New tandem cyclo- and/or addition reactions between N-arylisoindolines with benzyne and dimethyl acetylenedicarboxylate

Article abstract of DOI:10.1002/jhet.428

(Chemical Equation Presented) Reaction of N-arylisoindolines with benzyne afforded predominantly 10-arylisoindolo[2,1-f]phenanthridines. On the other hand, N-arylisoindolines react with dimethyl acetylenedicarboxylate to give dimethyl 2-(2-aryl-2H-isoindo

Full text of DOI:10.1002/jhet.428

September 2010
New Tandem Cyclo- and/or Addition Reactions between
N-Arylisoindolines with Benzyne and Dimethyl
Acetylenedicarboxylate
1079
Ashraf A. Aly,a* Alaa A. Hassan,a Kamal M. El-Shaieb,a
and Talaat I. El-Emaryb
aDepartment of Chemistry, Faculty of Science, El-Minia University, El-Minia,
61519-El-Minia, Egypt
bDepartment of Chemistry, Faculty of Science, Assiut University, Assiut, Egypt
*E-mail: ashrafaly63@yahoo.com
Received September 27, 2009
DOI 10.1002/jhet.428
Published online 13 July 2010 in Wiley Online Library (wileyonlinelibrary.com).
Reaction of N-arylisoindolines with benzyne afforded predominantly 10-arylisoindolo[2,1-f]phenan-
thridines. On the other hand, N-arylisoindolines react with dimethyl acetylenedicarboxylate to give di-
methyl 2-(2-aryl-2H-isoindol-1-yl)fumarates. Possible reaction mechanisms are discussed.
J. Heterocyclic Chem., 47, 1079 (2010).
INTRODUCTION
including benzyne aiming to synthesize various hetero-
cycles and heterophanes. Synthesis of biologically active
heterocycles has also been one of our interests [12,13].
Aryne chemistry has been applied to the synthesis of aryl
amines in a tandem reaction including two Diels-Alder
reactions, with three benzyne molecules reacting with
one imidazole molecule (Scheme 1) [14]. The reaction
proceeds via formation of 2-methyl-2H-isoindole (1),
which reacted with two more molecules of benzyne (2) to
give the corresponding N-methyl-N-phenylanthracen-9-
amine (3, Scheme 1) [14]. Accordingly, we were encour-
aged to investigate the reaction of N-arylisoindolines 4a–
d [2,15] with benzyne (2) and dimethyl acetylenedicar-
boxylate (DMAD, 11).
Previously, it was demonstrated that N-arylisoindo-
lines underwent charge-transfer complexation [1,2] and
deep seated chemical transformations with 1,4-benzo- or
1,4-naphthoquinones [2] under initial a-H-atom abstrac-
tion to give a-oxygenated products [3,4]. Also and in
a multistep reaction, 3,30-(2-aryl-2H-isoindol-1,3-ylene)-
di-(1,4-naphthoquinone-2-carbonitriles) have been formed
in 25–61% yield from a series of N-aryl-isoindolines
with (1,3-dioxo-2,3-dihydro-1H-inden-2-ylidene)propa-
nedinitrile in aerated pyridine [5]. On the other side,
N-arylisoindolines react with ethenetetracarbonitrile
(TCNE) in aerated benzene with the formation of [3-
(2-aryl-3-dicyanomethylene-2,3-dihydro-1H-isoindol-1-
ylidene)-2-aryl-2,3-dihydro-1H-isoindol-1-ylidene]propa-
nedinitriles, N-aryl-3-dicyanomethylene-isoindol-2-ones,
and N-aryl-phthalimides as well as ethanetetracarboni-
trile [4,6]. The highly reactive parent system, benzyne,
reacts with imine compounds to give (o-anilinobenzy-
hydryl)-aniline [7] and phenanthridine derivatives [8]
as well as acridines [8] via [2p þ 2p] and/or [4p þ 2p]
cycloaddition reactions. We investigated the cycloaddi-
tion reactions of aromatic diimines [9], azomethine com-
pounds having [2.2]paracyclophane [10] and ethenyl-
[2.2]-paracyclophanes [11] with selected dienophiles
RESULTS AND DISCUSSION
Herein, we report the cycloaddition reactions of N-
arylisoindolines 4a–d with benzyne (dehydrobenzene,
2), which was generated by diazotization of 1,2-anthra-
nilic acid [11,16–19]. We chose N-arylisoindolines 4a–d
bearing electron donating and withdrawing substituents
on the benzene ring, to examine their effect on the
course of reaction. Scheme 2 outlines the reaction of
4a–d with 2 in dry acetonitrile under N2 atmosphere.
C
V
2010 HeteroCorporation

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A. A. Aly, A. A. Hassan, K. M. El-Shaieb, and T. I. El-Emary
Vol 47
Scheme 1. Reaction of N-methylisoindolone with benzene.
The reaction proceeded to yield, after chromatographic
purification and recrystallization, compounds 8a–d (58–
68%) (Scheme 2). The NMR and mass spectra, and ele-
mental analyses, confirm the addition of two molecules
of 2 to 4 (Scheme 2).
should show the molecular symmetry, which is absent
from 8a. Autoxidation of 10a is reported to give ring
opening, not closure to 8a [22]; thus, we exclude 10a–d
as intermediates in our pathways leading to 8a–d. Pub-
lished syntheses of isoindoles from isoindolines proceed
via N-oxidation, followed by O-acylation and elimination
[17,23]. However, benzyne is reported to oxidize dihydro-
pyridines to pyridines [24], presumably by a hydrogen-
transfer mechanism like a diimide reduction. We,
therefore, propose that 2 oxidizes isoindolines 4a–d to the
corresponding isoindoles 5a–d, which undergo electro-
philic substitution by 2, selectively at C-1 [25], to give
compounds 6a–d. (The order of these steps may be
reversed: see below) Subsequently, compounds 6a–d
react with a second molecule of 2 by intermolecular
cycloaddition, followed by oxidation in situ to produce
the stable heterocyclic compounds 8a–d. Interestingly,
the reaction of isoindolines having electron-donating sub-
stituents in the arylidene groups, such as 4b and 4c, with
NMR spectra confirmed the absence of the isoindoline
CH2 protons and their corresponding carbons. In 8a, a
double-doublet at dH ¼ 8.46 corresponded to H-11 (J ¼
7.8, 1.2 Hz). Another multiplet at dH ¼ 8.40–8.34 was
assigned to H-8,12,13,14. Another two double-doublets at
dH ¼ 8.00 and 7.76 corresponded to H-5 and H-4 (J ¼
7.8, 1.2 Hz), respectively. The 13C NMR spectrum of 8a
showed C-14b, C-10a, C-4a, C-8a at dC ¼ 150.2, 141.0,
137.4, and 131.0, respectively. The absence of the sym-
metrical anthracene ring system from the 13C NMR spec-
tra [20] excluded the formation of compounds 9a-d. One
can also envision that the regioisomers 10a–d might be
formed. Of compounds 10a–d, 1,2,3-triphenylisoindole
(10a) is known [21]. However, the NMR spectra of 10a
Scheme 2. Reaction of N-arylisoindolines 4a–d with benzyne (2). 8a: 6 h, 62%; 8b: 8 h, 64%; 8c: 4 h, 68%; 8d: 10 h, 58%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2010 New Tandem Cyclo-and/or Addition Reactions between N-Arylisoindolines with
Benzyne and Dimethyl Acetylenedicarboxylate
1081
Scheme 3. Reaction of N-arylisoindolines 4a–d with DMAD (11). 12a: 14 h, 82%; 12b: 14 h, 82%; 12c: 12 h, 87%; 12d: 18 h, 78%.
yses were carried in Assiut Microanalysis Center of Assiut
University. Mass spectroscopy was performed with a Finnigan
Mat 8430 spectrometer at 70 eV Institute of Organic Chemis-
try, TU-Braunschweig. Germany. IR spectra were run on a
Shimadzu 470 spectrometer using KBr pellets.
Starting materials. 2-Aryl-2,3-dihydro-1H-isoindoles 4a–d
were prepared according to published procedures [2,15]. Di-
methyl acetylene-dicarboxylate (DMAD, 10) was bought from
Fluka.
Reaction of isoindolines 4a-d with benzyne (2).
Benzenediazonium carboxylate was prepared by the procedure
described in [16–19]. Under nitrogen atmosphere, 6 mmol of
benzyne (2) precursor was slowly added to the stirred and
refluxed solutions of 4a–d (2 mmol) in dry acetonitrile (250
mL) for 1 h. The reaction mixture was refluxed till the con-
sumption of the starting materials was completed (reaction
progress monitored by TLC analysis) in 4–10 h. The solvent
was concentrated and the residue was filtered off. The precipi-
tate was washed with dichloromethane (200 mL). The filtrate
was then concentrated in vacuum and the residue was applied
to PLC using toluene as an eluent. The migrating zones con-
tained the products 8a–d were recrystallized from the stated
solvents. All zones were extracted with acetone and the prod-
ucts recovered.
2 yielded the main products 8b,c in higher percentage
yields compared with 8d.
Surprisingly, the reactions of 4a–d with dimethyl ace-
tylenedicarboxylate (DMAD, 11), in refluxing ethanol,
afforded dimethyl 2(2-aryl-2H-isoindole-1-yl)fumarates
12a–d (Scheme 3). Structure 12a has formula
C20H17NO4, consistent with the molecular ion of m/z ¼
335. The 1H NMR spectrum of 12a showed the two
methyl esters as two singlets at dH ¼ 3.86 and 3.78.
Another singlet at dH ¼ 7.00 denoted the vinylic H of
the ethylenic bond. The 13C NMR spectrum of 12a
showed two carbonyl carbons at dC ¼ 170.0 and 168.5.
The remaining carbons of 12a showed signals at dC
¼
138.9, 138.4, 127.6, 123.2, 120.5, 120.0, 118.8, 116.2,
115.2, 112.8, 102.0, 52.0, and 51.7 corresponding to
(Ar-CAN), (vinylic-C-20), (Ar-CH-6), (Ar-CH-7), (Ar-
CH-5), (C-1), (Ar-CH-4), (CH-3), (C-3a), (vinylic-CH-
10), (C-7a), (ester-CH3) and (ester-CH3), respectively.
Formally, compounds 12a–d arise by ene reaction
between 11 and a tautomer of 4a–d, followed by oxida-
tion (Scheme 3). The same kind of sequence can be
written for reaction of 4a–d with benzyne, which would
lead the substitution invoked above (Scheme 2) to occur
before oxidation.
10-Phenylisoindolo[2,1-f]phenathridines (8a). Yellow crys-
tals (0.213 g, 62%), mp 240ꢁC (ethanol); [Found: C, 90.80; H,
4.90; N, 4.00. C26H17NO requires C, 90.93; H, 4.99; N,
4.08%]; mmax (potassium bromide) 3030–3000 (m, Ar-CH),
1580 (m, olefinic-CH) cmꢂ1; dH ¼ 8.46 (dd, J ¼ 7.8, 1.2 Hz,
1H, H-11), 8.40–8.34 (m, 4H, H-8,12,13,14), 8.00 (dd, J ¼
7.8, 1.2 Hz, 1H, H-5), 7.76 (dd, J ¼ 7.8, 1.2 Hz, 1H, H-4),
CONCLUSIONS
7.60–7.58 (m, 6H, Ar-H), 7.50–7.38 (m, 4H, Ar-H); dC
¼
In conclusion, N-arylisoindolines react with benzyne
to form arylisoindolophenanthridines and with DMAD
to form (2-aryl-2H-isoindol-1-yl)fumarates. The mecha-
nisms of these transformations are uncertain but appear
to involve both concerted reactions and oxidations.
150.2 (C-14b), 141.0 (C-10a), 137.4 (C-4a), 133.4 (Ph-C),
131.0 (C-8a), 130.0 (Ar-CH-p), 129.2 (Ar-CH-p), 128.6 (Ar-
2CH-m), 128.4 (Ar-2CH-o), 128.0, 127.6, 127.4, 127.0, 126.6
(Ar-CH), 126.4 (C-14a), 125.9, 125.6 (Ar-CH), 124.8 (C-4b),
124.0 (CH-11), 123.4 (CH-12), 123.0 (CH-13), 122.8 (CH-14),
118.0 (C-14c), 116.8 (C-10); m/z (70 eV, EI): 343 [Mþ] (100),
266 (30), 242 (18), 192 (20), 168 (28), 92 (20), 78 (24%).
6-Methyl-10-phenylisoindolo[2,1-f]phenathridines
(8b).
EXPERIMENTAL SECTION
Yellow crystals 8b (0.229 g, 64%), mp 260ꢁC (methanol);
[Found: C, 90.60; H, 5.39; N, 4.08. C27H19N requires C,
90.72; H, 5.36; N, 3.92%]; mmax (potassium bromide): 3065–
3008 (m, Ar-CH), 2980–2870 (w, aliph.ACH), 1582 (m, ole-
finic-CH) cmꢂ1; dH ¼ 8.38 (dd, J ¼ 7.6, 1.2 Hz, 2H, H-
11,14), 8.40–8.28 (m, 2H, H-12,13), 7.86 (m, 2H, H-5,4),
7.76–7.52 (6H, m), 7.40–7.30 (4H, m), 2.34 (s, 3H, CH3); dC
¼ 149.6 (C-14b), 141.2 (C-10a), 137.0 (C-4a), 133.0, 132.6
(Ar-C), 128.9 (C-8a), 128.4 (Ar-CH-p), 127.6 (Ar-2CH-m),
127.0 (Ar-2CH-o), 126.9 (C-14a), 126.6, 126.2, 125.8, 125.6,
125.4, 125.0, 124.8 (Ar-CH), 124.4 (C-4b), 124.0 (CH-11),
1
General. Melting points are uncorrected. H NMR and 13C
NMR spectra were measured in deuterochloroform solutions
on Bruker AM-400 or AV-400 spectrometers (400.13 MHz for
1H and 100.6 MHz for 13C). The AV-400 was purchased with
assistance from the National Science Foundation (CHE 03-
42251). For preparative thin layer chromatography (PLC),
glass plates (20 ꢀ 48 cm) were covered with a slurry of silica
gel Merck PF254 and air-dried using the solvents listed for de-
velopment. Zones were detected by quenching of indicator flu-
orescence upon exposure to 254 nm UV light. Elemental anal-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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A. A. Aly, A. A. Hassan, K. M. El-Shaieb, and T. I. El-Emary
Vol 47
123.6 (CH-12), 123.2 (CH-13), 122.6 (CH-14), 118.2 (C-14c),
116.6 (C-10), 21.8 (CH3); m/z (70 eV, EI): 357 [Mþ] (100),
342 (26), 264 (28), 242 (28), 190 (26), 168 (32), 92 (32), 78
(44%).
(70 eV, EI): 335 [Mþ] (100), 320 (22), 305 (24), 277 (18),
266 (30), 250 (18), 212 (40), 192 (20), 168 (28), 92 (20), 78
(24%).
Dimethyl 2-(2-(40-methylphenyl)-2H-isoindol-1-yl)fumarate
(12b). Yellow crystals (0.293 g, 84%), mp 240ꢁC (ethanol);
[Found: C, 72.30; H, 5.34; N, 4.00. C21H19NO4 requires C,
72.19; H, 5.48; N, 4.01%]; mmax (potassium bromide) 3085–3008
(m, Ar-CH), 2982–2840 (m, aliph.ACH), 1728–1715 (br, s, CO),
1586 (s, olefinic-CH) cmꢂ1; dH ¼ 8.36 (t, J ¼ 7.8 Hz, 1H, H-4),
8.32 (t, J ¼ 7.6 Hz, 1H, H-6), 8.08 (dd, J ¼ 7.8, 1.2 Hz, 1H, H-
5), 8.00 (dd, J ¼ 7.8, 1.2 Hz, 1H, H-5), 7.36 (d, J ¼ 7.7 Hz, 2H),
7.20 (d, J ¼ 7.8 Hz, 2H), 7.10 (s, 1H, vinylic-H-20), 6.90 (s, 1H,
H-3), 3.90 (s, 3H, CH3-ester), 3.86 (s, 3H, CH3-ester), 2.34 (s,
3H, CH3-Ar); dC ¼ 169.4 (CO-ester), 168.8 (CO-ester), 138.6
(Ar-CAN), 138.2 (vinylic-C-20), 135.4 (Ar-C), 129.2 (Ph-2CH-
m), 127.2 (Ar-CH-6), 124.4 (Ar-2CH-o), 123.2 (Ar-CH-7),
120.5 (Ar-CH-5), 120.2 (C-1), 119.2 (Ar-CH-4), 116.4 (CH-3),
115.4 (C-3a), 113.0 (vinylic-CH-10), 102.2 (C-7a), 52.2 (ester-
CH3), 51.2 (ester-CH3), 22.4 (Ar-CH3) m/z (70 eV, EI): 349
[Mþ] (100), 335 (24), 320 (20), 304 (18), 276 (26), 266 (30), 250
(18), 207 (34), 192 (20), 168 (28), 92 (40), 78 (34%).
6-Methoxy-10-phenylisoindolo[2,1-f]phenathridines
(8c).
Yellow crystals (0.254 g, 68%), mp 290ꢁC (acetonitrile); [Found:
C, 86.70; H, 5.10; N, 3.68. C27H19NO requires C, 86.84; H, 5.13;
N, 3.75%]; mmax (potassium bromide) 3080–3012 (m, Ar-CH),
2988–2860 (m, aliph.ACH), 1590 (s, olefinic-CH) cmꢂ1; dH
¼
8.38 (dd, J ¼ 7.6, 1.0 Hz, 2H, H-11,14), 8.30–8.20 (m, 2H, H-
12,13), 7.94 (t, J ¼ 7.8 Hz, 1H, H-8), 7.90 (dd, J ¼ 7.8, 1.2 Hz,
1H, H-1), 7.80 (dd, J ¼ 7.8, 1.2 Hz, 2H, H-5,4), 7.52–7.40 (6H,
m), 7.30–7.18 (2H, m), 3.90 (s, 3H, OCH3); dC ¼ 158.0 (H3CO-
Ar-C), 148.0 (C-14b), 141.2 (C-10a), 135.8 (C-4a), 133.2 (Ph-C),
128.6 (Ph-CH-p), 128.0 (Ph-2CH-m), 127.2 (Ph-2CH-o), 127.0
(C-8a), 126.9 (C-14a), 126.8, 126.6, 126.0, 125.4, 125.0 (Ar-CH),
124.6 (C-4b), 123.8 (CH-11), 123.6 (CH-12), 123.0 (CH-13),
122.8 (CH-14), 122.6 (CH-7), 117.6 (C-14c), 115.0 (C-10), 104.0
(CH-5), 55.8 (OCH3); m/z (70 eV, EI): 373 [Mþ] (100), 356 (18),
342 (26), 264 (28), 242 (30), 190 (34), 168 (22), 109 (22), 92 (30),
78 (34%).
6-Chloro-10-phenylisoindolo[2,1-f]phenathridines
(8d).
Dimethyl 2-(2-(40-methoxyphenyl)-2H-isoindol-1-yl)fuma-
rate (12c). Yellow crystals (0.318 g, 87%), mp 202ꢁC (metha-
nol); [Found: C, 68.90; H, 5.20; N, 3.90. C21H19NO5 requires C,
69.03; H, 5.24; N, 3.83%]; mmax (potassium bromide) 3090–3006
(m, Ar-CH), 2980–2850 (m, aliph.ACH), 1730–1712 (br, s, CO),
1585 (s, olefinic-CH) cmꢂ1; dH ¼ 8.40 (t, J ¼ 7.6 Hz, 1H, H-4),
8.34 (t, J ¼ 7.8 Hz, 1H, H-6), 8.12 (dd, J ¼ 7.6, 1.2 Hz, 1H, H-
5), 8.05 (dd, J ¼ 7.6, 1.2 Hz, 1H, H-5), 7.56 (d, J ¼ 7.8 Hz, 2H),
6.90 (d, J ¼ 7.8 Hz, 2H), 6.96 (s, 1H, vinylic-H-20), 6.90 (s, 1H,
H-3), 3.92 (s, 3H, CH3-ester), 3.80 (s, 3H, CH3-ester), 3.92 (s,
3H, CH3O-Ar); dC ¼ 169.7 (CO-ester), 168.2 (CO-ester), 156.9
(CH3O-Ar-C), 138.5 (Ar-CAN), 139.0 (vinylic-C-20), 127.2
(Ar-CH-6), 124.4 (Ar-2CH-o), 123.4 (Ar-CH-7), 120.5 (Ar-CH-
5), 120.2 (C-1), 119.6 (Ar-CH-4), 118.2 (Ar-2CH-m), 116.4
(CH-3), 115.4 (C-3a), 113.4 (vinylic-CH-10), 102.2 (C-7a), 52.0
(ester-CH3), 51.0 (ester-CH3), 50.8 (Ar-OCH3); m/z (70 eV, EI):
365 [Mþ] (100), 350 (14), 334 (16), 320 (20), 306 (22), 280 (24),
222 (30), 192 (20), 91 (38), 78 (36%).
Dimethyl 2-(2-(40-chlorophenyl)-2H-isoindol-1-yl)fumarate
(12d). Yellow crystals (0.288 g, 78%), mp 162ꢁC (methanol);
[Found: C, 64.96; H, 4.36; Cl, 9.59; N, 3.79. C20H16ClNO4
requires C, 64.80; H, 4.30; Cl, 9.70; N, 3.70%]; mmax (potassium
bromide): 3060–3005 (m, Ar-CH), 2980-2770 (m, aliph.ACH),
1732–1710 (br, s, CO), 1586 (s, olefinic-CH) cmꢂ1; dH ¼ 8.30–
8.26 (m, 2H, H-4,7), 8.12–8.08 (m, 2H, H-6,7), 7.42 (d, J ¼ 7.8
Hz, 2H), 7.30 (d, J ¼ 7.8 Hz, 2H), 7.03 (s, 1H, H-3), 6.95 (s, 1H,
vinylic-H-20), 3.95 (s, 3H, CH3-ester), 3.86 (s, 3H, CH3-ester);
dC ¼ 170.0 (CO-ester), 169.2 (CO-ester), 136.5 (Ar-CAN),
138.2 (vinylic-C-20), 131.0 (Ar-C-Cl), 129.0 (Ar-2CH-o), 127.0
(Ar-CH-6), 123.2 (Ar-CH-7), 120.4 (Ar-2CH-m), 120.3 (Ar-CH-
5), 120.0 (C-1), 119.4 (CH-3), 119.2 (Ar-CH-4), 114.4 (C-3a),
112.0 (vinylic-CH-10), 101.2 (C-7a), 52.4 (ester-CH3), 51.2
(ester-CH3); m/z (70 eV, EI): 370 [Mþ1] (32), 369 [Mþ] (100),
354 (24), 352 (26), 340 (14), 339 (18), 334 (22), 312 (16), 310
(18), 227 (20), 226 (24), 192 (24), 114 (42), 91 (38), 78 (39%).
Yellow crystals (0.219 g, 58%), mp 250ꢁC (ethyl acetate);
[Found: C, 82.50; H, 4.20; Cl, 9.50; N, 3.62. C26H16ClN
requires C, 82.64; H, 4.27; Cl, 9.38; N, 3.71%]; mmax (potas-
sium bromide) 3060–3009 (m, Ar-CH), 1585 (s, olefinic-CH)
cmꢂ1; dH ¼ 8.45 (dd, J ¼ 7.8, 1.2 Hz, 2H, H-8), 8.30 (t, J ¼
7.6 Hz, 1H, H-14), 8.20 (t, J ¼ 7.6 Hz, 1H, H-11), 8.08 (t, J
¼ 7.6 Hz, 1H, H-13), 8.04 (dd, J ¼ 7.6, 1.2 Hz,, 1H, H-5),
7.90–7.64 (10H, m); dC ¼ 149.0 (C-14b), 141.6 (C-10a), 136.2
(C-4a), 133.4 (Ph-C), 130.6 (CH-3), 131.2 (CH-7), 130.0 (CH-
8), 129.6 (CH-2), 129.4 (C-8a), 129.2 (Ar-2CH-m), 128.6 (CH-
1), 128.4 (Ar-CH-p), 128.0 (CH-1), 127.8 (Ar-2CH-o), 127.0
(Ar-CACl), 126.6 (C-14a), 125.8 (C-4b), 124.0 (CH-14), 123.6
(CH-5), 123.2 (CH-11), 123.0 (CH-12), 122.8 (CH-13), 119.2
(C-14c), 116.0 (C-10); m/z (70 eV, EI): 378 [Mþ1] (30), 377
[Mþ] (100), 344 (23), 342 (34), 266 (28), 242 (20), 192 (26),
168 (30), 112 (28), 92 (20), 78 (24%).
Reaction of isoindolines 4a–d with dimethyl acetylenedi-
carboxylate (DMAD, 11). A mixture of 4a–d (1 mmol) with
11 (0.142 g, 1 mmol) in absolute ethanol (50 mL) was refluxed
for 12–18 h (the reaction was followed by TLC analysis). The
solvent was removed under vacuum. The residue was applied
on column chromatography (silica gel) using dichloromethane
as eluent. The separated products 12a–d were recrystallized
from the stated solvents.
Dimethyl 2-(2-phenyl-2H-isoindol-1-yl)fumarate (12a).
Yellow crystals (0.275 g, 82%), mp 220ꢁC (methanol); [Found:
C, 71.50; H, 5.08; N, 4.18. C20H17NO4 requires C, 71.63; H,
5.11; N, 4.18%]; mmax (potassium bromide): 3090–3008 (m,
Ar-CH), 2980–2860 (m, aliph.ACH), 1730–1712 (br, s, CO),
1586 (s, olefinic-CH) cmꢂ1; dH ¼ 8.38 (t, J ¼ 7.6 Hz, 1H, H-
4), 8.30 (t, J ¼ 7.8 Hz, 1H, H-6), 8.10 (dd, J ¼ 7.8, 1.2 Hz,
1H, H-5), 8.06 (dd, J ¼ 7.6, 1.2 Hz, 1H, H-5), 7.36–7.20 (5H,
m), 7.00 (s, 1H, vinylic-H-20), 6.96 (s, 1H, H-3), 3.86 (s, 3H,
CH3-ester), 3.78 (s, 3H, CH3-ester); dC ¼ 170.0 (CO-ester),
168.5 (CO-ester), 138.9 (Ar-CAN), 138.4 (vinylic-C-20), 129.0
(Ph-2CH-m), 126.8 (Ar-CH-p), 127.6 (Ar-CH-6), 122.4 (Ar-
2CH-o), 123.2 (Ar-CH-7), 120.5 (Ar-CH-5), 120.0 (C-1),
118.8 (Ar-CH-4), 116.2 (CH-3), 115.2 (C-3a), 112.8 (vinylic-
CH-10), 102.0 (C-7a), 52.0 (ester-CH3), 51.7 (ester-CH3); m/z
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September 2010 New Tandem Cyclo-and/or Addition Reactions between N-Arylisoindolines with
Benzyne and Dimethyl Acetylenedicarboxylate
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