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Article

Synthesis, NMR and Crystallographic Studies of 2-Substituted Dihydroquinazolinones Derived from (S)-Phenylethylamine

1
Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos. Av. Universidad No. 1001, Col. Chamilpa, C.P. 62210 Cuernavaca-Mor. México
2
Universidad Autónoma Metropolitana, Area de Química. San Pablo No. 180, Col. Reynosa Tamaulipas, México 02200, D.F.
*
Authors to whom correspondence should be addressed.
Molecules 2007, 12(2), 173-182; https://doi.org/10.3390/12020173
Submission received: 5 December 2006 / Revised: 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 40-90% 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 before their NMR spectra in CDCl3 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.

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 stereogenic centers by 1H-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].
Molecules 12 00173 i001
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 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.
Scheme 1.
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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 to sp3 carbons are commented briefly (however, complete data is given in the Experimental section). In the 1H-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 (Δδ = δH2 of A − δH2 of B) and therefore, H2 can be 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 CDCl3 containing TMS at 25 °C.
Table 1. δH2 Values of dihydroquinazolinones 8-11, obtained from 400 MHz spectra of 0.5 M solutions in CDCl3 containing TMS at 25 °C.
Compoundδ diastereomer Aδ diastereomer BΔδ (ppb)
84.174, 4.463
94.194.535-340
106.0356.138-103
115.4815.674-193
Experience and MM2 calculations of the O=C-CHCH3Ph segment [5a] have shown that in the 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 δH2. Accordingly, diastereomers A must have H2 in 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 (ΔδCH = -750 ppb) and in similar way, methyl C10 of 10A and 11A lies in the diamagnetic zone of nitrophenyl ring (ΔδMe = -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 1H- NMR experiments.
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 1H- NMR experiments.
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X ray diffraction

To support the configurational analysis based on NMR spectra, the single crystals of 8, 9A, 10B, 11A and 11B were analyzed by X-ray diffraction [12]. The structures were solved with the 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 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-HO 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.
Figure 2. ORTEP drawing of compound 8 showing the syn-like conformation of carbonyl C4 and hydrogen attached to C9.
Molecules 12 00173 g002
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 -42.2°, 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]. Thus, in addition to the above mentioned C-HO 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.
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.
Molecules 12 00173 g003

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 CDCl3 solution and in the solid state. Based on this 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.

Experimental

General

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) was performed on an Elementar Vario EL III elemental analyzer. Proton and 13C-NMR spectra were obtained from 0.5 M solutions in CDCl3, containing a small amount of TMS, and recorded on an Inova 400 spectrometer equiped with a 5 mm 1H probe at 25 °C. All chemical shifts are from TMS signal and 1H-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 PtO2 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% yield): White solid, mp 119-121 °C; [α]D24 = -91.7 deg cm2 g-1¸ c = 1.0 in CH3OH; 1H-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), 7.99 (1H, dd, J = 7.8, 1.6 Hz); 13C-NMR δ 16.3, 49.8, 55.0, 115.0, 118.1, 119.9, 127.3, 127.6, 128.7, 129.2, 133.2, 140.2, 147.6, 163.4. Anal. calcd. for C16H16N2O: C, 76.10; H, 6.40; N, 11.02. Found: C, 76.16; 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 9B, respectively)

The crude mixture of 9A and 9B, obtained from 6 (1 g, 4.0 mmol) and isobutyraldehyde (0.5 mL, 5.0 mmol) was purified by flash chromatography (silica gel, hexane-dichloromethane-ethyl acetate 70:30:10) to afford 0.44 g of 9A and 0.30 g of 9B. Compound 9A was thus isolated as white solid, mp 137-139 °C; [α]D24 = -118 deg cm2 g-1¸ c = 0.7 in CHCl3; 1H-NMR δ 0.78 (3H, d, J = 6.8 Hz), 0.87 (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, m), 7.88 (1H, dd, J 7.7, 1.1 Hz); 13C-NMR δ 17.2, 18.7, 19.0, 36.6, 52.8, 70.1, 113.8, 118.6, 118.6, 127.8, 128.7, 128.7, 128.8, 133.4, 141.0, 146.5, 163.6; Anal. calcd. for C19H22N2O: 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 supporting information [12]. Diastereomer 9B was isolated as a white solid, mp 141-142 °C; [α]D24 = -24 deg cm2 g-1¸ c = 1.1 in CHCl3; 1H-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), 6.56 (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 = 7.6, 1.5 Hz); 13C-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, 128.9, 133.4, 133.2, 145.9, 163.3; Anal. Calcd. for C19H22N2O: C, 77.52; H, 7.53; N, 9.52. Found: C, 77.00; H, 7.20; N, 9.10.

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. Compound 10A was thus isolated as yellowish solid, mp 104 °C; [α]D24 = 31 deg cm2 g-1¸ c = 1 in CHCl3; 1H-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 (1H, m); 7.25 – 7.56 (9H, m), 7.63 (1H, dd, J = 8.0, 1.2 Hz); 13C-NMR δ 17.5, 51.5, 63.0, 115.2, 116.3, 119.6, 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 C22H19N3O3: C, 70.76; H, 5.13; N, 11.25. Found: C, 70.67; H, 5.45; N, 10.5. Diastereomer 10B was isolated as a yellowish solid, mp 173-175 °C; [α]D25 = - 359 deg cm2 g-1, c = 1 in methanol; 1H-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), 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 (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); 13C-NMR δ 17.2, 52.0, 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, 144.0, 146.5, 163.7; Anal. calcd. for C22H19N3O3: C, 70.76; H, 5.13; N, 11.25. Found: C, 70.80; H, 5.10; 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. Compound 11A was thus isolated as a yellowish solid, mp 180-182 °C; [α]D25 = 454.5 deg cm2 g-1¸ c = 1 in CHCl3; 1H-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), 6.37 (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, 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); 13C-NMR δ 17.7, 51.4, 66.8, 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; Anal. calcd. for C22H19N3O3: C, 70.76; H, 5.13; N, 11.25. Found: C, 70.78; H, 5.18; N, 11.17. Diastereomer 11B was isolated as a yellowish solid, mp 194-196 °C; [α]D25 = - 423 deg cm2 g-1, c = 1 in methanol; 1H-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 (1H, m), 7.17 – 7.81 (9H, m,), 8.02 (1H, dd, J = 7.8, 1.2 Hz); 13C-NMR δ 17.1, 51.8, 67.1, 115.3, 117.3, 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 C22H19N3O3: C, 70.76; H, 5.13; N, 11.25. Found: C, 70.57; H, 5.17; N, 11.05. X-Ray 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.

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  15. 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.
  16. Mei, X.; Wolf, C. Highly Congested Nondistorted Diheteroarylnaphthalenes: Model Compounds for the Investigation of Intramolecular π-Stacking Interactions. J. Org. Chem. 2005, 70, 2299–2305. [Google Scholar] [CrossRef]
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  • Sample Availability: Small samples (a few milligrams) of 8, 9, 10 and 11 are available from the authors.

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MDPI and ACS Style

Escalante, J.; Ortíz-Nava, C.; Flores, P.; Priego, J.M.; García-Martínez, C. Synthesis, NMR and Crystallographic Studies of 2-Substituted Dihydroquinazolinones Derived from (S)-Phenylethylamine. Molecules 2007, 12, 173-182. https://doi.org/10.3390/12020173

AMA Style

Escalante J, Ortíz-Nava C, Flores P, Priego JM, García-Martínez C. Synthesis, NMR and Crystallographic Studies of 2-Substituted Dihydroquinazolinones Derived from (S)-Phenylethylamine. Molecules. 2007; 12(2):173-182. https://doi.org/10.3390/12020173

Chicago/Turabian Style

Escalante, Jaime, Claudia Ortíz-Nava, Patricia Flores, Jaime M. Priego, and Cirilo García-Martínez. 2007. "Synthesis, NMR and Crystallographic Studies of 2-Substituted Dihydroquinazolinones Derived from (S)-Phenylethylamine" Molecules 12, no. 2: 173-182. https://doi.org/10.3390/12020173

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