2- Oxocyclohexanecarboxylic

A mixture of methyl and ethyl 2-oxocyclohexanecarboxylate, available from Aldrich Chemical Company, Inc., may also be used. The product obtained is a mixture of methyl and ethyl 2-methylcyclohexene-l-carboxylates. 

This procedure illustrates a new method for the preparation of 6-alkyl-a,g-unsaturated esters by coupling lithium dialkylcuprates with enol phosphates of g-keto esters. The procedure for the preparation of methyl 2-oxocyclohexanecarboxylate described in Part A Is based on one reported by Ruest, Blouin, and Deslongcharaps. Methyl 2-methyl-l-cyc1ohexene-l-carboxylate has been prepared by esterification of the corresponding acid with dlazomethane - and by reaction of methyl 2-chloro-l-cyclohexene-l-carboxyl ate with lithium dimethylcuprate. -... 

THE C-ARYLATION OF g-DICARBONYL COMPOUNDS ETHYL l-(p-METHOXYPHENYL)-2-OXOCYCLOHEXANECARBOXYLATE... 

B. Ethyl l-( p-methoxyphenyl I-2-oxoayotohexaneaar hoxylate. A 250 mL, one-necked, round-bottomed flask, equipped with a magnetic stirring bar, is charged with 22.2 g (45 mmol) of p-methoxyphenyl 1 ead triacetate, 10.8 g (135 mmol) of pyridine (Note 8), and 70 mL of chloroform (Note 9). To this solution 1s added 7.0 g (41 mmol) of ethyl 2-oxocyclohexanecarboxylate (Note 10), a calcium chloride drying tube Is put 1n place, and the mixture is stirred at 40°C (Note 11). 

The ethyl 2-oxocyclohexanecarboxylate used was Fluka AG practical grade, and was distilled (bp 106-108 C/12 mm) before use. 

The cyclic /3-keto ester produced in a Dieckmann cyclization can be further alkylated and decarboxylated by a series of reactions analogous to those used in the acetoacetic ester synthesis (Section 22.7). For example, alkylation and subsequent decarboxylation of ethyl 2-oxocyclohexanecarboxylate yields a 2-alkylcvclohexanone. The overall sequence of (1) Dieckmann cyclization, (2) /3-keto ester alkylation, and (3) decarboxylation is a powerful method for preparing 2-substituted cyclohexanones and cyclopentanones. 

Ethyl 2-oxocyclohexanecarboxylate was fluorinated with l-fluoro-2,4,6-trimethylpyridiniuin triflate (1 d) and then treated with sodium hydroxide to give sodium 1 -fluoro-2-oxocyclohexane-carboxylate (21, n = 2 R = Na) in 84% yield.69... 

Cyclocondensation of 2-aminopyridine and its methyl derivatives with ethyl 2-oxocyclohexanecarboxylate in a mixture of polyphosphoric acid and phosphoryl chloride gave 1,2,3,4-tetrahydro-l 1 //-pyrido[2,l -b]-quinazolin-ll-one and its 6-, 7-, 8-, and 9-methyl derivatives (87JMC1543). 

Keto esters also react with salicylaldehyde to yield fused pyrylium salts. For instance ethyl 2-oxocyclohexanecarboxylate affords the tetrahydroxanthylium salt (645), whilst the isochromanone derivative (646) yields the tetracyclic molecule (647), which possesses the skeleton of the anthocyanidin, peltogynidine, isolated from the heartwood of Peltogyne porphyrocardia (Scheme 253) (58JCS3174). 

Alkylation of 1. To a mixture of the ester 1 (5 g, 25 mmol) and 6% of Aliquat 336 (715 mg, 1.5 mmol) was added t-BuOK (3.3 g, 25 mmol, 1 equiv.) under magnetic stilling over 15 min alkyl bromide (25 mmol, 1 equiv.) was then added slowly. The flask was left under the experimental conditions indicated in Table 1. Finally, the mixture was diluted with ethyl acetate (50 ml) and filtered on Florisil (10 g). The crude products were analysed by GC and characterised by MS and HNMR. 2-Alkylcyclohexanones. A mixture of lithium bromide (1.73 g, 20 mmol), tetrabutylammonium bromide (323 mg, 1 mmol), water (360 mm, 0.36 mL, 20 mmol) and ethyl l-alkyl-2-oxocyclohexanecarboxylate 2 (10 mmol) was placed in a Pyrex tube. The tube was then introduced into a Maxidigest MX 350 Prolabo microwave reactor fitted with a rotational system. Microwave irradiation was carried out for a suitable power and time (Table 2). An approximate final temperature was measured by introducing a digital thermometer at the end of irradiation. The mixture was cooled to ambient temperature. After elution with ethyl acetate (50 mL) and subsequent filtration on Florisil, organic products were analyzed by GC and finally purified by chromatography on silica gel (pentane-ethyl acetate, 95 5). 

The preferred tautomer of the products derived from the condensation reaction of phenylenediamine with cyclic /3-keto esters (Scheme 5) is highly dependent on the structure of the /3-ketoester <2005JHC1001>. H and 13C NMR analysis of the l,5-benzodiazepin-2-one 34, formed from methyl 2-oxocyclohexanecarboxylate under micro-wave conditions, indicated the presence of the C(4)-N(5) imine <2005JHC1001>. In contrast, the products arising from condensation with methyl 2-oxocyclopentanecarboxylate and methyl l-alkyl-4-oxopiperidine-3-carboxylates were found to be in the enamine form 35. 

Substituied-4a-hydroxy-9//-cycloalkvl 1.2-< oxazolo 3,2- ]pyrimidin-9-ones (40) have been prepared by cyclocondensation of 5-substituted-2-amino-2-oxazolines (39) with ethyl 2-oxocyclohexanecarboxylate.64... 

The second example of a Dieckmann condensation shown earlier produces ethyl 3-methyl-2-oxocyclohexanecarboxylate in 90% yield. What other cyclic product might have been formed in this reaction Explain why the actual product is favored rather than this other product. 

Show the intermediate aldol product in the Robinson annulation reaction of ethyl 2-oxocyclohexanecarboxylate with 1 -penten-3-one. 

Ethyl 2-oxocyclohexanecarboxylate Cyclohexanecarboxylic acid, 2-oxo-, ethyl ester (8,9) (1655-07-8)... 

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