Preparation and x-ray crystal structure of 3-(4-(Dimethylamino)phenyl)-2- (phenylamino)isoquinolin-1(2H)-one, 3-(4-Methoxyphenyl)-2-(phenylamino) isoquinolin-1(2H)-one, and 2-Methyl-N′-(4-methylbenzoyl)-N′- phenylbenzohydrazide from Polylithiated 2-methylbenzoic Acid phenylhydrazide and methyl 4-dimethylaminobenzoate, methyl 4-methoxybenzoate, or methyl 4-methylbenzoate

Article abstract of DOI:10.1007/s10870-012-0342-5

2-Methylbenzoic acid phenylhydrazide was polylithiated with excess lithium diisopropylamide, and the resulting polylithiated intermediate was condensed with methyl 4-dimethylaminobenzoate or methyl 4-methoxybenzoate to afford C-acylated intermediates that were immediately acid cyclized to afford 3-(4-(dimethylamino)-phenyl)-2-(phenylamino)isoquinolin-1(2H)-one C ₂₃H₂₁N₃O or 3-(4-methoxyphenyl)-2-(phenylamino) isoquinolin-1(2H)-one C₂₂H₁₈N₂O₂. The polylithiated intermediate underwent N-acylation when it was condensed with methyl 4-methylbenzoate to give 2-methyl-N′-(4-methylbenzoyl)-N′- phenylbenzohydrazide C₂₂H₂₀N₂O₂. Crystals of C₂₃H₂₁N₃O 4a are triclinic, P $ overline{1} $, a = 9.138(2) A, b = 10.519(2) A, c = 11.082(2) A, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) A³, R ₁ = 0.0711 and wR ₂ = 0.1828 for reflections with I > 2σ(I); crystals of C₂₂H₁₈N₂O₂ 4b are monoclinic, P2₁/c, a = 8.821(1) A, b = 13.276(2) A, c = 15.482(3) A, β = 105.271(4)°, Z = 4, V = 1748.9(5) A³, R ₁ = 0.0416 and wR ₂ = 0.1030 for reflections with I > 2σ(I); crystals of C₂₂H₂₀N₂O₂ 3 are orthorhombic, Pbca, a = 13.505(3) A, b = 9.733(2) A, c = 28.601(6) A, Z = 8, V = 3759.4(13) A³, R ₁ = 0.1683 and wR ₂ = 0.3526 for reflections with I > 2σ(I). Index Abstract: X-ray crystal analysis was important for the confirmation of the structure of 3-(4-(dimethylamino)phenyl)-2-(phenylamino)isoquinolin-1(2H)-one C₂₃H₂₁N₃O 4a, 3-(4-methoxyphenyl)-2- (phenylamino)isoquinolin-1(2H)-one C₂₂H₁₈N ₂O₂ 4b, and 2-methyl-N′-(4-methylbenzoyl)-N′- phenylbenzohydrazide C₂₂H₂₀N₂O₂ 3 prepared from polylithiated 2-methylbenzoicacid phenylhydrazide and methyl 4-dimethylaminobenzoate, methyl 4-methoxybenzoate, or methyl 4-methylbenzoate. Crystals of C₂₃H₂₁N₃O 4a are triclinic, P, a = 9.138(2) A, b = 10.519(2) A, c = 11.082(2) A, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) A³, R ₁ = 0.0711 and wR ₂ = 0.1828 for reflections with I > 2σ(I); crystals of C₂₂H ₁₈N₂O₂ 4b are monoclinic, P2₁/c, a = 8.821(1) A, b = 13.276(2) A, c = 15.482(3) A, β = 105.271(4)°, Z = 4, V = 1748.9(5) A³, R ₁ = 0.0416 and wR ₂ = 0.1030 for reflections with I > 2σ(I); crystals of C₂₂H₂₀N₂O₂ 3 are orthorhombic, Pbca, a = 13.505(3) A, b = 9.733(2) A, c = 28.601(6) A, Z = 8, V = 3759.4(13) A³, R ₁ = 0.1683 and wR ₂ = 0.3526 for reflections with I > 2σ(I).

Full text of DOI:10.1007/s10870-012-0342-5

J Chem Crystallogr (2012) 42:952–959
DOI 10.1007/s10870-012-0342-5
ORIGINAL PAPER
Preparation and X-Ray Crystal Structure of 3-(4-
(Dimethylamino)phenyl)-2-(phenylamino)isoquinolin-1(2H)-one,
3-(4-Methoxyphenyl)-2-(phenylamino)isoquinolin-1(2H)-one,
and 2-Methyl-N0-(4-methylbenzoyl)-N0-phenylbenzohydrazide
from Polylithiated 2-methylbenzoic Acid Phenylhydrazide
and Methyl 4-dimethylaminobenzoate, Methyl
4-methoxybenzoate, or Methyl 4-methylbenzoate
•
William G. Shuler Ellyn A. Smith Sloan M. Hess Thomas M. C. McFadden
•
•
•
•
•
Clyde R. Metz Donald G. VanDerveer William T. Pennington
•
•
Phillip J. Mabe Shabree L. Knick Charles F. Beam
•
Received: 20 June 2011 / Accepted: 13 June 2012 / Published online: 26 July 2012
Ó Springer Science+Business Media, LLC 2012
3
˚
Abstract 2-Methylbenzoic acid phenylhydrazide was
polylithiated with excess lithium diisopropylamide, and the
resulting polylithiated intermediate was condensed with
methyl 4-dimethylaminobenzoate or methyl 4-methoxy-
benzoate to afford C-acylated intermediates that were
immediately acid cyclized to afford 3-(4-(dimethylamino)-
phenyl)-2-(phenylamino)isoquinolin-1(2H)-one C23H21N3O
or 3-(4-methoxyphenyl)-2-(phenylamino)isoquinolin-1(2H)-
one C22H18N2O2. The polylithiated intermediate underwent
N-acylation when it was condensed with methyl 4-meth-
ylbenzoate to give 2-methyl-N0-(4-methylbenzoyl)-N0-
phenylbenzohydrazide C22H20N2O2. Crystals of C23H21N3O 4a
Z = 8, V = 3759.4(13) A , R1 = 0.1683 and wR2 =
0.3526 for reflections with I [ 2r(I).
Keywords Multiple anion synthesis ꢀ Isoquinolinones ꢀ
N-acylated hydrazide
Introduction
The syntheses, biological potential and other uses of variously
substituted isoquinolin-1(2H)-ones (isocarbostyrils) have
recently been intensively studied and reviewed [1–6].
There are some recent reports dealing with the strong base
multiple anion preparation of 3-substituted or 4-substituted
and related substituted isoquinolin-1(2H)-ones [7–11].
While there is an abundance of information concerning
4-substituted isoquinolin-1(2H)-ones, there are fewer
reports dealing with the preparation of 2-substituted and
2,3-disubstituted isoquinolin-1(2H)-ones, especially amino
and anilino substituted [12–16]. For select isoquinolinones
only 2-amino-3-phenylisoquinolin-1(2H)-one, 3-phenyl-
amino-, and 4-phenylaminoisoquinolin-1(2H)-ones have
been reported [12–16]; 2-phenylaminoisoquinolin-1(2H)-
ones have not. Relatively recent molecular modeling
studies of select 3-arylisoquinolin-1(2H)-one antitumor
agents with some X-ray studies have been reported.
Recently the X-ray crystal analysis of 3-phenylisoquinolin-
1(2H)-one has been documented [17].
˚
are triclinic, P 1, a = 9.138(2) A, b = 10.519(2) A,
˚
˚
c = 11.082(2) A, a = 91.55(3)°, b = 108.92(3)°, c = 111.16(3)°,
3
Z = 2, V = 927.1(3) A , R1 = 0.0711 and wR2 = 0.1828
˚
for reflections with I [ 2r(I); crystals of C22H18N2O2 4b are
˚
monoclinic, P21/c, a = 8.821(1) A, b = 13.276(2) A,
˚
3
˚
˚
c = 15.482(3) A, b = 105.271(4)°, Z = 4, V = 1748.9(5) A ,
R1 = 0.0416 and wR2 = 0.1030 for reflections with
I [ 2r(I); crystals of C22H20N2O2 3 are orthorhombic,
˚
˚
˚
Pbca, a = 13.505(3) A, b = 9.733(2) A, c = 28.601(6) A,
W. G. Shuler ꢀ E. A. Smith ꢀ S. M. Hess ꢀ
T. M. C. McFadden ꢀ C. R. Metz ꢀ P. J. Mabe ꢀ
S. L. Knick ꢀ C. F. Beam (&)
Department of Chemistry and Biochemistry, College of
Charleston, Charleston, SC 29424, USA
e-mail: beamc@cofc.edu
Our attention has been focused on the strong base
multiple anion preparation of these compounds [18, 19].
The 2,3-disubstituted isoquinolin-1(2H)-ones have been
D. G. VanDerveer ꢀ W. T. Pennington
Department of Chemistry, Clemson University, Clemson,
SC 29634, USA
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J Chem Crystallogr (2012) 42:952–959
953
Scheme 1 Preparation of
3-aryl-2-
CH3
(phenylamino)isoquinolin-
1(2H)-ones 4a and 4b and
2-methyl-N0-(4-methylbenzoyl)-
phenylbenzohydrazide 3
O
C
O
O
C
O
C
C
N
Li
NH
NH C6H5
N
N
C6H5
N
H
C6H5
Li
CH2Li
CH3
1
2
CH3
3
O
O
H
C
N
H
N
C6H5
NH
N
CH2
C
C6H5
O
5
R
C-acylated intermediate
R = N(CH3)2 for 4a
R = OCH3 for 4b
OCH3
O
O
H
N
H
N
N
C6H5
N
C6H5
4b
4a
CH3
N
OCH3
CH3
prepared in this laboratory by multiple anion synthesis
procedures involving polylithiated 2-methylbenzamides
[18], and 2-(methylphenyl)hydrazinecarboxylic acid esters
[19]. Additional methods of preparation by others involved
O-methyl benzohydroxamates [8] or dilithiated N-meth-
ylbenzamides condensed with aromatic nitriles [7], fol-
lowed by hydrolysis-cyclization of intermediates. Other
strong base syntheses have involved lateral lithiation
reactions [9], cyclization of dilithiated N,2-dimethylbenz-
amide, and intramolecular olefination of 2-trimethylsilyl-
methyl-N-acyl-N-alkylbenzamides [10].
Absorption spectra was indicative of structure with sev-
eral readily identifiable absorptions: IR (cm-1), 3233 for 4a;
3244 for 4b; (NH); 1652 for 4a and 1646 for 4b (C=O); 1H
NMR (d) 6.47 for 4a; 6.56 for 4b (C4–H); 13C NMR 162.2
for 4a; 160.6 for 4b (C=O); 105.8 for 4a; 107.1 for 4b (C4).
The general structure was also clearly confirmed by X-ray
crystal analysis of isoquinolinones 4a and 4b. Both of the
compounds 4a and 4b are new, and combustion analysis for
C, H, and N provided additional support.
While the cyclization of C-acylated intermediate (brack-
eted in Scheme) to benzodiazapinone 5 is a possibility,
estimated relative stability calculations indicate that 4b is
greater than 6 kcal mol-1 more stable than 5 [20, 21].1 Other
spectral estimates, primarily 1H and 13C NMR, also ruled out
benzodiazepinone 5.
Results and Discussion
During this investigation 2-methylbenzoic acid phenylhydr-
azide 1 [6] was trilithiated with excess lithium diisopro-
pylamide (LDA) to afford reactive polylithiated
intermediate 2. This polylithiated intermediate 2 was con-
densed with methyl 4-dimethylaminobenzoate to afford
C-acylated intermediate compound that was not isolated, but
illustrated in Scheme 1. It was immediately cyclized with
3 M hydrochloric acid to afford 2-phenylaminoisoquinolin-
1(2H)-one 4a in a 97 % yield. A follow up reaction of
trilithiated hydrazide 2 with methyl 4-methoxybenzoate
followed by acid cyclization of the C-acylated intermediate
resulted in the preparation of 3-(4-methoxyphenyl)-2-(phen-
ylamino)isoquinolin-1(2H)-one 4b in 96 % yield.
Even though the procedures for 4a and 4b are repro-
ducible in very good yield, methyl 4-methylbenzoate
underwent N-acylation at the nitrogen bonded to the
benzene ring and this resulted in N-acylated hydrazide 3,
2-methyl-N0-(4-methylbenzoyl)-phenylbenzohydrazide in
67 % yield. This indicates that lithiation of the 2-methyl
carbon to form the trianion did not occur probably due to
1
Comparison of the enthalpies of formation calculated for isolated
molecules of 4b and 5 using MOPAC PM6 theory indicates that the
4b isomer is more stable than the 5 isomer by slightly greater than
6 kcal mol-1. Additional calculations using density functional theory
(B3LYP/6-31G(d)) indicate that the 4b isomer is more stable by
slightly greater than 10 kcal mol-1
.
123

954
J Chem Crystallogr (2012) 42:952–959
Fig. 1 ORTEP diagram (50 %
ellipsoids for non-hydrogen
atoms), 3-[4-
dimethylamino)phenyl]-2-
(phenylamino)isoquinolin-
1(2H)-one C23H21N3O 4a [23],
and conventional illustration
C13
C14
C12
C11
C15
C10
N2
O1
C7
C4
N1
C1
C8
C6
C9
C2
C21
C20
C3
C5
C23
C19
C16
C17
C18
N3
C22
Fig. 2 ORTEP diagram (50 %
ellipsoids for non-hydrogen
atoms), 3-(4-methoxyphenyl)-2-
(phenylamino)isoquinolin-
1(2H)-one C22H18N2O2 4b [23],
and conventional illustration
contamination, and acylation occurred at next most reac-
tive N-anion site. (see crystal studies on structurally related
N-acylhydrazides [22]).
The molecular structure of 3 is shown in Fig. 4 and
selected bond distances and angles are listed in Table 3.
The angles between the least squares best planes repre-
senting the rings containing C9 and C10 and containing
C10 and C16 are 89.60° and 41.66°, respectively. Figure 5
shows the hydrogen bonding in which each molecule is
hydrogen bonded to two molecules: the O2 atom is bonded
The molecular structure of 4a is shown in Fig. 1 and for
4b in Fig. 2. Selected bond distances and angles are listed
in Table 1 for 4a and Table 2 for 4b. For 4a, the bond
lengths agree with the assignment of the double bond
shown between C1 and C2 (see the ORTEP diagram for
numbering of atoms). The least squares best planes repre-
senting the rings containing N1 and C10 and the rings
containing N1 and C16 are nearly perpendicular with
angles of 88.2° and 75.6°, respectively, between them.
Each molecule forms two hydrogen bonds with a second
molecule in which the H atom on the N2 atom of each
˚
at a distance of 2.109 A to the H atom on N2 atom on the
first molecule and the H atom on the N2 atom to the O2
atom on the second.
Experimental
˚
molecule is bonded at a distance of 2.002 A to the O1 atom
Melting points were obtained with a Mel-Temp II melting
point apparatus in open capillary tubes and are uncorrected.
Fourier Transform infrared spectra were obtained with a
Mattson Genesis II FT-IR with Specac Golden Gate
Accessory. Proton and 13C NMR spectra were obtained
with a Varian Associates Mercury Oxford (300 MHz for
1H and 75 MHz for 13C) NMR spectrometer, and chemical
shifts are recorded in d ppm downfield from an internal
tetramethylsilane (TMS) standard. Mass spectra were
on the other molecule as shown in Fig. 3. The structure of
4b is nearly identical to that of 4a with the angles of the
least squares best planes of 87.1° and 71.7°, respectively.
The hydrogen bonding in 4b is identical to that of 4a
˚
except the distance is 2.115 A.
The single crystal X-ray analysis (see the ORTEP dia-
gram illustrated in Fig. 4) obtained for N-acylated product
3 indicated that cyclization between C2 and C3 did not
occur. Instead of C2 bonding to N2, it attached to N1.
recorded using
a Finnigan LCQ ESI-MS system.
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J Chem Crystallogr (2012) 42:952–959
955
˚
Table 1 Selected bond distances (A) and angles (°), C23H21N3O 4a
C1–C2
C2–C3
C8–C9
C9–N1
N1–C1
C1–C16
C19–N3
N3–C22
N3–C23
N1–N2
N2–C10
C9–O1
1.352(4)
1.449(4)
1.467(4)
1.397(4)
1.399(4)
1.481(4)
1.376(4)
1.452(4)
1.453(4)
1.409(3)
1.418(4)
1.224(4)
C1–C2–C3
C2–C1–N1
C1–N1–C9
N1–C9–C8
C1–N1–N2
C9–N1–N2
N1–N2–C10
N1–C1–C16
C19–N3–C22
C19–N3–C23
C22–N3–C23
121.5(3)
118.6(3)
125.1(3)
115.1(3)
116.8(2)
117.8(3)
114.4(2)
118.0(3)
120.5(3)
119.0(3)
118.6(3)
˚
Table 2 Selected bond distances (A) and angles (°), C22H18N2O2 4b
C1–C2
C2–C3
C8–C9
C9–N1
N1–C1
C1–C16
N1–N2
N2–C10
C9–O1
1.351(2)
1.434(2)
1.464(2)
1.392(2)
1.398(2)
1.484(2)
1.409(2)
1.414(2)
1.229(2)
C1–C2–C3
C2–C1–N1
C1–N1–C9
N1–C9–C8
C1–N1–N2
C9–N1–N2
N1–N2–C10
N1–C1–C16
121.5(1)
119.1(1)
124.3(1)
115.8(1)
117.4(1)
117.9(1)
114.8(1)
118.9(1)
Fig. 3 Intermolecular hydrogen bonding in 4a. The distance between
the H atom on the N2 atom of each molecule to the O1 atom on the
˚
other molecule is 2.002 A
Combustion analyses were performed by Quantitative
Technologies, Inc., P.O. Box 470, Whitehouse, NJ 08888.
dissolved in 25–35 mL of THF was added, during 5 min, to
trilithiated intermediate 2, and the solution was stirred for
1–2 h. This was followed by rapid addition of 100 mL of
3 M hydrochloric acid, and heating the well stirred mixture
under reflux for 30 min. The mixture was added to a large
flask containing ice. Before neutralization with solid
sodium bicarbonate, an additional 100 mL of solvent grade
ether was added to the mixture, and the two-phase mixture
was separated, followed by extraction of the aqueous layer
with ether (2 9 50 mL). The combined organic fractions
were extracted with 25 mL of 5 % sodium bicarbonate
solution, then 25 mL water. The resulting organic solution
was dried with MgSO4, decanted, and evaporated [roto-
evap. temp of water bath *40 °C]. An oil or a solid
resulted; the solid was recrystallized and the oil was taken
up in an approximate equal volume of methanol or ethanol.
Upon refrigeration of this solution/mixture, crystallization
occurred.
Preparation of 2-Phenylamino-3-arylisoquinolin-1(2H)-
ones 4a and 4b
Ratio of reagents—hydrazide: LDA: ester 1:5:1 for 4a and
1:4:1 for 4b.
In a typical reaction sequence, LDA was prepared by the
addition of 40 mL for 4a [33 mL for 4b] of 1.60 M
n-butyllithium [and 0.0630 mol for 4a and 0.0525 mol for
4b] in hexanes to a three-neck round-bottomed flask (e.g.,
500 mL), equipped with a nitrogen inlet tube, and a side-
arm addition funnel (e.g., 125 mL). The flask was cooled in
an ice water bath, 6.41 g (0.0630 mol) for 4a and 5.34 g
(0.0525 mol) for 4b of diisopropylamine (99.5 %—
Aldrich Chem. Co.), dissolved in 25–35 mL of dry THF
(freshly distilled from sodium) was added from the addi-
tion funnel at a fast drop wise rate during a 5 min (0 °C,
N2) period. The solution was stirred for an additional
15–20 min, and then treated via the addition funnel,
during 5 min, with 2-methylbenzoic acid phenylhydrazide
[6], 3.39 g (0.0150 mol) dissolved in 40–60 mL of
THF. After 3–4 h, a solution of 2.83 g of methyl
4-dimethylaminobenzoate for 4a and 2.62 g of methyl
4-methoxybenzoate for 4b (0.0158 mol 5 % molar excess)
3-[4-(Dimethylamino)phenyl]-2-
(phenylamino)isoquinolin-1(2H)-one (4a)
Compound 4a was obtained in a 97 % yield, 229–230 °C
(methanol) from condensation-cyclization of 2 with methyl
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956
J Chem Crystallogr (2012) 42:952–959
Fig. 4 ORTEP diagram (50 %
ellipsoids for non-hydrogen
atoms), 2-methyl-N0-(4-
methylbenzoyl)-N0-
phenylbenzohydrazide
C22H20N2O2 3 [23], and
conventional illustration
C13
C14
C12
C11
C15
C10
O1
O2
N1
C2
N2
C16
C21
C8
C1
C17
C18
C7
C9
C4
C5
C3
C6
C20
C19
C22
CH), 7.42 (d, 1H, CH, J = 8.7 Hz), 7.46 (m, 2H, CH), 7.70
(m, 1H, CH), 8.15 (d, 1H, CH, J = 8.1 Hz), 8.92 (s, 1H,
NH). 13C-NMR (DMSO-d6): d 41.0, 105.8, 111.6, 113.0,
120.0, 122.5, 125.3, 126.8, 127.1, 127.8, 129.0, 130.7,
133.5, 137.4, 147.3, 149.0, 151.0, 162.2. Anal. Calcd for
C23H21N3Oꢀ1/8 H2O: C, 77.23; H, 5.99; N, 11.75. Found:
C, 77.09; H, 5.85; N, 11.56.
˚
Table 3 Selected bond distances (A) and angles (°), C22H20N2O2 3
C1–C9
C1–O1
C1–N2
N2–N1
N1–C10
N1–C2
C2–O2
C2–C16
1.475(14)
1.232(15)
1.362(13)
1.402(10)
1.443(12)
1.357(13)
1.201(11)
1.497(13)
C9–C1–N2
114.0(10)
118.3(9)
116.7(8)
121.6(8)
117.7(9)
179.4(8)
100.4(10)
-61.8(12)
-24.4(14)
C1–N2–N1
N2–N1–C10
N2–N1–C2
N1–C2–C16
N1–N2–C1–C9
C10–N1–N2–C1
C2–N1–N2–C1
N2–N1–C2–C16
Single Crystal X-ray Structure Determination, 4a
Yellow crystals of C23H21N3O 4a were recrystallized from
an ethanol–water solution in order to give satisfactory
crystals for X-ray determination. Crystal data for X-ray
studies [24] were collected at 168 K on a Mercury CCD
area detector coupled with a Rigaku AFC8 diffractometer
with graphite monochromated Mo-Ka radiation. Data were
collected in 0.5° oscillations in x with 30 s exposures. A
sweep of data was done using x oscillations from -40.0°
to 90.0° at v = 45° and / = 0.0°; a second sweep was
performed using x oscillations from -40.0° to 90.0° at
v = 45° and / = 90.0°. The crystal-to-detector distance
was 27.728 mm. Details of the data collection are reported
Table 4. Data were collected, processed, and corrected for
Lorentz polarization and for absorption using CrystalClear
(Rigaku) [24, 25].
The non-hydrogen atoms were refined anisotropically.
Ideal hydrogen atom coordinates for the rings containing
C3, C10, and C16 (see numbering of atoms in ORTEP
diagram, Fig. 1); C2; and the methyl groups containing
C22 and C23 were calculated and the hydrogen atoms were
allowed to ride on their respective carbon atoms. The
hydrogen atom on N2 was located on a difference electron
density map. The temperature factors of all hydrogen atoms
were varied isotropically. Structure solution, refinement,
and the calculation of derived results were performed using
Fig. 5 Intermolecular hydrogen bonding in 3. The distances between
˚
the O2 atom and the H atom on the N2 atom are 2.109 A
4-dimethylaminobenzoate. IR: 1598, 1652, 3023,
1
3233 cm-1. H-NMR (DMSO-d6): d 3.36 (s, 6H, CH3),
6.47 (d, 2H, CH, J = 7.8 Hz), 6.64 (d, 2H, CH,
J = 8.7 Hz), 6.65 (s, 1H, CH), 6.70 (d, 2H, CH,
J = 7.2 Hz), 7.05 (t, 2H, CH, J = 7.8 Hz), 7.34 (s, 1H,
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J Chem Crystallogr (2012) 42:952–959
957
CH, J = 8.7 Hz), 7.12 (t, 1H, CH, J = 7.5 Hz), 7.47 (m,
3H, CH), 7.56 (d, 2H, CH, J = 7.5 Hz), 7.66 (t, 2H, CH,
J = 8.1 Hz), 8.38 (d, 1H, CH, J = 7.8 Hz). 13C-NMR
(DMSO-d6): d 55.4, 107.1, 113.4, 114.3, 122.0, 125.2,
126.3, 126.7, 127.1, 128.2, 129.2, 130.8, 136.8, 145.2,
147.6, 160.1, 162.6. LCMS, exact mass, 342.39: (M ? H)?,
343.05. Anal. Calcd for C22H18N2O2ꢀ1/2 H2O: C, 75.20; H,
5.45; N, 7.97. Found C, 75.18; H, 5.20; N, 7.95.
Table 4 Crystallographic Data, C23H21N3O 4a
CCDC deposit numbera
Color/shape
778252
Yellow/prism
0.34 9 0.24 9 0.10
Crystal dimensions (mm)
Formula
C23H21N3O
Formula mass
T (K)
355.43
168
Crystal system
Space group
Triclinic
P 1
Single Crystal X-ray Structure Determination, 4b
˚
a (A)
9.138(2)
10.519(2)
11.082(2)
91.55(3)
108.92(3)
111.16(3)
927.1(3)
2
˚
b (A)
Colorless crystals of 4b, C22H18N2O2 were recrystallized
from an ethanol–water solution in order to give satisfactory
crystals for X-ray determination. Crystal data for X-ray
studies werecollectedat188 K onthe systemdescribed above
using the same data collection parameters except the exposure
times were 20 s and the second x sweep range was -30.0° to
80.0°. The crystal-to-detector distance was 26.804 mm.
Details of the data collection are reported Table 5. Data were
collected, processed, and corrected as described above.
The non-hydrogen atoms were refined anisotropically.
Ideal hydrogen atom coordinates for the rings containing
C3, C10, and C16 (see numbering of atoms in ORTEP
diagram, Fig. 2) and the methyl group containing C22 were
calculated and the hydrogen atoms were allowed to ride on
their respective carbon atoms. The hydrogen atoms on C2
and N2 were located on a difference electron density map.
The temperature factors of all hydrogen atoms were varied
isotropically. Structure solution, refinement, and other
calculations are described above.
˚
c (A)
a (°)
b (°)
c (°)
3
˚
V (A )
Z
dcalc (g cm-3
)
1.273
˚
k (A)
0.71073
0.080
l (mm-1
F(000)
)
376
h range (°)
Reflections collected
2.90–25.15
7002
Miller indices
-10 B h B 10, -12 B k B 12,
-13 B l B 11
Unique reflections
3284
Unique reflections I [ 2r(I)
Max and min transmission
Data, restraints, parameters
Final R indices I [ 2r(I)
R indices all data
2116
1.000, 0.521
3284, 0, 250
R1 = 0.0711, wR2 = 0.1828
R1 = 0.1109, wR2 = 0.2379
1.028
2-Methyl-N0-(4-methylbenzoyl)-N0-
phenylbenzohydrazide (3)
Goodness of fit on F2
-3
)
˚
Largest diff peak and hole (e A
0.378, -0.317
Compound 3 was obtained [hydrazide:LDA:ester—1:4:1]
in a 67 % yield, 159–160 °C (ethanol) from the conden-
sation-cyclization of presumed 2 with methyl 4-meth-
CCDC 778252 for 4a, CCDC 882827 for 4b and CCDC 828909 for 3
contain the supplementary crystallographic data for this paper. These
data can be obtained free of charge from the Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif
ylbenzoate. IR: 1647, 1679, 2924, 3070, 3296 cm-1
.
1H-NMR (DMSO-d6): d 3.43 (s, 3H, CH3), 6.72 (t, 1H, CH,
J = 7.2 Hz), 6.83 (d, 2H, CH, J = 8.7 Hz), 7.09 (s, 1H,
CH), 7.21 (d, 2H, CH, J = 7.5 Hz), 7.36 (m, 3H, CH), 7.49
(d, 2H, CH, J = 7.5 Hz), 7.79 (t, 1H, CH, J = 7.8 Hz),
7.85 (d, 1H, CH, J = 8.1 Hz), 7.93 (d, 1H, CH,
J = 3.6 Hz), 11.31 (s, 1H, NH), 13C-NMR (DMSO-d6): d
21.7, 112.9, 124.7, 126.3, 127.6, 128.5, 129.5, 129.9,
130.0, 131.0, 131.3, 131.4, 133.1, 134.2, 136.7, 141.1,
142.7, 168.2. Anal. Calcd for C22H18N2Oꢀ1/8 H2O: C,
76.22; H, 5.89; N, 8.08. Found C, 76.24; H, 5.88; N, 8.14.
the SHELX-97 [26] package of computer programs. Neutral
atom scattering factors were those of Cromer and Waber
[27], and the real and imaginary anomalous dispersion
corrections were those of Cromer [27].
3-(4-Methoxyphenyl)-2-(phenylamino)isoquinolin-
1(2H)-one (4b)
Compound 4b was obtained in a 96 % yield, 177–178° C
(ethanol) from the condensation-cyclization of 2 with
methyl 4-methoxybenzoate. IR: 1510, 1600, 1646, 2964,
Single Crystal X-ray Structure Determination, 3
1
3244 cm-1. H-NMR (DMSO-d6): d 3.77 (s, 3H, OCH3),
Light yellow crystals of 3, C22H20N2O2 were recrystallized
from an ethanol–water solution in order to give satisfactory
6.56 (s, 1H, CH), 6.65 (d, 2H, CH, J = 7.8 Hz), 6.85 (d, 2H,
123

958
J Chem Crystallogr (2012) 42:952–959
Table 5 Crystallographic data, C22H18N2O2 4b
Table 6 Crystallographic data, C22H20N2O2 3
CCDC deposit numbera
Color/shape
882827
CCDC deposit numbera
Color/shape
828909
Colorless/prism
0.48 9 0.36 9 0.31
Yellow/prism
0.29 9 0.19 9 0.10
Crystal dimensions (mm)
Formula
Crystal dimensions (mm)
Formula
C22H18N2O2
C22H20N2O2
Formula mass
T (K)
342.38
188
Formula mass
T (K)
344.40
173
Crystal system
Space group
Monoclinic
P21/c
Crystal system
Space Group
Orthorhombic
Pbca
˚
a (A)
˚
a (A)
8.821(1)
13.276(2)
15.481(3)
105.271(4)
1748.9(5)
4
13.505(3)
9.733(2)
28.601(6)
3759.4(13)
8
˚
b (A)
˚
b (A)
˚
c (A)
˚
c (A)
3
V (A )
˚
b (°)
3
˚
V (A )
Z
Z
dcalc (g cm-3
)
1.217
dcalc (g cm-3
)
1.300
k (A)
0.71073
0.079
˚
k (A)
0.71073
0.084
l (mm-1
F(000)
)
˚
l (mm-1
)
1456
F(000)
720
h range (°)
Reflections collected
2.95–25.15
15186
h range (°)
Reflections collected
2.84–25.14
11490
Miller indices
-16 B h B 12, -11 B k B 9,
-34 B l B 34
Miller indices
-10 B h B 10, -14 B k B 15,
-18 B l B 18
Unique reflections
3280
Unique reflections
3108
Unique reflections I [ 2r(I)
Max and min transmission
Data, restraints, parameters
Final R indices I [ 2r(I)
R indices all data
1182
Unique reflections I [ 2r(I)
Max and min transmission
Data, restraints, parameters
Final R indices I [ 2r(I)
R indices all data
2764
1.000, 0.3577
3280, 0.237
1.000, 0.879
3108, 0, 244
R1 = 0.1683, wR2 = 0.3526
R1 = 0.3152, wR2 = 0.4897
1.185
R1 = 0.0416, wR2 = 0.1030
R1 = 0.0463, wR2 = 0.1098
1.069
Goodness of fit on F2
Goodness of fit on F2
0.547, -0.433
-3
)
˚
Largest diff peak and hole (e A
-3
)
˚
Largest diff peak and hole (e A
0.176, -0.219
CCDC 778252 for 4a, CCDC 882827 for 4b and CCDC 828909 for 3
contain the supplementary crystallographic data for this paper. These
data can be obtained free of charge from the Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif
CCDC 778252 for 4a, CCDC 882827 for 4b and CCDC 828909 for 3
contain the supplementary crystallographic data for this paper. These
data can be obtained free of charge from the Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif
above 30° were still quite weak. There are no solvent voids
and we are unable to explain the poor crystal quality.
However, the atom connectivity, bond lengths and angles,
and other molecular parameters determined from these data
are sufficiently precise to be meaningful.
crystals for X-ray determination. Crystal data for X-ray
studies were collected at 173 K on the system described
above using the same data collection parameters with 120 s
exposures. The crystal-to-detector distance was
27.267 mm. Details of the data collection are reported
Table 6. Data were collected, processed, and corrected as
described above.
Acknowledgments We wish to thank the following sponsors for
support: the Research Corporation, the Summer Undergraduate
Research Forum (SURF) of the College of Charleston, and the
Howard Hughes Medical Institute (HHMI) along with earlier grants
from the National Science Foundation (CHE # 9708014 and #
0212699) for Research at Undergraduate Institutions (NSF-RUI), and
the United States Department of Agriculture (NRICGP # 2003-35504-
12853).
The non-hydrogen atoms were refined anisotropically.
Ideal coordinates for all hydrogen atoms were calculated and
the hydrogen atoms were allowed to ride on their respective
carbon atoms. The temperature factors of all hydrogen atoms
were varied isotropically. Structure solution, refinement,
and other calculations are described above.
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