Of 2 - methyl -1,3 - cyclohexanedione

A. S-Uethyl-2-(Z-oxobutyl)-1,3-cyclohexanedione. A 1-L, round-bottomed flask equipped with a thermometer, and a reflux condenser capped with an argon-inlet tube, is charged with 126.1 g (1 mol) of 2-methyl-1,3-cyclohexanedione (Note 1) and 300 mL of distilled water. To the well-stirred suspension are added 3 mL of acetic acid, 1.1 g of hydroquinone, and 142 g (167 mL, 2 mol) of freshly distilled methyl vinyl ketone (Note 2). The reaction mixture 1s stirred under argon at 72-75°C for 1 hr, treated with... 

The 2-methyl-1,3-cyclohexanedione thus obtained (Note 9) can be purified by recrystallization from 95% ethanol, using about 20 ml. of ethanol for each 5 g. of product to give colorless crystals, m.p. 208-210° dec., with only minor loss of material. 

Methyl-1,3-cyclohexanedione has been used as starting material for the syntheses of several polycyclic compounds for projected syntheses of steroids and terpenoids.11 13 It has also been used to prepare l,6-diketo-8a-methyl-l,2,3,4,6,7,8,8a-octahydro-naphthalene.3 4 11 16... 

After Michael addition of 17 to 2-methyl-1,3-cyclohexanedione (19) and the first aldol condensation, the double bond in 20 is reduced to give 21. The acetoxy group in 21 is unmasked by hydrolysis and oxidation, and subsequent aldol condensation gives 22. Again, the terminal double bond in 22 is oxidized with PdCk to methyl ketone, and subsequent hydrogenation of the internal double bond affords the trione 23, from which the steroid A-ring 24 is formed by aldol condensation [34],... 

Do you remember Figure 12.13 2-Methyl-l,3-cyclopentanedione and 2-methyl-1,3-cyclohexanedione in acetic acid undergo Michael additions to methyl vinyl ketone to form 1,5-diketones. Their structure reappears in Figure 12.19 as the substrate A. In the discussion of the formation mechanism of these 1,5-diketones you were probably not at all surprised to... 

Thin layer chromatography was performed on silica gel with ethyl acetate hexane (3 2). Visualization of the spots was achieved by spraying the plates with 10% ceric sulfate in 10% sulfuric acid, heating the plates to ca. 120°C, and spraying again with 10% phosphomolybdic acid in Isopropyl alcohol. The product has 0.50 2-methyl-1,3-cyclohexanedione has Rf 0.30. 

The mechanism of the Robinson annulation consists of two parts a Michael addition to the a,p-unsaturated carbonyl compound to form a 1,5-dicarbonyl compound, followed by an intramolecular aldol reaction to form the six-membered ring. The mechanism is written out in two parts (Mechanisms 24.7 and 24.8) for Reaction [2] between methyl vinyl ketone and 2-methyl-1,3-cyclohexanedione. 

The important intermediate 66 of the steroid synthesis has been prepared by the application of the same reaction sequence to 2-methyl-1,3-cyclohexanedione (65) (Scheme 22). A synthesis of (+) 19-nortestosterone (69) starts with the Michael addition of the optically active oxo ester 67 to 1,7-octadien-3-one (59) catalyzed by sodium hydride, the ester group being removed by heating in aqueous HMPA with sodium iodide to give the dione 68. The aldol condensation catalyzed by sodium hydroxide proceeds in 90% yield. The terminal double bond is oxidized with PdCl2/CuCl to the methyl ketone and the internal olefinic double bond subsequently hydrogenated. The final reaction step involves aldol condensation in refluxing... 

An elegant synthesis of Warburganal (12) from the ketone (2) was reported by Kende and Blacklock [8] as depicted in Tig (1)". The ketone (2), prepared [3] by Robinson annelation of the 2-methyl-1,3-cyclohexanedione with ethyl vinyl ketone, on ketalization afforded (3) which was converted to the trans-decalone (4) by the reductive methylation procedure of Stork [9]. Wolff-Kishner reduction of (4) produced the ketal (5), which without purification was hydrolyzed with acid to obtain the trans-decalone (6) [10] in excellent yield. The present method for the synthesis of the decalone (6) appears more efficient and convenient than the methods previously reported [11,12], considering the overall yield and the stereoselectivity. 

Three approaches to the synthesis of 69 have been described." The first approach entailed the stereoselective introduction of the C-8a angular methyl group. The required starting material was the methoxy enone 71, prepared in 24% overall yield by a five-step sequence from 2-methyl-1,3-cyclohexanedione and l,4-dimethoxy-2-butenone, via annelation and reductive removal of the allylic oxygen." ... 

Methyl-1,3-cyclohexanedione (126.1 g, 1.0 mol) and 300 mL distilled water are placed into a 1 liter round-bottomed flask fitted with a reflux condenser and a thermometer. Acetic acid (3.0 mL), hydroquinone (1.1 g) and methyl vinyl ketone (142 g, 167 mL, 2 mol, freshly distilled) are added and the resulting mixture is heated for 1 h at 75 °C. After cooling to room temperature, the reaction mixture is saturated with 103 g of sodium chloride and poured into 400 mL of ethyl acetate. After separation of the layers, the aqueous phase is twice extracted with ethyl acetate (150 mL each). The combined organic extracts are washed with two 200 mL portions of brine solution, dried over sodium sulfate, filtered, and then concentrated in vacuo to yield 210.8 g of 2-methyl-2-(3-oxobutyl)-1,3-cyclohexanedione as a pale yellow oil. 

A mixture of 2-methyl-l,3-cyclohexanedione, methyl vinyl ketone, a few KOH-pellets, and abs. methanol refluxed 3 hrs., methanol and excess methyl vinyl ketone removed by distillation, the residual 2-niethyl-2-(3 -oxobutyl)-1,3-cyclo-hexanedione (Y 85% when isolated) dissolved in benzene, a Dean-Stark phase-separating head attached, traces of water and methanol removed by azeotropic distillation, cooled well below the boiling point, pyrrolidine added, refluxed until separation of water ceases after ca. 30 min., and refluxing continued for 15 min. l,6-dioxo-8a-methyl-l,2,3,4,6,7,8,8a-octahydronaphthalene. Y 63-65% based on dione. S. Ramachandran and M. S. Newman, Org. Synth. 4 1, 38 (1961) ring closure with an increased amount of pyrrolidine s. W. L. Meyer and A. S. Levinson, J. Org. Ghem. 28, 2184 (1963) Michael addition with NaOH instead of KOH s. T. A. Spences, K. K. Schmiegel, and K. L. Williamson, Am. Soc. 85, 3785 (1963). 

Another method for the synthesis of (418) consists in the condensation of the vinyl carbinol (413) with 2-methyl-1,3-cyclohexanedione [527, 528]. On mild acid hydrolysis, the diketone (414) so formed gives the triketone (415), and on cyclization with p-toluenesulfonic acid the diketone (418). 

To achieve a total synthesis of (-)-arisugacin A 6, R-83 was obtained readily from 2-methyl-1,3-cyclohexanedione... 

SCHEME 135. Oxidation of 3-methyl-l,2-cyclohexanedione and 2-methyl-1,3-cyclopentanedione... 

Dioxo-8a-methyl-l, 2,3,4,6,7,8,8a-octahydronaphthalene has been obtained through the reaction of 2-methyl-l,3-cyclohexane-dione with acetonedicarboxylic acid and formaldehyde,3 4-diethyl-amino-2-butanone methiodide,3 pyridine and 4-diethylamino-2-butanone,4 triethylamine and 4-diethylamino-2-butanone,5 and by cyclization of 2-methyl-2-(3-oxobutyl)-l,3-cyclohexanedione using either aluminum fer/-butoxide or piperidine phosphate as catalyst.6 7... 

To achieve synthesis of (-)-arisugacin A [1], (7 J-89 was obtained readily from 2-methyl-l,3-cyclohexanedione 88 in 4 steps with an overall yield of 46%, featuring vinylogous ester formation, Stork-Danheiser double alpha methylation,52,68,69 vinyl Grignard addition followed by acidic work-up,68 and an asymmetric CBS reduction [Scheme 21].70,71... 

Figure 2.47 shows our retrosynthetic analysis of O-methyl pisiferic acid (57).126 The starting material is the same (.S )-3-hydroxy ketone A as employed by us for the synthesis of glycinoeclepin A (see Figure 2.36). The ready availability of A by reduction of 2,2-dimethyl-1,3-cyclohexanedione with baker s yeast makes A a versatile starting material in terpene synthesis.104 Conversion of A to two diastereomeric compounds B and C enables the synthesis of both (+)-57 and (—)-57. ...

Give a synthesis of 2,2-dimethyl-1,3-cyclohexanedione from methyl 5-oxohexanoate. 

Michael additions to acceptor-substituted dienes are often followed by (spontaneous or induced) cyclizations. This was already noted by Vorlander and Groebel4 who obtained a substituted 1,3-cyclohexanedione by treatment of 6-phenyl-3,5-hexadien-2-one with diethyl malonate (equation 5). Obviously, the 1,4-addition product which is formed initially then undergoes cyclization, ester hydrolysis and decarboxylation. Similarly, reaction of methyl sorbate with methyl 4-nitrobutyrate gave the 1,6-adduct which was reductively cyclized to 6-methyl-l-azabicyclo[5.3.0]decane18 (equation 6). 

In an application of the Niki reaction,474 the alkylation of 1,3-cyclohexanedione with trans-1,4-dibromo-2-methyl-2-butene (a reaction previously mentioned in connection with compound 218 (Section IV,A,3,c,iv) leads to a similar product, without methyl groups in position 6.721... 

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