166. Alicyclic compounds. Part II. The preparation of cyclohexane-1 : 3-diones and their enol ethers

Abstract

Methylcyclohexane-1 : 3-dione, previously imperfectly characterised, has been made by three methods. Monoenol ethers are prepared from several cyclohexane-1 : 3-diones and (a) ethanol in presence of toluene-psulphonic acid, (b) ethyl iodide and sodium ethoxide, or (c) ethyl orthoformate and an acid catalyst. Method (a) is not applicable to %methyl-diones, and (b) is useful only with 2-methyl-diones. Method (c) is generally applicable, but under certain conditions gives complex compounds formed by the coupling of three dione molecules through a CH group.DURING experiments directed towards the synthesis of steroids and other natural have examined the preparation of certain cyclohexane-1 : 3-diones (3-hydroxycyclohex-2-enones) and their enol ethers.cycZoHexane-1 : 3-dione was most easily made by hydrogenation of resorcinol in alkaline solution, but conditions milder than those hitherto recommended were necessary to prevent further reduction. With methyl iodide and methanolic sodium methoxide it afforded the 2-methyl compound, but the maximum yield was only 58% (cf. Friedman and Robinson, Chem. and I d . , 1951, 777) ; and this was not improved by methylation in aqueous sodium hydroxide with a large excess of methyl iodide, partial ring scission to 5-ketohexanoic acid also occurring. Further methylation of 2-methylcyclohexane-1 : 3dione (in methanol) gave the enol ether ; the 2 : 2-dimethyl compound could not be isolated. In contrast, 5 : 5-dimethylcyclohexane-1 : 3-dione always gave a mixture of the 2-methyl and the 2 : 2-dimethyl derivative, as reported by Desai (J., 1932Desai (J., , 1079 and HirsjaM (Chem. A h . , 1948,42,2936). Gilling (J., 1913Gilling (J., , 2029 described the reduction of 4-methylresorcinol ; the product was believed to be 4-methylcyclohexane-1 : 3-dione, but was not satisfactorily characterised. We confirmed the formation of the 4-methyl-dione, a syrup, which rapidly oxidised in air to (crystalline) a-methylglutaric acid. The dione was characterised as the methylenebisderivative, and was synthesised by two further, interdependent methods. Methyl 4-carbe t hoxy-5-keto-2-met hylhexanoat e (from ethyl ace t oacet at e, methyl a-me t hylacrylate, and sodium ethoxide) on successive treatment with sodium ethoxide and alcoholic potassium hydroxide yielded a separable mixture of a-methylgutaric acid and the 4-methyl-dione, in proportions which varied widely in different experiments (Table 1).

Synthesis and Spectroscopic Characterization of [1′-14C]Ubiquinone-2, [1′-14C]-5-Demethoxy-5-hydroxyubiquinone-2, and [1′-14C]-5-Demethoxyubiquinone-2

“…[16] The only differences found for 1 were due to the shorter length of the isoprenoid chain. The 1 H NMR spectra of 5-demethoxy-5-hydroxyubiquinone-2 (2) and 5-demethoxyubiquinone-2 (3) were compared to the spectrum of 1.…”

“…[9] Purification by distillation gave ethyl bromoacetate in quantitative yield (Scheme 1). Triethyl phosphite was added to ethyl bromoacetate, to yield triethyl phosphonoacetate (16) by an Arbusov reaction in quantitative yield after distillation under reduced pressure. 6-Methyl-5-hepten-2-one was treated with lithiated triethyl phosphonoacetate in a Wittig reaction to yield pure ethyl 3,7-dimethyl-2,6-octadienoate (81%) after distillation.…”

“…6-Methyl-5-hepten-2-one was treated with lithiated triethyl phosphonoacetate in a Wittig reaction to yield pure ethyl 3,7-dimethyl-2,6-octadienoate (81%) after distillation. This metallation of triethyl phosphonoacetate (16) with NaH has also been described, [10] but we preferred nBuLi for the metallation, as this reagent reacts faster and is easier to work with. Furthermore the product ethyl 3,7-dimethyl-2,6-octadienoate was obtained in an apparently higher yield.…”

Alcoholysis of 3-alkoxy-2-cyclohexene-1-thiones

“…The benzene extract was dried with Na 2 SO 4 and evaporated in a vacuum. We obtained 0.26 g (96%) of methoxyketone Ib identical to an authentic sample [4]. 1 H NMR spectra were rgistered on a spectrometer Bruker DPX-400 (operating frequency 400.1 ΜHz) from solutions in CDCl 3 , internal reference HMDS.…”

Reactions of Ortho Esters Which Result in Carbon-Oxygen and Carbon-Halogen Bond Formation

“…Carbonyl compounds which have been converted to enol ethers by reaction with trialkyl orthoformates, either in a one-step process or by dealcoholation of an initially formed ketal, include dialkyl ketones (141a, 153a, 175), aryl alkyl ketones (119), cycloalkanones (12, 53a, 141a, 178a, 179a, 190, 207, 215, 216, 248), palmitaldehyde (260a), cyclic β-keto aldehydes (95a, 240), adiketones (286), β-diketones (67,198,214,286), β-ketonitriles (21a), a-keto esters (65,67), β-keto esters (14, 63, 64, 87a, 203), α-formyl esters (22a), alkyl vinyl ketones (8,244) and other α,β-unsaturated ketones (65,75,159), aryl alkoxy acetaldehydes and aryl cyanoacetaldehydes (241,295), terpene ketones (pulegone, menthone, and camphor) (9,48), codeinone (233), 3-keto steroids, (145,253) and 20-keto steroids (92,208). In general, when it is possible for the carbonyl compound to yield mixtures of cis-trans or position isomeric enol ethers, mixtures of products are obtained (8, 141a, 175, 244).…”