Two isomeric 2-[4-chloro-2-fluoro-5-(prop-2-ynyloxy)phenyl]hexahydro- isoindole-1,3-dione compounds

Article abstract of DOI:10.1107/S0108270104034146

The molecular structures of 2-[4-chloro-2-fluoro-5-(prop-2-ynyloxy)phenyl]- 1,3,4,5,6,7-hexahydroisoindole-1,3-dione, C₁₇H₁₃ClFNO ₃, (I), and the isomeric compound 2-[4-chloro-2-fluoro-5-(prop-2- ynyloxy)phenyl]-cis-1,3,3a,4,7,-7a-hexahydroisoindole-1,3-dione, (II), are, as anticipated, significantly different in their conformations and in the distances between the farthest two atoms. The six-membered ring of the 1,3,4,5,6,7-hexahydroisoindole-1,3-dione moiety in (I) adopts a half-chair conformation. The dihedral angle between the five-membered dione ring of (I) and the benzene ring is 50.96 (7)°. The six-membered ring of the cis-1,3,3a,4,7,7a-hexahydroisoindole-1,3-dione moiety in (II) adopts a boat conformation. The dihedral angle in (II) between the five-membered dione ring and the benzene ring is 61.03 (13)°. In the crystal structures, the molecules are linked by C-H...O hydrogen bonds and weak π-π interactions. Compound (I) is a much more potent herbicide than (II). The Cl...H distances between the farthest two atoms in (I) and (II) are 11.37 and 9.97 A, respectively.

Full text of DOI:10.1107/S0108270104034146

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
activity than chlorophthalim (Boger & Wakabayashi, 1999).
The X-ray structures and details of the herbicidal activities of
three PPO inhibitors, including chlorophthalim, viz. 2-(4-
chlorophenyl)-4,5,6,7-tetrahydroisoindole-1,3-dione (chloro-
phthalim), 3-(4-chloro-5-cyclopentyloxy-2-¯uorophenyl)-5-iso-
propylideneoxazolidine-2,4-dione and 2-chloro-1-(3-ethoxy-
4-nitrophenoxy)-4-(tri¯uoromethyl)benzene, have been re-
ported (Kohno et al., 1993). The X-ray structure of chloro-
phthalim indicated that the angle between the tetrahydro-
ISSN 0108-2701
Two isomeric 2-[4-chloro-2-fluoro-
5
-(prop-2-ynyloxy)phenyl]hexahydro-
isoindole-1,3-dione compounds
ꢀ
isoindole-1,3-dione and benzene ring planes is 43.6 , and the
Ê
distance between the farthest two atoms is 11.37 A. It was
a,b
a
c
b
assumed that both the angle and the distance have some
bearing on the herbicidal activity of the molecule.
Bin Li, Hai-Bin Song, Chi-Tung Hsu, Ke-Liang Zhang,
a
a
Chao Wu and Hua-Zheng Yang *
a
State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai
b
University, Tianjin 300071, People's Republic of China, Agrochemicals Division,
Shenyang Research Institute of Chemical Industry, Shenyang 110021, People's
c
Republic of China, and Applied Chemistry Department, Chaoyang University of
Technology, Taichung 41349, Taiwan
Correspondence e-mail: nk_yanghz@126.com
Received 10 December 2004
Accepted 22 December 2004
Online 31 January 2005
The molecular similarity between (I) and proto-
porphyrinogen IX has been investigated on the basis of their
computational conformation using MOPAC with MNDO-
PM3 parameterizations during a molecular modeling program
The molecular structures of 2-[4-chloro-2-¯uoro-5-(prop-
2-ynyloxy)phenyl]-1,3,4,5,6,7-hexahydroisoindole-1,3-dione,
C H ClFNO , (I), and the isomeric compound 2-[4-
1
7
13
3
(Uraguchi et al., 1997).
In an attempt to discover compounds that are more herbi-
chloro-2-¯uoro-5-(prop-2-ynyloxy)phenyl]-cis-1,3,3a,4,7,-
a-hexahydroisoindole-1,3-dione, (II), are, as anticipated,
7
cidally active, the novel compound 2-[4-chloro-2-¯uoro-5-
prop-2-ynyloxy)phenyl]-cis-1,3,3a,4,7,7a-hexahydroisoindole-
,3-dione, (II), an isomer of (I), was prepared. Unfortunately,
signi®cantly different in their conformations and in the
distances between the farthest two atoms. The six-membered
ring of the 1,3,4,5,6,7-hexahydroisoindole-1,3-dione moiety in
(
1
it was found that (II) is much less active than (I) (Li, 2005). In
order to carry out a three-dimensional quantitative structure±
activity relationship study on this series of compounds and to
interpret the differences in their herbicidal activity, we report
here the crystal structures of (I) and (II).
The molecular dimensions in (I) (Fig. 1) are unexceptional;
the six-membered ring (C3a/C4±C7/C7a) of the 1,3,4,5,6,7-
hexahydroisoindole-1,3-dione moiety adopts a half-chair
conformation, with atoms C5 and C6 on opposite sides
(
I) adopts a half-chair conformation. The dihedral angle
between the ®ve-membered dione ring of (I) and the benzene
ꢀ
ring is 50.96 (7) . The six-membered ring of the cis-
1,3,3a,4,7,7a-hexahydroisoindole-1,3-dione moiety in (II)
adopts a boat conformation. The dihedral angle in (II)
between the ®ve-membered dione ring and the benzene ring is
ꢀ
6
1.03 (13) . In the crystal structures, the molecules are linked
by CÐHÁ Á ÁO hydrogen bonds and weak ꢀ±ꢀ interactions.
Compound (I) is a much more potent herbicide than (II). The
ClÁ Á ÁH distances between the farthest two atoms in (I) and
Ê
II) are 11.37 and 9.97 A, respectively.
(
Comment
Many 2-(substituted phenyl)tetrahydroisoindole-1,3-diones
show good herbicidal activity (Ohta et al., 1976). One of these
compounds, chlorophthalim [2-(4-chlorophenyl)-4,5,6,7-hexa-
hydroisoindole-1,3-dione], was commercially available in 1973
(
Tomlin, 2003). It acts as a competitive inhibitor of the
enzyme protoporphyrinogen IX oxidase (PPO) by binding to
the same active site as the substrate protoporphyrinogen IX
(
Matringe & Scalla, 1988; Duke et al., 1989). Since 1990, one of
the title molecules, viz. 2-[4-chloro-2-¯uoro-5-(prop-2-ynyl-
oxy)phenyl]-1,3,4,5,6,7-hexahydroisoindole-1,3-dione, (I), has
been used as a reference compound during structure±activity
relationship (SAR) studies because it has greater herbicidal
Figure 1
The structure of (I), showing 30% probability displacement ellipsoids and
the atom-numbering scheme.
o114 # 2005 International Union of Crystallography
DOI: 10.1107/S0108270104034146
Acta Cryst. (2005). C61, o114±o117

organic compounds
Ê
[
deviating by 0.250 (6) and � 0.290 (6) A, respectively] of the
impossibly short intramolecular F1Á Á ÁO1 separation [the
Ê
present value is only 2.838 (3) A]. The orientation of the
C1/N2/C3/C3A/C4/C7/C7a plane. The dihedral angle between
the planes of these seven atoms and the benzene ring (C11±
C16) is 50.96 (7) . Any reduction in this value would lead to an
propargyl group relative to the aromatic ring is de®ned by the
ꢀ
ꢀ
C15ÐO3ÐC17ÐC18 torsion angle [73.8 (3) ]. The distance
between the farthest two atoms (atom Cl1 and the equatorial
Ê
H atom at C6) is 11.37 A.
In (I), there is a well de®ned acetylenic CÐHÁ Á ÁO hydrogen
bond between the C19ÐH19 group and carbonyl atom O1 of
an adjacent molecule (Table 1 and Fig. 2); this interaction
leads to the development of chains of molecules along [010]. A
search of the Cambridge Structural Database (July 2004
release; Allen, 2002) revealed 106 compounds with acetylenic
CÐHÁ Á ÁO hydrogen bonds. The hydrogen-bond dimensions in
(I) indicate that this CÐHÁ Á ÁO hydrogen bond is weaker than
Figure 2
A view showing the CÐHÁ Á ÁO hydrogen-bonded chains in (I) and the
centroid±centroid separations. Cg1 is the centroid of the phenyl ring.
Atoms marked with an asterisk (*) or a hash (#) are at the symmetry
positions (x, y � 1, z) and (2 � x, 1 � y, 1 � z), respectively.
Figure 4
Figure 3
Views showing (a) a chain of rings extending along [010] and (b) the weak
centroid±centroid interactions between chains. Cg1 is the centroid of the
phenyl ring. Atoms marked with an asterisk (*), a dollar sign ($) or a hash
(#) are at the symmetry positions (x, 1 + y, z), (1 � x, 1 � y, � z) and
(a) The structure of (II), showing 30% probability displacement
ellipsoids, the atom-numbering scheme and the major orientation of
the disordered propargyl group. (b) Aview of part of the molecule of (II),
showing the disorder of the propargyl group.
1
2
3
2
( � x, � y, � z), respectively.
ꢁ
Acta Cryst. (2005). C61, o114±o117
Li et al.
Two isomers of C17
H
13ClFNO
3
o115

organic compounds
those in o-chloro- and o-bromobenzoylacetylene (Ferguson &
Tyrrell, 1965; Ferguson & Islam, 1966). In the crystal structure
of (I), parallel chains are linked by weak ꢀ±ꢀ interactions; the
centroid±centroid distance between the planes of the benzene
Compound (I)
Crystal data
C
M
17
H
13ClFNO
= 333.73
Triclinic, P1ꢀ
3
Z = 2
= 1.417 Mg m
Mo Kꢁ radiation
� 3
r
D
x
rings at (x, y, z) and (2 � x, 1 � y, 1 � z) (# in Fig. 2) is
Ê
Ê
a = 9.313 (5) A
Cell parameters from 860
re¯ections
3
[
.736 (3) A, the shortest CÁ Á ÁC contacts being C11Á Á ÁC13#
Ê
b = 9.380 (5) A
Ê
Ê
3.452 (5) A] and C12Á Á ÁC13# [3.477 (4) A].
ꢀ
Ê
c = 10.485 (6) A
ꢄ = 3.3±26.0
ꢀ
� 1
Compound (II) has the solid-state conformation shown in
ꢁ = 99.663 (9)
ꢂ = 104.263 (9)
ꢃ = 112.778 (8)
Ê
V = 782.1 (7) A
ꢅ = 0.27 mm
T = 293 (2) K
ꢀ
ꢀ
Fig. 3(a), with normal dimensions. The six-membered C3a/C4±
C7/C7a ring adopts a simple boat conformation. The ®ve-
membered C1/N2/C3/C3a/C7a ring is planar; the mean
Prism, colorless
0.36 Â 0.24 Â 0.22 mm
3
Ê
Data collection
deviation from the plane is 0.005 A. The dihedral angle
between this plane and that of the benzene ring (C11±C16) is
Bruker SMART CCD area-detector
diffractometer
2747 independent re¯ections
2059 re¯ections with I > 2ꢆ(I)
ꢀ
6
1.03 (13) , slightly larger than that found in (I) and with a
'
and ! scans
Absorption correction: multi-scan
Rint = 0.017
ꢀ
concomitant small increase in the intramolecular F1Á Á ÁO1
ꢄmax = 25.0
Ê
separation to 3.004 (4) A. The propargyl group is disordered
(SADABS; Sheldrick, 1996)
h = � 11 ! 9
k = � 9 ! 11
l = � 10 ! 12
Tmin = 0.906, Tmax = 0.943
071 measured re¯ections
unequally [0.549 (5):0.451 (5)] over two orientations (see
Fig. 3b), with the orientations relative to the aromatic ring
4
ꢀ
Re®nement
de®ned by the C15ÐO3ÐC17ÐC18 [� 179.1 (5) ] and C15Ð
2
2
2
o
2
ꢀ
Re®nement on F
2
w = 1/[ꢆ (F ) + (0.045P)
O3ÐC17AÐC18A [� 76.5 (9) ] torsion angles. The longest
2
R[F > 2ꢆ(F )] = 0.043
wR(F ) = 0.111
S = 1.03
+ 0.3951P]
where P = (Fo + 2F )/3
Ê
atom±atom separation in (II) is 9.97 A, between atom Cl1 and
2
2
2
c
the axial H atoms at atoms C4 and C7.
The packing of (II) is controlled by weak acetylenic CÐ
(Á/ꢆ)max = 0.002
Ê
� 3
Áꢇmax = 0.39 e A
2
2
747 re¯ections
08 parameters
Áꢇmin = � 0.28 e AÊ
� 3
HÁ Á ÁO hydrogen bonds, which generate centrosymmetric
H-atom parameters constrained
2
2
dimers with R (10) rings (Bernstein et al., 1995) (Table 2 and
Fig. 4a). These dimers are linked by CÐHÁ Á ÁO hydrogen
Table 1
Hydrogen-bond geometry (A, ) for (I).
bonds involving the phenyl C13ÐH13 group and an adjacent
2
Ê
ꢀ
carbonyl O atom (O2), generating R (32) rings. In this way,
2
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
chains of rings are developed along [010]. These chains are
linked by weak ꢀ±ꢀ interactions, as shown in Fig. 4(b) [e.g.
i
C19ÐH19Á Á ÁO1
0.93
2.59
3.295 (4)
133
1
3
between the benzene rings at (x, y, z) and ( � x, � y, � z) (#
2
2
Symmetry code: (i) x; y � 1; z.
Ê
in Fig. 4b)]; the centroid±centroid separation is 3.830 (3) A
and the shortest CÁ Á ÁC separations are C12Á Á ÁC14#
Ê
Ê
[
3.376 (5) A] and C13Á Á ÁC13# [3.461 (5) A]. The acetylenic
Compound (II)
moiety of the minor-occupancy propargyl group takes no part
in any hydrogen bonding.
Crystal data
�
3
From the conformational data made available by this study,
it might be implied that the almost ¯at conformation of the
hexahydroisoindole-1,3-dione ring in (I) compared with the
folded conformation in (II) plays an important role in main-
taining the herbicidal activity of (I) compared with that of (II).
C H ClFNO
7
D = 1.418 Mg m
x
Mo Kꢁ radiation
1
13
3
M
r
= 333.73
Monoclinic, C2/c
Cell parameters from 885
re¯ections
Ê
a = 22.712 (15) A
b = 7.474 (5) AÊ
Ê
c = 18.655 (12) A
ꢂ = 99.061 (11)
Ê
V = 3127 (4) A
Z = 8
ꢀ
ꢄ = 3.0±24.4
� 1
ꢅ = 0.27 mm
T = 293 (2) K
ꢀ
3
Prism, colorless
0.34 Â 0.28 Â 0.20 mm
Experimental
Data collection
The title compounds were synthesized according to the procedure
reported by Nagano et al. (1982), by re¯uxing 4-chloro-2-¯uoro-5-
Bruker SMART CCD area-detector
diffractometer
3206 independent re¯ections
2058 re¯ections with I > 2ꢆ(I)
(prop-2-ynyloxy)phenylamine with the corresponding anhydrides in
'
and ! scans
Absorption correction: multi-scan
SADABS; Sheldrick, 1996)
min = 0.902, Tmax = 0.948
627 measured re¯ections
Rint = 0.027
ꢀ
acetic acid for 1 h. The crude products were puri®ed by silica-gel
column chromatography and then grown from acetone to afford
colorless single crystals suitable for X-ray diffraction. For (I), m.p.
ꢄmax = 26.4
(
T
h = � 28 ! 27
k = � 5 ! 9
8
l = � 22 ! 23
1
4
09±410 K (409.4 K; Nagano et al., 1982); H NMR (p.p.m.): 1.82±1.84
(m, 2H), 2.58 (t, 1H, J = 2.4 Hz, C*CH), 2.44±2.75 (m, 4H), 4.75 (d,
Re®nement
2
2
2
2
2
9
6
H, J = 2.4 Hz, CH C*C), 6.98 (d, 1H, J = 6.6 Hz, Ph), 7.29 (d, 1H, J =
2
Hz, Ph). For (II), m.p. 368±369 K; elemental analysis requires: C
Re®nement on F
2
w = 1/[ꢆ (F ) + (0.0569P)
o
2
R[F > 2ꢆ(F )] = 0.060
wR(F ) = 0.155
S = 1.02
+ 5.1958P]
where P = (Fo + 2F )/3
2
2
2
c
1
1.18, H 3.93, N 4.20%; found: C 61.22, H 4.01, N 4.24%; H NMR
(Á/ꢆ)max < 0.001
(
p.p.m.): 2.35±2.39 (m, 2H), 2.58 (t, 1H, J = 2.4 Hz, C*CH), 2.68±2.73
m, 2H), 3.30±3.32 (m, 2H), 4.75 (d, 2H, J = 2.4 Hz, CH C*C), 5.99±
.01 (m, 2H), 6.96 (d, 1H, J = 6.6 Hz, Ph), 7.29 (d, 1H, J = 9 Hz, Ph).
Ê
� 3
Áꢇmax = 0.31 e A
3
2
206 re¯ections
30 parameters
Áꢇmin = � 0.25 e AÊ �
3
(
2
6
H-atom parameters constrained
ꢁ
o116 Li et al. Two isomers of C17
H
13ClFNO
3
Acta Cryst. (2005). C61, o114±o117

organic compounds
Table 2
Hydrogen-bond geometry (A, ) for (II).
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: FG1803). Services for accessing these data are
described at the back of the journal.
Ê
ꢀ
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
i
C13ÐH13Á Á ÁO2
0.93
0.93
2.51
2.78
3.345 (4)
3.400 (6)
149
125
ii
C19ÐH19Á Á ÁO3
References
Symmetry codes: (i) x; y ‡ 1; z; (ii) � x ‡ 1; � y ‡ 1; � z.
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For both (I) and (II), H atoms were found in difference maps and
were subsequently allowed for in the re®nements as riding atoms,
Ê
with CÐH distances of 0.93, 0.97 and 0.98 A, and with Uiso(H) =
1.2Ueq(C). In (II), it soon became apparent that the propargyl group
was disordered unequally over two orientations (see supplementary
material for a plot of the electron density in the relevant plane).
Ê
DFIX restraints [1.428 (3), 1.158 (3) and 2.396 (3) A] were used to
control the re®nement of the propargyl CÐC distances in the two
components (C17/C18/C19 and C17A/C18A/C19A), whose occu-
pancies re®ned to 0.549 (5) and 0.451 (5).
For both compounds, data collection: SMART (Bruker, 1998); cell
re®nement: SMART; data reduction: SAINT (Bruker, 1999); struc-
ture solution: SHELXS97 (Sheldrick, 1997); structure re®nement:
SHELXL97 (Sheldrick, 1997) in WinGX (Farrugia, 1999); molecular
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The authors acknowledge the ®nancial support of the
National Natural Science Foundation of China (grant No.
2
(
0372040) and the National Key Project for Basic Research
grant No. 2003CB114400). Thanks are also expressed to
Professor George Ferguson and Mr Chang-Sheng Yao for
their help during the preparation of this manuscript.
ꢁ
Acta Cryst. (2005). C61, o114±o117
Li et al.
Two isomers of C17
H
13ClFNO
3
o117