A regioselective three-component reaction for synthesis of novel 1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione derivatives

Article abstract of DOI:10.1016/j.tet.2009.02.037

A ring opening and regioselective three-component reaction of isatoic anhydride, isatins, and aromatic or aliphatic primary amines in the presence of catalytic amount of KAl(SO₄)₂·12H₂O (alum) to yield a novel series of 1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione is described.

Full text of DOI:10.1016/j.tet.2009.02.037

Tetrahedron 65 (2009) 3804–3808
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A regioselective three-component reaction for synthesis of novel 10H-
spiro[isoindoline-1,20-quinazoline]-3,40(30H)-dione derivatives
*
*
Ali A. Mohammadi , M. Dabiri , H. Qaraat
Department of Chemistry, Faculty of Science, Shahid Beheshti University, PO Box 19395-4716, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A ring opening and regioselective three-component reaction of isatoic anhydride, isatins, and aromatic or
aliphatic primary amines in the presence of catalytic amount of KAl(SO4)2$12H2O (alum) to yield a novel
series of 10H-spiro[isoindoline-1,20-quinazoline]-3,40(30H)-dione is described.
Ó 2009 Published by Elsevier Ltd.
Received 18 September 2008
Received in revised form 28 January 2009
Accepted 13 February 2009
Available online 24 February 2009
Keywords:
Three-component reaction
Regioselective
Isatoic anhydride
Isatins
Amines
Spirooxindole
1. Introduction
like spirotryprostatins A, B, and strychnophylline.15 The unique
structural array and the highly pronounced pharmacological ac-
Combinatorial chemistry is now routinely applied to find out
novel biologically active compounds. In this context, multicompo-
nent reactions (MCRs) are powerful tools in the modern drug dis-
covery process in terms of lead finding and lead optimization.1–6
However, the range of easily accessible and functionalized small
heterocycles is rather limited. The development of new, rapid, and
robust routes toward focused libraries of such heterocycles is
therefore of great importance.
2,3-Dihydroquinazoline-4(3H)-ones and spirooxindole de-
rivatives are important classes of heterocyclic compounds.
2,3-Dihydroquinazolin-4(3H)-ones possess a broad spectrum of bio-
logical and pharmaceutical activities, such as analgesic, antitumor,
anticancer, diuretic, and herbicide activities.7 In addition, these
compounds can easily be oxidized to their quinazolin-4(3H)-one
analogues,8 which also include important pharmacologically active
compounds.9 Several methods have been reported for the synthesis
of 2,3-dihydroquinazolinones.10–13
tivity displayed by this class of spirooxindole compounds have
made them attractive synthetic targets.16 Oxa and azaspiro de-
rivatives are well-known,16–18 but the preparation of corresponding
quinazolinone analogues has not yet evolved.
2. Results and discussions
We have concentrated most of our recent studies on the prep-
aration of bioactive nitrogen-containing heterocycles, and have
already described simple, efficient procedures, and MCRs19 for
preparation of 2,3-dihydroquinazolin-4(3H)-one,20 oxindole,21 and
spirooxindole.22 We have designed the regioselective three-com-
ponent one-pot synthesis of 10H-spiro[indoline-3,20-quinazoline]-
2,40(30H)-diones 4a–m from isatoic anhydride 1, isatins 2a–c, and
primary amines 3a–m using non-toxic and easily available alum as
a heterogeneous catalyst (Scheme 1).23–26
When a mixture of isatoic anhydride 1, isatin 2a, and aniline 3b
in ethanol was stirred and refluxed in the presence of a catalytic
amount of alum KAl(SO4)2$12H2O, the reaction was complete
within 8 h. Workup of the reaction mixture showed that 10H-spi-
ro[indoline-3,20-quinazoline]-2,40(30H)-dione 4b was prepared in
88% yield. Interestingly, we have found that this reaction is
highly regioselective in the preparation of 10H-spiro[indoline-3,20-
quinazoline]-2,40(30H)-diones 4, since there is no evidence for
the formation of iminoisatins 5,27 6-arylimino-6H-indolo[2,1-
The heterocyclic spirooxindole ring system is a widely distrib-
uted structural framework that is present in a number of phar-
maceuticals and natural products,14 including cytostatic alkaloids
* Corresponding authors. Fax: þ98 21 22431663.
E-mail addresses: a-mohammadi@sbu.ac.ir (A.A. Mohammadi), m-dabiri@
sbu.ac.ir (M. Dabiri).
0040-4020/$ – see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tet.2009.02.037

A.A. Mohammadi et al. / Tetrahedron 65 (2009) 3804–3808
3805
b]quinazolin-12-one 628 or indolo[2,1-b]quinazoline-6,12-dione 729
(Schemes 2 and 3).
8 from isatoic anhydride and amines, then intermediates 8 reaction
with isatin in the presence of alum gives the intermediate 9. Once
intermediate 9 is formed, a nucleophilic attack takes place by the
nitrogen group and the final product is produced (Scheme 4).
O
O
The structures of products were characterized by IR, 1H NMR, 13
NMR, MS spectra, and elemental analysis.
C
R2
R2NH2
3a-m
O
O
N
Alum (20 mol%)
EtOH/Reflux
+
N
H
O
N
H
NH
1
3. Conclusions
O
4a-m
R1
R1
O
In summary, we have described a successful strategy, an
efficient and convenient synthesis for the preparation of
10H-spiro[indoline-3,20-quinazoline]-2,40(30H)-diones via a three-
component cyclocondensation of isatoic anhydride, isatins, and
amines, using the inexpensive, non-toxic, and easily available
KAl(SO4)2$12H2O catalyst. The method offers several advantages
including high yield of products and easy experimental workup
procedure. Surprisingly, this reaction is regioselective in the prep-
aration of 10H-spiro[indoline-3,20-quinazoline]-2,40(30H)-diones,
which makes it a useful process for the synthesis of 10H-spi-
ro[indoline-3,20-quinazoline]-2,40(30H)-diones.
N
H
2a-c
Scheme 1.
R2
N
R2
R1
O
N
R2NH2
R1
R1
O
3
1
O
N
N
N
5 H
N
H
2
6
O
4. Experimental
Scheme 2.
4.1. General methods
O
O
O
R1
R1
O
Melting points were obtained in open capillary tubes and were
measured on an electro-thermal 9200 apparatus. Mass spectra
were recorded on a Shimadzu QP 1100 BX mass spectrometer. The
IR spectra were recorded on KBr pellets on a Shimadzu IR-470
spectrophotometer. 1H and 13C NMR spectra were determined on
a Bruker 300 DRX Avance instrument at 300 and 75 MHz. Ele-
mental analysis for C, H, and N was performed using a Heraus CHN
rapid analyzer. The chemical used in this work were purchased
from Merck and Fluka, and KAl(SO4)2$12H2O was from Merck.
N
O
+
N
N
H
N
H
O
2
1
7
O
Scheme 3.
Encouraged by this success, we extended this reaction of isatoic
anhydride with a range of other isatins 2 and amines 3 under
similar conditions, furnishing the respective 10H-spiro[indoline-
3,20-quinazoline]-2,40(30H)-diones 4 in good yields. The optimized
results are summarized in Table 1.
It is noticeable that when the isatoic anhydride 1, isatin 2a–m,
and amines 3a–m in the presence of alum were stirred at reflux for
within 1.5 h, in all cases the reaction led to the formation of the
intermediates 8 that could be isolated and characterized by spec-
troscopic methods. Furthermore, the continuation of reaction for
4 h led to a mixture of 4a–m and intermediates 8 (monitored by
TLC and spectroscopic methods), meanwhile after the times in-
dicated in Table 1, just 4a–m were obtained and the intermediates 8
were not detected in the final mixture.
4.2. General experimental procedure for synthesis of 10H-
spiro[isoindoline-1,20-quinazoline]-3,40(30H)-dione
A mixture of isatoic anhydride 1 (1 mmol), isatin 2 (1 mmol),
primary amines 3 (1 mmol), 0.1 g (0.2 mmol) alum, and 10 ml EtOH
in a 50 ml flask was stirred at reflux for the time period as indicated
in Table 1. After completion of the reaction (monitored by TLC, ethyl
acetate/n-hexane, 1:1), 25 ml EtOH was added to the reaction
mixture, and recrystallized from ethanol to afford pure product.
4.3. Typical experimental procedure
Notably, imines 5 were not detected in this reaction pathway.
According to these results, the reaction can be mechanistically
considered to proceed via the initial formation of the intermediates
4.3.1. 10H-Spiro[indoline-3,20-quinazoline]-2,40(30H)-dione (4a)
Cream powder; mp 261–263 ꢀC dec; IR (KBr) (nmax, cmꢁ1): 3491
(NH), 3227(NH), 2964, 1725 (C]O), 1642 (C]O), 1614, 1526; 1H
NMR (300 MHz, DMSO-d6): dH 6.60 (d, 1H, J¼8.0, ArH), 6.68 (t, 1H,
J¼7.4, ArH), 6.84 (d, 1H, J¼7.7, ArH), 7.05 (t, 1H, J¼7.4, ArH), 7.22 (t,
1H, J¼7.2, ArH), 7.28 (s, 1H, NH), 7.33 (t, 1H, J¼7.8, ArH), 7.47 (d, 1H,
J¼7.3, ArH), 7.59 (d, 1H, J¼7.4, ArH), 8.36 (s, 1H, NH), 10.30 (s, 1H,
NH); 13C NMR (75 MHz, DMSO-d6): dC 71.41, 110.53, 114.31, 114.76,
117.61, 122.73, 125.81, 127.30, 129.89, 131.26, 133.75, 142.58, 147.28,
164.40, 176.47; MS (EI, 70 eV) (m/z, %): 265 (Mþ, 25), 263 (50), 237
(100), 119 (95), 92 (60), 63 (35), 50 (30), 39 (40). Anal. Calcd for
C15H11N3O2: C, 67.92; H, 4.18; N, 15.84. Found: C, 67.80; H, 4.11; N,
15.73.
Table 1
The synthesis of 10H-spiro[isoindoline-1,20-quinazoline]-3,40(30H)-dione 4a–m
Product 4 R1 R2
Time (h) Yielda (%) Mp (ꢀC)
Lit. mp (ꢀC)
a
b
c
d
e
f
g
h
i
H
H
H
H
H
H
H
H
Ph
6
8
7
8
8
8
7
8
9
10
10
11
11
92
91
93
92
86
85
92
89
88
78
82
84
81
261–263 dec
251–253 dec
271–273 dec
269–271 dec
213–215 dec
264–266 dec
190–192 dec
150–152 dec
245–247 dec
274–276 dec
204–206 dec
216–218 dec
237–239 dec
d
d
d
d
d
d
d
d
d
d
d
d
d
p-CH3C6H4
p-CH3OC6H4
p-BrC6H4
p-ClC6H4
PhCH2
Br p-CH3C6H4
F
H
H
H
H
p-CH3C6H4
Et
n-Pr
n-Bu
n-Pen
4.3.2. 30-Phenyl-10H-spiro[indoline-3,20-quinazoline]-2,40(30H)-
dione (4b)
j
k
l
Yellow powder; mp 251–253 ꢀC dec; IR (KBr) (nmax, cmꢁ1): 3428
(NH), 3265 (NH), 2916, 1727 (C]O), 1642 (C]O), 1616; 1H NMR
(300 MHz, DMSO-d6): dH 6.63 (d, 1H, J¼7.7, ArH), 6.70–6.78 (m, 2H,
m
a
Yields of pure isolated product based on isatin.

3806
A.A. Mohammadi et al. / Tetrahedron 65 (2009) 3804–3808
Alum
O
R1
Alum
O
O
O
N
O
R2
N
O
N
2
R2
O
+
H
2
N
H
R NH2
3
H
-CO2
N
H
O
NH2
-H2O
1
8
9
NH
O
R1
R2
O
N
N
H
NH
4
R1
Scheme 4.
ArH), 6.92 (t, 1H, J¼7.4, ArH), 6.98 (d, 2H, J¼7.0, ArH), 7.12–7.23 (m,
4H, ArH), 7.30 (t, 1H, J¼7.0, ArH), 7.53 (d, 1H, J¼7.3, ArH), 7.63 (s, 1H,
NH), 7.66 (d, 1H, J¼7.0, ArH), 10.42 (s, 1H, NH); 13C NMR (75 MHz,
DMSO-d6): dC 76.85, 110.57, 114.57, 115.04, 118.17, 122.59, 126.96,
127.75, 127.90, 128.10, 129.11, 129.74, 131.29, 134.16, 138.55, 142.12,
146.58, 164.08, 175.96; MS (EI, 70 eV) (m/z, %): 341 (Mþ, 5), 313
(100), 269 (15), 249 (15), 221 (25), 194 (25), 167 (15), 120 (60), 92
(30), 77 (80), 63 (35), 51 (50), 39 (40). Anal. Calcd for C21H15N3O2: C,
73.89; H, 4.43; N, 12.31. Found: C, 73.80; H, 4.32; N, 12.25.
127.93, 131.53, 131.99, 132.21, 134.34, 137.91, 142.13, 146.59, 164.08,
175.77; MS (EI, 70 eV) (m/z, %): 419 (Mþ, 5), 391 (100), 301 (15), 272
(15), 249 (35), 221 (15),194 (25),171 (35),155 (20),120 (90), 92 (45),
77 (60), 63 (65), 51 (65), 39 (55). Anal. Calcd for C21H14BrN3O2: C,
60.02; H, 3.36; N, 10.00. Found: C, 59.83; H, 3.26; N, 9.89.
4.3.6. 30-(4-Chlorophenyl)-10H-spiro[indoline-3,20-quinazoline]-
2,40(30H)-dione (4f)
Yellow powder; mp 264–266 ꢀC dec; IR (KBr) (nmax, cmꢁ1): 3427
(NH), 3337 (NH), 2964, 1739 (C]O), 1643 (C]O), 1608, 1491; 1H
NMR (300 MHz, DMSO-d6): dH 6.66–6.78 (m, 3H, ArH), 6.92–7.02
(m, 3H, ArH), 7.16 (t, 1H, J¼7.5, ArH), 7.28–7.33 (m, 3H, ArH), 7.56 (d,
1H, J¼7.3, ArH), 7.63 (d, 1H, J¼7.3, ArH), 7.66 (s, 1H, NH), 10.46 (s, 1H,
NH); 13C NMR (75 MHz, DMSO-d6): dC 76.86, 110.73, 114.65, 114.76,
118.24, 122.75, 126.98, 127.47, 127.93, 129.25, 131.52, 131.66, 132.66,
134.34, 137.47, 142.14, 146.60, 164.13, 175.79; MS (EI, 70 eV) (m/z, %):
375 (Mþ, 5), 347 (100), 249 (35), 228 (15), 192 (25), 166 (25), 120
(70), 92 (35), 75 (60), 63 (65), 51 (60), 39 (60). Anal. Calcd for
C21H14ClN3O2: C, 67.12; H, 3.75; N, 11.18. Found: C, 67.01; H, 3.76; N,
11.09.
4.3.3. 30-p-Tolyl-10H-spiro[indoline-3,20-quinazoline]-2,40(30H)-
dione (4c)
Cream powder; mp 271–273 ꢀC dec; IR (KBr) (nmax, cmꢁ1): 3420
(NH), 3258 (NH), 2964, 1708 (C]O), 1644 (C]O), 1613, 1503; 1H
NMR (300 MHz, DMSO-d6): dH 2.17 (s, 3H, CH3), 6.63–6.77 (m, 3H,
ArH), 6.85 (d, 2H, J¼8.2, ArH), 6.93 (d, 2H, J¼7.5, ArH), 6.99 (d, 2H,
J¼8.2, ArH), 7.15 (t, 1H, J¼7.2, ArH), 7.29 (t, 1H, J¼7.0, ArH), 7.53 (d,
1H, J¼7.3, ArH), 7.60 (s, 1H, NH), 7.64 (d, 1H, J¼7.0, ArH),10.40 (s, 1H,
NH); 13C NMR (75 MHz, DMSO-d6): dC 21.00, 76.86, 110.59, 114.51,
115.04, 118.09, 122.60, 126.90, 127.88, 127.96, 129.65, 131.26, 134.08,
135.91, 137.30, 142.10, 146.56, 164.12, 175.96; MS (EI, 70 eV) (m/z, %):
355 (Mþ, 5), 353 (15), 327 (100), 249 (15), 235 (25), 208 (25), 120
(50), 91 (35), 77 (20), 65 (45), 51 (30), 39 (30). Anal. Calcd for
C22H17N3O2: C, 74.35; H, 4.82; N, 11.82. Found: C, 74.24; H, 4.73; N,
11.74.
4.3.7. 30-Benzyl-10H-spiro[indoline-3,20-quinazoline]-2,40(30H)-
dione (4g)
Cream powder; mp 190–192 ꢀC dec; IR (KBr) (nmax, cmꢁ1): 3480
(NH), 3329 (NH), 2924, 1729 (C]O), 1623 (C]O), 1610; 1H NMR
(300 MHz, DMSO-d6): dH 4.15–4.20 (d, J¼15.3, 1H, CH2), 4.47–4.52
(d, J¼15.3, 1H, CH2), 6.67 (d, 1H, J¼7.9, ArH), 6.76 (t, 1H, J¼7.4, ArH),
6.81 (d, 1H, J¼7.6, ArH), 6.90–6.92 (m, 3H, ArH), 7.14–7.16 (t, 2H,
ArH), 7.24–7.34 (m, 3H, ArH), 7.48 (s, 1H, NH), 7.73 (d, 1H, J¼7.5,
ArH), 10.36 (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6): dC 46.31,
75.54, 110.91, 114.41, 115.06, 118.12, 122.41, 126.71, 126.76, 127.27,
127.82, 127.87, 128.24, 131.73, 133.86, 137.83, 142.97, 146.47, 164.53,
175.47; MS (EI, 70 eV) (m/z, %): 355 (Mþ, 5), 353 (20), 327 (100), 249
(20), 235 (25), 208 (25), 120 (50), 91 (30), 77 (30), 65 (35), 51 (20),
39 (35). Anal. Calcd for C22H17N3O2: C, 74.35; H, 4.82; N, 11.82.
Found: C, 74.23; H, 4.71; N, 11.70.
4.3.4. 30-(4-Methoxyphenyl)-10H-spiro[indoline-3,20-quinazoline]-
2,40(30H)-dione (4d)
Cream powder; mp 269–271 ꢀC dec; IR (KBr) (nmax, cmꢁ1): 3426
(NH), 3287(NH), 2964, 1726 (C]O), 1638 (C]O), 1612, 1510; 1H
NMR (300 MHz, DMSO-d6): dH 3.64 (s, 3H, OCH3), 6.67–6.75 (m, 5H,
ArH), 6.89–9.91 (m, 3H, ArH), 7.16–7.29 (m, 2H, ArH), 7.55 (s, 1H,
NH), 7.59–7.68 (m, 2H, ArH), 10.40 (s, 1H, NH); 13C NMR (75 MHz,
DMSO-d6): dC 55.54, 77.03, 110.59, 114.23, 114.50, 115.01, 118.09,
122.63, 126.85, 127.92, 128.08, 131.02, 131.23, 134.08, 142.08, 146.59,
158.61, 164.27, 175.97; MS (EI, 70 eV) (m/z, %): 371 (Mþ, 5), 369 (15),
343 (100), 328 (90), 249 (35), 221 (25), 192 (25), 120 (40), 91 (45),
77 (60), 65 (45), 51 (45), 39 (50). Anal. Calcd for C22H17N3O3: C,
71.15; H, 4.61; N, 11.31. Found: C, 71.06; H, 4.53; N, 11.20.
4.3.8. 5-Bromo-30-p-tolyl-10H-spiro[indoline-3,20-quinazoline]-
2,40(30H)-dione (4h)
Yellow powder; mp 150–152 ꢀC dec; IR (KBr) (nmax, cmꢁ1): 3450
(NH), 3236 (NH), 1736 (C]O), 1645 (C]O), 1613, 1512; 1H NMR
(300 MHz, DMSO-d6): dH 2.08 (s, 3H, CH3), 6.60 (d, 1H, J¼8.2, ArH),
6.67 (d, 1H, J¼7.7, ArH), 6.74 (t, 1H, ArH), 6.89 (d, 2H, J¼6.7, ArH),
7.03 (d, 1H, J¼7.8, ArH), 7.28–7.35 (m, 2H, ArH), 7.65–7.69 (m, 2H,
ArH), 7.76 (s, 1H, NH), 10.55 (s, 1H, NH); 13C NMR (75 MHz, DMSO-
d6): dC 21.03, 76.87, 112.66, 114.17, 114.54, 114.98, 118.34, 127.94,
129.68, 129.81, 130.15, 134.03, 134.21, 135.69, 137.61, 141.44, 146.27,
163.91, 175.64; MS (EI, 70 eV) (m/z, %): 434 (Mþ, 10), 405 (95), 327
(25), 286 (35), 250 (15), 209 (15), 192 (25), 166 (25), 146 (20), 120
4.3.5. 30-(4-Bromophenyl)-10H-spiro[indoline-3,20-quinazoline]-
2,40(30H)-dione (4e)
Yellow powder; mp 213–215 ꢀC dec; IR (KBr) (nmax, cmꢁ1): 3429
(NH), 3252 (NH), 2964, 1725 (C]O), 1642 (C]O), 1614; 1H NMR
(300 MHz, DMSO-d6): dH 6.67–6.79 (m, 3H, ArH), 6.93–6.97 (m, 3H,
ArH), 7.16 (t, 1H, J¼7.6, ArH), 7.31 (t, 1H, J¼7.2, ArH), 7.41 (d, 2H,
J¼8.4, ArH), 7.56 (d, 1H, J¼7.3, ArH), 7.67 (s, 1H, NH), 7.69 (d, 1H,
J¼7.0, ArH), 10.47 (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6): dC
76.81, 110.74, 114.65, 114.75, 118.25, 120.71, 121.24, 126.97, 127.46,

A.A. Mohammadi et al. / Tetrahedron 65 (2009) 3804–3808
3807
(100), 91 (85), 77 (60), 65 (95), 51 (60), 39 (70). Anal. Calcd for
C22H16BrN3O2: C, 60.84; H, 3.71; N, 9.68. Found: C, 60.74; H, 3.62; N,
9.57.
4.3.13. 30-n-Pentyl-10H-spiro[indoline-3,20-quinazoline]-2,40(30H)-
dione (4m)
Reddish powder; mp 237–239 ꢀC dec; IR (KBr) (nmax, cmꢁ1):
3284 (NH), 1729 (C]O), 1627 (C]O); 1H NMR (300 MHz, DMSO-
d6): dH 0.70 (t, 3H, J¼7.0, CH3), 1.01–1.08 (m, 4H, 2CH2), 1.23–1.28
(m, 1H, CH2), 1.33–1.42 (m, 1H, CH2), 2.74–2.86 (m, 1H, CH2), 3.10–
3.19 (m, 1H, CH2), 6.62 (d, 1H, J¼8.0, ArH), 6.71 (t, 1H, J¼7.5, ArH),
6.93 (d, 1H, J¼7.7, ArH), 7.07 (t, 1H, J¼7.5, ArH), 7.22 (t, 1H, J¼7.5,
ArH), 7.36–7.41 (m,1H, ArH,1H, NH), 7.51 (d,1H, J¼7.3, ArH), 7.64 (d,
1H, J¼7.6, ArH), 10.56 (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6): dC
14.05, 21.84, 27.79, 28.88, 43.29, 75.68, 111.07, 114.20, 115.03, 117.96,
122.87, 126.29, 127.57, 127.85, 131.74, 133.60, 142.63, 146.18, 163.85,
175.90; MS (EI, 70 eV) (m/z, %): 306 (MþꢁEt, 100), 291 (40), 264
(35), 250 (75), 237 (95), 221 (25), 119 (65), 92 (55), 77 (35), 65 (30),
50 (25), 41 (75). Anal. Calcd for C20H21N3O2: C, 71.62; H, 6.31; N,
12.53. Found: C, 71.51; H, 6.21, N, 12.41.
4.3.9. 5-Fluoro-30-p-tolyl-10H-spiro[indoline-3,20-quinazoline]-
2,40(30H)-dione (4i)
Cream powder; mp 245–247 ꢀC dec; IR (KBr) (nmax, cmꢁ1): 3440
(NH), 3264 (NH), 1720 (C]O), 1640 (C]O), 1484; 1H NMR
(300 MHz, DMSO-d6): dH 2.18 (s, 3H, CH3), 6.62–6.67 (m, 2H, ArH),
6.67 (t, 1H, J¼7.6, ArH), 6.90 (d, 2H, J¼7.5, ArH), 6.97–7.05 (m, 3H,
ArH), 7.65 (t, 1H, J¼7.7, ArH), 7.50 (d, 1H, J¼7.7, ArH), 7.63–7.65 (m,
1H, ArH), 7.67 (s, 1H, NH), 10.45 (s, 1H, NH); 13C NMR (75 MHz,
DMSO-d6): dC 21.00, 77.09, 111.54, 111.64, 114.51, 114.67, 114.97,
118.29, 127.91, 129.34, 129.47, 129.78, 134.19, 135.71, 137.56, 138.35,
146.34, 163.99, 176.19; MS (EI, 70 eV) (m/z, %): 373 (Mþ, 10), 345
(100), 329 (15), 269 (25), 253 (25), 226 (35), 120 (50), 91 (45), 77
(40), 65 (45), 51 (30), 39 (35). Anal. Calcd for C22H16FN3O2: C, 70.77;
H, 4.32; N, 11.25. Found: C, 70.66; H, 4.22; N, 11.13.
Acknowledgements
4.3.10. 30-Ethyl-10H-spiro[indoline-3,20-quinazoline]-2,40(30H)-
dione (4j)
We gratefully acknowledge financial support from the Research
Council of Shahid Beheshti University.
Yellowish powder; mp 274–276 ꢀC dec; IR (KBr) (nmax, cmꢁ1):
3294 (NH), 1724 (C]O), 1635 (C]O), 1615; 1H NMR (300 MHz,
DMSO-d6): dH 0.89 (t, 3H, J¼6.9, CH3), 2.81–2.92 (m, 1H, CH2), 3.13–
3.24 (m, 1H, CH2), 6.60 (d, 1H, J¼8.0, ArH), 6.70 (t, 1H, J¼7.3, ArH),
6.92 (d, 1H, J¼7.7, ArH), 7.10 (t, 1H, J¼7.4, ArH), 7.22 (t, 1H, J¼7.1,
ArH), 7.36–7.41 (m,1H, ArH,1H, NH), 7.51 (d,1H, J¼7.3, ArH), 7.63 (d,
1H, J¼7.3, ArH), 10.55 (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6): dC
14.01, 38.30, 75.68, 111.14, 114.17, 114.92, 117.97, 122.99, 126.20,
127.51, 127.98, 131.77, 133.65, 142.60, 146.13, 163.66, 175.95; MS (EI,
70 eV) (m/z, %): 264 (MþꢁEt, 100), 249 (35), 119 (25), 92 (35), 77
(30), 63 (30), 51 (30), 39 (30). Anal. Calcd for C17H15N3O2: C, 69.61;
H, 5.15; N, 14.33. Found: C, 69.53; H, 5.06; N, 14.22.
References and notes
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4.3.11. 30-n-Propyl-10H-spiro[indoline-3,20-quinazoline]-2,40(30H)-
dione (4k)
Yellow powder; mp 204–206 ꢀC dec; IR (KBr) (nmax, cmꢁ1): 3263
(NH), 1722 (C]O), 1687 (C]O), 1624; 1H NMR (300 MHz, DMSO-
d6): dH 0.61 (t, 3H, J¼7.2, CH3), 1.24–1.34 (m, 1H, CH2), 1.35–1.40 (m,
1H, CH2), 2.69–2.79 (m, 1H, CH2), 3.06–3.16 (m, 1H, CH2), 6.60 (d,
1H, J¼8.0, ArH), 6.70 (t, 1H, J¼7.4, ArH), 6.92 (d, 1H, J¼7.7, ArH), 7.09
(t, 1H, J¼7.4, ArH), 7.22 (t, 1H, J¼7.5, ArH), 7.36–7.39 (m, 1H, ArH, 1H,
NH), 7.50 (d, 1H, J¼7.3, ArH), 7.63 (d, 1H, J¼7.5, ArH), 10.31 (s, 1H,
NH); 13C NMR (75 MHz, DMSO-d6): dC 11.73, 21.81, 45.07, 75.69,
111.11, 114.20, 114.99, 117.97, 122.91, 126.24, 127.58, 127.88, 131.76,
133.64, 142.61, 146.17, 163.91, 175.84; MS (EI, 70 eV) (m/z, %): 278
(MþꢁEt, 100), 263 (45), 237 (70), 119 (55), 92 (45), 79 (30), 65 (30),
51 (30), 39 (35). Anal. Calcd for C18H17N3O2: C, 70.34; H, 5.58; N,
13.67. Found: C, 70.25; H, 5.49; N, 13.60.
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4.3.12. 30-n-Butyl-10H-spiro[indoline-3,20-quinazoline]-2,40(30H)-
dione (4l)
Orange powder; mp 216–218 ꢀC dec; IR (KBr) (nmax, cmꢁ1): 3260
(NH), 1724 (C]O), 1685 (C]O), 1622; 1H NMR (300 MHz, DMSO-
d6): dH 0.64 (t, 3H, J¼7.2, CH3), 0.96–1.07 (m, 1H, CH2), 1.17–1.25 (m,
1H, CH2), 1.27–1.36 (m, 1H, CH2), 2.75–2.85 (m, 1H, CH2), 3.08–3.18
(m,1H, CH2), 6.60 (d,1H, J¼8.0, ArH), 6.70 (t,1H, J¼7.4, ArH), 6.91 (d,
1H, J¼7.7, ArH), 7.10 (t, 1H, J¼7.5, ArH), 7.22 (t, 1H, J¼7.8, ArH), 7.36–
7.41 (m, 1H, ArH, 1H, NH), 7.50 (d, 1H, J¼7.3, ArH), 7.62 (d, 1H, J¼7.6,
ArH), 10.55 (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6): dC 13.77,
19.96, 30.41, 43.00, 75.66, 111.06, 114.18, 115.01, 117.95, 122.88,
126.33, 127.55, 127.82, 131.77, 133.61, 142.63, 146.17, 163.82, 175.88;
MS (EI, 70 eV) (m/z, %): 292 (MþꢁEt, 100), 277 (30), 263 (25), 249
(55), 237 (85), 119 (55), 92 (35), 77 (25), 65 (25), 41 (25). Anal. Calcd
for C19H19N3O2: C, 71.01; H, 5.96; N, 13.08. Found: C, 70.92; H, 5.81;
N, 13.00.
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