Synthesis of novel quinoxalinone derivatives by conventional and microwave methods and assessing their biological activity

Article abstract of DOI:10.1007/s12272-011-1004-4

In this study, twenty-one arylaminoquinoxalinone derivatives were synthesized and their antibacterial activities against Staphylococci aureus, Pseudomonas aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi, and Shigella pneumoniae were evaluated relative to known antibiotics; augmentin, ampicillin, and chloramphenicol. The insecticidal activities of the prepared compounds were also investigated against Tribolium castaneum using permethrin as a standard insecticide. The derivatives were synthesized using both conventional and microwave techniques. Their structures were confirmed using spectral techniques and elemental analysis.

Full text of DOI:10.1007/s12272-011-1004-4

Arch Pharm Res Vol 34, No 10, 1605-1614, 2011
DOI 10.1007/s12272-011-1004-4
Synthesis of Novel Quinoxalinone Derivatives by Conventional and
Microwave Methods and Assessing their Biological Activity
Waqar Nasir1, Munawar Ali Munawar1, Ejaz Ahmed1, Ahsan Sharif1, Saeed Ahmed2, Amjad Ayub3,
Misbahul Ain Khan1, and Faizul Hassan Nasim4
2
1Institute of Chemistry, University of the Punjab, Quaid-e-Azam Campus, Lahore 54590, Pakistan, Gomal University, D.
3
4
I. Khan, Pakistan, PCSIR Laboratories Complex, Lahore 54600, Pakistan, and The Islamia University Bhawalpur, Bagh-
dad-ul-Jadeed Campus, Bhawalpur, Pakistan
(Received February 27, 2011/Revised June 15, 2011/Accepted June 16, 2011)
In this study, twenty-one arylaminoquinoxalinone derivatives were synthesized and their
antibacterial activities against Staphylococci aureus, Pseudomonas aureus, Escherichia coli,
Bacillus subtilis, Salmonella typhi, and Shigella pneumoniae were evaluated relative to known
antibiotics; augmentin, ampicillin, and chloramphenicol. The insecticidal activities of the pre-
pared compounds were also investigated against Tribolium castaneum using permethrin as a
standard insecticide. The derivatives were synthesized using both conventional and micro-
wave techniques. Their structures were confirmed using spectral techniques and elemental
analysis.
Key words: 3,4-Dihydroquinoxalin-2(1H)-one, 4-(Chloroacetyl)-3,4-dihydroquinoxaline-2(1H)-one,
Antibacterial, Insecticidal, Phytotoxic
Csikós et al., 1999; Kim and Kim, 2003). Various func-
tionalized quinoxalines have been synthesized under
INTRODUCTION
Quinoxalines represent an important class of het- microwave irradiation (Zhao et al., 2004; Zhang et al.,
erocyclic compounds. Several quinoxaline derivatives 2006). In this study, a series of quinoxalinone compounds
are associated with a broad range of physiological containing arylamino moieties were synthesized and
activities such as antimalarial (Haworth and Robinson, their bioactivity evaluated.
1948), antibacterial (Khan, 2008), antifungal (Ali et al.,
2000), anticancer (Toshima et al., 2003), antidiabetic
(Sarges, 1990), antitubercular (Jaso et al., 2005), and
anticonvulsant (Cai et al., 1997). They are also used as
fluorescent dyes and effective dyeing photo initiators
MATERIALS AND METHODS
Chemistry
Melting points were determined using a Gallenkamp
1
for free radical polymerization (Kucybala and melting point apparatus and were uncorrected. H-
Paczkowski, 1999; Rangnekar and Sonawane, 2000). and 13C-NMR spectra were acquired in DMSO-d6 and
Previous studies have revealed that both the recorded at 400 MHz and 100 MHz, respectively, on a
substituted and unsubstituted 1,2,3,4-tetrahydro qui- Brucker/XWIN-NMR instrument. Chemical shifts are
noxalines exhibit good antioxidant properties (Sakata given in ppm relative to (Me)4Si, which was used as
et al., 2005). Quinoxalines have been synthesized by an internal standard (s, singlet; d, doublet; t, triplet;
the condensation of o-phenylenediamine using a variety m, multiplet). Mass spectra were recorded on Jeol
of bifunctional compounds (Perkin and Riley, 1923; MSRoute and IR spectra were acquired using a Perkin
Elmer FTIR Spectrometer Spectrum RX 1 as KBr
pellets. Elemental analyses were performed in H.E.J.
Correspondence to: Munawar Ali Munawar, Institute of Chem-
Research Institute, Karachi University, Karachi and
istry, University of the Punjab, Lahore 54590, Pakistan
were within the range of ± 0.4% of the predicted
Tel: 92-42-923-0463, Fax: 92-42-9923-0998
values for all the compounds. Reagent grade materials
E-mail: mamunawar@chem.pu.edu.pk
1605

1606
W. Nasir et al.
were purchased from Aldrich Chemical Co. and were 125.5 (CH), 130.6 (C), 141.3 (C), 148.6 (C), 167.1 (C=O)
used without further purification. 3,4-Dihydroquino- and 169.0 (C=O); EIMS m/z: 281 (M+), 148, 119, 106,
xalin-2(1H)-one was synthesized using method pre- 92, 77 and 65. Anal. calcd for C16H15N3O2: C, 68.31; H,
viously published method (Perkin and Riley, 1923).
5.37; N, 14.94; O, 11.37. Found: C, 68.27; H, 5.39; N,
14.96.
Synthesis of 4-{(arylamino)acetyl}-3,4-dihydro-
4-{[(4-Methylphenyl)amino]acetyl}-3,4-dihydroqui-
quin oxalin-2(1
4-(Acetyl)-3,4-dihydroquinoxalin-2(1
4-(Acetyl)-3,4-dihydroquinoxalin-2(1 )-one (
H)-ones
H
)-one (3)
noxalin-2(1H)-one (4b)
H
3
) was White crystals, m.p. 172oC; IR
ν
max (cm−1): 3347 (NH),
1
synthesized by the dropwise addition of chloroacetyl 3192 (NH), 1693 (C=O) and 1665 (lactam C=O); H-
chloride to an ice cold solution of 3,4-dihydroquinoxalin- NMR (DMSO-d6, 300 MHz):
2(1 )-one ( ) in DMF and then stirred at room tem- ), 6.42-7.64 (m, 8H, Ar ), 5.55 (t,
perature for one h (An and Peng, 2003). The contents CH2N -Ar), 4.36 (s, 2H, cyclic CH2), 4.05 (d,
in the reaction flask were then poured slowly into Hz, 2H, COCH2) and 2.12 (s, 3H, ArCH3); 13C-NMR
sodium bicarbonate solution and the resulting precipi- (DMSO-d6, 100 MHz): 40.1 (CH2), 45.1 (CH2), 112.4
δ
10.69 (s, 1H, lactam
= 5.7 Hz, 1H,
= 5.6
H
2
NH
H
J
H
J
δ
tates were filtered, washed and dried in an oven at (CH), 112.4 (CH), 116.4 (CH), 122.2 (CH), 124.1 (CH),
100oC. The dried product (Yield: 95%) melted at 191oC 124.7 (CH), 129.2 (CH), 129.2 (CH), 126.1 (C), 131.9
(lit. An and Peng, 2003, 191-192oC).
(C), 137 (C), 145.8 (C), 167.3 (C=O), 169.7 (C=O); EIMS
m/z: 295 (M+), 148, 120, 119, 92, 91, 77 and 65. Anal.
calcd for C17H17N3O2: C, 69.14; H, 5.80; N, 14.23. Found:
Method A (conventional)
Aniline derivative (5.57 mmol) and a catalytic amount C, 69.33; H, 5.70; N, 14.32.
of KI (0.18 g, 1.11 mmol) was added to a suspension of
4-(chloroacetyl)-3,4-dihydro quinoxalin-2(1
g, 5.57 mmol) and NaHCO3 (0.7 g, 8.35 mmol) in 2-pro- noxalin-2(1
panol (50 mL). The reaction mixture was refluxed for White crystals, m.p. 214oC; IR
H)-one (1.25 4-{[(3-Methylphenyl)amino]acetyl}-3,4-dihydroqui-
H)-one (4c)
ν
max (cm−1): 3416 (NH),
1
eight to twelve h and the progress of the reaction was 3195 (NH), 1680 (C=O) and 1660 (lactam C=O); H-
monitored by TLC using CHCl3 and EtOAc as solv- NMR (DMSO-d6, 400 MHz):
ents (7:3). The solid obtained upon cooling was filter- ), 6.29-7.64 (m, 8H, Ar ), 5.70 (t,
ed, washed with chloroform and ethyl acetate and CH2N -Ar), 4.36 (s, 2H, cyclic CH2), 4.06 (d,
Hz, 2H, COCH2) and 2.13 (s, 3H, ArCH3); 13C-NMR
(DMSO-d6, 100 MHz): 21.0 (CH3), 39.0 (CH2), 45.0
δ
10.68 (s, 1H, lactam
= 5.6 Hz, 1H,
= 5.6
NH
H
J
H
J
recrystallized from acetone DMF mixture.
δ
(CH2), 109.4 (CH), 116.3 (CH), 122.2 (CH), 122.2 (CH),
Method B (Microwave)
4-(Chloroacetyl)-3,4-dihydroquinoxalin-2(1H)-one (1.25 124.1 (CH), 126,7 (CH), 129.7 (CH), 130.4 (CH), 121.7
g, 5.57 mmol) and NaHCO3 (0.7 g, 8.35 mmol) was (C), 132.0 (C), 137.1 (C), 145.7 (C), 167.3 (C=O) and
suspended in 2-propanol (25 mL) and the aniline 169.6 (C=O); EIMS m/z: 295 (M+), 148, 120, 119, 92,
derivative (5.57 mmol) was added. After the addition 91, 77 and 65. Anal. calcd for C17H17N3O2: C, 69.14; H,
of a catalytic amount of KI (0.18 g, 1.11 mmol), the 5.80; N, 14.23. Found: C, 69.01; H, 5.70; N, 14.20.
reaction flask was irradiated in a modified household
microwave oven (900 watt) that was equipped with a 4-{[(2-Methylphenyl)amino]acetyl}-3,4-dihydroqui-
water condenser for five to fifteen min. Compounds noxalin-2(1H)-one (4d)
4a-4u were synthesized using both of the above methods White crystals, m.p. 256-258oC; IR νmax (cm−1): 3416
A & B and are presented in the Table I.
(NH), 3196 (NH), 1680 cm−1 (C=O) and 1660 cm−1
(lactam C=O); 1H-NMR (DMSO-d6, 300 MHz):
10.68
(s, 1H, cyclic N ), 6.42-7.64 (m, 8H, Ar ), 5.54 (t, 1H,
= 5.8 Hz, CH2N -Ar), 4.36 (s, 2H, cyclic CH2), 4.05
White crystals, m.p. 218-220oC; IR νmax (cm−1): 3347 (d,
= 5.4 Hz, 2H, COCH2) and 2.12 (s, 3H, ArCH3);
(NH), 3191 (NH), 1691 (C=O) and 1665 (C=O); 1H-NMR 13C-NMR (DMSO-d6, 100 MHz):
21.0 (CH3), 35.0 (CH2),
(DMSO-d6, 400 MHz): 10.67 (s, 1H, lactam N ), 6.51- 48.0 (CH2), 109.4 (CH), 116.3 (CH), 122.2 (CH), 122.2
7.64 (m, 8H, Ar ), 5.72 (t, = 5.6 Hz, 1H, CH2N (CH), 124.1 (CH), 126,7 (CH), 129.7 (CH), 130.4 (CH),
Ar), 4.36 (s, 2H, cyclic CH2), 4.07 (d, = 5.5 Hz, 2H, 121.7 (C), 132.0 (C), 137.1 (C), 145.7 (C), 167.3 (C=O)
COCH2); 13C-NMR (DMSO-d6, 100 MHz): 40.1 (CH2), and 169.6 (C=O); EIMS m/z: 295 (M+), 148, 120, 119,
δ
4-{(Phenylamino)acetyl}-3,4-dihydroquinoxalin-
H
H
2(1H)-one (4a)
J
H
J
δ
δ
H
H
J
H-
J
δ
45.1 (CH2), 112.4 (CH), 112.4 (CH), 116.4 (CH), 122.2 92, 91, 77 and 65. Anal. calcd for C17H17N3O2: C, 69.14;
(CH), 124.1 (CH), 124.7 (CH), 129.2 (CH), 129.2 (CH), H, 5.80; N, 14.23. Found: C, 69.03; H, 5.83; N, 14.08.

Synthesis and Biological Studies of Quinoxalinones
1607
4-{[(4-Methoxyphenyl)amino]acetyl}-3,4-dihydro-
(DMSO-d6, 300 MHz):
δ
10.68 (s, 1H, lactam N
H
), 6.43-
quinoxalin-2(1
H
)-one (4e)
7.67 (m, 7H, ArH), 5.00 (t, J = 5.3 Hz, 1H, CH2NH-
White crystals, m.p. 175-178oC; IR νmax (cm−1): 3379 Ar), 4.38 (s, 2H, cyclic CH2), 4.12 (d,
J = 5.2 Hz, 2H,
(NH), 3191 (NH), 1680 cm− (C=O) and 1660 cm−1 COCH2), 2.17 (s, 3H, ArCH3), 1.97 (s, 3H, ArCH3); 13C-
1
(lactam C=O); 1H-NMR (DMSO-d6, 400 MHz):
(s, 1H, lactam N ), 6.47-7.63 (m, 8H, Ar ), 5.34 (t,
= 5.8 Hz, 1H, CH2N -Ar), 4.36 (s, 2H, cyclic CH2), 4.02 (CH), 122.2 (CH), 124.1 (CH), 125.8 (CH), 126.0 (CH),
(d, 2H, = 5.7 Hz, COCH2) and 3.61 (s, 3H, ArOCH3); 119.9 (C), 132.0 (C), 137.1 (C), 145.6 (C), 167.3 (C=O)
13C-NMR (DMSO-d6, 100 MHz): 55.3 (CH3), 40.1 and 169.8 (C=O); EIMS m/z: 309 (M+), 148, 147, 135,
δ
10.67 NMR (DMSO-d6, 100 MHz):
δ 12.4 (CH3), 20.3 (CH3),
H
H
J
40.1 (CH2), 45.5 (CH2), 107.8 (CH), 116.3 (CH), 118.7
H
J
δ
(CH2), 45.8 (CH2), 113.3 (CH), 113.3 (CH), 114.4 (CH), 134, 132, 119, 92, 91, 77 and 65. Anal. calcd for
114.4 (CH), 116.4 (CH), 122.2 (CH), 126.1 (CH), 126.6 C18H19N3O2: C, 69.14; H, 5.80; N, 14.23. Found: C,
(CH), 132.0 (C), 137.1 (C), 142.3 (C), 151.1 (C), 167.3 69.06; H, 5.94; N, 14.27.
(C=O) and 169.8 (C=O); EIMS m/z: 311 (M+), 148, 136,
120, 119, 92, 77 and 65. Anal. calcd for C17H17N3O2: C, 4-{[(2,4-Dimethylphenyl)amino]acetyl}-3,4-dihydro-
65.58; H, 5.50; N, 13.50. Found: C, 65.49; H, 5.59; N, quinoxalin-2(1H)-one (4i)
13.37.
White crystals, m.p. 235-236oC; IR νmax (cm−1): 3420
1
(NH), 3194 (NH), 1681.2 (C=O) and 1660 (C=O); H-
4-{[(3-Methoxyphenyl)amino]acetyl}-3,4-dihydro-
NMR (DMSO-d6, 300 MHz):
δ
10.68 (s, 1H, lactam N
H),
quinoxalin-2(1H)-one (4f)
6.74-7.66 (m, 7H, ArH), 4.84 (t,
J
= 5.6 Hz, 1H, CH2NH-
White crystals, m.p. 147oC; IR
ν
max (cm−1): 3350 (NH), Ar), 4.38 (s, 2H, cyclic CH2), 4.10 (d,
J
= 5.4 Hz, 2H,
1
3191 (NH), 1692 (C=O) and 1665 (lactam C=O); H- COCH2), 2.11 (s, 3H, ArCH3), 2.03 (s, 3H, ArCH3); 13C-
NMR (DMSO-d6, 400 MHz):
6.06-7.64 (m, 8H, Ar ), 5.77 (t,
Ar), 4.36 (s, 2H, cyclic CH2), 4.06 (d,
COCH2) and 3.62 (s, 3H, ArOCH3); 13C-NMR (DMSO- 124.7 (C), 126.5 (C), 131.9 (C), 141.3 (C), 143.4 (C),
d6, 75 MHz):
54.7 (CH3), 39.9 (CH2), 45.7 (CH2), 98.1 167.2 (C=O) and 169.7 (C=O); EIMS m/z: 309 (M+),
δ
10.67 (s, 1H, lactam NH), NMR (DMSO-d6, 75 MHz):
= 4.2 Hz, 1H, CH2N 39.9 (CH2), 45.0 (CH2), 109.6 (CH), 116.3 (CH), 122.2
= 4.1 Hz, 2H, (CH), 124.1 (CH), 126.1 (CH), 126.8 (CH), 130.5 (CH),
δ 17.2 (CH3), 20.0 (CH3),
H
J
H-
J
δ
(CH), 102 (CH), 105.3 (CH), 116.4 (CH), 122.2 (CH), 148, 135, 134, 119, 92, 91, 77 and 65. Anal. calcd for
124.1 (CH), 126.6 (CH), 129.5 (CH), 132.0 (C), 137.0 C18H19N3O2: C, 69.14; H, 5.80; N, 14.23. Found: C,
(C), 149.5 (C), 160.3 (C), 167.3 (C=O) and 169.5 (C=O); 69.17; H, 5.86; N, 14.33.
EIMS m/z: 311 (M+), 148, 136, 120, 119, 92, 77 and
65. Anal. calcd for C17H17N3O2: C, 65.58; H, 5.50; N, 4-{[(2,5-Dimethylphenyl)amino]acetyl}-3,4-dihydro-
13.50. Found: C, 65.60; H, 5.54; N, 13.37.
quinoxalin-2(1H)-one (4j)
White crystals, m.p. 219-221oC; IR νmax (cm−1): 3422
1
4-{[(2-Methoxyphenyl)amino]acetyl}-3,4-dihydro-
(NH), 3197 (NH), 1691.2 (C=O) and 1665 (C=O); H-
quinoxalin-2(1
H
)-one (4g)
NMR (DMSO-d6, 300 MHz):
), 6.31-7.66 (m, 7H, Ar ), 4.99 (t,
-Ar), 4.38 (s, 2H, cyclic CH2), 4.10 (d,
), 6.54- Hz, 2H, COCH2), 2.12 (s, 3H, ArCH3), 2.01 (s, 3H,
= 5.4 Hz, 1H, CH2N 16.9 (CH3),
-Ar), ArCH3); 13C-NMR (DMSO-d6, 75 MHz):
4.37 (s, 2H, cyclic CH2), 4.10-4.12 (d, = 5.3 Hz, 2H, 21.1 (CH3), 40.3 (CH2), 46.1 (CH2), 110.2 (CH), 116.4
COCH2) and 3.30 (s, 3H, ArOCH3); 13C-NMR (DMSO- (CH), 117.0 (CH), 122.2 (CH), 124.2 (CH), 126.1 (CH),
d6, 75 MHz): 55.4 (CH3), 40.4 (CH2), 46.2 (CH2), 109.8 129.6 (CH), 118.7 (C), 132.0 (C), 135.5 (C), 143.0 (C),
δ
10.69 (s, 1H, lactam
= 5.7 Hz, 1H,
= 5.5
White crystals, m.p. 214oC; IR
ν
max (cm−1): 3370 (NH),
NH
H
J
1
3187 (NH), 1712 (C=O) and 1667 (C=O); H-NMR CH2N
(DMSO-d6, 400 MHz):
H
J
δ 10.67 (s, 1H, cyclic NH
7.68 (m, 8H, Ar ), 5.16 (t,
H
J
H
δ
J
δ
(CH), 116.3 (CH), 116.4 (CH), 121.0 (CH), 122.5 (CH), 145.5 (C), 167.3 (C=O) and 169.8 (C=O); EIMS m/z
:
124.0 (CH), 126.0 (CH), 126.6 (CH), 132.0 (C), 137.3 309 (M+), 148, 134, 119, 92, 91, 77 and 65. Anal. calcd
(C), 146.5 (C), 151.0 (C), 167.2 (C=O) and 169.3 (C=O); for C18H19N3O2: C, 69.14; H, 5.80; N, 14.23. Found: C,
EIMS m/z: 311 (M+), 148, 136, 120, 119, 92, 77 and 65. 69.01; H, 5.76; N, 14.12.
Anal. calcd for C17H17N3O2: C, 65.58; H, 5.50; N, 13.50.
Found: C, 65.52; H, 5.44; N, 13.45.
4-{[(2,6-Dimethylphenyl)amino]acetyl}-3,4-dihydro-
quinoxalin-2(1 )-one (4k)
H
4-{[(2,3-Dimethylphenyl)amino]acetyl}-3,4-dihydro- White crystals, m.p. above 250oC; IR max (cm−1): 3440
ν
quinoxalin-2(1 )-one (4h)
(NH), 3197 (NH), 1691 (C=O) and 1665 (C=O); 1H-NMR
White crystals, m.p. 228-232oC; IR νmax (cm−1): 3420 (DMSO-d6, 300 MHz):
10.68 (s, 1H, lactam NH), 6.43-
(NH), 3194 (NH), 1681 (C=O) and 1660 (C=O); 1H-NMR 7.66 (m, 7H, Ar
), 5.00 (t, = 5.7 Hz, 1H, CH2N
H
δ
H
J
H-

1608
W. Nasir et al.
Ar), 4.38 (s, 2H, cyclic CH2), 4.10 (d,
J
= 5.4 Hz, 2H, 46.1 (CH2), 113.7 (CH), 113.7 (CH), 116.3 (CH), 119.4
COCH2), 2.11 (s, 3H, ArCH3), 2.02 (s, 3H, ArCH3); 13C- (CH), 122.2 (CH), 124.0 (CH), 128.4 (CH), 128.4 (CH),
NMR (DMSO-d6, 100 MHz):
δ 16.9 (CH3), 16.9 (CH3), 126.0 (C), 131.9 (C), 137.1 (C), 147.1 (C), 167.2 (C=O)
39.8 (CH2), 45.0 (CH2), 116.3 (CH), 120.3 (CH), 121.8 and 169.1 (C=O); EIMS m/z: 317 (M++2), 315 (M+),
(CH), 122.9 (CH), 123.6 (CH), 123.6 (CH), 124.9 (CH), 148, 142, 140, 119, 105, 92, 91, 77 and 65. Anal. calcd
123.7 (C), 123.7 (C), 130.6 (C), 141.3 (C), 147.3 (C), 167.3 for C16H14ClN3O2: C, 60.86; H, 4.47; N, 13.31. Found:
(C=O) and 169.6 (C=O); EIMS m/z: 309 (M+), 148, 147, C, 60.70; H, 4.50; N, 13.40.
135, 134, 132, 119, 92, 91, 77 and 65. Anal. calcd for
C18H19N3O2: C, 69.14; H, 5.80; N, 14.23. Found: C, 4-{[(3-Chlorophenyl)amino]acetyl}-3,4-dihydroqui-
68.95; H, 5.84; N, 14.27.
noxalin-2(1
H)-one (4o)
White crystals, m.p. 194-196oC; IR νmax (cm−1): 3447
4-{[(3,4-Dimethylphenyl)amino]acetyl}-3,4-dihydro- (NH), 3191 (NH), 1692 (C=O) and 1661.6 cm−1 (C=O);
quinoxalin-2(1 )-one (4l) 10.68 (s, 1H, cyclic
1H-NMR (DMSO-d6, 300 MHz):
White crystals, m.p. 270oC; IR
), 6.43-7.66 (m, 8H, Ar ), 5.8 (t, = 5.6 Hz, 1H,
3189 (NH), 1692 cm−1 (C=O) and 1666 (lactam C=O); CH2N
-Ar), 4.38 (s, 2H, cyclic CH2), 4.10 (d, = 5.4
1H-NMR (DMSO-d6, 400 MHz): 10.71 (s, 1H, lactam Hz, 2H, COCH2); 13C-NMR (DMSO-d6, 100 MHz):
), 6.25-7.63 (m, 7H, Ar ), 5.49 (t, = 5.7 Hz, 1H, 40.1 (CH2), 45.0 (CH2), 111.1 (CH), 111.4 (CH), 115.5
CH2N -Ar), 4.36 (s, 2H, cyclic CH2), 4.02 (d, = 5.4 (CH), 116.3 (CH), 122.1 (CH), 124.0 (CH), 130.1 (CH),
Hz, 2H, COCH2), 2.05 (s, 3H, ArCH3), 2.03 (s, 3H, 130.1 (CH), 126.5 (C), 131.8 (C), 137.5 (C), 149.7 (C),
H
δ
ν
max (cm−1): 3446 (NH),
NH
H
J
H
J
δ
δ
NH
H
J
H
J
ArCH3); 13C-NMR (DMSO-d6, 100 MHz):
δ
18.1 (CH3), 167.2 (C=O) and 169.1 (C=O); EIMS m/z: 317 (M++2),
19.7 (CH3), 40.1 (CH2), 37.8 (CH2), 109.9 (CH), 116.3 315 (M+), 142, 140, 119, 105, 92, 91, 77 and 65. Anal.
(CH), 122.1 (CH), 124.1 (CH), 124.2 (CH), 126.1 (CH), calcd for C16H14ClN3O2: C, 60.86; H, 4.47; N, 13.31.
129.7 (CH), 123.6 (C), 131.9 (C), 136.1 (C), 137.1 (C), Found: C, 61.0; H, 4.36; N, 13.39.
146.1 (C), 167.2 (C=O) and 169.7 (C=O); EIMS m/z
:
309 (M+), 148, 134, 119, 92, 91, 77 and 65. Anal. calcd 4-{[(4-Bromophenyl)amino]acetyl}-3,4-dihydroqui-
for C18H19N3O2: C, 69.14; H, 5.80; N, 14.23. Found: C, noxalin-2(1H)-one (4p)
69.19; H, 5.70; N, 14.30.
White crystals, m.p. 232-234oC; IR νmax (cm−1): 3550
(NH), 3194 (NH), 1680.5 (C=O) and 1660 cm−1 (C=O);
4-{[(3,5-Dimethylphenyl)amino]acetyl}-3,4-dihydro- 1H-NMR (DMSO-d6, 400 MHz):
δ
10.66 (s, 1H, lactam
), 5.98 (t, = 5.6 Hz, 1H,
-Ar), 4.35 (s, 2H, cyclic CH2), 4.08 (d, = 5.3 Hz,
40.4
), 6.43- (CH2), 46.1 (CH2), 114.3 (CH), 116.3 (CH), 122.2 (CH),
= 5.7 Hz, 1H, CH2N 124.0 (CH), 126.5 (CH), 126.5 (CH), 131.2 (CH), 131.2
Ar), 4.38 (s, 2H, cyclic CH2), 4.10 (d, = 5.4 Hz, 2H, (CH), 115.7 (C), 131.9 (C), 137.0 (C), 147.5 (C), 167.2
COCH2), 2.11 (s, 3H, ArCH3), 2.02 (s, 3H, ArCH3); 13C- (C=O) and 169.1 (C=O); EIMS m/z: 361 (M++2), 359
NMR (DMSO-d6, 100 MHz):
21.3 (CH3), 21.3 (CH3), (M+), 186, 184, 148, 119, 105, 92, 77 and 65. Anal. calcd
quinoxalin-2(1
H
)-one (4m)
NH
), 6.50-7.64 (m, 8H, Ar
H
J
White crystals, m.p. 242oC; IR
ν
max (cm−1): 3440 (NH), CH2N
H
J
3197 (NH), 1691 (C=O) and 1665 (C=O); H-NMR 2H, COCH2); 13C-NMR (DMSO-d6, 75 MHz):
δ
1
(DMSO-d6, 300 MHz):
δ 10.68 (s, 1H, lactam NH
7.66 (m, 7H, Ar ), 5.00 (t,
H
J
H-
J
δ
40.1 (CH2), 45.0 (CH2), 113.7 (CH), 113.7 (CH), 116.3 for C16H14BrN3O2: C, 53.35; H, 3.92; N, 11.67. Found:
(CH), 122.2 (CH), 124.0 (CH), 126.0 (CH), 128.0 (CH), C, 53.51; H, 54.06; N, 11.50.
131.9 (C), 139.0 (C), 139.0 (C), 139.0 (C), 147.1 (C), 167.2
(C=O) and 169.2 (C=O); EIMS m/z: 309 (M+), 148, 134, 4-{[(4-Iodophenyl)amino]acetyl}-3,4-dihydroqui-
119, 92, 91, 77 and 65. Anal. calcd for C18H19N3O2: C, noxalin-2(1
69.14; H, 5.80; N, 14.23. Found: C, 69.26; H, 5.71; N, White crystals, m.p. 199oC; IR
14.34.
3193.6 (NH), 1692.4 (C=O) and 1660.8 (C=O); 1H-NMR
(DMSO-d6, 400 MHz): 9.86 (s, 1H, lactam N ), 5.58-
4-{[(4-Chlorophenyl)amino]acetyl}-3,4-dihydroqui- 6.82 (m, 8H, Ar ), 5.19 (t, = 5.5 Hz, 1H, CH2N
= 5.3 Hz, 2H,
39.9 (CH2),
H)-one (4q)
ν
max (cm−1): 3354.6 (NH),
δ
H
H
J
H-
noxalin-2(1
H
)-one (4n)
Ar), 3.53 (s, 2H, cyclic CH2), 3.27 (d, J
White crystals, m.p. 241-243oC; IR νmax (cm−1): 3447 COCH2); 13C-NMR (DMSO-d6, 100 MHz):
δ
1
(NH), 3191 (NH), 1692 (C=O) and 1661.6 (C=O); H- 44.7 (CH2), 115.0 (CH), 116.3 (CH), 116.3 (CH), 122.1
NMR (DMSO-d6, 300 MHz):
6.55-7.66 (m, 7H, Ar ), 5.98 (t,
Ar), 4.36 (s, 2H, cyclic CH2), 4.10 (d,
COCH2); 13C-NMR (DMSO-d6, 100 MHz):
δ
10.68 (s, 1H, lactam N
= 5.5 Hz, 1H, CH2N
= 5.2 Hz, 2H,
40.4 (CH2), Anal. calcd for C16H14IN3O2: C, 47.19; H, 3.47; N,
H
H-
), (CH), 124.0 (CH), 126.0 (CH), 76.7 (C), 131.9 (C), 136.9
(C), 147.9 (C), 167.2 (C=O) and 169.1 (C=O); EIMS m/
: 409 (M+), 232, 148, 147, 119, 92, 91, 77, 76 and 65.
H
J
J
z
δ

Synthesis and Biological Studies of Quinoxalinones
1609
1
10.32. Found: C, 47.01; H, 3.30; N, 10.21.
3191 (NH), 1692 (C=O) and 1660 (C=O); H-NMR
(DMSO-d6, 400 MHz): 10.68 (s, 1H, lactam N ), 6.43-
7.65 (m, 8H, Ar ), 5.88 (t, = 5.7 Hz, 1H, CH2N
Ar), 4.36 (s, 2H, cyclic CH2), 4.08 (d, = 5.3 Hz, 2H,
White crystals, m.p. 240-242oC; IR νmax (cm−1): 3356 COCH2), 2.13 (s, 3H, ArCH3); 13C-NMR (DMSO-d6
(NH), 3231 (NH), 1704 (C=O) and 1654 (C=O); 1H-NMR 100 MHz):
18.4 (CH3), 39.9 (CH2), 44.9 (CH2), 111.5
(DMSO-d6, 400 MHz): 10.64 (s, 1H, lactam N ), 8.54 (CH), 112.0 (CH), 116.3 (CH), 122.1 (CH), 124.0 (CH),
(s, 1H, O ), 7.53-5.94 (m, 8H, Ar ), 5.5 (t, = 5.5 Hz, 126.0 (CH), 131.0 (CH), 121.9 (C), 131.9 (C), 133.4 (C),
1H, CH2N -Ar), 4.32 (s, 2H, cyclic CH2), 4.28 (d,
5.3 Hz, 2H, COCH2); 13C-NMR (DMSO-d6, 75 MHz):
δ
H
4-{[(4-Hydroxyphenyl)amino]acetyl}-3,4-dihydro-
H
J
H-
quinoxalin-2(1H)-one (4r)
J
,
δ
δ
H
H
H
J
H
J
=
δ
137.0 (C), 147.6 (C), 167,2 (C=O) and 169.3 (C=O);
EIMS m/z: 331 (M+2, 2.2%), 329 (M+), 156, 154, 148,
40.3 (CH2), 46.1 (CH2), 113.4 (CH), 113.4 (CH), 115.4 125, 119, 118, 92, 91, 77 and 65. Anal. calcd for
(CH), 115.4 (CH), 116.3 (CH), 122.1 (CH), 124.1 (CH), C17H16ClN3O2: C, 61.91; H, 4.89; N, 12.74. Found: C,
126.4 (CH), 132.0 (C), 137.1 (C), 141.1 (C), 149.0 (C), 61.83; H, 4.93; N, 12.65.
167.3 (C=O) and 169.5 (C=O); EIMS m/z: 297 (M+), 148,
122, 119, 92, 77 and 65. Anal. calcd for C16H15N3O3: C,
64.64; H, 5.09; N, 14.13. Found: C, 64.50; H, 4.99; N,
14.08.
Antibacterial protocol
The antibacterial activities of the synthesized com-
pounds were investigated in vitro using the disc dif-
fusion technique (Atta-ur-Rehman et al., 1999). The
4-{[(3-Hydroxyphenyl)amino]acetyl}-3,4-dihydro-
organisms tested included Staphylococci aureus
domonas aureus Escherrichia coli Bacillus subtilis
White crystals, m.p. 224-226oC; IR νmax (cm−1): 3356 Salmonella typhi, and Shigella pneumoniae. One
(NH), 3231 (NH), 1704 (C=O) and 1654 (C=O); 1H-NMR hundred L of a suspension containing 108 colony-
(DMSO-d6, 400 MHz): 10.66 (s, 1H, lactam N ), 8.90 forming units (CFU/mL) was spread on Muller Hinton
(s, 1H, O ), 5.94-7.63 (m, 8H, Ar ), 5.6 (t, = 5.4 Hz, agar medium. Discs of 6 mm impregnated with 500
1H, CH2N -Ar), 4.36 (s, 2H, cyclic CH2), 4.02 (d, per disc of the test compound were placed on the in-
5.3 Hz, 2H, COCH2); 13C-NMR (DMSO-d6, 100 MHz): oculated discs. Augmentin, ampicilin and chloram-
40.3 (CH2), 46.2 (CH2), 99.4 (CH), 103.7 (CH), 104 phenicol (100 g per disc) were used as a positive con-
, Pseu-
quinoxalin-2(1H)-one (4s)
,
,
,
µ
δ
H
H
H
J
µg
H
J =
δ
µ
(CH), 116.4 (CH), 122.2 (CH), 124.0 (CH), 126.0 (CH),
129.4 (CH), 132.0 (C), 137.1 (C), 149.4 (C), 158.1 (C),
167.3 (C=O) and 169.5 (C=O); EIMS m/z: 297 (M+),
148, 122, 119, 92, 77 and 65. Anal. calcd for C16H15N3O3:
C, 64.64; H, 5.09; N, 14.13. Found: C, 64.53; H, 5.15;
N, 14.17.
Table I. Comparison of the microwave and conventional
synthesis
Time in h Time in min % Age yield % Age yield
Comp.
(conventional) (microwave) (conventional) (microwave)
4a
4b
4c
4d
4e
4f
4g
4h
4i
18
19
19
19
19
19
19
19
10
10
12
10
19
19
17
19
19
19
19
19
19
12
12
12
12
12
12
12
15
15
15
15
15
15
15
15
15
15
15
15
18
12
87.5
65.2
66.3
75.9
77.7
63.9
61,7
64.7
75.8
72.8
40.0
74.7
74.3
71.0
75.0
77.6
73.3
55.1
50.6
48.9
78.0
93.2
75.3
74.5
81.7
80.3
75.8
78.6
73.6
75.1
74.2
49.0
70.0
79.1
83.0
84.0
71.5
80.4
61.2
63.5
59.3
82.0
4-{[(2-Hydroxyphenyl)amino]acetyl}-3,4-dihydro-
quinoxalin-2(1H)-one (4t)
White crystals, m.p. 264-266oC; IR νmax (cm−1): 3356
(NH), 3231 (NH), 1704 (C=O) and 1654 (C=O); 1H-NMR
(DMSO-d6, 400 MHz):
(s, 1H, O ), 5.94-7.6 (m, 7H, Ar
1H, CH2N -Ar), 4.36 (s, 2H, cyclic CH2), 4.03 (d,
5.4 Hz, 2H, COCH2); 13C-NMR (DMSO-d6, 100 MHz):
40.1 (CH2), 46.3 (CH2), 111.5 (CH), 116.0 (CH), 116.3
δ
10.67 (s, 1H, lactam N
H), 8.9
H
H
), 5.60 (t, = 5.4 Hz,
J
H
J =
4j
4k
4l
δ
(CH), 121.8 (CH), 122.0 (CH), 124.0 (CH), 126.6 (CH),
128.7 (CH), 131.8 (C), 137.6 (C), 145.0 (C), 151.6 (C),
167.0 (C=O) and 169.1 (C=O); EIMS m/z: 297 (M+), 148,
122, 119, 92, 91, 77 and 65. Anal. calcd for C16H15N3O3:
C, 64.64; H, 5.09; N, 14.13. Found: C, 64.50; H, 5.03;
N, 14.01.
4m
4n
4o
4p
4q
4r
4s
4t
4-{[(3-Chloro-4-methylphenyl)amino]acetyl}-3,4-di-
hydroquinoxalin-2(1
H
)-one (4u)
White crystals, m.p. 200oC; IR
ν
max (cm−1): 3447 (NH),
4u

1610
W. Nasir et al.
Ar = -Ph, 4-Me-Ph, 3-Me-Ph, 2-Me-Ph, 4-MeO-Ph, 3-MeO-Ph, 2-MeO-Ph, 2,3-diMe-Ph, 2,4-diMe-Ph, 2,5-diMe-
Ph, 2,6-diMe-Ph, 3,4-diMe-Ph, 3,5-diMe-Ph, 4-Cl-Ph, 3-Cl-Ph, 4-Br-Ph, 4-I-Ph, 4-Hydroxy-Ph, 3-Hydroxy-Ph, 2-
Hydroxy-Ph, 3-Chloro-2-Methyl-Ph.
Scheme 1. Reagents and conditions: (a) ClCH2COOH, NH4OH, H2O; (b) ClCH2COCl, NaHCO3, DMF; (c) Aniline derivative,
KI, NaHCO3, 2-propanol
trol to determine the sensitivity of each microbial spe- perature of 37oC for 18 and 24 h. The numbers of
cies tested. The inoculated plates were incubated at seeds germinated were counted. Water was used as a
37oC for 24 h. The antimicrobial activity was deter- blank control. The percentage of ungerminated seeds
mined by measuring the zone of inhibition in mm was used to determine the phytotoxic characteristics
against all test organisms.
of the test compounds.
Insecticidal protocol
Wheat flour (1 gm) was added to petri plates, fol-
Phytotoxicity protocol (Agro infusion)
The agro infusion technique was derived from agro-
lowed by the addition of the test compounds at concen- infilteration, which is an established plant molecular
trations of 100, 500 and 1000 ppm per gram of flour biology technique. The advantage of the Agro infusion
(Atta-ur-Rehman et al., 2001). Thirty insects, Tribolium technique is that it induces host responses more rapid
castaneum (red flour beetle), collected from wheat than that of viron inoculation (Palanichelvam et al.,
grains and flour depots were placed in each petri plate 2000).
containing the contaminated feed. Permithrin (500
µg/
Plants: tobacco plant, petunia (a flowering plant);
g) was used as standard drug. Insects were exposed to (Agro infusion) Procedure: 0.1 mL test sample (0.2%
the test compounds for 24 h and their percentage and 2%) was infused while moderate pressure was
mortality rates were calculated using the following applied underneath the leaf of the selected plant using
formula:
a syringe. The solution seeped into the surface tissue
of the leaf without damaging it.
The effect of different test samples on the health of
infusion areas of the leaves were observed after 18
and 24 h.
% age mortality = No of insects dead
× 100 /
No of insects added to petri dish
Phytotoxicity protocol
Seeds were soaked in the solution (10%) for 15, 30,
and 45 min and after washing with distilled water,
the seeds were presoaked on double layered filter
paper in petri dishes (Atta-ur-Rehman, 1991). The
RESULTS AND DISCUSSION
In this study, derivatives of 3,4-dihydroquinoxalin-
petri dishes were placed in the incubator at a tem- 2(1H)-one were synthesized using conventional and
Table II. In vitro antibacterial activity
Bacillus
subtilis
Staphylococci
aureus
Escherichia
coli
Pseudomonas
aeroginosa
Salmonella
typhi
Shigella
pneumoniaea
Test
Comp
(Gram-positive) (Gram-positive) (Gram-negative) (Gram-negative) (Gram-negative) (Gram-negative)
3
4d
4k
4o
4t
NIL
15
11
NIL
NIL
NIL
11
NIL
15
18
NIL
NIL
22
NIL
NIL
20
15
10
19
11
11
10
17
15
12
11
NIL
NIL
10
NIL
19
19
19
NIL
29
16
10
18
NIL
NIL
11
Augmentin
Ampicillin
Chloramphenicol
17
17
16
21
15
14
17
Conc of standard drug = 100 µg per disc; Conc of tested compounds = 500 µg per disc; Zone of inhibition = mm

Synthesis and Biological Studies of Quinoxalinones
1611
Table III. Continued
Concen- Total No. of
Table III. Insecticidal activity of 4a-4u
% age death
R
tration insects dead
g/g) used insects
± STD
(µ
100
500
1000
30
30
30
12
15
15
40 ± 1.00
50 ± 1.73
50 ± 1.00
3-Cl-C6H4
(4o)
Concen- Total No. of
tration insects dead
% age death
± STD
R
3
100
500
1000
30
30
30
2
5
7
6.6 ± 0.57
16.6 ± 0.57
23.3 ± 0.57
(µg/g)
used insects
4-Br-C6H4
(4p)
100
500
1000
30
30
30
19
19
21
63.3 ± 1.52
63.3 ± 1.52
70 ± 1.00
100
500
1000
30
30
30
17
24
28
56.6 ± 1.52
80 ± 2.00
93.3 ± 1.15
4-I-C6H4
(4q)
100
500
1000
30
30
30
15
17
21
50 ± 1.00
56.66 ± 1.5
70 ± 1.00
C6H5
(4a)
100
500
1000
30
30
30
8
8
7
26.6 ± 1.15
26.6 ± 1.52
23.3 ± 0.57
4-OH-C6H4
(4r)
100
500
1000
30
30
30
21
22
28
70 ± 1.00
73.3 ± 2.00
93.33 ± 1.00
4-CH3-C6H4
(4b)
100
500
1000
30
30
30
9
8
8
30 ± 1.00
26.6 ± 1.15
26.6 ± 0.57
3-OH-C6H4
(4s)
100
500
1000
30
30
30
11
19
26
36.6 ± 0.57
63.3 ± 1.52
86.6 ± 0.57
3-CH3-C6H4
(4c)
100
500
1000
30
30
30
16
21
20
53.3 ± 1.52
70 ± 1.00
66.6 ± 1.52
2-OH-C6H4
(4t)
100
500
1000
30
30
30
10
11
9
33.3 ± 1.52
36.6 ± 1.52
30 ± 1.00
2-CH3-C6H4
(4d)
100
500
1000
30
30
30
15
18
28
50 ± 1.00
60 ± 1.00
93.3 ± 1.15
3-Cl-4-CH3-C6H4
(4u)
100
500
1000
30
30
30
7
8
13
23.3 ± 0.57
26.6 ± 1.52
43.3 ± 1.15
4-OCH3-C6H4
(4e)
Standard drug = Permethrin; Conc of Permetrin = 500 µg/g
100
500
1000
30
30
30
13
22
18
43.3 ± 0.57
73.3 ± 0.57
60 ± 1.00
3-OCH3-C6H4
(4f)
microwave-assisted synthetic techniques. Microwave
assisted synthesis proved to be more efficient and not
only reduced the reaction time but also enhanced the
yields (Table I). The 3,4-dihydroquinoxalin-2(1H)-one
and 4-(chloroacetyl)-3,4-dihydroquinoxalin-2(1H)-one
were prepared using a previously published protocol
(Perkin and Riley, 1923; An and Peng, 2003). Treat-
ment of 4-(chloroacetyl)-3,4-dihydro quinoxalin-2(1H)-
100
500
1000
30
30
30
14
19
15
46.6 ± 0.57
63.3 ± 1.52
50 ± 1.00
2-OCH3-C6H4
(4g)
100
500
1000
30
30
30
18
20
25
60 ± 1.00
66.6 ± 1.15
83.3 ± 1.52
2,3-diCH3C6H4
(4h)
one (
sodium bicarbonate and catalytic amount of potassium
iodide at reflux produced the target compounds 4a 4u
3) with various anilines in 2-propanol containing
100
500
1000
30
30
30
22
26
23
73.3 ± 1.52
86.6 ± 0.57
76.6 ± 1.52
2,4-diCH3-C6H4
(4i)
-
(Scheme 1). The reaction time and the corresponding
yields imply that arylamino derivatives containing
strong electron donating groups especially at the para
position gave better yields, which was expected. The
100
500
1000
30
30
30
14
24
30
46.6 ± 0.57
80 ± 1.00
100 ± 0.00
2,5-diCH3-C6H4
(4j)
100
500
1000
30
30
30
2
3
2
6.6 ± 0.57
10 ± 0.00
6.6 ± 0.57
2,6-diCH3-C6H4
(4k)
yields of the reported compounds (4a-4u) ranged from
49-94% (Table I).
100
500
1000
30
30
30
5
14
23
16.6 ± 0.57
46.6 ± 0.57
76.6 ± 1.00
Compounds 4a-4u were evaluated based on spectral
3,4-diCH3-C6H4
(4l)
data. In the IR spectra, the band around 3350 and
3190 cm−1, can be attributed to NH stretching and the
intense absorption bands appearing at around 1680
and 1660 cm−1 could be assigned to C=O stretching of
100
500
1000
30
30
30
15
5
8
50 ± 1.73
16.6 ± 0.57
26.6 ± 1.15
3,5-diCH3-C6H4
(4m)
1
amide and lactam moieties. The H- and 13C-NMR
100
500
1000
30
30
30
16
30
30
53.3 ± 2.30
100 ± 0.00
100 ± 0.00
spectra further confirmed the formation of arylamino-
4-Cl-C6H4
(4n)
quinoxalinone derivatives (4a-4u). The signals of the
methylene protons were observed in the range of
δ

1612
W. Nasir et al.
Table IV. Phytotoxicity of the arylaminoquinoxalinones
Table IV. Continued
Treatment 18 h 18 h 24 h 24 h
time (min) 2% 0.20% 2% 0.20%
R
15
30
45
30
16
20
60
50
56
30
23
23
60
53
56
4-Cl-C6H4
(4m)
Treatment 18 h 18 h 24 h 24 h
time (min) 2% 0.20% 2% 0.20%
R
15
30
45
20
16
16
53
53
46
23
20
20
56
56
50
3-Cl-C6H4
(4n)
15
30
45
13
16
13
63
40
36
16
20
16
46
40
40
3
15
30
45
16
13
26
50
43
40
20
16
33
50
46
43
4-Br-C6H4
(4o)
15
30
45
13
16
6
50
30
33
16
16
10
53
36
36
C6H5
(4a)
15
30
45
13
6
16
60
50
40
16
13
23
63
50
43
4-I-C6H4
(4p)
15
30
45
16
23
20
53
46
43
16
23
23
53
50
50
4-CH3-C6H4
(4b)
15
30
45
26
16
16
40
50
40
26
20
20
43
50
43
4-OH-C6H4
(4r)
15
30
45
20
06
13
50
30
40
20
10
16
53
33
40
3-CH3-C6H4
(4c)
15
30
45
10
30
33
50
46
40
16
30
33
53
46
46
3-OH-C6H4
(4s)
15
30
45
16
16
10
16
50
53
20
20
13
63
50
56
2-CH3-C6H4
(4d)
15
30
45
26
20
36
46
53
33
30
23
40
46
56
33
2-OH-C6H4
(4t)
15
30
45
33
23
40
60
50
40
36
26
40
60
50
43
4-OCH3-C6H4
(4e)
15
30
45
26
30
16
66
40
43
33
33
23
70
43
46
3-Cl-4-CH3-CH3C6H3
(4u)
15
30
45
16
13
16
40
50
56
16
20
56
53
53
53
3-OCH3-C6H4
(4f)
15
30
45
60
66
60
60
70
63
Water
(Positive control)
15
30
45
16
23
20
53
46
43
16
23
23
53
50
50
2-OCH3-C6H4
(4g)
15
30
45
23
13
30
50
30
40
26
16
30
53
33
40
4.03 to 4.1 (2H, d,
J = 5.6 Hz, CH2-NH-Ar). A charac-
2,3-diCH3-
C6H3 (4h)
teristic triplet integrated for one proton of a secondary
nitrogen appeared around 5.0 (1H, t, = 5.6 Hz,
-Ar), while the NH proton (lactam) was observed
as a singlet at 10.6, which demonstrated that a lac-
δ
J
15
30
45
13
13
16
66
46
40
13
13
20
43
53
46
NH
2,4-diCH3-C6H3
(4i)
δ
tam moiety was present in DMSO. The EIMS spectra
gave characteristic M+ peaks corresponding to the
15
30
45
23
16
26
50
30
43
23
20
24
53
33
46
2,5-diCH3-C6H3
(4j)
molar mass of the target compounds (4a-4u).
The antibacterial properties of the quinoxalinones
were tested in vitro against six strains of bacteria
(gram-positive & gram-negative). In these screening
15
30
45
13
10
23
50
30
46
16
13
23
53
36
50
2,6-diCH3-C6H3
(4k)
experiments, the only compound 3, 4d, 4k, 4o and 4t
showed mild to medium activity when compared to
standard drugs (augmentin, ampicillin and chloram-
phenicol) (Table II). Compounds 4d and 4k showed
medium activity against all the selected strains while
4o was active against Escherichia coli and Salmonella
typhi and 4t showed mild activity against only
15
30
45
40
23
30
50
50
36
43
26
33
50
53
43
3,4-diCH3-C6H3
(4l)
15
30
45
33
16
30
63
46
26
33
20
33
63
50
26
3,5-diCH3-C6H3
(263)
Escherichia coli
.

Synthesis and Biological Studies of Quinoxalinones
1613
Table V. Phytotoxicity of arylaminoquinoxalinones
Insecticidal activities of the target compounds were
tested against Tribolium castaneum (Table II). The
results indicated that in general the activity of aryl-
aminoquinoxalinone derivatives increased at higher
concentrations of the target compounds. Most of the
tested compounds showed activity above 60% at a
concentration of 500 µg/g. Test compounds 4b, 4f, 4j,
4q, and 4t showed activity greater than 70% while
compound 4-{[(4-chlorophenyl)amino]acetyl}-3,4-dihy-
Concentration
in %
Phytotoxic
R
3
effect
++
+
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
droquinoxalin-2(1
active as permethrin at 500
All the tested compounds (4a
H
)-one (4n) was found to be as
g/g.
4u) (Table IV) showed
++
+
+
+
+
+
+
+
+
+
++
+
++
+
+
+
+
+
+
+
+
+
++
+
+
+
+
+
+
+
+
+
+
+
++
+
++
+
C6H5
(4a)
µ
-
4-CH3-C6H4
(4b)
3-CH3-C6H4
(4c)
varying degree of phytotoxicity. 3-methyl, 2,6-dimethyl,
4-iodo, and 3-hydroxy, substituted arylaminoacetyl-
quinoxalinones showed enhanced phytotoxicity than
4-(2-chloroacetyl)-3,4-dihydroquinoxalin-2(1H)-one (3),
while the rest of the derivatives showed no significant
change in phytotoxic activity.
The results obtained in the agro infusion tests
revealed that the substitution of the chloro group from
4-(2-chloroacetyl)-3,4-dihydroquinoxalin-2(1H)-one (3)
to arylamines produced no pronounced effect on the
phytotoxicity of the resulting compounds (Table V).
All compounds showed activity similar to 4-(2-chloro-
2-CH3-C6H4
(4d)
4-OCH3-C6H4
(4e)
3-OCH3-C6H4
(4f)
2-OCH3-C6H4
(4g)
2,3-diCH3-C6H3
(4h)
acetyl)-3,4-dihydroquinoxalin-2(1H)-one (3) at a con-
2,4-diCH3-C6H3
(4i)
2,5-diCH3-C6H3
(4j)
centration of 1%.
ACKNOWLEDGEMENTS
2,6-diCH3-C6H3
(4k)
The authors acknowledge the role of the Higher
Education Commission of Islamabad, Pakistan and
appreciate its financial support through the “Indigen-
ous PhD” program. We are also thankful to the H.E.J.
Research Institute of Chemistry University of Karachi
for CHN analysis and spectral measurements.
3,4-diCH3-C6H3
(4l)
3,5-diCH3-C6H3
(4m)
4-Cl-C6H4
(4n)
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