Synthesis of a novel series of pyrimido- and triazino[4,5-b] quinolines

Article abstract of DOI:10.3184/030823410X12852490447544

New tetrahydropyrimido[4,5-,b]quinolines, hexahydropyrimido[4,5-,b] quinolines, a thioxohexahydropyrimido[4,5-,b] quinoline, an octahydropyrimido[4, 5-,b]quinoline and a tetrahydro[1,2,3]triazino[4,5-,b]quinoline have been synthe- sised. A series of S-alkyltetrahydroprimido[4,5-,b]quinolines was obtained by the reaction of the thioxohexahydropy- rimido[4,5-b]quinoline with allyl bromide, propargyl bromide or with epichlorohydrin. All newly synthesised compounds were characterised by IR, 1H, 13C NMR and elemental analysis.

Full text of DOI:10.3184/030823410X12852490447544

528 RESEARCH PAPER
SEPTEMBER, 528–532
JOURNAL OF CHEMICAL RESEARCH 2010
Synthesis of a novel series of pyrimido- and triazino[4,5-b] quinolines
Said A. Said and Ahmed H. Moustafa*
Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt
New tetrahydropyrimido[4,5-b]quinolines, hexahydropyrimido[4,5-b]quinolines, a thioxohexahydropyrimido[4,5-b]
quinoline, an octahydropyrimido[4,5-b]quinoline and a tetrahydro[1,2,3]triazino[4,5-b]quinoline have been synthe-
sised. A series of S-alkyltetrahydroprimido[4,5-b]quinolines was obtained by the reaction of the thioxohexahydropy-
rimido[4,5-b]quinoline with allyl bromide, propargyl bromide or with epichlorohydrin. All newly synthesised
compounds were characterised by IR, 1H, 13C NMR and elemental analysis.
Keywords: pyrimido[4,5-b]quinolines, thioxopyrimido[4,5-b]quinoline, triazino[4,5-b] quinoline and S-alkylprimido[4,5-b]
quinolines
Quinolines and symmetrical heterocycles bearing pyrimido or
triazinoquinoline moieties have been found to possess a broad
spectrum of pharmacological and medicinal1,2 properties,
including antimicrobial,3–9 antihypertensive,10 CNS depres-
sant,11 anti-HIV infective,12 antimalarial,13 antihistaminic,14
antitumour15 activities and more recently for the treatment
of pain,16 antithrombotic activity17 and as new inhibitions of
bacterial DNA gyrase B.18 In addition, quinolines were reported
to exert antifungal,19 anticancer,20 antiviral,21 analgesic22 and
antiinflammatory activities.23 Also, several reduced quinoline
derivatives have shown significant anticancer activity.24
The reaction of compound 1 with carbon disulfide provided
4 whilst acylation with acetic anhydride in pyridine generated
the pyrimido[4,5-b]quinolinedione 5 as shown in Scheme 1.
The IR spectrum of compound 4 gave absorption bands at
3430 (NH) and at 1690 and 1666 cm−1 for two C=O groups.
1
The H and 13C NMR spectra and elemental analysis of com-
pound 4 are collated in the experimental section. Characteris-
1
tic H NMR signals for compound 5 appeared at δ 2.38 and
4.89 for the CH3 group at C-2 and the H-5 proton respectively,
the 13C NMR spectrum was also fully consistent with the con-
stitution of this compound. The pyrimidine ester 6 was obtained
by condensation of 1 with diethyl oxalate in presence of
sodium ethoxide in absolute ethanol (Scheme 1). The spectral
Recently, several pyrimidine derivatives were reported to
26
have antimicrobial,25,
antiinflammatory9 and antioxidant22
1
activities. In the light of these facts, we now report the synthe-
sis of series of reduced quinoline, pyrimidoquinoline, and
triazinoqunoline derivatives.
data (IR, H, 13C NMR) and elemental analysis of 6 were
in agreement with the assigned structure (see experimental
section).
Cyclocondensation of 1 with carbonyl compounds gave
the pyridopyrimidine derivatives 7–9. Treatment of 1 with an
equimolar amount of benzaldehyde provided 7 (60%) whilst
condensation with cyclohexanone afforded the spirocycle 8
(70%). Acylation of 1 with, 4-nitrobenzoyl chloride in pyridine
provided the pyrimidinedione 9 in 70% yield (Scheme 2).
Structures of these compounds were fully supported by their
spectral data i.e IR, 1H, 13C NMR as well as elemental analysis.
Compound 7 was isolated by crystallisation as a single isomer,
Results and discussion
In this investigation, a series of new pyrimido[4,5-b]quinolines
2–9, triazino[4,5-b]quinoline 10, and S-alkylpyrimido[4,5-b]
quinolines 11–13 were designed and synthesised. 2-Amino-
7,7-dimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroquinoline-
3-carboxamide 1 was prepared according to the literature
procedure.27–29 Reaction of the carboxamide 1 with formic
acid, or triethyl orthoformate or formamide afforded the
pyrimido[4,5-b]quinoline derivative 2 as shown in Scheme 1.
The IR spectrum of compound 2 displayed adsorption bands at
3470 (NH) and at 1692 and 1672 cm−1 for two amide C=O
groups. The 1H NMR spectrum of 2 showed signals at δ 0.97,
1.04, 1.96, 2.29, and 4.82 ppm for two CH3 groups, two CH2
groups and the CH-Ph proton, in addition to signals at δ 9.28
and 10.1 ppm for two NH groups. The 13C NMR spectrum
showed signals at δ 26.9, 27.7 (2 × CH3), 32.7 C(CH3)2, 39.9
C-5 (CH-Ph), 40.1 (C-9) and 50.72 (C-7). Treatment of com-
pound 1 with phenyl and methyl isothiocyanate in the presence
of acetic acid led, remarkably, to the formation of the thioxo-
2,3,7,8,9,10-hexahydropyrimido[4,5-b]quinoline-4,6(1H,5H)-
diones 3a, b (Scheme 1). Nucleophilic attack of the C-2 amino
group of compound 1 on the isothiocyanate produces the
corresponding thiourea derivative, which in turn cyclizes onto
the amide group to give 3a, b. A similar pathway resulting in
the formation of fused pyrimidinediones has been noted pre-
1
which was confirmed by the H and 13C NMR spectra. The
1H NMR spectrum of 7 indicated the presence of signals at
δ 4.88 and 5.98 which correlated to the CH-Ph (H-5) and
the NCHPhN (H-2) protons respectively, whilst the 13C NMR
spectrum showed signals at δ 51.8 and 62.1 characteristic for
C-7 and C-2 respectively. The IR spectrum of compound 8
exhibited bands for an NH, two amide C=O groups and an α,β-
unsaturated ketone at 3408, 1695 and 1668 cm−1, respectively.
1
In the H NMR spectrum of 8 multiplet signals in the range
δ 1.43–1.53 correspond to three CH2 units of the cyclohexane
ring whilst a further two methylene groups resonated as a
broad triplet centred at 1.73 ppm. The C-5 methine proton
absorbed at 4.82 ppm in addition to an NH signal correspond-
ing to three protons at δ 10.01. The 13C NMR spectrum of 8
showed signals at 23.5, 25.8 and 35.9 ppm characteristic of
five cyclohexane-ring carbons, in addition to a signal at
1
50.8 ppm for the quaternary C-2 carbon. The H NMR spec-
trum of compound 9 revealed the presence of a signal at δ 4.89
ppm for the C-5 methine proton, in addition to signals charac-
teristic of the p-nitrophenyl protons at δ 8.18 and 8.31 ppm
(d, J = 8.80 Hz).
1
viously.30 The H NMR spectrum of compound 3a showed a
signal at δ 4.82 ppm characteristic of the (H-5) CH-Ph proton.
In the 13C NMR spectrum, signals for the C=S and two C=O
groups appeared at 162.2, 170.7 and 194.8 ppm, respectively.
The 13C NMR spectrum of 9 exhibited a signal at δ 39.9 ppm
for C-5, in addition to 15 signals for the sp2 and aromatic
carbon atoms, C=N unit and two C=O groups.
1
Whilst, the H NMR spectrum for compound 3b showed
signals at δ 3.39 and 4.78 ppm for the NCH3 and (H-5) CH-Ph
protons respectively, in addition to multiplet aromatic signals
at δ 7.12–7.33 ppm for the phenyl group.
Diazotisation of 1 by treatment with sodium nitrite in HCl–
AcOH gave the triazino[4,6-b]quinolinedione 10 in 60% yield
1
(Scheme 2). The H NMR spectrum of the latter showed
* Correspondent. E-mail:ah_hu_mostafa@yahoo.com
signals at δ 4.78 and 10.01 ppm for the C-5 and NH protons

JOURNAL OF CHEMICAL RESEARCH 2010 529
Scheme 1
respectively, whilst the 13C spectrum gave signals at δ 50.5,
170.7 and 194.9 ppm characteristic for C-5, and two C=O
groups.
and CH2S units of the 2,3-epoxypropyl group, in addition to,
signal at 4.78 ppm for H-5.
Alkylation of 3a with allyl bromide, propargyl bromide or
with epichlorohydrin in presence of potasium carbonate in dry
acetone afforded the corresponding S-alkylated derivatives
11–13 (Scheme 3). The IR spectra of these compounds revealed
the absence of bands at 1230 cm−1 characteristic for C=S
groups, in addition to the presence of bands for the two C=O
groups.
Experimental
All melting points were taken on an Electrothermal IA 9100 series
digital melting point apparatus. The IR spectra (KBr) discs were
recorded on a Perkin-Elmer 1650 spectrometer (USA). 1H, 13C NMR
spectra were determined on Bruker AC-300 MHz instrument. Chemi-
cal shifts are expressed as δ (ppm) relative to TMS as internal standard
and DMSO-d6 as solvent. The elemental analysis was carried by the
Micro-analytical Centre, Cairo University.
1
The H NMR spectrum of compound 11 showed signals at
2-Amino-7,7-dimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroquinoline-
3-carboxamide (1): A mixture of dimedone (5,5-dimethyl-1,3-cyclo-
hexane dione) (1.40 g, 10 mmol), benzylidenecyanoacetamide28,29
(1.70 g, 10 mmol) and ammonium acetate (1.15 g, 15 mmol) was
heated under reflux for 5 h then poured into ice-water. The solid
product was filtered off, dried and recrystallised from ethanol to give
1 as yellowish white solid. Yield 70%; m.p. 229–230 °C. IR (KBr):
δ 3.48 and 4.80 for CH2S and H-5 protons respectively, in
addition to signals at δ 5.08, 5.18 and 6.03 characteristic for
the alkenic protons of the allyl group. Its 13C NMR spectrum
exhibited signals at δ 40.8 and 51.5 for CH2S and C-5 carbons,
in addition to the aromatics and other sp2 signals (experimental
section). The IR, 1H, 13C NMR and elemental analysis data of
compound 12 were in agreement with the assigned structure.
3510–3420 (NH), 1665 (C=O, amide), 1698 cm−1 (C=O). H NMR
(DMSO-d6): δ = 0.95 (s, 3H, CH3), 1.06 (s, 3H, CH3), 2.07 (s, 2H,
CH2), 2.34 (s, 2H, CH2), 5.10 (s, 1H, CH-Ph), 7.06–7.35 (m, 5H,
1
1
The H NMR spectrum of 13 indicated the presence of
signals in the range δ 2.38–3.12 as multiplets for CH2O, CHO

530 JOURNAL OF CHEMICAL RESEARCH 2010
Scheme 2
Scheme 3

JOURNAL OF CHEMICAL RESEARCH 2010 531
ArH), 8.08 (br, 2H, NH2), 8.51 (s, 2H, CONH2). Anal. Calcd for
C18H21N3O2 (311.38): C, 69.43; H, 6.80; N, 13.49. Found: C, 69.28; H,
6.82; N, 13.48%.
8,8-Dimethyl-5-phenyl-7,8,9,10-tetrahydropyrimido[4,5-b]quinoline-
4,6(3H,5H)-dione (2): Method (A): A mixture of 1 (3.11 g, 10 mmol)
and formic acid (20 mL) was refluxed for 6 h. After cooling, the solid
product was filtered off, dried and recrystallised from methanol to
give 2 as yellow solid. Yield 60%. m.p. 262–264 °C.
Method (B): A mixture of 1 (3.11 g, 10 mmol) and triethyl ortho-
formate (15 mL) was refluxed for 3 h. After cooling, the reaction
mixture was poured into cold water the solid product was filtered off,
washed with water, dried and recrystallised from methanol to give 2.
Yield 62%. m.p. 262–264 °C
(s, 3H, CH3), 1.03 (s, 3H, CH3), 1.88 (s, 2H, CH2), 2.34 (s, 2H, CH2),
2.38 (s, 3H, CH3), 4.89 (s, 1H, CH-Ph), 7.22–7.38 (m, 5H, ArH), 9.20
(s, 1H, NH), 10.20 (s, 1H, NH). 13C NMR (DMSO-d6): δ = 25.9, 27.3,
27.8 (3 × CH3), 32.8 (C-8), 39.8 (C-5), 40.21 (C-9), 51.2 (C-7), 101.1,
111.8, 125.6, 126.9, 128.4, 128.9, 143.4, 149.7, 153.2, 170.2 and
195.2 (ArC, C=N and 2 × C=O). Anal. Calcd for C20H21N3O2 (335.40):
C, 71.62; H, 6.31; N, 12.53. Found: C, 71.70; H, 6.36; N, 12.52%.
Ethyl 8,8-dimethyl-4,6-dioxo-5-phenyl-3,4,5,6,7,8,9,10-octahydropy-
rimido[4,5-b]quinoline-2-carboxylate (6): A mixture of 1 (3.11 g,
10 mmol), diethyl oxalate (1.46 g, 10 mmol) and sodium ethoxide
(15 mmol) in absolute ethanol (20 mL) was heated under reflux for
6 h. After cooling the reaction mixture was poured into ice-cold dil.
HCl, the solid product was filtered off, dried and recrystallised from
ethanol to give 6 as white crystals. Yield 65%. m.p. 218–219 °C.
IR (KBr): 3438 (NH), 1725 (C=O, ester), 1695 (C=O) and 1670 cm−1
Method (C): A mixture of 1 (3.11 g, 10 mmol) and formamide
(20 mL) was boiled under reflux for 2 h. After cooling the reaction
mixture was poured into cold water, the product was filtered off,
washed with water, dried and recrystallised from methanol to give 2.
Yield 50%. m.p. 262– 264 °C. IR (KBr): 3470 (NH), 1692 and
1
(C=O, amide). H NMR (DMSO-d6): δ = 0.85 (s, 3H, CH3), 1.04 (s,
3H, CH3), 1.29 (t, 3H, J = 7.0 Hz, CH3CH2), 1.88 (s, 2H, CH2), 2.35
(s, 2H, CH2), 4.13 (q, 2H, J = 7.0 Hz CH2CH3), 4.82 (s, 1H, CH-Ph),
7.02–7.29 (m, 5H, ArH), 9.28 (s, 1H, NH), 10.19 (s, 1H, NH). 13C
NMR (DMSO-d6): δ = 13.9, 27.1, 27.6 (3 × CH3), 32.7 (C-8), 39.8
(C-5), 40.1 (C-9), 51.0 (C-7), 59.8 (OCH2), 100.8, 112.8, 125.9, 126.9,
128.0, 128.9, 143.4, 147.6, 149.7, 153.1, 170.7 and 194.9 (ArC, C=N
and 3 × C=O). Anal. Calcd for C22H23N3O4 (393.44): C, 67.16; H,
5.89; N, 10.68. Found: C, 66.98; H, 5.88; N, 10.69%.
1
1672 cm−1 for (2C=O). H NMR (DMSO-d6): δ = 0.97 (s, 3H, CH3),
1.04 (s, 3H, CH3), 1.96 (s, 2H, CH2), 2.29 (s, 2H, CH2), 4.82 (s, 1H,
CH-Ph), 7.02–7.50 (m, 6H, ArH), 9.28 (s, 1H, NH), 10.1 (s, 1H, NH).
13C NMR (DMSO-d6): δ = 26.9, 27.7 (2 × CH3), 32.7 (C-8), 39.9
(C-5), 40.1 (C-9), 50.72 (C-7), 101.2, 111.9, 125.7, 126.9, 128.9,
143.4, 147.6, 149.7, 153.1, 170.7 and 194.8 (ArC, C=N and 2 × C=O).
Anal. Calcd for C19H19N3O2 (321.37): C, 71.01; H, 5.96; N, 13.08.
Found: C, 71.20; H, 5.98; N, 13.12%.
8,8-Dimethyl-3,5-diphenyl-2-thioxo-2,3,7,8,9,10-hexahydropyrimido
[4,5-b]quinoline-4,6(1H,5H)-dione (3a): A mixture of 1 (3.11 g,
10 mmol) and phenyl isothiocynate (1.35 g, 10 mmol) in acetic acid
(20 mL) was refluxed for 4 h. After cooling the solid product was
filtered off, dried and recrystallised from ethanol to give 3a as red
crystals. Yield 75%. m.p. 214–215 °C. IR (KBr): 3480 (NH), 1698
(C=O), 1668 (C=O, amide), 1230 cm−1 (C=S). 1H NMR (DMSO-d6):
δ = 0.98 (s, 3H, CH3), 1.03 (s, 3H, CH3), 1.89 (s, 2H, CH2), 2.28 (s,
2H, CH2), 4.82 (s, 1H, CH-Ph), 6.25–7.33 (m, 10H, ArH), 9.28 (s, 1H,
NH), 10.2 (s, 1H, NH). 13C NMR (DMSO-d6): δ = 26.9, 27.8 (2 ×
CH3), 32.8 (C-8), 39.8 (C-5), 40.0 (C-9), 50.6 (C-7), 80.2 (C-4a),
111.9, 125.9, 126.9, 128.0, 128.3, 128.9, 143.4, 144.4, 147.6, 149.7,
153.1, 162.2, 170.7 and 194.8 (ArC, 2 C=O and C=S). Anal. Calcd for
C25H23N3O2S (429.53): C, 69.91; H, 5.40; N, 9.78. Found: C, 69.94; H,
5.41; N, 9.80%.
8,8-Dimethyl-2,5-diphenyl-2,3,7,8,9,10-hexahydropyrimido[4,5-b]
quinoline-4,6(1H,5H)-dione (7): To a solution of 1 (3.11 g, 10 mmol)
in acetic acid (20 mL), benzaldehyde (1.06 g, 10 mmol) was added,
then the reaction mixture was heated under reflux for 6 h. The solid
product was filtered off, dried and recrystallised from chloroform
1
to give 7 as yellow crystals. Yield 60%. m.p. 240–242 °C. H NMR
(DMSO- d6): δ = 0.89 (s, 3H, CH3), 1.24 (s, 3H, CH3), 1.88 (s, 2H,
CH2), 2.30 (s, 2H, CH2), 4.88 (s, 1H, CH-Ph), 5.98 (s, 1H, NCHPhN),
7.10–7.51 (m, 10H, ArH), 8.94 (s, 1H, NH), 10.23 (s, 2H, 2NH). 13
C
NMR (DMSO-d6): δ = 27.2, 27.8 (2 × CH3), 32.8 (C-8), 39.8 (C-5),
40.1 (C-9), 51.8 (C-7), 62.1 (C-2), 108.9, 112.8, 126.9, 127.2, 127.4,
128.9, 129.0, 129.6, 143.4, 143.8, 153.1, 168.9, 170.7 and 194.9 (ArC
and 2 × C=O). Anal. Calcd for C25H25N3O2 (399.48): C, 75.16; H,
6.31; N, 10.52. Found: C, 75.28; H, 6.50; N, 10.53%.
8p,8p-Dimethyl-5p-phenyl-7p,8p,9p,10p-tetrahydro-1pH-spiro[cyclohexane-
1p,2p-pyrimido[4,5-b]quinoline]-4p,6p(3pH,5pH)-dione (8): A mixture
of 1 (3.11 g, 10 mmol), cyclohexanone (0.98 g, 10 mmol) and sodium
acetate (2.00 g) in acetic acid (20 mL) was refluxed for 5 h. The prod-
uct was filtered off, dried and recrystallised from methanol to give 8
as white crystals. Yield 70%. m.p. 223–224 °C. IR (KBr): 3408 (NH),
1695 (C=O), 1668 cm−1 (C=O, amide). 1H NMR (DMSO-d6): δ = 0.97
(s, 3H, CH3), 1.04 (s, 3H, CH3), 1.43 (m, 2H, CH2, cyclohexane), 1.47
(m, 2H, CH2, cyclohexane), 1.53 (m, 2H, CH2, cyclohexane), 1.73
(br.t, 4H, 2 × CH2, cyclohexane), 1.89 (s, 2H, CH2), 2.31(s, 2H, CH2),
3,8,8-Trimethyl-5-phenyl-2-thioxo-2,3,7,8,9,10-hexahydropyrimido
[4,5-b]quinoline-4,6(1H,5H)-dione (3b): A mixture of 1 (3.11 g,
10 mmol) and methyl isothiocyanate (0.73 g, 10 mmol) in acetic acid
(20 mL) was refluxed for 4 h. After cooling the solid product was
filtered off, dried and recrystallised from ethanol to give 3a. Yield
72%. m.p. 208–210 °C.
1H NMR (DMSO-d6): δ = 0.97 (s, 3H, CH3), 1.04 (s, 3H, CH3), 1.88
(s, 2H, CH2), 2.27 (s, 2H, CH2), 3.39 (s, 3H, NCH3), 4.78 (s, 1H, CH-
Ph), 7.12–7.33 (m, 5H, ArH), 9.10 (s, 1H, NH), 10.01 (s, 1H, NH).
Anal. Calcd for C20H21N3O2S (367.46): C, 65.37; H, 5.76; N, 11.44.
Found: C, 63.35; H, 5.81; N, 11.64%.
4.82 (s, 1H, CH-Ph), 7.02–7.42 (m, 5H, ArH), 10.01 (s, 3H, 3NH). 13
C
NMR (DMSO-d6): δ = 23.5, 25.8, 35.9 (cyclohexane-CH2), 27.2, 27.5
(2 × CH3), 32.8 (C-8), 39.8 (C-5), 40.1 (C-9), 50.8 (C-2), 51.4 (C-7),
85.5 (C-4a), 112.8, 126.9, 127.2, 128.6, 128.9, 143.4, 153.1, 170.7,
and 194.9 (ArC and 2 × C=O). Anal. Calcd for C24H29N3O2 (391.51):
C, 73.63; H, 7.47; N, 10.73. Found: C, 73.65; H, 7.50; N, 10.82%.
8,8-Dimethyl-2-(4-nitrophenyl)-5-phenyl-7,8,9,10-tetrahydropyrim-
ido[4,5-b]quinoline-4,6(3H,5H)-dione (9): A mixture of 1 (3.11 g,
10 mmol), and 4-nitrobenzoyl chloride (1.86 g, 10 mmol) in dry pyri-
dine (20 mL) was refluxed for 5 h. After cooling the reaction mixture
was poured into ice cold HCl, the product was filtered off, dried and
recrystallised from ethanol to give 9 as yellow crystals. Yield 70%.
m.p. 236–237 °C. 1H NMR (DMSO-d6): δ = 0.97 (s, 3H, CH3), 1.03 (s,
3H, CH3), 1.88 (s, 2H, CH2), 2.33 (s, 2H, CH2), 4.89 (s, 1H, CH-Ph),
7.01–7.33 (m, 5H, ArH), 8.18 (d, 2H, J = 8.8 Hz ArH), 8.31 (d, 2H,
J = 8.8 Hz, ArH), 10.21 (s, 2H, 2 × NH). 13C NMR (DMSO-d6):
δ = 27.2, 27.4 (2 × CH3), 32.7 (C-8), 39.9 (C-5), 40.2 (C-9), 51.2
(C-7), 100.2, 111.9, 124.1, 126.9, 128.0, 128.2, 128.9, 131.1, 136.8,
149.7, 150.5, 153.1, 166.2, 170.7 and 194.9 (ArC, C=N and 2 C=O).
Anal. Calcd for C25H22N4O4 (442.47): C, 67.86; H, 5.01; N, 12.66.
Found: C, 67.85; H, 5.21; N, 12.76%.
8,8-Dimethyl-5-phenyl-2-thioxo-2,3,7,8,9,10-hexahydropyrimido
[4,5-b]quinoline-4,6(1H,5H)-dione (4): A mixture of 1 (3.11 g,
10 mmol) and carbon disulfide (1.56 g, 20 mmol) in dry pyridine
(20 mL) was refluxed for 20 h (until the evolution of H2S was com-
plete). After cooling the reaction mixture was poured into cold dil.
HCl, the solid product was filtered off, dried and recrystallised from
methanol to give 4 as yellow crystals.Yield 60%. m.p. 226–227 °C. IR
(KBr): 3430 (NH), 1690 (C=O), 1666 (C=O, amide) and 1235 cm−1
(C=S). 1H NMR (DMSO-d6): δ = 0.97 (s, 3H, CH3), 1.04 (s, 3H, CH3),
1.93 (s, 2H, CH2), 2.33 (s, 2H, CH2), 4.80 (s, 1H, CH-Ph), 7.02–7.25
(m, 5H, ArH), 8.29 (s, 1H, NH), 10.0 (s, 2H, 2NH). 13C NMR (DMSO-
d6): δ = 27.0, 27.6 (2CH3), 32.9 (C-8), 39.8 (C-5), 40.01 (C-9),
50.0 (C-7), 87.8 (C-4a), 111.9, 125.9, 126.9, 128.0, 128.9, 143.4,
149.7, 153.1, 170.7 and 194.8 (ArC, 2 × C=O and C=S). Anal. Calcd
for C19H19N3O2S (353.44): C, 64.57; H, 5.42; N, 11.89. Found: C,
64.70; H, 5.46; N, 11.92%.
2,8,8-Trimethyl-5-phenyl-7,8,9,10-tetrahydropyrimido[4,5-b]quinoline-
4,6(3H,5H)-dione (5): Compound 1 (3.11 g, 10 mmol) was added to a
mixture of acetic anhydride and pyridine (3:1, 20 mL), then refluxed
for 3 h. After cooling, the reaction mixture was poured into cold dil.
HCl, the product was filtered off, dried and recrystallised from diox-
ane to give 5. Yield 75%. m.p. 242–244 °C. IR (KBr): 3402 (NH),
1695 (C=O), 1662 cm−1 (C=O, amide). 1H NMR (DMSO-d6): δ = 0.95
8,8-Dimethyl-5-phenyl-7,8,9,10-tetrahydro[1,2,3]triazino[4,5-b]
quin-oline-4,6(3H,5H)-dione (10): To a cold solution of 1 (3.11 g,
10 mmol), in a mixture of hydrochloric acid (15 mL) and acetic acid
(15 mL), a solution of sodium nitrite (2.00 g)in water (15 mL) was
added with stirring. After complete addition, the reaction mixture
was stirred at room temperature for another 2 h. The solid product was

532 JOURNAL OF CHEMICAL RESEARCH 2010
filtered off, dried and recrystallised from methanol to give 10 as white
crystals. Yield 60%. m.p. 218–220 °C. 1H NMR (DMSO-d6): δ = 0.97
(s, 3H, CH3), 1.04 (s, 3H, CH3), 2.10 (s, 2H, CH2), 2.41 (s, 2H, CH2),
References
1
2
3
4
5
D. Carlunescu, A.D. Lopez, E.G. Iriarte, G. Tina, G. Gomez, R. Tena and
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4.78 (s, 1H, CH-Ph), 7.10–7.27 (m, 5H, ArH), 10.01 (s, 2H, 2NH). 13
C
NMR (DMSO-d6): δ = 27.7, 27.9 (2 × CH3), 32.7 (C-8), 39.9 (C-5),
40.8 (C-9), 51.5 (C-7), 111.9, 112.8, 126.9, 128.9, 132.0, 143.3, 149.5,
153.1, 170.7, and 194.9 (ArC and 2 C=O). Anal. Calcd for C18H18N4O2
(322.36): C, 67.07; H, 5.63; N, 17.38. Found: C, 67.17; H, 5.58;
N, 17.29%.
S-Alkyltetrahydropyrimido[4,5-b]quinoline-4,6(1H,5H)-diones
(11–13): general procedure: A mixture of 3a (10 mmol), potassium
carbonate (10 mmol) and the appropriate alkylating agent, i.e. allyl
bromide, propargyl bromide or epichlorohydrin (10 mmol) in dry
acetone (20 mL) was heated under reflux for 6 h. After cooling, the
mixture was filtered off. The filterate was concentrated to afforded the
products which were recrystallised from ethanol.
6
7
U.S. Pathak, S. Singh and J. Padh, Indian J. Chem. Sect. B 1991, 30, 618.
C.J. Shishoo, M.B. Devani, V.S. Bhadti, K.S. Jain, I.S. Rathod, R.K. Goyal,
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A.B.A. El-GazzaR, H.N. Hafez and G.A.M. Nawwar, Eur. J. Med. Chem.,
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10 J.P. Osselaere, J. Pharm. Belg. 1974, 29, 145.
11 K. Noda, A. Nakagawa, S. Miyata and H. Ide, Jpn. Kokai, 75 52, 095
2-(Allylthio)-8,8-dimethyl-1,5-diphenyl-7,8,9,10-tetrahydropyrimido
[4,5-b]quinoline-4,6(1H,5H)-dione (11): Brown crystals, Yield 75%.
m.p.152–153 °C. IR (KBr): 3458 (NH), 1685(C=O), 1668 cm−1 (C=O,
(1973). (Chem. Abstr., 1975, 83, 193367 v).
1
amide); H NMR (DMSO-d6): δ = 0.99 (s, 3H, CH3), 1.04 (s, 3H,
12 D. Dorjsuren, A. Burnette, G.N. Gray, X. Chen, W. Zhu, P.E. Roberts, M.J.
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CH3), 1.92 (s, 2H, CH2), 2.30 (s, 2H, CH2), 3.48 (d, 2H, J = 5.5 Hz,
SCH2), 4.80 (s, 1H, CH-Ph), 5.08 (d, J = 9.8 Hz, =CHH), 5.18 (d,
1H, J = 15.9 Hz, =CHH ), 6.03 (m, 1H, CH=CH2), 6.25–7.33 (m, 10H,
ArH), 10.01 (s, 1H, NH). 13C NMR (DMSO-d6): δ = 27.2, 27.8
(2 × CH3), 32.8 (C-8), 34.2 (SCH2), 39.9 (C-5), 40.8 (C-9), 51.3 (C-7),
95.2 (C-4a), 111.4, 118.3, 122.4, 122.8, 126.9, 128.0, 129.5, 131.5,
141.2, 143.8, 144.4, 149.7, 157.5, 163.2, 170.1 and 194.8 (ArC, C=C,
C=N and 2 × C=O). Anal. Calcd for C28H27N3O2S (469.60): C, 71.61;
H, 5.80; N, 8.95. Found: C, 71.68; H, 5.88; N, 8.79%.
8,8-Dimethyl-1,5-diphenyl-2-(prop-2-ynylthio)-7,8,9,10-tetrahydropyr-
imido[4,5-b]quinoline-4,6(1H,5H)-dione (12): Pale brown crystals,
Yield 77%. m.p. 149–150 °C. IR (KBr): 3458 (NH), 1692(C=O),
1665 cm−1 (C=O, amide). 1H NMR (DMSO-d6): δ = 0.98 (s, 3H, CH3),
1.02 (s, 3H, CH3), 1.88 (s, 2H, CH2), 2.27 (s, 2H, CH2), 2.39 (d, 1H,
J = 2.3 Hz, C≡CH), 4.35 (app.d, 2H, J = ~2 Hz, SCH2), 4.79 (s, 2H,
CH-Ph), 6.25–7.33 (m, 10H, ArH), 10.01 (s, 1H, NH). Anal. Calcd for
C28H25N3O2S (467.58): C, 71.92; H, 5.39; N, 8.99. Found: C, 72.01; H,
5.38; N, 8.98%.
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8,8-Dimethyl-2-[(oxiran-2-ylmethyl)thio]-1,5-diphenyl-7,8,9,10-tetrah-
ydropyrimido[4,5-b]quinoline-4,6(1H,5H)-dione (13): Yellow crys-
tals,Yield 65%. m.p. 170–172 °C. IR (KBr): 3450 (NH), 1695 (C=O),
1
1670 (C=O, amide), 1185 cm−1 (cyclic ether). H NMR (DMSO-d6):
δ = 0.99 (s, 3H, CH3), 1.04 (s, 3H, CH3), 1.89 (s, 2H, CH2), 2.28 (s,
2H, CH2), 2.38 (m, 1H), 2.63 (m, 1H), 2.85(m, 1H), 2.89–3.12 (m, 2H,
SCH2), 4.78 (s, 1H, CH-Ph), 6.23–7.35 (m, 10H, ArH), 10.04 (s, 1H,
NH). 13C NMR (DMSO- d6): δ = 27.2, 27.8 (2 × CH3), 28.8 (SCH2),
32.8 (C-8), 39.8 (C-5), 40.4 (C-9), 48.5 (CH2O, oxirane), 51.1 (C-7),
51.9 (CHO, oxirane), 90.9 (C-4a), 119.1, 122.4, 122.8, 125.7, 127.7,
128.6, 129.5, 141.2, 144.5, 149.5, 157.8, 164.3, 170.1 and 194.8 (ArC,
C=N and 2 × C=O). Anal. Calcd for C28H27N3O3S (485.60): C, 69.25;
H, 5.60; N, 8.65. Found: C, 69.38; H, 5.62; N, 8.67%.
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Received 1 May 2010; accepted 29 July 2010
Paper 1000098 doi: 10.3184/030823410X12852490447544
Published online: 7 October 2010
30 J. Clark and G. Hitiris, J. Chem. Soc. Perkin Trans., 1, 1984, 2005.

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