Chloro-4,4-dimethoxy-2-butanone

A solution of sodium methoxide (305 g, 5.64 mol) in methanol (3.781) is added to the above enone (523 g, 3.76 mol) in a slow stream, keeping the temperature at 0°C. After 30 min at 0°C, acetic acid (107 ml, 1.88 mol) is added, methanol is rotary evaporated off, and the residue is dissolved in isopropyl ether (1.51). After washing with water (11) and saturated sodium bicarbonate solution (250 ml), the extract is dried (MgS04), filtered and concentrated in vacuo. The residue is distilled to give the product as a colourless liquid (488.4 g, 78%), bs 66-75 C. 

A mixture of 3-chloro-4,4-dimethoxy-2-butanone (3.33 g, 20 mmol), benzami-dine hydrochloride (4.70 g, 30 mmol) and sodium acetate (4.10g, 50 mmol) is refluxed (42h) in dioxane (100 ml). After cooling, the salts are removed by filtration and the filtrate concentrated to an oil under reduced pressure. This oil is taken up in ethyl acetate (100 ml) and extracted with IM HQ (3 X 20 ml). The combined aqueous extracts are washed with ethyl acetate, and carefully basified with solid sodium carbonate. The aqueous solution is extracted with chloroform (3 x 20 ml), and the combined extracts are dried (MgS04), filtered and concentrated, to give the cmde product (3.23 g), which can be recrystallized from cyclohexane/toluene as fine yellow needles (2.33 g, 60%), m.p. 155-157°C. Similarly prepared are 4-acetyl-2-methyl- (46%) and 4-acetyl-2-hexylimidazoles (26%). 

The jd-formylacrylate (11) is conveniently prepared by acid hydrolysis of ihe coiresponding ethyl a-phenyl- -formylacrylate dimethylhydrazone methiodide, which in turn is available in quantitative yield when the corresponding //JV-dimethylhydrazone ester is quatemized with 

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Acylainino-4-acylimidazoles have been made from 3-amino-l,2,4-oxadiazoles and 1,3-dicarbonyl reagents (see Section 2.2.1 and Scheme 2.2.5). 4(5)-Acylimidazoles can be derived from 4-acylaininoisoxazoles (see Section 6.1.2 and Scheme 6.1.3). (See also the discussion in Section 2.2.1 on 4-acylimidazole synthesis.) 5-Acyl-l-arylimidazoles can be made from or-oxoketene-SJV-acetals and nitrosoaromatics (see Section 3.2 and Scheme 3.2.5), and 4-acyl-imidazoles by nitration of 1,3-dicarbonyl compounds in their enolic forms, reduction to iV-alkenylformamides and subsequent cyclization (see Section 3.2 and Scheme 3.2.4). Examples have also been isolated from reactions of 2-oximino-l,2,3-tricarbonyls and amines (see Section 4.1 and Scheme 4.1.7), from compounds such as 3-chloro-4,4-dimethoxy-2-butanone and 3,4-disubstituted 3-buten-2-ones (see Section 4.3 and Scheme 4.3.5), and by ultraviolet irradiation of 1-alkenyltetrazoles which bear an acyl group conjugated with the exocyclic double bond (see Section 6.1.2.3). 

The Reformatsky reactions of methyl or ethyl bromoacetate with 4-acetoxy-,2,24 4-benzyloxy-,2 4-tetrahydropyranyloxy-,2 4-chloro-,8 and 4,4-dimethoxy-2-butanone1418 have been carried out. The adducts were converted to mevalonolactone by hydrolysis and, in the case of the acetal reactant, by appropriate reduction and oxidation procedures. The same Reformatsky-type syntheses of mevalonolactone have also been performed using the lithium and magnesium carbanions of acetate esters5,19 25 26 and the dianion of acetic acid28,27 instead of the usual zinc reagent. The intramolecular Reformatsky reaction of 4-(bromoacetoxy)-2-butanone gives mevalonolactone directly.28 A related route to mevalonolactone involves boron trifluoride-catalyzed cycloaddition of ketene to 4-acetoxy-2-butanone followed by hydrolysis.183... 

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