Diethylamino-3-butanone

Submitted by Alfred L. Wilds, Robert M. Nowak, and Kirtland E. McCai.eb.1 

In a 3-1. round-bottomed flask equipped with a reflux condenser (Note 1) are placed 176 g. (1.60 moles) of diethylamine hydrochloride (Note 2), 68 g. (2.26 moles) of paraformaldehyde, 600 ml. (8.1 moles) of acetone, 80 ml. of methanol, and 0.2 ml. of concentrated hydrochloric acid. The mixture is heated for 12 hours at a moderate to vigorous rate of reflux (Note 3). The light-yellow solution, in which a small amount of gelatinous solid remains, is cooled, and a cold solution of 65 g. of sodium hydroxide in 300 ml. of water is added. The mixture is extracted with three 200-ml. portions of ether, the combined extracts are washed with two 150-ml. portions of saturated sodium chloride solution, and the washes are re-extracted with two 150-ml. portions of ether. 

A good grade of commercial diethylamine hydrochloride (Eastman Kodak white label or Matheson, Coleman and Bell) is satisfactory without purification. 

At first some bumping may. occur if the heating is too vigorous mechanical stirring may reduce this, but does not improve the yield. The submitters found an electrically heated oil bath or a steam bath to be satisfactory, but not a heating mantle. 

Unless the condenser is efficient, some product will be lost a Dry-Ice-cooled trap located between the receiver and the pump is recommended. 

A mixture of 22 g. (0.20 mole) of diethylamine hydrochloride, 60 ml. (0.82 mole) of acetone, 8.4 g. (0.28 mole) of paraformaldehyde, and 40 ml. of ethanol is refluxed on a steam bath for 20 hours. The resulting solution is filtered and concentrated by heating under reduced pressure. To the concentrate are added 50 ml. of water and excess 45% aqueous potassium hydroxide solution. The resulting solution is saturated with potassium carbonate and extracted with ether. The ethereal solution is washed two times with saturated sodium chloride solution and dried over sodium sulfate and then over Drierite. Distillation from a modified Claisen flask gives 15.7-17.0 g. (55-59% yield) of the amino ketone boiling at 76-78°/16 mm. Analytically pure product is obtained by two redistillations, b.p. 70-70.5°/ll mm., ng 1.4333. 

A solution of 205 g. (1.75 moles) of 2-diethylaminoethyl alcohol in 500 ml. of dry thiophene-free benzene is cooled in an ice-salt bath 

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Derivatives. Small amounts of alkyl quiaolines are present ia the tars resulting from the carbonization and Hquefaction of coal (111). Good yields of 4-methyl quinoline, 4,6-dimethyl quinoline [826-77-7], and 4,8-dimethyl quinoline [13362-80-6] are obtained from 4-(diethylamino)-2-butanone and the appropriate aniline. This approach is a promising addition to the traditional syntheses discussed eadier (112). Vlaylacetylene reacts with mercuric chloride and either aniline or -toluidine to yield 4-methyl- and 4,6-dimethyl quinoline, respectively (113). 

Diethylamino-2-butanone, 46, 82 [/3 (Diethylamino)ethyl]triphenylphos-phonium bromide, 48, 130... 

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... 

Diethyl (3-oxobutyl)phosphonate 354 The methiodide obtained from 4-(diethylamino)-2-butanone (7.15 g, 0.05 mole) and methyl iodide (7.15 g) is heated with triethyl phosphite (0.25 mole, 41.5 g) for 1 h at 130°. After cooling, the triethylmethylammonium iodide formed (10.6 g, 87%) is filtered off and washed with benzene. On evaporation the filtrate and wash-benzene leave a pale yellow oil which is distilled in a vacuum (yield 8.4 g, 81 % b.p. 89-97°/ 0.08 mm) and on redistillation gives the phosphonic ester (7.5 g, 72%), b.p. 96-98°/0.14 mm, nD25 1.4352. 

Some work has to be done on the enolization of ketones with tertiary amino groups [105, 106]. The reactions of these compounds with iodine are complex processes which consume several moles of iodine per mole of ketone. Nevertheless, the pH-rate profile for enolization of 4-dimethylaminobutan-2-one appears to be sigmoid with the rare proportional to the concentration of the deprotonated form. The plateau rate constant and that for the enolization of 4-diethylamino-butanone and 5-ethylaminopentan-2-one are seven to eight powers of ten greater than the rate constants for the spontaneous enolization of simple aliphatic ketones. The results suggest that these compounds react with intramolecular catalysis. A mechanism as symbolized by 70 seems unlikely since the plateau rate constant for the enolization of 71 is similar to that for the enolization of 72 [105]. Instead, the kinetically equivalent process, involving reaction of the protonated form with hydroxide ion seems more likely. If this is correct, reaction via the six-membered cyclic transition state 73 is faster than via the... 

Diethylamino-3-butanone, 37,18 3-Diethylaminopropionitrile, 36, 7 Diethylaniline, 31, 111 Diethylaniline hydrochloride, 31, 112 Diethyl benzalmalonate, 30, 84 N,N-Diethylbenzenesulfenamide, 35, 101 N,N -Diethylbenzidine, 36, 21 Diethyl benzoylmalonate, 37, 20 Diethyl bromoacetal, 35, 52, 53 Diethyl carbonate, 30, 44 Diethyl cetylmalonate, 34,13 Diethylchloroacetal, 34, 46 Diethylcyanamide, 36, 25 Diethyl A2-cyclopentenylmalonate,... 

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,... 

Pavatrine hydrochloride [fluorine-9 carboxylic acid, 2>(diethylamino)ethyl ester hydrochloride] [548-65-2] M 333.7, m 143-144 , pKEst 9.0 Recrystallise the salt from isopropanol, EtOAc/isoPrOH and dry it over P2O5 t vacuo. The metho-bromide has m 111-117 (from butanone). [Beilstein 9 m 3412, 9IV 2596.]... 

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