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CHAPTER - 3
HYPOXANTHINE, DERIVATIVES.
3.1 INTRODUCTION:
muscle relaxant and antianginal. Triptan drugs are used for the
3.2.1. 1,2,4-TRIAZOLE
.. Scheme - 3.1
.. Scheme - 3.2
dihydro-4-(4-methylphenyl)-5-(pyridyl)-3H-1,2,4-triazole (42)
(Scheme-3.3).
.. Scheme - 3.3
.. Scheme - 3.4
.. Scheme - 3.5
.. Scheme - 3.6
.. Scheme - 3.7
71
3.2.2. 1,3,4-THIADIAZOLE
.. Scheme - 3.8
N-(1-oxo-3-phenyl-1-(2-(p-tolylcarbamothioyl)hydrazinyl) propan-2-
..Scheme - 3.9
..Scheme - 3.10
formation of (3-chlorophenyl)(3-((5-(phenylamino)-1,3,4-thiadiazol-2-
..Scheme - 3.11
(naphthalen-1-yl)-5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine (67)
(Scheme-3.12).
.Scheme - 3.12
74
.Scheme - 3.13
(Scheme-3.14).
75
.Scheme - 3.14
3.15).
.Scheme - 3.15
76
afforded (2-isopropylphenyl)imino-5,5-dimethyl-5,6-dihydro-4H-1,3-
.Scheme - 3.16
.Scheme - 3.17
6-(iodomethyl)-4,6-dimethyl-5,6-dihydro-4H-1,3-thiazin-2-yl)benz
3.18).
.Scheme - 3.18
3.2.4. HYPOXANTHINE
.Scheme - 3.19
Glasky et. al. [127] reported that the condensation of ethyl 4-(3-
.Scheme - 3.20
.Scheme - 3.21
active molecules.
(NCES).
80
.Scheme - 3.22
spectral data. The characteristic peaks at 2185 and 2140 cm1 in the
The peaks at 1310 cm-1 and 1122 cm-1 confirming the asymmetric and
spectrum (Fig. 3.2) showed signals at 2.51 (d, J=4.1 HZ, 3H, -
NHCH3), 3.00-3.20 (t, 2H, Ar-CH2), 3.40-3.50 (t, 2H, -SO2CH2), 7.00
(m, 1H, -NHCH3, D2O exchangable), 7.60 (d, J=8.05 HZ, 2H, Ar-H),
8.20 (d, J=8.05 HZ, 2H, Ar-H). Its APCI mass spectrum (Fig. 3.3)
256.
.Scheme - 3.23
hydrazide 107:
group and a peak at 1693 cm1 conforming the carbonyl group. Peaks
at 1292 cm-1 and 1141 cm-1 have been attributed to the asymmetric
showed signals at 2.50 (d, J=4.8 HZ, 3H, -NHCH3), 2.9-3.00 (t, J=7.6
HZ, 2H, Ar-CH2), 3.40-3.50 (t, 2H, J=7.6 HZ, -SO2CH2), 7.00 (m, 1H, -
NHCH3), 7.30 (d, J=8.0 HZ, 2H, Ar-H), 7.50 (d, J=8.0 HZ, 2H, Ar-H,),
7.90 (d, J=4.8 HZ, 2H, pyridine ring protons,), 8.80 (d, J=4.8 HZ, 2H,
pyridine ring protons,), 9.90 (br, s, 2H, -NH-NH- portons), 10.90 (s,
1H, NH, D2O exchangable). Its APCI mass spectrum (Fig. 3.6) showed
13C NMR spectrum (Fig. 3.7) showed signals at 28.97, 29.06, 50.70,
on the above spectral data, the compound was assigned the structure
107c.
.Scheme - 3.24
spectral data
(3-mercapto-5-(pyridin-4-yl)-4H-1,2,4-triazol-4-yl)phenyl)-N-methyl
attributed to SH and peaks at 1322 cm-1 and 1130 cm-1 confirming the
14.20 in its 1H-NMR confirmed the proton of -SH. Its mass spectrum
signals at 2.50 (d, J=4.1 HZ, 3H, -NHCH3), 2.9-3.00 (t, 2H, -Ar-CH2),
3.40-3.50 (t, 2H, -SO2CH2), 7.00 (m, 1H, -NHCH3, D2O exchangable),
7.20-7.40 (m, 4H, Ar-H), 7.60 (d, J=5.0 Hz, 2H, pyridine ring
protons), 8.70 (d, J=5.0 Hz, 2H, pyridine ring protons), 14.20 (s, 1H,
SH, D2O exchangable). Its APCI mass spectrum (Fig. 3.10) showed
13C NMR spectrum (Fig. 3.11) showed the peaks at 28.94, 29.20,
150.43 and 159.60. Based on the above spectral data, the compound
.Scheme 3.25
was further confirmed by 1H-NMR and mass spectral data. Its 1H NMR
J=4.8 Hz, 3H, -NHCH3), 2.9-3.00 (t, 2H, -Ar-CH2), 3.30-3.40 (t, 2H, -
SO2CH2), 7.00 (m, 1H, -NHCH3, D2O exchangable), 7.2 (d, J=6.0 Hz,
2H, pyridine ring protons ), 7.3 (d, J=8.4 Hz, 2H, Ar-H), 7.4 (d, J=8.4
Hz, Ar-H), 8.50 (d, J= 6.0 Hz, 2H, pyridine ring protons), 10.80 (s, 1H,
13C NMR spectrum (Fig. 3.15) showed the peaks at 28.94, 29.20,
85
155.42 and 165.78. Based on the above spectral data, the structure of
.Scheme - 3.26
1322 cm-1 and 1130 cm-1 confirmed the asymmetric and symmetric
showed signals at 1.70 (m, 2H, CH2 Thiazine ring), 2.60 (d, J=4.5 HZ,
3H, -NHCH3), 2.80 (m, 2H, CH2 Thiazine ring), 3.00 (m, 2H, -Ar-CH2)
3.10 (m, 2H, CH2 Thiazine ring), 3.40 (m, 2H, -SO2CH2), 6.90 (m, 1H, -
86
NHCH3), 7.00-7.20 (m, 4H, Ar-H), 8.50 (s, 1H, NH, D2O exchangable).
Its APCI mass spectrum (Fig.3.18) showed M++1 ion peak at 314
128.33, 130.93, 142.54 and 147.10. Based on the above spectral data,
.Scheme - 3.27
acid has been found to be a general one and has been extended to
Thus, its IR (KBr) spectrum (Fig. 3.20) showed peaks at 3423 cm-1
(due to the NH2 stretching), 1640 cm-1 (due to the amide carbonyl)
and at 1315 and 1143 cm-1 (due to the -SO2). Its 1H NMR (DMSO-
d6/TMS) spectrum (Fig. 3.21) showed signals at 2.60 (d, J=4.4 HZ,
87
3H, -NHCH3), 2.9-3.00 (t, 2H, -Ar-CH2), 3.30-3.40 (t, 2H, -SO2CH2),
5.70 (s, 2H, NH2, D2O exchangable), 6.8-6.9 (d, 2H, NH2) 7.00 (m, 1H,
4H, Ar-H). Its APCI mass spectrum (Fig.3.22) showed M++1 ion peak
.Scheme - 3.28
general one and has been extended to substituted amines 26a and
cm-1 (due to the -NH) and at 1712 cm-1 (sharp, strong, due to the
88
carbonyl) and 1309 and 1131 cm-1 (due to -SO2 group). Its 1H NMR
spectrum (Fig.3.25) at 2.60 (d, 3H J=4.8, -NHCH3), 3.00 (t, 2H, -Ar-
CH2), 3.30-3.40 (t, 2H, -SO2CH2), 7.00 (m, 1H, -NHCH3, D2O
exchangable), 7.50 (d, 2H J=8.4 HZ, Ar-H), 7.70 (d, 2H J=8.4 HZ, Ar-
H), 8.10 (s, 1H, CH pyrimidine), 8.50 (s, 1H, CH imidazole), 12.50
3.26) in APCI mode showed the M++1 ion peak at 334 confirming the
molecular mass of the compound as 333. Its 13C NMR spectrum (Fig.
above spectral data the compound was assigned the structure 112c.
.Scheme 3.29
.Scheme - 3.30
method, nicotinic acid (115) was converted into ethyl ester to yield
.Scheme - 3.31
.Scheme - 3.32
.Scheme - 3.33
91
c):
by TLC. The organic layer was seperated and washed with excess of
water and finally with brine solution. The organic layer was dried over
was stirred with hexane (20 mL) for I hour at room tempreature. The
solid was filtered, washed with hexane to give pure compound 107(a-
c).
(KBr, cm-1) 2185 and 2140 (-N=C=S), 1310 and 1122 (-SO2); 1H NMR
4H, pyrrolidine), 4.40 (s, 2H, -SO2CH2), 7.60 (d, 2H, Ar-H), 8.20 (d,
(KBr, cm-1) 2185 and 2140 (-N=C=S), 1310 and 1122 (-SO2); 1H NMR
7.00 (m, 1H, -NH, D2O exchangable), 7.60 (d, 2H, Ar-H), 8.20 (d, 2H,
92
(KBr, cm-1) 2185 and 2140 (-N=C=S), 1310 and 1122 (-SO2); 1H NMR
3.40-3.50 (t, 2H, -SO2CH2), 7.00 (m, 1H, -NH, D2O exchangable), 7.60
(d, 2H, Ar-H), 8.20 (d, 2H, Ar-H); M++1: 257; Anal.Calcd for
H, 4.70; N, 10.90.
mol) in absolute ethanol was added into the solution of hydrazide with
the mixture was cooled to room temperature. The resultant white solid
107(a-c).
(KBr, cm-1) 1292 (-C=S), 1693 (C=O), 1310 and 1122 (-SO2); 1H NMR
4H, pyrrolidine), 4.40 (s, 2H, -SO2CH2), 7.00 (s, 1H, -NH, D2O
exchangable), 7.20-7.40 (m, 4H, Ar-H), 7.90 (d, 2H, pyridine ring
protons), 8.80 (d, 2H, pyridine ring protons), 9.90 (s, 2H, -NH-NH
93
(KBr, cm-1) 1292 (-C=S) 1693 (C=O), 1310 and 1122 (-SO2); 1H NMR
7.00 (s, 1H, -NH, D2O exchangable), 7.20-7.40 (m, 4H, Ar-H), 7.90 (d,
2H, pyridine ring protons), 8.80 (d, 2H, pyridine ring protons), 9.90 (s,
2H, -NH-NH protons), 10.90 (s, 1H, -NH, D2O exchangable); M++1:
(KBr, cm-1) 1292 (-C=S) 1693 (C=O), 1310 and 1122 (-SO2); 1H NMR
3.40-3.50 (t, 2H, -SO2CH2), 7.00 (s, 1H, -NH, D2O exchangable), 7.20-
7.40 (m, 4H, Ar-H), 7.90 (d, 2H, pyridine ring protons), 8.80 (d, 2H,
pyridine ring protons), 9.90 (s, 2H, -NH-NH portons), 10.90 (s, 1H, -
NH, D2O exchangable); M++1: 394; 13C NMR 28.97, 29.06, 50.70,
The reaction mass was cooled to room temperature and filtered. The
precipitated solid was filtered, washed thoroughly with water (20 mL),
(KBr, cm-1) 2726 (-SH), 1310 and 1122 (-SO2); 1H NMR (DMSO-
d6/TMS) at 1.90 (m, 4H, pyrrolidine), 3.20 (m, 4H, pyrrolidine), 4.40
(s, 2H, -SO2CH2), 7.20-7.40 (m, 4H, Ar-H), 7.60 (d, 2H, pyridine ring
protons), 8.70 (d, 2H, pyridine ring protons), 14.20 (s, 1H, -SH, D2O
(KBr, cm-1) 2726 (-SH), 1310 and 1122 (-SO2); 1H NMR (DMSO-
d6/TMS) at 2.60 (d, 3H, -NHCH3), 4.40 (s, 2H, -SO2CH2), 7.00 (m,
1H, -NH, D2O exchangable), 7.20-7.40 (m, 4H, Ar-H), 7.60 (d, 2H,
pyridine ring protons), 8.70 (d, 2H, pyridine ring protons), 14.20 (s,
19.33.
(KBr, cm-1) 2726 (-SH), 1310 and 1122 (-SO2); 1H NMR (DMSO-
d6/TMS) at 2.50 (d, 3H, -NHCH3), 2.9-3.00 (t, 2H, -Ar-CH2), 3.40-
3.50 (t, 2H, -SO2CH2), 7.00 (s, 1H, -NH, D2O exchangable), 7.20-7.40
95
(m, 4H, Ar-H), 7.60 (d, 2H, pyridine ring protons), 8.70 (d, 2H,
pyridine ring protons), 14.20 (s, 1H, -SH, D2O exchangable); M++1:
376; 13C NMR 28.94, 29.20, 50.28, 122.25, 128.94, 129.92, 132.88,
H, 4.52; N, 18.60.
wise to Con. sulfuric acid (25 mL) at 0 C with continuous stirring. The
The reaction mass was poured into crushed ice (100 gm) and stirred
from a mixture of acetic acid and water (1:1) to get compounds 109(a-
c).
(KBr, cm-1) 3440 (-NH), 1310 and 1122 (-SO2); 1H NMR (DMSO-
d6/TMS) at 1.90 (d, 4H, pyrrolidine), 3.20 (d, 4H, pyrrolidine), 4.40
(s, 2H, -SO2CH2), 7.20-7.60 (m, 4H, Ar-H), 7.80 (d, 2H, pyridine ring
protons), 8.80 (d, 2H, pyridine ring protons), 10.80 (s, 1H, -NH, D2O
(KBr, cm-1) 3440 (-NH), 1310 and 1122 (-SO2); 1H NMR (DMSO-
d6/TMS) at 2.60 (d, 3H, -NHCH3), 4.40 (s, 2H, -SO2CH2), 7.00 (m,
96
1H, -NH, D2O exchangable), 7.20-7.60 (m, 4H, Ar-H), 7.80 (d ,2H,
pyridine ring protons), 8.80 (d, 2H, pyridine ring protons), 10.80 (s,
19.33.
109c: R = -NHCH3, n=2, Yield: 0.75 gm (80 %); M.R: >300 C; IR (KBr,
2.60 (d, 3H, -NHCH3), 2.9-3.00 (t, 2H, -Ar-CH2), 3.30-3.40 (t, 2H, -
SO2CH2), 7.00 (m, 1H, -NHCH3 D2O exchangable), 7.20-7.60 (m, 4H,
Ar-H), 7.80 (d, 2H, pyridine ring protons), 8.80 (d, 2H, pyridine ring
protons), 10.80 (s, 1H, -NH, D2O exchangable), M++1: 376; Its 13C
(0.014 mol, 1.08 gm) at room temperature. The reaction mixture was
was cooled to room temperature and added Con.HCl (3.8 gm). The
was added water (20 mL) and the pH adjusted to neutral with
(KBr, cm-1) 1625 (-C=N), 1310 and 1150 (-SO2); 1H NMR (DMSO-
d6/TMS) at 1.90 (d, 4H, pyrrolidine), 2.00 (m, 2H, CH2), 2.40 (m,
2H, CH2), 3.00 (m, 2H, CH2), 3.20 (d, 4H, pyrrolidine), 4.40 (s, 2H, -
SO2CH2), 7.20-7.60 (m, 4H, Ar-H), 8.80 (s, 1H, -NH, D2O
(KBr, cm-1) 3278 (-NH), 1624 (-C=N), 1310 and 1150 (-SO2); 1H NMR
(DMSO-d6/TMS) at 1.90 (m, 2H, CH2), 2.6 (d, 3H, -NHCH3), 2.90 (m,
2H, CH2), 3.50 (m, 2H, CH2), 4.20 (s, 2H, -SO2CH2), 6.90 (s, 1H, -NH
D2O exchangable), 7.20-7.60 (m, 4H, Ar-H), 8.40 (s, 1H, -NH, D2O
(KBr, cm-1) 3288 (-NH), 1625 (-C=N), 1310 and 1150 (-SO2) ; 1H NMR
(DMSO-d6/TMS) at 1.80 (m, 2H, CH2), 2.6 (d, 3H, -NHCH3), 2.80 (m,
2H, CH2), 3.00 (t, 2H, -Ar-CH2), 3.20 (t, 2H, -SO2CH2), 3.40 (m, 2H,
CH2), 6.90 (s, 1H, -NH, D2O exchangable), 7.20-7.60 (m, 4H, Ar-H),
8.40 (s, 1H, -NH, D2O exchangable); M++1: 314; Anal.Calcd for
98
H, 6.08; N, 13.39.
(KBr, cm-1) 3445 (-NH), 1648 (-C=O) 1315 and 1143 (-SO2); 1H NMR
pyrrolidine), 4.40 (s, 2H, -SO2CH2), 5.80 (s, 2H, -CONH2 D2O
exchangable), 6.7-6.9 (d, 2H, -NH2 D2O exchangable), 7.40 (s, 1H,
(KBr, cm-1) 3435 (-NH), 1644 (-C=O) 1315 and 1143 (-SO2); 1H NMR
5.80 (s, 2H, -CONH2, D2O exchangable), 6.7-6.9 (d, 2H, -NH2, D2O
exchangable), 7.00 (m, 1H, -NH, D2O exchangable), 7.40 (s, 1H, CH
H, 4.87; N, 22.61.
(KBr, cm-1) 3423 (-NH2), 1640 (-C=O) 1315 and 1143 (-SO2); 1H NMR
3.40 (m, 2H, -SO2CH2), 5.80 (s, 2H, -CONH2, D2O exchangable), 6.7-
6.9 (d, 2H, -NH2, D2O exchangable), 7.00 (m, 1H, -NHCH3, D2O
M++1: 324; 13C NMR 28.99, 29.11, 50.44, 113.36, 124.93, 130.04,
H, 5.28; N, 21.61.
c):
A mixture of 111(a-c) (0.005 mol) and formic acid (20 mL) was
refluxed for 1 hour. The solution was cooled, and then poured into
water (50 mL). The solid that seperated was collected and crystallized
(KBr, cm-1) 3440 (-NH), 1712 (-C=O), 1519 and 1131 (-SO2); 1H NMR
pyrrolidine), 4.40 (s, 2H, -SO2CH2), 7.40-7.60 (m, 4H, Ar-H), 8.10 (s,
1H, CH pyrimidine), 8.50 (s, 1H, CH imidazole), 12.50 (s, 1H, -NH,
H, 4.75; N, 19.45.
112b: R = -NHCH3, n=1, Yield: 1.2 gm (80 %); M.R: >270 C; IR (KBr,
cm-1) 3440 (-NH), 1712 (-C=O), 1519 and 1131 (-SO2); 1H NMR
7.00 (m, 1H, -NH, D2O exchangable), 7.20-7.60 (m, 4H, Ar-H), 8.10
(s, 1H, CH pyrimidine), 8.50 (s, 1H, CH imidazole), 12.50 (s, 1H, -NH,
H, 4.08; N, 21.89.
112c: R=-NHCH3, n=2, Yield: 1.1gm (70 %); M.R: >270 C; IR (KBr,
cm-1) 3443 (-NH), 1712 (-C=O), 1309 and 1131 (-SO2); 1H NMR
8.10 (s, 1H, CH pyrimidine), 8.50 (s, 1H, CH imidazole), 12.50 (s, 1H, -