Two (Z)-N-aryl-3-benzylideneisoindolin-1-ones

Article abstract of DOI:10.1107/S0108270199012445

Two isoindolin-1-one derivatives, (Z)-3-benzylidene-N-phenylisoindolin-1-one, C₂₁H₁₅NO, (II), and (Z)-3-benzylidene-N-(4-methoxyphenyl)isoindolin-1-one, C₂₂H₁₇NO₂, (III), were synthesized by the palla

Full text of DOI:10.1107/S0108270199012445

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
et al., 1998; Kundu et al., 1999; Guha et al., 1999). The mole-
cular con®gurations, E or Z, of these compounds are in¯u-
enced by the type of substituents. To study the effect of
ISSN 0108-2701
Two (Z)-N-aryl-3-benzylideneisoin-
dolin-1-ones
substitution on the conformation of the resulting compounds
and to build up a hierarchy for such systems, X-ray analyses of
a
a
b
Alok K. Mukherjee, * Subhadra Guha, M. Wahab Khan,
b
c
Nitya G. Kundu and Madeleine Helliwell
(
Z)-3-benzylidene-N-phenylisoindolin-1-one, (II), and (Z)-
a
b
Department of Physics, Jadavpur University, Calcutta 700 032, India, Department
of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur,
c
Calcutta 700 032, India, and Department of Chemistry, University of Manchester,
Manchester M13 9PL, England
Correspondence e-mail: akm@juphys.ernet.in
Received 22 March 1999
Accepted 29 September 1999
Two isoindolin-1-one derivatives, (Z)-3-benzylidene-N-
phenylisoindolin-1-one, C H NO, (II), and (Z)-3-benzyl-
2
1
15
idene-N-(4-methoxyphenyl)isoindolin-1-one,
C H NO ,
22 17 2
(III), were synthesized by the palladium-catalysed hetero-
annulation. The molecules of both compounds have a Z
con®guration. The interplanar angles between the ®ve- and
six-membered rings of the isoindolinone moiety in (II) and
ꢀ
(
at the N-position in (II) and (III) are twisted out of the C N
III) are 1.66 (11) and 2.26 (7) , respectively. The phenyl rings
4
ꢀ
ring plane by 62.77 (11) and 67.10 (7) , respectively. The
substitutions at the N and C-3 positions of the isoindolinone
system have little in¯uence on the molecular dimensions of the
resulting compounds.
Figure 1
The molecular structure of (II) showing the 50% probability displace-
ment ellipsoids.
Comment
The isoindolinone (phthalimidine) system (I) is present in a
number of natural products. Many isoindolinone derivatives
display biological activity as potential anti-in¯ammatory
agents, antipsychotics (Zhuang et al., 1998; Linden et al., 1997)
and inhibitors of human CCRF-CEM lymphoblastic
leukaemic cells (Taylor et al., 1997). The majority of structu-
rally determined isoindolinone systems are either N-substi-
tuted or have a hydroxy substituent at the 3-position (Brady et
al., 1998; McNab et al., 1997; Barrett et al., 1996; Feeder &
Jones, 1996). As part of an ongoing program on the synthesis
and characterization of new heterocyclic systems containing
an isoindolinone moiety, we have recently reported the crystal
structures of several N and C-3 substituted derivatives (Khan
Figure 2
The molecular structure of (III) showing the 50% probability displace-
ment ellipsoids.
Acta Cryst. (2000). C56, 85±87
Alok K. Mukherjee et al. ꢁ
C
22
H
17NO
2
and C21
H15NO 85

organic compounds
3-benzylidene-N-(p-methoxyphenyl)isoindolin-1-one, (III),
were undertaken.
The Z con®guration of the molecules of (II) and (III), which
contain essentially planar isoindolinone and phenyl moieties
(Kundu et al., 1999) while the alkyl/aryl substitutions at both
the N and C-3 positions introduce considerable puckering in
the resulting molecules.
(
see Figs. 1 and 2), are established by the torsion angle NÐ
Experimental
ꢀ
C14ÐC15ÐC16 of 5.4 (5) and 3.3 (4) in (II) and (III),
respectively. The bond lengths and angles observed for the
heterocyclic ring in (II) and (III) are similar to those reported
for substituted isoindolinone structures (Kundu et al., 1999;
Khan et al., 1998; McNab et al., 1997; Feeder & Jones, 1996).
The angles between the ®ve- and six-membered rings of the
0
2
-(2 -Phenylethynyl)-N-phenyl benzamide (PEPB) was synthesized
by stirring a mixture of 2-iodo-N-phenyl benzamide (1 mmol) with
phenylacetylene (1.2 mmol) in dimethylformamide (DMF) (5 ml) at
353 K for 16 h in the presence of bis(triphenylphosphine)-
palladium(II) chloride (3.5 mol%), copper iodide (8 mol%) and
triethylamine (4 mmol). After usual workup and puri®cation by
chromatography (silica gel 60±80 mesh), the product (PEPB) was
cyclized to 3-benzylidene-N-phenylisoindolin-1-one, (II), m.p.
isoindolinone system in (II) and (III) are 1.66 (11) and
ꢀ
2
for an atom in either ring plane is 0.009 (3) A for C7 in (II),
.26 (7) , respectively; the maximum deviation from planarity
Ê
4
70 (1) K, by re¯uxing with sodium ethoxide in ethanol for 4 h. Single
crystals suitable for X-ray analysis were obtained from ethanol.
Elemental analysis: calculated for C21 15NO: C 84.82, H 5.08, N
.71%; found: C 84.49, H 5.13, N 4.60%. Starting with 2-iodo-N-p-
Ê
Ê
with the carbonyl-O atom 0.030 (3) A [in (II)] and 0.004 (2) A
in (III)] away from the C N planes. The phenyl rings (C1Ð
C6) and (C16ÐC21) in (II) are twisted out of the C N ring
H
[
4
4
0
4
anisyl benzamide, the procedure as described above yielded 2-(2 -
phenylethynyl)-N-p-methoxyphenylbenzamide (PEMB), which on
cyclization afforded 3-benzylidene-N-(4-methoxyphenyl)isoindolin-
1-one, (III), m.p. 441 (1) K. Single crystals suitable for X-ray analysis
were obtained from ethanol. Elemental analysis: calculated for
ꢀ
plane with dihedral angles 62.77 (11) and 55.72 (10) , respec-
ꢀ
tively; the corresponding values are 67.10 (7) and 55.05 (7) in
(
(
III). In the fused six-membered ring (C8ÐC13) of (II) and
ꢀ
III), the angles at C9 and C12 are less than 118 , an effect
22 2
C H17NO , C 80.91, H 5.23, N 4.27%; found: C 80.90, H 5.36, N
previously noted by McNab et al. (1997). The cis orientation of
O2ÐC22 with respect to C3ÐC4 about the O2ÐC3 bond in
4.13%.
(
because of this the bond angle C4ÐC3ÐO2 is increased by
III) results in repulsion between the C4 and C22 atoms and
Compound (II)
ꢀ
about 9 (Table 3) compared to C2ÐC3ÐO2. The torsion
ꢀ
angle C4ÐC3ÐO2ÐC22 is 7.3 (3) . In both the structures, the
carbonyl atoms are involved in weak CÐHÁ Á ÁO inter-
Crystal data
C H NO
2
1
15
Cu Kꢀ radiation
Cell parameters from 25
re¯ections
M
r
= 297.34
Orthorhombic, P2 2 2
molecular contacts (Tables 2 and 4).
1
1
1
A comparison of geometrical parameters of various isoin-
dolinone derivatives (Table 5) reveals that substitutions at N
and/or C-3(C14) positions have apparently little in¯uence on
the molecular dimensions. The dihedral angles between the
isoindolinone moiety and the planar parts of the R1/R2 groups
in different compounds (Table 5) indicate an approximate
molecular coplanarity for the N-unsubstituted derivative
ꢀ
Ê
a = 9.366 (3) A
ꢁ = 25.1±29.8
b = 19.875 (1) AÊ
�
1
ꢂ = 0.622 mm
T = 293 (2) K
Prism, colourless
Ê
c = 8.204 (9) A
Ê
V = 1527.2 (17) A
3
Z = 4
D = 1.293 Mg m
0.40 Â 0.30 Â 0.25 mm
�
3
x
Table 3
Selected geometric parameters (A, ) for (III).
Ê
ꢀ
NÐC7
NÐC14
NÐC6
O1ÐC7
O2ÐC3
1.400 (3)
1.417 (3)
1.432 (3)
1.211 (3)
1.366 (2)
O2ÐC22
C7ÐC8
C13ÐC14
C14ÐC15
C15ÐC16
1.424 (3)
1.476 (3)
1.473 (3)
1.340 (3)
1.475 (3)
Table 1
Selected geometric parameters (A, ) for (II).
Ê
ꢀ
NÐC7
NÐC14
NÐC6
OÐC7
1.395 (3)
1.421 (3)
1.423 (3)
1.216 (3)
C7ÐC8
1.473 (4)
1.467 (4)
1.333 (4)
1.474 (4)
C13ÐC14
C14ÐC15
C15ÐC16
C7ÐNÐC14
O2ÐC3ÐC4
O2ÐC3ÐC2
C10ÐC9ÐC8
111.9 (2)
124.5 (2)
115.5 (2)
117.6 (2)
C13ÐC12ÐC11
C15ÐC14ÐN
C14ÐC15ÐC16
118.0 (2)
129.4 (2)
131.1 (2)
C7ÐNÐC14
C10ÐC9ÐC8
C11ÐC12ÐC13
111.4 (2)
117.5 (3)
117.7 (3)
C15ÐC14ÐN
C14ÐC15ÐC16
129.4 (2)
130.6 (2)
C6ÐNÐC7ÐC8
C6ÐNÐC14ÐC15
175.9 (2)
4.9 (3)
NÐC14ÐC15ÐC16
C13ÐC14ÐC15ÐC16
3.3 (4)
� 176.0 (2)
C6ÐNÐC7ÐC8
C6ÐNÐC14ÐC15
175.7 (3)
6.4 (5)
NÐC14ÐC15ÐC16
C13ÐC14ÐC15ÐC16
5.4 (5)
� 173.2 (3)
Table 2
Table 4
Ê
ꢀ
Intermolecular CÐHÁ Á ÁO contacts (A, ) for (II).
Intermolecular CÐHÁ Á ÁO contacts for (III).
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
i
i
C11ÐH11Á Á ÁO
0.93
2.64
3.339 (5)
132.6 (2)
C18ÐH18Á Á ÁO1
0.93
2.58
3.389 (3)
146.4 (1)
1
2
1
2
1
2
Symmetry code: (i) x; y; z � 1.
Symmetry code: (i) ‡ x; � y; ‡ z.
86
Alok K. Mukherjee et al. ꢁ
C
22
H
17NO
2
and C21
H15NO
Acta Cryst. (2000). C56, 85±87

organic compounds
Table 5
A comparison of geometrical parameters (A, ) of substituted isoindolinone compounds.
Ê
ꢀ
No rules?
Dihedral angles
Molecular
con®guration
Torsion angles
C(R2)
2
^
^
^
R1
R2
N
C
C
C
O
Csp
N
A B
A R1
A R2
Reference
CH
H
2
C
6
H
5
3
C
C
6
H
H
5
4
Z
Z
Z
E
Z
Z
� 3.1 (2)
0.6 (3)
� 2.7 (8)
177.9 (4)
5.4 (5)
1.222 (1) 1.384 (2)±1.412 (2) 0.67 (4)
1.225 (2) 1.358 (2)±1.400 (2) 0.79 (6)
1.221 (4) 1.387 (4)±1.417 (4) 0.86 (14)
1.212 (4) 1.388 (5)±1.402 (5) 2.81 (12)
1.216 (4) 1.395 (4)±1.421 (3) 1.66 (11)
1.211 (3) 1.400 (3)±1.417 (3) 2.26 (7)
98.21 (4)
±
78.94 (14)
111.11 (4)
11.91 (6)
±
45.68 (12) (3)
55.72 (10) (4)
(1)
(2)
(2)
6
OCH
3
C
CH
6
H
4
CH
C(OH)(CH
CO(C
C
C
3
)
2
3
6
H
5
)
C
C
6
H
H
5
4
6
H
H
5
5
62.7 (11)
112.90 (7)
6
OCH
3
6
3.3 (4)
55.05 (7)
(4)
²
References: (1) Khan et al. (1998); (2) Kundu et al. (1999); (3) Guha et al. (1999); (4) this work.
re®nement: MSC/AFC Diffractometer Control Software; data reduc-
tion: TEXSAN (Molecular Structure Corporation, 1995); program(s)
used to solve structure: MULTAN88 (Debaerdemaeker et al., 1988);
program(s) used to re®ne structure: SHELXL93 (Sheldrick, 1993);
molecular graphics: ZORTEP (Zsolnai, 1995); software used to
prepare material for publication: SHELXL93 and PARST (Nardelli,
1995).
Data collection
ꢀ
ꢁmax = 79.70
Rigaku AFC-5R diffractometer
!
±2ꢁ scans
Absorption correction: empirical
North et al., 1968)
min = 0.815, Tmax = 0.856
h = 0 ! 11
k = 0 ! 23
l = 0 ! 10
(
T
3 standard re¯ections
every 100 re¯ections
intensity decay: <2%
1
1
1
589 measured re¯ections
589 independent re¯ections
403 re¯ections with I > 2ꢃ(I)
Financial support from the Council of Scienti®c and Industrial
Research [grant No. 01 (1385)/95/EMR±II to NGK], New Delhi, is
gratefully acknowledged.
Re®nement
2
Re®nement on F
2
H-atom parameters constrained
2
2
2
2
R[F > 2ꢃ(F )] = 0.0436
wR(F ) = 0.1058
S = 1.116
w = 1/[ꢃ (F
o
) + (0.0652P) ]
2 2
2
o c
where P = (F + 2F )/3
(Á/ꢃ)max = � 0.005
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: FR1206). Services for accessing these data are
described at the back of the journal.
Ê
� 3
1
2
589 re¯ections
08 parameters
Áꢄmax = 0.16 e A
Áꢄmin = � 0.23 e AÊ
� 3
Compound (III)
References
Crystal data
Barrett, D. M. Y., Kahwa, I. A. & Williams, D. J. (1996). Acta Cryst. C52, 2069±
2071.
�
3
C
22
H17NO
2
D
x
= 1.330 Mg m
M
r
= 327.37
Cu Kꢀ radiation
Brady, F., Gallagher, J. F. & Kenny, P. T. M. (1998). Acta Cryst. C54,
1523±1525.
Debaerdemaeker, T., Germain, G., Main, P., Refaat, L. S., Tate, C. &
Monoclinic, P2 =n
Ê
a = 8.577 (6) A
b = 10.542 (4) A
Ê
c = 18.272 (4) A
ꢅ = 98.34 (4)
V = 1634.7 (13) A
Z = 4
Cell parameters from 25
re¯ections
1
Ê
ꢀ
ꢁ = 28.8±39.9
Woolfson, M. M. W. (1988). MULTAN88. A System of Com-
� 1
ꢂ = 0.678 mm
T = 293 (2) K
puter Programs for the Automatic Solution of Crystal Structures
from X-ray Diffraction Data. Universities of York, England, and Louvain,
Belgium.
Feeder, N. & Jones, W. (1996). Acta Cryst. C52, 913±919.
Guha, S., Mukherjee, A. K., Khan, M. W. & Kundu, N. G. (1999). Acta Cryst.
C55, 818±819.
ꢀ
Ê
3
Prism, colourless
0.35 Â 0.25 Â 0.10 mm
Data collection
ꢀ
Khan, M. W., Guha, S., Mukherjee, A. K. & Kundu, N. G. (1998). Acta Cryst.
C54, 119±120.
Kundu, N. G., Khan, M. W., Guha, S. & Mukherjee, A. K. (1999). Acta Cryst.
C55, 239±241.
Linden, M., Hadler, D. & Hofman, S. (1997). Human Psychopharmacol. 12,
Rigaku AFC-5R diffractometer
ꢁmax = 78.92
!±2ꢁ scans
h = 0 ! 10
Absorption correction: empirical
North et al., 1968
k = 0 ! 13
l = � 22 ! 22
Tmin = 0.878, Tmax = 0.934
3 standard re¯ections
every 100 re¯ections
intensity decay: <2%
4
45±452.
McNab, H., Parsons, S. & Shannon, D. A. (1997). Acta Cryst. C53,
098±1099.
2
2
2
810 measured re¯ections
810 independent re¯ections
220 re¯ections with I > 2ꢃ(I)
1
Molecular Structure Corporation (1993). MSC/AFC Diffractometer Control
Software. MSC, 3200 Research Forest Drive, The Woodlands, TX 77381,
USA.
Molecular Structure Corporation (1995). TEXSAN. Single Crystal Structure
Analysis Software. Version 1.7±1. MSC, 3200 Research Forest Drive, The
Woodlands, TX 77381, USA.
Re®nement
2
Re®nement on F
2
H-atom parameters constrained
2
2
2
2
) + (0.0252P) +
R[F > 2ꢃ(F )] = 0.0483
wR(F ) = 0.1029
S = 1.095
w = 1/[ꢃ (F
o
2
2
2
c
0.5728P] where P = (F
(Á/ꢃ)max = � 0.004
o
+ 2F
)/3
Ê
� 3
Áꢄmax = 0.15 e A
Nardelli, M. (1995). J. Appl. Cryst. 28, 659.
North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351±
2
2
810 re¯ections
26 parameters
Áꢄmin = � 0.15 e AÊ
� 3
359.
Sheldrick, G. M. (1993). SHELXL93. Program for the Re®nement of Crystal
Structures. University of G oÈ ttingen, Germany.
All H-atoms were generated using HFIX in SHELX93 (Sheldrick,
993). Uiso for H atoms were assigned as 1.2 times Ueq of the parent
non-H atoms before anisotropic re®nement.
Taylor, E. C., Zhou, P., Jenning, L. D., Mao, Z., Hu, B. & Jun, J.-G. (1997).
Tetrahedron Lett. 38, 521±524.
Zhuang, Z. P., Kung, M.-P., Mu, M. & Kung, H.-F. (1998). J. Med. Chem. 41,
1
157±162.
For both compounds, data collection: MSC/AFC Diffractometer
Control Software (Molecular Structure Corporation, 1993); cell
Zsolnai, L. (1995). ZORTEP. An Interactive ORTEP Program. University of
Heidelberg, Germany.
Acta Cryst. (2000). C56, 85±87
Alok K. Mukherjee et al. ꢁ
C
22
H
17NO
2
and C21
H15NO 87