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Synlett 2013; 24(20): 2768-2772
DOI: 10.1055/s-0033-1339922
DOI: 10.1055/s-0033-1339922
letter
One-Pot DBU-Promoted Synthesis of Hydroacridinones and Spirohexahydropyrimidines
Further Information
Publication History
Received: 21 August 2013
Accepted after revision: 09 September 2013
Publication Date:
05 November 2013 (online)
Abstract
The potential hydroacridinone synthesis using simple and inexpensive starting materials, namely 1,3-dicarbonyl compounds, anilines, formaldehyde and DBU as a stoichiometric base was explored. As a result, from the reaction of 1,3-cyclohexanedione and dimedone tetrahydroacridinones were the main reaction products along with small yields of their oxidation products, the dihydroacridinones, whereas in the case of 2-acetylcyclohexanone spirohexahydropyrimidines were isolated in very good yields. Plausible mechanistic schemes for the formation of all products are proposed.
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References and Notes
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- 22a 3,3,7-Trimethyl-3,4,9,10-tetrahydroacridin-1(2H)-one (3f): white crystals; mp 230–232 °C; yield: 73%. 1H NMR (300 MHz, CDCl3): δ = 1.09 (s, 6 H, 2 × Me, 3-Me), 2.236 (s, 2 H, 4-H), 2.245 (s, 3 H, 7-Me), 2.27 (s, 2 H, 2-H), 3.67 (s, 2 H, 9-H), 5.87 (br s, 1 H, NH), 6.50 (d, J = 7.9 Hz, 1 H, 5-H), 6.85 (dd, J = 7.9, 1.7 Hz, 1 H, 6-H), 6.91 (d, J = 1.7 Hz, 1 H, 8-H). 13C NMR (300 MHz, CDCl3): δ = 20.7 (7-Me), 24.2 (C-9), 28.5 (2 × Me, 3-Me), 32.6 (C-3), 42.4 (C-4), 50.7 (C-2), 104.3 (C-9a), 114.6 (C-5), 122.8 (C-8a), 127.4 (C-6), 130.5 (C-8), 133.1 (C-7), 134.2 (C-10a), 151.3 (C-4a), 194.8 (C-1). LC–MS (ESI, 1.65 eV): m/z = 242 (100) [M + H]+. Anal. Calcd for C16H19NO (241.33): C, 79.63; H, 7.94; N, 5.80. Found: C, 79.78; H, 7.78; N, 5.96.
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General Experimental Procedure for the DBU-Promoted Mannich Reaction: A mixture of 4-methylaniline (1.0 mmol), formaldehyde (9 equiv, 36% aq solution), DBU (1 equiv) and dimedone (1 equiv) in EtOH (20 mL) was refluxed for 10 min to dissolve all the reactants, and then the reaction mixture was stirred for 3 h at r.t. The solvent was distilled off and the resulting residue was subjected to column chromatography on silica gel using petroleum ether–EtOAc (10:1) as eluent, to give the product 3f along with a small amount of 4f. In an analogous manner, using 2-acetylcyclohexanone (2.0 mmol) product 10b was isolated.