Synthesis and X-ray structure of stable 2H-isoindoles

Article abstract of DOI:10.1039/a908641b

Stable 2H-isoindoles with electron-withdrawing groups were prepared using the reaction of dinitrobenzene derivatives with isocyanoacetate in the presence of DBU. The use of acetonitrile as the solvent or a phosphazene base (BTPP) as a non-ionic base improved the yields. The structure was confirmed by X-ray crystallographic analysis of the compound 2e′. According to the X-ray analysis, this substance existed in the solid phase only as the 2H-isomer. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/a908641b

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Synthesis and X-ray structure of stable 2H-isoindoles
a
a
a
a
a
Takashi Murashima,* Ryuji Tamai, Keiji Nishi, Kentaroh Nomura, Ken-ichi Fujita,
b
a
Hidemitsu Uno and Noboru Ono*
1
a
Department of Chemistry, Faculty of Science, Ehime University, Bunkyo-cho 2-5,
Matsuyama 790-8577, Japan
Advanced Instrumentation Center for Chemical Analysis, Ehime University, Bunkyo-cho 2-5,
Matsuyama 790-8577, Japan
b
Received (in Cambridge, UK) 29th October 1999, Accepted 31st January 2000
Stable 2H-isoindoles with electron-withdrawing groups were prepared using the reaction of dinitrobenzene
derivatives with isocyanoacetate in the presence of DBU. The use of acetonitrile as the solvent or a phosphazene
base (BTPP) as a non-ionic base improved the yields. The structure was confirmed by X-ray crystallographic
analysis of the compound 2eЈ. According to the X-ray analysis, this substance existed in the solid phase only
as the 2H-isomer.
Table 1 Preparation of nitro isoindoles 2, 3 and nitro pyrrole 4
Introduction
Pyrroles fused with polyaromatic hydrocarbons have been
Isocyano-
acetate
Reaction
Time/h
Product
(%)
widely investigated as precursors of highly conjugated por-
phyrins and of electronically conducting polypyrroles. Recent
developments in the efficient synthesis of these compounds
have afforded a variety of polyaromatic annulated pyrroles. One
of the most convenient preparations of such compounds has
been the reaction of polyaromatic nitro compounds with ethyl
a
Substrate
Solvent
THF
1
a
CNCH CO Et
24
24
24
24
24
48
4
2a (9)
2a (18)
2a (9)
2a (8)
2
2
1a
1a
CH CN
CNCH CO Et
3
2
2
DMF
DMSO
THF
CNCH
CO
Et
2
2
1
a
CNCH CO Et
2
2
b
1
1a
CNCH
2
CO
2
Et
2a (29)
isocyanoacetate in the presence of DBU.
b
1
1
b
c
THF
CNCH CO Et
2b (9)
2
2
Some polyaromatic nitro compounds and heteroaromatic
nitro compounds showed low reactivity and in some cases, we
could not obtain the expected pyrroles and the corresponding
pyrimidine N-oxides were formed. These drawbacks could be
CH CN
CNCH CO Et
2c (7)
3
2
2
3
c (2)
4 (3)
1c
1d
CH
CH
CN
CN
CNCH
CNCH
CO
CO
t-Bu
6
7
2cЈ (16)
3cЈ (7)
2d (16)
3
2
2
1c
largely overcome by using other non-ionic bases such as
2
3
3
2
2
Et
proazaphosphatrane or iminophosphorane. In spite of these
studies, attempts to prepare the true 2H-isoindole type com-
pounds by the condensation of simple nitro aromatic com-
pounds with a carbanion derived from ethyl isocyanoacetate,
were unsuccessful. Thus, the remaining challenge in this field
was the synthesis of isoindoles derived from simple nitro
aromatic compounds.
3
4
d (5)
(3)
1
e
CH CN
CNCH CO Et
5
3
24
2e (64)
2eЈ (55)
2f (7)
3
2
2
1e
1f
CH CN
CNCH CO t-Bu
3
2
2
CH
CN
CNCH
CO
Et
3
2
2
5
(27)
a
b
Yields refer to pure isolated products. BTPP was used instead of
DBU.
Results and discussion
Isoindoles without nitrogen substituents are particularly
reactive because of the occurrence of tautomeric equilibria
with the 1H-isomer (imine-type compound). Unsubstituted
To our surprise, we found that 1,3-dinitrobenzene 1a under-
goes nucleophilic addition and sequential cyclization using 2
equivalents of the reagent (See Table 1). A typical procedure
was as follows: 1,3-dinitrobenzene (1 mmol) and 2 equivalents
of ethyl isocyanoacetate were dissolved in 2 ml of THF,
then 2.2 equivalents of DBU was added dropwise into the
solution at 0 ЊC. The resulting mixture was stirred for 24 h
after which it was worked up (experimental) and purified by
silica gel column chromatography (ethyl acetate–hexane) to give
pure ethyl 5-nitro-2H-isoindole-1-carboxylate 2a in 10% yield
(Scheme 1).
When this reaction was conducted in acetonitrile under simi-
lar conditions, the yield of 2a was raised to 18%. Other solvents
such as DMF and DMSO were not so effective. Thus, it may be
concluded that acetonitrile is the most suitable solvent for these
reactions. When THF was chosen as the solvent, the use of tert-
butyliminotri(pyrrolidino)phosphorane (BTPP) as base im-
proved the yield of 2a to 29%. In all cases, the product was free
of the possible isomer, ethyl 7-nitro-2H-isoindole-1-carboxyl-
ate. The reaction of 2,4-dinitrotoluene 1b at room temperature
for 48 h gave ethyl 6-methyl-5-nitro-2H-isoindole-1-carboxylate
2b as the sole pyrrolic compound in 9% yield with a large
4
isoindole was first synthesized by the pyrolysis of N-meth-
oxycarbonyloxyisoindoline and was isolated in 1972, but this
compound was extremely labile and rapidly decomposed at
ambient temperature.
Thus, the preparation of more stable isoindoles has been
the object of extensive research. Most of the isoindoles so
far prepared have been classified into two groups, that is, N-
5
6
substituted and 1,3-disubstituted isoindoles. N-Substituted
isoindoles are sufficiently stable and can be alkylated at the
7
α-position. Although these stabilizations were convenient and
effective, the resulting isoindoles have not been utilized for the
synthesis of conducting polymers and porphyrins.
So long as we used the standard reaction conditions,
our approach to prepare the stable 2H-isoindole from 1,3- or
1
,4-dinitrobenzenes was unproductive owing to the low yields
and difficult separation of the pyrrolic compounds from the
resulting mixture. Therefore, we examined the effect of several
solvents and bases under various conditions.
DOI: 10.1039/a908641b
J. Chem. Soc., Perkin Trans. 1, 2000, 995–998
This journal is © The Royal Society of Chemistry 2000
995

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Scheme 1 Reagents and conditions: CNCH CO Et or CNCH CO t-Bu, DBU or BTPP, solvent, RT.
2
2
2
2
amount of tarry matter. Unfortunately, 1,2- or 1,4-dinitro-
benzenes and other electron-deficient aromatics such as methyl
nitrobenzoate and dimethyl nitroterephthalate afforded com-
plex mixtures.
Methyl 3,5-dinitrobenzoate 1c reacted with ethyl isocyano-
acetate in the presence of DBU in acetonitrile to give a mixture
of ethyl 7-methoxycarbonyl-5-nitro-2H-isoindole-1-carboxyl-
ate 2c and ethyl 5-methoxycarbonyl-7-nitro-2H-isoindole-1-
carboxylate 3c in yields of 7% and 2%, respectively. The
reaction of ethyl 3,5-dinitrobenzoate 1d gave a similar mixture
with slightly better yields. In both cases, the unexpected nitro-
pyrrole 4 was formed as an impurity. The mechanism of the
formation of 4 is not clear at present.
3
,5-Dinitrobenzonitrile 1e was reacted smoothly with ethyl
isocyanoacetate in the presence of DBU, giving ethyl 7-cyano-
5
6
-nitro-2H-isoindole-1-carboxylate 2e as the sole product in
4% yield (Table 1).
The nitroisoindoles prepared here have an ester function at
the α-position and, therefore, they have no potential as pre-
cursors for porphyrins and polypyrroles as they stand. Decarb-
oxylation was attempted by heating with KOH in ethylene
glycol at 170 ЊC, but the desired α-free pyrroles were not
obtained. In order to effect decarboxylation, the reaction of 1c
and 1e was conducted with tert-butyl isocyanoacetate and the
corresponding pyrroles 2cЈ and 2eЈ were prepared. The com-
pound 2eЈ was successfully converted to the α-free pyrrole 6eЈ
by treatment with toluene-p-sulfonic acid in toluene at reflux
temperature for 5 min in 27% yield (Scheme 2). This compound
Fig. 1 (a) X-Ray crystal structure of isoindole 2eЈ. Hydrogens and
solvent are omitted for clarity. Bond distance (Å) and angles (Њ): N1–C1
1
.381, N1–C8 1.320, C1–C2 1.387, C7–C8, 1.388; C1N1C8 112.0Њ,
N1C1C2 106.5Њ, N1C8C7 108.5Њ, C1C2C7 107.0Њ, C2C7C8 106.5Њ. (b)
Edge-on view of 2eЈ.
1
by the H NMR and elemental analysis of these single crystals
(
Anal. Calcd. for C H N O ؒ1/2CH Cl : C, 52.82; H, 4.28;
14 13 3 4 2 2
N, 12.74; Found: C, 52.69; H, 4.26; N, 12.65%). When single
crystals were grown from a CHCl3 solution, a chloroform
molecule was incorporated in the single crystals and the
proportion of 2eЈ and solvent was the same as that of
dichloromethane containing single crystals.
Scheme 2 Reagents and conditions: toluene-p-sulfonic acid, toluene,
reflux, 5 min.
When the bond length of N(1)–C(1) 1.380(9) Å is com-
pared with that of N(1)–C(8) 1.319(9) Å, there is a small differ-
ence, which is mainly attributed to the contribution of the
polarized canonical structure derived from the existence of
was not so labile as compared with the unsubstituted isoindole
because of the existence of two electron-withdrawing substitu-
ents (nitro and cyano). On the NMR timescale, it is stable in air
at ambient temperature.
8
the α-carbonyl group. Thus, in this case, the possibility of the
X-Ray diffraction-grade single crystals of compound 2eЈ
occurrence of tautomeric equilibrium with the 1H-isomer
were grown by careful recrystallization from a dilute CH Cl2
(imine-type structure) is not observed in the solid phase.
2
1
solution of the isoindole (Fig. 1). The resulting X-ray structure
reveals that there are two isoindole molecules and one solvent
molecule in the unit cell. The solvent molecule is disordered and
shares one position between two orientations in a half-and-half
fashion, the equivalent temperature factors of two Cl atoms
show relatively large values. Existence of a dichloromethane
molecule in the single crystals of compound 2eЈ was confirmed
According to the H NMR result, the 2H-isomer is present
almost exclusively in chloroform mainly because of the pres-
9
ence of nitro and cyano groups on the six-membered ring. The
isoindole ring is fairly planar and the dihedral angle between
the nitro group and the benzene plane of the isoindole unit is
173.46Њ. The imino proton of pyrrole is linked by a hydrogen
bond to the nitrile nitrogen of the neighboring molecule.
9
96
J. Chem. Soc., Perkin Trans. 1, 2000, 995–998

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1
3
In all the reactions of dinitro arenes described above, only
one of the nitro alkene moieties reacted with isocyanoacetate.
However, when 2,4-dinitroanisole 1f was reacted with 1 equiv.
of ethyl isocyanoacetate in the presence of DBU, it gave a
mixture of the monocyclization product, ethyl 6-methoxy-5-
nitroisoindole-1-carboxylate 2f and the double cyclization
product, diethyl 4-methoxy-2,7-dihydropyrrolo[3,4-e]isoindole-
and 13.75 (1H, br, NH); C-NMR (CD SOCD ) δ 14.48, 20.89,
3 3
59.74, 110.83, 121.03, 121.18, 122.02, 122.27, 127.09, 127.22,
144.85 and 160.28; νmax (KBr)/cm 3200, 1676, 1632, 1558,
1506, 1442, 1420, 1386, 1340, 1320, 1292, 1172, 1142 and 768;
m/z (EI) 248 (M , 56%), 231 (19), 203 (9), 185 (100), 156 (17)
and 128 (10); Anal. Calcd. for C H N O : C, 58.06; H, 4.87;
N, 11.29; Found: C, 57.65; H, 4.86; N, 11.15%.
Ϫ1
ϩ
12
12
2
4
1
,6-dicarboxylate 5 in 7% and 27% yields respectively.
In conclusion, stable isoindoles were obtained from highly
Reaction of 1c,d with ethyl isocyanoacetate
electron-deficient nitroarenes with isocyanoacetate using
acetonitrile or THF as the solvent in the presence of DBU
or BTPP as the base. Only 2,4-dinitroanisole 1f reacted with
isocyanoacetate to give the double cyclization product 5. The
decarboxylation of tert-butyl ester 2eЈ was successful, and the
resulting α-free isoindole 6eЈ was a stable 2H-isoindole without
any substituent on the α- and N-positions.
To a stirred solution of 1c or 1d (2 mmol) and ethyl isocyano-
acetate (0.450 g, 4 mmol), 1,8-diazabicyclo[5.4.0]undec-7-
ene (0.66 ml, 4.4 mmol) was added dropwise at 0 ЊC and the
resulting mixture was stirred for 24 h at ambient temperature.
It was worked up and the products 2c, 3c, 4 or 2d, 3d, 4
were separated by silica gel column chromatography (ethyl
acetate–hexane). The pure products could be obtained by the
recrystallization of the resulting solids from chloroform
solutions.
Experimental
General procedures
Ethyl 7-methoxycarbonyl-5-nitro-2H-isoindole-1-carboxylate 2c
Melting points were measured by a Yanaco hot stage apparatus
and are uncorrected. NMR spectra were recorded on a JEOL-
JNM-GSX 270 or JNM-EX 400 spectrometer at ambient tem-
perature by using CDCl , acetone-d or DMSO-d as a solvent
1
Yield 7%; mp 182–183 ЊC; H-NMR (CDCl
) δ 1.42 (3H, t,
), 4.41 (2H, q, J 7.12, CH ),
7.84 (1H, d, J 3.67, ArH), 8.21 (1H, d, J 1.22, ArH), 8.70
3
J 7.17, CH
CH
), 3.98 (3H, s, CH
3
2
3
2
3
6
6
1
13
13
and tetramethylsilane as an internal standard for H and
C
(1H, d, J 1.22, ArH) and 11.30 (1H, br, NH); C-NMR (CD
SOCD ) δ 14.28, 52.15, 60.28, 112.60, 118.50, 121.97, 122.69,
123.10, 124.13, 126.41, 141.01, 159.56 and 167.41; νmax (KBr)/
cm 3216, 1736, 1652, 1336, 1292 and 1200; m/z (EI) 292 (M ,
65%), 246 (M Ϫ EtOH, 100), 215 (11) and 188 (54); Anal.
-
3
and J values are given in Hz. IR spectra were obtained with a
Hitachi 270-30 spectrophotometer. Mass spectra were meas-
ured with a Hitachi M80B-LCAPI spectrometer under the fol-
lowing ionizing conditions: electron impact, 20 eV; high boiling
PFK as a standard. THF was freshly distilled from sodium
benzophenone ketyl. Ethyl isocyanoacetate was prepared from
3
Ϫ1
ϩ
ϩ
Calcd. for C13
H N O : C, 53.42; H, 4.14; N, 9.59; Found: C,
12 2 6
53.38; H, 4.09; N, 9.51%.
10
ethyl N-formylglycinate using POCl3 and triethylamine.
Unless otherwise specified, all nitro aromatics which were not
commercially available were prepared by the conventional
nitration methods of aromatics using HNO –Ac O or HNO –
Ethyl 5-methoxycarbonyl-7-nitro-2H-isoindole-1-carboxylate 3c
1
Yield 2%; mp 177–179 ЊC; H-NMR (CDCl ) δ 1.41 (3H, t,
3
3
2
3
J 7.17, CH CH ), 3.98 (3H, s, CH ), 4.40 (2H, q, J 7.12, CH ),
H SO .
3
2
3
2
2
4
7
.84 (1H, s, ArH), 8.21 (1H, d, J 1.22, ArH), 8.70 (1H, d, J 1.22,
13
ArH) and 11.25 (1H, br, NH); C-NMR (CD SOCD ) δ 14.05,
3
3
Ethyl 5-nitro-2H-isoindole-1-carboxylate 2a
tert-Butyliminotri(pyrrolidino)phosphorane (BTPP) (0.687 g,
.2 mmol) was added dropwise to a solution of 1,3-
dinitrobenzene (0.168 g, 1 mmol) and ethyl isocyanoacetate
5
1.85, 60.07, 112.59, 118.28, 121.79, 122.26, 122.75, 123.96,
Ϫ1
126.32, 140.94, 159.41 and 167.19; νmax (KBr)/cm 3204, 1716,
1658, 1632, 1540, 1442, 1298, 1286, 1234 and 1202; m/z (EI) 292
(M , 100%), 246 (M Ϫ EtOH, 94), 215 (14), 188 (13) and 171
2
ϩ
ϩ
3
(
0.225 g, 2 mmol) in THF (2 cm ) at 0 ЊC. The resulting mixture
(15); Anal. Calcd. for C H N O : C, 53.42; H, 4.14; N, 9.59;
13
12
2
6
was stirred for 24 h at ambient temperature, after which it was
Found: C, 53.09; H, 4.04; N, 9.59%.
3
treated with dilute hydrochloric acid (10 cm ) and extracted
3
with ethyl acetate (3 × 10 cm ). The combined organic phase
Ethyl 4-nitropyrrole-2-carboxylate 4
was washed with aq. sodium hydrogen carbonate, water and
brine, dried over sodium sulfate and evaporated. The residue
was purified by silica gel column chromatography (ethyl
acetate–hexane) to give pure ethyl 5-nitro-2H-isoindole-1-
1
Yield 3%; mp 165–166 ЊC; H-NMR (CDCl
) δ 1.40 (3H, t,
), 7.40 (1H, dd,
J 2.44, 1.83, ArH), 7.77 (1H, dd, J 3.66, 1.53, ArH) and 9.96
3
J 7.17, CH CH ), 4.39 (2H, q, J 7.22, CH
3
2
2
1
13
carboxylate 2a (0.068 g, 29% yield), mp 221–223 ЊC; H-NMR
(1H, br, NH); C-NMR (CD SOCD ) δ 14.98, 62.12, 110.50,
3 3
Ϫ1
(
CD SOCD ) δ 1.38 (3H, t, J 7.08, CH ), 4.37 (2H, q, J 7.16,
124.47, 124.88, 138.90 and 160.84; νmax (KBr)/cm 3268, 1716,
1688, 1510, 1422, 1390, 1366, 1324, 1208 and 756; m/z (EI) 184
3
3
3
CH ), 7.95 (1H, dd, J 9.28, 1.96, ArH), 8.08 (1H, d, J 4.39,
2
ϩ
ϩ
ArH), 8.09 (1H, d, J 4.72, ArH), 8.83 (1H, d, J 1.95, ArH)
(M , 99%), 156 (100) and 139 (M Ϫ EtO, 94); Anal. Calcd.
for C : C, 45.65; H, 4.38; N, 15.22; Found: C, 45.40; H,
13
and 13.90 (1H, br, NH); C-NMR (CD SOCD ) δ 14.46,
H N O
7 8 2 4
3
3
5
1
1
9.93, 111.96, 118.16, 120.77, 121.17, 122.36, 123.03, 127.47,
4.33; N, 15.15%.
Ϫ1
42.22 and 160.28; νmax (KBr)/cm 3216, 1676, 1530, 1434,
ϩ
ϩ
366, 1302 and 1142; m/z (EI) 234 (M , 92%), 188 (M Ϫ
Ethyl 7-ethoxycarbonyl-5-nitro-2H-isoindole-1-carboxylate 2d
EtOH, 100), 206 (8), 158 (17) and 142 (28); Anal. Calcd. for
C H N O : C, 56.41; H, 4.30; N, 11.96; Found: C, 56.26; H,
1
Yield 16%; mp 160–163 ЊC; H-NMR (CD SOCD ) δ 1.29 (3H,
3
3
1
1
10
2
4
t, J 7.08, CH CH ), 1.32 (3H, t, J 7.16, CH CH ), 4.30 (2H, q,
3
2
3
2
4
.35; N, 11.84%.
J 7.08, CH CH ), 4.35 (2H, q, J 7.16, CH CH ), 8.00 (1H, s,
3
2
3
2
Other isoindoles 2b and 2e were prepared by the similar pro-
cedures as described in the preparation of 2a using appropriate
base and solvent and the conditions are shown in Table 1.
ArH), 8.18 (1H, s, ArH), 8.96 (1H, s, ArH) and 14.08 (1H,
13
br, NH); C-NMR (CD SOCD ) δ 13.89, 14.30, 60.23, 61.03,
3
3
1
1
1
12.66, 118.47, 121.98, 122.58, 123.06, 124.14, 126.62, 141.01,
Ϫ1
59.55 and 166.93; νmax (KBr)/cm 3210, 1731, 1649, 1332,
Ethyl 6-methyl-5-nitro-2H-isoindole-1-carboxylate 2b
ϩ
ϩ
288 and 1203; m/z (EI) 306 (M , 87%), 260 (M Ϫ EtOH, 46),
1
Yield 9%; mp 211–213 ЊC; H-NMR (CD SOCD ) δ 1.37 (3H,
232 (91), 215 (13), 188 (100) and 142 (31); Anal. Calcd. for
C H N O : C, 54.90; H, 4.61; N, 9.15; Found: C, 54.83; H,
3
3
t, J 7.08, CH CH ), 2.55 (3H, s, CH ), 4.35 (2H, q, J 7.00, CH ),
3
2
3
2
14 14
2
6
7
.84 (1H, s, ArH), 7.92 (1H, d, J 3.42, ArH), 8.54 (1H, s, ArH)
4.57; N, 9.12%.
J. Chem. Soc., Perkin Trans. 1, 2000, 995–998
997

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Ethyl 5-ethoxycarbonyl-7-nitro-2H-isoindole-1-carboxylate 3d
112.52, 112.86, 116.71, 116.87, 119.91, 121.63, 128.00, 152.31,
Ϫ1
1
1
60.57 and 160.98; νmax (KBr)/cm 3260, 1650, 1628, 1538,
1
Yield 5%; mp 152–154 ЊC; H-NMR (CD SOCD ) δ 1.30 (3H,
3
3
494, 1432, 1396, 1280, 1156, 1132, 1118, 1040 and 774; m/z
t, J 7.08, CH CH ), 1.35 (3H, t, J 7.16, CH CH ), 4.26 (2H, q,
3
2
3
2
ϩ
ϩ
(
EI) 330 (M , 92%), 284 (M Ϫ EtOH, 100) and 238 (87); Anal.
J 7.08, CH CH ), 4.35 (2H, q, J 7.16, CH CH ), 8.05 (1H, s,
3
2
3
2
Calcd. for C H N O : C, 61.81; H, 5.49; N, 8.48; Found: C,
17
18
2
5
ArH), 8.20 (1H, s, ArH), 8.76 (1H, s, ArH) and 14.17 (1H, br,
6
1.45; H, 5.54; N, 8.41%.
13
NH); C-NMR (CD SOCD ) δ 14.00, 14.12, 60.38, 61.11,
3
3
1
1
1
1
11.06, 116.00, 119.80, 121.71, 121.90, 126.89, 130.09, 142.93,
4
-Cyano-6-nitro-2H-isoindole 6eЈ
Ϫ1
59.54 and 164.59; νmax (KBr)/cm 3212, 1719, 1660, 1638,
ϩ
546, 1446, 1298, 1288, 1240 and 1225; m/z (EI) 306 (M ,
A solution of isoindole tert-butyl ester (2eЈ) (0.0574 g, 0.2
mmol) and a catalytic amount of toluene-p-sulfonic acid in
toluene (2 cm ) was stirred at reflux temperature for 5 min. The
ϩ
00%), 260 (M Ϫ EtOH, 81), 232 (15) and 215 (22); Anal.
3
Calcd. for C H N O : C, 54.90; H, 4.61; N, 9.15; Found: C,
14
14
2
6
5
4.68; H, 4.54; N, 9.19%.
resulting mixture was quenched with aq. sodium hydrogen
carbonate and extracted with chloroform. The organic phase
was washed with water and brine, dried and evaporated. The
residue was purified by silica gel column chromatography (ethyl
acetate–hexane) to give pure title compound 6eЈ.
Ethyl 7-cyano-5-nitro-2H-isoindole-1-carboxylate 2e
1
Yield 64%; mp 235–238 ЊC; H-NMR (CDCl ) δ 1.52 (3H, t,
J 7.17, CH ), 4.59 (2H, q, J 7.12, CH ), 7.96 (1H, d, J 3.66,
ArH), 8.57 (1H, d, J 2.13, ArH), 8.95 (1H, d, J 2.13, ArH) and
3
3
2
1
Yield 27%; H-NMR (CD COCD ) δ 7.65 (1H, s, ArH), 8.05
3
3
(
0
1H, s, ArH), 8.15 (1H, d, J 1.95, ArH), 9.00 (1H, dd, J 1.96,
13
13
1
1
1
1
6
1.13 (1H, br, NH); C-NMR (CD SOCD ) δ 13.78, 59.88,
03.10, 112.55, 116.75, 121.61, 123.61, 123.94, 125.33, 127.62,
40.51 and 159.09; νmax (KBr)/cm 3176, 1658, 1606, 1510,
3 3
.98, ArH) and 12.56 (1H, br, NH); C-NMR (CD SOCD )
3 3
δ 102.40, 109.63, 117.00, 118.73, 120.89, 121.34, 121.92, 126.00
Ϫ1
ϩ
ϩ
and 140.05; m/z (EI) 187 (M , 100%), 157 (M Ϫ NO, 8), 141
ϩ
480, 1446, 1354, 1334, 1312, 1276 and 774; m/z (EI) 259 (M ,
ϩ
(
M Ϫ NO , 95), 129 (18) and 114 (41).
ϩ
2
5%), 213 (M Ϫ EtOH, 100), 183 (14), 167 (18) and 139 (17);
Crystal data for 2eЈؒ1/2CH Cl : C H N O Cl, M = 329.74,
2
2
14.5 14
3
4
Anal. Calcd. for C H N O : C, 55.60; H, 3.50; N, 16.21;
Found: C, 55.61; H, 3.62; N, 15.94%.
12
9
3
4
monoclinic, space group P2 , a = 9.5471(7), b = 14.619(1),
1
/a
3
c = 11.4954(8) Å, β = 97.993(5)Њ, U = 1588.8(2) Å , Z = 4,
Ϫ3
Ϫ1
D = 1.378
g
cm , µ = 23.40 cm , Cu-Kα radiation,
c
tert-Butyl 7-cyano-5-nitro-2H-isoindole-1-carboxylate 2eЈ
λ = 1.54178 Å, T = 296 K, 2737 determined 2570 independent,
1384 observed reflections [I > 2σ(I)], R = 0.080, Rw = 0.075.
Non-hydrogen atoms were refined anisotropically. Hydrogen
atoms were included but not refined. CCDC 207/398. See http://
www.rsc.org/suppdata/p1/a9/a908641b/ for crystallographic
files in .cif format.
1
Yield 55%; mp >300 ЊC; H-NMR (CDCl ) δ 1.60 (9H, s, t-Bu),
7
d, J 2.14, ArH) and 11.10 (1H, br, NH); C-NMR (CD3-
SOCD ) δ 27.98, 82.07, 102.88, 113.84, 117.00, 120.93, 122.85,
3
.90 (1H, d, J 3.67, ArH), 8.53 (1H, d, J 1.83, ArH), 8.93 (1H,
13
3
Ϫ1
1
3
1
23.78, 125.26, 127.27, 140.15 and 158.73; νmax (KBr)/cm
232, 1700, 1608, 1510, 1392, 1342, 1290, 1278, 1196, 1164,
138, 1044 and 1018; m/z (EI) 287 (M , 13%), 231 (M Ϫ
ϩ
ϩ
References
ϩ
(
CH ) C᎐CH , 100), 213 (M Ϫ t-BuOH, 79), 197 (4), 183 (6),
3 2 2
1
67 (8) and 141 (8); Anal. Calcd. for C H N O : C, 58.53;
1 (a) N. Ono, H. Hironaga, K. Simizu, K. Ono, K. Kuwano and
T. Ogawa, J. Chem. Soc., Chem. Commun., 1994, 1019; (b) T.
Murashima, K. Fujita, K. Ono, T. Ogawa, H. Uno and N. Ono,
J. Chem. Soc., Perkin Trans. 1, 1996, 1403; (c) T. Murashima,
R. Tamai, K. Fujita, H. Uno and N. Ono, Tetrahedron Lett., 1996,
14
13
3
4
H, 4.56; N, 14.63; Found: C, 58.65; H, 4.56; N, 14.65%.
Reaction of 1f with ethyl isocyanoacetate
3
7, 8391; (d) N. Ono, H. Hironaga, K. Ono, S. Kaneko, T.
The typical reaction conditions were described above. The
products 2f and 5 could be obtained in pure form by silica gel
column chromatography (ethyl acetate–hexane) and following
recrystallization of the resulting solids from chloroform
solutions.
Murashima, T. Ueda, C. Tsukamura and T. Ogawa, J. Chem. Soc.,
Perkin Trans. 1, 1996, 417; (e) N. Ono, C. Tsukamura, Y. Nomura,
H. Hironaga, T. Murashima and T. Ogawa, Adv. Mater. (Weinheim,
Ger.), 1997, 9, 149.
2 H. Schmidt, C. Lensink, S. K. Xi and J. G. Verkade, Z. Anorg. Allg.
Chem., 1989, 578, 75; J. Tang and J. G. Verkade, Tetrahedron Lett.,
1
Soc., 1993, 115, 5015.
3 R. Schwesinger, C. Hasenfratz, H. Schlemper, L. Walz, E.-M. Peters
and H. G. Schnering, Angew. Chem., Int. Ed. Engl., 1993, 32, 1361.
993, 34, 2903; J. Tang, J. Dopke and J. G. Verkade, J. Am. Chem.
Ethyl 6-methoxy-5-nitroisoindole-1-carboxylate 2f
1
Yield 7%; mp 226–229 ЊC; H-NMR (CD SOCD ) δ 1.38 (3H,
3
3
t, J 7.08, CH ), 3.92 (3H, s, CH O), 4.34 (2H, q, J 7.16, CH ),
3
3
2
4
R. Bonnett and R. F. C. Brown, J. Chem. Soc., Chem. Commun.,
972, 393.
5 L. J. Kricka and J. M. Vernon, J. Chem. Soc., Perkin Trans. 1, 1972,
04; B. Jaques and R. G. Wallace, Tetrahedron, 1977, 33, 581;
7
1
5
1
1
1
4
5
.46 (1H, s, ArH), 7.85 (1H, s, ArH), 8.38 (1H, s, ArH) and
1
13
3.59 (1H, br, NH); C-NMR (CD SOCD ) δ 14.45, 56.03,
3
3
9.57, 99.84, 110.66, 117.91, 120.88, 121.20, 127.56, 138.47,
9
Ϫ1
48.89 and 160.31; νmax (KBr)/cm 3180, 1668, 1628, 1558,
E. Chacko, J. Bornstein and D. J. Sardella, Tetrahedron, 1979, 35,
1055; Y. Watanabe, S. C. Shim, H. Uchida, T. Mitsudo and Y.
Takegami, Tetrahedron, 1979, 35, 1433.
H. Fletcher, Tetrahedron, 1966, 22, 2481; C. O. Bender and
R. Bonnett, J. Chem. Soc. (C ), 1968, 3036.
R. Kreher and G. Use, Angew. Chem., Int. Ed. Engl., 1980, 19, 320.
R. Bonnett and S. A. North, Advances in Heterocyclic Chemistry,
Academic Press, Inc., New York, 1981, pp. 341–399.
528, 1506, 1480, 1436, 1422, 1346, 1324, 1292, 1266, 1232,
ϩ
ϩ
218 and 1182; m/z (EI) 264 (M , 100%), 218 (M Ϫ EtOH,
6
7), 188 (10) and 171 (21); Anal. Calcd. for C H N O : C,
12
12
2
5
4.55; H, 4.58; N, 10.60; Found: C, 54.28; H, 4.52; N, 10.57%.
7
8
Diethyl 4-methoxy-2,7-dihydropyrrolo[3,4-e]isoindole-1,6-
dicarboxylate 5
9 R. Kreher, N. Kohl and G. Use, Angew. Chem., Int. Ed. Engl., 1982,
2
1, 621.
1
Yield 27%; mp 274–277 ЊC; H-NMR (CD SOCD ) δ 1.38 (6H,
10 U. Schöllkopf, D. Hoppe and R. Jentsch, Chem. Ber., 1975, 108,
3
3
m, CH ), 3.92 (3H, s, CH O), 4.35 (4H, m, CH ), 6.96 (1H, s,
1580.
3
3
2
ArH), 7.47 (1H, d, J 3.42, ArH), 8.08 (1H, d, J 3.41, ArH),
13
1
2.30 (1H, br, NH) and 12.53 (1H, br, NH); C-NMR
(
CD SOCD ) δ 14.56, 14.60, 54.61, 59.17, 59.62, 91.09, 111.82,
Paper a908641b
3
3
9
98
J. Chem. Soc., Perkin Trans. 1, 2000, 995–998