A facile microwave-assisted synthesis of some fused pyrimidine derivatives

Article abstract of DOI:10.13005/ojc/300209

The highly accelerated synthesis of thienopyrimidinones, theino- pyrimidines, thioxotheinopyrimidinones and a thienotriazolopyrimidinone derivatives under microwave irradiation is reported. Compared to conventional conditions, microwaves method offered se

Full text of DOI:10.13005/ojc/300209

ISSN: 0970-020 X
CODEN: OJCHEG
2014, Vol. 30, No. (2):
Pg. 469-477
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
A Facile Microwave-Assisted Synthesis
of Some Fused Pyrimidine Derivatives
S. A. AL-ISSA
Department of Chemistry, Faculty of Science,
Princess Nora Bint Abdul Rahman University, Riyadh, Saudi Arabia.
*Corresponding author E-mail: Seham.alissa@gmail.com
http://dx.doi.org/10.13005/ojc/300209
(Received: March 05, 2014; Accepted: March 31, 2014)
ABSTRACT
The highly accelerated synthesis of thienopyrimidinones, theino- pyrimidines,
thioxotheinopyrimidinones and a thienotriazolopyrimidinone derivatives under microwave irradiation
is reported. Compared to conventional conditions, microwaves method offered several advantage
likes short time, good yields, simple procedure, mild conditions and easy workup. The structure of
synthesized compounds have been characterized on the basis of their elemental analysis and
spectral data, and screened for their antimicrobial activity.
Key words: Thienopyrimidine, Thioxothienopyrimidine,
Triazolopyrimidinone, Microwave Irradiation.
INTRODUCTION
in reaction times, good yields and cleaner reaction
than conventional procedure11-16. There are several
examples describing the advantage of using
microwave irradiation for synthesis the thieno [2,3-
d]pyridine-4(3H)ones for example , Hesse
reported the synthesis of thieno[2,3-d]pyrimidin-
4(3H)-ones under microwave irradiation in good
yield17.
Pyrimidines and fused pyrimidines
compounds, are a big family of the heterocyclic
compounds, which have been focus of great interest
because of their wide range of biological and
pharmacological activities as antibacterial and
antifungal activities1-4 anticancer5-8
,
anti-
,
inflammatory9 and many thieno[2,3-d] pyrimidine
derivatives have been proved to use in case of
Alzheimer and Parkinson disease10.
It seemed most interesting to extend the
scope of synthesize of pyrimidine derivatives having
active moieties under microwave irradiation with
the aim to evaluate their biological activity as
antibacterial or antifungal agents.
Microwave irradiation has attracted
attention of organic synthesis due to the reduction

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AL-ISSA, Orient. J. Chem., Vol. 30(2), 469-477 (2014)
EXPERIMENTAL
Melting point are uncorrected . Microwave
5,6,7,8-Tetrahydro-3H-benzo[4,5]thieno[2,3-
d]pyrimidin-4-one(4b)
M.p. 257-259oC, IR(cm-1): br. 3400, 1670;
reaction were performed on a microwave oven start 1H-NMR (DMSO-d6): 1.8-1.87 (m, 4H, CH2 at C-6
SYNTH-Milestone-open vessel. IR spectra were and C-7), 2.65-2.70 (m, 2H, CH2 at C-5); 2.80-2.89
recorded in potassium bromide on Perkin-Elmer (m, 2H, CH2 at C-8), 7.80 (s, 1H, pyrimidine -H),
1
380 and 387 spectrometer. H-NMR spectra were 10.90 (br. s, 1H, NH); MS: m/z (%) 206 [M+](90)
run on a JEOL-JNMGX-300 and Junm Ex-400 in (C10H10N2OS); CHN Anal. Calcd . % : C, 58.25;
DMSO-d6 or CDCl3 using TMS as internal standard H,4.85; N, 13.59 Found: C, 58.30; H, 4.83; N, 13.60.
and chemical shift were expressed as part of million,
ppm ( values) against TMS and internal references. 3,5,6,7,8,9-Hexahydrocyclohepta[4,5]thieno[2,3-
Electron impact (E1) MS spectra were obtained with d]pyrimidin-4-one (4c)
aid of a ShimaDZU Gemsqp 5050. A spectrometers
at 70 ev. Elemental analysis were recorded on a 1H-NMR(DMSO-d6): 1.56-1.58 (m, 4H, 2CH2 at C-6
M.p.: 212-215oC; IR (cm-1): br 3410, 1710;
Heruss CHN analyser.
d C-7); 1.83-189 (m, 2H, CH2 at C-8), 2.70-283 (m,
2H, CH2 at C-5), 2.96-3.0 (m, 2H, CH2 at C-9), 8.01
General procedure for synthesis of 5,6- (s, 1H, pyrimidine -H) 12.5( br. s, 1H, NH); MS: m/z
disubtituted thieno[2,3-d]pyrimidin-4(3H)-ones (%) 220[M+] (100) (C11H12N2OS); CHN . Anal. Calcd.
(4a-c
)
%: C:60.00; H:5.45, N: 12.72; Found: C: 60.10, H:
A mixture of 1a,b ( 1 mmol) and formamide 5.47; N: 12.70.
( 5-6 mmol) in ( 1 mmol) acetic acid, was irradiation
in the microwave oven for10 min. at (300 W) 130oC. 4-Chloro-5,6,7,8-tetrahydrobenzo[4,5] thieno[2,3-
The reaction mixture was cooled and poured into d] pyrimidine (7):
iced-cold water, filtered, washed and recrystallized Conventional method
from ethanol.
A mixture of 4b (5 mmol) and phosphorus
oxychloride (15 ml) was heated under reflux for 20
5,6-Dimethyl-3H-thieno[2,3-d]pyrimidin-4-one (4a) h. After completion of reaction, The excess
M.p. 180-183oC; IR(cm-1): 3320, 1670; 1H- phosphorus oxychloride was removed by distillation
NMR(DMSO-d6) 1.7(s, 3H, CH3), 2.0(s, 3H, CH3), under reduced pressure ,the residue left was titrated
7.80 (1H, s, pyrimidine -H), 10.00 (br. s, 1H, NH); with sodium bicarbonate solution (10%); the solid
MS: m/z (%), 180[M+] (95) (C8H8N2OS);CHN anal. separated was filtered, dried and recrystallized from
calcd %: C:53.33; H: 4.44; N:15.55; Found: C: 53.45; toluene.
H: 4.30; N:15.56.
R2
a
R1
CH3
X= OH, NH2
CH3
b
c
(CH2)4
(CH2)5
Scheme 1:

AL-ISSA, Orient. J. Chem., Vol. 30(2), 469-477 (2014)
471
Microwave method
A mixture of 4b(5 mmol) and phosphorus
General procedure for synthesis of 4-N-(aryl)-
5,6,7,8-tetrahydrobenzo [4,5]thieno[2,3-d]
pyrimidines (8):
oxychloride (15 ml) was irradiated in microwave
oven at( 60 W) 120oC for 15 min.. After completion
of reaction, The workup was carried out as
described for conventional method. M.p: 93-96oC ;
conventional method
A solution of compound 7 (10 mmol) and
aryl amine (2.0 mmol) in 2-propanol (30 mL) was
stirred under reflux for 12h., the solvent was
removed under reduced pressure and the solid
product was filtered dried and washed several times
with petroleum ether.
1
IR (cm-1): 1620, 1580; H-NMR(DMSO-d6): 1.90-
1.94, (m, 4H, 2CH2, at C6 & C7), 2.90-2.94 (m, 2H,
CH2 , C-5), 3.00-3.40 (m, 2H, CH2 at C-8), 8.72 (d,
1H pyrimidine -H); MS: m/z (%) 224[M+] (56%) (
C10H935Cl N2S), 226[M+2] (30)( C10 H937ClN2S);CHN:
Anal. Calcd.: C: 53. 57: H: 4.01; N: 12.50.Found C:
53.21, H: 4.20, N: 12.49.
Microwave Method:
A mixture of compound 7 (1.0 mmol) and
aryl amine (2.0 mmol) in 2-propanol (10 mL) was
stirred for 5 min., then the mixture was irradiated in
Scheme 2:
Compound No. R1, R2 Ar
8a
8b
8c
(CH2)4 4-CH3
(CH2)4 3-CF3
(CH2)4 2,5-di CH3
Scheme 3:

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AL-ISSA, Orient. J. Chem., Vol. 30(2), 469-477 (2014)
the microwave oven at (60W) 100oC for 20 min.The 1H-NMR (DMSO-d6): 1.80-1.87(m, 4H, 2CH2 at C-6
workup was carried out as described for d C-7), 2.40-2.60(m, 2H, CH2 at C-5), 2.93-3.00 (m,
conventional method.
2H, CH2, at C-8), 7.31 -7.80 (m, 4H, Ar-H), 8.10(s,
1H, pyrimidin-H) ,8.7-8.9 (br. s, 1H, NH); MS: m/z
4-N-(4-methylphenyl)-5,6,7,8-tetrahydro[4,5] (%) 349(100) ( C17H14F3N3S); CHN : Anal. Calcd. (%)
thieno[2,3-d] pyrimidine (8a) C: 58.45; H: 4.01; N: 12.03; Found: C, 58.36; H: 4.36;
M.p . oC : 235-237oC; IR (cm-1): br. 3410; N: 12.98.
1620; 1H-NMR(DMSO-d6): 1.85-1.98 (m, 4H, CH2 at
C-6, C-7) 2.28(s, 3H, CH3), 2.34-2.64 (m, 2H, CH2 at 4-N-(2,5-Dimethylphenyl)-5,6,7,8-[4,5]thieno[2,3-
C-5) 2.9-3.04 (m, 2H, CH2 at C-8), 7.1-7.80 (m,4H,Ar- d] pyrimidine(8c)
H) , 7.95-8.1, ( br.s, 1H, NH), 8.22 (s, 1H, pyrimidin-
H). MS: m/z (%) 295[M+] (95%).( C17H17N3S); CHN: 1H-NMR (DMSO-d6): 1.80-1.87 (m, 4H, 2CH2 at C-6
Anal. Calcd .:C:69.15.H: 5.76; N: 14.23. Found: d C-7), 2.31(s, 3H, CH3), 2.40 (s, 3H, CH3), 2.44 (m,
C: 69.30, H: 5.31; N: 14.34.
M.poC.213-215oC;IR (cm-1):br.3140, 1610;
2H, CH2 at C-5), 2.94-2.97 (m, 2H, CH2 at C-8),
7.16-7.80 (m, 3H, Ar-H), 8.18 (s, 1H, pyrimidine -H)
4-N-(3-Trifluoromethylphenyl)-5,6,7,8- ,8.41( br. s, 1H, NH); MS: m/z (%); 309 (60%).
tetrahydrobenzo[4,5]thieno [2,3-d] pyrimidine (8b) C18H19N3S; CHN :Anal. Calcd. (%): C, 69.90, H: 6.14,
M.poC.224-225 oC;IR (cm-1):br.3390, 1610; N: 13.59; Found: C: 69.93; H 6.92.
Scheme 4: Synthetic route of compounds 11-14

AL-ISSA, Orient. J. Chem., Vol. 30(2), 469-477 (2014)
473
General procedure for synthesis of 3,5,6-
trisubtituted-1H-2-thioxo thieno[2,3,-d] pyrimidin-
4-ones(11)
A mixture of 1b ( 1 mmol) and the
appropriate isothiocyanate (1.1 mmol) in (10 ml)
acetic acid, the mixture was irradiated in microwave
oven at (300 W)120oC for 20 min. The cold reaction
was poured onto crushed ice, the solid obtained
was filtered, washed with water, dried and
recrystallized from ethanol.
(15 ml) was submitted to microwave irradiation for
5 min. at( 60W) 100oC. After cooling the reaction
mixture poured into ice cooled water and stirred for
10 min the solid product was filtered, dried and
recrystallized from ethanol.
3-Allyl-2-hydrazino-5,6,7,8-tetrahydro-3H-
benzo[4,5]thieno[2,3-d] pyrimidin-4-one(12a)
M.p.196-199oC; IR (cm-1): 3390, 3310,,
1610, 1580, 1H-NMR: 1.70-1.73 (m, 4H, 2CH2 at C-
6 d C-7); 2.61-2.68(m, 2H, CH2 at C-5); 2.80-2.82(m,
2H, CH2 at C-8), 4.01-4.30 (br. s, 2H, NH2), 4.50-
4.56(m, 2H, NCH2), 4.96(d d, 1H, J =10.5 Hz, =CH2),
5.12, (dd, 1H, J= 17.5 Hz, =CH2), 5.80-5.84(m, 1H,
CH=);8.5 (br.s, 1H, NH).MS:m/z(%) 276 [M+] (90%),(
C13H16N4OS); CHN Anal. Calcd.%: C, 56.52; H, 5.
79; N, 20.28; Found :C,56.56; H, 5.83; N,20.24.
3-Allyl-2-thioxo-2,3,5,6,7,8-hexahydro-1H-
benzo[4,5]thieno[2,3-d] pyrimidin-4-one(11a)
M.p.: 234-237oC, IR (cm-1) 3330, 1710,
1210; 1H-NMR (DMSO-d6): 1.68-1.73, (m, 4H, 2CH2
at C-6 d C-7), 2.30-2.50(m, 2H, CH2 at C-5), 2.89-
2.90(m, 2H, CH2 at C-8);4.35-4.50(br.m, 2H, NCH2),
5.41-5.60 (m, 2H, =CH2); 5.89-6.30 (m, 1H, HC=),
11.9(s, 1H, NH); MS: m/z (%); 278(100) (
C13H14N2OS2 ); CHN: Anal. Calcd.: C, 56.11; H: 5.03;
N: 10.07; Found: C: 56.60; H: 4.34; N: 9.85.
3-(4-Chlorophenyl)-2-hydrazino-5,6,7,8-
tetrahydro-3H-benzo[4,5]-thieno[2,3-d]pyrimidin-
4-one(12b)
M.p.204-206oC; IR(cm-1), 3410 (br.),1610,
3-(Phenyl)-2-thioxo-5,6,7,8-tetrahydro-1H-
benzo[4,5]thieno[2,3-d] pyrimidin-4-one(11b)
M.p.:261-263oC;IR(cm-1): 3400, 1700,
1200; 1H-NMR(CDCl3): 1.80-1.84 (m, 4H, 2CH2 at
C-6 & C-7), 2.58-2.61 (m, 2H, CH2 at C-5), 2.85-
2.90 (m, 2H, CH at C-8), 7.30-7.60 (m, 5H, Ar-H),
11.5(br.s, 1H, NH) MS: m/z (%) 314[M+](100)
C16H14N2OS2; CHN :Anal. Calcd, C: 61.14; H: 4.45;
N: 8.91, Found: C: 61.20; H:4.53; N: 8.90.
1580 ; 1H-NMR (DMSO-d6): 1.74-1.80(m, 4H, 2CH2
at C-6 d C-7); 2.63-2.70( m, 2H, CH2 at C-5), 2.80-
2.83 (m, 2H, CH2 at C-8), 4.3 (br. s, 2H, NH2), 7.4-
7.9 (m, 4H, Ar-H), 8.01 (br. s, 1H, NH); MS: m/z(%)
346 [M+] (90) (C16 H15 35Cl N4OS), 348[ M+2] (25)
(C16H1537ClH4OS); CHN : Anal. Calcd: C,55.49; H,
4.33; N , 16.18 ; Found: C, 55.45; H: 4.30; N: 16.14.
4-Allyl-6,7,8,9-tetrahydro-4H-benzo[4,5] thieno
[2,3-d] [1,2,4]triazolo [3,4,-b]pyrimidin-5-one
(13a)
3-(4-Chlorophenyl)-2-thioxo-5,6,7,8-tetrahydro-
1H-benzo[4,5]thieno [2,3-d]pyrimidine-4-one
(11c)
A mixture of compound 12a(1.0 mmol) and
formic acid (10 ml) was submitted to microwave
irradiation for 10 min. at (60 W)800C after cooling
the reaction mixture was poured into ice-cooled
water, the formed solid was collected by filtration
washed several time with ethanol, dried and
recrystallized from ethanol.: M.p. 213-215oC, IR (cm-
1), 1680, 1610, 1H-NMR (CDCl3): 1.80-1.86 (m, 4H,
2CH2 at C7 and C-8), 2.60-2.78( m, CH2 at C-6),
3.00-3.42 (m, 2H, CH2 at C-9); 4.50-4.56(m, 2H,
NCH2), 4.96(dd, 1H, J =10.5 Hz, =CH2), 5.12, (dd,
1H, J= 17.5 Hz, =CH2), 5.80-5.84(m, 1H, C-H=); 8.5
(br. s, 1H, NH); 9.30 (s, 1H, triazolo -H); MS, m/z =
286 (90) (C14H14N4OS); CHN : Anal. Calcd :C, 58.74
;H, 4.89; N: 19.58. Found: C: 58.79; H: 4.80; N; 19.55.
M.p.: 289-291oC, IR (cm-1) 3200, 1700,
1220; 1H-NMR(CDCl3): 1.70-1.76 (m, 4H, CH2 at C6
& C7) 2.60-2.64 (m, 2H, CH2 at C-5); 2.71-2.74 (m,
2H, CH2 at C8), 7.30-7.50 (m, 4H, Ar -H); 8.5(br.s,
1H, NH); MS: m/z (%) 348[M+] (90) C16H13Cl35N2OS,
350[M+2] (25)( C16H13Cl37N2OS2); CHN: Anal. Calcd
(%): C, 55.09; H,3.73; N, 8.03; Found: C, 55.30; H,
3.76; N, 8.09.
General procedure for synthesis of : 3-
Substituted-2-hydrazino-5,6,7,8-tetrahydro-3H-
benzo[4,5]thieno[2,3-d]pyrimidin-4-ones.(12).
A mixture of compound 11b (1.0 mmol),
and hydrazine hydrate (99%)(2.0 mmol) in ethanol

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AL-ISSA, Orient. J. Chem., Vol. 30(2), 469-477 (2014)
General procedure for synthesis of: 4- 4-Allyl-1-mercapto-6,7,8,9- tetrahydrobenzo[b]
Substituted-1-methyl-6,7,8,9-tetrahydro-4H- thieno[2,3-d][1,2,4] triazolo[3,4-b] pyrimidin 5(4H)
benzo[4,5]thieno[2,3-d][1,2,4]triazolo[3,4-b] one (14a)
Pyrimidine 5-ones(13b,c
)
m.p. : 246-248 oC, IR (Cm-1): 3200, 1680,
A mixture of compound 12a,b (1.0 mmol) 1210; 1H-NMR (CDCl3) 1.78-1.81(m, 4H, CH2 at C-
and acetic acid (10 ml) was submitted to microwave 7 d C-8), 2.65-2.71 (m, 2H, CH2 at C-6); 2.95-3.00
irradiation for 10 min at ( 60W )80oC. After cooling (m, 2H, CH2 at C-9); 4.48-4.60 (m, 2H, N-CH2), 5.00
the reaction mixture was poured into ice-cooled (dd, 1H, J= 9.8 Hz, =CH2); 5.27 (dd, 1H, J= 16.8 Hz,
water. The solid product was collected by filtration =CH2) 5.86-5.91 (m, 1H, HC=); 10.6 (br. s, 1H, SH);
washed several time with ethanol, dried and MS: m/z(%) ,[M+] 318 (100) (C14H14N4OS2); CHN:
recrystallized from ethanol.
Anal. Cacld. (%): C, 52.83; H , 4.40; N, 17.61. Found
C: 52.89; H: 4.48; N: 17.69.
4-Allyl-1-methyl-6,7,8,9-tetrahydro-4H-benzo
[4,5] thieno[2,3-d][1,2,4] triazolo [3,4-b] pyrimidin- 4-(Chlorophenyl)-1-mercapto-6,7,8,9-
5-one (13b)
tetrahydrobenzo[b]thieno[2,3-b] [1,2,4] triazolo
M.p.: 228-230oC; IR (cm-1):1700, 1610; 1H- [3,4-b] pyrimidin-5 (4H)-one (14b)
o
NMR (DMSO-d6): 1.78-1.89 (m, 4H, 2CH2 at C-7&
M.p.: 260-263 C, IR (cm-1): 3300, 1600,
1
C-8), 2.6 (m, 2H, CH2 at C-6) ,2.76 (s, 3H, CH3),2.96- 1610, 1200; H-NMR (CDCl3): 1.80-1.84 (m, 4H,
3.2 (m, 2H at C-9); 4.57-4.70 (m, 2H, N-CH2), 5.10 2CH2 at C-7 d C-8); 2.50-2.62 (m, 2H, CH2 at C-6);
(dd, 1H, J= 19.8, CH2=), 5.40 (dd, H, J = 17.5, CH2=) 2.95-3.2(m, 2H, CH2 at C-9), 7.1-7.80 (m, 4H, Ar-H),
6.03(m, 1H, HC=); MS: m/z [M+] 300 (100); 11.5 (br. s, 1H, SH); MS: m/z(%) ,[M+] 388 (90)
C15H16N4OS. CHN : Anal. Calcd: C,60.00; H, 5.33; N, (C17H1335ClN4OS2),390[M+2] (25) (C17H1337ClN4OS2);
18.66, Found: C,60.50; H, 5.40; N,18.65.
CHN Anal. Calcd. (%) : C, 52.50; H , 3.34; N, 14.41.
Found: C, 52.59; H, 3.40; N, 14.40.
4-(4-Chlorophenyl)-1-methyl-6,7,8,9-tetrahydro-
4H-benzo[4,5] thieno[2,3-d][1,2,4] triazolo[3, 4,-b]
pyrimidin-5 -one (13c)
RESULTS AND DISCUSSION
M.p.: 300<, IR (cm-1): 1680, 1610; 1H-NMR
The starting materials, namely 2-amino-3-
(DMSO-d6): 1.80-1.86 (m, 4H, 2CH2 at C-7 d C-8) (carboxyamide or carboxylic acid)-4,5-disubtituted
2.5 -268(m, 2H, CH2 at C-6); 2.73 (s, 3H, CH3), thiophene 1a,b were prepared according to the
3.00-3.20 (m, 2H, CH2 at C-9) 7.30-7.70 (m, 4H, corresponding literature methods18,19
Ar-H); MS: m/z(%) 370 [M+] (100) (C18H1535ClN4OS;
The reaction of 1a,b and formamide under
C: 58.29; H: 4.04; N: 15.11. Found :C, 58.62; H, 4.09; a microwave irradiation with reactants ratio of 1:2 at
.
372[M+2] (40)(C18H1537ClN4OS); CHN: Anal. Calcd.
N, 15.12.
1:5-6 in the presence of one equivalent of acetic
acid at (300 W) for 10 min 130oC yielded
General procedure for synthesis of: 4- thienopyrimidinone derivatives 4a-c (Scheme 1, Table
Substituted-1-mercapto-6,7,8,9-tetrahydro-4H- 1).
benzo[4,5]thieno[2,3-d][1,2,4]triazolo[3,4-
b]pyrimidin-5-ones (14a,b).
The next step we converted 3H-
A mixture of 12a,b (1.0 mmol) and carbon thieno[2,3-d]pyrimidin-4-one 4b in to 4-
disulphide (10 mL) in pyridine (10 mL) was stirred chlorothieno[2,3-d]pyrimidine derivatives 7 by the
for 10 min., then submitted to microwave irradiation action of phosphorous oxychloride using both
for 10 min at (60 W) 40oC. The mixture was classical and microwave reaction(11,12,20-22); the latter
evaporated under reduced pressure and the residue method afforded higher yields of the required
was treated with ethanol. The formed solid was products in shorter time.(Scheme 3, Table 2)
filtered and washed several times with water, dried,
and recrystallized from ethanol.
Substitution with an aromatic amine was
performed on chloro derivatives under classical

AL-ISSA, Orient. J. Chem., Vol. 30(2), 469-477 (2014)
475
and microwave irradiation to produce the anilino
derivatives 8a-c. (Scheme 3, Table 2) .The structure
of synthesized compounds were assigned on the
basis of its spectral data and elemental analysis.
Next attention was focused on the prep. In the
classical synthesis of this compounds, a mixture of
starting material reacted with alkyl or aryl thio
isocyanates in ethanol. This method provided low
to moderate yield and long reaction time(22). We have
recently synthesis the target compounds 11a-c using
microwave irradiation in acetic acid (Scheme 4,
Table 3).
Table 1: Microwave experimental condition for the synthesis of compound 4:
Compound
No.
R1
R2
X
Substrate Temp. Power in Yield
M.p.
(0C)
Lit..m.p24
(0C)
ratio
(0C)
put (W)
(%)
1a
1b
1c
1a
1b
1c
CH3
CH3
CH3
NH2
NH2
NH2
OH
OH
OH
1:6
1:5
1:5
1:6
1:5
1:5
130
130
130
130
130
130
300
300
300
300
300
300
85
86
81
79
83
81
180-183
257-259
210-211
180-183
257-259
210-211
(CH2)4
(CH2)5
CH3
(CH2)4
(CH2)5
255-275
209-211
—
255-275
209-211
Table 2: Experimental conditions used for the microwave assisted
and classical methods synthesis of compounds 7 & 8
Compound.
No.
Ar
Microwave methoda
Classical Methodb
Reaction Yield %
time (h.)
M.p.
(0C)
Lit..m.p24
(0C)
Reaction
Yield %
time (min.)
7a
8a
8b
8c
—
15
20
20
20
75
85
76
84
20
12
12
12
48
13
12
15
93-95
90-92
—-
224-226
—-
4-CH3-C6H4
3-CF3C6H4
2,5-CH3C6H4
235-237
224-225
213-215
a; Reaction conditions: 2-PrOH, reflux under MW irradiation (60 W)
b: Reaction conditions: 2-PrOH, reflux temperature.
Table 3: Microwave experimental conditions for the synthesis of compounds 11-14:
Comp.
No.
R
Temp.
(oC)
Power in
put (W)
Time
(min.)
Yield
(%)
M.P.
(oC)
Lit.m.p24
(oC)
11a
11b
11c
12a
12b
13a
13b
13c
14a
14b
CH2CH=CH2
C6H5
4-ClC6H4
CH2CH=CH2
4-ClC6H4
CH2CH=CH2
CH2CH=CH2
4-ClC6H4
120
120
120
100
100
80
80
80
40
40
300
300
300
60
60
60
60
60
60
60
20
20
20
5
85
87
85
80
86
87
83
85
83
87
234-235
261-263
289-291
196-198
204-206
213-215
228-230
>300
-
259-261
289-290
-
5
204-204
10
10
10
10
10
-
-
300
-
-
CH2CH=CH2
4-ClC6H4
246-248
260-263

476
AL-ISSA, Orient. J. Chem., Vol. 30(2), 469-477 (2014)
The MW method requires higher yields,
Antimicrobial activity
The antimicrobial activity of the
compounds considered was tested on the following
organisms:
short reaction time, and eco friendly. Reaction of
11a-c with hydrazine hydrate under microwave
irradiation at 60 W(100oC) for 5 min., afforded 2-
hydrazino derivatives 12a,b.(Scheme 4, Table 3).
Cyclization of compound 12a,b by aliphatic
carboxylic acid, namely Formic or acetic acid under
MW irradiation for 10 min at (60W) 80oC gave the
triazolo derivatives 13a and 13b,c respectively
(Scheme 4,Table 3).
1
2
3
4
Candida albicans ATCC No. 10231
Staphylocoecus Aureus ATCC No. 6538.
Eschierichia Coli ATCC No. 8739.
Proteus mirabilis ATCC No. 29906.
The biological activity was planned
according to the cup-plate method adopted with
Finally, treatment of 12a,b with carbon
disulphide under microwave irradiation for 10 min.
yielded mercaptotriazolo derivatives 14a,b (Scheme
4, Table 3).
some modify23
.
What man No. 2 filter paper disk (6.5 cm)
was impregnated with 200 mg of the compound.
The disk was placed on the surface of the cold solid
medium petridishes vaccinated with considered
organisms and then incubated at 5oC for 1h. to
permit good diffusion and then transferred to an
incubated at 28oC for 24 h.
The structure of compounds 11-14 were
confirmed from their spectral data and elemental
analysis.
A summary of the biological activity results
is shown in Table 4.
Table 4: Antimicrobial activity of the compounds against bacteria and fungi
Test
Compounds
Organism
5
7
8 b
11a
12b
13a
13b
14a
1
2
3
4
+
+
+
-
+
++
+
-
+
-
+
-
-
-
-
-
-
-
-
-
+
+
+
-
-
+
+
-
-
-
+
+
The sensitivity of microorganisms to the compound is identified in the following manner:
+++ = highly sensitive (inhibition zone 1.2-1.5 mm)
++ = fairly sensitive (inhibition zone 1.2-0.9 mm)
+ = Slightly sensitive (inhibition zone 0.9-0.6 mm)
-
= not sensitive.
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