Uses
1-(3-Hydroxyphenyl)-1-propanone is a reactant used to synthesize tricyclic fused pyridines, a family of alkaloids with antimalarial activity.
Preparation
Preparation by diazotization of m-aminopropiophenone, followed by decomposition of the diazonium salt obtained, (71%)
Also obtained by saponification of 3-acetoxypropiophenone (b.p.2 127–128°) with refluxing 10% sodium hydroxide for 2–3 h (83%)
Also obtained by reductive deamination of 2-amino-5-hydroxypropiophenone (diazotization, followed by decomposition of the diazonium salt formed with copper powder in ethanol)
Also obtained by reaction of ethylmagnesium bromide with 3-hydroxy-N, N-diethylbenzamide in refluxing n-butyl ether for 4 h (75%)
Also obtained by treatment of 3-methoxypropiophenone (b.p.0.05 70–76°) with pyridinium chloride at 210° for 30 min (85%)
Also obtained by treatment of 1-hydroxy-1-(3-hydroxyphenyl)propane (m.p. 105–107°) with DDQ in dioxane for 72 h (97%).
Synthesis
1. Aluminum chloride (8.0 g, 0.0594 mol) was slowly added to a stirred solution of m-methoxyacetophenone (6.5 g, 0.0396 mol) in toluene (100 mL) through a powder addition funnel. The reaction was carried out at room temperature under nitrogen atmosphere.2. The stirred reaction mixture was heated to reflux under nitrogen atmosphere for 5 h. 3. Upon completion of the reaction, the mixture was allowed to cool to room temperature, and then slowly poured into a 10% aqueous HCl solution (200 mL).4. The reaction mixture was transferred to a partitioning funnel to separate the organic layer from the aqueous layer.5. The aqueous phase was extracted with ethyl acetate (3 x 150 mL).6. The combined The organic layer was washed once with brine (50 mL) and then dried over anhydrous sodium sulfate.7. The dried organic layer was filtered and the filtrate was concentrated to give the crude product.8. The crude product was purified by column chromatography to give m-hydroxypropiophenone (5.580 g, 94% yield) as a solid.1H NMR (400 MHz, CDCl3): δ 1.23 (t, J = 7.6 Hz, 3H ), 2.99 (q, J = 7.2 Hz, 2H), 7.10-7.12 (dd, J1 = 8.0 Hz, J2 = 2.4 Hz, 1H), 7.32 (app t, J = 8.0 Hz, 1H), 7.51 (br d, J = 8.0 Hz, 1H), 7.62 (app t, J = 2.4 Hz, 1H).
References
[1] Patent: WO2007/62190, 2007, A2. Location in patent: Page/Page column 30
[2] Patent: WO2007/62145, 2007, A2. Location in patent: Page/Page column 41
[3] Journal of Medicinal Chemistry, 1991, vol. 34, # 7, p. 2176 - 2186
[4] Patent: US2016/235065, 2016, A1. Location in patent: Paragraph 0487
