New 2,3-disubstituted quinazolin-4(3H)-ones from 2-undecyl-3,1-benzoxazin- 4-one

Article abstract of DOI:10.3184/030823407X248315

2-undecyl-4H-3,1-benzoxazin-4-one (2) was prepared and reacted with primary and secondary amines affording compounds 3-7, while with hydrazine hydrate it gave the quinazolinone derivative 8. The reaction of 8 with 3,4,5- trimethoxybenzaldehyde followed by

Full text of DOI:10.3184/030823407X248315

JOURNAL OF CHEMICAL RESEARCH 2007
SEPTEMBER, 541–544
RESEARCH PAPER 541
New 2,3-disubstituted quinazolin-4(3H)-ones from 2-undecyl-
3,1-benzoxazin-4-one
Mahmoud R. Mahmoud, Eman A.A. El-Bordany, Naglaa F. Hassan and Fatma S.M. Abu El-Azm*
Chemistry Department, Faculty of Science, Ain Shams University, Abbassia 11566, Cairo, Egypt
2-undecyl-4H-3,1-benzoxazin-4-one (2) was prepared and reacted with primary and secondary amines affording
compounds 3–7, while with hydrazine hydrate it gave the quinazolinone derivative 8. The reaction of 8 with 3,4,5-
trimethoxybenzaldehyde followed by thioglycollic acid yielded 9 and 10, respectively. Acylation of 8 using cinnamoyl
chloride gave 11. Furthermore, treatment of 2 with hydrazine derivatives provided 12 and 13. Fusion of 2 with
ammonium acetate gave the quinazolinone derivative 14 which upon treatment with ethyl chloroacetate yielded the
ester 15. The hydrazide 17 was obtained from hydrazinolysis of the ester 15.
Keywords: quinazolinones, 3,1-benzoxazinones
CO2H
O
CO2H
NH2
Benzoxazinones temporarily inhibit the catalytic activity of
serine proteases by accumulation of a catalytically inactive
acyl-enzyme intermediate.1 In continuation of our program
exploring the chemical reactivity of the oxazinone moiety
present in 4H-3,1-benzoxazin-4-one derivatives with saturated
aliphatic substituents at position 2 (the so-called dynamic
benzoxazinones),2-7 and derivatives with bulky substituents
involving strong conjugation power (which are so-called static
benzoxazinones),8-16 we report here on the synthesis of a new
2-substituted 3,1-benzoxazin-4-one and the corresponding
2,3-disubstituted 4-quinazolinones.
a
N
H
(CH2)10CH3
1
b
O
O
N
2
Reagents: a, C11H23COCl/pyridine; b, Ac2O
Results and discussion
Scheme 1
The title compound 2-undecyl-3,1-benzoxazin-4-one (2) was
prepared in fairly good yield upon treatment of anthranilic
acid with dodecanoyl chloride in the presence of pyridine to
give 2-dodecanamidobenzoic acid (1) which was cyclised to 2
using freshly distilled acetic anhydride (Scheme 1).
When the lactone 2 reacted with cyclohexylamine in
refluxing pyridine it afforded N-cyclohexyl-2-dodecanamido-
benzamide (3), but its reaction with other primary amines
such as benzylamine and/or p-phenylenediamine yielded the
2,3-disubstituted quinazolin-4(3H)-one derivatives 4 and 5,
respectively. Reaction of 2 with secondary amines such as
morpholine or thiomorpholine yielded N-[2-(morpholine-
4-carbonyl)phenyl]dodecanamide 6 and the corresponding
thiomorpholine derivative 7, respectively (Scheme 2).
O
N
O
O
NH
O
a
(CH2)10CH3
N
H
(CH2)10CH3
2
3
b
c
O
O
X
R
N
O
N
N
H
(CH2)10CH3
(CH2)10CH3
N
Stirring the 3,1-benzoxazin-4-one
2 with hydrazine
hydrate (80%) at room temperature for one hour resulted in
the formation of 3-amino-2-undecylquinazolin-4(3H)-one
(8). Treatment of the N-aminoquinazolinone 8 with 3,4,5-
trimethoxybenzaꢀdehyde in refluxing ethanoꢀ yieꢀded the aniꢀ
9 which with thioglycollic acid in dry benzene afforded the
thiazolidin-4-one 10. Acylation of 8 by cinnamoyl chloride
4, R = CH2Ph
5, R = C6H4NH2-p
6, X = O
7, X = S
Reagents: a, cyclohexylamine / pyridine;
b, RNH2 ; c, morpholine or thiomorpholine / EtOH
Scheme 2
yielded
3-cinnamoylamino-2-undecylquinazolin-4(3H)-
one (15) rather than the O-alkylation product 16.17
Hydrazinolysis of the ester 15 in refluxing ethanoꢀ formed the
hydrazide derivative 17 (Scheme 4).
Compounds 2–8, 10, 11, 13, 15 were found to possess
marked activity against Bacillus subtilis, Escherichia coli and
Candida albicans.
one (11). The reaction of the lactone 2 with the hydrazine
derivatives ethyl carbazate and thiosemicarbazide afforded 3-
(ethoxycarbonylamino)-2-undecylquinazolin-4(3H)-one (12)
and
3-(thiocarbamoylamino)-2-undecylquinazolin-4(3H)-
one (13), respectively. An attempt to prepare the hydrazide
derivative from 12 failed; with hydrazine hydrate in boiling
ethanoꢀ the isoꢀated product was identified as 3-amino-2-
undecylquinazolin-4-one (8) (Scheme 3).
Experimental
Fusion of 2 with ammonium acetate in oil-bath at 170°C for
two hours yielded 2-undecylquinazolin-4(3H)-one (14) which
withethylchloroacetateinthepresenceofanhydrouspotassium
carbonate in dry acetone afforded the N-alkylation product
3-(ethoxycarbonylmethyl)-2-undecylquinazolin-4(3H)-
All melting points were measured using a Gallenkamp electric melting
point apparatus. IR spectra were recorded on a Pye-Unicam SP1200
spectrophotometer using the KBr wafer technique for solid materials.
The ¹H NMR and 13C NMR spectra were determined on a Varian
Gemini 200 or MHz Bruker AC-200 MHz instrument using TMS as
internal standard. Mass spectra were determined using an HP model
MS-5988 in EI mode with electron energy 70 eV. Elemental analyses
were carried out at the Microanalytical Unit, Faculty of Science, Cairo
* Correspondent. E-mail: ftmsaber@yahoo.com
PAPER: 07/4719

542 JOURNAL OF CHEMICAL RESEARCH 2007
O
O
O
N
O
N
S
NHCSNH
NHCO Et
2
2
N
N
N
f
N
e
2
Ar
H
(CH ) CH
(CH ) CH
2 10 3
2
10
3
N
(CH ) CH
2 10
3
13
12
10
Ar = C H (OMe) (3,4,5-)
a
a
c
6
2
3
O
N
O
O
N
NH-COCH=CHPh
NH
N=CHAr
2
d
N
N
N
b
(CH ) CH
2 10
3
(CH ) CH
(CH ) CH
2 10 3
2
10
3
N
11
8
9
Reagents and conditions: a, N H .H O, stir, r.t.; b, ArCHO / EtOH; c, HSCH CO H / dry benzene;
2
4
2
2
2
d, cinnamoyl chloride; e, H NNHCO Et / dry benzene; f, H NNHCSNH / EtOH
2
2
2
2
Scheme 3
O
N
O
N
O
4
CH2CO2Et
3
2
NH
N
5
6
O
b
a
2
10
12
16
14
13
18
(CH2)10CH3
(CH2)10CH3
8
1
N
15
17
19
9
11
7
14
15
Table 1 13C NMR of compound 2, in CDCl3
Atom no. d (ppm) Atom no. d (ppm) Atom no. d (ppm)
c
CH2CO2Et
N
O
N
O
C-1
C-2
C-3
C-4
C-5
163.8
161.7
110.6
128.2
126.1
C-6
C-7
C-8
C-9
130.7
127.1
143.3
30.9
C-10
C-11–C-17
C-18
20.6
29.6
21.9
14.7
CH2CONHNH2
(CH2)10CH3
N
(CH2)10CH3
C-19
N
16
17
Reagents: a, NH4OAc, fusion; b, ClCH2CO2Et / K2CO3 / dry
acetone; c, N2H4.H2O / EtOH
dried and then recrystallised from petroleum ether (b.p. 60–80°C) to
give 3 as colourless crystals (1.21 g., 72%), m.p. 35–37°C. IR (KBr):
1
3263 br. (NH), 1690, 1676 cm-1 (C=O). H NMR (CDCl3): δ 11.02
Scheme 4
(s, 1H, Ar-NHCO), 8.69 (d, 1H, NH-C6H11), 7.3–6.9 (m, 4Harom),
3.9 (br.d, 1H, NH–CH), 2.4 (t, 2H), 2.0 (d,d, 2H), 1.79–1.6 (m, 10H,
cyclohexyl protons), 1.4 (m, 16H), 0.9 (t, 3H). MS: m/z (%) 401 (M+
+ 1, 22.9), 302 (34.2), 218 (100), 136 (53.9), 120 (73.2), 92 (12.7).
Anal. Calcd. for C25H40N2O2 (400.61): C, 74.95; H, 10.06; N, 6.99.
Found: C, 74.71; H, 9.83; N, 6.63%.
University using a Perkin-Elmer 2400 CHN Elemental Analyser.
The monitoring of the progress of all reactions and the homogeneity
of the synthesised compounds were carried out by TLC.
2-Dodecanamidobenzoic acid (1): Dodecanoyl chloride (30 ml,
0.15 mol) was added dropwise with stirring at room temperature to a
solution of anthranilic acid (14 g, 0.1 mol) in pyridine (50 ml) over a
period of 0.5 h. The mixture was then refluxed for 2 h. After cooꢀing,
the reaction mixture was diꢀuted with water and acidified with coꢀd
dilute hydrochloric acid. The solid product that precipitated was
fiꢀtered off, washed with coꢀd water, dried, and then recrystaꢀꢀised
from petroleum ether (b.p. 80–100°C) to give 1 as colourless crystals
(26.8 g., 84%), m.p. 98–99°C. IR: 3335 br (NH, OH), 1680 cm-1
(C=O). 1H NMR (CDCl3): δ 12.5 (s, 1H, COOH, exchangeabꢀe with
D2O), 9.7 (s, 1H, NH, exchangeable with D2O), 8.4–7.4 (m, 4Harom),
2.3 (t, 2H), 1.6 (m, 2H), 1.31–1.2 (m, 16H), 0.9 (t, 3H). MS: m/z (%)
320 (M + 1, 2.4), 276 (1.9), 137 (100), 119 (30). Anal. Calcd. for
C19H29NO3 (319.45): C, 71.44; H, 9.15; N, 4.38. Found: C, 71.58; H,
8.92; N, 4.13%.
3-Benzyl-2-undecylquinazolin-4(3H)-one (4): The benzoxazinone
2 (1 g, 3.3 mmol) and benzylamine (0.36 ml, 3.3 mmol) were heated
to reflux in ethanoꢀ (25 mꢀ) for 3 h. Most of the soꢀvent was distiꢀꢀed
off and the reaction mixture was then acidified with coꢀd diꢀute
hydrochloric acid to afford an oily substance (one spot in TLC)
which did not solidify even with light-petroleum ether (b.p.40–60°C)
1
to give 4 as a yellow oil (1.03 g, 80%). IR: 1684 cm-1 (C=O). H
NMR (CDCl3): δ 8.04–7.05 (m, 9Harom), 4.38 (dd, 2H), 1.7–1.2 (m,
20H), 0.86 (t, 3H). MS: m/z (%) 390 (M+, 2.3), 348 (3.5), 207 (12),
181 (0.7), 165 (100), 91 (16).
3-(4-Aminophenyl)-2-undecylquinazolin-4(3H)-one (5): The benzox-
azinone 2 (1 g, 3.3 mmol) and p-phenylenediamine (0.35 g, 3.3 mmol)
were refluxed in n-butanoꢀ (15 mꢀ) for 10 h. The soꢀid product that
separated out after distilling off the excess solvent and cooling was
coꢀꢀected by fiꢀtration, dried and then recrystaꢀꢀised from petroꢀeum
ether (b.p.60–80°C) to give 5 as colourless crystals (0.45 g., 35%)
m.p. 96–97°C. IR (KBr): 3419, 3358 (NH2), 1673 cm-1 (C=O).
1H NMR (CDCl3): δ 8.3–6.75 (m, 8Harom), 3.88 (br.s, 2H, NH2,
exchangeable with D2O), 2.4 (t, 2H), 1.74 (m, 2H), 1.25 (m, 16H),
0.79 (t, 3H). MS m/z (%): 391 (M+, 12), 264 (21), 251 (100), 106
(20). Anal. Calcd. for C25H33N3O (391.57): C, 76.68; H, 8.49; N,
10.73. Found: C, 76.69; H, 8.68; N, 10.37%.
2-Undecyl-4H-3,1-benzoxazin-4-one (2): A solution of 1 (3.2 g,
0.01 mol) in freshly distilled acetic anhydride (10 ml) was heated
under reflux for 2 h, ꢀeft to cooꢀ, diꢀuted with coꢀd water. The crude
white solid that separated out was collected, washed with aqueous
sodium carbonate (10%), then with cold water. It was dried and
recrystallised from petroleum ether (b.p. 40–60°C) to give 2 as
colourless crystals (2.9 g., 90%) m.p. 30–32°C. IR (KBr): 1764 cm-1
1
(lactone C=O). H NMR (CDCl3): δ 8.1–7.4 (m, 4Harom), 2.67 (t,
2H), 1.8 (m, 2H), 1.36–1.2 (m, 16H), 0.82 (t, 3H). MS: m/z (%) 301
(M+, 13), 161 (100), 90 (33). Anal. Calcd. for C19H27NO2 (301.43):
C, 75.71; H, 9.02; N, 4.64. Found: C, 75.30; H, 9.25; N, 4.62%.
N-Cyclohexyl-2-dodecanamidobenzamide (3): The benzoxazinone
2 (1 g, 3.3 mmol) and cyclohexylamine (0.32 ml, 3.3 mmol) in
pyridine (10 mꢀ) were heated under reflux for 3 h, then ꢀeft to cooꢀ
and acidified with coꢀd diꢀute hydrochꢀoric acid. The soꢀid product
that deposited was coꢀꢀected by fiꢀtration, washed with coꢀd water,
N-[2-(Morpholine-4-carbonyl)phenyl]dodecanamide (6) and N-[2-
(thiomorpholine-4-carbonyl)phenyl]dodecanamide (7): The benzox-
azinone 2 (1 g, 3.3 mmol) and morpholine (0.28 ml, 3.3 mmol) or
thiomorpholine (0.35 ml, 3.3 mmol) in ethanol (30 ml) were heated
under reflux for 3 h. An oiꢀy substance was produced after distiꢀꢀation
of the soꢀvent and acidification with coꢀd diꢀute hydrochꢀoric acid.
The oil (one spot on TLC) did not solidify even with light petroleum
(b.p.40–60°C) to give 6 and 7, respectively.
PAPER: 07/4719

JOURNAL OF CHEMICAL RESEARCH 2007 543
4
(100), 103 (37.9), 77 (19.9). Anal. Calcd. for C28H35N3O2 (445.61):
C, 75.47; H, 7.91; N, 9.42. Found: C, 75.57; H, 8.16; N, 9.32%.
O
3
O
7
6
N
O
1
5
8
9
3-Ethoxycarbonylamino-2-undecylquinazolin-4(3H)-one
(12):
2
The benzoxazinone 2 (1 g, 3.3 mmol) and ethyl carbazate (0.35 g,
3.3 mmoꢀ) in dry benzene (15 mꢀ) were heated under reflux for 6 h.
An oily substance (one spot in TLC) was produced after distillation
of the solvent which we could not solidify even by light-petroleum
ether (b.p. 40–60°C) to give 12 as a yellow oil (0.96 g, 75%). IR:
3255 (NH), 1756, 1701 cm-1 (C=O). 1H NMR (DMSO-d6): δ 10.4 (s,
1H, NH, exchangeable with D2O), 8.1–7.4 (m, 4Harom), 4.2–4.04 (q,
2H), 1.7–1.2 (m, 20H), 0.9–0.84 (m, 6H). MS: m/z (%) 387 (M+, 3.1),
247 (54), 175 (22), 104 (65), 77 (10.5), 57 (100).
Treatment of 12 with hydrazine hydrate Compound 12 (1 g,
2.6 mmol) was stirred in ethanol (25 ml) while hydrazine hydrate
(80%, 0.5 ml, 0.01 mol) was added dropwise over 30 min at room
temperature. The soꢀid that deposited was recrystaꢀꢀised and identified
as the amine 8.
14
16
20
18
22
12
11
N
H
17
19
21
23
13
15
10
Table 2 13C NMR of compound 6, in CDCl3
Atom no. d (ppm) Atom no. d (ppm) Atom no. d (ppm)
C-1, C-4
C-2, C-3
C-5
43.9
65.7
170.1
133.9
128.1
125.3
130.2
C-10
C-11
C-12
C-13
C-14
C-15
126.4 C-16, C-17
135.2 C-18, C-19
172.4
36.9
26.3
28.1
29.3
29.4
29.7
30.7
22.6
14.3
C-20
C-21
C-22
C-23
C-6
C-7
C-8
C-9
3-Thiocarbamoylamino-2-undecylquinazolin-4(3H)-one (13): The
benzoxazinone 2 (1 g, 3.3 mmol) and thiosemicarbazide (0.3 g,
3.3 mmoꢀ) was refluxed in ethanoꢀ (25 mꢀ) for 3 h. After removaꢀ
of most of the soꢀvent the residue was coꢀꢀected by fiꢀtration, dried
and recrystallised from petroleum ether (b.p.80–100°C) to give 13 as
colourless crystals (0.85 g, 69%), m.p: 101–102°C. IR: 3473, 3367,
Morpholide (6): Yellow oil (0.69 g., 54%). IR: 3308 cm-1 (NH), 1732,
1687 cm-1 (C=O). 1H NMR (CDCl3): δ 9.9 (s, 1H, NH, exchangeabꢀe
with D2O), 7.87–7.3 (m, 4Harom), 3.61 (m, 4H, CH2OCH2), 3.54
(m, 4H, CH2NCH2), 2.59 (t, 2H), 1.66 (t, 2H), 1.4–1.2 (m, 16H), 0.9
(t, 3H). MS m/z (%): 388 (M+., 1.2), 302 (61), 206 (17), 137 (61), 120
(100), 92 (25).
Thiomorpholide (7): Yellow oil (0.60 g., 45%). IR: 3265 (NH),
1732, 1686 cm-1 (C=O). 1H NMR (CDCl3): δ 9.1 (s, 1H, NHCO,
exchangeable with D2O), 7.81–7.3 (m, 4Harom), 3.51 (m, 4H,
CH2NCH2), 2.57 (m, 4H, CH2SCH2), 2.51 (t, 2H), 1.66 (t, 2H), 1.3–
1.2 (m, 16H), 0.9 (t, 3H). MS: m/z (%) 404 (M+, 14), 302 (100), 222
(5.6), 136 (30), 120 (62), 92 (26).
1
3274, 3155 (NH, NH2), 1687 (C=O), 1170 cm-1 (C=S). H NMR
(CDCl3): δ 10.1 (br.s, 2H, NH2, exchangeable with D2O), 8.5 (br.s,
1H, NH, exchangeable with D2O), 8.1–7.6 (m, 4Harom), 1.4–1.19
(m, 20H), 0.9 (t, 3H). MS: m/z (%) 341 (M+ – H2S, 17.8), 173 (41),
160 (100), 120 (13). Anal. Calcd. for C20H30N4OS (374.55): C, 64.13;
H, 8.07; N, 14.95; S, 8.56%. Found: C, 63.82; H, 7.78; N, 5.16; S,
8.24%.
2-Undecylquinazolin-4(3H)-one (14): The benzoxazinone 2 (1 g,
3.3 mmol) and ammonium acetate (3 g) was fused in an oil-bath at
170°C for 2 h. After cooling, the reaction mixture was poured into
water then the soꢀid that was deposited was coꢀꢀected by fiꢀtration,
dried and then recrystallised from petroleum ether (b.p. 60–80°C) to
give 14 as colourless crystals (0.95 g, 94%), m.p. 94–95°C. IR: 3358,
3172 (NH, OH), 1674 cm-1 (C=O). 1H NMR (CDCl3): δ 11.08 (s, 1H,
NH, exchangeable with D2O), 8.1–7.6 (m, 4Harom), 1.46–1.2 (m,
20H), 0.96 (t, 3H). MS: m/z (%) 300 (M+, 4.5), 257 (3.4), 215 (6.5),
173 (34), 160 (100). Anal. Calcd. for C19H28N2O (300.45): C, 75.95;
H, 9.39; N, 9.32. Found: C, 75.78; H, 9.37; N, 9.06%.
Ethyl (3,4-dihydro-4-oxo-2-undecylquinazolin-3-yl)acetate (15):
The quinazolinone 14 (0.5 g, 1.6 mmol), ethyl chloroacetate (0.6 ml,
4.8 mmoꢀ) and anhydrous potassium carbonate (1 g) was refluxed
in dry acetone (25 ml) on water bath for 30 h. Most of the solvent
was distilled off and the reaction mixture was then diluted with
water to afford a soꢀid product that was coꢀꢀected by fiꢀtration and
recrystallised from benzene to give 15 as pale yellow crystals (0.44
g, 71%), m.p. 80–81°C. IR (KBr): 1732, 1670 cm-1 (C=O). 1H NMR
(DMSO-d6): δ 8.1–6.75 (m, 4Harom), 4.9 (s, 2H, N-CH2CO), 4.2 (q,
2H), 2.79 (t, 2H), 2.03 (t, 3H), 1.68 (t, 2H), 1.4–1.2 (m, 16H), 0.85
(m, 3H). MS: m/z (%) 357 (M+ – C2H4- H., 8.2), 174 (100), 146 (19).
Anal. Calcd. for C23H34N2O3 (386.54): C, 71.47; H, 8.86; N, 7.24.
Found: C, 71.25; H, 9.18; N, 7.62%.
2-(3,4-Dihydro-4-oxo-2-undecylquinazolin-3-yl)acetohydrazide
(17): The ester 15 (0.5 g, 1.3 mmol) and hydrazine hydrate 80%
(0.3 mꢀ, 6 mmoꢀ) in ethanoꢀ (25 mꢀ) was refluxed for 2 h. After
distillation of most of the solvent, a colourless solid was formed
which was coꢀꢀected by fiꢀtration and recrystaꢀꢀised from benzene
to give 17 as colourless crystals (0.42 g, 87%), m.p. 165–166°C.
IR: 3333 br. (NH, NH2), 1681, 1655 cm-1 (C=O). MS: m/z (%) 372
(M+, 2.6), 342 (91), 341 (100), 314 (42), 313 (45). Anal. Calcd. for
C21H32N4O2 (372.52): C, 67.71; H, 8.65; N, 15.03. Found: C, 67.49;
H, 8.51; N, 14.97%.
3-Amino-2-undecylquinazolin-4(3H)-one (8): The benzoxazinone
2 (1 g., 3.3 mmol) and hydrazine hydrate 80% (0.5 ml, 0.01 mol) in
ethanol (15 ml) were stirred at room temperature for 1 h. The solid
that precipitated was fiꢀtered off, washed with ꢀight petroꢀeum (b.p.
60–80°C), dried, and then recrystallised from light petroleum (b.p.80–
100°C) to give 8 as colourless crystals (0.67 g., 64%), m.p. 97–99°C.
IR: 3322, 3261 (NH2), 1652 cm-1 (C=O). 1H NMR (CDCl3):δ 8.1–7.6
(m, 4Harom), 5.32 (br.s, 2H, NH2, exchangeable with D2O), 1.3–1.2
(m, 20H), 0.89 (t, 3H). MS: m/z (%) 315 (M+., 6.4), 175 (100), 146
(27), 118 (4.9), 77 (8.5). Anal. Calcd. for C19H29N3O (315.46): C,
72.34; H, 9.26; N, 13.32. Found: C, 71.92; H, 9.80; N, 13.08%.
3-(3,4,5-Trimethoxybenzylideneamino)-2-undecylquinazolin-
4(3H)-one (9): The aminoquinazolinone 8 (0.5 g, 1.58 mmol) and
3,4,5-trimethoxybenzaldehyde (0.3 g, 1.58 mmol) were heated
in refluxing ethanoꢀ (10 mꢀ) for 3 h. Most of the soꢀvent was then
distilled off. Cooling the resulting solution gave a solid which was
coꢀꢀected by fiꢀtration, dried and then recrystaꢀꢀised from petroꢀeum
ether (b.p.80–100°C) to give 9 as pale yellow crystals (0.43 g, 55%),
m.p. 78–80°C. IR: 1664 cm-1 (C=O). H NMR (DMSO-d6): δ 8.89
1
(s, 1H, CH=N), 8.1–7.3 (m, 6Harom), 3.94 (s, 6H, 2OMe), 3.8 (s,
3H, OMe), 1.39–1.21 (m, 20H), 0.86 (t, 3H). MS: m/z (%) 494 (M+
+ 1, 28), 300 (5.2), 193 (100), 160 (42). Anal. Calcd. for C29H39N3O4
(493.66): C, 70.56; H, 7.96; N, 8.51. Found: C, 70.31; H, 8.27; N,
8.63%.
3-[4-Oxo-2-(3,4,5-trimethoxyphenyl)thiazolidin-3-yl]-2-undecyl-
quinazolin-4(3H)-one (10): The imine 9 (0.5 g, 1 mmol) and
thioglycollic acid (0.1 ml, 1 mmol) in dry benzene (15 ml) was heated
under reflux for 12 h. Most of the soꢀvent was distiꢀꢀed off to give an
oily substance which on trituration with boiling light-petroleum ether
(b.p.40–60°C) gave a pale yellow solid which recrystallised from
petroleum ether (b.p.80–100°C) to give 10 as pale yellow crystals
(0.37 g, 66%), m.p. 40–42°C. IR: 1718, 1661 cm-1 (C=O). 1H NMR
(CDCl3): δ 8.1–7.07 (m, 6Harom), 6.1 (s, 1H, NCHS), 3.95 (d,d, 2H,
SCH2CO), 3.83 (s, 9H, 3OMe), 1.3–1.2 (m, 20H), 0.9 (t, 3H). MS
m/z (%): 495 (M+. – CH2S–CO + 2H., 51), 298 (40), 194 (36), 54
(100). Anal. Calcd. for C31H41N3O5S (567.76): C, 65.58; H, 7.27; N,
7.4; S, 5.64. Found: C, 66.01; H, 7.55; N, 7.31; S, 5.92%.
3-Cinnamoylamino-2-undecylquinazolin-4(3H)-one (11): The
aminoquinazolinone 8 (0.5 g, 1.58 mmoꢀ) was refluxed with
cinnamoyl chloride (0.26 g, 1.58 mmol) in pyridine (15 ml) for 8 h.
The reaction mixture was acidified with coꢀd diꢀute hydrochꢀoric acid.
The soꢀid that precipitated was fiꢀtered off, washed with coꢀd water,
dried and then recrystallised from benzene to give 11 as colourless
crystals (0.60 g, 86%), m.p 107–108°C. IR: 3344 (NH), 1696, 1671
cm-1 (C=O). 1H NMR (CDCl3): δ 8.9 (s, 1H, NH, exchangeabꢀe
with D2O), 8.1–7.3 (m, 9Harom), 7.0 (s, 1H), 7.3 (s, 1H), 1.3–1.2
(m, 20H), 0.92 (t, 3H). MS: m/z (%) 445 (M+, 13.9), 305 (35.7), 131
Received 29 June 2007; accepted 25 September 2007
Paper 07/4719 doi: 10.3184/030823407X248315
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