L-Diethylamino-3-butanone

Cyclic ketones may be converted to olefinic cyclic ketones containing One additional ring. The sodium enolate of the ketone is treated with a Mannich base such as l-diethylamino-3-butanone. The last substance is a source of methyl vinyl ketone, which condenses with the cyclic ketone... 

AWticih (Aldrich also supplies l-diethylamino-3-butanone). Methyl vinyl ketone is made commercially by hydration of vinylacetylene. The du Pont material, an azeotrope containing 85% methyl vinyl ketone and 15% water, can be dried by treat- me t with excess anhydrous potassium carbonate the organic layer is separated, chilled in ice, dried first over calcium chloride and then potassium carbonate, and distilled b.p. 30-32°/120 mm., or 35-36°/140 mm. Material from Matheson, Coleman and Bell can be used as received. 

Steroid synthesis. In developing a method of cyclization which has been of immeasurable -walue in the total synthesis of steroids, Robinson at first experimented with the condensation of ketones with methyl vinyl ketone itself, but encountered difficulties associated with the tendency of the ketone to polymerize. He then turned to possible prectnsors and met with some success with methyl /3-chloroacetyl ketone, CHsCOCHzCH CI. Still better, however, was the methiodide (2) of the Mannich base (1), l-diethylamino-3-butanone. Treated with a strong base such as sodamide in... 

A method for the preparation of l-diethylamino-3-butanone, first reported by Wilds and Shunk in 1943, is described in more detail in Organic Syntheses A... 

I lagemeycr found that l-diethylamino-3-butanone can be cleaved to methyl vinyl ketone by suspending the /-amine in Dowtherm, an inert heat-exchange liquid,... 

The first stage of the synthesis, the preparation of the unsaturated cyclic ketone (140) is illustrated in Scheme 94. Here the starting material is 5-methoxy-2-tetralone (51), which was obtained in two stages from 2, 5-dihydroxynaphthalene with an over-all yield of 73% (Chapter HI, Scheme 56). Condensation of the tetralone (51) with l-diethylamino-3-pentanone methio-dide led to a mixture of the A - and A -tricyclic ketones (138). The next stage, the formation of ring A, can be carried out both with methyl vinyl ketone (yield 75%) and with l-diethylamino-3-butanone methiodide (yield 64%). The isolation of the tricyclic ketones (138) was not necessary, and by successively condensing the tetralone (51) with the diethylaminopen-tanone methiodide and methyl vinyl ketone it was possible to obtain the tetracyclic product (140) with an over-all yield of 34% [915, 916]. 

The addition of rings B and A to ketone (277) was carried out by the same methods as in the case of its 5-methoxy analog (51) (see Scheme 94). Condensation with l-diethylamino-3-pentanone methiodide led to the tricyclic ketone (279), consisting of a mixture of double-bond isomers. The reaction of ketone (279) with l-diethylamino-3-butanone methiodide at —5°C enabled a mixture of epimeric ketols (278) to be obtained which, on boiling with sodium methoxide, gave the tetracyclic ketone (281). For the preparation of (281) from (277) without the isolation of the tricyclic ketone (279), methyl vinyl ketone has been used for the second condensation the over-all yield of (281) in two stages then amounted to 46% [28, 649, 955, 956]. 

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... 

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