Home Crystal structure of 2-(6-methoxynaphthalen-2-yl)-N-(4-morpholinophenyl)propanamide, C24H26N2O3
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Crystal structure of 2-(6-methoxynaphthalen-2-yl)-N-(4-morpholinophenyl)propanamide, C24H26N2O3

  • Qing Zhang , De-Dong Xue ORCID logo and Li-Wei Han EMAIL logo
Published/Copyright: May 23, 2025

Abstract

C24H26N2O3, monoclinic, P21/n (no. 14), a = 6.565(3) Å, b = 36.126(13) Å, c = 8.423(3) Å, β = 97.745(15)°, V = 1979.4(14) Å3, Z = 4, Rgt (F) = 0.0329, wRref (F 2) = 0.0884, T = 100(2) K.

CCDC no.: 2440464

The molecular structure is shown in the figure. Table 1 contains the crystallographic data.

Table 1:

Data collection and handling.

Crystal: Colourless block
Size: 0.12 × 0.11 × 0.10 mm
Wavelength: Mo Kα radiation (0.71073 Å)
μ: 0.09 mm−1
Diffractometer, scan mode: Bruker APEX2, φ and ω scans
θ max, completeness: 27.5°, 100 %
N(hkl)measured, N(hkl)unique, R int: 86648, 9084, 0.032
Criterion for I obs, N(hkl)gt: I obs > 2 σ(I obs), 8,720
N(param)refined: 528
Programs: Bruker 1 , Olex2 2 , SHELX 3

1 Source of materials

Naproxen acylchloride was synthesized according to the literature method. 4 4-Morpholinoaniline (0.01 mol, 1.78 g) and 4-(dimethylamino)-pyridin (DMAP, 0.0015 mol, 0.18 g) were dissolved in dry tetrahydrofuran (20 mL) and triethylamine (0.015 mol, 2 mL). The solution of naproxen acylchloride in dry tetrahydrofuran was dropwise added at 0 °C. The reaction mixture was stirred for 2 h at room temperature. The reaction mixture was filtrated to remove the solid and the filtrate was concentrated under vacuum to remove the solvent. The residue was dissolved in dichloromethane, successively washed with 5 % NaOH solution and water to pH = 7, and dried with anhydrous Na2SO4. The solution was filtrated, and concentrated under vacuum to obtain crude product. The crude product was purified by recrystallization in ethanol. The single crystals were obtained from tetrahydrofuran solution.

2 Experimental details

Coordinates of hydrogen atoms were refined with constraints or restraints. The U iso values were set to be 1.5U eq of the carrier atom for methyl H atoms and 1.2U eq for the remaining H atoms.

3 Comment

Naproxen is one of the most widely prescribed drugs for the treatment and management of inflammatory diseases. Long term use of naproxen can cause serious adverse reactions, such as erosion, narrowing, bleeding, and perforation in the gastrointestinal tract. The pharmacological effects of naproxen are related to the inhibition of COX-1 and COX-2 enzymes. However, due to poor selectivity, naproxen is associated with severe gastrointestinal toxicity. COX-1 inhibition leads to depletion of the gastrointestinal mucosa, which is related to gastrointestinal toxicity. In addition, naproxen contains a free carboxyl group, which, when ionized, leads to an increase in acidity, a decrease in gastric pH, and complicates the problem. 5 , 6 Research has shown that using naproxen as a prodrug for esterification can reduce the gastrointestinal side effects of naproxen and improve its bioavailability. 7 In this study, we prepared a new prodrug of naproxen that masked the free carboxylic acid groups of naproxen, thereby reducing related side effects.

The title structure contains two twist 2-(6-methoxynaphthalen-2-yl)-N-(4-morpholinophenyl)propanamide molecules in the asymmetric unit (see the Figure). The title compound contains one benzene ring, one morpholine ring and one naphthyl moiety. The C=O double bond lengths in the independent molecule are 1.233(2) Å (C11=O2) and 1.231(3) Å (C35=O5), respectively, exhibiting the double bond character. The dihedral angles of ring 1 (O1–C1–C2–C3–C4–N1) and ring 2 (C5–C6–C7–C8–C9–C10), ring 3 (O4–C25–C26–C27–C28–N3) and ring 4 (C29–C30–C31–C32–C33–C34) are 7.8°, 13.3° respectively, showing a relatively large difference. The other bond distances and angles are in their normal ranges according to the previously reported compounds. 8 , 9


Corresponding author: Li-Wei Han, Dongying Hospital of Affiliated Hospital of Shandong University of Traditional Chinese Medicine, DongyingChina, E-mail:

  1. Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Received: 2025-03-09
Accepted: 2025-04-02
Published Online: 2025-05-23
Published in Print: 2025-08-26

© 2025 the author(s), published by De Gruyter, Berlin/Boston

This work is licensed under the Creative Commons Attribution 4.0 International License.

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