Methyl 4-[(Benzoylamino)methoxy]benzoate

Abstract

Methylparabene (2) was simply benzamidomethylated with (benzamidomethyl)-triethylammonium chloride (1) in aqueous medium to afford methyl 4-(benzamido-methoxy)benzoate (3) in high yield. The title compound was characterized by elemental analysis, FT-IR, ¹H-NMR and ¹³C-NMR spectroscopy.

This paper aims to present a compound similar to methyl 4-methoxybenzoate in which methyl from the methoxy group is replaced with a benzamidomethyl group. Methyl 4-methoxybenzoate, also known as methyl anisate, has been frequently used as pharmaceutical intermediate and in many organic syntheses [1] and in food as flavoring agent [2,3]. In addition, it can be found as volatile component in many plants and mushrooms [4,5,6,7,8].

Although (benzamidomethyl)triethylammonium chloride (1) is an excellent reagent for benzamido-methylation of phenols [9], in our previous work [10] we demonstrated that the phenol group at 4-hydroxybenzoic acid cannot be benzamidomethylated with 1 in aqueous media. The carboxylic group as a weak nucleophile in aqueous media does not react [11], but it deactivates the phenol group in the molecule of 4-hydroxybenzoic acid. Since in methylparabene (2) the carboxylic group is protected, the hydroxy group can be easily benzamidomethylated with 1 in aqueous media to give methyl 4-[(benzoylamino)methoxy]benzoate (3) (Scheme 1).

Scheme 1. Synthetic route to the title compound 3.

Scheme 1. Synthetic route to the title compound 3.

Experimental

Compound 1 is not commercially available and it was synthesised as described previously [9].

Methyl 4-[(benzoylamino)methoxy]benzoate (3)

To a mixture of powdered 1 (1.058 g, 3.9 mmol), 2 (0.501 g, 3.3 mmol), ethanol (20 mL) and triethylamine (0.2 mL), water was continually added, drop by drop, until a clear solution was obtained. The mixture was stirred for 5 h at room temperature. Then, water was added to the mixture until occurrence of a precipitate. The typical yield of crude colorless crystals with mp of 133–140 °C was 80%. Purification was performed by dissolving the product in acetone followed by precipitation with water and subsequent recrystallization from toluene.

Melting point of pure crystals: 142–143 °C (uncorrected).

FT-IR (KBr): 3,290 (νNH), 1,718 (νOC=O), 1,663 (Amide I), 1,555 cm⁻¹ (Amide II)

¹H-NMR (250 MHz, DMSO-d₆): δ/ppm 9.64 (t, J = 6.6 Hz, 1H, NH); 7.93–7.15 (9H, Ar); 5.41 (d, J = 6.6 Hz, 2H, N-CH₂-O); 3.81 (s, 3H, CH₃)

¹³C-NMR (63 MHz, DMSO-d₆): δ/ppm 167.0 (C=O); 165.9 (C=O); 68.7 (CH₂); 51.9 (CH₃); Ar: 160.8, 133.3, 132.1, 131.2, 128.6, 127.5, 122.3, 115.2.

Anal. Calcd. (found) for C₁₆H₁₅NO₄: C, 67.36 (67.55); H, 5.30 (5.41); N, 4.91 (5.07).