Novel isocoumarin and isoquinoline derivatives

Article abstract of DOI:10.3184/030823408X296212

A number of novel isoquinoline-1,3-dione derivatives have been synthesised using the readily obtainable anhydride formed from the Stobbe-type condensation of diethyl homophthalate with p-anisaldehyde. Primary amines form amides at the C-1 carbonyl group; recyclisation gives 4-(4-methoxybenzylidene)isoquinoline-1, 3-diones.

Full text of DOI:10.3184/030823408X296212

86 RESEARCH PAPER
FEBRUARY, 86–88
JOURNAL OF CHEMICAL RESEARCH 2008
Novel isocoumarin and isoquinoline derivatives
Mahmoud R. Mahmouda, Manal M. El-Shahawia*, and Samira E. Farahatb
aChemistry Department, Faculty of Science, Ain Shams University, Abbassia 11 566, Cairo, Egypt
b7th of April University, Gharian, Libya
A number of novel isoquinoline-1,3-dione derivatives have been synthesised using the readily obtainable anhydride
formed from the Stobbe-type condensation of diethyl homophthalate with p-anisaldehyde. Primary amines form
amides at the C-1 carbonyl group; recyclisation gives 4-(4-methoxybenzylidene)isoquinoline-1,3-diones.
Keywords: isocoumarins, isoquinolinediones, 2-benzopyran-1,3-diones, fused 1,2,4,5-tetrazines, 2-thiouracils
In a recent paper1 we described the synthesis of the anhydride
1 starting from dimethyl homophthalate. Here we report on
the products formed by opening of the pyrandione ring, in
many cases followed by recyclisation to form isoquinoline-
derived products.
with benzylamine in refluxing pyridine afforded 2-[2'-(N-
cyclohexylcarbonyl)phenyl]-N-benzyl-4-methoxycinnamide
7. Furthermore, the reaction of 5a with malononitrile gave the
isoquinoline derivative 8 (Scheme 1).
Reaction of the anhydride 1 with 6-aminothiouracil in
boiling pyridine yielded a product insoluble in hot pyridine
which was identified as 6-[(4-methoxybenzylidene)amino]
thiouracil 9; a fraction soluble in pyridine afforded 10
upon acidification. (Scheme 2) Treatment of 10 with acetic
anhydride gave the isoquinoline derivative 11, which upon
hydrazinolysis yielded the sulfur-free compound 12.
Reaction of isocoumarin derivative 1 in refluxing ethanol
with the hydrazine derivative ethyl carbazate afforded the
isoquinolinedione 13, which with hydrazine in pyridine
yielded the [1,2,4,5]tetrazino[2,3-a]isoquinoline derivative 14.
Finally, when treated with anhydrous aluminium chloride in
acetylene tetrachloride under Friedel-Crafts reaction conditions
compound 1 yielded the indenone derivative 15 along with
the neutral keto-lactone 16, which has been reported earlier1
(Scheme 2).
Results and discussion
When the anhydride 1 was treated with primary amines
such as cyclohexylamine, benzylamine, p-toluidine, 2-
aminobenzonitrile, and 3-amino-5-methylpyrazole in refluxing
ethanol, ring-opening afforded the homophthalamic acid
derivatives 2a–e rather than the isomeric products 3 (Scheme 1)
This could be interpreted on the basis that interaction of
the primary amines with the isocoumarin derivative 1 takes
place on the benzoyl carbonyl function rather than cinnamoyl
carbonyl, firstly because the benzoyl carbonyl is sterically
more accessible, and secondly, that the electrophilicity of the
benzoyl carbonyl function is greater than that of the cinnamoyl
moiety.
Attempted cyclisation of the compounds 2a–c using freshly
distilled acetic anhydride afforded the isoquinoline derivatives
4a–c, while in the presence of a mixture of acetic anhydride and
perchloric acid at 0ºC under the conditions described by Boyd
et al.2-4 it yielded the homophthalisoimidium perchlorates 5a–
c. When the isoimidium salts 5a–c were allowed to react with
benzene or toluene in the presence of anhydrous aluminium
chloride under Friedel-Crafts reaction conditions, they yielded
the aromatic ketones 6a–c. Compound 5a upon treatment
Experimental
Equipment and settings were as reported in our earlier paper,1
where the synthesis of the anhydride 1 is also described.
Synthesis of 2-(2-carbamoylphenyl)cinnamic acids 2a–e. General
procedure
A mixture of compound 1 (1.12 g, 4 mmol) and cyclohexylamine,
benzylamine, p-toluidine or 3-amino-5-methylpyrazole (4 mmol)
in absolute ethanol (20 ml) was heated under reflux for 3 h (TLC).
Ar
H
Ar
Ar
H
H
Ar
H
O
O
b
CO H
2
a
CONHR
O
N
CONHR
R
CO H
2
O
H
O
3
2a-e
4a-c
1
c
Ar
O
Ar
H
H
Ar
O
Ar
H
Ar'
C(CN)
NHCH Ph
2
2
d
e
f
O
5a
O
N
CONHR
C H
6
CONHC H
6
11
11
HN
ClO
O
4
6: a, R = C H , Ar' = Ph
6
11
R
b, R = C H , Ar' = p-tolyl
6
11
8
5a-c
7
c, R = Ar' = p-tolyl
Ar = p-MeOC H throughout
6
4
CH
3
CH
d, R =
3
e, R =
2, 4, 5: a, R =
H C
2
c, R =
b, R =
NH
N
NC
Scheme 1 Reagents: a, RNH2/EtOH; b, Ac2O; c, Ac2O, HClO4, 0°C; d, Ar'H/AlCl3; e, PhCH2NH2/pyridine; f, CH2(CN)2
* Correspondent. E-mail: elshahawi31@yahoo.com
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JOURNAL OF CHEMICAL RESEARCH 2008 87
Ar
H
Ar
H
Ar
H
O
H
N
CO H
2
N
b
S
O
NH
c
O
N
NH
O
O
HN
NH
HN
NH
O
Ar
N
10
11
H
9
S
S
a
O
Ar
N
H
Ar
O
H
Ar
O
H
O
O
N
H N-N
2
N
NH
NH
d
e
N
NHCO Et
NH-NH
2
O
2
N
H
12
O
O
N-NH
2
1
13
14
O
MeO
O
f
HO
O
HO C
2
O
Ar = p-MeOC H throughout
16
6
4
15
Scheme 2 Reagents: a, 6-amino-2-thiouracil/py; b, Ac2O; c, N2H4.H2O; d, H2N.NHCO2Et; e, N2H4.H2O/py; f, AlCl3/C2H2Cl4
The solid deposited was in each case filtered off, dried and
recrystallised from the indicated solvent to give 2a–e. For the reaction
with 2-aminobenzonitrile (0.47 g, 4 mmol), heating was continued
for 6 h in n-butanol (20 ml), and the product was isolated at the end
of the reaction by extraction into ether.
N-Cyclohexyl amide 2a: Separated from the hot solvent as white
crystals (82%) (methanol), m.p. 235°C. IR: νmax 3412 (OH, NH),
1706, 1642 cm-1 (C=O). NMR (DMSO-d6): δH 12.7 (s, 1H, CO2H),
8.0 (d, 1H, NH), 7.9–6.7 (m, 9Harom., =CH), 3.68 (s, 3H, OMe),
1.7–1.08 (two m, 11H, C6H11). MS: m/z (%) 380 (M + 1, 13.9), 379
(M+, 8.9), 278 (36), 235 (21), 165 (19), 121 (100). Anal. Calcd. for
C23H25NO4 (379.46): C, 72.80; H, 6.64; N, 3.69. Found: C, 73.09; H,
6.53; N, 4.0%.
N-Benzyl amide 2b: Product separated after cooling and slow
evaporation; colourless crystals (76%) (benzene–ethanol), m.p. 150–
151°C. IR: νmax 3425br (OH, NH), 1690, 1656 cm-1 (C=O). NMR
(DMSO-d6): δH 12.5 (s, 1H, CO2H), 8.1 (s, 1H, NH), 8.3–6.7 (m,
14H, arom., =CH), 4.4 (t, 2H, CH2Ph), 3.85 (s, 3H, OMe). MS: m/z
(%) 387 (M+., 23.5), 280 (71.5), 235 (18.4), 165 (50),121 (45), 118
(20), 91 (100). Anal. Calcd. for C24H21NO4 (387.44): C, 74.40; H,
5.46; N, 3.62. Found: C, 74.57; H, 5.06; N, 3.33%.
washed several times with water, dried and recrystallised from the
indicated solvent to give 4a and 4c. In the case of 4b an oil separated
and was extracted (Et2O), dried, and purified by chromatography on
alumina, eluting with CH2Cl2.
2-Cyclohexyl compound 4a: Orange crystals (89%) (benzene),
m.p. 120–121°C. IR: νmax 1765, 1731 cm-1 (C=O). NMR (CDCl3):
δH 7.95–6.94 (m, 9Harom, =CH), 3.87 (s, 3H, OMe), 2.03–0.85
(m, 11H, C6H11). MS: m/z (%) 361 (M+, 27), 280 (100), 279 (24),
278 (31), 193 (30), 165 (88), 104 (16). Anal. Calcd. for C23H23NO3
(361.44): C, 76.43; H, 6.14; N, 3.88. Found: C, 76.64; H, 6.23;
N, 4.0%.
2-Benzyl compound 4b:Yellow oil (76%). IR: 1773, 1701 cm-1 (C=O).
MS: m/z (%) 369 (M+, 88), 368 (28), 324 (6.3), 165 (43), 91 (100).
2-p-Tolyl compound 4c: Yellow crystals (87%) (light petroleum
ether 60–80°C), m.p. 91–92°C. IR: νmax 1774, 1707 cm-1 (C=O).
NMR (CDCl3): δH 8.26–7.2 (m, 12Harom), 6.8 (s, 1H, =CH), 3.86
(s, 3H, OMe), 2.4 (s, 3H, CH3-Ar). MS: m/z (%) 369 (M+, 88), 368
(100), 324 (21), 165 (22), 91 (12.4). Anal. Calcd. for C24H19NO3
(369.42): C, 78.08; H, 5.18; N, 3.73. Found: C, 78.35; H, 5.44;
N, 4.0%.
N-(4-Methylphenyl) amide 2c: Separated after cooling and slow
evaporation as white crystals (81%) (methanol), m.p. 195–196°C.
IR: νmax 3402 (OH, NH), 1715, 1654 cm-1 (C=O). NMR (DMSO-d6):
δH 12.8 (br. s, 1H, CO2H), 9.6 (s, 1H, NH), 8.09–7.1 (m, 12H arom),
6.7 (s, 1H, =CH), 3.74 (s, 3H, OMe), 2.9 (s, 3H, Me-Ar). MS:
m/z (%) 387 (M+, 7.3), 280 (20), 235 (27), 165 (32), 107 (100). Anal.
Calcd. for C24H21NO4 (387.44): C, 74.40; H, 5.46; N, 3.62. Found: C,
74.28; H, 5.26; N, 3.76%.
N-(2-Cyanophenyl) amide 2d: Separated after cooling and slow
evaporation as a brown oil (72%). IR: νmax 3469, 3371, 3230 (OH, NH),
2215 (C≡N), 1702, 1668 cm-1 (C=O). MS: m/z (%) 354 (M+-CO2),
298 (23), 253 (40), 235 (48), 165 (48), 121 (100).
N-(5-Methylpyrazol-3-yl) amide 2e: Separated after cooling and
slow evaporation as pale pink crystals (64%) (benzene–ethanol), m.p.
200–201°C. IR: νmax 3279 (OH, NH), 1704, 1679 cm-1 (C=O). NMR
(DMSO-d6): δH 12.3 (br s, 1H, CO2H), 10.3 (s, 1H, NH), 7.9 (s, 1H,
NH), 7.5-7.3 (m, 9Harom, =CH), 6.2 (s, 1H, C4-H pyrazole), 4.07 (s,
3H, OMe), 2.2 (s, 3H, Me). MS: m/z (%) 377 (M+., 18), 333 (44), 256
(100), 165 (21), 121 (49). Anal. Calcd. for C21H19N3O4 (377.40): C,
66.83; H, 5.07; N, 11.13. Found: C, 66.51; H, 4.83; N, 10.88%.
N-Aryl(alkyl)-4-methoxybenzylidenehomophthalisoimidium perchlorates
5a–c. General procedure
Compounds 2a–c (3 mmol) were suspended in freshly distilled acetic
anhydride (5 ml) containing 3–4 drops of perchloric acid (70%)
and the mixture was stirred at room temperature for a few minutes
until the suspension cleared and orange crystals began to be formed.
Stirring was continued while cooling the solution in an ice bath.
The deposited crystals were filtered off and washed with dry ether to
give 5a–c.
N-Cyclohexyliminium salt 5a: M.p. 111–112°C (yield 95%). IR:
νmax 3412br (N+H), 1792 (C=O), 1646 cm-1 (C=N). MS: m/z (%) 361
(M+-HClO4, 26.3), 360 (37.4), 277 (87), 235 (23), 234 (33.5), 164
(73), 165 (46), 121 (100), 120 (39).
N-Benzyliminium salt 5b: M.p. 174–175°C (yield 98%). IR: νmax
3421br (N+H), 1791 (C=O), 1659 cm-1 (C=N). MS: m/z (%) 369
(M+-HClO4, 100), 324 (9.5), 265 (10.4), 209 (8.5), 165 (29.1), 106
(7.5), 91 (48.7), 77 (18.3).
N-(4-Methylphenyl)iminium salt 5c: M.p. 249–250°C (yield 97%).
IR: νmax 3446br (N+H), 1791 (C=O), 1639 cm-1 (C=N). MS: m/z (%)
367 (M+-HClO4-2, 100), 24 (26), 268 (14), 133 (11).
4-Methoxybenzylideneisoquinoline-1,3(4H)-diones 4a–c.
General procedure
The amides 2a–c (3 mmole) was heated under reflux for two hours in
freshly distilled acetic anhydride (5 ml), monitoring the progress by
TLC. The reaction mixture was allowed to cool, then poured into ice-
cold water and stirred for 30 min.. The solid obtained was filtered off,
2-[1'-Aryl-3'-(4-methoxyphenyl)-1'-oxoprop-2'-enyl]benzamides 6a-c.
General procedure
A mixture of the isoimidium perchlorate 5a or 5c (2 mmol) and
anhydrous aluminium chloride (2 g, 0.015 mol) was stirred at room
temperature for 5 h (TLC) in dry aromatic hydrocarbon (benzene
or toluene) (20 ml). The reaction mixture was treated with iced
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88 JOURNAL OF CHEMICAL RESEARCH 2008
hydrochloric acid and the excess of solvent was removed by steam
distillation. The solid obtained in each case was filtered off, dried and
recrystallised from a suitable solvent to give 6a–c.
which was collected by filtration, dried and recrystallised to give 11
as light brown crystals (85%) (dioxan), m.p. 255–256°C. IR: νmax
3391, 3159 (NH), 1743, 1717 cm-1 (C=O). NMR (DMSO-d6): δH
12.03 (s, 1H, NH), 11.1 (s, 1H, NH), 8.4-6.9 (m, 9Harom + =CH), 5.9
(s, 1H, pyrimidine C5-H), 3.9 (s, 3H, OMe). MS: m/z (%) 405 (M+,
7.8), 404 (14), 143 (100). Anal. Calcd. for C21H15N3O4S (405.44): C,
62.21; H, 3.73; N, 10.36; S, 7.91. Found: C, 62.52; H, 3.95; N, 10.08;
S, 7.76%
N-Cyclohexyl-1'-phenyl amide 6a: Brown crystals (61%), from
light petroleum ether (80–100°C), m.p. 120–121°C. IR: νmax 3422–
3145w (NH), 1711, 1700 cm-1 (C=O). NMR (CDCl3): δH 8.3 (s,
1H, NH), 8–7.2 (m, 13Harom), 6.6 (s, 1H, =CH), 3.8(s, 3H, OMe),
1.8–0.9 (m, 11H, C6H11). MS: m/z (%) 313 [M+–R-NHCO] (4.9),
197 (5.7), 165 (7.6), 121 (100), 107 (23), 77 (16). Anal. Calcd. for
C29H29NO3 (439.56): C, 79.24; H, 6.65; N, 3.19. Found: C, 78.95;
H, 6.38; N, 3.10%.
2-(2-Hydrazino-6-oxo-1,6-dihydropyrimidin-4-yl)-1-hydrazono-4-
(p-methoxybenzylidene)isoquinolin-3(2H)-one (12)
N-Cyclohexyl-1'-p-tolyl amide 6b: Yellow crystals (65%) from
benzene, m.p. 70–72°C. IR: νmax 3166br (NH), 1716, 1698 cm-1
(C=O). MS: m/z (%) 327 (M+-RNHCO, 100), 211 (82), 196 (18),
165 (32), 121 (86), 107 (69). Anal. Calcd for C30H31NO3 (453.58): C,
79.44; H, 6.87; N, 3.09. Found: C, 79.13; H, 6.61; N, 2.99%.
N,1'-di-p-tolyl amide 6c: Yellow crystals (57%) from benzene,
m.p. 150–151°C. IR: νmax 3420 (NH), 1742, 1674 cm-1 (C=O). NMR
(CDCl3): δH 8.6 (s, 1H, NH), 8–7.2 (m, 16Harom), 6.7 (s, 1H, =CH),
3.83 (s, 3H, OMe), 2.1 (s, 6H, 2CH3-Ar). MS: m/z (%) 461 (M+, 13),
429 (48), 337 (100), 260 (55), 251 (14), 164 (38.5), 118 (52.5). Anal.
Calcd. for C31H27NO3 (461.56): C, 80.67; H, 5.90; N, 3.03. Found: C,
80.44; H, 6.67; N, 3.11%.
Compound 11 (1 g, 2.5 mmol) and hydrazine hydrate (0.12 ml,
2.5 mmol) were refluxed for 3 h in pyridine (15 ml) (TLC). After
cooling the reaction mixture was acidified with ice-cold hydrochloric
acid, and the brown solid deposited was filtered off and recrystallised
to give 12 as light brown crystals (89%) (methanol), m.p. 255–257°C.
IR: νmax 3185, 3065, 2927 (NH), 1700, 1650 cm-1 (C=O). MS: m/z
(%) 417 (M+, 44), 402 (86), 401 (57), 143 (100). Anal. Calcd. for
C21H19N7O3 (417.43): C, 60.43; H, 4.59; N, 23.49. Found: C, 60.67;
H, 4.40; N, 23.10%.
2-Ethoxycarbonylamino-4-(4-methoxybenzylidene)isoquinoline-
1,3(4H)-dione (13)
The anhydride 1 (1 g, 4 mmol) and ethyl carbazate (0.37 g, 4 mmol)
were refluxed in ethanol (20 ml) for two hours (TLC). The solution
was then allowed to evaporate slowly. A white solid obtained was
filtered off, dried and recrystallised to give 13 as colourless crystals
(70%) (ethanol/benzene), m.p. 170–171°C. IR: νmax 3395, 3306
(NH), 1745, 1695 cm-1 (C=O). NMR (DMSO-d6): δH 9.2 (s, 1H,
NH), 8.0–6.7 (m, 9H, arom., =CH), 4.05 (q, 2H, OCH2CH3), 3.98
(s, 3H, Ar-OMe) and 1.18 (t, 3H, OCH2CH3). MS: m/z (%) 366 (M+,
54), 365 [(M-1)+, 60], 294 (64), 279 (57), 236 (32), 165 (75). Anal.
Calcd. for C20H18N2O5 (366.38): C, 65.57; H, 4.95; N, 7.65. Found:
C, 65.71; H, 5.05; N, 7.34%.
2-[2-(N'-cyclohexylaminocarbonyl)phenyl)]-N-benzyl-4-methoxy-
cinnamide (7)
Compound 5a (1 g, 2 mmol) and benzylamine (0.2 g, 2 mmol) in
pyridine (15 ml) were stirred at room temperature for 3 h (TLC), and
then left to stand overnight. The reaction mixture was poured onto
ice-cold hydrochloric acid, the yellow solid deposited was filtered
off, dried and recrystallised (light petroleum ether 60–80°C) to give
7 as yellow crystals (76%), m.p. 70–72°C. IR: νmax 3266, 3417 (NH),
1687, 1648 cm-1 (C=O). NMR (CDCl3): δH 8.4 (br s, 2H), 7.9–7 (m,
13Harom), 6.7 (s, 1H, =CH), 5.5 (d, 2H, CH2Ph), 3.86 (s, 3H, OMe),
1.9–1.1 (m, 11H, C6H11). MS: m/z (%) 469 (M + 1, 11), 342 (80.5),
234 (4), 91 (100). Anal. Calcd. for C30H32N2O3 (468.60): C, 76.90; H,
6.88; N, 5.98. Found: C, 77.12; H, 6.56; N, 6.18%.
6-Hydrazono-11-(4-methoxybenzylidene)-6,11-dihydro-2H-[1,2,4,5]
tetrazino[2,3-b]isoquinolin-3(4H)-one (14)
The isoquinolinedione 13 (1 g, 3 mmol) in pyridine (15 ml) was
heated under reflux with hydrazine hydrate (0.14 ml, 3 mmol) for 2 h
(TLC). The cooled mixture was triturated with ice-cold hydrochloric
acid to give a deep brown solid, which was filtered off, dried and
recrystallised (benzene) to give the fused tetrazine 14 as brown
crystals (54%), m.p. 78–80°C. IR: νmax 3419, 3395 (NH), 1701 cm-1
(C=O). MS: m/z (%) 348 (M+, 7.7), 347 (26), 91 (100). Anal. Calcd.
for C18H16N6O2 (348.37): C, 62.06; H, 4.63; N, 24.12, Found: C,
61.84; H, 4.32; N, 23.87%.
2-Cyclohexyl-3-dicyanomethylene-3,4-dihydro-4-(4-methoxybenzylidene)
isoquinolin-2(1H)-one (8)
Compound 5a (1 g, 2 mmol) and malononitrile (0.14 ml, 2 mmol) in
pyridine (15 ml) were stirred at room temperature for 3 h (TLC), and
then left overnight. The reaction mixture was poured into ice-cold
hydrochloric acid, and the pink solid obtained was filtered off, dried
and recrystallised (benzene) to give 8 as pink crystals 50%), m.p.
80–81°C. IR: νmax 2219 (C≡N), 1704 cm-1 (C=O). NMR (CDCl3):
δH7.8–7 (m, 9Harom + =CH), 3.8 (s, 3H, OMe), 1.87–1.1 (m, 11H,
C6H11). MS: m/z (%) 302 (9), 261 (42), 238 (11.5). Anal. Calcd. for
C26H23N3O2 (409.49): C, 76.26; H, 5.66; N, 10.26. Found: C, 76.45;
H, 5.36; N, 9.96%.
6-Hydroxy-1-oxo-1H-inden-2-yl)benzoic acid (15) and 4b,10b-dihydro-
2-methoxyindeno[1,2-c][2]benzopyran-6,11-dione (16) by internal
Friedel–Crafts reaction
The anhydride 1 (1 g, 4 mmol) and anhydrous aluminium chloride
(1.5 g, 0.01 mole) in acetylene tetrachloride (20 ml) were stirred for
6 h. at room temperature, and then the mixture was heated on a water
bath for another two hours (TLC). The reaction mixture was cooled
and treated with cold dilute hydrochloric acid to give two products.
The product soluble in acetylene tetrachloride was separated by
steam distillation, recrystallised to give the keto-lactone1 16 (14%).
The fraction which was precipitated and insoluble in acetylene
tetrachloride was collected by filtration, dried and recrystallised from
ethanol to give the acid 15 as grey crystals (57%), m.p. 291–292°C.
IR: νmax 3394 (OH), 1715 (C=O acid), 1681 cm-1 (C=O ketone).
NMR (DMSO-d6): δH 11.4 (s, 1H, COOH), 8.7–8 (m, 7H arom), 5.9
(s, 1H), 4.1 (br s, 1H, OH). MS: m/z (%) 266 (M+, 91), 238 (100), 165
(73). Anal. Calcd. for C16H10O4 (266.26): C, 72.18; H, 3.79. Found:
C, 71.86; H, 3.66%.
Reaction of anhydride 1 with 6-amino-2-thiouracil
Compound 1 (1 g, 4 mmol) and 6-aminothiouracil (0.5 g, 4 mmol)
were heated under reflux in pyridine (15 ml) for 6 h (TLC). The
white solid (9) which separated while hot was separated by filtration.
The rest of the reaction mixture in pyridine was acidified with cold
dilute hydrochloric acid to precipitate 10 as a buff solid.
6-(4-Methoxybenzylideneamino)-2-thiouracil (9): Colourless
crystals (20%) from dioxan, m.p. 261°C. IR: νmax 3392, 3282, 3154
(NH), 1652 cm-1 (C=O). NMR (DMSO-d6): δH 12.4 (s, 1H, NH),
11.2 (s, 1H, NH), 9.1 (s, 1H, N=CH), 8.1–7 (m, 4Harom), 6.1 (s, 1H,
C5-H), 3.9 (s, 3H, OMe). MS: m/z (%) 261 (M+, 12), 260 [(M-1)+,
23], 143 (96). Anal. Calcd. for C12H11N3O2S (261.30): C, 55.16;
H, 4.24; N, 16.08; S,12.27. Found: C, 55.41; H, 4.08; N, 15.83; S,
11.93%.
Acid amide 10: Buff crystals (55%) (ethanol), m.p. 245–246°C.
IR: νmax 3400, 3181 (NH), 1705, 1689 cm-1 (C=O). MS: m/z (%)
421 [(M-2)+, 9], 403 (100), 248 (6.6). Anal. Calcd. for C21H17N3O5S
(423.45): C, 59.57; H, 4.05; N, 9.92; S, 7.57. Found: C, 59.28; H,
3.92; N, 10.16; S, 7.71%.
Received 17 July 2007; accepted 22 February 2008
Paper 06/4750A doi: 10.3184/030823408X296212
References
4-(4-Methoxybenzylidene)-2-(4-oxo-2-thioxo-1,2,3,6-tetrahydro-
pyrimidin-4-yl)-isoquinoline-1,3(4H)-dione (11)
Compound 10 (1 g, 2 mmol) was heated under reflux for 2 h in
freshly distilled acetic anhydride (1 ml). The reaction mixture was
allowed to cool and poured into ice-cold water to give a brown solid,
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PAPER: 07/4750