Ethyl-3,4-diaroyl-2-cyanobutyrate: A Synthon for novel heterocycles

Article abstract of DOI:10.1002/jhet.214

(Chemical Equation Presented) A new class of aminopyrazolones, aminoisoxazolones, aminopyrimidinones, and thioxopyrimidinones were synthesized from Michael adduct, ethyl-3,4-diaroyl-2-cyanobutyrate, on reaction with different nucleophiles, hydrazine hydra

Full text of DOI:10.1002/jhet.214

November 2009
Ethyl-3,4-diaroyl-2-cyanobutyrate: A Synthon for Novel
Heterocycles
1239
Adivireddy Padmaja,* Thalari Payani, Konda Mahesh,
and Venkatapuram Padmavathi
Department of Chemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh 517502, India
*E-mail: advireddyp@yahoo.co.in
Received February 3, 2009
DOI 10.1002/jhet.214
Published online 6 November 2009 in Wiley InterScience (www.interscience.wiley.com).
A new class of aminopyrazolones, aminoisoxazolones, aminopyrimidinones, and thioxopyrimidinones
were synthesized from Michael adduct, ethyl-3,4-diaroyl-2-cyanobutyrate, on reaction with different
nucleophiles, hydrazine hydrate, hydroxylamine hydrochloride, and urea derivatives.
J. Heterocyclic Chem., 46, 1239 (2009).
INTRODUCTION
dione (1) in the presence of K2CO3 in MEK to get
ethyl-3,4-diaroyl-2-cyanobutyrate (2) (Scheme 1 and
Table 1). The IR spectra of 2 displayed absorption
bands at 2241–2250 (CN), 1698–1715 (ArCO), 1731–
A large number of heterocyclic compounds play a vital
role as drugs and pharmaceutical agents. A number of
barbiturate and thiobarbiturate derivatives exhibit anti-
convulsant, anaesthetic, sedative, and hypnotic properties
[1–5]. In fact, phenobarbital and mephobarbital are used
for clinical treatment of epilepsy [6]. Besides, methohexi-
tal is still used worldwide in hospitals as injection nar-
cotics [7]. Increasing evidence suggests that pyrazole and
isoxazole derivatives possess a broad spectrum of biolog-
ical activity such as bacteriostatic, antidiabetic, analgesic,
antiarrhythmic, anti-inflammatory, antifungal, and antivi-
ral properties [8–13]. Celecoxib, a pyrazole derivative,
valdecoxib, an isoxazole derivative are now being used
as anti-inflammatory drugs [14]. Thus, the development
of practical and convenient method for the construction
of nitrogen containing heterocycles is an important goal.
Michael adducts afford a rich and diverse array of options
for the synthesis of variety of five and six membered het-
erocycles. In fact, we have exploited a variety of Michael
adducts to develop different heterocycles [15–19]. In a
continuing quest for further ways of utilizing Michael
adducts, the present work has been taken up.
1
1748 cmꢀ1 (CO2Et) (Table 2). The H NMR spectrum
of 2a showed a doublet at 4.53 (C2AH), a multiplet at
4.02–4.07 (C3AH), and two double doublets at 3.27 and
3.35 ppm (C4AH). Apart from these, a quartet and a tri-
plet are observed at 3.54, 1.25 ppm due to carboethoxy
group (Table 3). The gem-cyanoester functionality in 2
is exploited to get the desired heterocycles. The cyclo-
condensation of 2 with hydrazine hydrate in the pres-
ence of piperidine in ethanol produced 3-amino-4(10,20-
diaroylethyl)-1H-pyrazol-5(4H)-one (3). Likewise, the
reaction of 2 with hydroxylamine hydrochloride gave
3-amino-4-(10,20-diaroylethyl)isoxazolo-5(4H)-one
(4)
(Scheme 1 and Table 1). The IR spectra of 3 and 4 dis-
played absorption bands at 3342–3375, 3438–3479
(NH2), 1604–1624 (C¼¼N), 1624–1636 (CONH), 1692–
1711 (Ar-CO), and at 1738–1749 cmꢀ1 (COAO) (Table
1
2). The H NMR spectra of 3a and 4a exhibited a dou-
blet at 4.37, 4.34 for C4AH, a multiplet at 4.17–4.22,
4.15–4.24 for C10AH and two double doublets at 3.14
and 3.82 and 3.11 and 3.72 ppm for C20AH. Further, a
broad singlet is observed at 5.87, 5.90 ppm due to NH2
which disappeared on deuteration (Table 3). Similar
reaction of 2 with urea, N,N0-dimethylurea, and thiourea
produced 6-amino-5-(10,20-diaroylethyl)-2-hydroxypyri-
midine-4(5H)-one (5), 6-imino-5-(10,20-diaroylethyl)-1,3-
RESULTS AND DISCUSSION
The synthetic scheme involves the Michael addition
of ethyl cyanoacetate to (E)-1,4-diaroylbut-2-ene-1,4-
C
V
2009 HeteroCorporation

1240
A. Padmaja, T. Payani, K. Mahesh, and V. Padmavathi
Vol 46
Scheme 1
dimethyl-pyrimidine-2,4(5H)-dione (6), and 6-amino-5-
(10,20-diaroylethyl)-2-mercapto-pyrimidine-4(5H)-one
(7), respectively (Scheme 1 and Table 1). The IR spec-
tra of 5–7 showed absorption bands in the regions
3345–3460 (NH2), 1625–1645 (COAN), and 1695–1715
cmꢀ1 (Ar-CO). In addition to these, the compound 5
displayed a band at 3315–3321 (OH), 6 at 1629–1642
(C¼¼O of pyrimidine ring), and 3311–3238 cmꢀ1 (NH),
while 7 at 2543–2564 cmꢀ1 (SH). The compounds 5
and 7 also showed an absorption band at 1603–1617
C5AH, a multiplet at 4.18–4.24, 4.15–4.21, 4.13–4.25
for C10AH and two doublet of doublets at 3.08 and 3.82,
307 and 3.76, 3.04 and 3.77 ppm for C20AH. Besides
these, 6a showed two singlets at 2.73 and 2.75 for N-
methyl protons and a broad singlet at 9.24 ppm for
¼¼NH. The compounds 5a and 7a also displayed a broad
singlet at 5.87 and 5.73 ppm for NH2. Another singlet is
observed at 6.90 in 5a due to OH and at 1.33 ppm in 7a
due to SH. The signals of NH, NH2, OH, and SH are
disappeared on deuteration. The structures of all the
new compounds are further confirmed by 13C NMR
spectra (Table 3).
1
cmꢀ1 (C¼¼N) (Table 2). The H NMR spectra of 5a, 6a,
and 7a displayed a doublet at 4.37, 4.39, 4.33 for
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
Ethyl-3,4-diaroyl-2-cyanobutyrate: A Synthon for Novel Heterocycles
1241
Table 1
Physical and analytical data of compounds 2–10.
Analysis % Calcd./Found
Compound
Mp (ꢁC)
116–118
Yield (%)
72
Ar
C6H5
Ar0
C6H5
Molecular formula
C
H
N
2a
C21H19NO4 (349.38)
72.19
72.29
73.19
73.22
60.30
60.24
72.71
72.67
65.71
65.79
66.42
66.51
68.05
68.00
69.41
69.50
56.45
56.38
68.75
68.81
61.71
61.76
62.58
62.52
67.85
67.89
69.22
69.18
56.31
56.35
68.56
68.60
61.55
61.58
62.42
62.38
66.11
66.08
67.51
67.57
55.57
55.61
66.83
66.89
60.38
60.35
61.24
61.28
67.51
67.45
68.72
68.80
57.40
57.45
68.13
68.19
62.05
62.09
62.80
62.87
5.48
5.46
6.14
6.12
4.10
4.06
5.82
5.85
4.73
4.71
5.07
5.02
5.11
5.15
5.82
5.80
3.74
3.71
5.48
5.50
4.36
4.40
4.73
4.70
4.79
4.84
5.53
5.51
3.48
3.49
5.18
5.17
4.08
4.06
4.45
4.48
4.72
4.71
5.41
5.45
3.50
3.51
5.07
5.10
4.05
4.04
4.41
4.44
5.41
5.42
6.01
6.00
4.16
4.14
5.72
5.75
4.73
4.71
5.04
5.02
4.01
4.14
2b
2c
2d
2e
2f
130–132
144–146
138–140
152–154
126–128
156–158
165–167
172–174
175–177
180–182
166–168
151–153
164–166
170–172
176–178
161–163
154–156
182–184
201–203
215–217
188–190
194–196
207–209
186–188
204–206
219–221
193–195
198–200
211–213
70
78
74
76
73
85
82
87
80
78
84
75
77
72
74
70
67
65
68
70
73
76
69
64
66
62
65
68
63
P-CH3C6H4
P-ClC6H4
C6H5
P-CH3C6H4
P-ClC6H4
P-CH3C6H4
P-ClC6H4
P-ClC6H4
C6H5
C23H23NO4 (377.43)
C21H17Cl2NO4 (418.27)
C22H21NO4 (363.41)
C21H18ClNO4 (383.82)
C22H20ClNO4 (397.85)
C19H17N3O3 (335.36)
C21H21N3O3 (363.41)
C19H15Cl2N3O3 (404.25)
C20H19N3O3 (349.38)
C19H16ClN3O3 (369.8)
C20H18ClN3O3 (383.83)
C19H16N2O4 (336.34)
C21H20N2O4 (364.39)
C19H14Cl2N2O4 (405.23)
C20H18N2O4 (350.37)
C19H15ClN2O4 (370.79)
C20H17ClN2O4 (384.81)
C20H17N3O4 (363.37)
C22H21N3O4 (391.42)
C20H15Cl2N3O4 (432.26)
C21H19N3O4 (377.39)
C20H16ClN3O4 (397.81)
C21H18ClN3O4 (411.84)
C22H21N3O4 (391.42)
C24H25N3O4 (419.47)
C22H19Cl2N3O4 (460.31)
C23H23N3O4 (405.45)
C22H20ClN3O4 (425.86)
C23H22ClN3O4 (439.89)
3.71
3.75
3.35
3.37
3.85
3.80
3.65
3.67
3.52
3.50
C6H5
P-CH3C6H4
C6H5
3a
3b
3c
3d
3e
3f
12.53
12.59
11.56
11.66
10.39
10.45
12.03
12.09
11.36
11.30
10.95
11.02
8.33
P-CH3C6H4
P-ClC6H4
C6H5
P-CH3C6H4
P-ClC6H4
P-CH3C6H4
P-ClC6H4
P-ClC6H4
C6H5
C6H5
P-CH3C6H4
C6H5
4a
4b
4c
4d
4e
4f
8.37
7.69
7.66
6.91
6.94
8.00
8.08
7.56
P-CH3C6H4
P-ClC6H4
C6H5
P-CH3C6H4
P-ClC6H4
P-CH3C6H4
P-ClC6H4
P-ClC6H4
C6H5
C6H5
7.52
7.28
P-CH3C6H4
C6H5
7.24
5a
5b
5c
5d
5e
5f
11.56
11.66
10.74
10.80
9.72
P-CH3C6H4
P-ClC6H4
C6H5
P-CH3C6H4
P-ClC6H4
P-CH3C6H4
P-ClC6H4
P-ClC6H4
C6H5
9.80
11.13
11.20
10.56
10.60
10.20
10.15
10.74
10.71
10.02
10.08
9.13
C6H5
P-CH3C6H4
C6H5
6a
6b
6c
6d
6e
6f
P-CH3C6H4
P-ClC6H4
C6H5
P-CH3C6H4
P-ClC6H4
P-CH3C6H4
P-ClC6H4
P-ClC6H4
9.08
10.36
10.42
9.87
9.82
9.55
C6H5
P-CH3C6H4
9.59
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1242
A. Padmaja, T. Payani, K. Mahesh, and V. Padmavathi
Vol 46
Table 1
(Continued)
Analysis % Calcd./Found
Compound
Mp (ꢁC)
195–197
Yield (%)
74
Ar
C6H5
Ar0
C6H5
Molecular formula
C
H
N
7a
7b
7c
7d
7e
7f
C20H17N3O3S (379.43)
63.31
63.28
64.85
64.89
53.58
53.57
64.10
64.13
58.04
58.00
58.94
58.97
4.52
4.51
5.19
5.22
3.37
3.40
4.87
4.86
3.90
3.88
4.24
4.27
11.07
11.14
10.31
10.36
9.37
214–216
220–222
218–220
205–207
225–227
72
66
77
71
69
P-CH3C6H4
P-ClC6H4
C6H5
P-CH3C6H4
P-ClC6H4
P-CH3C6H4
P-ClC6H4
P-ClC6H4
C22H21N3O3S (407.49)
C20H15Cl2N3O3S (448.32)
C21H19N3O3S (393.46)
C20H16ClN3O3S (413.88)
C21H18ClN3O3S (427.9)
9.32
10.68
10.74
10.15
10.17
9.82
C6H5
P-CH3C6H4
9.88
Table 2
IR data of compounds 2–10.
IR (KBr) cmꢀ1
Compound
CBN/C¼N
C¼O
Ar-C¼O
CO2Et
OH/SH
NH
NH2
2a
2b
2c
2d
2e
2f
3a
3b
3c
3d
3e
3f
4a
4b
4c
4d
4e
4f
5a
5b
5c
5d
5e
5f
6a
6b
6c
6d
6e
6f
7a
7b
7c
7d
7e
7f
2243
2250
2246
2241
2245
2244
1608
1613
1606
1624
1619
1621
1605
1609
1613
1610
1604
1610
1603
1610
1612
1618
1616
1609
–
–
1710
1702
1698
1704
1715
1701
1695
1702
1707
1698
1690
1696
1703
1700
1692
1695
1704
1711
1707
1713
1699
1711
1702
1709
1715
1712
1697
1692
1701
1694
1702
1709
1705
1699
1711
1702
1733
1735
1731
1736
1742
1748
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
3210
3204
3209
3201
3206
3200
–
–
1634
1628
1631
1636
1630
1624
1741
1749
1746
1738
1744
1742
1644
1634
1640
1636
1638
1645
1634
1642
1632
1629
1634
1631
1633
1639
1643
1637
1635
1640
–
–
3361
3357
3361
3358
3342
3350
3352
3349
3364
3375
3357
3338
3351
3347
3361
3359
3361
3352
–
3472
3479
3474
3444
3438
3442
3449
3451
3448
3452
3445
3443
3457
3449
3452
3445
3448
3454
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
3328
3315
3331
3324
3322
3319
–
–
–
–
–
–
–
–
–
–
–
–
–
3211
3216
3234
3222
3227
3238
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
1610
1612
1601
1609
1604
1617
2564
2557
2545
2543
2559
2561
3350
3346
3362
3351
3362
3353
3451
3446
3454
3444
3446
3453
–
–
–
–
–
–
–
–
–
–
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
Ethyl-3,4-diaroyl-2-cyanobutyrate: A Synthon for Novel Heterocycles
1243
Table 3
1H and 13C NMR data of compounds 2–7.
Compound
1H NMR (CDCl3/DMSO-d6) d, ppm
13C NMR (CDCl3/DMSO-d6) d, ppm
13.9 (OCH2CH3), 36.1 (C-3), 41.6 (C-2), 52.9 (C-4),
61.1 (OCH2CH3), 116.2 (CN), 166.8 (CO2Et), 205.8
(Ar-CO), 206.2 (Ar0-CO), 125.7, 127.7, 128.5,
129.1, 131.4, 134.2, 134.7, 135.9 (aromatic
carbons)
2a
1.25 (t, 3H, OCH2CH3), 3.27 (dd, 1H, C4AH, J ¼ 8.6,
14.4 Hz), 3.35 (dd, 1H, C4AH, J ¼ 4.2, 14.6 Hz), 3.54
(q, 2H, OCH2CH3), 4.02–4.07 (m, 1H, C3AH), 4.53
(d, 1H, C2AH, J ¼ 8.6 Hz), 7.16–7.48 (m, 10H, Ar-H)
2b
1.28 (t, 3H, OCH2CH3), 2.26 (s, 6H, Ar-CH3 and Ar0-
CH3), 3.24 (dd, 1H, C4AH, J ¼ 9.0, 14.3 Hz), 3.29
(dd, 1H, C4AH, J ¼ 4.5, 14.8 Hz), 3.51 (q, 2H,
OCH2CH3), 3.97–3.99 (m, 1H, C3AH), 4.48 (d, 1H,
C2AH, J ¼ 8.5 Hz), 7.21–7.46 (m, 8H, Ar-H)
1.31 (t, 3H, OCH2CH3), 3.28 (dd, 1H, C4AH, J ¼ 8.8,
14.5 Hz), 3.31 (dd, 1H, C4AH, J ¼ 4.4, 14.6 Hz), 3.57
(q, 2H, OCH2CH3), 3.92–4.01 (m, 1H, C3AH), 4.51
(d, 1H, C2AH, J ¼ 8.7 Hz), 7.26–7.58 (m, 8H, Ar-H)
1.27 (t, 3H, OCH2CH3), 2.25 (s, 3H, Ar0-CH3), 3.25 (dd,
1H, C4AH, J ¼ 8.5, 14.2 Hz), 3.34 (dd, 1H, C4AH,
J ¼ 4.6, 14.4 Hz), 3.55 (q, 2H, OCH2CH3), 3.91–4.03
(m, 1H, C3AH), 4.54 (d, 1H, C2AH, J ¼ 8.6 Hz),
7.21–7.51 (m, 9H, Ar-H)
22.7 (Ar-CH3 and Ar0-CH3), 13.4 (OCH2CH3), 36.8
(C-3), 42.1 (C-2), 51.6 (C-4), 62.0 (OCH2CH3),
114.9 (CN), 167.6 (CO2Et), 205.1 (Ar-CO), 206.6
(Ar0-CO), 126.1, 128.4, 128.9, 129.7, 132.5, 134.3,
134.7, 135.1 (aromatic carbons)
13.7 (OCH2CH3), 37.4 (C-3), 42.9 (C-2), 52.1 (C-4),
62.6 (OCH2CH3), 114.2 (CN), 167.9 (CO2Et), 205.9
(Ar-CO), 206.0 (Ar0-CO), 126.8, 128.9, 129.9,
132.2, 134.5, 134.2, 136.9 (aromatic carbons)
13.0 (OCH2CH3), 22.4 (Ar0-CH3), 37.1 (C-3), 42.4
(C-2), 52.3 (C-4), 62.2 (OCH2CH3), 114.8 (CN),
167.2 (CO2Et), 205.6 (Ar-CO), 206.8 (Ar0-CO),
126.2, 128.4, 129.3, 132.0, 134.1, 134.8, 135.1
(aromatic carbons)
2c
2d
2e
2f
1.34 (t, 3H, OCH2CH3), 3.21 (dd, 1H, C4AH, J ¼ 8.3,
14.5 Hz), 3.31 (dd, 1H, C4AH, J ¼ 4.5, 14.3 Hz), 3.58
(q, 2H, OCH2CH3), 3.94–4.01 (m, 1H, C3AH), 4.52
(d, 1H, C2AH, J ¼ 8.6 Hz), 7.28–7.67 (m, 9H, Ar-H)
1.26 (t, 3H, OCH2CH3), 2.27 (s, 3H, Ar-CH3), 3.25 (dd,
1H, C4AH, J ¼ 8.2, 14.2 Hz), 3.34 (dd, 1H, C4AH,
J ¼ 4.6, 14.4 Hz), 3.50 (q, 2H, OCH2CH3), 3.93–4.04
(m, 1H, C3AH), 4.50 (d, 1H, C2AH, J ¼ 8.8 Hz),
7.31–7.74 (m, 9H, Ar-H)
13.2 (OCH2CH3), 37.6 (C-3), 42.7 (C-2), 52.6 (C-4),
62.8 (OCH2CH3), 114.3 (CN), 167.1 (CO2Et), 205.7
(Ar-CO), 206.4 (Ar0-CO), 126.8, 127.9, 129.2,
132.8, 134.7, 135.9, 135.1 (aromatic carbons)
13.8 (OCH2CH3), 21.9 (Ar-CH3), 37.3 (C-3), 42.9
(C-2), 52.3 (C-4), 62.0 (OCH2CH3), 114.1 (CN),
167.1 (CO2Et), 205.2 (Ar-CO), 206.9 (Ar0-CO),
126.1, 127.6, 129.0, 132.2, 133.4, 134.9, 136.4
(aromatic carbons)
3a
3b
3.14 (dd, 1H, C20AH, J ¼ 4.3, 14.1 Hz), 3.82 (dd, 1H,
C20AH, J ¼ 9.1, 14.3 Hz), 4.17–4.22 (m, 1H, C10AH),
4.37 (d, 1H, C4AH, J ¼ 5.6 Hz), 5.87 (bs, 2H, NH2),
7.10–7.85 (m, 10H, Ar-H), 9.11 (bs, 1H, NH)
2.24 (s, 6H, Ar-CH3 and Ar0-CH3), 3.10 (dd, 1H, C20AH,
J ¼ 4.1, 14.0 Hz), 3.79 (dd, 1H, C20AH, J ¼ 9.2, 14.1
Hz), 4.12–4.25 (m, 1H, C10AH), 4.35 (d, 1H, C4AH,
J ¼ 5.4 Hz), 5.82 (bs, 2H, NH2), 7.12–7.81 (m, 8H,
Ar-H), 9.19 (bs, 1H, NH)
53.1 (C-20), 55.8 (C-10), 62.9 (C-4), 156.6 (C-5),
171.5 (C-3), 205.5 (Ar-CO), 206.2 (Ar0-CO), 129.6,
130.2, 131.8, 132.9, 133.6, 134.9, 135.4, 136.2
(aromatic carbons)
22.4 (Ar-CH3 and Ar0-CH3), 53.8 (C-20), 56.1 (C-10),
63.3 (C-4), 156.9 (C-5), 169.5 (C-3), 205.6
(Ar-CO), 206.6 (Ar0-CO), 128.5, 129.1, 130.6,
131.5, 132.2, 133.5, 134.1, 135.4 (aromatic
carbons)
3c
3.08 (dd, 1H, C20AH, J ¼ 4.0, 14.2 Hz), 3.74 (dd, 1H,
C20AH, J ¼ 9.1, 14.3 Hz), 4.15–4.21 (m, 1H, C10AH),
4.34 (d, 1H, C4AH, J ¼ 5.4 Hz), 5.84 (bs, 2H, NH2),
7.14–7.86 (m, 8H, Ar-H), 9.78 (bs, 1H, NH)
53.3 (C-20), 56.5 (C-10), 63.9 (C-4), 157.1 (C-5),
169.9 (C-3), 205.2 (Ar-CO), 206.9 (Ar0-CO), 128.9,
129.7, 130.2, 131.2, 132.9, 133.9, 134.9, 136.4
(aromatic carbons)
3d
2.28 (s, 3H, Ar0-CH3), 3.12 (dd, 1H, C20AH, J ¼ 4.3, 14.4
Hz), 3.78 (dd, 1H, C20AH, J ¼ 9.2, 14.4 Hz), 4.11–4.24
(m, 1H, C10AH), 4.38 (d, 1H, C4AH, J ¼ 5.7 Hz), 5.89
(bs, 2H, NH2), 7.10–7.82 (m, 9H, Ar-H), 9.86 (bs, 1H,
NH)
21.5 (Ar0-CH3), 53.5 (C-20), 56.3 (C-10), 63.6 (C-4),
156.7 (C-5), 169.1 (C-3), 205.0 (Ar-CO), 206.2
(Ar0-CO), 128.1, 129.4, 130.8, 131.9, 132.1, 133.7,
134.2, 135.9 (aromatic carbons)
3e
3f
3.07 (dd, 1H, C20AH, J ¼ 4.1, 14.2 Hz), 3.74 (dd, 1H,
C20AH, J ¼ 9.0, 14.3 Hz), 4.16–4.27 (m, 1H, C10AH),
4.36 (d, 1H, C4AH, J ¼ 5.4 Hz), 5.86 (bs, 2H, NH2),
7.19–7.69 (m, 9H, Ar-H), 9.71 (bs, 1H, NH)
2.25 (s, 3H, Ar-CH3), 3.16 (dd, 1H, C20AH, J ¼ 4.4, 14.4
Hz), 3.77 (dd, 1H, C20AH, J ¼ 9.2, 14.5 Hz), 4.18–4.28
(m, 1H, C10AH), 4.42 (d, 1H, C4AH, J ¼ 5.7 Hz), 5.89
(bs, 2H, NH2), 7.16–7.85 (m, 8H, Ar-H), 9.77 (bs, 1H,
NH)
52.6 (C-20), 56.0 (C-10), 63.2 (C-4), 157.2 (C-5),
169.6 (C-3), 205.4 (Ar-CO), 206.8 (Ar0-CO), 128.5,
129.9, 130.2, 131.2, 132.2, 133.3, 134.8, 135.2
(aromatic carbons)
22.1 (Ar-CH3), 52.8 (C-20), 55.6 (C-10), 62.7 (C-4),
156.6 (C-5), 169.4 (C-3), 205.9 (Ar-CO), 206.4
(Ar0-CO), 128.7, 129.2, 130.9, 131.7, 132.1, 133.9,
134.7, 136.9 (aromatic carbons)
4a
4b
3.11 (dd, 1H, C20AH, J ¼ 4.6, 14.7 Hz), 3.72 (dd, 1H,
C20AH, J ¼ 9.1, 14.6 Hz), 4.15–4.24 (m, 1H, C10AH),
4.34 (d, 1H, C4AH, J ¼ 5.4 Hz), 5.90 (bs, 2H, NH2),
7.22–7.74 (m, 10H, Ar-H)
2.22 (s, 6H, Ar-CH3 and Ar0-CH3), 3.04 (dd, 1H, C20AH,
J ¼ 4.5, 14.5 Hz), 3.69 (dd, 1H, C20AH, J ¼ 9.0, 14.7
Hz), 4.19–4.27 (m, 1H, C10AH), 4.36 (d, 1H, C4AH, J ¼
5.4 Hz), 5.92 (bs, 2H, NH2), 7.08–7.65 (m, 8H, Ar-H)
53.1 (C-20), 57.2 (C-10), 63.0 (C-4), 159.3 (C-3),
174.1 (C-5), 205.1 (Ar-CO), 206.8 (Ar0-CO), 128.1,
129.5, 130.1, 131.2, 132.6, 133.2, 134.0, 135.2
(aromatic carbons)
22.9 (Ar-CH3 and Ar0-CH3), 53.8 (C-20), 57.7 (C-10),
62.8 (C-4), 158.8 (C-3), 174.6 (C-5), 205.9 (Ar-
CO), 206.1 (Ar0-CO), 128.7, 129.3, 130.9, 131.9,
132.2, 133.9, 134.8, 135.1 (aromatic carbons)
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1244
A. Padmaja, T. Payani, K. Mahesh, and V. Padmavathi
Vol 46
Table 3
(Continued)
Compound
1H NMR (CDCl3/DMSO-d6) d, ppm
13C NMR (CDCl3/DMSO-d6) d, ppm
53.4 (C-20), 57.6 (C-10), 61.7 (C-4), 158.0 (C-3),
173.7 (C-5), 204.9 (Ar-CO), 206.7 (Ar0-CO), 128.1,
129.8, 131.4, 132.3, 133.7, 134.8, 135.2, 136.9
(aromatic carbons)
22.3 (Ar0-CH3), 52.6 (C-20), 58.7 (C-10), 61.5 (C-4),
158.9 (C-3), 173.9 (C-5), 205.2 (Ar-CO), 206.3
(Ar0-CO), 128.7, 129.4, 131.7, 132.5, 133.1, 134.2,
135.1, 136.2 (aromatic carbons)
52.1 (C-20), 58.2 (C-10), 61.8 (C-4), 158.1 (C-3),
173.6 (C-5), 205.7 (Ar-CO), 206.2 (Ar0-CO), 127.9,
128.6, 130.4, 131.5, 132.9, 134.2, 135.6, 136.9
(aromatic carbons)
4c
4d
4e
4f
3.09 (dd, 1H, C20AH, J ¼ 4.7, 14.4 Hz), 3.71 (dd, 1H,
C20AH, J ¼ 9.1, 14.6 Hz), 4.13–4.24 (m, 1H, C10AH),
4.32 (d, 1H, C4AH, J ¼ 5.5 Hz), 5.84 (bs, 2H, NH2),
7.12–7.77 (m, 8H, Ar-H)
2.24 (s, 3H, Ar0-CH3), 3.12 (dd, 1H, C20AH, J ¼ 4.6, 14.6
Hz), 3.76 (dd, 1H, C20AH, J ¼ 9.0, 14.4 Hz), 4.17–4.27
(m, 1H, C10AH), 4.35 (d, 1H, C4AH, J ¼ 5.7 Hz), 5.86
(bs, 2H, NH2), 7.08–7.71 (m, 9H, Ar-H)
3.07 (dd, 1H, C20AH, J ¼ 4.5, 14.5 Hz), 3.78 (dd, 1H,
C20AH, J ¼ 8.9, 14.6 Hz), 4.12–4.23 (m, 1H, C10AH),
4.30 (d, 1H, C4AH, J ¼ 5.5 Hz), 5.94 (bs, 2H, NH2),
7.10–7.75 (m, 9H, Ar-H)
2.22 (s, 3H, Ar-CH3), 3.10 (dd, 1H, C20AH, J ¼ 4.7, 14.7
Hz), 3.72 (dd, 1H, C20AH, J ¼ 8.3, 14.4 Hz), 4.14–4.27
(m, 1H, C10AH), 4.31 (d, 1H, C4AH, J ¼ 5.3 Hz), 5.89
(bs, 2H, NH2), 7.15–7.79 (m, 8H, Ar-H),
21.9 (Ar-CH3), 53.7 (C-20), 57.9 (C-10), 62.4 (C-4),
157.8 (C-3), 174.4 (C-5), 204.6 (Ar-CO), 206.1
(Ar0-CO), 127.2, 128.9, 130.7, 131.1, 132.2, 134.9,
135.2, 136.1 (aromatic carbons)
5a
5b
3.08 (dd, 1H, C20AH, J ¼ 4.4, 14.5 Hz), 3.82 (dd, 1H,
C20AH, J ¼ 9.0, 14.4 Hz), 4.18–4.24 (m, 1H, C10AH),
4.37 (d, 1H, C5AH, J ¼ 5.3 Hz), 5.87 (bs, 2H, NH2),
6.90 (bs, 1H, OH), 7.20–7.71 (m, 10H, Ar-H)
2.23 (s, 6H, Ar-CH3 and Ar0-CH3), 3.09 (dd, 1H, C20AH,
J ¼ 4.5, 14.3 Hz), 3.76 (dd, 1H, C20AH, J ¼ 9.1, 14.1
Hz), 4.12–4.21 (m, 1H, C10AH), 4.34 (d, 1H, C5AH,
J ¼ 5.0 Hz), 5.80 (bs, 2H, NH2), 6.86 (bs, 1H, OH),
7.20–7.62 (m, 8H, Ar-H)
52.9 (C-20), 57.7 (C-10), 64.2 (C-5), 158.6 (C-6),
164.3 (C-2), 174.2 (C-4), 205.9 (Ar-CO), 206.8
(Ar0-CO), 127.9, 129.9, 130.9, 131.8, 132.1, 133.6,
134.9, 135.4 (aromatic carbons)
22.7 (Ar-CH3 and Ar0-CH3), 51.8 (C-20), 55.1 (C-10),
64.9 (C-5), 157.8 (C-6), 164.9 (C-2), 170.6 (C-4),
205.1 (Ar-CO), 206.2 (Ar0-CO), 127.1, 129.3,
130.2, 131.4, 132.9, 133.4, 134.4, 136.9 (aromatic
carbons)
5c
3.11 (dd, 1H, C20AH, J ¼ 4.6, 14.6 Hz), 3.83 (dd, 1H,
C20AH, J ¼ 9.0, 14.4 Hz), 4.11–4.23 (m, 1H, C10AH),
4.36 (d, 1H, C5AH, J ¼ 5.3 Hz), 5.84 (bs, 2H, NH2),
6.87 (bs, 1H, OH), 7.25–7.81 (m, 8H, Ar-H)
52.4 (C-20), 55.8 (C-10), 64.0 (C-5), 158.3 (C-6),
163.7 (C-2), 170.9 (C-4), 205.6 (Ar-CO), 206.7
(Ar0-CO), 127.8, 129.4, 130.8, 131.6, 132.3, 133.9,
135.8, 136.9 (aromatic carbons)
5d
2.26 (s, 3H, Ar0-CH3), 3.07 (dd, 1H, C20AH, J ¼ 4.4, 14.2
Hz), 3.79 (dd, 1H, C20AH, J ¼ 8.9, 14.3 Hz), 4.13–4.21
(m, 1H, C10AH), 4.32 (d, 1H, C5AH, J ¼ 5.1 Hz), 5.82
(bs, 2H, NH2), 6.89 (bs, 1H, OH), 7.16–7.61 (m, 9H,
Ar-H)
21.8 (Ar0-CH3), 52.3 (C-20), 55.2 (C-10), 64.7 (C-5),
159.1 (C-6), 164.2 (C-2), 170.2 (C-4), 205.3
(Ar-CO), 206.8 (Ar0-CO), 127.2, 129.5, 130.4,
131.7, 132.0, 134.6, 135.1, 136.7 (aromatic
carbons)
5e
5f
3.10 (dd, 1H, C20AH, J ¼ 4.6, 14.5 Hz), 3.84 (dd, 1H,
C20AH, J ¼ 8.6, 14.4 Hz), 4.18–4.23 (m, 1H, C10AH),
4.35 (d, 1H, C5AH, J ¼ 5.5 Hz), 5.86 (bs, 2H, NH2),
6.82 (bs, 1H, OH), 7.21–7.78 (m, 9H, Ar-H)
2.21 (s, 3H, Ar-CH3), 3.14 (dd, 1H, C20AH, J ¼ 4.7, 14.4
Hz), 3.81 (dd, 1H, C20AH, J ¼ 8.3, 14.1 Hz), 4.16–4.25
(m, 1H, C10AH), 4.30 (d, 1H, C5AH, J ¼ 5.3 Hz), 5.89
(bs, 2H, NH2), 6.87 (bs, 1H, OH), 7.20–7.72 (m, 8H,
Ar-H)
52.8 (C-20), 56.0 (C-10), 64.1 (C-5), 159.8 (C-6),
164.7 (C-2), 169.9 (C-4), 205.7 (Ar-CO), 207.2
(Ar0-CO), 127.9, 128.7, 130.9, 131.6, 132.9, 134.1,
135.8, 136.4 (aromatic carbons)
22.4 (Ar-CH3), 52.5 (C-20), 55.6 (C-10), 63.7 (C-5),
159.2 (C-6), 164.1 (C-2), 169.6 (C-4), 206.0
(Ar-CO), 207.4 (Ar0-CO), 127.0, 128.5, 130.6,
131.9, 132.3, 134.8, 135.2, 136.8 (aromatic
carbons)
6a
6b
2.73 and 2.75 (s, 6H, NACH3), 3.07 (dd, 1H, C20AH, J ¼
4.0, 14.1 Hz), 3.76 (dd, 1H, C20AH, J ¼ 8.1, 14.0 Hz),
4.15–4.21 (m, 1H, C10AH), 4.39 (d, 1H, C5AH, J ¼ 5.1
Hz), 7.01–7.48 (m, 10H, Ar-H), 9.24 (bs, 1H, NH)
26.8 (NACH3), 27.4 (NACH3), 52.4 (C-20), 54.8
(C-10), 64.0 (C-5), 159.9 (C-2), 163.7 (C-6), 174.2
(C-4), 205.1 (Ar-CO), 207.0 (Ar0-CO), 126.4,
127.2, 128.2, 130.1, 131.5, 132.0, 134.5, 135.7
(aromatic carbons)
22.1 (Ar-CH3 and Ar0-CH3), 26.2 (NACH3), 27.9
(NACH3), 51.9 (C-20), 54.1 (C-10), 64.7 (C-5),
158.8 (C-2), 164.1 (C-6), 173.9 (C-4), 204.8
(Ar-CO), 207.6 (Ar0-CO), 126.9, 128.4, 128.9,
130.4, 131.4, 132.7, 133.8, 134.1, 135.4
(aromatic carbons)
2.26 (s, 6H, Ar-CH3 and Ar0-CH3), 2.74 and 2.79 (s, 6H,
NACH3), 3.11 (dd, 1H, C20AH, J ¼ 4.2, 14.3 Hz), 3.68
(dd, 1H, C20AH, J ¼ 8.0, 14.1 Hz), 4.12–4.24 (m, 1H,
C10AH), 4.31 (d, 1H, C5AH, J ¼ 5.3 Hz), 7.12–7.71
(m, 8H, Ar-H), 9.12 (bs, 1H, NH)
6c
2.71 and 2.76 (s, 6H, NACH3), 3.06 (dd, 1H, C20AH,
J ¼ 4.0, 14.2 Hz), 3.71 (dd, 1H, C20AH, J ¼ 8.0,
14.0 Hz), 4.16–4.23 (m, 1H, C10AH), 4.36 (d, 1H,
C5AH, J ¼ 5.1 Hz), 7.04–7.88 (m, 8H, Ar-H),
8.99 (bs, 1H, NH)
27.9 (NACH3), 28.4 (NACH3), 51.1 (C-20), 54.7
(C-10), 64.2 (C-5), 158.2 (C-2), 164.9 (C-6), 173.4
(C-4), 205.3 (Ar-CO), 207.9 (Ar0-CO), 126.1,
128.9, 129.4, 130.9, 131.7, 132.3, 133.6, 135.8,
139.4 (aromatic carbons)
6d
2.25 (s, 3H, Ar0-CH3), 2.74 and 2.79 (s, 6H, NACH3),
3.10 (dd, 1H, C20AH, J ¼ 4.1, 14.3 Hz), 3.74 (dd, 1H,
C20AH, J ¼ 8.2, 14.2 Hz), 4.13–4.24 (m, 1H, C10AH),
4.30 (d, 1H, C5AH, J ¼ 5.1 Hz), 7.08–7.68 (m, 9H,
Ar-H), 9.17 (bs, 1H, NH)
22.1 (Ar0-CH3), 28.3 (NACH3), 29.7 (NACH3), 52.8
(C-20), 54.1 (C-10), 65.4 (C-5), 158.7 (C-2), 164.2
(C-6), 173.8 (C-4), 205.9 (Ar-CO), 207.1(Ar0-CO),
125.6, 127.8, 128.6, 130.1, 131.2, 132.6, 133.9,
134.4 (aromatic carbons)
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
Ethyl-3,4-diaroyl-2-cyanobutyrate: A Synthon for Novel Heterocycles
1245
Table 3
(Continued)
Compound
1H NMR (CDCl3/DMSO-d6) d, ppm
13C NMR (CDCl3/DMSO-d6) d, ppm
6e
2.78 and 2.81 (s, 6H, NACH3), 3.16 (dd, 1H, C20AH, J ¼
4.3, 14.4 Hz), 3.78 (dd, 1H, C20AH, J ¼ 8.3, 14.3 Hz),
4.18–4.27 (m, 1H, C10AH), 4.37 (d, 1H, C5AH, J ¼ 5.3
Hz), 7.11–7.77 (m, 9H, Ar-H), 9.06 (bs, 1H, NH)
28.0 (NACH3), 29.9 (NACH3), 52.3 (C-20), 54.8
(C-10), 65.0 (C-5), 158.1 (C-2), 164.9 (C-6), 174.3
(C-4), 205.2 (Ar-CO), 207.4 (Ar0-CO), 125.2,
128.4, 130.9, 131.8, 132.2, 133.2, 134.7, 136.4
(aromatic carbons)
6f
2.24 (s, 3H, Ar-CH3), 2.71 and 2.79 (s, 6H, NACH3),
3.12 (dd, 1H, C20AH, J ¼ 4.0, 14.2 Hz), 3.72 (dd, 1H,
C20AH, J ¼ 8.0, 14.1 Hz), 4.11–4.23 (m, 1H, C10AH),
4.32 (d, 1H, C5AH, J ¼ 5.2 Hz), 7.21–7.89 (m, 8H,
Ar-H), 9.09 (bs, 1H, NH)
21.9 (Ar-CH3), 28.5 (NACH3), 28.7 (NACH3), 52.9
(C-20), 54.0 (C-10), 65.5 (C-5), 158.9 (C-2), 164.2
(C-6), 173.9 (C-4), 205.4 (Ar-CO), 208.1 (Ar0-CO),
125.9, 128.1, 130.1, 131.2, 132.9, 133.6, 134.1,
136.9 (aromatic carbons)
7a
7b
1.33 (bs, 1H, SH), 3.04 (dd, 1H, C20AH, J ¼ 4.1, 14.2
Hz), 3.77 (dd, 1H, C20AH, J ¼ 9.1, 14.1 Hz), 4.13–4.25
(m, 1H, C10AH), 4.33 (d, 1H, C5AH, J ¼ 5.3 Hz), 5.73
(bs, 2H, NH2), 7.11–7.79 (m, 10H, Ar-H)
2.21 (s, 6H, Ar-CH3 and Ar0-CH3), 1.39 (bs, 1H, SH),
3.01 (dd, 1H, C20AH, J ¼ 4.0, 14.1 Hz), 3.73 (dd, 1H,
C20AH, J ¼ 9.0, 14.2 Hz), 4.12–4.23 (m, 1H, C10AH),
4.36 (d, 1H, C5AH, J ¼ 5.4 Hz), 5.78 (bs, 2H, NH2),
7.10–7.69 (m, 8H, Ar-H)
52.1 (C-20), 55.0 (C-10), 63.8 (C-5), 161.6 (C-6),
174.3 (C-4), 184.2 (C-2), 205.1 (Ar-CO), 206.4
(Ar0-CO), 127.2, 129.4, 130.2, 131.6, 132.4, 133.1,
134.9, 135.6 (aromatic carbons)
22.6 (Ar-CH3 and Ar0-CH3), 52.6 (C-20), 55.4 (C-10),
63.1 (C-5), 161.9 (C-6), 174.0 (C-4), 184.6 (C-2),
205.7 (Ar-CO), 206.9 (Ar0-CO), 127.8, 129.2,
130.6, 131.3, 132.9, 133.5, 134.6, 135.1 (aromatic
carbons)
7c
1.32 (bs, 1H, SH), 3.08 (dd, 1H, C20AH, J ¼ 4.1, 14.3
Hz), 3.77 (dd, 1H, C20AH, J ¼ 9.2, 14.4 Hz), 4.18–4.27
(m, 1H, C10AH), 4.32 (d, 1H, C5AH, J ¼ 5.3 Hz), 5.72
(bs, 2H, NH2), 7.14–7.89 (m, 8H, Ar-H)
52.9 (C-20), 54.7 (C-10), 63.7 (C-5), 161.3 (C-6),
174.7 (C-4), 184.9 (C-2), 206.4 (Ar-CO), 207.7
(Ar0-CO), 127.2, 129.9, 130.1, 131.8, 132.2, 133.9,
135.9, 136.3 (aromatic carbons)
7d
2.26 (s, 3H, Ar0-CH3), 1.37 (bs, 1H, SH), 3.02 (dd, 1H,
C20AH, J ¼ 4.0, 14.2 Hz), 3.73 (dd, 1H, C20AH, J ¼
9.1, 14.3 Hz), 4.11–4.25 (m, 1H, C10AH), 4.33 (d, 1H,
C5AH, J ¼ 5.4 Hz), 5.79 (bs, 2H, NH2), 7.12–7.77 (m,
9H, Ar-H)
22.4 (Ar0-CH3), 52.2 (C-20), 53.9 (C-10), 63.1 (C-5),
161.8 (C-6), 174.1 (C-4), 184.4 (C-2), 205.5 (Ar-
CO), 206.1 (Ar0-CO), 127.6, 129.2, 130.6, 131.4,
132.6, 133.2, 134.2, 135.4 (aromatic carbons)
7e
7f
1.35 (bs, 1H, SH), 3.06 (dd, 1H, C20AH, J ¼ 4.1, 14.4
Hz), 3.70 (dd, 1H, C20AH, J ¼ 9.0, 14.2 Hz), 4.13–4.23
(m, 1H, C10AH), 4.37 (d, 1H, C5AH, J ¼ 5.6 Hz), 5.84
(bs, 2H, NH2), 7.16–7.79 (m, 9H, Ar-H)
2.27 (s, 3H, Ar-CH3), 1.31 (bs, 1H, SH), 3.09 (dd, 1H,
C20AH, J ¼ 4.2, 14.5 Hz), 3.74 (dd, 1H, C20AH, J ¼
9.1, 14.3 Hz), 4.16–4.27 (m, 1H, C10AH), 4.35 (d, 1H,
C5AH, J ¼ 5.5 Hz), 5.76 (bs, 2H, NH2), 7.18–7.83
(m, 9H, Ar-H)
52.9 (C-20), 54.5 (C-10), 62.8 (C-5), 162.4 (C-6),
174.7 (C-4), 184.1 (C-2), 205.0 (Ar-CO), 207.0
(Ar0-CO), 127.1, 129.8, 130.9, 131.1, 132.3, 133.5,
134.8, 136.2 (aromatic carbons)
22.9 (Ar-CH3), 52.2 (C-20), 54.0 (C-10), 62.3 (C-5),
163.1 (C-6), 173.4 (C-4), 183.7 (C-2), 205.3
(Ar-CO), 207.4 (Ar0-CO), 127.8, 129.2, 130.1,
131.8, 132.4, 133.9, 134.1, 136.8 (aromatic
carbons)
EXPERIMENTAL
tents of the flask were diluted with water and extracted with
dichloromethane. The organic layer was washed with water,
brine and dried (anhyd. Na2SO4). The solvent was removed
in vacuo. The resultant solid was recrystallized from 2-
propanol.
3-Amino-4(10,20-diaroylethyl)-1H-pyrazol-5(4H)-one (3):
General procedure. The compound 2 (10 mmol), hydrazine
hydrate (15 mmol), ethanol (20 mL), and piperidine (5 mL)
was refluxed for 6–8 h. It was cooled and poured onto crushed
ice containing conc. HCl. The reaction mixture was extracted
with ethyl acetate. The organic layer was washed with brine,
dried over anhydrous Na2SO4, and the solvent was removed
under reduced pressure. The resultant solid was recrystallized
from methanol.
3-Amino-4-(10,20-diaroylethyl)isoxazolo-5(4H)-one (4):
General procedure. To a solution of 2 (10 mmol) in ethanol
(20 mL), hydroxylamine hydrochloride (10 mmol) and
piperidine (5 mL) were added and refluxed for 4–6 h. It
was cooled and poured onto crushed ice containing conc. HCl.
The reaction mixture was extracted with ethyl acetate. The
organic layer was washed with brine and dried over
General. Melting points were determined in open capillaries
on a Mel-Temp apparatus and are uncorrected. The purity of
the compounds was checked by TLC (silica gel H, BDH, ethyl
acetate/hexane, 1:3). The IR spectra were recorded on a
Thermo Nicolet IR 200 FT-IR spectrometer as KBr pellets and
the wave numbers were given in cmꢀ1. The H NMR spectra
1
were recorded in CDCl3/DMSO-d6 on a Varian EM-360 spec-
trometer (300 MHz). The 13C NMR spectra were recorded in
CDCl3/DMSO-d6 on a Varian VXR spectrometer operating at
75.5 MHz. All chemical shifts are reported in d (ppm) using
TMS as an internal standard. The microanalyses were per-
formed on a Perkin-Elmer 240C elemental analyzer. The start-
ing compounds (E)-1,4-diaroylbut-2-ene-1,4-dione (1) was pre-
pared by the literature procedure [20].
Ethyl-3,4-diaroyl-2-cyanobutyrate (2): General procedure. A
mixture of ethyl cyanoacetate (15 mmol), methyl ethyl ke-
tone (5 mL), and potassium carbonate (10 mmol) was cooled
to 5–10ꢁC. To this, compound 1 (10 mmol) was added and
stirred for 3–5 h maintaining the same temperature. The con-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1246
A. Padmaja, T. Payani, K. Mahesh, and V. Padmavathi
Vol 46
REFERENCES AND NOTES
anhydrous Na2SO4. Removal of the solvent under vacuum
gave crude product which was purified by recrystallization
from methanol.
[1] Goodman, L. S.; Gilman, A. The Pharmacological Basis of
Therapeutics; McGraw-Hill: New Delhi, 1991; p 358.
[2] Andres, G. Medical Pharmacology; The CV Mosby Com-
pany: Saint Louis, 1976; p 243.
6-Amino-5-(10,20-diaroylethyl)-2-hydroxy-pyrimidine-4(5H)-
one (5): General procedure. The compound 2 (10 mmol)
was dissolved in ethanol (10 mL). To this, urea (10 mmol)
in ethanol (10 mL) and piperidine (5 mL) were added and
refluxed for 6–10 h. The contents were cooled, poured
onto crushed ice containing conc. HCl, and extracted with
ethyl acetate. The organic layer was washed with brine
and dried over anhydrous Na2SO4. Removal of the solvent
in vacuo gave crude product which was recrystallized from
methanol.
[3] Foye, W. O. Principles of Medicinal Chemistry; Lea &
Febiger: London, 1989; p 159.
[4] Meyers, F. H.; Jawetz, E.; Goldfien, A. Review of Medical
Pharmacology; Lange Medical Publications: Los Altos, CA, 1976; p 222.
[5] Wilson, Gisvold’s. Text Book of Organic, Medical and
Pharmaceutical Chemistry; J. B. Lippincott Co: Philadelphia, 1991; p,
368.
6-Imino-5-(10,20-diaroylethyl)-1,3-dimethyl-pyrimidine-2,4(5H)-
dione (6): General procedure. A mixture of 2 (10 mmol), 1,3-
dimethylurea (10 mmol), ethanol (15 mL), and piperidine (5
mL) was refluxed for 8–12 h. The contents were diluted with
ice-cold water, acidified with conc. HCl, and extracted with
ethyl acetate. The organic layer was washed with brine and
dried over anhydrous Na2SO4. Removal of the solvent with
rotary evaporator afforded crude product which was purified
by recrystallization from methanol.
6-Amino-5-(10,20-diaroylethyl)-2-mercapto-pyrimidine-4(5H)-
one (7): General procedure. To an equimolar mixture
(10 mmol) of 2 and thiourea, ethanol (20 mL) and piperidine
(5 mL) were added and refluxed for 10–15 h. The reaction
mixture was cooled, poured onto crushed ice containing conc.
HCl, and extracted with ethyl acetate. The organic layer was
washed with brine and dried over anhydrous Na2SO4. The sol-
vent was removed under reduced pressure. The resultant solid
was recrystallized from methanol.
[6] Hardman, J. G.; Limbird, L. E. Goodman & Gilman’s The
Pharmacological Basis of Therapeutics; McGraw-Hill: New York,
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CONCLUSION
[16] Bhaskar Reddy, D.; Chandrasekhar Babu, N.; Padmavathi,
V. Heteroatom Chem 2001, 12, 131.
The gem-cyanoester functionality in ethyl-3,4-diaroyl-
2-cyanobutyrate is conveniently exploited to get a new
class of aminopyrazolones, isoxazolones, pyrimidine-
diones, and thioxopyrimidinones adopting facile, simple,
and well-versed synthetic methodologies.
[17] Padmavathi, V.; Balaiah, A.; Venugopal Reddy, K.; Pad-
maja, A.; Bhaskar Reddy, D. Ind J Chem 2002, 41B, 1670.
[18] Padmavathi, V.; Subbaiah, D. R. C. V.; Rajagopala Sarma,
M.; Balaiah, A. Heteroatom Chem 2004, 15, 477.
[19] Padmavathi, V.; Subbaiah, D. R. C. V.; Mahesh, K.; Radha
Lakshmi, T. Chem Pharm Bull 2007, 55, 1704.
Acknowledgment. The authors thank UGC, New Delhi, for
financial assistance under minor research project.
[20] William Lown, J.; Erik Landberg, B. Can J Chem 1975, 53,
3782.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet