Methylpentane-2,4-dione

N-Iodosuccinimide reacts with enol acetates derived from ketones to give a-iodoketones, and the reaction has found application in the steroid field/ The iodination of the enol acetates seems to proceed by an ionic mechanism, and preliminary work indicates that N-iodosuccinimide is not capable of at least some of the radical-chain iodinations analogous to radical-chain brominations brought about by N-bromosuccinimide.  

Submitted by A. W. Johnson, E. Markham, and R. Price. Checked by Virgil Boekelheide and M. Kunstmann. 

A mixture of 65.2 g. (0.65 mole) of pentane-2,4-dlone, 113 g. (0.80 mole) of methyl iodide, 84 g. of anhydrous potassium carbonate (Note 1), and 125 ml. of acetone is placed in a 500-ml. round-bottomed flask fitted with a reflux condenser and a calcium chloride guard tube. The mixture is heated under reflux for 20 hours and is then allowed to cool. The insoluble material is removed by filtration and washed with acetone (Note 2). The combined filtrate and acetone washings are concentrated on the steam bath (Note 3), and the residual oil is distilled. There is 

Thorough washing of the inorganic residues is essential and requires about 200 ml. of acetone. 

During removal of the acetone, potassium iodide is deposited and it is advisable to decant the crude 3-methylpentane-2,4-dione from this material before distillation. 

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Methylpentane-2,4-dione has been prepared by the reaction of the sodium derivative of pentane-2,4-dione with methyl iodide in a sealed tube at 140°, and from the sodium and potassium derivatives of pentane-2,4-dione and methyl iodide in alcoholic solution. It has also been prepared by the reaction of methyl iodide and pentane-2,4-dione in the presence of potassium carbonate in alcoholic or ethereal solution and in acetone solution, and by heating 2-aminopenten-4-one with methyl iodide at 100°. The present modification affords improved yields. 

S g. (0.84 g. atom) of zinc dust, and 52.5 g. (0.46 mole) of 3-methylpentane-2,4-dione (Note 1). The contents of the flask are stirred vigorously (Note 2), and a solution of 42 g. (0.415 mole) of diacetyl monoxime in 150 ml. of glacial acetic acid is added from a separatory funnel at a rate to maintain the temperature of the mixture at 65-70°. The addition takes 1 hour. When the addition is complete, the mixture is refluxed with stirring for an additional 30 minutes. The flask is then fitted for distillation with steam under nitrogen 500 ml. of water is added and steam is introduced. Steam distillation (Note 3) is continued until no more tetramethylpyrrole comes over. This takes 1-2 hours and the distillate amounts to 1-2 1. The tetramethylpyrrole crystallizes from the steam distillate and is collected by filtration, washed with water, and dried over phosphorus pentoxide in a vacuum desiccator. There is obtained 15-18 g. of white plates, m.p. 110-111° (lit., m.p. 112°). 

The use of [,3CJformaldehyde resulted in the formation of 80% of the dilabeled ethylene glycol, indicating that the ethylene glycol formation proceeds preferentially via reductive carbon-carbon coupling over hydro-formylation of formaldehyde the catalytic turnover is not given (166). Ru3(CO),2 was also found to catalyze the reductive alkylation of active methylene compounds with formaldehyde under synthesis gas. For example, pentan-2,4-dione is converted into 3-methylpentan-2,4-dione... 

However, attempts to apply the sequence to a number of other 1,3-dicarbonyl compounds led only to tar formation. Abramenko15 also reported the above reaction and, in addition, prepared the corresponding dimethylthieno[3,2-6 pyridine from the same dione and 3-aminothiophene double salt, using zinc chloride in ethanol.16 Klemm13 used zinc chloride in dioxane to effect cyclization of 10 and also prepared 4,5.6-trimethylthieno 3,2-Z>]pyridine via the 3-methylpentane-2,4-dione/2-aminothiophene Schiff s base. The acetals and ketals of 1,3-dicarbonyl compounds are also effective in this synthesis. Thus Klemm1 has prepared the parent systems by condensation-cyclization of 2- and 3-aminothiophene double salts with malondialdehyde tetraethyl acetal (MTA) [Eq. (3). ... 

Radical addition reactions were also recently added to the repertoire of 2-nitroin-dole (21), previously dominated by nucleophilic reactions [17]. Treatment of the indole with activated methylene compounds such as dimethyl malonate, malonitrile and pentane-2,4-dione in a refluxing solution of Mn(0Ac)3-2H20 in acetic acid gave mainly 2-oxo-indolin-ylidenes 22 after an in situ Nef reaction. The expected 3-subsitiuted 2-nitroinole 23, however, was only observed with the methine compounds 3-methylpentane-2,4-dione and 5-oxo-4-propionyUieptane-nitrile. 

Thallous ethoxide added all at once with stirring to 1.1 moles acetylacetone in petroleum ether, stirring continued 2-3 min., chilled and filtered acetylaceto-natothallium(I) (Y ca. 100%) suspended in methyl iodide, stirred and refluxed 4 hrs. -> 3-methylpentane-2,4-dione (Y ca. 100%). - This synthesis proceeds cleanly without any side reactions. F. e., also G-acetylation with acetyl fluoride and 0-acelylation with acetyl chloride, s. E. C. Taylor, G. H. Hawks, III, and A. McKillop, Am. Soc. 90, 2421 (1968). 

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