New compounds in ring-opening reaction of 5-substituted epoxyisoindolines

Article abstract of DOI:10.1002/jhet.5570390205

Methoxy or nitro group present in the furan ring of tertiary alkenylfurfurylamine changes the expected results of both, the intramolecular [4+2]cycloaddition and the acid catalyzed ring-opening reaction of the derived oxatricycloadduct. With a 5-methoxy group, in addition to the expected 5-methoxyisoindoline 3, the corresponding hydroxy derivative 5 was obtained. On the other hand a 5-nitro group changes the outcome of the reaction even more profoundly. Instead of the expected 5-nitroisoindoline 12, 5-nitro-substituted epoxyisoindoline 6 submitted to ring-opening reaction with the mixture of hydrobromic and acetic acid, yielded the mixture of bromo-substituted epoxy compounds 7, 8, 9 and/or bromo-substituted isoindolines 10 and 11.

Full text of DOI:10.1002/jhet.5570390205

Mar-Apr 2002
New Compounds in Ring-opening Reaction of 5-Substituted
Epoxyisoindolines
277
Ana Dunja Mance*, Branko Borovicˇka and Kresˇimir Jakopcˇic´
Faculty of Chemical Engineering and Technology of the University of Zagreb,
Department of Organic Chemistry, Marulic´ev trg 20, HR 10000, Zagreb, Croatia
Gordana Pavlovic´
Faculty of Science of the University of Zagreb, Chemistry Department, Laboratory for General and Inorganic
Chemistry, Kralja Zvonimira 8, HR 10000, Zagreb, Croatia
and
Ivan Leban
Faculty of Chemistry and Chemical Technology of the University of Ljubljana, Laboratory of Inorganic
Chemistry, P.O. Box 537, 1001, Ljubljana, Slovenia
Received March 16, 2001
Methoxy or nitro group present in the furan ring of tertiary alkenylfurfurylamine changes the expected
results of both, the intramolecular [4+2]cycloaddition and the acid catalyzed ring-opening reaction of the
derived oxatricycloadduct. With a 5-methoxy group, in addition to the expected 5-methoxyisoindoline 3, the
corresponding hydroxy derivative 5 was obtained. On the other hand a 5-nitro group changes the outcome of
the reaction even more profoundly. Instead of the expected 5-nitroisoindoline 12, 5-nitro-substituted epoxy-
isoindoline 6 submitted to ring-opening reaction with the mixture of hydrobromic and acetic acid, yielded
the mixture of bromo-substituted epoxy compounds 7, 8, 9 and/or bromo-substituted isoindolines 10 and 11.
J. Heterocyclic Chem., 39, 277 (2002).
The intramolecular Diels-Alder reaction (IMDA reac-
than three decades ago [6a]. Since that time the IMDAF
reaction has been used by us [3,4,7] and others [8] as a sim-
ple synthetic step towards nitrogen containing heterocycles
and for studies of substituent effects in cyclization reactions.
Further reactions which include the epoxy- bridge of
IMDAF adducts may lead to sometimes rare heterocycles or
natural products difficult to approach by other procedures.
The ring-opening reaction of substituted oxatricy-
cloadduct (epoxyisoindoline), in acidic media is usually
straightforward [5], but the process is dependant on sub-
stituents [3], leading to the corresponding isoindoline.
Unexpectedly, during a study of the substituent influence
on the reaction we found a bridgehead methoxy or nitro
substituents to generate a specific outcome.
tion) has proved over the years to be the most versatile key
step in the synthesis of condensed carbo- or heterocyclic
systems and has been included in many natural product
syntheses. In spite of the fact that examples of intramolec-
ular Diels-Alder reactions with a furan nucleus as the
dienic component (IMDAF reaction [1]) are less numer-
ous, a number of papers have appeared in recent years
illustrating its scope and usefulness in many syntheses [2].
Recently we suggested a useful procedure to convert
simple furans to substituted isoindolines via epoxyisoindo-
lines (Scheme 1) [3]. The process includes the intramolec-
ular Diels-Alder reaction of tertiary N-alkenyl-N-aryl-2-
furfurylamine [4] and subsequent aromatization of the
formed oxatricycloadduct through the ring-opening reac-
tion [5] by hydrobromic acid in glacial acetic acid.
Regarding 5-methoxy derivatives, we found profound
enhancement of the spontaneous ring-opening reaction of
oxatricycloadducts [9] which prevented the isolation of
epoxyisoindolines 2 [3,4]. The isolation of the crude reac-
tion product containing the majority of 5-methoxyisoindo-
The early example of intramolecular [4+2]cycloaddition
with simple furans, that is N-alkenyl-N-aryl-N-(2-
furfuryl)amines, was reported from our laboratory more
Scheme 1

278
A. D. Mance, B. Borovicˇka, K. Jakopcˇic´, G. Pavlovic´ and I. Leban
Vol. 39
Scheme 2
line 3b (R = CH ) and a small amount of hydroxyenone 4b
to those reported for direct reaction of 2a to 5a [3].
Hydroxyenones 4a and 4b obtained during the present
reinvestigation were duly characterized by elemental
analyses, ir, nmr and mass spectra.
Additionally, a single crystal X-ray diffraction con-
firmed the structure of 4a. The crystallographic data, final
atomic coordinates for non-hydrogen atoms and bond dis-
tances and angles are summarized in Tables 1-3. The
ORTEP view of 4a made by the PLATON98 program [11]
is shown in Figure 1.
3
[7e], prompted us to study these transformations (Scheme 2)
more closely. Obviously, the presence of a 5-methoxy group
in N-alkenyl-N-furfuryl-N-arylamine improves not only the
reactivity in the sense of IMDAF reaction but even more,
the susceptibility to ring-opening reaction for the formed
oxatricycloadduct. Both, 1a (R = H) and 1b (R = CH ) sub-
3
jected to IMDAF reaction produce epoxyisoindolines 2a
and 2b [4] but only 2a was possible to isolate and purify by
crystallization of the crude product. The presence of
4-methyl group in 1b both activates the molecule and, with
formation of 2b, drives the spontaneous aromatization via
ring-opening reaction of the epoxy-bridge. This aromatiza-
tion prevented the isolation of 2b [10]. The reaction condi-
tions applied, allowed in fact two kinds of epoxyisoindoline
ring openings. Beside the dominant, above mentioned,
aromatization 2b→3b, the transformation 2b→4b took
place as well (Scheme 2). It is proposed that both reactions
are initiated by traces of atmospheric moisture attacking the
epoxy-bridge in 2b as soon as it was formed by the IMDAF
reaction of 1b. As a consequence, the reaction product is
comprised of 3b and 4b (10:1 respectively). Since we
believed that hydroxyisoindolone may be the intermediate
in the aromatization of 2 to 5 we found essential within the
present study to prepare 4 for the full characterization.
The similar set of reactions was carried out with 2a to
prove the outcome and allow further conclusions about the
influence of a 4-methyl substituent to studied reactions.
The ring-opening reaction of pure oxatricycloadduct 2a,
isolated by the crystallization of crude IMDAF adduct was
performed by heating of their chloroform solution in the
presence of silica gel yielding exclusively 4a (92%).
Under the same reaction conditions but with alumina
instead of silica gel, the mixture of 3a (70%) and 4a (15%)
was obtained. Separated hydroxyenone 4a was success-
fully aromatized by heating of the solution in the mixture
of hydrobromic and acetic acid, with the yield comparable
Table 1
General and Crystal Data and Summary of Intensity Data
Collection and Structure Refinement of 4a
Formula
C H NO
15 16 2
M
243.30
Colorless, Plate
r
Color and habit
Crystal system, Space group
Crystal dimensions (mm )
Monoclinic, P 2 /c
0.23 × 0.17 × 0.06
1
3
Unit cell parameters:
a (Å)
b (Å)
c (Å)
10.482(5)
10.892(5)
11.491(5)
101.44(2)
o
β ( )
3
V (Å )
1285.9(10)
Z
4
-3
D (gcm )
µ (mm )
1.257
0.083
c
-1
F(000)
520
Temperature (K)
Diffractometer
293
Philips PW 1100 updated
by STOE
Radiation: MoK , λ (Å)
2θ range for data collection ( )
h, k, l range
0.71073
4 - 54
-13 to 13, 0 to 13, 0 to 14
α
o
Scan type
ω
No. measured reflections
No. independent reflections
No. refined parameters
No. observed reflections, I ≥ 2σ(I)
R [a], wR [I ≥ 2σ(I)]
R, wR [b] [all data]
2942
2802 (R ) = 0.0783
int
165
555
0.0471, 0.1079
0.2910, 0.1589

Mar-Apr 2002
New Compounds in Ring-opening Reaction of 5-Substituted Epoxyisoindolines
279
Table 1 (continued)
0.62
2
Goodness of fit on F , S [c]
2
g , g in w [d]
0.0810, 0
0.21; -0.21
<0.001
1
-3
Max., min. electron density (e Å )
Maximum ∆/σ
2
2 2
2 2 1/2
[a] R = Σ
[c] S = Σ[w(F - F ) /(N - N
F
- F /Σ
F
; [b] wR = [Σ(F - F ) /Σw(F ) ]
;
o
c
o
o
c
o
2
2 2
1/2
2
2
)] ; [d] w =1/[σ (F ) + g P +
o
c
2
obs
param
o
1
2
g P] where P = (F + 2F )/3.
2
o
c
Table 2
Atomic Coordinates and Equivalent Isotropic
2
Displacement Parameters (Å ) for 4a
Figure 1. A perspective view and atom labeling scheme for the molecular
Atom
x
y
z
Ueq [a]
structure of 4a.
O1
O2
N
C1
C2
C3
C4
C5
C6
C7
C8
C9
C10
C11
C12
C13
C14
C15
-0.3727(3)
-0.5658(3)
-0.1262(3)
-0.1417(3)
-0.2774(4)
-0.3133(4)
-0.4036(4)
-0.4688(4)
-0.4187(4)
-0.2822(3)
-0.2206(3)
-0.0258(4)
-0.0128(4)
0.0901(4)
0.1842(4)
0.1712(3)
0.0691(3)
0.2977(4)
0.2297(3)
-0.0328(3)
0.1292(3)
0.2045(4)
0.1693(4)
0.1864(4)
0.1158(4)
0.0176(4)
-0.0161(4)
0.0343(4)
0.0286(4)
0.1440(4)
0.0686(4)
0.0822(4)
0.1725(4)
0.2480(4)
0.2360(4)
0.1859(4)
-0.0758(3)
-0.3310(3)
0.0413(3)
-0.0651(3)
-0.1316(3)
-0.2618(3)
-0.3262(3)
-0.2734(4)
-0.1456(3)
-0.1011(3)
0.0304(3)
0.1366(3)
0.2371(4)
0.3327(3)
0.3353(4)
0.2370(4)
0.1410(4)
0.4398(3)
0.0640(11)
0.0810(14)
0.0539(16)
0.0493(17)
0.0405(16)
0.0499(17)
0.0559(19)
0.0528(17)
0.0546(17)
0.0400(16)
0.0447(16)
0.0429(16)
0.0473(16)
0.0538(19)
0.0475(17)
0.0498(16)
0.0475(16)
0.0713(19)
Quite different behavior was observed with the electron
withdrawing nitro group. The influence of bridgehead
nitro group in oxatricycloadducts retarded the reaction
with hydrobromic acid/acetic acid reagent so efficiently
that aromatization was detected only if the additional elec-
trondonor (4-methyl group in 6) was present. Although the
aromatization was operable, the expected N-(4-methyl-
phenyl)-4-methyl-5-nitroisoindoline (12) was not
Table 4
General and Crystal Data and Summary of Intensity Data Collection and
Structure Refinement of 11
Formula
C H Br NO
16 15 2
M
397.09
Colorless needle
r
[a] Ueq is the one third of the trace of the orthogonalized U tensor.
Color and habit
Crystal system, Space group
Crystal dimensions (mm )
Monoclinic, P 2 /a (No. 14)
0.4 × 0.08 × 0.1
1
3
Table 3
Unit cell parameters:
Bond Lengths (Å) and Bond Angles (°) for 4a
a (Å)
b (Å)
c (Å)
15.4750(5)
4.5060(5)
Bond lengths
21.2270(5)
99.050(2)
1461.74(17)
4
1.804
5.5
784
200
O1-C2
O2-C5
N-C8
N-C9
N-C1
C1-C2
C2-C3
C2-C7
C3-C4
C4-C5
1.448(5)
1.227(5)
1.465(5)
1.370(5)
1.454(5)
1.524(5)
1.480(5)
1.515(6)
1.326(6)
1.464(6)
C5-C6
C6-C7
C7-C8
C9-C10
C9-C14
C10-C11
C11-C12
C12-C13
C13-C14
C12-C15
1.504(6)
1.523(5)
1.522(5)
1.402(6)
1.406(6)
1.386(6)
1.389(6)
1.382(6)
1.382(6)
1.521(6)
o
β ( )
V (Å )
3
Z
-3
D (gcm )
µ (mm )
c
-1
F(000)
Temperature (K)
Diffractometer
KappaCCD Nonius
0.71073
4 - 54
Radiation: MoK , λ (Å)
α
o
2θ range for data collection ( )
h, k, l range
Bond angles
-19 to 20, -5 to 5, -27 to 27
Scan type
ω
9196
3310 (R )=0.090
182
C1-N-C9
C8-N-C9
C1-N-C8
N-C1-C2
O1-C2-C1
O1-C2-C7
C1-C2-C3
O1-C2-C3
C3-C2-C7
C1-C2-C7
C2-C3-C4
C3-C4-C5
O2-C5-C6
C4-C5-C6
O2-C5-C4
123.1(3)
123.7(3)
112.9(3)
102.5(3)
108.7(3)
106.3(3)
120.0(3)
109.3(3)
110.0(3)
101.5(3)
120.1(4)
122.2(3)
120.6(4)
118.8(4)
120.5(4)
C5-C6-C7
C2-C7-C8
C6-C7-C8
C2-C7-C6
N-C8-C7
N-C9-C14
C10-C9-C14
N-C9-C10
C9-C10-C11
C10-C11-C12
C11-C12-C13
C11-C12-C15
C13-C12- C15
C12-C13- C14
C9-C14-C13
111.3(3)
104.0(3)
120.3(3)
110.1(3)
101.6(3)
122.6(4)
115.8(4)
121.6(4)
121.6(4)
122.0(4)
116.7(4)
121.7(4)
121.6(4)
122.1(4)
121.8(4)
No. measured reflections
No. independent reflections
No. refined parameters
No. observed reflections, I ≥ 2σ(I)
R [a], wR [I ≥ 2σ(I)]
R, wR [b] [all data]
int
1947
0.068, 0.113
0.137, 0.134
1.14
0.0218, 3.4744
0.40; -0.37
<0.001
2
Goodness of fit on F , S [c]
2
g , g in w [d]
1
-3
Max., min. electron density (e Å )
Maximum ∆/σ
2
2 2
2 2 1/2
[a] R = Σ
F
- F /Σ F [b] wR = [Σ(F - F ) /Σw(F ) ] ; [c] S =
o
c
o
o
c
o
2
2 2
1/2
2
2
Σ[w(F - F ) /(N - N
)]
; [d] w =1/[σ (F ) + [g P + g P]
o
c
obs
param
o 1 2
2
2
where P = (F + 2F )/3.
o
c

280
A. D. Mance, B. Borovicˇka, K. Jakopcˇic´, G. Pavlovic´ and I. Leban
Vol. 39
Scheme 3
detected. Instead, under the applied reaction condition
monobromo- and/or dibromoisoindolines 10 and 11 were
isolated. Besides, by the modification of reaction condi-
tions (surplus of the reagent, temperature and reaction
time) small quantities of bromo substituted epoxy-com-
pounds 7, 8 and 9 were also separated (Scheme 3).
The presence of the compound 8 could be explained by
the addition of hydrogen bromide to the epoxyisoindoline
Table 6
Bond Lengths (Å) and Bond Angles (°) for 11
Bond lengths
Br1-C4
Br2-C10
O-C5
C13-C14
N-C1
N-C9
N-C8
C1-C2
C2-C7
C2-C3
C3-C4
1.897(6)
1.909(6)
1.362(7)
1.381(9)
1.461(8)
1.391(8)
1.457(8)
1.482(9)
1.380(9)
1.379(9)
1.370(9)
C4-C5
C5-C6
C6-C16
C6-C7
C7-C8
C9-C14
C9-C10
C10-C11
C11-C12
C12-C15
C12-C13
1.397(9)
1.380(9)
1.507(9)
1.390(9)
1.483(9)
1.399(9)
1.393(9)
1.378(9)
1.358(9)
1.505(9)
1.387(9)
Table 5
Atomic Coordinates and Equivalent Isotropic
2
Displacement Parameters (Å ) for 11
Atom
x
y
z
Ueq [a]
Br1
Br2
O
0.33597(4)
0.08515(5)
0.2034(3)
0.0419(3)
0.1180(4)
0.1485(4)
0.2191(4)
0.2375(4)
0.1863(4)
0.1150(4)
0.0979(4)
0.0262(4)
-0.0134(4)
0.16328(15)
1.1323(2)
0.3944(9)
0.38249(3)
0.08375(4)
0.46570(19)
0.2319(2)
0.2190(3)
0.2809(3)
0.2966(3)
0.3580(3)
0.4041(3)
0.3887(3)
0.3264(3)
0.2973(3)
0.1899(3)
0.1270(3)
0.0903(3)
0.1130(3)
0.1756(3)
0.2127(3)
0.0729(4)
0.4365(3)
0.0598(3)
0.0840(3)
0.0525(17)
0.0495(17)
0.051(2)
0.0444(19)
0.048(2)
0.0443(19)
0.045(2)
0.0431(17)
0.0451(17)
0.048(2)
0.048(2)
0.051(2)
0.055(2)
0.052(2)
0.054(2)
0.052(2)
0.065(3)
0.062(3)
N
1.0173(12)
0.8495(14)
0.7018(13)
0.5146(13)
0.4119(12)
0.4898(13)
0.6746(13)
0.7792(13)
0.9779(14)
1.1959(13)
1.2677(14)
1.4489(14)
1.5781(13)
1.5122(14)
1.3278(14)
1.7762(15)
0.7592(15)
Bond angles
C1
C2
C3
C4
C5
C6
C7
C8
C9
C9-N-C1
C9-N-C8
C1-N-C8
N-C1-C2
C3-C2-C7
C3-C2-C1
C7-C2-C1
C4-C3-C2
C3-C4-C5
C3-C4-Br1
C5-C4-Br1
O-C5-C6
127.7(5)
120.2(5)
112.1(5)
102.7(5)
120.0(5)
128.2(5)
111.8(5)
118.3(5)
121.7(5)
119.8(4)
118.5(5)
116.3(5)
123.2(5)
120.5(5)
117.1(5)
122.2(5)
120.7(6)
C2-C7-C6
C2-C7-C8
C6-C7-C8
N-C8-C7
C10-C9-N
C10-C9-C14
N-C9-C14
C11-C10-C9
C11-C10-Br2
C9-C10-Br2
C12-C11-C10
C11-C12-C13
C11-C12-C15
C13-C12-C15
C14-C13-C12
C13-C14-C9
122.5(6)
109.2(5)
128.3(5)
104.2(5)
128.1(5)
114.4(6)
117.5(5)
122.4(6)
113.5(5)
124.0(5)
122.8(6)
116.3(6)
122.8(6)
120.9(6)
121.5(6)
122.7(6)
C10 -0.0067(4)
C11 -0.0663(4)
C12 -0.1345(4)
C13 -0.1429(4)
C14 -0.0843(4)
C15 -0.1995(4)
O-C5-C4
C6-C5-C4
C5-C6-C7
C5-C6-C16
C7-C6-C16
C16
0.0569(4)
[a] Ueq is the one third of the trace of the orthogonalized U tensor.

Mar-Apr 2002
New Compounds in Ring-opening Reaction of 5-Substituted Epoxyisoindolines
281
double bond of 6. The 7-bromo-compound 8 were isolated
without any sign of aromatization. Similarly, the formation
of N-(2-bromo-4-methylphenyl) derivative 9 could be
explained by the intermediate formation of N-(2-bromo-4-
methylphenyl)-4-methyl-5-nitro-3a,4,5,7a-tetrahydro-
5,7a-epoxyisoindoline (7) via o-bromination of the N-aryl
group in 6 [12], followed by the addition of hydrogen bro-
mide to epoxyisoindoline double bond. The 7-bromo
derivative 9 was isolated, like with compound 8, without
any sign of aromatization.
The obtained bromo-compounds 10 and 11 were fully
characterized by elemental analyses, ir, nmr and mass
spectra. Additionally, the structure of 11 was confirmed by
X-ray crystallographic measurement. The crystallographic
data, final atomic coordinates for non-hydrogen atoms and
bond distances and angles are summarized in Tables 4-6.
The ORTEP drawing of 11 is depicted in Figure 2.
Figure 3. N-Aryl-7-bromo-4-methyl-5-nitro-3a,4,5,6,7,7a-hexahydro-
5,7a-epoxy-isoindolines 8 and 9.
Perhaps the most compelling resonance assignment in
compound 8 is that of the resonance of the proton C7-H at
4.35 ppm, which is well within the normal range for the
hydrogen at this position (at bromine bearing C-atom). The
HMBC spectra shows the correlation with carbon 3a-C at
52.6 ppm and the correlation with the nitrogen bearing car-
3
bon 5-C at 112.4 ppm both of which are three-bond ( J
)
CH
correlations (Figure 4).
Figure 2. A perspective view and atom labeling scheme for the molecular
structure of 11.
Figure 4. Selected HMBC correlation in compound 8 and 9.
To explain the presence of the undoubtedly confirmed 5-
hydroxy group in 10 and 11 we tentatively suggest the
ring-opening reaction under nucleophylic attack at C7a
[3,5], with formation of the corresponding very unstable
geminal hydroxy-nitro intermediate, which possibly could
lead to aromatized compounds 10 and 11. On the other
hand, the attack at C7a and the ring-opening reaction, in
case of saturated 7-bromo epoxy-compounds 8 and 9 must
be more or less suppressed by the vicinity of bromine, pre-
venting the expected aromatization and making possible
the isolation of the corresponding 5-nitro-hexahydroe-
poxyisoindoline.
The similarity of HMBC spectral data of 9, showing the
3
J
correlation between proton C7-H at 4.85 ppm with
CH
carbons 3a-C and 5-C at 52.5 and 113.0 ppm approved the
analogy of structures 8 and 9 (Figure 4).
The NOESY spectra indicate the exo-oriented bromine,
which allowed the possibility of a through-space interaction
of protons C7-H and C3a-H. The other two- and three-bond
correlation in HMBC spectra of the two 7-bromo com-
pounds are in full agreement with the proposed structure.
The structure of aromatized product 10 was deducted
1
13
from its full spectroscopic assignments (ir, H, C nmr
and mass spectra) including NOE correlation. The bal-
ances of the long-range heteronuclear correlation in the
HMBC spectrum were fully consistent with the proposed
structure (Figure 5).
The structure determination of hexahydroepoxyisoin-
dolines 8 and 9, especially regarding the position of the
bromine, rests mostly on an elaborate spectroscopic
1
13
analysis (ir, H, C nmr and mass spectra). The proton-
proton and proton-carbon correlation found within
1
13
The question on the location of the bromine atom at 6-C
in compound 10 with proton C7-H at 7.22 ppm was
H and C nmr spectra using additional techniques
(NOESY, COSY and HMBC) allow us to select the most
probable structures (Figure 3).
1
13
resolved from the long range H- C correlation. The pro-

282
A. D. Mance, B. Borovicˇka, K. Jakopcˇic´, G. Pavlovic´ and I. Leban
Vol. 39
D O exchangeable) for C7a-OH group, 7.22 (d, 1H, J = 9.8 Hz)
2
and 6.10 (d, 1H, J = 9.8 Hz) for enone C7-H and C6-H respec-
tively, 3.52 (d, 1H, J = 10.0 Hz) and 3.46 (d, 1H, J = 10.0 Hz) for
protons at C1, 3.51 (t, 1H, J = 9.6) and 3.34 (t, 1H, J = 9.6 Hz) for
protons at C3, 2.65 (d, 1H, J = 17.2 Hz for C3a-H, 2.61 (d, 1H,
J = 17.2 Hz) and 2.87 (dd, 1H, J = 17.2 Hz, J' = 4.0 Hz) for pro-
tons at C4, 7.07 (d, 2H, J
= 8.5 Hz) and 6.49 (d, 2H, J
=
A2X2
A2X2
8.5 Hz) for p-phenylene protons at C3,3' and C2,6' respectively,
13
2.26 ppm (s, 3H) for p-CH ; C nmr (deuteriochloroform): δ
3
145.4 (d) and 132.0 (d) for unsaturated isoindolone carbons 7-C
and 6-C respectively, 198.7 (s) for carbonyl 5-C; 57.5 (t), 49.5 (t),
44.0 (d), 35.7 (t) and 72.9 (s) for saturated isoindolone carbons 1-
C, 3-C, 3a-C, 4-C and 7a-C respectively, 145.2 (s), 111.3 (d),
129.6 (d) and 125.5 (s) for p-phenylene ring carbons 1'-C, 2'-C,
Figure 5. Selected HMBC correlation in compound 10.
ton C7-H couples with carbons 3a-C at 138.7 ppm and 5-C
3'-C and 4'-C respectively, 20.0 ppm (q) for p-CH ; ms (EI, 10
3
3
at 149.2 ppm via J . The eventually supposed correla-
CH
+
+
eV): m/z (relative intensity) 244 (20, [M+H] ), 243 (100, M ),
134 (15), 133 (95), 120 (10), 105 (45), 91 (5); hrms: [M ] calcd
for C NO : 243.12593; found: 243.11283.
tion of the proton C6-H for 7-bromo substituted analogue
+
'
4
via J to 3a-C should be considerably less reasonable.
CH
H
15 17
2
The structure of N-(2-bromo-4-methylphenyl)-6-bromo-5-
hydroxyisoindoline (11) was similarly deducted from its full
spectroscopic assignments (ir, H, C nmr and mass spectra)
and was confirmed by X-ray structure determination..
Anal. Calc'd. for C
5.76%; found: C 74.19, H 7.07, N 5.78%.
H NO (M =243.30): C 74.05, H 7.04, N
15 17 2 r
1
13
Single Crystal X-ray Structural Determination of 4a.
Colorless monoclinic crystals in a form of thin plates were
obtained by repeated recrystallization from acetone/water 5:2.
Suitable crystals were formed on very slow crystallization during
5 days at –3 °C. Data collection was carried out on a four-circle
automatic PW 1100 diffractometer. The program STADI4 [15]
was used for data collection and the program X-RED for data
reduction [16]. The structure was determined by the program
DIRDIF-96 [17] by fitting of known structural fragment of pro-
nounced rigidity i.e. N-p-tolyl moiety, on the basis of vector
search methods. The initial chemically reasonable isotropic
model was further refined by using SHELXL97 program [18].
EXPERIMENTAL
Melting points were determined on an "Original Kofler
Mikroheitztisch" apparatus (Reichardt, Wien) and are not cor-
rected. Infrared spectra were taken in potassium bromide pellets
with a Perkin-Elmer Model 297 instrument. The proton nmr
spectra were obtained using a Varian GEMINI 300 spectrometer,
a Brucker AVANCE DPX 300 or a Brucker AVANCE DRX 500
nmr spectrometer (working at 500.13 MHz) with tetramethylsi-
2
All non-hydrogen atoms were refined anisotropically based on F
13
lane as the internal standard. The Carbon nmr spectra were
by full-matrix least-squares method. All hydrogen atoms were
included in calculated positions as riding atoms with the
SHELXL97 [18] default parameters.
recorded on a Varian GEMINI 300 instrument at 75 MHz using
the APT technique and a BRUCKER AVANCE DPX 300 or a
Brucker AVANCE DRX 500 nmr spectrometer (working at
125.77 MHz). Mass spectra were recorded on the Extrel FTMS
2001 DD spectrometer by a direct insertion probe using electron
impact or N laser ionization. The molecular structure was deter-
mined by X-ray diffraction using the Philips PW 1100 or the
KappaCCD Nonius diffractometer.
N-(4-Methylphenyl)-7a-hydroxy-4-methyl-3a,4,5,7a-tetrahy-
droisoindolin-5-one (4b).
2
The tertiary amine 1b (1.36 g, 5 mmol) dissolved in dried
benzene was heated for 48 hours at 50 °C. The formation of 2b
1
was indicated by H nmr spectra in the experiment carried out
N-(4-Methylphenyl)-7a-hydroxy-3a,4,5,7a-tetrahydroisoindolin-
5-one (4a).
in deuteriochloroform solution of 1b standing at –18 °C for sev-
eral months. The compound 2b was not isolated due to the
spontaneous aromatization to 3b [7e]. After evaporation, the
crude product was purified by a column chromatography on
neutral aluminum oxide with hexane/chloroform 5:1 and
hexane/ether 10:1. After the separation of 3b (75%) and a small
amount of starting compound, pure crystalline hydroxyenone
4b (0.9 g, 7%) melting at 164-165 °C was obtained; ir (potas-
sium bromide): ν 3500s (OH), 2920m, 2840w, 1675s (C=O),
Procedure A.
Silica gel (4.0 g, chromatographic grade) was added to the solu-
tion of 129 mg (5 mmol) of N-(4-methylphenyl)-5-methoxy-5,7a-
epoxy-3a,4,5,7a-tetrahydroisoindoline (2a) [7b] in 10 ml of chlo-
roform. The reaction mixture was heated under reflux for 3 hours.
Silica gel was removed by filtration and the solvent evaporated.
Crude crystalline 4a (93.8 mg, 92%) melted at 205-206 °C.
-1
1
1620m (C=C), 1525vs, 1380m, 920m, 800s cm ; H nmr (deu-
teriochloroform): δ 2.03 (s, 1H, D O exchangeable) for C7a-
2
Procedure B.
OH group, 7.15 (d, 1H, J = 9.8 Hz) and 6.08 (d, 1H, J = 9.8 Hz)
for enone C7-H and C6-H respectively, 3.52 (d, 1H, J = 10.0
Hz) and 3.46 (d, 1H, J = 10.0 Hz) for protons at C1, 3.40 (t, 1H,
J = 9.0) and 3.37 (t, 1H, J = 9.0 Hz) for protons at C3, 2.97-2.86
(m, 1H) for C4-H; 1.21 (d, 3H, J = 6.9 Hz) for isoindolinone
From 2a by the reaction procedure as mentioned above, only
with neutral aluminum oxide (Grade I) instead of silicagel. N-(4-
Methylphenyl)-7a-hydroxy-3a,4,5,7a-tetrahydroisoindolin-5-one
(4a) was obtained as colorless crystals, yield 15%, mp 206-207
°C [14]; ir (potassium bromide): 3480bs (OH), 1675s (C=O),
C4-CH , 2.40-2.30 (m, 1H) for C3a-H, 7.15 (d, 2H, J
= 8.0
3
A2X2
-1
1
1620s (C=C) cm ; H nmr (deuteriochloroform): δ 1.94 (s, 1H,
Hz) and 6.50 (d, 2H, J
= 8.0 Hz) for p-phenylene protons at
A2X2

Mar-Apr 2002
New Compounds in Ring-opening Reaction of 5-Substituted Epoxyisoindolines
283
C3,5' and C2,6' respectively, 2.26 ppm (s, 3H) for p-CH ;
C nmr (deuteriochloroform): δ 144.4 (d) and 132.1 (d) for
for phenylene 4'-C, 20.1 (q) for p-CH and 12.9 ppm (q) for
methyl group at isoindoline 4-C; ms (LDI, 337 nm): m/z (relative
3
3
13
+
81
79
unsaturated isoindolinone 7-C and 6-C respectively, 201.5 (s)
for carbonyl 5-C, 57.8 (t), 48.9 (t), 50.4 (d), 40.1 (d) and 73.5 (s)
for saturated isoindolinone 1-C, 3-C, 3a-C, 4-C and 7a-C respec-
tively, 12.5 (q) for methyl at 4-C, 145.4 (s), 111.5 (d), 129.8 (d)
and 125.7 (s) for p-phenylene carbons 1'-C, 2'-C, 3'-C and 4'-C
intensity) 319/317 (29/30, M [ Br/ Br]), 318/316 (96/100, [M-
+
H] ), 238 (65), 237 (45), 184 (15), 120 (10), 118 (10), 91 (20) and
52 (60) ; hrms: [M ] calcd for C H
+
'
79
BrNO: 317.04153; found:
16 16
79
317.04071 [ Br].
Anal. Calc'd. for C
H BrNO (M = 318.21): C 60.39, H 5.07,
16 16 r
respectively, 20.0 ppm (q) for p-CH ; ms (EI, 10 eV): m/z (rela-
N 4.40%; found: C 60.28, H 5.01, N 4.28%.
3
+
+
tive intensity) 258 (30, [M+H] ), 257 (100, M ), 224 (45), 196
N-(4-Methylphenyl)-7-bromo-4-methyl-5-nitro-3a,4,5,6,7,7a-
hexahydro-5,7a-epoxyisoindoline (8).
+
(5), 149 (5), 134 (10), 133 (45), 120 (10), 105 (40); hrms: [M ]
'
calc d for C
H NO : 257.14158; found: 257.14103.
16 19 2
This compound (200 mg, 11%, Rf=0.42) was obtained from
slower moving fractions. Colorless crystals melting at 232-234
°C; ir (potassium bromide): ν 3020w, 2960m, 2930w, 2905w,
2880w, 2840m, 1615m, 1550s, 1515s, 1470m, 1455m, 1440m,
1360s, 1335m, 1270w, 1180m, 1110w, 1070m, 950m, 905w,
855m, 830m, 800s, 740w and 630w cm ; H nmr (deuteriochlo-
roform): δ 3.78 (d, 1H, J = 13.5 Hz) and 3.73 (d, 1H, J = 13.5 Hz)
for protons at C1, 3.94 (t, 1H, J = 8.7 Hz) and 3.28 (t, 1H, J = 8.7
Hz) for protons at C3, 2.27-2.21 (m, 1H) for C3a-H, 2.66-2.57
(m, 1H) for C4-H, 1.30 (d, 3H, J = 7.1 Hz) for methyl at C4, 3.40
Anal. Calc'd. for C
H NO (M =257.33): C 74.68, H 7.44, N
16 19 2 r
5.44%; found: C 74.56, H 7.47, N 5.55%.
N-(4-Methylphenyl)-5-hydroxyisoindoline (5a).
The Preparation from Isolated 4a.
-1
1
The solution of hydroxyenone 4a (49 mg, 2 mmoles) in a mix-
ture of glacial acetic and 48% hydrobromic acid (1:1) was heated
at 60 °C for 3 days under protection from light. The reaction mix-
ture was poured into ice-cold water and carefully neutralized
with 5% sodium hydroxide solution (pH 6-7). The solution was
extracted with diethyl ether. From the dried etheral solution 5a
was isolated on a silica gel column protected from light, using
petroleumether/ether 5:1 as eluent. Colorless crystals (43 mg,
95%) melting at 159-160 °C proved to be identical with the orig-
inal sample [3] by the comparison of their elemental analysis, ir,
nmr and mass spectra.
(dd, 1H, J = 14.0 Hz, J = 7.5 Hz) and 2.71 (dd, 1H, J = 14.0 Hz,
1
2
1
J = 3.0 Hz) for protons at C6, 4.35 (dd, 1H, J = 7.5 Hz, J = 3.0
2
1
2
Hz) for C7-H, 7.05 (d, 2H, J
= 8.2 Hz) and 6.48 (d, 2H,
A2X2
J
= 8.2 Hz) for p-phenylene protons at C3,5' and C2,6'
A2X2
13
respectively and 2.26 ppm (d, 3H, J = 7.1) for p-CH ; C nmr
3
(deuteriochloroform): δ 52.6 (t) [19] and 55.2 (t) for 1-C and 3-
C, 52.6 (d) [19] for 3a-C, 47.2 (d) and 46,8 (d) for 4-C and 7-C,
14.5 (q) for carbon of methyl group at 4-C, 112.4 (s) for 5-C, 41.2
(t) for 6-C, 94.8 (s) for 7a-C, 144.8 (s), 112.2 (d), 129.9 (d) and
126.4 (s) ppm for phenylene 1'-C, 2'-C, 3'-C and 4'-C respec-
tively, and 20.1 ppm (q) for methyl of p-tolyl group; ms (LDI,
Reaction of N-(4-Methylphenyl)-4-methyl-5-nitro-3a,4,5,7a-
tetrahydro-5,7a-epoxyisoindoline (6) with Hydrobromic
Acid/Acetic Acid Mixture.
Procedure A.
+
337 nm): m/z (relative intensity) 368/366 (15/15, M
[
81
79
+
Br/ Br]), 367/365 (49/50, [M-H] ), 322 (10), 320 (10), 318
Epoxyisoindoline 6 (1.43 g, 5 mmole) was added to a mixture
of 10 ml glacial acetic acid and 10 ml 66% hydrobromic acid.
The reaction mixture protected from exposure to light was heated
at 60-70 °C for 48 hours. The dark colored reaction mixture was
poured into 100 ml of ice-cold water and neutralized to pH 6-7
with the 5% sodium hydroxide solution. The neutralized solution
was extracted with ether (3x20 ml). The organic extracts were
dried over the anhydrous magnesium sulfate and the solvent
evaporated. The crude reaction product was subjected to silica
gel column chromatography with petroleum ether/ether 5–10 %
in the column protected from light.
(15), 316 (15), 289 (15), 287 (15), 280 (10), 279 (50), 241 (25),
240 (100), 238 (30), 210 (10), 184 (20) 143 (10) and 141 (10);
+
'
79
hrms: [M ] calc d for C
H
BrN O : 366.05790; found:
16 19 2 3
79
366.05169 [ Br].
Anal. Calc'd. for C
H N O (M =367.24): C 52.33, H 5.21,
16 19 2 3 r
N 7.63%; found: C 52.35, H 5.19, N 7.61%.
Procedure B.
Similarly as in procedure A, but at lower temperature and with
substantially higher quantity of hydrobromic acid/acetic acid
mixture. Epoxyisoindoline 6 (1.43 g, 5 mmole) was added to 40
ml of acid mixture and was heated in the reaction vessel protected
from light at 40-50 °C. After 48 hours of heating and usual elab-
oration hexahydroisoindoline 7 was isolated. The remaining
material was starting compound 6 (more than 90 %) and traces of
some resinous material.
N-(4-Methylphenyl)-6-bromo-5-hydroxy-4-methylisoindoline (10).
This compound (1.0 g, 64%, Rf=0.85) was obtained by evapo-
ration of the more mobile fractions. Colorless crystals, mp. 174-
175 °C; uv (methanol): λ
246, 275 nm (sh); ir (potassium bro-
max
mide): ν 3460s (OH), 2920m, 2860m, 2820m, 1630s (C=C),
1530vs, 1470s, 1380vs, 1310vs, 1180m, 1070m, 850m, 800vs,
N-(2-Bromo-4-methylphenyl)-4-methyl-5-nitro-3a,4,5,7a-
tetrahydro-5,7a-epoxyisoindoline (7).
-1
1
780s cm ; H nmr (acetone-d ): δ 7.74 (s, 1H, D O exchange-
6
2
able) for C5-OH group, 7.37 (s, 1H) for isoindoline C7-H, 4.52 (s,
2H) for protons at C1; 4.53 (s, 2H) for protons at C3, 7.06 (d, 2H,
This compound was obtained as yellow crystals (91 mg, 5%)
melting at 171-173 °C; ir (potassium bromide): ν 3080w, 2920m,
2840w, 1620m, 1560s, 1530s, 1480m, 1460w, 1410w, 1380m,
1360s, 1310w, 1270w, 1230w, 1170m, 1150m, 1120m, 1040w,
J
= 8.5 Hz) and 6.62 (d, 2H, J
= 8.5 Hz) for p-phenylene
A2X2
A2X2
protons at C3,5' and C2,6' respectively, 2.29 (s, 3H) for p-CH ,
3
13
2.23 ppm (s, 3H) for isoindoline C4-CH ; C nmr (acetone-d ): δ
3
6
-1
1000w, 950m, 900w, 860m, 840m, 800s, 710s and 690w cm ;
53.0 (t) and 53.4 (t) for isoindoline 1-C and 3-C, 138.7 (s) for
3a-C, 120.1 (s) for 4-C, 149.2 (s) for 5-C, 108.9 (s) for 6-C, 122.6
1
H nmr (deuteriochloroform): δ 7.0 (d, 1H, J = 5.6 Hz) and 6.76
'
(d, 1H, J = 5.6 Hz) for C7-H and C6-H, 4.53 (d, 1H, J = 12.5 Hz)
and 3.18 (d, 1H, J = 12.5 Hz) for protons at C1, 3.70 (t, 1H, J =
(d) for 7-C and 130.7 (s) for 7a-C, 145.0 (s) for phenylene 1-C,
'
'
'
'
111.4 (d) for 2-C and 6-C, 129.9 (d) for 3-C and 5-C, 125.4 (s)

284
A. D. Mance, B. Borovicˇka, K. Jakopcˇic´, G. Pavlovic´ and I. Leban
Vol. 39
9.5 Hz) and 3.27 (t, 1H, J = 9.5 Hz) for protons at C3, 2.04 (dt,
1H, J = 9.5 Hz, J = 3.0 Hz) for C3a-H, 2.55 (dq, 1H, J = 7.0 Hz,
KappaCCD Nonius diffractometer. Program Denzo-SMN [20]
was used for data reduction. No absorption correction has been
applied, only scaling. Structure has been solved using the
SHELXS97 program [21]. All non-hydrogen atoms were refined
1
2
1
J = 3.0 Hz) for C4-H, 1,10 (d, 3H, J = 7.0) for methyl protons at
2
isoindoline C4, 7.35 (dd, 1H, J = 1.3 Hz), 7.07 (dd, 1H, J = 8.5
2
1
2
Hz, J = 1.3 Hz) and 7.01 (d, 1H, J = 8.5 Hz) and for protons at
anisotropically based on F by full-matrix least-squares method.
2
aryl carbons C3', C5' and C6' respectively and 2.23 ppm (s, 3H)
All hydrogen atoms were included in calculated positions as rid-
ing atoms with the SHELXL97 [18] default parameters.
13
for p-CH ; C nmr (deuteriochloroform): δ 139.6 (d) and 131.3
3
(d) for isoindoline unsaturated 7-C and 6-C respectively, 115.0
(s), 95.1 (s), 55.8 (t), 53.0 (t), 53.7 (d) and 44.4 (d) for isoindoline
saturated 5-C, 7a-C, 1-C, 3-C, 3a-C and 4-C respectively, 15.5 (q)
for methyl carbon at isoindoline 4-C, 145.4 (s), 115.7 (s), 134.6
(d), 132.9 (s), 129.0 (d) and 119.7 (d) for p-phenylene carbons 1'-
C, 2'-C, 3'-C, 4'-C, 5'-C and 6'-C respectively, 19.4 ppm (q) for
carbon of p-methyl group; ms (EI, 20 eV): m/z (relative intensity)
N-(2-Bromo-4-methylphenyl)-7-bromo-4-methyl-5-nitro-5,7a-
epoxy-3a,4,5,6,7,7a-hexahydroisoindoline (9).
During chromatographic separation of the crude reaction prod-
ucts beside 10 and 11 as described above a small quantity of com-
pound 9 was separated. Light yellow crystals (112 mg, 5%,
Rf=0.62) melting at 86-88 °C; ir (potassium bromide): ν 3010w,
2960w, 2920s, 2840m, 1605m, 1550s, 1490s, 1460m, 1360m
1320m, 1260m, 1160m, 1050m, 950m, 830m, 830m, 810s,
+
+
81
79
367/365 (20/20, [M+H] ), 366/364 (97/100, M
[ Br/ Br]),
333 (10), 332 (15), 331 (10), 330 (15), 312 (24), 310 (25), 287
(25), 286 (40), 285 (25), 266 (15), 257 (40), 239 (10) and 184
-1
1
750m, 600s cm ; H nmr (acetone-d ): δ 4.21 (d, 1H, J = 12.0
6
+
'
79
(10); hrms: [M ] calcd for C
H
BrN O : 364.04225 , found:
Hz) and 3.37 (d, 1H, J = 12.0 Hz) for protons at C1, 3.75 (t, 1H,
J = 9.0 Hz) and 3.44 (t, 1H, J = 9.0 Hz) for protons at C3, 2.45 (dt,
16 17 2 3
79
364.03644 [ Br].
1H, J = 9.0 Hz, J = 4.7 Hz) for C3a-H, 2.67-2.61 (m, 1H) for
1
2
Procedure C.
C4-H, 1.32 (d, 3H, J = 7.0 Hz) for methyl at C4, 3.62 (dd, 1H,
J = 14.5 Hz, J = 7.5 Hz) and 2.67 (dd, 1H, J = 14.5 Hz, J = 3.0
In a repeated experiment with the same quantity of 6 as in pro-
cedure B, during heating at 40-50 °C for 5 days, two additional
portions of the same acid mixture (2x20 ml) were added.
Column chromatography after a careful neutralization of reac-
tion mixture yielded 318 mg (20%) of the compound 10 which
was identical with the sample from procedure A and pure
dibromo derivative 11.
1
2
1
2
Hz) for protons at C6, 4.85 (dd, 1H, J = 7.5 Hz, J = 3.0 Hz) for
1
2
C7-H, 7.40 (d, 1H, J = 2.0 Hz), 7.14 (dd, 1H, J = 8.2 Hz, J = 2.0
1
2
Hz) and 7.08 (d, 1H, J = 8.2 Hz) for protons C3', C5' and C6' at
13
aryl group respectively and 2.27 ppm (s, 3H) for p-CH ; C nmr
3
(acetone-d ): δ 55.3 (t) and 58.0 (t) for 1-C and 3-C, 52.5 (d) for
6
3a-C, 46.6 (d) and 49.0 (d) for 4-C and 7-C, 13.5 (q) for carbon of
methyl group at 4-C, 113.0 (s) for 5-C, 41.8 (t) for 6-C, 95.4 (s)
for 7a-C, 145.0 (s), 115.8 (s), 134.6 (d), 133.6 (s), 129.1 (d) and
102.0 (s) for aromatic 1'-C, 2'-C, 3'-C, 4'-C, 5'-C and 6'-C respec-
tively and 19.5 ppm (q) for carbon of p-methyl group; ms (EI, 70
N-(2-Bromo-4-methylphenyl)-6-bromo-5-hydroxy-4-methyliso-
indoline (11).
This compound was obtained as colorless micro crystals (1.03
g, 52%) melting at 120-122 °C (Rf=0.9); uv (methanol): λ
220, 245 (sh); ir: ν 3420s (OH), 2925s, 2860m, 1620s (C=C),
1510vs, 1465vs, 1370vs, 1320s, 1260m, 1220m, 1070s, 860s,
790vs, 780s cm ; H nmr (acetone-d ): δ 7.70 (s, 1H, D O
exchangeable) for C5-OH, 7.33 (s, 1H) for isoindoline C7-H,
4.61 (s, 2H) for protons at C1, 4.64 (s, 2H) for protons at C3, 7.42
+
max
eV): m/z (relative intensity) 448/446/444 (48/100/50, M
81
79
[
Br/ Br]), 398 (6), 396 (10), 394 (6), 367 (30), 365 (30), 320
+
'
79
(15) and 318 (15); hrms: [M ] calc d for C
H
Br N O :
16 18 2 2 3
-1
1
79
6
2
443.96841 , found: 443.95691 [ Br].
Anal. Calc'd. for C
H N O (M =446.13): C 43.07, H 4.07,
16 18 2 3 r
N 6.28%; found: C 43.29, H 4.23, N 6.32%.
(d, 1H, J = 1.4 Hz), 7.13 (dd, 1H, J = 1.4 Hz, J = 8.5 Hz) and
1
2
7.21 (d, 1H, J = 8.5 Hz) for protons C3'-H, C5'-H and C6'-H,
Acknowledgements.
2.27 (s, 3H) for protons of p-CH , and 2.24 ppm (s, 3H) for pro-
3
We thank the Ministry of Science, Technology and
Information, Republic of Croatia for their financial support
through the grant 125004. We also acknowledge with thanks the
financial contribution of the Ministry of Science and Technology,
Republic of Slovenia through grant Packet X-2000 and PS-511-
103, which made possible the purchase of the KappaCCD Nonius
diffractometer in the Laboratory of Inorganic Chemistry, Faculty
of Chemistry and Chemical Technology, University of Ljubljana,
Slovenia.
We are especially indebted to the staff of the Central
Analytical Service, the Laboratory for nmr and the Laboratory
for mass spectrometry of the "Rugjer Bosˇkovic´" Institute for
elemental analyses and recording the nmr and mass spectra.
13
tons of isoindoline C4-CH
C nmr (acetone-d ): δ 55.7 (t) for
3;
6
isoindoline 1-C, 56.2 (t) for 3-C, 139.3 (s) for 3a-C, 119.9 (s) for
4-C, 149.1 (s) for 5-C, 108.6 (s) for 6-C, 122.4 (d) for 7-C, 131.6
(s) for 7a-C, 20.1 (q) for methyl group at isoindoline 4-C, 145.1
'
'
(s) for p-phenylene carbon 1-C, 115.6 (s) for 2-C, 135.0 (d) for
'
'
'
'
3-C, 132.7 (s) for 4-C, 128.7 (d) for 5-C and 119.7 (d) for 6-C,
and 13.0 ppm (q) for p-methyl carbon; ms (EI, 85 eV): m/z (rela-
tive intensity) 399/397/395 (24/50/25, M
398/396/394 (49/100/50, [M-1] ), 319 (25), 318 (30), 317 (40),
316 (30), 315 (30), 237 (10), 111 (20), 109 (20), 97 (25), 95 (30)
and 91 (30); hrms: [M ] calcd for C
+
81
79
[ Br/ Br]),
+
+
'
79
H
Br NO: 394.95204,
16 15 2
79
found: 394.94973 [ Br].
Anal. Calc'd. for C
H Br NO (M = 397.10): C 48.39, H
16 15 2 r
3.81, N 3.53%; found: C 48.53, H 3.95, N 3.64%.
REFERENCES AND NOTES
Single Crystal X-ray Structural Determination of 11.
Colorless monoclinic crystals in a form of thin needles were
obtained by repeated recrystallization from acetone/water 5:2.
Suitable crystals were formed on very slow crystallization during
5 days at –3 °C. Data collection was carried out on the
*
Author to whom correspondence should be addressed.
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Mar-Apr 2002
New Compounds in Ring-opening Reaction of 5-Substituted Epoxyisoindolines
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1
[10] The formation of 2b was indicated by H nmr spectra in
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ˇ
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