Synthesis, NMR and crystallographic studies of 2-substituted dihydroquinazolinones derived from (S)-phenylethylamine

Article abstract of DOI:10.3390/12020173

2,3-Dihydro-3-[(S)-1-phenethyl]quinazolinone and some new 2-substituted derivatives bearing isopropyl, o-nitrophenyl and p-nitrophenyl groups were prepared in 40-90% yield by amidation of isatoic anhydride with (S)-phenylethylamine, followed by condensati

Full text of DOI:10.3390/12020173

Molecules 2007, 12, 173-182
molecules
ISSN 1420-3049
http://www.mdpi.org
Full Paper
Synthesis, NMR and Crystallographic Studies of 2-Substituted
Dihydroquinazolinones Derived from (S)-Phenylethylamine
1
,*
1
1
1
Jaime Escalante , Claudia Ortíz-Nava , Patricia Flores , Jaime M. Priego and
2
,*
Cirilo García-Martínez
1
Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos. Av.
Universidad No. 1001, Col. Chamilpa, C.P. 62210 Cuernavaca-Mor. México.
Universidad Autónoma Metropolitana, Area de Química. San Pablo No. 180, Col. Reynosa
Tamaulipas, México 02200, D.F.
2
*
Authors to whom correspondence should be addressed; E-mails: jaime@ciq.uaem.mx or
gmc@correo.azc.uam.mx
Received: 5 December 2006; in revised form: 2 February 2007 / Accepted: 5 February 2007 /
Published: 12 February 2007
Abstract: 2,3-Dihydro-3-[(S)-1-phenethyl]quinazolinone and some new 2-substituted
derivatives bearing isopropyl, o-nitrophenyl and p-nitrophenyl groups were prepared in
4
0-90% yield by amidation of isatoic anhydride with (S)-phenylethylamine, followed by
condensation with triethyl orthoformate, isopropylaldehyde, o-nitro- and p-nitro-
benzaldehyde, respectively. The two 2-subtituted dihydroquinazolinones obtained either
by using isopropylaldehyde, o-nitro- or p-nitrobenzaldehyde, were separated and purified
3
before their NMR spectra in CDCl solutions were recorded. The detection of the low
energy conformation of O=C-N-phenethyl segment in solution allowed the correlation of
the NMR data with the configuration of newly stereogenic carbon C-2; thus, one
diastereomer was labeled SS while the other was RS. Configurations determined by the
NMR method were corroborated by X-ray diffraction analysis. X-ray structures of each
diastereomeric series showed characteristic conformational types: a propeller-like for the
SS and a hairpin for the RS series. Interatomic distances of the hairpin conformation
suggest the existence of intramolecular face-to-face interactions between two aromatic
rings.

Molecules 2007, 12
174
Keywords: Chiral dihydroquinazolinones, π-stacking interactions, NMR method,
configurational analysis.
Introduction
Amidation of chiral primary amines with single enantiomers of methoxytrifluoromethylphenyl-
acetyl chloride and related derivatizing agents is commonly used to determine the configuration of new
1
stereogenic centers by H-NMR spectrocopy [1]. The detection of the low energy conformation 1 of
the resulting amides is fundamental to establish the correlation between the chemical shifts (δ) of the
hydrogen nuclei of the amine moiety and the configuration of the chiral derivatizing agent [2].
Although this strategy can be used to study the configuration of cyclic secondary amines, inherent ring
conformations and slow rotation about amide bonds (see 2) make it difficult to interpret the NMR
spectra [3]. In this context, incorporation of a 1-arylethyl group as the amidic nitrogen substituent,
might be the recommended strategy to avoid free rotation about amide bond. Studies carried out with
chiral four- and five-membered cyclic amides prepared from a single enantiomer of either arylethyl-
isocyanates [4] or phenylethylamine [5], showed that interaction between the methine hydrogen of the
1
-phenethyl group and the carbonyl-oxygen favors the low-energy conformer 3. Thus, the
configuration of new stereogenic centers located in the neighborhood of the 1-phenethyl group, were
readily determined from the chemical shifts and the orientation of phenyl ring [4,5].
Me
N
O
H Ph
N
R1
H
OCH3
O
H
R
CF3
N
Ph
Me
CF3
O
Ph OMe
OEt
2
3
1
Since the 1-phenethyl group can be removed from the heterocycle by hydrogenolysis [6], this
strategy is comparable to classical chiral derivatizing methods. In a previous report [5b], we studied
the effect of bulky substituents on the orientation of 1-phenethyl group of five-membered ring amides;
this time we wish to report the applicability of 1-phenethyl group to six-membered ring amides. Herein
we report the synthesis and configurational analysis of some new 2,3-dihydro-3-[(S)-1-phenethyl]-
quinazolinones 8-11.
Results and Discussion
Synthesis of dihydroquinazolinones
The studied products were prepared by the sequence shown in Scheme 1 [7,8]. The reaction of
isatoic anhydride (4) with (S)-1-phenylethylamine (5) gave benzamide 6, which was treated with
triethyl orthoformate and p-toluenesulfonic acid to give 7. Catalytic hydrogenation of 7 gave 2,3-
dihydro-3-[(S)-1-phenethyl]-4-quinazolinone (8). It should be noted that under these conditions

Molecules 2007, 12
175
reductive cleavage of the 1-phenethyl group did not occur, due to the fact that the likelihood of
removing this group from an amide is minimal. On the other hand, reactions of 6 with iso-
butyraldehyde, o-nitro- or p-nitrobenzaldehyde, gave the corresponding 2-substituted 2,3-dihydro-3-
[(S)-1-phenethyl]quinazolinones 9-11 in nearly 3:2 diastereomeric ratio and 40-90% yields (see
Experimental section). Based on the assumption that the configuration of (S)-1-phenylethylamine does
not change in the two-reaction process [9], we assigned the S configuration to the C9 carbon of 8 (see
the numbering system in Scheme 1). Consequently, the configurations of new compounds 9-11 could
only be SS and SR. Pure diastereomers 9-11 were successfully separated by flash chromatography [10]
and analyzed independently by NMR to produce two data sets for each diastereomeric pair. The first
eluted diastereomer was labeled as the "less polar" and the next one, as the "more polar". Hereafter, we
use the notation A and B for the "less polar" and "more polar" diastereomer, respectively.
Scheme 1
CH3
O
O
CH3
Ph
O
10CH3
5
8
3
N
2
H N
2
Ph
4a
6
7
4
9
O
N
H
RCHO
Ph
5
8
a
N
H
O
N1
H
R
NH2
6
9-11
4
HC(OC H )
2
5 3
Toluene / pTsOH
O
N
CH3
Ph
O
CH3
Ph
N
2
H - PtO2
N
EtOH
N
H
7
8
9
, R = i-Pr; 10, R = o-O NC H ; 11, R = p-NO C H
2 6 4 2 6 4
Structure and chemical shift correlations
The studied 2,3-dihydro-3-[(S)-1-phenethyl]quinazolinones have rigid structures with limited
degrees of freedom for single bond rotation. Their low energy molecular models, constructed with the
MM2 subroutine of CS Chem 3D Pro® program [11], show little pyramidalization of the N1 and N3
nitrogens, which are both almost coplanar with the fused carbocyclic ring. The half chair conformation
of the six-membered heterocyclic ring shows C2 out of the plane, with one pseudo-axial and one
pseudo-equatorial bond. The substituent attached to C2 is invariably pseudo-axial.
To highlight the usefulness of the NMR method, only δ values of specific hydrogen atoms attached
3
to sp carbons are commented briefly (however, complete data is given in the Experimental section). In
1
the H-NMR spectrum of 8, the diastereotopic hydrogens attached to C2 (H2) constitute the AB part of
an ABC system. In the spectra of 9A and 9B, H2 constitutes the A part of an ABC system, while in the
spectra of 10 and 11, H2 constitutes the A part of an AB spin-spin system. For any diastereomeric pair,
δ values of H2 (Table 1) showed large differences (∆δ = δH2 of A − δH2 of B) and therefore, H2 can be

Molecules 2007, 12
176
used as the pivotal nucleus to determine the configuration of C2. To fulfill the configurational analysis,
one needs to know the dominant conformation of 1-phenethyl group.
Table 1. δH2 Values of dihydroquinazolinones 8-11, obtained from 400
MHz spectra of 0.5 M solutions in CDCl
3
containing TMS at 25 °C.
Compound
δ diastereomer A δ diastereomer B ∆δ (ppb)

8
9
4.174, 4.463
4.19
−
−
4.535
6.138
5.674
-340
-103
-193
1
1
0
1
6.035
5.481
Experience and MM2 calculations of the O=C-CHCH Ph segment [5a] have shown that in the
3
absence of a large substituent in the proximity of such segment, the most stable conformation of the
1
-phenethyl group is that in which the methine hydrogen eclipses the carbonyl carbon [4,5]. Assuming
that the steric interaction of the substituent at C2 does not alter this low energy conformer, the position
of H2 and the phenyl ring could be inferred from δ . Accordingly, diastereomers A must have H2 in
H2
front of the phenyl ring, so that the configuration of C2 in these diastereomers must be S, and R that of
diastereomers B (Figure 1). The same conclusion can be drawn by applying this interpretation to the
observed δCH of isopropyl group of 9A and 9B, as well as to the observed δMe (C10) of 10A and 10B or
11A and 11B. In 9B, for instance, the methine hydrogen of the isopropyl lies in the diamagnetic zone
of the phenyl ring (∆δCH = -750 ppb) and in similar way, methyl C10 of 10A and 11A lies in the
diamagnetic zone of nitrophenyl ring (∆δMe = -509 and -464 ppb, respectively).
Figure 1. The conformation of 1-phenethyl group, is the key point to assign the absolute
configuration of new stereogenic carbon C2 of diastereomers A and B by routine
1
H- NMR experiments.
H
N
O R
CH3
Ph
H
H
H
CH3
N
H
O
H
R
Ph
diastereomer A
diastereomer B
X ray diffraction
To support the configurational analysis based on NMR spectra, the single crystals of 8, 9A, 10B,
1A and 11B were analyzed by X-ray diffraction [12]. The structures were solved with the
1
SHELXS97® program [13], under the assumption that the stereogenic carbon of the 1-phenethyl
moiety retained the configuration of (S)-1-phenylethylamine. The ORTEP drawing of 8 (Figure 2)
contains the following features: a peri-type interaction of the carbonyl with H5 twists the half-chair
conformation of the heterocyclic ring, deviating N3 and C4 from the plane of the fused carbocyclic
ring. The pyramidal N1 is aligned with the latter ring and the tetrahedral methylene C2 is out of the

Molecules 2007, 12
177
plane, with one hydrogen pseudo-axial and other pseudo-equatorial. Methine hydrogen H9 is
practically coplanar with the carbonyl group (φ H9-C9-N3-C4 = -5.0°) and close to the carbonyl-
oxygen; the distance between H9 and O4 is 2.33 Å. These features prove that the low energy
conformation of the 1-phenethyl group is not only a consequence of pure steric interactions of the
…
substituents attached to C2 and N3, but also of the C-H O hydrogen bond. According to the
conformation of crystalline 8, H2pseudo-equatorial is within the shielding zone of the phenyl ring and its
NMR signal should be expected at high field. The observed chemical shifts of H2pseudo-equatorial and
H2pseudo-axial are consistent with this expectation, see Table 1.
Figure 2. ORTEP drawing of compound 8 showing the syn-like conformation of
carbonyl C4 and hydrogen attached to C9.
The X-ray structures of 9A, 10B, 11A and 11B show that isopropyl, o-nitro and p-nitro groups do
not alter the typical conformation of the 1-phenethyl group. We chose 11A and 11B to summarize the
molecular features of these 2-substituted 2,3-dihydro-3-[(S)-1-phenethyl]quinazolinones. Thus, X-ray
structures 11A and 11B (Figure 3), show essentially the same half-chair conformation of the
heterocyclic ring described above for 8. Due to the allylic 1,3-effect [14], the p-nitrophenyl group is
oriented pseudo-axial. In 11A, the aromatic ring of p-nitrophenyl group is oriented towards the N3-C2
bond while in 11B, it is oriented towards the heterocyclic ring (φ N3-C2-Cipso-Cortho = 15.5° and -
4
2.2°, respectively). In 11A, the methine hydrogen of the 1-phenethyl group is much more deviated
from the carbonyl plane than in 11B (φ H15-C15-N3-C4 = 44.3° and -18.1°, respectively) but the
distance between H15 and O4 is still within the accepted values for hydrogen bonding [15]. The
relative orientation of p-nitrophenyl and phenyl rings is the marked difference between structures of
11A and 11B. In the crystalline structure, 11A assumes a propeller-like conformation. In contrast, 11B
assumes a hairpin conformation in which the phenyl and p-nitrophenyl rings are syn-like and slightly
displaced from each other, so their planes are not parallel. Interatomic distances between ipso carbons
C9-C17 (3.12 Å) and para carbons C12-C20 (4.57 Å), however, are small enough to suggest the
existence of a stabilizing intramolecular π-stacking interaction between the two aromatic rings [16].

Molecules 2007, 12
178
…
Thus, in addition to the above mentioned C-H O hydrogen bond, the crystal lattice 11B might be
stabilized by intramolecular face-to-face and intermolecular face-to-edge interactions. The analysis of
X ray structures of 10B, 2,3-dihydro-2-(S)-phenyl-3-[(R)-1-phenethyl]- and 2,3-dihydro-2-(S)-o-
methoxy-phenyl-3-[(R)-1-phenethyl] quinazolinone [7], are consistent with the features mentioned
above for 11B.
Figure 3. ORTEP drawings showing the propeller-like and hairpin conformations of
compounds 11A and 11B, respectively. It should be noticed that substituents are labeled
with a particular numbering system.
11B
11A
11B
Conclusions
We have prepared the new compounds 8, 9A, 9B, 10A, 10B, 11A and 11B, and have characterized
them by NMR, elemental analysis and X-ray diffraction. Experimental data of studied compounds
revealed that a syn-like conformation of the methine hydrogen of the phenethyl group and the carbonyl
oxygen is the dominant conformation in CDCl solution and in the solid state. Based on this
3
conformation and on the shielding effect caused by phenyl ring on neighboring protons, we assigned
the SS configuration to 9A, 10A and 11A, and the RS one to 9B, 10B and 11B. The crystalline
structure of the SS diastereomeric series derived from monosubstituted benzaldehydes has a propeller-
like conformation while the RS series assumes a hairpin conformation. Interatomic distances of the
latter arrangement suggest the existence of stabilizing intramolecular π-stacking interaction between
two aromatic rings.

Molecules 2007, 12
Experimental
General
179
All melting points were determined with a Büchi apparatus and are uncorrected. Specific rotations
was measured in a PerkinElmer 341 polarimeter at 24 °C and λ = 589 nm. Elemental analysis (CHN)
1
3
was performed on an Elementar Vario EL III elemental analyzer. Proton and C-NMR spectra were
obtained from 0.5 M solutions in CDCl , containing a small amount of TMS, and recorded on an Inova
3
1
4
1
00 spectrometer equiped with a 5 mm H probe at 25 °C. All chemical shifts are from TMS signal and
H-NMR data are given in the standard format: δ units, integration, signal multiplicity and coupling
constants in Hertz. X-ray diffraction analysis was carried out with an APEX-Bruker diffractometer.
The structures were solved by SHELXS97 method and refined by full-matrix least squares. For each
crystal, heavy atoms were refined anisotropically while hydrogen atoms were located in the calculated
positions.
Synthesis of dihydroquinazolinones
2
,3-Dihydro-3-[(S)-1-phenethyl]-4(1H)-quinazolinone (8) and its 2-substituted derivatives 9-11,
were prepared by minor variations of published procedures [17,7]. The physical and spectroscopic data
reported herein were obtained with pure diastereomers recrystallized from dichloromethane-hexane.
2
,3-Dihydro-3-[(S)-1-phenethyl]-4(1H)-quinazolinone (8)
Quinazolinone 7 was prepared according to a known procedure [17] and then it was hydrogenated
in the following way: a solution of 7 (0.5 g) in EtOH (10 mL) was mixed with commercial PtO
2
catalyst (0.05 g) and exposed to 30 psi of hydrogen during 2 h at 25 °C with shaking in a Parr
®
hydrogenator. The catalyst was filtered through Celite and the resulting solution was concentrated in
a rotavapor. The crude residue was purified via flash chromatography to give compound 8 (0.48 g, 95%
2
D
4
2
-1
1
yield): White solid, mp 119-121 °C; [α]
3
= -91.7 deg cm g ¸ c = 1.0 in CH OH; H-NMR δ1.57
(3H, d, J = 7.2 Hz), 4.17 (1H, dd, J = 2.4, 9.2 Hz), 4.22 (1H, s), 4.46 (1H, dd, J = 2.0, 9.2 Hz), 6.10
(
1H, q, J = 7.1 Hz), 6.63 (1H, d, J = 8.0 Hz), 6.88 (1H, ddd, J = 7.9, 7.9, 0.8 Hz,), 7.24 – 7.41 (6H, m),
1
3
7
1
7
.99 (1H, dd, J = 7.8, 1.6 Hz); C-NMR δ 16.3, 49.8, 55.0, 115.0, 118.1, 119.9, 127.3, 127.6, 128.7,
29.2, 133.2, 140.2, 147.6, 163.4. Anal. calcd. for C H N O: C, 76.10; H, 6.40; N, 11.02. Found: C,
1
6
16
2
6.16; H, 6.39; N, 11.10. X-Ray crystallographic data of 8 is available as supporting information [12].
2
,3-Dihydro-(2S)- and 2,3-dihydro-(2R)-isopropyl-3-[(S)-1-phenethyl]-4(1H)-quinazolinone (9A and
B, respectively)
9
The crude mixture of 9A and 9B, obtained from 6 (1 g, 4.0 mmol) and isobutyraldehyde (0.5 mL,
.0 mmol) was purified by flash chromatography (silica gel, hexane-dichloromethane-ethyl acetate
0:30:10) to afford 0.44 g of 9A and 0.30 g of 9B. Compound 9A was thus isolated as white solid, mp
5
7
1
2
4
2
-1
1
37-139 °C; [α]
D
3
= -118 deg cm g ¸ c = 0.7 in CHCl ; H-NMR δ 0.78 (3H, d, J = 6.8 Hz), 0.87

Molecules 2007, 12
180
(
3H, d, J = 6.8 Hz), 1.68 (3H, d, J = 7.4 Hz), 2.00 (1H, m), 4.19 (1H, dd, J = 3.6, 7.6 Hz), 4.28 (1H, s),
6
.08 (1H, q, J = 7.4 Hz), 6.52 (1H, d, J = 8.0 Hz), 6.76 (1H, ddd, J = 7.8, 7.8, 0.7 Hz), 7.18 – 7.41 (6H,
1
3
m), 7.88 (1H, dd, J 7.7, 1.1 Hz); C-NMR δ 17.2, 18.7, 19.0, 36.6, 52.8, 70.1, 113.8, 118.6, 118.6,
27.8, 128.7, 128.7, 128.8, 133.4, 141.0, 146.5, 163.6; Anal. calcd. for C19 O: C, 77.52; H, 7.53;
N, 9.52. Found: C, 77.30; H, 7.32; N, 9.00. X-Ray crystallographic data of 9A is available as
1
22 2
H N
2
D
4
supporting information [12]. Diastereomer 9B was isolated as a white solid, mp 141-142 °C; [α] = -
2
2
-1
1
4 deg cm g ¸ c = 1.1 in CHCl
3
; H-NMR δ 0.60 (3H, d, J = 7.0 Hz), 0.65 (3H,d, J = 7.0 Hz), 1.25
(
1H, m), 1.75 (3H, d, J = 7.0 Hz), 4.47 (1H, s), 4.53 (1H, dd, J = 7.4, 3.0 Hz), 5.81 (1H, q, J = 7.0 Hz),
6
7
1
7
.56 (1H, d, J = 8.0 Hz), 6.78 (1H, ddd, J = 7.5, 7.5, 1.2 Hz), 7.19 – 7.51 (6H, m), 7.87 (1H, dd, J =
1
3
.6, 1.5 Hz); C-NMR δ 17.1, 17.7, 18.7, 34.9, 54.2, 71.5, 113.7, 118.8, 118.8, 127.8, 128.0, 128.7,
28.9, 133.4, 133.2, 145.9, 163.3; Anal. Calcd. for C19
7.00; H, 7.20; N, 9.10.
22 2
H N O: C, 77.52; H, 7.53; N, 9.52. Found: C,
2
,3-Dihydro-(2S)- and 2,3-dihydro-(2R)-o-nitrophenyl-3-[(S)-1-phenethyl]-4(1H)-quinazolinone (10A
and 10B, respectively)
The crude mixture of 10A and 10B, obtained from 6 (1 g, 4.0 mmol) and o-nitrobenzaldehyde
(
0.75 g, 5 mmol) was purified by flash chromatography to afford 0.75 g of 10A and 0.70 g of 10B.
2
4
2
-1
Compound 10A was thus isolated as yellowish solid, mp 104 °C; [α]
CHCl
D
= 31 deg cm g ¸ c = 1 in
1
3
; H-NMR δ 1.18 (3H, d, J = 7.2 Hz), 5.19 (1H, br d, J ≈ 2.4 Hz), 6.03 (1H, d, J = 3.2 Hz), 6.26
(
1H, q, J = 7.2 Hz), 6.45 (1H, dd, J = 8.0, 0.4 Hz), 6.86 (1H, ddd, J = 7.4, 7.4, 0.8 Hz), 7.20 – 7.24
1
3
(
1H, m); 7.25 – 7.56 (9H, m), 7.63 (1H, dd, J = 8.0, 1.2 Hz); C-NMR δ 17.5, 51.5, 63.0, 115.2, 116.3,
19.6, 125.8, 127.8, 128.1, 128.8, 128.9, 129.0, 129.7, 134.0, 134.0, 136.7, 140.3, 143.9, 146.9, 163.8.
Anal. calcd. for C22 : C, 70.76; H, 5.13; N, 11.25. Found: C, 70.67; H, 5.45; N, 10.5.
1
19 3 3
H N O
2
D
5
2
-1
Diastereomer 10B was isolated as a yellowish solid, mp 173-175 °C; [α]
in methanol; H-NMR δ 1.69 (3H, d, J = 6.8 Hz), 5.24 (1H, br d, J ≈ 2.0 Hz), 6.14 (1H, d, J = 2.8 Hz),
= - 359 deg cm g , c = 1
1
6
.17 (1H, q, J = 7.5 Hz), 6.45 (1H, ddd, J = 8.1, 0.9, 0.5 Hz), 6.85 (1H, ddd, J = 7.5, 7.5, 1.2 Hz), 7.16
1
3
(1H, ddd, J = 7.5, 7.5, 1.2 Hz), 7.19 – 7.63 (9H, m), 8.02 (1H, dd, J = 7.8, 0.8 Hz); C-NMR δ 17.2,
5
1
5
2.0, 62.8, 114.9, 116.7, 119.6, 124.7, 128.0, 128.2, 128.4, 128.6, 128.7, 133.3, 133.9, 136.0, 137.4,
44.0, 146.5, 163.7; Anal. calcd. for C22 : C, 70.76; H, 5.13; N, 11.25. Found: C, 70.80; H,
19 3 3
H N O
.10; N, 11.24. X-Ray crystallographic data of 10B is available as supporting information [12].
2
,3-Dihydro-(2S)- and 2,3-dihydro-(2R)-p-nitrophenyl-3-[(S)-1-phenethyl]-4(1H)-quinazolinone (11A
and 11B, respectively)
The crude mixture of 11A and 11B, obtained from 6 (1 g, 4 mmol) and p-nitrobenzaldehyde (0.75
g, 5 mmol) was purified by flash chromatography to afford 0.39 g of 11A and 0.21 g of 11B.
2
5
2
-1
Compound 11A was thus isolated as a yellowish solid, mp 180-182 °C; [α]
D
= 454.5 deg cm g ¸ c =
1
1
6
in CHCl
3
; H-NMR δ 1.27 (3H, d, J = 6.8 Hz), 4.60 (1H, br d, J ≈ 2.4 Hz), 5.48 (1H, d, J = 3.2 Hz),
.37 (1H, q, J = 7.2 Hz) 6.46 (1H, dd, J = 8.8, 0.6 Hz) 6.90 (1H, ddd, J = 7.3, 7.3, 0.8 Hz), 7.23 (1H,
1
3
ddd, J = 6.9, 6.9, 1.2 Hz), 7.21 – 8.14 (9H, m) 8.04 (1H, dd, J = 7.6, 1.6 Hz); C-NMR δ 17.7, 51.4,
6.8, 115.5, 117.3, 120.4, 124.3, 126.7, 127.41, 128.1, 128.9, 134.0, 140.2, 143.5, 148.1, 149.0, 162.8;
6

Molecules 2007, 12
181
Anal. calcd. for C22
H
19
N
3
O
3
: C, 70.76; H, 5.13; N, 11.25. Found: C, 70.78; H, 5.18; N, 11.17.
2
5
2
-1
Diastereomer 11B was isolated as a yellowish solid, mp 194-196 °C; [α]
D
= - 423 deg cm g , c = 1
1
in methanol; H-NMR δ 1.73 (3H, d, J = 7.2 Hz), 4.63 (1H, d, J = 2.0 Hz), 5.67 (1H, d, J = 2.4 Hz),
6
.21 (1H, q, J = 7.1Hz), 6.47 (1H, dd, J = 8.4, 0.4 Hz), 6.91 (1H, ddd, J = 7.5, 7.5, 0.9 Hz), 6.96 – 7.02
1
3
(
1H, m), 7.17 – 7.81 (9H, m,), 8.02 (1H, dd, J = 7.8, 1.2 Hz); C-NMR δ 17.1, 51.8, 67.1, 115.3,
17.3, 120.4, 123.5, 126.3, 128.0, 128.2, 128.3, 128.8, 134.0, 138.4, 143.8, 147.4, 148.0, 162.6; Anal.
calcd. for C H N O : C, 70.76; H, 5.13; N, 11.25. Found: C, 70.57; H, 5.17; N, 11.05. X-Ray
1
2
2
19
3
3
crystallographic data of 11A and 11B is available as supporting information [12].
Acknowledgments
We are grateful to Consejo Nacional de Ciencia y Tecnología de México for grants 38187E, 48356-
Q, 32261E, and scholarships awarded to Flores P., Priego J. M., and Ortiz-Nava, C.
References and Notes
1
2
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2. Crystallographic data of 8, 9A, 10B, 11A and 11B are deposited with the Cambridge
Crystallographic Data Center (CCDC # 627346, 264374, 264375, 264376, and 264377,
respectively). These data can be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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1
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Herradón, B.; Hidber, P.; Irwin, J.; Locher, R.; Maestro, M.; Maetzke, T.; Mouriño, A.;
Pfammatter, E.; Plattner, D.; Schickli, C.; Schweizer, W.; Seiler, P.; Stucky,G.; Petter, W.;
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1
1
5. The interatomic distance, in angstroms, between the methine hydrogen at C9 or C15 and the
oxygen at C4 is as follows: 9A, 2.275; 10B, 2.280; 11A, 2.486; 11B, 2.316.
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004, 15, 3545-3549.
Sample Availability: Small samples (a few milligrams) of 8, 9, 10 and 11 are available from the
authors.
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2007 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.