2-(1-Hexyn-1-yl)benzoic Acid

Abstract

[120870-47-5] C13H14O2 (MW 202.25) InChI = 1S/C13H14O2/c1-2-3-4-5-8-11-9-6-7-10-12(11)13(14)15/h6-7,9-10H,2-4H2,1H3,(H,14,15) InChIKey = SOVPOMRAGXHBFS-UHFFFAOYSA-N (reagent preferably used for the preparation of glycosyl ortho-hexynylbenzoates, which can be used as glycosyl donors in glycosylation reactions under the catalysis of a gold(I) complex) Physical Data: mp 35–36 °C. Preparative Methods: to a single-necked, flame-dried, 500 mL round-bottomed flask containing a magnetic stir bar, PdCl2(PPh3)2 (4.20 g, 6.0 mmol), CuI (1.14 g, 6.0 mmol), and PPh3 (3.14 g, 12.0 mmol) were added. The flask was evacuated, sealed with a rubber septum, and charged with an argon balloon. Dry iPr2NH (180 mL) and methyl 2-iodobenzoate (18.0 mL, 120.0 mmol) were syringed into the flask. After stirring at rt for 1 h, the mixture was cooled down to 0 °C with an ice bath and then 1-hexyne (20.8 mL, 180.0 mmol) was slowly added for 20 min. The resulting mixture was allowed to stir at 60 °C for 8 h. Saturated NH4Cl (200 mL) was added to quench the reaction. After vigorously stirring for 30 min, the mixture was extracted with petroleum ether (400 mL) once and with hexane/EtOAc (150 mL, 100:1) three times. The combined organic layers were washed sequentially with H2O and brine and then dried over Na2SO4 and concentrated. The crude product was purified by column chromatography on silica gel (hexane/EtOAc, 50:1) to provide methyl 2-(hex-1-ynyl)benzoate (25.9 g, 99%) as a yellow oil. Methyl 2-(hex-1-ynyl)benzoate (25.9 g, 120 mmol) was dissolved in THF (300 mL) in a single-necked 1000 mL round-bottomed flask containing a magnetic stir bar. Aqueous NaOH (1 N, 300 mL) was added. After stirring at 50 °C for 12 h, the solution was cooled to 0 °C with an ice bath and then acidified with HCl (3 N) to pH ∼4. After the removal of THF by rotary evaporation, the residue was extracted with CH2Cl2 (150 mL) five times. The combined organic layers were dried over Na2SO4 and then concentrated to afford 2-(1-hexyn-1-yl)benzoic acid as a yellow oil (24.1 g, 98%), which became a light yellow solid when stored at −20 °C.1, 2 Alternatively, 2-(1-hexyn-1-yl)benzoic acid can be prepared from 1-bromo-2-iodobenzene in two steps: (i) 1-hexyne, Pd(PPh3)2Cl2, CuI, iPr2NH, PPh3, 80 °C, 12 h; (ii) tBuLi, CO2, THF, −78 °C, 1 h, then rt, 12 h.3, 4 Handling, Storage, and Precaution: 2-(1-hexyn-1-yl)benzoic acid is a rather stable yellow oil at rt, but it cyclizes slowly to give the isocoumarin if traces of Pd catalyst remain or upon exposure to acid or high temperatures. Storage under dry atmosphere and refrigeration is recommended.