"Synthesis, Reaction and Antitumor Screening of Some New Quinoline and
Substituted 4-amino Quinoline Derivatives.
Mohamed M. Ismail1, Saber E.S. Barakat2, Ashraf H. Bayomi3, Helmy M. Sakr2
and Kamal M. A. El-Gamal3
1
Department of Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
2
Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Boys),
Al-Azhar University, Cairo, Egypt.
3
Department of
Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University,
Cairo, Egypt.
Abstract
Vilsmeier formulation of acetanilide I followed by treatment with hydroxyl amine produced
2-chloroquinoline-3-carbonitrile II that was condenced with different amines to give III that
was hydrolyzed by sodium hydroxide to produced IV. Treatment of II with thiourea yielded
2-mercaptoquinoline-3-carbonitrile V which was converted to its potassium salt VI that was
reacted with substituted chloroacetanilide or substituted proponilide produce IX. But
condensation of VI with N-benzyl chloroacetamide, ethoxy ethyl chloride, substituted
chloroacetophenone will produce compounds X, XI, XII, respectively. Some of the
synthesized were screened for antitumor activity and that was found the screened compound
has not any antitumor activity.
Introduction
The quinoline moiety was found to be incorporated in large number of significant
compounds designed to have cytotoxic and antitumor activity(1) moreover, the substituted
quinoline-3-carboxamide was found to be used in inflammatory and/or allergic disease(2). As
an extension of our effort towards the development of convenient synthetic approaches for the
synthesis of 2-chloroquinoline-3-carbonitrile (II) which is a good starting material for the
prepration of different quinoline derivatives(3). Accordingly, it was decided to prepar some
new 2-substituted quinoline derivatives III, IV, IX and XII as shown in scheme (1) with the
aim to screening their antitumor activity.
Experimental
All melting points were carried on Gallen Kamp point apparatus and are uncorrected. The
infrared spectra were recorded on Brucker- Vector-22-F T-IR spectrophotometer using the
potassium bromide disc technique. The 1HNMR spectra were recorded or varian-Gemini300-MHz spectrophotometer using CDCl3 or DMSO-d6 as a solvents and TMS as internal
1
reference. The chemical shift value were recorded in  ppm downfield the TMS signal. The
Mass spectra were recorded on AZH-ph-AR-XO2 Mass spectrometer. Elemental analyses
were performed on CHN analyzer. All spectral measurements have been performed at the
Micro analytical Center, Cairo University, Egypt.
Following reported procedures, 2-chloroquinoline-3-carbonitrile II(4) 2-mercapto quinoline-3carbonitrile(5) and it’s salt(6) and 2-(methyl oxo carbonyl methyl thio) quinoline-3-carbanitrile
VII(6) were prepared.
2-Substituted aminoquinoline-3-carboxamide (IIIa-d)
A mixture of 2-chloroquinoline-3-carbonitrile (IV) (1.89g, 0.01 mol) and aryl amine (0.01
mol) in n-butanol (25 ml) was heated under reflux for 3 hours. Then the mixture was allowed
to cool. The separated solid was collected, filtered off, dried, washed with ethanol and
recrystallized from absolute ethanol. (Table 1)
Table (1): The physical data and elemental analysis of 2Substituted aminoquinoline-3- carbonitrile (IIIa-d)
Comp.
R
No
C6H4Br(3)
a
m.p.
(oC)
135-
Yield
80
137
C6H4F(4)
b
180-
75
182
C6H3(OCH3)2(2,4)
c
154-
60
156
C6H3(CH3)2(2,6)
d
145-
55
147
Mol. Form.
(M.Wt.)
Elemental analysis
C
H
C16H10BrN3
59.27 3.10 12.96
324.17
59.41 3.10 12.96
C16H10FN3
72.98 3.82 15.96
263.27
73.00 3.80 15.80
C18H15N3O2
70.80 4.95 13.76
305.32
71.00 5.00 13.80
C18H15N3
79.18 5.53 15.39
273.02
79.52 5.80 15.60
III-a : IR: (KBr, cm-1), 3358.2 (s,NH), 3049 (s,C-H, aromatic), 2223.1 (s,C N), 1622-1542
(s,C=C, C=N, aromatic).
III-a : Ms: (m/z, abound %), 324 (100, M), 325 (50.9, M+1) 326(28.4, M+2H), 323(77, M-1),
244 (49.9, M-Br), 243(41.9, M-HBr), 242(24, M-H2Br), 153(28.7, cyanoquinoline
cation)
2
N
III-b : IR: (KBr, cm-1), 3358.5 (s,NH), 3049.8 (s,C-H, aromatic), 2223.1 (s,C N), 1622.41542 (s,C=C, C=N, aromatic).
Ms: (m/z, abound %), 263 (100, M), 262 (93.6, M-H) 153(18.1, cyanoquinoline
cation).
III-c : 1HNMR: (CDCl3,  ppm), 8.78 (s,1H, H-4), 8.75 (s,1H, -NH-), 8.30 (s,1H, H—3 of
phenyl ring), 7.82-7.78 (d,1H, H-5), 7.71-7.69 (d,2H, H-5,6 of phenyl ring), 7.667.63 (d,1H, H-8), 7.36-7.27 (t,1H, H-6), 6.62-6.57(t,1H, H-7), 3.95(s,3H,-OCH3,
. 3 at ortho position in phenyl ring).
at para position phenyl ring), 3.85 (s,3H, OCH
: IR: (KBr, cm-1), 3366.3 (s,NH), 3055 (s,C-H, aromatic), 2215.6(s,C N), 1619-
III-d
1588.5 (s,C=C, C=N, aromatic).
2-Substituted aminoquinoline-3-carboxamide (IVa-d)
To a mixture of 2-Substituted aminoquinoline-3-carbonitrile (V) (0.01 mole) in aqueous
ethanol (70 %) (50 ml) was added sodium hydroxid (0.399 g , 0.01 mol) and the mixture then
heated under reflux for 2 hours. Then the mixture was allowed to cool and just acidified with
dil HCl (10%), dropwise until just acidic using litmus paper with stirring until the crude
crystal was precipitated out, filtered, dried and recystallized from absolute ethanol table (2).
Table (2): The physical data and elemental analysis of 2Substituted aminoquinoline-3-carboxaldehyde (IVa-d)
Comp.
No
R
C6H4Br(3)
m.p.
Yield
(oC)
180-182
70
a
C6H4F(4)
250-252
60
b
C6H3(OCH3)2(2,4)
215-217
40
c
C6H3(CH3)2(2,6)
290-292
35
d
3
Mol. Form.
Elemental analysis
(M.Wt.)
C
H
N
C16H12N3OBr
56.15
3.53
12.28
342.18
56.70
3.60
12.57
C16H12FN3O
59.17
5.54
19.25
218.28
59.40
5.15
19.10
C18H17N3O3
66.85
5.30
12.99
323.34
66.10
5.10
13.00
C18H17N3O
74.29
5.88
14.42
291.34
74.35
6.00
14.10
IV-a : IR: (KBr, cm-1), 3444.8 (b, NH2), 3255.2 (b, NH), 3053.1 (s,C-H, aromatic), 1775.8
(s,C=O).
Ms: (m/z, abound %), 342/344 (0/50.8, M+), 217 (42.4, M-CONH2Br) .
IV-b : IR: (KBr, cm-1), 3443.6 (b,NH2), 3105.1 (b, NH), 3046.7(s, C-H, aromatic), 1776.8
(s,C = O).
Ms: (m/z, abound %), 281 (52.7, M+), 282 (92, M-H), 237(100,M-CONH2) ,263 (42,
M-F), 236 (64.4, M-CONH3), 235 (28.5 M-CONH2 + H2), 238 (19, M-CONH).
IV-c : 1HNMR: (CDCl3, ppm), 10.84 (s,1H, NH), 8.92 (s,1H, H-4), 8.89-8.86 (d,1H, H-5),
7.90-7.87 (d,1H, H-8), 7.86-7.68(t,1H, H-6), 7.67 (s,1H, H-3 of phenyl ring),
7.33-7.28 (t,1H, H-7) , 7.68-7.60 (d,1H, H-6 of phenyl ring), 6.59-6.56 (d,1H, H-5
of phenyl ring), 3.71-3.53(s,2H, NH2), 3.84 (s,3H,-OCH3, at para position), 3.79
.(s,3H, OCH3 at ortho position).
.
IV-d : IR: (KBr, cm-1), 3431.4 (b,NH2), 3167.5 (b, NH), 3032.8(s, C-H, aromatic), 2986.6
.
(s,C – H aliphatic), 1717.4 (s,C=O).
2-(3-Cyanoquinoline-2-yl-thio) acetohydrazide (VIII)
To a will stirred suspension of 3-cyanoquinoline-2-yl sulfanyl acetic acid methyl ester (2.58
g, 0.01 mol) in absolute ethanol (100 ml) hydrazine hydrate (80%) (10 ml) (0.01 mol) was
added. The reaction mixture was heated under reflux with stirring for three hours. The
precipitated solid was filtered off while hot, washed with absolute ethanol, dried at 200oC in
vacuum and crystallized from ethanol.
m.p.
>300
yield
90%
C12H10N4OS (258.35). Calc. (found C% 55.78 (55.67), H% 3.90 (3.56), N% 21.68 (22.00).
VIII: 1HNMR: (DMSO, ppm): 9.04 (s,1H, H-4), 8.09-8.03(d,1H, H-5), 7.89-7.86 (d, 1H, H8),
7.85-7.83(t,1H, H-6), 7.80-7.62(t,1H, H-7), 7.61 (s, 2H, S-CH2), 7.59-7.29 (broad , t,
.
. 2)
1H,. NH-NH2), 4.52 (broad , d, 2H, NH-NH
Ms : (m/z, abound %) : 258(50.5, M), 259 (22.6, M+1), 228(16.7, M-N2H2), 227 (100,
N2H3), 199 (35, M-CH3N2O), 155 (39.7, C10H7N2),128(25.7, cyanoquinoline cation).
2-(3-Cyanoquinoline-2-yl-thio)-N-(substituted
phenyl)
acetamid
(IXa1-7)
A mixture of potassium salt of 2-mercaptoquinoline-3-carbonitrile (VIII) (2.24 g, 0.01 mol)
and the appropriate chloroacetanilide (0.01 mol) in dry dimethylformamide (30 ml) was
4
heated for five hours at 100oC with stirring. The reaction mixture was poured onto ice-cooled
water and the solid produced was filtered off, dried and crystallized from ethanol. (Table 3)
Table (3): The physical data and elemental analysis of 2-(3-cyanoquinoline-2-yl-thio)-N-(substituted phenyl) acetamide
(IXa1-7)
Comp.
No
C6H4COOH(4)
m.p.
(oC)
278-280
C6H4Cl(4)
285-287
45
C6H4Br(4)
240-242
55
C6H4F(4)
260-262
60
C6H4OH(4)
230-232
45
C6H4COOCH3 (2)
170-172
40
C6H3(CH3)2(2,6)
258-260
30
R
Yield
60
1
2
3
4
5
6
7
Mol. Form.
(M.Wt.)
C19H13N3O3S
363.37
C18H12ClN3OS
353.81
C18H12BrN3OS
398.26
C18H12FN3OS
337.36
C18H13N3O2S
335.36
C20H15N3O3S
377.40
C20H17N3OS
347
Elemental analysis
C
H
N
62.79 3.60 11.56
62.80 4.40 11.32
61.10 3.41 11.87
61.18 3.56 11.95
55.67 3.11 10.82
55.73 3,05 10.51
64.07 3.58 12.45
64.43 3.52 11.92
64.46 3.90 12.52
64.22 3.34 12.45
63.64 4.00 11.13
64.23 3.94 11.12
69.13 4.93 12.09
69.40 4.61 11.87
IX-a-1 : Ms: (m/z, abound %), 363 (11.00, M+), 364 (10.4, M+1), 228(32.4, C12H18N2OS),
227(91.6, C12H17N2OS), 200 (57.6, C13H8N2S), 199(100,C13H7N2S), 154(29.1,
C12H6N2), 153(39.8, cyanoquinoline cation).
IXa-3 : IR: (KBr, cm-1), 3449.2 (b, C-H, aromatic), 3239.6 (b, NH), 2223.4(s, CN), 1739
(s,C = O), 1658.3 – 1585.4 (s,C=N, C=C aromatic)
Ms: (m/z, abound %), 398 (3.5, M+), 399 (10.3, M+1), 228(15.6, C12H18N2OS),
227(100, C12H17N2OS), 200 (31.1, C13H8N2S), 199(58.8,C13H7N2S), 155(20,
C12H7N2), 153(30.3, cyanoquinoline cation).
IXa-4 : Ms: (m/z, abound %), 337 (3.5, M+), 338 (3.7, M+1), 228(17.1, M-NH-C6H4F), 227
O
O
(100, C12H17N2OS), 200 (4 1, M C, NH C6H4F+H ), 199
( 83, M C NH C6H4F ),
154 (12.8, C12H6N2), 153 (35.4, cyanoquinoline cation).
IXa-5 : IR: (KBr, cm-1), 338.2 (broad, OH and NH)), 3057 (s,C-H aromatic), 2937.5 (s,C-H,
aliphatic), 2224 (s, CN), 1763.5 (s,C = O), 1683.6 -1582.1 (s,C=C , C=N
aromatic).
5
1HNMR:
(DMSO, ppm), 10.56 (s,1H, NH), 9.04-8.98 (d,2H, H-5, H-8), , 8.05-
793(t,1H, H-6), 7.70-7.61 (t,1H, H-7), 7.86(s, 1H, H-4), 7.11-7.07 (d,2H, H-3,5 of
O
phenyl), 4.50 (s,2H, s H2C C ), 4.32 (s,1H, OH), 3.37-3.36 .(d,2H, H-2,6 of
phenyl)
IXa-6
: 1HNMR: (CDCl3, ppm), 11.62 (s,1H, NH), 8.69-8.65 (d,1H, H-3 of phenyl),
8.37(s,1H, H-4), 7.98-7.92 (d,2H, H-5, H-8), 7.78-7.71 (t,2H, H-4,5 of phenyl),
O
7.55-7.47 (t,2H,H-6,H-7), 7.09-7.01 (d,1H, H-5 of phenyl),4.29 (s,2H, S CH2 C ),
3.79 (s,3H,COOCH3)
.
IXa-7 IR: (KBr, cm-1), 3244(broad, NH), 3031.5 (s,C-H, aromatic), 2921(s,C-H, aliphatic),
2225.1(s,C N), 1739(s,C=O), 1659.8-1530.6(s,C=C, C=N aromatic)
Ms: (m/z, abound %), 347 (15.6, M+), 228 (13.5, M-NHC6H3-(CH3)2+H), 227(61.6,
O
M-NHC6H3(CH3)2). 200 (100, M C NH-C 6H3(CH 3)2 ),
199
(66.7,
M-
NHC6H3(CH3)2), 153(35.4, cyanoquinoline cation)
1HNMR:
(DMSO, ppm), 9.67(s,1H,NH), 9.03(s,1H, H-4), 8.20-8.15(d,2H, H-5, H-8),
8.00-7.98(t,1H, H-6), 7.75-7.6(t,1H, H-4 of phenyl), 7.05 (d,2H, H-3,5 of phenyl)
7.00 (t,1H, H-7), 4.37 (s,2H,
O
S CH2 C
), 2.10(s,6H, Ph-(CH3)2).
3-(3-Cyanoquinoline-2-yl-thio)-N-(substituted
phenyl)propamide
(IXb1-5)
To a will dried powder of potassium salt of 2-mercaptoquinoline-3-carbonitrile (VIII) (2.24
g , 0.01 mol) in dry dimethyl formamide (30 ml) added the appropriate chloropropanilide
(0.01 mol) was added and heated for eight hours at 100oC with stirring, then the reaction
mixture was allowed to cool, purred onto ice-cooled water and the solid produced was
filtered off, dried and recrystallzied from ethanol (Table 4)
6
Table (4): The physical data and elemental analysis of 3-(3-cyanoquinoline-2-yl-thio)-N-(substituted
phenyl)
propamid
(IXb1-5)
Comp.
No
m.p.
R
(oC)
C6H4Br(4)
Mol. Form.
Yield
192-194
50
(M.Wt.)
C
H
N
C19H14BrN3OS
55.34
3.42
10.19
412.28
55.30
3.11
10.60
C19H13Cl2N3OS
56.72
3.25
10.44
402.28
57.35
3.02
10.60
C19H14FN3OS
64.94
4.01
11.95
351.38
64.93
4.07
11.95
C21H19N3OS
69.77
5.29
11.62
361.44
70.20
5.11
12.06
C21H19N3O3S
64.10
4.86
10.68
393.44
64.78
4.28
10.95
1
C6H3Cl2(2,6)
202-204
40
2
C6H4F(4)
229-231
55
3
C6H4(CH3)2(2,6)
185-187
30
4
C6H3(OCH3)2(2,4)
158-160
35
Elemental analysis
5
IXb-1 IR: (KBr, cm-1), 3352(s, NH), 2937.5 (s,C-H, aliphatic), 2225.2(s,C N),
1739(s,C=O), 1585.9- (s, C=N aromatic)
Ms: (m/z, abound %), 412 (5.2, M), 411 (5.9,M+), 413(5.7, M+2H),
O
213(32.4, M H
C NH C6H4Br
O
),212 (36.2,
M
C NH C6H4Br
) , 186 (25.6, M-
C9H8BrNO), 153( 20.2, cyanoquinoline cation)
IXb-2 Ms: (m/z, abound %), 402 ((13.6, m), 403(4.8, M+H), 241 (16.7, M-NHC6H4Cl2), 213
(22.6, M-C7H5Cl2NO), 212(43.4, M-C7H6Cl2NO), 186 (17.4, M-C9H7Cl2NO),
153 (15.3, cyanoquinoline)
IXb-4 1HNMR: (DMSO, ppm), 9.29 (s,1H,NH), 8.98(s,1H, H-4), 8.00-7.79(m,3H, H-5,H7, H-6), 7.65(t,1H, H-4 of phenyl ring), 7.05 (d, 3H, H-8, H-3,5 of phenyl ring)
. C6H3(CH3)2(2,6))
3.67 (t,2H, s-CH2-CH2), 2.90(t,2H, s-CH2-CH2), 2.15 (s,6H,
.
. 8.25-8.22 (d,1H, H-5), 7.97-7.82(d,1H,HIXb-5 1HNMR: (DMSO, ppm), 8.33(s,1H,H-4),
8), 7.78-7.75(t,1H,H-6),7.60(s,1H,NH), 7.55-7.53(t,1H, H-7), 7.25(s,1H,H-3 of
phenyl ring), 7.25 (d,1H, H-5 of phenyl ring), 6.47-6.45(d,1H, H-6 of phenyl
.
7
.
O
ring), 3.82-3.73(t,2H, s-CH2), 2.94-2.89(t,2H, HC C ) , 1.53(s,6H, C6H3(OCH3)2
(2,4)).
2-[(Substituted pheny)carbonyl(methyl thio)quinoline-3-crbonitrile
(XIIa-c).
To a very fine and will dried powder of potassium salt of 2-mercapto quinoline-3-carbonitrile
(VIII) (2.24 g , 0.01 mol) in dimethyl formamide (50 ml) the appropriate derivatives of
chloro acetophenone (0.01 mol) was added then the reaction mixture was heated at 100oC for
five hours and allowed to cool, then the reaction mixture was poured onto ice-cooled water
with stirring, the resulting product was filtered off, dried and crystallized from ethanol
(Table 5)
Table (5): The physical data and elemental analysis of 2(substituted phenyl)carbonyl methyl-thio)quinoline-3carbonitrile (XIIa-c)
Comp.
R
No
C6H4Cl(4)
m.p.
Yield
(oC)
170-172
65
a
C6H4CH3(4)
130-132
55
b
C6H4NO2(4)
350-352
65
c
Elemental analysis
Mol. Form.
(M.Wt.)
C
H
N
C18H11ClN2OS
63.80
3.27
8.27
338.80
63.95
3.23
8.90
C19H14N2OS
71.67
4.43
8.80
318.38
71.40
4.50
8.85
C18H11N3O3S
61.88
3.17
12.02
349.35
61.90
3.52
11.95
XIIa IR : (KBr, cm-1): 3060.3 (s,C-H aromatic), 2338 (s, C N), 1678 (s,C=O)
Ms : (m/z, abound %) : 338 (17.0, M), 339 (6.8, M+1), 240 (7.0, M+2H),199(16.9 , MC7H4ClO), 139 (100, C7H4ClO)
XIIb 1HNMR: (CDCl3, ppm): 8.32(s,1H, H-4), 8.03-8.00 (d,1H, H-5), 7.75-7.72(d,2H, H-2,6
of phenyl ring),7.71-7.69 (d,1H, H-8), 7.66-7.60 (t,1H, H-7), 7.51-7.46 (t,1H, H6),
7.34-7.25 (d,2H, H-3,5 of phenyl ring), 4.78(s,2H,
.
S CH 2 C
phenyl-CH3).
XIIc IR : (KBr, cm-1) 3126 (s,C-H, aromatic), 226(s,CN), 1696 (s, C=O).
8
O
), 2.46(s,3H-
Antitumor screening of the (E.A.C)(7).
A set of sterile test used 2.5 x 105 tumor cells per ml were suspended in phosphate buffer
saline, then 25,50,100 µg / ml from nine compounds (VIII), IXa-2, IXa-7, Xb-2, Xb-3, X, XI,
XIIa, XIIb) were added to the suspension, kept at 37oC for 2 hours. Trypan blue dye
exclusion test was then carried out to calculate the per centage of non viable cells, it was
found that the test compound displayed no inhibitory activity against the experimental system
tested.
Result and discussion.
2-chloroquinoline-3-carbonitrile (II) was prepared by one-pot reaction via vilsmeier
formulation of acetanilide (I) using (DMF/POCl3)(8-10) followed by treating with
hydroxylamine hydrochloride where by 44% yield of (II) was obtained 2-chloroquinoline-3carbonitrile (II) was condensed with a variety of aromatic amines in n-butanol whereby
several new 2-substituted aminoquinoline-3-carbonitrile (III) were obtained. The structure of
(III) were confirmed by elemental analysis and spectral data obtained from IR, NMR and
mass spectra. The IR spectra of compound (III) in KBr are characterized by strong absorbtion
band at 3366 cm-1 (due to N-H stretching) and sharp intense band around 2223 cm-1 (due to C
 N stretching). The 1HNMR spectra of compound (III) are characterized by the presence of
abroad singlet of one proton at about 8.75 ppm and the aromatic protons of quinoline nucleus
displayed a triplet of one proton at 7.36-7.27 (H-6), amultiplet of three protons at 7.82-6.57
ppm (H-5, H-8, H-7) and singlet of one proton at 8.78 ppm (H-4). The El mass spectra of
compound (III) show prominent molecular peak which represent the base peak anhydrolysis
of (III) with aqueous sodium hydroxide will afforded the compound (IV). The structure of
(IV) were confirmed by elemental analysis and spectral data obtained from IR, NMR and
mass spectra. The IR spectra of compound (IV) in KBr are characterized by broad band at
3167 cm-1 (due to NH2 and sharp intense band at 1717 cm-1 (due to C=O stretching). The
1
HNMR spectra of compound (IV) are characterized by singlet of protons at 3.71- 3.75 ppm
(due to –NH2). The El-mass of compound (IV) showed prominent molecular ion peaks. The
fragmentation patterns of these compound are characterized by loss of amid group which
represent the base peak. Moreover, 2-chloroquinoline-3-carbonitrile (II) is allowed to react
with thiourea in the presence of sodium hydroxide to give 2-mercapto quinoline-3carbonitrile (V)(5) which was treated with potassium hydroxide in absolute ethanol to give the
corresponding potassium salt(VI)(6). Condensation of (VI) with methylchloroacetats will
9
afforded (VII)(6), reaction of (VII) with hydrazine hydrate in ethanol 95% yielding 2-(3cyanoquinoline-2-ylthio) acetohydrazide (VIII). The structure of (VIII) were confirmed by
elemental analysis and spectral data obtained from NMR and Mass spectra. The 1HNMR
spectra of compound (VIII) shows. Triplet of one protons at 7.49- 7.29 ppm that was
dispeared on equilibration with D2O (due to NH) and douplet of two broaded proton at 4.52
ppm that disappeared on equilibration with D2O (due to NH2). The El mass of compound
(VIII) shows prominent molecular ion peak and the fragmentation pattern are characterized
by loss of NH-NH2 moiety to produce the base peak. In addition, potassium salt of 2-mercpto
quinoline-3-carbonitrile
(VI)can
be
also
condensed
with
variant
derivatives
of
chloroacetanilides and chloropropanilides to produce (IX). The structure of (IX) were
confirmed by elemental analysis and spectral data obtained from IR, 1HNMR, Mass spectra.
The IR spectra of compound (IXa) in KBr are characterized by broad band at 3338 cm-1 (due
to NH), …… sharp intense band at 2224 cm-1 (due to C N stretching) and strong absorbtion
band at 1763 cm-1 (due to C=O stretching). The 1HNMR spectro of compound (IXa) are
characterized by presence of singlet of one proton at 8.37 ppm (due to N) and singlet of two
O
proton at 4.29 ppm (due to
S CH2 C
). The El mass of compound (IXa) shows prominent,
molecular ion peaks and the fragmentation pattern are characterized by loss of aryl amino
group which might produce the base peak. Furthermore, the IR spectra of compound (IXb) in
KBr are characterized by sharpe intense band at 3352 cm-1 (due to NH) and strong band at
2225 cm-1 (due to C N stretching) and strong intense band at 1677 cm-1 (due to C=O
stretching). The 1HNMR spectra of compound (IXb) shows two different. Triplet each of two
O
protons one at 7.65 ppm (S-CH2) and the other at 2.90 ppm (
CH 2 C
), also the patern
was characterized by presence of downfield singlet of one proton at 9.29 ppm that
disappeared on equilibration with D2O (due to NH). The El mass of compound (IXb)
shows prominent molecular ion peak and the fragmentation pattern are characterized by loss
of aryl amino carbonyl group which might produce the base peak. Also condensation of (VI)
with N-benzyl chloro acetamind will afforded (X) which were confirmed by elemental
analysis and spectra data obtained from IR and 1HNMR. The IR spectra of (X) in KBr are
characterized abroad band at 3350 cm-1 (due to NH) and sharp intense band at 1710 cm-1 (due
to C=O stretching). The 1HNMR spectra of compound (X) show abroad douplet of one
proton at 7.55 ppm.(-NH-), adouplet of two protons at 4.45 ppm ( NH-CH2-) and singlet of
two protons at 4.08 ppm (
O
S CH2 C
). But condensation of (VI) with ethoxy ethyl chloride will
afforded a new ether compound (XI) that was confirmed by elemental and spectral data
obtained from particulary 1HNMR that reveals by presence of three. Triplet one at 3.81-3.80
10
ppm (CH2-CH2-O) of two protons and the other one at 1.54 (S-CH2) and the last one at 1.261.22 (O-CH2-CH3) which due to three protons and the spectra were characterized by the
presence of quartet of two protons at 3.63 -3.58 ppm (O-CH2-CH3).
Lastly the condensation of (VI) with variant derivatives of chloroacetophenone will afforded
(XII) the structure of (XII) were confirmed by elemental and spectral data obtained from IR,
1
HNMR and Mass spectra. The IR spectra of compound (XII) are characterized by sharp
intense band at 1720 cm-1 (due to stretching) and sharp intense band at 2227 cm-1 (due to C
N stretching). The 1HNMR are characterized in addition to the characteristic signal of
aromatic and quinoline protons by the presence of singlet of two protons at 4.78 ppm
(
O
S CH2 C
) and the El-Mass spectra of compound (XII) show prominent
molecular ion peaks and the fragmentation pattern are characterized by loss of
aryl carbonyl moiety which in addition to that loss of CH 2, N and S to produce
the base peak.
11
H3C
O
+
N
H
POCl3 l 80oC
H
NH2OH.HCl
N
H3C
CH 3
O
CN
N
CN
R NH 2
n-butanol
Cl
N
R
III
II
I
NH
R = C6H4Br(3)
= C6H4F(4)
= C6H4(OCH3)2(2,4)
= C6H4(CH3)2(2,6)
S
H2N
NH 2
CN
NaOH
N
SH
O
V
C
KOH
EtOH
N
NH 2
NH
R
IV
CN
N
CN
Cl-CH2COOCH3
R = C6H4Br(3)
= C6H4F(4)
= C6H3(OCH3)2(2,4)
= C6H3(CH3)2(2,6)
OCH3
S
N
SK
O
VII
VI
CN
N
NH-NH 2
S
O
VIII
R
R
NH
C O
O
(CH2)n
O
R
Cl
Cl
Cl
CN
CN
N
S
Cl
O
HN
CN
O
(CH2)n
IX
N
H
R
N
H
N
S
R
O
N
S
O
XI
CN
X
R = C6 H 5
n =1 R = C6H4COOH(4),
= C6H4Cl(4)
= C6H4Br(4)
= C6H4F(4)
= C6H4OH(4)
= C6H4COOCH3(2)
= C6H3(CH3)2 (2,6)
n =2 R = C6H4Br(4),
= C6H4Cl(2,6)
= C6H3(CH3)2 (2,6)
= C6H4F(4)
= C6H3(OCH3)2(2,4)
Scheme 1
12
N
XII
R
S
O
References
1)
Zhang,N., Wu, B. , Eudy, N., Wang, Y., Ye., F., Powell, D.,
Wissner, A., Feldberg, L.R., Kim, S.C., Mallon,R., Kovacs, E.D.,
Toral-Barza, L. and Koher, C.A., Bioorg. Med. Chem., Lett., 11
(11), 1407-10(2001).
2)
Edlin, C.D., Eldred, C.D., Keeling, S.P., Lunniss, C.J., Redfern,
T.J., Redgrave, A.J., Woodrow, M., Uk. Pat., 30,212 (2005);
Through Chem. Abstr., 142, 373698z(2005).
3)
T.L. Wright, U.S. Pat., 4, 540, 786 (1985).
4)
Bell, M.R. and Ackerman, J.H., U.S. pat. 4,920, 128 (1990).
5)
Bakhite, E.A.G., Collect Czech Chem. Cemmun,57, 2359 (1992).
6)
Monir, A.A., Mohammed, M.I., Saber, E.B., Ashraf, A.A. , Ashraf,
H.B. and Kamal, M.A.E., Bull Pharma. Sci, Assiut University, Vol.
27, part 2, December, 2004 , pp. 237-245.
7)
Melimans, W.F., Davis, E.V., Glover, F.L. and rake, G. W., J.
Immunol, 79, 428 (1957).
8)
Meth-Chon, O., Narine, B. and Tarnowski, B., J. Chem. Soc.,
Perkin trans I, 1520-1536 (1981) and Meth. Cohn, O., Rhouati, S.,
Tarnowsk, B. and Robinson, A., ibid, 1537-1542 (1981).
9)
Vilsmier, a. and Haack, A., Ber., 60B, 119 (1927).
10)
Pizey, J.S., “Synthetic Reagents” Vol. 1,1-99 Wiley, New York
(1974).
13
‫الملخص العربى‬
‫*محمد محسن اسماعيل ‪ **،‬صابر السيد بركات ‪ ***،‬أشرف حسن بيومى ‪** ،‬حلمى مصطفى صقر‪،‬‬
‫*** كمال محمد أحمد الجمل‬
‫*قسم الكيمياء العضوية ـ كلية الصيدلة ـ جامعة القاهرة‬
‫** قسم الكيمياء الصيدليه ـ كلية الصيدله (بنين) ـ جلمعة األزهر ـ القاهرة‬
‫*** قسم الكيمياء العضوية ـ كلية الصيدلة (بنين) ـ جامعة األزهر القاهرة‬
‫تم تفاعل فالسيماير على االسيتانيليد )‪ (I‬ثم معالجة الناتج بالهيدروكسييل أميين أعطيى ‪2‬ـي كليورو كينيولين‬
‫ـ‪3‬ـ كاربونيتريل )‪ (II‬الذى تم تكاثفيه ميب بعيأل األمينيات ليعطيى األمينوكينولينيات المقابلية )‪ (III‬والتيى‬
‫عند تحللها بهيدروكسيد الصوديوم أنتجت )‪ (IV‬معالجة )‪ (II‬بالثيويوريا أنتج ـ‪2‬ـ ميركابتوكينولين ـ‪3‬ـي‬
‫كربوناتيريل )‪ (V‬الذى تم تحويله الى الملح البوتاسييومى واليذى عنيد تفاعليه ميب بعيأل مكيتقات كليورو‬
‫األسيتانيليد أو مكتقات كلورو البروبانيليد كلورو األسيتوينون أنتج)‪ (IX‬أما تكاثف )‪ (VI‬ميب نن بنيييل‬
‫كلورواسييتاميد ‪ ،‬نيثوكسيى نيثيييل كلورييد ‪ ،‬مكييتقات كليورو األسيييتوفينون أنيتج المركبييات )‪، (XI) ، (X‬‬
‫)‪ (XII‬على التوالى وقد تم أختبار بعأل المركبات الجديدة بيولوجييا كمضيادات للسير ان حييد وجيد أن‬
‫كل المركبات التى أختبرت ليست لها فاعلية‪.‬‬
‫‪14‬‬