Three tetrahydroisoquinolinedione derivatives.

Article abstract of DOI:10.1107/S0108270102000896

N-(2-Chlorobenzyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione, C(16)H(12)ClNO(2), crystallizes in P2(1)/n with three crystallographically independent molecules in the asymmetric unit, which differ slightly in conformation, N-(2-bromo-4-methylphenyl)-1,2,3,4

Full text of DOI:10.1107/S0108270102000896

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
are also useful as key intermediates in the synthesis of iso-
quinoline alkaloids, such as cherylline and lati®ne (Honda et
al., 2001). Isoquinoline fused-ring systems, such as
pyrroloisoquinoline, show valuable pharmacological activity,
e.g. antileukemic (Anderson et al., 1998), muscaricinic,
agonostic (Loesel et al., 1987) and antidepressant properties
(Elwan et al., 1996). Their marked antidepressant, tranqui-
lizing (Sulkowski & Willie, 1969), analgesic and sedative
(Hamamato & Kajiwara, 1966) activity renders 1(2H)-iso-
quinolinones an important class of compounds. These
compounds have also been used as intermediates in the
synthesis of a number of naturally occurring alkaloids
(Kobayashi, 1950; Walker et al., 1964). A variety of 1,2,3,4-
tetrahydroisoquinoline derivatives have been studied exten-
sively in the past in order to elucidate their antidepressant-like
activity. The title compounds, N-(2-chlorobenzyl)-1,2,3,4-
tetrahydroisoquinoline-1,3-dione, (I), N-(2-bromo-4-methyl-
phenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione, (II), and
N-(2,3-dichlorophenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-
dione, (III), are of interest as intermediates in the synthesis of
ISSN 0108-2701
Three tetrahydroisoquinolinedione
derivatives
A. Subbiah Pandi,a V. Rajakannan,a D. Velmurugan,a*
Masood Parvez,b Moon-Jib Kim,c A. Senthilveland and
S. Narasinga Raoe
aDepartment of Crystallography and Biophysics, University of Madras, Guindy
Campus, Chennai 600 025, India, bDepartment of Chemistry, 2500 University Drive
NW, Calgary, Alberta, Canada T2N 1N4, cDepartment of Physics, Soonchunhyang
University, PO Box 97 Asan, Chungnam 336-600, South Korea, dDepartment of
Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India,
and eUniversity of Central Oklahoma, Edmond, Oklahoma, USA
Correspondence e-mail: d_velu@yahoo.com
Received 8 January 2002
Accepted 16 January 2002
Online 20 February 2002
N-(2-Chlorobenzyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione,
C16H12ClNO2, crystallizes in P21/n with three crystallographi-
cally independent molecules in the asymmetric unit, which
differ slightly in conformation, N-(2-bromo-4-methylphenyl)-
1,2,3,4-tetrahydroisoquinoline-1,3-dione, C16H12BrNO2, crys-
tallizes in P21/n with one molecule in the asymmetric unit and
N-(2,3-dichlorophenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-
dione, C15H9Cl2NO2, crystallizes in P21/c with one molecule in
the asymmetric unit. In all three structures, the heterocyclic
rings adopt approximately planar conformations. The pyridine
rings are orthogonal to the substituted phenyl rings. In all
three structures, the crystal packing is stabilized by inter-
molecular CÐHÁ Á ÁO hydrogen bonds.
Comment
Isoquinoline is a well known ligand that has been used in
studies of the formation of various adducts of group IVA
Figure 1
A view of the three independent molecules of (I) with the atom-
numbering scheme. Displacement ellipsoids are drawn at the 30%
probability level.
halides (Miller & Onyszchuk, 1967). Tetrahydroisoquinolines
represent a class of biologically active phenyl ethylamines
(Brzezinska, 1994), and these compounds are of great interest
due to their biological and pharmacological properties. They
Figure 2
A view of the molecular structure of (II) with the atom-numbering
scheme. Displacement ellipsoids are drawn at the 50% probability level.
o164 # 2002 International Union of Crystallography
DOI: 10.1107/S0108270102000896
Acta Cryst. (2002). C58, o164±o167

organic compounds
moiety and the phenyl ring are comparable with those
observed in similar structures (Ammon & Wheeler, 1974).
In addition to normal van der Waals interactions, the crystal
packing in all three structures is stabilized by intermolecular
CÐHÁ Á ÁO hydrogen bonds. In (I), ®ve intermolecular CÐ
HÁ Á ÁO hydrogen bonds occur, with HÁ Á ÁO distances less than
the sum of the van der Waals radii (Bondi, 1964). In this
structure, the symmetry-related isoquinoline molecules are
arranged in a head-to-head manner and are alternately
parallel to each other. This type of stacking is also found in
1,4-dihydroisoquinoline (Minter et al., 1996). In (II), an
intermolecular CÐHÁ Á ÁO hydrogen bond between atoms C5
and O1 stabilizes the crystal packing. The interesting feature
of the crystal structure of (III) is that a single CÐHÁ Á ÁO
hydrogen bond links the molecules into cyclic centrosym-
metric dimers formed by an R22(16) ring system. This is a
layered structure, with layers parallel to the ac plane. Details
of the hydrogen-bond geometry in (I), (II) and (III) are given
in Tables 2, 4 and 6, respectively.
Figure 3
A view of the molecular structure of (III) with the atom-numbering
scheme. Displacement ellipsoids are drawn at the 50% probability level.
alkaloids such as corgoine (Kametani et al., 1975) and
sendaverine (Kametani et al., 1979).
The structures in the present study consist of an iso-
quinoline moiety and a substituted phenyl ring. Structure (I)
contains three molecules in the asymmetric unit, designated
(IA), (IB) and (IC) (Fig. 1). Structures (II) (Fig. 2) and (III)
(Fig. 3) contain one molecule per asymmetric unit.
The C O bond lengths in all three structures, and bond
length Csp2ÐBr in (II) and Csp2ÐCl in (III), are comparable
with the values found in a search of the Cambridge Structural
Database (2001 Release; Allen et al., 1987). The bond
distances and angles of the isoquinoline moiety in these
structures are in good agreement with the values reported for
other 1,2,3,4-tetrahydroisoquinoline derivatives (Bellard et al.,
1982; Pøywaczyk et al., 1984). Selected geometric parameters
for (I), (II) and (III) are given in Tables 1, 3 and 5, respec-
tively.
In (I), the phenyl rings of the benzyl groups are twisted with
respect to the isoquinoline system. The torsion angles around
the N1ÐC16 and C16ÐC10 single bonds are almost equal for
(IB) and (IC), but are different for (IA). This shows that the
orientation of the benzyl group in (IA) is different from that in
(IB) and (IC).
The most remarkable feature of the crystal structure of (II)
is the existence of a short intermolecular halogenÁ Á ÁO contact,
i
1
Br1Á Á ÁO2 3.012 (3) A [symmetry code: (i) 2 x, y + 12, 23 z],
Ê
between the phenyl ring and the isoquinoline moiety.
Experimental
The title compounds were synthesized from homophthalic acid and
the corresponding substituted aromatic amines. The yield was 75%
(m.p. 435±437 K) for (I), 71% (m.p. 395±397 K) for (II) and 68%
(m.p. 471±473 K) for (III). The compounds were dissolved in a
mixture of ethyl acetate and hexane (4:1). Slow evaporation of the
solvent at room temperature produced crystals from which the
experimental samples were obtained.
Compound (I)
Crystal data
3
The isoquinoline moiety is slightly folded about the line
passing through atoms C8 and C9, and the dihedral angle
between the two halves ranges from 2.2 (1) to 3.7 (1)ꢀ. The
phenyl ring in all three structures is orthogonal to the iso-
quinoline moiety, forming a dihedral angle of 87.6 (1)ꢀ in (IA),
85.7 (1)ꢀ in (IB), 84.5 (1)ꢀ in (IC), 76.6 (1)ꢀ in (II) and 69.9 (1)ꢀ
in (III). It can be seen that the value in (III) is lower than that
in (II), and this is probably a result of the heavier substituents
on the phenyl ring of (II).
C16H12ClNO2
Mr = 285.72
Monoclinic, P21=n
Ê
a = 7.7922 (14) A
b = 21.538 (4) A
Ê
c = 24.351 (5) A
ꢀ = 98.92 (2)ꢀ
V = 4037.4 (13) A
Z = 12
Dx = 1.410 Mg m
Cu Kꢁ radiation
Cell parameters from 25
re¯ections
ꢂ = 20±30ꢀ
ꢃ = 2.52 mm
T = 293 K
Ê
1
3
Ê
Prism, colourless
0.50 Â 0.41 Â 0.20 mm
The dihedral angle between the least-squares planes of the
substituted phenyl and benzo-fused rings is 88.2 (1)ꢀ for (IA),
85.2 (1)ꢀ for (IB), 84.4 (1)ꢀ for (IC), 75.6 (0)ꢀ for (II) and
69.3 (1)ꢀ for (III). The deviations of atoms O1 and O2 from
Table 1
Selected geometric parameters (A, ) for (I).
ꢀ
Ê
Cl1AÐC11A
N1AÐC1A
N1AÐC7A
N1AÐC16A
O1AÐC1A
O2AÐC7A
Cl1BÐC11B
N1BÐC7B
N1BÐC1B
1.743 (4)
1.385 (4)
1.396 (4)
1.462 (4)
1.213 (4)
1.212 (4)
1.742 (3)
1.388 (4)
1.394 (4)
N1BÐC16B
O1BÐC1B
O2BÐC7B
Cl1CÐC11C
N1CÐC1C
N1CÐC7C
N1CÐC16C
O1CÐC1C
O2CÐC7C
1.472 (4)
1.210 (4)
1.218 (4)
1.751 (4)
1.391 (4)
1.394 (4)
1.459 (4)
1.205 (4)
1.209 (4)
the mean planes de®ned by atoms N1, C1, C2, C9, C8 and C7
Ê
are
0.098 (2) and 0.040 (1) A, respectively, in (IA),
Ê
0.084 (3) and 0.071 (3) A, respectively, in (IB), 0.108 (3)
Ê
and 0.086 (3) A, respectively, in (IC), 0.072 and 0.016 A,
Ê
Ê
respectively, in (II), and 0.237 (2) and 0.149 (2) A, respec-
tively, in (III).
In all three structures, the bond lengths and angles, the
dihedral angles between the two halves of the isoquinoline
moiety, and the dihedral angles between the isoquinoline
C1AÐN1AÐC16AÐC10A 80.2 (4)
C1BÐN1BÐC16BÐC10B
C1CÐN1CÐC16CÐC10C
C15AÐC10AÐC16AÐN1A 19.3 (5)
C15BÐC10BÐC16BÐN1B 29.8 (5)
C15CÐC10CÐC16CÐN1C 30.8 (4)
81.8 (4)
83.1 (4)
ꢁ
Acta Cryst. (2002). C58, o164±o167
A. Subbiah Pandi et al.
C16H12ClNO2, C16H12BrNO2 and C15H9Cl2NO2 o165

organic compounds
Table 2
Hydrogen-bonding geometry (A, ) for (I).
Data collection
ꢀ
Ê
Enraf±Nonius FR-590
diffractometer
h = 18 ! 18
k = 0 ! 9
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
Non-pro®led !/2ꢂ scans
2554 measured re¯ections
2421 independent re¯ections
1818 re¯ections with I > 2ꢄ(I)
Rint = 0.019
l = 0 ! 13
3 standard re¯ections
every 100 re¯ections
frequency: 120 min
intensity decay: 1%
C5AÐH5AÁ Á ÁO1Ci
C5CÐH5CÁ Á ÁO1Bii
C2AÐH2A2Á Á ÁO1Ciii
C2BÐH2B2Á Á ÁO1Biv
C5BÐH5BÁ Á ÁO1Av
0.95
0.95
0.99
0.99
0.95
2.45
2.51
2.46
2.56
2.59
3.294 (4)
3.238 (5)
3.292 (5)
3.391 (5)
3.265 (5)
148
133
141
141
129
ꢂmax = 25ꢀ
1
2
1
2
1
2
3
2
Symmetry codes: (i) x
x; 1 y; z; (v) x 1; y; z.
;
y; 12 ‡ z; (ii) ‡ x; 21 y; 12 ‡ z; (iii)
x; 12 ‡ y; 12 z; (iv)
Re®nement
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.042
wR(F2) = 0.126
S = 1.02
2421 re¯ections
w = 1/[ꢄ2(Fo2) + (0.0839P)2
+ 0.3218P]
where P = (Fo2 + 2Fc2)/3
(Á/ꢄ)max = 0.002
Data collection
3
Enraf±Nonius CAD-4
diffractometer
!/2ꢂ scans
Absorption correction: empirical
via scans (North et al., 1968)
Tmin = 0.366, Tmax = 0.633
7916 measured re¯ections
7348 independent re¯ections
5013 re¯ections with I > 2ꢄ(I)
Rint = 0.039
ꢂ
max = 68.2ꢀ
Ê
Áꢅmax = 0.59 e A
3
Ê
0.83 e A
182 parameters
H-atom parameters constrained
Áꢅmin
=
h = 0 ! 9
k = 0 ! 25
l = 29 ! 28
3 standard re¯ections
every 200 re¯ections
intensity decay: 0.6%
Compound (III)
Crystal data
3
C15H9Cl2NO2
Mr = 306.13
Dx = 1.561 Mg m
Mo Kꢁ radiation
Re®nement
Monoclinic, P21=c
Cell parameters from 25
re¯ections
Ê
a = 15.6702 (8) A
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.065
wR(F2) = 0.200
S = 1.06
7348 re¯ections
542 parameters
H-atom parameters
constrained
w = 1/[ꢄ2(Fo2) + (0.1067P)2
+ 1.2945P]
ꢂ = 6.2±10.3ꢀ
Ê
b = 6.1560 (5) A
Ê
c = 14.5889 (7) A
1
ꢃ = 0.50 mm
T = 293 (2) K
where P = (Fo2 + 2Fc2)/3
(Á/ꢄ)max < 0.001
ꢀ = 112.236 (4)ꢀ
V = 1302.67 (14) A
Z = 4
3
Ê
Prism, colourless
0.25 Â 0.25 Â 0.20 mm
3
Ê
Áꢅmax = 0.38 e A
3
Ê
0.34 e A
Áꢅmin
=
Extinction correction: SHELXL97
(Sheldrick, 1997)
Extinction coef®cient: 0.0016 (2)
Data collection
Enraf±Nonius CAD-4
diffractometer
Rint = 0.015
ꢂmax = 25ꢀ
Non-pro®led !/2ꢂ scans
Absorption correction: empirical
via scan (North et al., 1968)
Tmin = 0.886, Tmax = 0.907
2391 measured re¯ections
2287 independent re¯ections
1872 re¯ections with I > 2ꢄ(I)
h = 18 ! 17
k = 0 ! 7
Compound (II)
l = 0 ! 17
3 standard re¯ections
every 100 re¯ections
frequency: 120 min
intensity decay: 1%
Crystal data
3
C16H12BrNO2
Mr = 330.18
Dx = 1.586 Mg m
Mo Kꢁ radiation
Cell parameters from 25
re¯ections
Monoclinic, P21=n
Ê
Ê
a = 15.847 (2) A
b = 7.9190 (7) A
Re®nement
ꢂ = 5.0±10.2ꢀ
1
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.036
wR(F2) = 0.156
S = 1.01
2287 re¯ections
181 parameters
H-atom parameters constrained
w = 1/[ꢄ2(Fo2) + (0.128P)2]
where P = (Fo2 + 2Fc2)/3
(Á/ꢄ)max < 0.001
Ê
c = 11.0602 (11) A
ꢃ = 2.97 mm
T = 293 (2) K
ꢀ = 94.750 (9)ꢀ
V = 1383.2 (3) A
Z = 4
3
Ê
Prism, colourless
0.35 Â 0.30 Â 0.30 mm
3
Ê
Áꢅmax = 0.24 e A
3
Ê
0.23 e A
Áꢅmin
=
Table 3
Selected geometric parameters (A, ) for (II).
ꢀ
Ê
Table 5
Selected geometric parameters (A, ) for (III).
ꢀ
Ê
Br1ÐC11
N1ÐC1
N1ÐC7
1.881 (4)
1.393 (4)
1.407 (5)
N1ÐC10
O1ÐC1
O2ÐC7
1.431 (4)
1.200 (4)
1.198 (4)
Cl1ÐC11
Cl2ÐC12
N1ÐC1
1.722 (2)
1.727 (3)
1.398 (3)
1.403 (3)
N1ÐC10
O1ÐC1
O2ÐC7
1.441 (3)
1.203 (3)
1.207 (3)
N1ÐC7
C1ÐN1ÐC10ÐC15
102.7 (4)
C1ÐN1ÐC10ÐC11
74.0 (3)
Table 4
Hydrogen-bonding and short-contact geometry (A, ) for (II).
ꢀ
Ê
Table 6
Hydrogen-bonding geometry (A, ) for (III).
ꢀ
Ê
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
DÐHÁ Á ÁA
C13ÐH13Á Á ÁO1i
Symmetry code: (i) 1 x; 12 ‡ y; 23 z.
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
C6ÐH6Á Á ÁO2
0.93
0.93
2.53
2.61
2.808 (5)
3.451 (5)
98
151
C5ÐH5Á Á ÁO1i
0.93
2.52
3.161 (3)
126
Symmetry code: (i) ‡ x; 12 y; 21 ‡ z.
1
2
ꢁ
o166 A. Subbiah Pandi et al.
C16H12ClNO2, C16H12BrNO2 and C15H9Cl2NO2
Acta Cryst. (2002). C58, o164±o167

organic compounds
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Ê
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ꢁ
Acta Cryst. (2002). C58, o164±o167
A. Subbiah Pandi et al.
C16H12ClNO2, C16H12BrNO2 and C15H9Cl2NO2 o167