On the reactivity of isoindolo[2,1-a]quinazoline-5-ones

Article abstract of DOI:10.1016/j.tet.2010.08.013

Base- and acid-catalyzed nucleophilic addition of 11H-isoindolo[2,1-a] quinazoline-5-one to aromatic aldehydes and maleimides was investigated. The aldol adducts and condensation products were obtained stereoselectively. Main diastereomers of the Michael adducts were isolated in 74-89% yield, and converted by N-methylation to new stable α-substituted isoindole derivatives, for which 6-methylisoindolo[2,1-a]]quinazoline-5-one stands as the unsubstituted reference. The stability of the latter was monitored in moist aerated CDCl₃ solution, and one of the oxidative hydrolysis product was characterized by X-ray diffraction analysis as the corresponding N-arylphthalimide. The reactivity of the unsubstituted 6-methylisoindolo[2,1-a]] quinazoline-5-one was also investigated with acetylenic Michael acceptors. Fully conjugated isoindole derivatives possessing an original pull-push-pull structure were obtained. The conformations and molecular orbitals of the dibenzoylacetylene adduct were studied at the DFT level of theory. Its static quadratic hyperpolarizabilty β₀ was also calculated at the ZINDO level.

Full text of DOI:10.1016/j.tet.2010.08.013

Tetrahedron 66 (2010) 8214e8222
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
On the reactivity of isoindolo[2,1-a]quinazoline-5-onesq
,
a
a
a,b,c,d
Zoia V. Voitenko a , Oleksandr I. Halaev , Volodymyr P. Samoylenko , Sergey V. Kolotilov
,
*
,
,
,d,
*
Christine Lepetit c d, Bruno Donnadieu c d, Remi Chauvin c
a Kiev National Taras Shevchenko University, 60 Volodymyrska St, 01033 Kiev, Ukraine
b L.V.Pisarzhevskii Institute of Physical Chemistry of NAS, pr. Nauki 31, Kiev, Ukraine
c CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse, France
d Université de Toulouse, UPS, INPT, LCC, F-31077 Toulouse, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 June 2010
Received in revised form 29 July 2010
Accepted 5 August 2010
Available online 12 August 2010
Base- and acid-catalyzed nucleophilic addition of 11H-isoindolo[2,1-a]quinazoline-5-one to aromatic
aldehydes and maleimides was investigated. The aldol adducts and condensation products were ob-
tained stereoselectively. Main diastereomers of the Michael adducts were isolated in 74e89% yield, and
converted by N-methylation to new stable
a-substituted isoindole derivatives, for which 6-methyl-
isoindolo[2,1-a]]quinazoline-5-one stands as the unsubstituted reference. The stability of the latter was
monitored in moist aerated CDCl3 solution, and one of the oxidative hydrolysis product was character-
ized by X-ray diffraction analysis as the corresponding N-arylphthalimide. The reactivity of the un-
substituted 6-methylisoindolo[2,1-a]]quinazoline-5-one was also investigated with acetylenic Michael
acceptors. Fully conjugated isoindole derivatives possessing an original pullepushepull structure were
obtained. The conformations and molecular orbitals of the dibenzoylacetylene adduct were studied at
the DFT level of theory. Its static quadratic hyperpolarizabilty b0 was also calculated at the ZINDO level.
Ó 2010 Published by Elsevier Ltd.
Keywords:
Acceptoredonoreacceptor chromophores
Aldol condensation
Aromatic aldehydes
Dibenzoylacetylene
Isoindoles
Isoindolo[2,1-a]quinazolines
Maleimides
Michael addition
Quadratic hyperpolarizability
1. Introduction
N-substitution and exocyclic conjugation at C-1 with a more
acidic NeH tautomeric source allows for a relative stabilization of
The influence of aromaticity on tautomeric equilibria1 is well
illustrated by the isoindole case where the bicyclic o-quinodi-
methane motif is stabilized with respect to the unicyclic iso-
indolenine tautomeric form by the topological aromaticity
the isoindolenine form. The isoindole form is however not sup-
pressed provided that its 10- -electron system is part of a more
extended -system. This is exemplified with the 20- -electron
p
p
p
tetracycle 1, exhibiting an equilibrium between the isoindolenine
(quantified by topological resonance energy, TRE) of both the 6-
p
form 1a and the isoindole form 1b (Scheme 2). Assuming a CþeOꢀ
electron rings and the 10-
p
electron peripheral macrocycle (TRE
polarization of the amide carbonyl group, 1b contains a 18-p
(isoindole)¼0.323>TRE(isoindolenine)¼0.233) (Scheme 1).2
electron peripheral macrocycle,3 but its reactivity is similar to that
of other 1,2-disubstituted isoindoles.4,5 In the presence of maleic
imides, 11H-isoindolo[2,1-a]quinazoline-5-one 1 is indeed capable
to generate new rearrangement products,6 or give classical Mi-
chael: DielseAlder adducts in a 1:2 ratio.7 In the presence of other
substrates possessing activated double or triple bonds, 1 reacts in
a different manner, which has not been reported before.
N
H
N
H
H
H
isoindole (TRE = 0.323)
isoindolenine (TRE = 0.233)
Derivatives of 11H-isoindolo[2,1-a]quinazoline-5-one 1 exhibit
Scheme 1. Isoindole/insoindolenine tautomeric equilibrium and corresponding topo-
biological activities,8 which were shown to strongly depend on the
logical resonance energy values (in units of a uniform resonance integral
adjacent pz orbitals).2
b between
nature of the a
-substituent at the imidazo[2,1-a]isoindole core.8,9
Several reports have dealt with electrophilic functionalization of
annelated isoindoles with an activated methylene group.9 The
acidic character of the benzylic methylene group of the imido main
form 1a of 1 is illustrated by the tautomerism with the amido form
q
Investigations performed within the framework of the GDRI ‘Groupement
Franco-Ukrainien en Chimie Moleculaire’.
* Corresponding authors. Fax: þ33 5 61 55 30 03; e-mail addresses: z_voitenko@
mail.univ.kiev.ua (Z.V. Voitenko), chauvin@lcc-toulouse.fr (R. Chauvin).
0040-4020/$ e see front matter Ó 2010 Published by Elsevier Ltd.
doi:10.1016/j.tet.2010.08.013

Z.V. Voitenko et al. / Tetrahedron 66 (2010) 8214e8222
8215
O
The presence of the OH groups in 4aeb was checked by IR
OeH¼3300e3000 cmꢀ1) and by 1H NMR (deuterium exchange
O
H
(n
N
N
with D2O), and their structure was confirmed by other spectro-
scopic and elemental analyses. The isomeric purity of 4a and 4b
was suggested by TLC and checked by 1H NMR analysis (only traces
of a second diastereomer could be detected). The elimination
products were not obtained, likely because of the relative meso-
meric destabilization of the benzylic carbenium ion through the
influence of nitro substituent of 4a and 4b in para- and ortho-po-
sitions, respectively. Under prolonged reflux in acetic anhydride
however, the electron-rich p-dimethylaminobenzaldehyde 3c lead
to the condensation product 5c in 58% yield (E-isomer in Scheme 4).
The structure of 5c was established by elemental and spectro-
scopic analyses. Its isomeric purity was controlled by TLC and
checked by 1H NMR analysis (only traces of a second isomer could
be detected). Considering that the thermodynamic conditions used
(refluxing Ac2O, 6 h) should favor the formation of the most stable
isomer, it is reasonably assumed that 5c is formed in the less
strained (E)-configuration. The donor p-dimethylamino group
should indeed favor a E1 process by stabilizing the carbenium ion
resulting from the dissociation of the intermediate acetate 4c.
N
N
H
H
H
1a
1
1b
MeOTs base
O
Me
O
Me
N
N
N
N
H
H
2a
2
2b
Scheme 2. 11H-Isoindolo[2,1-a]quinazoline-5-one 1, its major and minor tautomeric
forms 1a and 1b, and its N-methyl derivative 2 described by mesomeric forms 2a and 2b.
1b (Scheme 2), which is similar to that observed for thieno
[30,20:5,6]pyrimido[2,1-a]isoindol-4-(10H)one.10 Both mesomeric
and tautomeric flexibility thus suggest that 1 behaves as an ambi-
dent nucleophile (Scheme 2). The N-nucleophilicity of 1 was
revealed in its reaction with a hard electrophile, i.e., methyl tosy-
late, locking the isoindole form 1b in the methyl derivative 2, which
can be described by the mesomeric forms 2a and 2b.11
1.3. Addition to Michael acceptors and subsequent deproto-
N-methylation
1.1. C-Nucleophilicity of 11H-isoindolo[2,1-a]quinazoline-5-one 1
Previous experiments showed that 1 could behave as an active
methylene reactant. On the other hand, maleimides are classical
dienophiles or Michael electrophiles, and many of their derivatives
possess useful biological properties.13 The reaction between both
kinds of compounds was thus naturally envisioned.
By analogy with a recently reported study in the thieno-fused
series,12 two kinds of quite soft C-electrophiles were first in-
vestigated, namely aromatic aldehydes and maleimides.
1.2. Addition and condensation with aromatic aldehydes
1.3.1. Michael addition to maleimides. Under base-catalyzed con-
ditions, reaction of maleimide 6aec with 1 afforded the thermo-
dynamic adduct 7aec in good yield (Scheme 5).
In order to shorten the reaction times, other conditions were
then attempted. In acetic acid (Scheme 4), maleimides 6aei affor-
ded mixtures of diastereomers of 7aei, from which a main di-
astereomer (out of two possible) could be isolated in 74e89% yield
(Scheme 6). Although the exact threo or threo configuration could
Condensation of 1 with aromatic aldehydes bearing electron-
withdrawing or -donating substituents was first considered. Stan-
dard base-catalyzed conditions lead to mixtures of products, which
were difficult to separate and identify. In acetic acidic medium
however, the electron-poor aldehydes 3a and 3b produced the aldol
products 4a and 4b in 73% and 76% yield, respectively (Scheme 3).
O
O
O
O
N
N
O
N
t
N
BuONa
O
H
[AcONa]
(0.07 equiv.)
N
+
Ar
N
N
R
+
AcOH, 90 °C, 2 h
N
N
pyridine
r. t., 30 days
O
R
O
OH
Ar
1
a : Ar = 4-NO2-C6H4
b : Ar = 2-NO2 -C6H4
N
3a-3b
4a: 73 %; 4b:76 %
1
6a : R = 4-Me-C6H4
6b : R = CH -Ph
6c: R = 4-OMe-C6H4
7a-c
(single diastereomers)
2
O
Scheme 3. Aldol reaction of 11H-isoindolo[2,1-a]quinazoline-5-one with nitro-
aromatic aldehydes in acetic acid medium, in the presence of a catalytic amount of
sodium acetate.
Scheme 5. Michael addition of 11H-isoindolo[2,1-a]quinazoline-5-one 1 to maleic
imides under strongly basic conditions.
O
N
O
O
N
N
N
1
Ac2O
N
+
N
reflux, 6 h
O
H
Me2N
OAc
Me2N
Me2N
3c
4c
5c: 58 %
Scheme 4. Aldol condensation of 11H-isoindolo[2,1-a]quinazoline-5-one 1 with an electron-rich aldehyde in acetic anhydride medium.

8216
Z.V. Voitenko et al. / Tetrahedron 66 (2010) 8214e8222
O
2 days before 2 became a minor component of the decomposition
O
N
O
mixture. Although most of the degradation products could not be
isolated, crystals of one of them deposited and could be character-
ized by X-ray diffraction analysis as the phthalimide derivative 10
resulting from hydrolysis of the amidine CeNC(O) bond and com-
plete oxidation of the C-11 carbon atom (Scheme 8, Fig.1). Although
theyield in 10 could notbe determined from the sample of the in situ
N
[AcONa]
rac-
N
N
R
+
N
AcOH
R1
Hc
O
90 °C, 2h
Hd
O
O
Hb
R1
N
R
1
6a-j
7a-j
NMR monitoring, the latter process is anyway not possible for a-
a : R = 4-Me-C6H4, R1 = Ha: 85 %
f: R = 2,5-Me2 -C6H4 , R1 = Ha: 79 %
g: R = Ph, R1 = Ha: 74 %
b : R = CH -Ph, R1 = Ha : 75 %
substituted isoindoles 9a and 9j, which are therefore expected to be
more stable than 2 with this respect. It must be mentioned that
several examples of pyrrole ring oxidation to isoindolo[2,1-a]qui-
nazoline-5,11-diones under acidic conditions have been reported,
and that isoindolo[2,1-a]quinazoline-5,11-diones give phtalimi-
dines under basic conditions, and give products with two rings
opened after a prolonged treatment.17e19
2
c: R = 4-OMe-C6H4, R1 = Ha
:
82 %
89 %
h: R = 2-Br-C6 H4, R1 = Ha
:
83 %
i: R = 2-NO2-C6H4, R1 = Ha: 85 %
j: R = Ph, R1 = Me: major isomer: 80 % ; minor isomer: 11 %
d: R = 4-n-C6H1 3-C6 H4, R1 = Ha
e: R = Me, R1 = Ha: 81 %
:
Scheme 6. Michael addition of 11H-isoindolo[2,1-a]quinazoline-5-one to maleimide
derivatives under acidic conditions. Yields are given for the main diastereomers.
not be assigned, it might be the same for the adducts 7aei dis-
playing almost isochronous 1Hd resonances in the range
3
6.05e6.21 ppm (in DMSO-d6) and small JHcHd coupling constants
Me
(in the range 0e4 Hz for 7aee and 7gei).14 In the case of the
3-methylmaleimide substrate 6j, two diastereomers of the adduct
7j (out of four possible) could be isolated in 80% and 11% yield,
respectively. The relative stereochemistry could not be assigned,
but it is noteworthy that for both the isomers, the 1Hd resonances
(6.21 ppm and 6.09 ppm) and 3JHcHd coupling constants (2.9 Hz and
<1 Hz) are in the same range as for the non-substituted repre-
sentatives 7aei.15
O
Me
O
HN
O
N
CDCl3
N
+ unidentified products
N
air and
moisture
O
H
> 2 days
10
2
Scheme 8. Oxidative hydrolysis of the 6-methylisoindolo[2,1-a]quinazoline-5-one 2
(unsubstituted at C-11) to phthalimide 10 (Fig. 1).
The proposed structures 7aej were otherwise confirmed by
elemental analysis and 1H and 13C NMR spectroscopy. Additional
evidence for structure 7b was provided by its 1He1H COSY
spectrum.
1.3.2. N-Methylation of Michael adducts to
a-substituted iso-
indoles. Alkylation of 1 by maleimides takes place at the C-11 po-
sition exclusively (no N-alkylation was observed). The resulting
steric hindrance of the C-11 center in 7 rules out the possibility of
a second C-alkylation, while the soft character of the maleimide
electrophile disfavors N-alkylation. Nevertheless the possibility of
a second alkylation was investigated using a hard and small elec-
trophile, such as methyl tosylate. The Michael adducts 7a,b were
thus found to undergo N-methylation to 8a,b. The isoindoleninium
salt 8a was then readily deprotonated to the isoindole 9a, while the
Michael adduct 7j was directly N-methylated/deprotonated to the
isoindole 9j (without characterization of the intermediate salt 8j).
The original C-11 methylene center of 7 is no longer stereogenic in
9, and pure diastereomers of 9a and 9j were isolated in 79% and 98%
yield, respectively (Scheme 7).
Although the behavior of the isoindole framework under oxida-
tive treatment can be remarkably selective,16 it is noteworthy that
the isoindoles 2 (Scheme 2) and 9 are quite stable in the solid state
and in the air with respect to possible polymerization or oxidative
degradation. The stability of the parent isoindole 2 in moist non-
deaerated CDCl3 solution was thus monitored at r. t by 1H NMR. New
unidentified signals started to appear after 6 h, but it took more than
Figure 1. ORTEP view of the X-ray crystal structure of phthalimide 10 (Scheme 8), with
50% probability displacement ellipsoids for non-hydrogen atoms (R1¼4.26%). Selected
ꢀ
bond lengths in A: N(1)eC(8)¼1.397(3); N(1)eC(1)¼1.398(3); N(1)eC(9)¼1.424(3); O
(1)eC(1)¼1.215(3); O(2)eC(8)¼1.207(3); C(1)eC(2)¼1.469(4); C(7)eC(8)¼1.477(4); N
(2)eC(15)¼1.335(3); C(10)eC(15)¼1.487(4); O(3)eC(15)¼1.227(3). Selected bond an-
gles in degrees: C(1)eN(1)eC(9)¼124.4(2); C(8)eN(1)eC(9)¼124.6(2); C(1)eN(1)eC
(9)¼124.4(2); O(1)eC(1)eN(1)¼124.0(2); O(1)eC(1)eC(2)¼129.7(2); N(1)eC(1)eC
(2)¼106.3(2); O(2)eC(8)eN(1)¼124.0(2); O(2)eC(8)eC(7)¼129.9(2); N(1)eC(8)eC
(7)¼106.1(2).
Me
O
Me
O
O
N
N
N
K2CO3
or
TsO
MeOTs
(3 equiv.)
NH4OH
N
N
N
H2O
²
130 °C
6h
H
H
O
O
O
R1
R1
R1
N
N
N
R
R
R
O
O
O
7a, 7b, 7j
8a: 82 %; 88b: 74 %; [8j]
9a: 79 %; 9j: 98 %
j: R = Ph, R1 = Me
a : R = 4-Me-C6H4 , R1 = H
b : R = CH -Ph, R1 = H
2
Scheme 7. N-Methylation/deprotonation of maleimide adducts of 11H-isoindolo[2,1-a]quinazoline-5-one to the corresponding isoindoles.

Z.V. Voitenko et al. / Tetrahedron 66 (2010) 8214e8222
8217
1.4. C-nucleophilicity of 6-methylisoindolo[2,1-a]
quinazoline-5-one 2
indole analogues.26 The calculated structure of the most stable con-
former exhibits a cisoid/cisoid conformation of the O]CeC]CeC]O
side chain (Fig. 3), but the cisoid/transoid and transoid/transoid confor-
mations are found only 1.9 and 3.0 kcal/mol higher in energy, re-
spectively. A mixture of these conformers is therefore expected in the
experimental product. The isoindole core of 14b is planar, but the qui-
nazoline moiety is slightly distorted in order to minimize van der Waals
repulsion between O-1 and H-1 while preserving residual p-conjuga-
tion between the isoindole system and the the C]O-2 bond (Fig. 3).
The near-frontier orbitals of 14b (Fig. 4) highlight the donor ability
As shown in Section 1, the ‘masked isoindole’ 1 reacts as a C-
nucleophile with activated electrophiles, such as nitro-aromatic
aldehydes and maleimides to give primary adducts 4 or 7, which
may then undergo N-methylation (Scheme 7). Reverting the C-al-
kylation/N-methylation sequence,11 the ‘locked isoindole’ 2 was
found to react as a C-nucleophile with dimethyl acetylenedi-
carboxylate 11 (DMAD) to give the Michael adduct 12 in 62% yield
(Scheme 9), instead of the possibly competing DielseAlder cyclo-
adduct.20 The structure of 12 was assigned to the (E)-configuration
by a 2D NMR NOESY experiment (Fig. 2).
of the isoindole core (HOMO), and the acceptor ability of both the a-
ene-dione side chain (LUMO) and the quinazoline-5-one moiety
(LUMOþ1).
Me
N
O
Me
N
O
CO2Me
N
+
N
EtOH
reflux, 10 min
CO2Me
CO2 Me
MeO2C
62 %
12
11
2
Scheme 9. Reaction of 6-methylisoindolo[2,1-a]quinazoline-5-one with
a strongly
activated acetylenic electrophile.
Figure 3. Front and side views of the most stable conformer of 14b calculated at the
B3LYP/6-31G** level. On the left view, torsion angles are given in degrees.
4.12
CH3
O
N
7.93
7.17
8.47
7.47
7.68
6.93
7.09
N
7.87
CO2CH3
3.43
H3 CO2C
3.63
7.09
Figure 2. Chemical shifts and NOESY correlations (400 MHz, CDCl3) of the E adduct 12
(Scheme 9).
Otheracetylenic Michaelacceptors were theninvestigated. Reaction
of 2 with methyl propiolate 13a thus afforded the isoindoloacrylate 14a
in 68% yield as a 1:1 mixture of E and Z isomers (Scheme 10).
Me
O
O
Me
N
N
E
R
N
+
N
MeOH
r. t., 30 min
H
R
H
E
2
13a: R = H, E = CO2Me……………………14a: 85 % (E isomer)
13b: R = E = C(O)Ph…….….……………..14b: 93 % (mixture of Z andE isomers)
Scheme 10. Reaction of 6-methylisoindolo[2,1-a]quinazoline-5-one with acetylenic
Michael acceptors.
Beyond monocarbonylacetylenes,21 dibenzoylacetylene 13b is
a diketonic alternative tothe diester 11,22 which has beenwidely used as
a C4 synthon for making the edges of N-oxy-[N]pericyclynes (N¼5, 6).23
Reaction of 13b with 2afforded the Michael adduct 14b in 93% yield and
90:10 E/Z stereoselectively (according to 1H NMR). The iso-
indolylenedione 14b was also tested as Michael acceptor in the pres-
ence of a second equivalent of 2, but no further reaction was observed.
The chromophores 14a and 14b exhibit an extended ‘accept-
oredonoreacceptor’ conjugation path, which might induce particular
optical properties, such as two-photon absorption ability.24 The struc-
ture of (E)-14b was investigated in detail. In the absence of suitable
X-ray diffraction data, the gas phase geometry of 14b was calculated at
the B3LYP/6-31G
*
level of theory.25 This level of calculation indeed
Figure 4. Frontier and near-frontier orbitals of the most stable conformer of 14b cal-
proved to be suitable for the structural and electronic description of
culated at the B3LYP/6-31G** level.

8218
Z.V. Voitenko et al. / Tetrahedron 66 (2010) 8214e8222
Efficient pushepull nonlinear optical chromophores containing
out, washed with small quantities of acetic acid and diethylether,
and then dried in the air. Product 4a was obtained as a white fine-
grained substance (3.0 g, 73%).
indole cores have been reported recently.27 Indole nuclei may are
also encountered as side groups in chromophoric polymers.28 In the
isoindole series, the gas phase static quadratic hyperpolarizability b0
of the various conformers of 14b has been calculated using the sum-
over-states method implemented in ZINDO.29 The highest value is
obtained for the most stable cisoid/cisoid conformer (Fig. 3), but it
remains however quite low: b0¼14.2 10e30 esu units.
Mp>300C. IR (KBr),
n
: 3300e3000 (OeH), 1645 (C]O), 1600
: 5.82 (1H,
s, OH), 6.10 (1H, dd, JHcOH¼5.9 Hz, Hc), 6.31 (1H, d, JHcHd¼2.9 Hz,
(C/N),1535 (NO2 as.),1350 (NO2, s). 1H NMR (DMSO-d6),
d
3
3
3
3
Hd), 6.35 (1H,d, JH1H2¼6.8 Hz, H1), 7.40 (1H, dd, JH3H2¼7.8 Hz,
3JH3H4¼7.8 Hz, H3), 7.52 (1H, dd, JH7H8¼7.8 Hz, JH8H9¼6.8 Hz, H8),
3
3
3
3
7.56 (1H, dd, JH9H8¼6.8 Hz, 3JH9H10¼7.8 Hz, H9), 7.85 (2H, d, JH-o,H-
¼8.8 Hz, H20, H60), 7.88 (1H, dd, 3JH2H3¼7.8 Hz, 3JH1H2¼6.8 Hz, H2),
m
2. Summary and conclusion
7.99 (1H, d, 3JH9H10¼7.8 Hz, H10), 8.13 (1H, d, 3JH7H8¼7.8 Hz, H7), 8.20
3
3
(1H, d, JH4H3¼7.8 Hz, H4), 8.29 (2H, d, JH-o,H-m¼8.8 Hz, H30, H50).
The nucleophilic reactivity and selectivity of isoindolo[2,1-a]-
quinazoline-5-ones 1 and 2 have been illustrated towards three
kinds of substrates: nitro-aromatic aldehydes, maleimide de-
rivatives, and acetylenic Michael acceptors. The main results can be
summarized as follows.
Elemental analysis (C22H15N3O4), found: % N 9.91 (calcd: % N 10.9).
3.1.3. 11-Hydroxy(2-nitrophenyl)methyl-5,11-dihydroisoindolo[2,1-a]-
quinazolin-5-one (4b). In a round-bottom flask (50 ml) equipped
with a backflow condenser, 11H-isoindolo[2,1-a]quinazoline-5-one
1 (3.2 g, 0.0134 mol.), o-nitrobenzaldehyde 3b (2.02 g, 0.0134 mol.)
and a catalytic amount of sodium acetate were dissolved in ice
acetic acid (15 mL). The mixture was heated at 90 ꢁC for 2 h. The
mixture slowly turned to light yellow. The precipitate was filtered
out, washed with small quantities of acetic acid and diethylether,
and then dried in the air. Product 4b was obtained as a white fine-
grained substance (3.9 g, 76%).
(i) Condensation of 11H-isoindolo[2,1-a]quinazoline-5-one with
aromatic aldehydes takes place readily in acidic medium.
Elimination products of aldol adduct were obtained
stereoselectively.
(ii) Stereoselective Michael addition of 11H-isoindolo[2,1-a]qui-
nazoline-5-one to ethylenic or acetylenic
a,b-unsaturated
amides, esters, and ketones takes place under either base- or
acid-catalyzed conditions.
Mp¼290e293 ꢁC. IR (KBr),
n: 3500e3300 (OeH), 3300e3000
(OeH), 1650 (C]O), 1600 (C/N), 1530 (NO2 as.), 1345 (NO2 s.). 1H
(iii) New stable a-substituted isoindoles were obtained from the
NMR (DMSO-d6), d: 6.02e6.18 (3H, m, Hc,Hd,H1), 6.32 (1H, br s,
Michael adducts.
OH), 7.33 (1H, dd, 3JH3H4¼7.8, Hz, 3JH3H2¼6.8 Hz, H3), 7.42e7.58 (3H,
m, H2, H8, H9), 7.64e7.75 (2H, m, H40,H60), 7.88 (1H, dd,
These results pave the way to further studies of chemical re-
activity, biological activity, and optical properties (in particular for
fully conjugated chromophores 5c, 14a, 14b). With the aim of pre-
paring symmetrically bridged bisisoindoles from 1 and 2, general-
ization of these results to dielectrophiles is the next challenge.
3
3
3
0
0
0
0
3
0
JH5 H4 ¼7.8 Hz, JH5 H6 ¼6.8 Hz, H5 ), 7.99 (1H, d, JH9H10¼7.8 Hz,
3
H10), 8.03 (1H, d, JH7H8¼7.8 Hz, H7), 8.20 (1H, d, JH4H3¼7.8 Hz,
3
H4), 8.25 (1H, d, JH3 ,H4 ¼7.8 Hz, H30). Elemental analysis
0
0
(C22H15N3O4), found: %N 11.34 (calcd: % N 10.9).
3.1.4. 11-[(E)-1-(4-Dimethylaminophenyl)methylidene]-5,11-dihy-
droisoindolo[2,1-a]quinazolin-5-one (5c). In a round-bottom flask
(50 ml) equipped with a backflow condenser, 11H-isoindolo[2,1-a]
quinazoline-5-one 1 (3.3 g, 0.014 mol) and p-N,N-dimethylamino-
benzaldehyde (2.08 g, 0.014 mol) were dissolved in acetic anhy-
dride (10 mL). This mixture is heated at reflux for 6 h. The reacting
mixture became insensibly deep red. The sediment was filtered and
washed out with small amounts of acetic acid, and then dried in the
Fisher’s pistol. The product was separated from the mixture by
column chromatography on silica gel. The elution was carried out
with a mixture of MeOH and CHCl3 in a 1:16 ratio. The product 5c
was obtained as a white fine-grained substance (3.12 g, 58%).
3. Experimental
3.1. General
1H NMR and 13C NMR spectra were recorded on Bruker-200,
Bruker-250 or Varian-400 instruments in specified deuterated sol-
vents. NMR chemical shifts
values to high frequency relative to the tetramethylsilane reference;
coupling constants J are in hertz. IR spectra were recorded on a Pye
Unicam SP3-300 spectrometer in CHCl3 solution or in KBr pellets. IR
d are in parts per million, with positive
absorptions frequencies
n
are given in cmꢀ1. UV spectra were
recorded on a Specord UVevis instrument. UVevis absorption wave
lengths are given in nanometer. The mass spectra were recorded on
a Nermag R10 spectrometer. The melting temperatures were de-
termined on a Boetius instrument Monitoring of the reaction and
checking of the purity of the obtained substances were achieved
with the help of thin-layer cromatography (Silufol UV-254).
Mp¼255e258 ꢁC. 1H NMR (CDCl3),
d: 3.09 (6H, s, N(CH3)2), 6.81
(2H, d, 3JHoeHm¼8.8 Hz, H30, H50), 7.39e7.52 (5H, m, H8, H9, H3, H20,
H60), 7.65 (1H, s, Holefin), 7.73 (1H, dd, 3JH1eH2¼8.0 Hz, 3JH2eH3¼7.2 Hz,
3
3
H2), 7.82 (1H, d, JH9eH10¼7,6 Hz, H10), 8.10 (1H, d, JH7eH8¼8.8 Hz,
H7), 8,22 (1H, d, 3JH4eH3¼7.6 Hz, H4), 8,47 (1H, d, 3JH1eH2¼8.0 Hz, H1).
Elemental analysis (C24H19N3O), found: % N 9.48 (calcd: % N 10.96).
3.1.1. 11H-Isoindolo[2,1-a]quinazoline-5-one (1). It was obtained
following the described procedure.11,30 Mp¼320e323 ꢁC. IR (KBr),
3.1.5. 1-(4-Methylphenyl)-3-(5-oxo-5,11-dihydroisoindolo[2,1-a]qui-
nazolin-11-yl)-pyrrolidin-2,5-dione (7a) under acidic conditions. In
a round-bottom flask (50 ml) equipped with a backflow condenser,
11H-isoindolo[2,1-a]quinazoline-5-one 1 (5.1 g, 0.022 mol) and p-N-
methylphenylmaleimide (4.08 g, 0.022 mol) and catalytic amount of
sodium acetate were dissolved in ice acetic acid (30 mL). The mixture
was heated at reflux for 2 h, while it became insensibly light yellow.
The precipitate was filtered and washed out with small amounts of
acetic acid, then with diethylether, and then dried in the air. Product
7a was obtained as a white fine-grained substance (7.8 g, 85%).
n
: 1645 (C]O), 1600 (C/N). 1H NMR (100 MHz, DMSO-d6),
d: 5.46
(2H,s, NeCH2), 7.42e8.22 (8H, m, aromatic CH). Elemental analysis
(C15H10N2O), found: % N 11.79 (calcd: % N 11.96).
3.1.2. 11-Hydroxy(4-nitrophenyl)methyl-5,11-dihydroisoindolo[2,1-a]-
quinazolin-5-one (4a). In a round-bottom flask equipped with
a backflow condenser, 11H-isoindolo[2,1-a]quinazoline-5-one 1
(2.5 g, 0.0107 mol.), p-nitrobenzaldehyde 3a (1.62 g, 0.0107 mol.)
and a catalytic amount of sodium acetate were dissolved in ice
acetic acid (15 mL). The mixture was heated for 2 h at 90 ꢁC. The
mixture slowly turned to light yellow. The precipitate was filtered
Mp¼275e277 ꢁC. IR (KBr),
n: 1765 and 1690 (C(O)NC(O)), 1660
(C]O), 1595 (C]N). 1H NMR (DMSO-d6),
d: 1.76 (1H, d,
3
2JHaHb¼18.1 Hz, Hb), 2.40 (3H, s, CH3), 2.68 (1H, dd, JHaHc¼9.3 Hz,

Z.V. Voitenko et al. / Tetrahedron 66 (2010) 8214e8222
8219
3
3
Ha), 4.77 (1H, m, 3JHbHc¼4.4 Hz, Hc), 6.12 (1H, d, 3JHcHd¼2.9 Hz, Hd),
(4H, m.), 8.17 (1H, d, JHH¼7.6 Hz), 8.28 (1H, d, JHH¼7.6 Hz). Ele-
3
7.10 (2H, d, JHeoH-m¼7.8 Hz, Ho-tolyl), 7.29 (2H, d, Hm-tolyl), 7.45
mental analysis (C19H17N3O3), found: % N 10.28 (calcd: % N 10.31).
(1H, d, 3JH1H2¼7.8 Hz, H1), 7.56 (1H, t, 3JH2H3¼7.8 Hz, H3), 7.66e7.83
(3H, m, H7, H8, H9), 7.86 (1H, t, H2), 8.17 (1H, t, 3JH9H10¼7.8 Hz, H10),
3.1.12. 1-(2-Bromophenyl)-3-(5-oxo-5,11-dihydroisoindolo[2,1-a]-
quinazolin-11-yl)-pyrrolidin-2,5-dione (7h). Yield 83%. Mp >300 ꢁC.
3
8.26 (1H, d, JH3H4¼7.8 Hz, H4). Elemental analysis (C26H19N3O3),
found: % N 9.78 (calcd: % N 9.97).
1H NMR (DMSO-d6),
d
: 1.80 (1H, s), 2.59 (1H, dd), 5.00 (1H, s), 6.21
3
3
Similar procedures were used for the synthesis of the following
products 7bej.
(1H, d, JHH¼4 Hz), 7.43e7.85 (10H, m.), 8.15 (1H, d, JHH¼8.4 Hz),
8.27 (1H, d, 3JHH¼8 Hz). Elemental analysis (C25H16N3O3Br), found:
%N 8.69 (calcd: % 8.64), found: % Br 16.41 (calcd: % Br 16.45).
3.1.6. 1-Benzyl-3-(5-oxo-5,11-dihydroisoindolo[2,1-a]quinazolin-11-
yl)-pyrrolidin-2,5-dione (7b). Yield 75%. Mp¼245e247 ꢁC. IR (KBr),
3.1.13. 1-(4-Nitrophenyl)-3-(5-oxo-5,11-dihydroisoindolo[2,1-a]qui-
n
: 1770 and 1690 (C(O)NC(O)), 1665 (C]O), 1600 (C]N). 1H NMR
nazolin-11-yl)-pyrrolidin-2,5-dione (7i). Yield 85%. Mp >300 ꢁC. 1H
(CDCl3, CD3CN),
d
: 1.43 (1H, dd, 2JHaHb¼18.4 Hz, 3JHbHc¼4.9 Hz, Hb),
NMR (DMSO-d6), d: 1.75 (1H, s), 2.74 (1H, dd), 4.85 (1H, dd), 6.14 (1H, d),
3
3
3
2.26 (1H, dd, JHaHc¼9.3 Hz, Ha), 4.07 (1H, m, Hc), 4.57 (1H, d,
7.49 (1H, d, JHH¼7.2 Hz), 7.55 (1H, dd, JHH¼8.0, 6.8 Hz), 7.61 (2H, d,
3JHH¼9.2 Hz), 7.70e7.79 (3H, m.), 7.85 (1H, dd, 3JHH¼8.0 , 6.8 Hz), 8.17
(1H, d, 3JHH¼7.6 Hz),8.27(1H,d,3JHH¼8.0 Hz), 8.36(2H, d, 3JHH¼8.8 Hz).
Elemental analysis (C18H16N4O5), found: % N 12.46 (calcd: % N 12.38).
2JHeHf¼14 Hz, CHeHf), 4.69 (1H, d, CHeHf), 6.05 (1H, d,
3JHcHd¼3.8 Hz, Hd), 6.68 (1H, d, JH10H9¼7.7 Hz, H10), 7.10 (1H, dd,
3
3JH2H3¼7.7 Hz, 3JH3H4¼7.6 Hz, H3), 7.27e7.37 (5H, m, Ph), 7.40e7.50
3
3
(3H, m, Harom), 7.75 (1H, dd, JH1H2¼6.4 Hz, JH3H2¼7.7 Hz, H2),
3
3
8.10 (1H, d, JH7H8¼7.7 Hz, H7), 8.32 (1H, d, JH3H4¼7.6 Hz, H4). 13
C
3.1.14. 3-Methyl-4-(5-oxo-5,11-dihydroisoindolo[2,1-a]quinazolin-11-
yl)-1-phenyl-pyrrolidin-2,5-dione (7j, major isomer). In a round-bottom
flask (50 ml) equipped with a backflowcondenser,11H-isoindolo[2,1-
a]quinazoline-5-one 1 (2.5 g, 0.011 mol), N-phenylcitraconylimide
(2.0 g, 0.011 mol) and a catalytic amount of sodium acetate were
disolved in ice acetic acid (15 mL). The mixture was heated at reflux
for 2 h, while it became insensibly light yellow. The precipitate was
filtered and washed out with a small quantity of acetic acid, thenwith
diethylether, and then dried in the air. Product 7j was obtained as
a white fine-grained substance (3.6 g, 80%). Mp¼300e303 ꢁC. IR
NMR (CDCl3, CD3CN),
d: 28.0 (CH2C]O), 41.5 (CHC]O), 42.9
(NCH2), 61.7 (CHN), 114.2, 122.6, 124.8, 126.3, 128.4, 128.8 (two
signals), 129.4 (two signals), 129.7, 130.5, 133.6, 134.3 (HCarom),
116.6 (two signals), 135.2, 137.5, 138.9, 142.4 (Carom); 174.6, 175.8,
178.0 (C]O). Elemental analysis (C26H19N3O3), found: % N 10.14
(calcd: % N 9.97).
3.1.7. 1-(4-Methoxyaphenyl)-3-(5-oxo-5,11-dihydroisoindolo[2,1-a]-
quinazolin-11-yl)-pyrrolidin-2,5-dione (7c). Yield 82%. Mp>300 ꢁC.
2
1H NMR (DMSO-d6),
d
: 1.72 (1H, d, JHaHb¼18.0 Hz, Hb), 2.64 (1H,
(KBr),
NMR (DMSO-d6),
n
: 1775 and 1700 (C(O)NC(O)), 1670 (C]O), 1600 (C]N). 1H
3JHaHc¼8.8 Hz, Ha), 3.82 (3H, s, OCH3), 4.77 (1H, m, Hc), 6.11 (1H, d,
3JHcHd¼2.9 Hz, Hd), 6.99 (2H, d, 3JHeoH-m¼7.8 Hz, H30, H50), 7.13 (2H,
d
: 0.94 (3H, d,3JHbCH3¼6.8 Hz, CH3),1.93 (1H, m, Hb),
4.60 (1H, dd, 3JHbHc¼4.9 Hz, Hc), 6.21 (1H, d, 3JHcHd¼2.9 Hz, Hd), 7.27
3
d, H20, H60), 7.44 (1H, d, JH1H2¼7.8 Hz, H1), 7.55 (1H, dd,
(2H, d, 3JHeoH-m¼7.8 Hz, H20, H60), 7.40e7.59 (5H, m, H30, H40 H50, H1,
3JH7H8¼6.8 Hz, JH8H9¼7.8 Hz, H8), 7.67e7.80 (3H, m, H3, H9, H10),
H3), 7.68e7.82 (3H, m, H8, H9, H10), 7.86 (1H, dd, JH1H2¼7.8 Hz,
3
3
3
3
3
7.85 (1H, dd, JH1H2¼7.8 Hz, JH2H3¼7.8 Hz, H2), 8.16 (1H, d,
3JH2H3¼7.8 Hz, H2), 8.17 (1H, d, JH7,H8¼7.8 Hz, H7), 8.28 (1H, d,
3
3JH7H8¼6.8 Hz, H7), 8.26 (1H, d, JH3H4¼8.8 Hz, H4). Elemental
3JH3H4¼7.8 Hz, H4). Elemental analysis (C26H19N3O3), found: % N 8.94
analysis (C26H19N3O4), found: % N 10.1 (calcd: % N 9.6).
(calcd: % N 9.97).
3.1.8. 1-(4-Hexylphenyl)-3-(5-oxo-5,11-dihydroisoindolo[2,1-a]quina-
3.1.15. 3-Methyl-4-(5-oxo-5,11-dihydroisoindolo[2,1-a]quinazolin-
11-yl)-1-phenyl-pyrrolidin-2,5-dione (7j minor isomer). The mother
liquors of previous synthesis experiment were diluted by 10 mL of
water. The formed precipitate was filtered and washed out with small
amounts of acetic acid, thenwith diethylether, and then dried in the air.
The product 7j was obtained as a white fine-grained substance (0.5 g,
zolin-11-yl)-pyrrolidin-2,5-dione (7d). Yield 89%. Mp¼283e284 ꢁC.
1H NMR (DMSO-d6),
d: 0.93 (3H, s), 1.77e1.35 (9H, m, CH2), 2.61 (1H,
dd), 3.98 (2H, dd), 4.80 (1H, dd), 6.13 (1H, d, 3JHH¼5.6 Hz), 6.96 (2H,
d, 3JHH¼8.8 Hz), 7.12 (2H, d, 3JHH¼8.8 Hz), 7.45 (1H, d, 3J¼6.8 Hz), 7.54
3
3
(1H, dd, JHH¼7.6 Hz, JHH¼6.8 Hz), 7.86e7.69 (4H, m), 8.17 (1H, d,
3JHH¼7.2 Hz), 8.27 (1H, d, JHH¼8.0 Hz). Elemental analysis
11%). Mp¼274e276 ꢁC. 1H NMR (DMSO-d6),
d
: 1.04 (3H, d,3JHbCH3
¼
3
(C31H29N3O3), found: % N 8.61 (calcd: % N 8.55).
6.8 Hz, CH3), 2.65 (1H, m, Hb), 3.90 (1H, d, 3JHbHc¼5.9 Hz, Hc), 6.09 (1H,
3
s, Hd), 7.24 (2H, d, JHeoH-m¼7.8 Hz, H20, H60), 7.32e7.96 (9H, m,
3.1.9. 1-Methyl-3-(5-oxo-5,11-dihydroisoindolo[2,1-a]quinazolin-11-
Harom), 8.11 (1H, d, 3JH7H8¼7.8 Hz, H7), 8.24 (1H, d, 3JH3H4¼7.8 Hz, H4).
yl)-1-phenyl-pyrrolidin-2,5-dione (7e). Yield 81%. Mp¼265e266 ꢁC.
Elemental analysis (C26H19N3O3), found: % N 9.04 (calcd: % N 9.97).
2
1H NMR (DMSO-d6),
d
: 1.50 (1H, d, JHH¼13.6 Hz), 2.50 (1H), 2.94
3
Compounds 7aec and 7j were also synthesized by the method
using basic conditions (Scheme 5). All physical and spectral data for
compounds obtained by the two different methods were identical.
For example:
(3H, s), 4.66 (1H, s), 6.07 (1H, d, JHH¼3.6 Hz), 7.30 (1H, d,
3JHH¼4.4 Hz), 7.53 (1H, dd, 3JHH¼7.2 Hz, 3JHH¼7.1 Hz), 7.67 (2H, m),
3
3
3
7.75 (1H, d, JHH¼8.0 Hz), 7.83 (1H, dd, JHH¼7.2 Hz, JHH¼8.0 Hz),
3
3
8.15 (1H, d, JHH¼6.0 Hz), 8.25 (1H, d, JHH¼8.0 Hz). Elemental
analysis (C18H15N3O3), found: % N 12.81 (calcd: % N 12.70).
3.1.16. 1-(4-Methylphenyl)-3-(5-oxo-5,11-dihydroisoindolo[2,1-a]-
quinazolin-11-yl)-pyrrolidin-2,5-dione (7a) under basic conditions.
11H-Isoindolo[2,1-a]quinazoline-5-one 1 (3.3 g, 14 mmol), N-(4-
methylphenyl)maleimide (2.64 g, 14 mmol) and t-BuONa (0.1 g,
1.04 mmol) were mixed in dry pyridine (20 mL). The mixture was
stirred during 30 days at ambient temperature. The dark final
mixture was filtered to give 4.3 g of a colorless fine-crystalline
substance 7a. Spectroscopical data were identical to those of 7a
obtained from 1 using acidic conditions (see above).
3.1.10. 1-(2,5-Dimethylphenyl)-3-(5-oxo-5,11-dihydroisoindolo[2,1-
a]quinazolin-11-yl)-pyrrolidin-2,5-dione (7f). Yield 79%. Mp¼278e
279 ꢁC. 1H NMR (DMSO-d6),
d: 1.85 (1H, d), 2.08 (3H, s), 2.34 (3H, s),
4.84 (1H, d), 6.13 (1H, d, 3JHH¼13.2 Hz), 7.14e7.19 (2H, m), 7.50e7.85
(8H, m), 8.09e8.28 (2H, m), 8.64 (1H, dd). Elemental analysis
(C26H21N3O3), found: % N 9.71 (calcd: % N 9.65).
3.1.11. 3-(5-Oxo-5,11-dihydroisoindolo[2,1-a]quinazolin-11-yl)-1-
phenyl-pyrrolidin-2,5-dione (7g). Yield 74%. Mp >300 ꢁC. 1H NMR
2
3.1.17. 6-Methyl-11-[1-(4-methylphenyl)-2,5-dioxotetrahydro-1H-3-
pyrrolyl]-5-oxo-5,11-dihydroisoindolo[2,1-a]quinazolin-6-ium 4-methyl-
(DMSO-d6),
d
: 1.78 (1H, d, JHH¼18 Hz), 2.67 (1H, dd), 4.82 (1H, s),
6.14 (1H, s), 7.25 (2H, d, 3JHH¼7.2 Hz), 7.43e7.57 (5H, m.), 7.72e7.87

8220
Z.V. Voitenko et al. / Tetrahedron 66 (2010) 8214e8222
1-benzenesulfonate (8a). In a round-bottom flask (50 mL) were placed
4.0 g of 1-(4-methylphenyl)-3-(5-oxo-5,11-dihydroisoindolo[2,1-a]
quinazoline-11-yl)-pyrrolidin-2,5-dione 7a (0.00949 mol) and 5.3 g of
methyl tosylate (0.0285 mol). The mixture was thoroughly shuffled
and heated at 125e130 ꢁC over 6 h. The reacting mixture was fusing
and darkening, while the mass did not solidify. The mixture was fi-
nally quenched and rubbed over with diethylether until a spongiform
mass was formed. Product 8a was obtained as a white fine-grained
(10 mL) of ammonia under vigorous stirring. The resulting red pre-
cipitatewasfilteredandwashedwithsmallamountsofethanoltogive
9j asawhitefine-grainedsubstance(1.96 g,98%). Mp¼193e195 ꢁC.1H
NMR (CDCl3),
d
: 1.52 (3H, d, 3JHbCH3¼7.8 Hz, CeCH3), 3.33 (1H, m, Hb),
3
4.20 (3H, s, NCH3), 4.46 (1H, d, JHbHc¼6.8 Hz, Hc), 6.87 (1H, dd,
3
3
3JH3H4¼7.8 Hz, JH3H2¼8.8 Hz, H3), 7.10 (1H, dd, JH2H3¼8.8 Hz,
3JH2H1¼7.8 Hz, H2), 7.24 (1H, d, 3JH1H2¼7.8 Hz, H1), 7.38e7.45 (2H, m,
3
H9, H7), 7.49e7.59 (5H, m, C6H5), 7.76 (1H, dd, JH7H8¼7.8 Hz,
3
substance (4.7 g, 82%). Mp¼220e223 ꢁC. IR (KBr),
n: 1770 and 1695 (C
3JH8H9¼7.8 Hz, H8), 7.91 (1H, d, JH9H10¼8.8 Hz, H10), 8.42 (1H, d,
(O)NC(O)), 1740e1580 (C]O and C]N). 1H NMR (DMSO-d6),
d: 1.77
3JH3H4¼7.8 Hz, H4). Elemental analysis (C27H21N3O3), found: % N 9.71
2
(1H, d, JHaHb¼17.6 Hz, Ha), 2.34 (3H, s, CeCH3), 2.40 (3H, s, CeCH3),
(calcd: % N 9.65).
3
2.67 (1H, dd, JHbHc¼8.8 Hz, Hb), 4.53 (3H, s, NeCH3), 4.78 (1H, m,
3JHaHc¼3.9 Hz, Hc), 6.12 (1H, sh.s, Hd), 7.00e8.00 (14H, m, Harom), 8.18
(1H, d, 3JH9H10¼6.8 Hz, H10), 8.27 (1H, d, 3JH3H4¼7.8 Hz, H4). Elemental
analysis (C34H29N3O6S), found: % N 7.02 (calcd: % N 6.91).
3.1.21. (E)-2-(6-Methyl-5-oxo-5,6-dihydroisoindolo[2,1-a]quinazolin-
11-yl)-2-butendioate (12). Dimethyl acetylenedicarboxylate 11
(0.359 mL, 2.9 mmol) was added dropwise to a suspension of 6-
methyl-5,6-dihydroisoindolo[2,1-a]quinazoline-5-one
2
(0.725 g,
3.1.18. 11-(1-Benzyl-2,5-dioxotetrahydro-1H-3-pyrrolyl)-6-methyl-5-
oxo-5,11-dihydroisoindolo[2,1-a]quinazolin-6-ium 4-methyl-1-benze-
nesulfonate (8b). In a ground-bottom flask (50 mL) were placed 3.0 g
(0.00712 mol) of 1-benzyl-3-(5-oxo-5,11-dihydroisoindolo[2,1-a]
quinazoline-11-yl)-pyrrolidin-2,5-dione 7b and 4.0 g (0.0214 mol) of
methyl tosylate. The mixture was thoroughly shuffled and heated at
125e130 ꢁC over 3 h. The reacting mixture was fusing and solidified,
and was quenched and rubbed over with diethylether. Product 8b
was obtained as a white fine-grained substance (3.2 g, 74%).
2.9 mmol) in EtOH (20 mL). The dark red reaction mixture was then
refluxed for 10 min, and the formed solid was filtered out to give the E
isomer of isoindole 12 as red crystals (0.71 g, 62%). Mp¼192e194 ꢁC.
IR (KBr), n: 1715 (C]O, CO2Me), 1660 (C]O, C(O)N), 1250 (CeO, as),
1160 (CeO, s). UVevis (EtOH, c¼1.5 10e5 M),
l (log e): 230.5 (4.63),
252.0 (4.58), 297.5 (3.98), 404.5 (3.74), 507.5 (3.77). MS (DCI, NH3) m/z
(%): 408 (0.803, [MNH4]þ), 396 (0.665), 395 (3.034), 394 (5.629), 393
(26.081), 392 (28.410), 391 (100, MHþ), 390 (14.050), 389 (1.064), 335
(0.815), 334 (0.541), 333 (1.338), 332 (0.949), 331 (1.906), 330 (1.550),
Mp¼238e240 ꢁC. IR (KBr),
n
: 1765 and 1700 (C(O)NC(O)), 1680 (C]
272 (0.973), 249 (1.373), 110 (0.655). 1H NMR (400 MHz, CDCl3),
d:
O), 1600 (C]N). 1H NMR (DMSO-d6),
d
: 2.28 (3H, s, CeCH3), 3,30 (1H,
3.43 (3H, s, OCH3), 3.63 (3H, s, OCH3), 4.12 (3H, s, NCH3), 6.93 (1H, dd,
2
3
3
3
3
dd, JHaHb¼19.1 Hz, JHaHc¼9.6 Hz, Ha), 3.46 (1H, dd, JHbHc¼4.4 Hz,
Hb), 4.18 (3H, s, NeCH3), 4.10e4.20 (2H, m, CH2Ph), 4.56 (1H, m, Hc),
6.56 (1H, d, 3JHdHc¼1.7 Hz, Hd), 6.40e6.85 (15H, m, Harom), 8.48 (1H,
3JH8H7¼8.95 Hz, JH8H9¼6.39 Hz, H8), 7.09 (1H, dd, JH9H10¼8.81 Hz,
3
H9), 7.09 (1H, s), 7.17 (1H, d, H10), 7.47 (1H, dd, JH3H4¼7.92 Hz,
3JH3H2¼8.03 Hz, H3), 7.68 (1H, dd, JH1H2¼8.19 Hz, H2), 7.87 (1H, d,
3
d, JH7H8¼7.9 Hz, H7), 8.63 (1H, d, JH3H4¼7.8 Hz, H4). 13C NMR
H1), 7.93 (1H, d, H7), 8.47 (1H, d, JH4H2¼1.55 Hz, H4). 13C NMR
3
3
4
(DMSO-d6),
d: 20.7 (CeCH3), 30.9 (CH2eC]O), 32.5 (CHeC]O), 41.1
(CDCl3), d: 32.12 (NCH3), 52.15, 53.04 (OCH3), 97.70, 100.88, 109.56,
(NeCH3), 41.7 (NeCH2), 64.4 (NeCH); 117.0, 127.3, 134.9, 135.5, 137.5,
142.5, 157.7, 158.6 (Carom); 118.5, 123.6, 125.4 (2), 126.8 (2), 127.9 (2),
128.2 (2), 137.3, 135.9, 131.1, 129.6, 128.8, 128.5, 127.1(HCarom); 174.7
(C]O), 174.9 (C]O), 175.1 (C]O). MS (FAB, DMSO): 436 ([MꢀTsO]þ,
100%), 248 ([MꢀTsOꢀ{CHC(O)}2NCH2Ph]þ, 25%). Elemental analysis
(C34H29N3O6S), found: % N 7.12 (calcd: % N 6.91).
118.14, 127.71, 135.03 (CaromþColefin); 117.70, 118.33, 120.78, 121.28,
124.73, 125.49, 125.99, 129.60, 133.96 (HCaromþHColefin); 137.43
(NeC]N), 158.14 (C(O)N), 165.83, 166.86 (CO2Me). Elemental analysis
(C22H18N2O5), found: % N 7.33 (calcd: % N 7.18).
3.1.22. Methyl-3-(6-methyl-5-oxo-5,6-dihydroisoindolo[2,1-a]quina-
zolin-11-yl)-acrylate (14a). Methyl propiolate 13a (0.34 mL, 0.34 g,
4.03 mmol) was added at room temperature to a solution of 6-
methylisoindolo[2,1-a]]quinazoline-5-one 2 (1.00 g, 4.03 mmol.) in
methanol (5 mL). After stirring for 30 min, a red-orange precipitate
was filtered and dried under vacuum. Isoindole 14a was obtained as
a reddish solid (1.28 g, 96%). After heating in methanol, re-
crystallization afforded pure (thermodynamic) E-isomer (85%).
IR (mixture of isomers, CHCl3), 3621 (sharp), 3462 (br) (H2O),
3018, 2976 (sp2-CeH), 2926, 2896 (sp3-CeH), 1711 (OC]O), 1669,
1602 (C/N), 1546, 1486, 1446, 1389 (C]C), 1223, 1046. MS (DCI/
3.1.19. 3-(6-Methyl-5-oxo-5,6-dihydroisoindolo[2,1-a]quinazoline-11-
yl)-1-(4-methylphenyl)-2,5-pyrrolidinedione (9a). In a flask (50 ml),
4.0 g (0.00658 mol) of 6-methyl-11-[1-(4-methylphenyl)-2,5-dioxo-
tetrahydro-1H-3-pyrrolyl]-5-oxo-5,11-dihydroisoindolo[2,1-a]quina-
zoline-6-ium tosylate 8a was dissolved in hot water (20 mL). The
solution was added under vigorous stirring to a concentrated aque-
ous solution (20 mL) of potassium carbonate (1.5 g, 0.011 mol). The
resulting red precipitate was extracted with chloroform, and the
organic layer was separated and evaporated to dryness. The residue
was recrystallizated from dry chloroform to give 9a as a white fine-
grained substance (2.3 g, 79%). Mp¼182e183 ꢁC.
NH3): 433 (100%, [MH]þ). UVevis (CHCl3, c¼1.5 10e5 M),
l (absor-
bance): 299.0 (0.27), 309.8 (0.27), 372.6 (0.12), 562.4 (0.22). 1H NMR
MS (DCI, NH3) m/z: 469 ([Mþ2NH3]þ, 12%), 452 ([MþNH3]þ,
46.5%), 436 (MHþ, 100%), 249 ([MHꢀ{CHC(O)}2NC6H4CH3]þ, 8%). 1H
NMR (DMSO-d6),: 2.37 (3H, s, CeCH3), 3.01 (1H, dd, 2JHaHb¼17.2 Hz,
(E isomer, 250 MHz, CDCl3), d: 3.83 (3H, s, OCH3), 4.08 (3H, s, NCH3),
3
3
6.27 (1H, d, JHH¼15.4 Hz; MeO2CeCH), 7.02 (1H, dd, JHH¼7.7 Hz,
4JHH¼1.6 Hz), 7.24 (1H, pseudo t, JHH¼8.9 Hz), 7.55 (1H, pseudo
3
3
3
3
3JHaHc¼6.1 Hz, Ha), 3.29 (1H, dd, JHbHc¼9.3 Hz, Hb), 4.24 (3H, s,
t, JHH¼7.6 Hz), 7.79e7.85 (2H, m), 7.95 (1H, d, JHH¼8.8 Hz), 8.10
(1H, d, 3JHH¼8.5 Hz), 8.21 (1H, d, 3JHH¼15.4 Hz; MeO2CC]CH), 8.47
(1H, dd, 3JHH¼7.8, 1.1 Hz). Few 1H NMR data for the Z isomer could
be deduced from selective irradiations in the spectrum of the
NCH3), 5.30 (1H, dd, Hc), 6.86 (1H, dd, 3JH3H4¼8.8 Hz, 3JH3H2¼6.4 Hz,
3
3
H3), 7.10 (1H, dd, JH2H1¼9.1 Hz, H2), 7.28 (2H, d, JHeoH-m¼7.8 Hz,
Ho-tolyl), 7.36 (2H, d, Hm-tolyl), 7.66 (1H, d, H1), 7.77e7.90 (3H, m,
3
H7, H8, H9), 8.10 (1H, d, JH9H10¼8.7 Hz, H10), 8.31 (1H, d, H4). El-
mixture d: 3.63 (3H, s, OCH3), 4.11 (3H, s, NCH3), 5.97 (1H, d,
emental analysis (C27H21N3O3), found: % N 9.48 (calcd: % N 9.65).
3JHH¼11.5 Hz; MeO2CeCH), 7.32 (1H, d, 3JHH¼11 Hz; MeO2CC]CH),
other signals overlap with those of the E isomer. 13C NMR
3.1.20. 3-Methyl-4-(6-methyl-5-oxo-5,6-dihydroisoindolo[2,1-a]qui-
nazolin-11-yl)-1-phenyl-2,5-pyrrolidine (9j). In a flask (50 mL), 6-
methyl-11-[3-methyl-2,5-dioxo-1-phenyltetrahydro-1H-3-pyrrolyl]-
5-oxo-5,11-dihydroisoindolo[2,1-a]quinazoline-6-ium 4-methyl-1-
benzenesulfonate 8j (2.0 g, 0.00329 mol) was dissolved in hot water
(15 mL). The solution was added to a concentrated aqueous solution
(62.9 MHz, CDCl3), d: 32.0 (NCH3), 51.4 (OCH3), 109.3 (CH), 110.4,
111.3, 118.6, 118.9 (CH), 119.7 (CH), 120.9 (CH), 121.8 (CH), 126.3 (CH),
126.7 (CH), 127.9, 128.7, 129.4 (CH), 133.6 (CH), 134.2 (CH), 136.5,
157.9 (NC]O), 168.6 (OC]O) (CH assignments on the basis of rel-
ative intensities). Elemental analysis for 14a$2H2O (C20H20N2O3),
found: % C 68.6, % H 4.1, % N 8.06 (calcd: % C 68.2, % H 5.7, % N 7.95).

Z.V. Voitenko et al. / Tetrahedron 66 (2010) 8214e8222
8221
3.1.23. 1,4-Diphenyl-2-(6-methyl-5-oxo-5,6-dihydroisoindolo[2,1-a]
Acknowledgements
quinazolin-11-yl)-but-2-en-1,4-dione (14b). A solution of diben-
zoylacetylene 13b (0.94 g, 4.03 mmol) in methanol (4 mL) was
added at room temperature to a solution of 6-methylisoindolo[2,1-
a]]quinazoline-5-one 2 (1.00 g, 4.03 mmol) in methanol (5 mL). A
dark-blue precipitate formed immediately and was filtered out af-
ter 30 min, washed with methanol and dried under vacuum. Iso-
indole 14b was obtained as a purple solid consisting in a mixture of
Z and E isomers (1.81 g, 93%).
R.C., S.K. and C.L. thank the Centre National de la Recherche
Scientifique (CNRS) for providing working expedients and the Re-
search Associate fellowship of S.K. The authors also thank the Paul
Sabatier University for the support of the Kiev-Toulouse collabo-
ration, and CALMIP (Calcul intensif en Midi-Pyrénées, Toulouse,
France) for computing facilities.
IR (CHCl3), n
: 3621 (sharp), 3463 (br) (H2O), 3018, 2976 (sp2-CeH),
Supplementary data
2926, 2896 (sp3-CeH),1661 (br, C]O),1620,1602 (C/N),1500,14,861,
460, 1448, 1390 (C]C), 1238, 1046. MS (DCI/NH3): 483 (100%, [MH]þ).
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.08.013.
UVevis (CHCl3, c¼6.2 10e5 M),
l
(absorbance): 404.4 (0.30), 549.8
: 1.62 (broad, H2O), 4.10 (pseudo s,
(0.55). 1H NMR (250 MHz, CDCl3),
d
3H, NCH3), 6.95e7.01 (1H, pseudo dt), 7.07e7.11 (1H, pseudo dt), 7.25
(1H, pseudo s), 7.28e7.32 (2H, pseudo d), 7.36e7.39 (2H, pseudo d),
7.41e7.50 (4H, pseudo dd), 7.67e7.71 (1H, pseudo dt), 7.78e7.86 (4H,
pseudo t), 7.92e7.96 (1H, pseudo d), 8.36e8.40 (1H, pseudo dd),
8.44e8.47 (1H, d) (19 differentiated sp2-CH signals were found, as
References and notes
1. For recent examples, see: (a) Zubatyuk, R. I.; Shishkin, O. V.; Gorb, L.; Leszc-
zynski, J. J. Phys. Chem. A 2009, 113, 2943; (b) Klubaa, M.; Lipkowskib, P.;
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W. M. F.; Antonov, L.; Nedeltcheva, D.; Kamounah, F. S.; Taylor, P. J. J. Phys. Chem.
A 2004, 108, 7603.
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2010, 12, 5295; (b) Chauvin, R.; Lepetit, C.; Maraval, V.; Leroyer, L. Pure Appl.
Chem. 2010, 82, 769.
3. (a) Kreher, R. P.; Hildebrand, T. Angew. Chem., Int. Ed. Engl. 1987, 26, 1262; (b)
Balaban, A. T.; Oniciu, D.; Katritzky, A. R. Chem. Rev. 2004, 104, 2777.
4. Kovtuneko, V. A.; Voitenko, Z. V. Russ. Chem. Rev. (Translation of Usp. Khim.)
1994, 63, 1064 (Russian Edition).
expected for one of the isomers). 13C NMR (62.9 MHz, CDCl3),
d (major
signals): 32.3 (NCH3),119.2,119.9,121.5,121.6,122.4,127.0,128.0,129.5,
132.8, 133.1, 134.0 (11 CH signals of similar intensities, as expected for
one of the isomers),128.4,128.5,128.7,128.8 (4 (CH)2 signals of similar
intensities, as expected for one of the isomers), 159.5 (NC]O), 188.1
(PhC]O), 196.3 (PhC]O). Other minor signals (in particular at: 32.2,
111.5, 112.0, 132.0, 136.3, 136.9 and 145.5 ppm) were observed (but it
could not be determined whether they correspond to quaternary
carbons of the major isomer or to CH carbons of the minor one). Ele-
5. Kovtunenko, V. A.; Voitenko, Z. V.; Sheptun, V. L.; Savranskii, L. I.; Tyltin, A. K.;
Babichev, F. S. Ukr. Khim. Zh. (Russ. Ed.) 1985, 51, 976.
6. Voitenko, Z. V.; Samoylenko, V. P.; Kovtunenko, V. A.; Gurkevich, V. Y.; Tyltin, A.
K.; Shcherbakov, M. V.; Shishkin, O. V. Chem. Heterocycl. Compd. (Translation of
Khim. Geterotsikl. Soedin.) 1999, 35, 600.
mental analysis for 14b$0.6H2O (C32H23$2N2O3.6), found: %C 80.3, % H
4.11, % N 5.86 (calcd: % C 80.5, % H 4.87, % N 5.87).
7. Samoylenko, V. P.; Voitenko, Z. V.; Donnadieu, B.; Bonnet, J.-J. Tetrahedron 2002,
58, 610.
8. Babichev, F. S.; Kovtunenko, V. A. Chemistry of Isoindoles; Russian Edition: Kiev,
1983.
3.2. Crystallographic and structural parameters for 10 (Fig. 1)
9. Voitenko, Z. V.; Yegorova, T. V.; Kovtunenko, V. A. Chem. Heterocycl. Compd.
(Translation of Khim. Geterotsikl. Soedin.) 2002, 38, 1019 (Russian Edition).
10. Voitenko, Z. V.; Kysil, A. I.; Wolf, J. G. C. R. Chimie 2007, 10, 813.
11. Babichev, F. S.; Tyltin, A. K. Ukr. Khim. Zh. (Russ. Ed.) 1970, 36, 175.
12. Kysil, A. I.; Voitenko, Z. V.; Wolf, J.-G. Collect. Czech. Chem. Commun. 2008, 73, 247.
13. Patent. 2176242 RU C2 C07D 207/40,207/444,209/48, A 61 K 31/40, A 61 P 65/
00. Succinimide and maleinimide inhibitors of cytokines, pharmaceutical
composition on their basis and the methods of inhibition TNFa, Seldgin Cor-
poration (US) Request 04.10.96 Published 27.11.2001.
X-ray crystallographic structure determination. Data were col-
lected on a Stoe Imaging Plate Diffraction System (IPDS), equiped
with an Oxford Cryosystems Cryostream Cooler Device, and using
graphite-monochromated Mo Ka radiation. The final unit cell pa-
rameters were obtained by means of a least-squares refinement of
a set of well-measured reflections, and crystal decay was monitored
during data collection; no significant fluctuations in intensity were
observed The structures were solved by Direct Methods using the
program SIR92,31 and refined by least-squares procedures on F2
with SHELXL-97.32 All hydrogen atoms were located on a difference
Fourier map, but introduced and refined by using a riding model.
All non-hydrogen atoms were anisotropically refined.
3
14. For 7f bearing a very bulky o-xylyl N-substituent, the JHcHd coupling constant
is much higher (13.2 Hz) in comparison to 7aee, 7gei. It is however difficult to
determine whether this extreme value is due to a change in stereochemistry or
to a change in conformation (especially in the angle between the planes of the
isoindole and pyrrolidin-2,5-dione rings).
15. It remains however possible that both diastereomers of 7j may possess the
same cis configuration with respect to the pyrrolidin-1,5-dione ring, as sug-
3
gested by the similarity of the weak JHbHc coupling constants of 4.9 Hz and 5.
Crystal data and structure refinement.
9 Hz in the major and minor stereoisomers, respectively. In the non-substituted
3
series 7aei, the JHbHc values for the cis vicinal protons are indeed generally
Empirical formula
Formula weight
C16H12N2O3
280.28
3
close to 5 Hz, while the JHaHc values for the trans vicinal protons are close to
9 Hz.
Temperature
Wavelength
180(2) K
0.71073 A
16. See for example: (a) Claessens, S.; Jacobs, J.; Van Aeken, S.; Abbaspour Tehrani,
A.; De Kimpe, N. J. Org. Chem. 2008, 73, 7555; (b) Deblander, J.; Van Aeken, S.;
Jacobs, J.; De Kimpe, N.; Abbaspour Tehrani, A. Eur. J. Org. Chem. 2009, 4882.
17. Crippa, G. B.; Carracci, R. Gazz. Chim. Ital. 1938, 68, 109; (b) Suh, M. E. Yakhak
Hoechi. 1990, 34, 133.
18. (a) Pokholenko, A. A.; Voitenko, Z. V.; Kovtunenko, V. A. Russ. Chem. Rev. 2004,
73, 771; (b) Voitenko, Z. V.; Rudyuk, S. O.; Samoylenko, V. P.; Ryabov, S. V.;
Zubatyuk, R. I.; Shishkin, O. V. Dopov. Nats. Akad. Nauk Ukr. 2005, 8, 132.
ꢀ
Crystal system, space group
Unit cell dimensions
Orthorhombic, P b c a
ꢀ
ꢀ
a¼12.829(3) A, b¼7.5405(15) A,
ꢀ
c¼27.710(6) A
3
ꢀ
Volume
2680.6(9) A
Z, calculated density
Absorption coefficient
F(000)
8, 1.389 mg mꢀ3
0.098 mmꢀ1
19. (a) Houlihan, W.J.; Sandoz, AG. Patent 3609139 US, A61K27/00,
p812304, 3 p;
1168
(b) Aeberli, P.; Houlihan, W. J. J. Heterocycl. Chem. 1978, 15, 1141.
Theta range for data collection
Index ranges
Reflections collected/unique
(2.16e23.26) ø
20. For recent examples, see: Solé, D.; Serrano, O. Org. Biomol. Chem. 2009, 7, 3382.
21. Another monocarbonyl acetylene substrate, p-NO2-C6H4eC(O)eC^CeSiMe3
(13c), was tested. Since trimethylsilylpropynal is known to undergo nucleo-
philic attack at the carbonyl center exclusively, the case of 13c in the presence
of the soft isoindole 2 deserved examination. To solution of 2 (1.00 g, 4.
03 mmol) in methanol (5 mL), a solution of 13c (1.00 g, 4.03 mmol) in methanol
(4 mL) was thus added at room temperature. A violet-blue precipitate formed
immediately, which was filtered out, washed with methanol, and dried under
vacuum. The purple product (1.75 g, 86%) was submitted to MS analysis,
showing that it corresponds to the stoichiometric addition 2þ13c
(C28H25N4O4Si¼495). The exact structure of the product could not be de-
termined, but the absence of carbonyl absorption in the IR spectrum shows that
ꢀ30ꢂlꢂ30, ꢀ14ꢂhꢂ14, ꢀ8ꢂkꢂ8
18,173/18,173/1,925 [R(int)¼0.0539]
99.9%
Completeness to 2
Refinement method
q
¼46.52
Full-matrix least-squares on F2
1925/0/196
Data/restraints/parameters
Goodness-of-fit on F2
1.032
Final R indices [I>2
R indices (all data)
Extinction coefficient
Largest diff. peak and hole
s
(I)]
R1¼0.0426, wR2¼0.1065
R1¼0.0662, wR2¼0.1202
0.0024(12)
(0.146 and ꢀ0.124) e Aꢀ3

8222
Z.V. Voitenko et al. / Tetrahedron 66 (2010) 8214e8222
the C]O group has indeed been attacked. Crude spectroscopic data are listed
25. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.;
Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz,
J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.;
Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B. W.; Wong, W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision C.02;
Gaussian: Wallingford CT, 2004.
below. MS (DCI/NH3): 496 (100%, [MH]þ), 514 (12%, [MNH4]þ). IR (CHCl3): 3621
(sharp), 3463 (br), 3022 (br), 1521 (br), 1479, 1425, 1215, 1207 (br). UVevis
(CHCl3, c¼3.5 10ꢀ2 M),
l
(absorbance): 371.4 (0.65), 565.3 (1.06). 1H NMR
(250 MHz, CDCl3),
d
(the broadness of the signals are possibly due to in-
associations): 0.16 (9H, br; Si(CH3)3), 3.46 (3H, br, NCH3), 4.
15e4.25 (0.8H, br), 5.59 (1H, br), 7.96e8.33 (16H, br m; sp2-CH). 13C NMR (62.
9 MHz, CDCl3), : 0.9 (Si(CH3)3), 33.0 (NCH3), 70.0, 91.0, 928, 93.4 (CH), 120.9,
termolecular
pep
d
122.5, 123.9 (p-nitrophenyl m- or o-(CH)2), 126.1 (p-nitrophenyl o- or m-(CH)2),
126.9 (CH), 127.3 (CH), 127.8 (CH), 128.5 (CH), 129.2 (CH), 130.0 (CH), 132.4 (CH),
134.5 (CH), 137.6, 143.0, 147.6, 148.0, 158.0, 162.6 (tentative assignment is based
on the shift range and relative intensity, but weak signals can correspond to
either quaternary carbons of the main product or to CH signals of a minor
component).
22. Zhang, Z. Z.; Schuster, G. B. J. Am. Chem. Soc. 1989, 111, 7149.
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C.; Maurette, L.; Sui-Seng, C.; Zou, C.; Soleilhavoup, M.; Vendier, L.; Chauvin, R.
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24. (a) Barzoukas, M.; Blanchard-Desce, M. J. Chem. Phys. 2000, 113, 3951; (b)
Albota, M.; Beljonne, D.; Brédas, J.-L.; Ehrlich, J. E.; Fu, J.-Y.; Heikal, A. A.; Hess,
S. E.; Kogej, T.; Levin, M. D.; Marder, S. R.; McCord-Maughon, D.; Perry, J. W.;
26. (a) Somers, K. R. F.; Ceulemans, A. J. Phys. Chem. A 2004, 108, 7577; (b) Vash-
chenko, A. V.; Vasil’tsov, A. M.; Shmidt, E. Y.; Mikhaleva, A. I.; Trofimov, B. A.
J. Struct. Chem. 2006, 47, 616.
27. (a) Gong, W.; Li, Q.; Li, Z.; Lu, C.; Zhu, J.; Li, S.; Yang, J.; Cui, Y.; Qin, J. J. Phys. Chem. B
2006, 110, 10241; (b) Guthmuller, J.; Simon, D. J. Phys. Chem. A 2006, 110, 9967.
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