Crystal structure of 3-phenylpropyl 2-(6-methoxynaphthalen-2-yl)propanoate, C₂₃H₂₄O₃

Source of materials

Naproxen (0.02 mol, 4.60 g) was dissolved in dichloromethane (20 mL), and oxalyl chloride (0.024 mol, 2.2 mL) and two drops of DMF were dropwise added at 0 °C. The solution was stirred for 3 h at room temperature. After the solvent and excess oxalyl chloride was removed by vacuum distillation, a yellow solid was obtained. Phenylpropanol (0.02 mol, 2.72 g) and DMAP (0.0015 mol, 0.18 g) were dissolved in dry dichloromethane (40 mL) and triethylamine (0.03 mol, 4 mL). The naproxen acylchloride in dry dichloromethane was dropwise added at 0 °C. The mixture was stirred for 1 h at room temperature. The reaction mixture was filtrated 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 finally dried with anhydrous Na₂SO₄. The solution was filtrated, and concentrated under vacuum to obtain the crude product. The crude product was purified by recrystallization in ethanol. The crystals were obtained from tetrahydrofuran.

Experimental details

The hydrogen atoms were positioned geometrically (C–H = 0.95–0.99 Å). The U_iso values of the hydrogen atoms of methyl groups were set to 1.5 U_eq (C) and the U_iso values of all other hydrogen atoms were set to 1.2 U_eq(C).

Discussion

Phenylpropanol is a phenyl-alcohol choleretic (proprietary name, livonal) with a superactive cholretic effect. It exerts its powerful effect as a high performance choleretic secretion promoter and a mild spasmolytic. In clinical practice, the indications for livonal include the treatment of cholecystitis, cholelithiasis, biliary tract infection, and biliary tract postoperative syndrome [4]. The clinical formulation of phenylpropanol is soft capsule. But the orally taking of this preparation has a great thrill with discomfort of stomach, easily brought some adverse reaction such as nausea, disgorge and so on. Naproxen is a kind of nonsteroidal anti-inflammatory drugs, has obvious inhibition of prostaglandin synthesis, clinically as a treatment for diseases such as rheumatism, rheumatoid arthritis, osteoarthritis [5, 6]. Now studies have also shown that naproxen also has antiviral [7] and anticancer [8] effects. However, such drugs also have many disadvantages, such as poor water solubility, low bioavailability and great irritation to gastrointestinal mucosa. In this paper, phenylpropanol and naproxen were esterified by prodrug principle, in an attempt to find drugs with better clinical effect and fewer side effects.

The title compound contained one phenyl and one naphthyl moiety. The C–O bond distances are 1.367(3) Å (O3–C20), 1.426(3) Å (O3–C23), 1.345(4) Å (O2–C10), 1.458(4) Å (O2–C9), 1.204(4) Å (O1–C10), respectively. In the molecule of the title compound bond lengths and angles are very similar to those given in the literature [9–11].