; Eliopoulos, G. M.; Reiszner, E.; Moellering, R. C. Antimicrob
oC. Agents Chemoth. 1987, 31, 1997‐2001.
On the other hand, treatment of 14a with hydrazine [18]. Khalil, Z. H.; Geies, A. A. Phosphorus, Sulfur, Silicon and Relat. Elem.
1991, 60, 223‐231.
hydrate gave 3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐ [19]. Hozien, Z. A.; Abdel‐Wahab, A. A.; Hassan, K. M.; Atta, F. M.; Ahmed, S.
4‐yl)‐4‐phenylthieno‐[2,3‐b]pyridine‐2‐carbohydrazide (22). A. Pharmazie 1997, 52, 753‐758.
Structure of 22 was confirmed by elemental analysis, spectral [20]. Munchhof, M. J.; Sobolov‐Jaynes, S. B.; Marx, A. M. (Pfizer Inc., USA) U.
data and chemical transformation. Thus, 22 was reacted with S. Pat. 6, 492, 83 (Cl. 514‐301; A61K31/44); Chem. Abstr. 2003, 138,
24721e.
each of ethyl acetoacetate, acetylacetone or nitrous acid
[21]. Kharizomenova, I. A.; Grinev, A. N.; Samsonova, N. V.; Panisheva, E. K.;
afforded 2‐[3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐ Kaplina, N. V.; Nikolaeva, I. S.; Pushkina, T. V.; Pershin, G. N. Khim.
yl)‐4‐phenylthieno[2,3‐b]pyridine‐2‐carbonyl]‐5‐methyl‐ Farm. Zh. 1981, 15(9), 40‐44.
2,4‐dihydro‐pyrazol‐3‐one (23a), [3‐amino‐6‐(5‐methyl‐1‐ [22]. Kaplina, N. V.; Grinev, A. N.; Bogdanova, G. A.; Alekseeva, L. N.;
phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐phenyl‐thieno[2,3‐b]‐pyridin‐ Pushkina, T. V.; Fomina, A. N. Khim. Farm. Zh. 1987, 21(2), 197‐200.
[23]. Pathak, U. S.; Alagarsamy, V. Acta Pharm. Turc. 1999, 41, 37‐41.
2‐yl]‐(3,5‐dimethyl‐pyrazol‐1‐yl)‐methanone (23b) and (3‐ [24]. Ismail, M. A. ‐H.; Aboul‐Einein, M. N. Y.; Abouzid, K. A. M.; Kandil, S. B.
amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐4‐ A. Alexandria J. Pharm. Sci. 2002, 16, 143‐151.
phenylthieno[2,3‐b]‐pyridin‐2‐yl)azidomethanone (26), [25]. Ninomya, K.; Nitsuta, K.; Tobe, A.; Egawa, M.; Kikumoto, R. (Mitsubishi
respectively (Scheme 4). Structures 23 were elucidated by Chem Ind) Jpn. Kokai Tokkyo Koho Jp 06 16, 55794 16, 557; Chem.
elemental analysis, spectral data and chemical transformation. Abstr. 1994, 120, 290120.
[26]. Shishoo, C. J.; Shirsath, V. S.; Rathod, I. S.; Yande, V. D. Eur. J. Med.
Thus, benzenediazonium chloride was reacted with 23a and Chem. 2000, 35, 351‐358.
23b in ethanolic sodium acetate solution at 0 oC afforded 2‐[3‐ [27]. Moneer, A. A. Bull. Fac. Pharm. (Cairo Univ.) 2001, 39, 27‐34.
amino‐6‐(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐ [28]. Ammar, Y. A.; Ismail, M. M.; El‐Gaby, M. S. A.; Zahran, M. A. Indian J.
phenylthieno[2,3‐b]pyridine‐2‐carbonyl]‐5‐methyl‐4‐(phenyl‐ Chem. 2002, 41B, 1486‐1491.
[29]. Chambhare, R. V.; Bobade, A. S.; Khadse, B. G. Indian J. Heterocycl.
hydrazono)‐2,4‐dihydro‐pyrazol‐3‐one (24a) and [3‐amino‐6‐
Chem. 2002, 12, 67‐68.
(5‐methyl‐1‐phenyl‐1H‐[1,2,3]triazol‐4‐yl)‐4‐phenyl‐ [30]. Sayed, A. Z. Adv. Colour Sci. Techn. 2002, 5, 24‐30.
thieno[2,3‐b]pyridin‐2‐yl]‐(3,5‐dimethyl‐4‐phenylazoyrazol‐1‐ [31]. Shah, M.; Patel, P.; Parekh, H. Orient. J. Chem. 2002, 18, 159‐161.
yl)‐methanone (24b), respect‐tively. Also, compounds 24a,b [32]. Oganisyan, A. Kh.; Noravyan, A. S.; Dzhagatspanyan, I. A.; Melikyan, G.
were obtained by reaction of 22 with the appropriate of ethyl G. Pharm. Chem. J. 2003, 37, 13‐14.
[33]. Abdelhamid, A. O.; Afifi, M. A. M. Phosphorus, Sulfur, Silicon and Rela.
2‐(2‐phenylhydrazono)‐3‐oxobutanoate (25a) and 3‐(2‐ Elem. 2008, 183, 2703‐2713.
phenylhydrazono)pentane‐2,4‐dione (25b), respectively. [34]. Abdelhamid, A. O.; Afifi, M. A. Synth. Commun. 2010, 40, 1539‐1550.
Compound 26 was reacted with the appropriate aniline, 4‐ [35]. Abdelhamid, A. O.; Abdelall, E. K. A.; Zaki, Y. H. J. Heterocycl Chem.
toluidine, 4‐anisidine, 3‐amino‐5‐phenylpyrazole, anthranilc 2010, 47, 477‐ 482.
acid, phenol, 4‐nitrophenol or picric acid afforded urea [36]. Abdelhamid, A. O. J. Heterocycl. Chem. 2009, 46, 680‐686.
[37]. Abdelhamid, A. O.; Abdelall, E. K. A.; Abdel‐Riheem, N. A.; Ahmed, S. A.
derivatives 27a‐d, 3‐(3‐amino‐6‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐ Phosphorus, Sulfur, Silicon and Relat. Elem. 2010, 185, 709‐718.
triazol‐4‐yl)‐4‐phenylthieno‐[2,3‐b]pyridin‐2‐yl)quinazoline‐ [38]. Abdelhamid, A. O.; Afifi, M. A. J. Adv. Res. 2010, 1, 137‐144.
2,4(1H,3H)‐dione (28) and aryl 3‐amino‐6‐(5‐methyl‐1‐phenyl‐ [39]. Abdelhamid, A. O.; Fahmi, A. A.; Halim, K. M. N. Eur. J. Chem. 2011,
1H‐1,2,3‐triazol‐4‐yl)‐4‐phenylthieno‐[2,3‐b]pyridin‐2‐ 2(3), 317‐323.
[40]. Abdelhamid, A. O.; Fahmi, A. A.; Ali, A. B. Eur. J. Chem. 2011, 2(4), 544‐
ylcarbamate 29a‐c, respectively.
551.
[41]. Abdelhamid, A. O.; Shokry, S. A.; Tawfiek, S. M. J. Heterocycl. Chem.
4. Conclusion 2012, 49, 116‐124.
[42]. Shawali, A. S.; Abdelhamid, A. O. Bull. Soc. Japan 1976, 49, 321‐332.
The present work describes the synthesis of 5‐ [43]. Eweiss, N. F.; Osman, A. J. Heterocycl. Chem. 1980, 17, 1713‐1717.
[44]. Wang, H. C.; Li, R. S.; Dong, H. R.; Dong, H. S. Indian J. Chem. 2010, 49B,
arylazothiazole, pyridine and thieno[2,3‐b]pyridine derivatives 521‐525.
contaninig 1,2,3‐triazole moiety in a good yields by reaction of [45]. Dong, H. S.; Wang, H. C.; Gao, Z. L.; Li, R. S.; Cui, F. H. J. Heterocycl. Chem.
1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)‐3‐phenylprop‐2‐ 2010, 47, 389‐395.
en‐1‐one and different reagents. [46]. Bellamy, L. J. The infrared Spectra of Complex Molecules, 3th edition,
Published by Chapman and Hall Ltd. London EC4p 4EE, 1975, pp. 305.

References

[1]. Grosscurt, A. C.; Hes, R. V.; Wellinga, K. J. Agric. Food Chem. 1979, 27,
406‐409.
[2]. Keats, G. H. Brit. Pat. 1, 209, 631, (1970); Chem. Abstr. 1971, 74,
141787b.
[3]. Kedar, R. M.; Vidhale, N. N.; Chincholkar, M. M. Orient. J. Chem. 1997,
13, 143‐148.
[4]. Singh, A.; Rathod, S.; Berad, B. N.; Patil, S. D.; Dosh, A. G. Orient. J. Chem.
2000, 16, 315‐317.
[5]. Khalil, Z. H.; Yanni, A. S. J. Indian Chem. Soc. 1981, 58, 168‐170.
[6]. Das, N. B.; Mittra, A. S. Indian J. Chem. 1978, 16B, 638‐640.
[7]. Regaila, H. A.; El‐Bayouki, A. K.; Hammad, M. Egypt J. Chem. 1977, 20,
157‐166.
[8]. Raman, K.; Pandey, B. R.; Barthwal, J. P.; Parmar, S. S. Eur. J. Med. Chem.