Grignard reagents reaction with acetone

The various Grignard reagents react with a variety of aldehydes and ketones to yield primary alcohols (yield, 27 6%), secondary alcohols (yield, 13 1-71 1%), and tertiary alcohols (yield, 24 9-81 7%) Products of the reactions with acetone are given in Table 4... 

An interesting appetite suppressant very distantly related to hexahydroamphetamines is somanta-dine (24). The reported synthesis starts with conversion of 1-adamantanecarboxylic acid (20) via the usual steps to the ester, reduction to the alcohol, transformation to the bromide (21), conversion of the latter to a Grignard reagent with magnesium metal, and transformation to tertiary alcohol 22 by reaction with acetone. Displacement to the fomiamide (23) and hydrolysis to the tertiary amine (24) completes the preparation of somantadine [6]. 

Thiophen Analogues of Tropylium Ions and Related Compounds.—Condensation of 3,4-diformyl-2,5-dimethylthiophen with acetone or diethyl ketone yields the tropone (496). The reaction with acetone differs from that of phthalaldehyde, which only yields indanones." The reduction of (496) with LiAlH, and also the reaction with Grignard reagents, gave ethereal solutions of alcohols, which with HCIO4 gave the deep-blue tropylium-type perchlorates (497), which are stable in acetic acid." " The carbonium ion (497 R = Me) is less stable than the tropylium ion itself, as a mixture of (498 R = Me) and (499 R = Me) is obtained upon reaction with cyclo-... 

Other Rea.ctlons, The anhydride of neopentanoic acid, neopentanoyl anhydride [1538-75-6] can be made by the reaction of neopentanoic acid with acetic anhydride (25). The reaction of neopentanoic acid with acetone using various catalysts, such as titanium dioxide (26) or 2irconium oxide (27), gives 3,3-dimethyl-2-butanone [75-97-8] commonly referred to as pinacolone. Other routes to pinacolone include the reaction of pivaloyl chloride [3282-30-2] with Grignard reagents (28) and the condensation of neopentanoic acid with acetic acid using a rare-earth oxide catalyst (29). Amides of neopentanoic acid can be prepared direcdy from the acid, from the acid chloride, or from esters, using primary or secondary amines. 

A solution of 6.3 g (0.9 moles) ethoxyacetylene in 50 ml ether is added dropwise during 30 min to a Grignard reagent prepared from 2.18 g (90 mg-atoms) magnesium and 9.81 g (90 mmoles) ethyl bromide. The reaction mixture is stirred for 1 hr at room temperature and then a solution of 3 g (9 mmoles) 3) -acetoxyandrost-5-en-I7-one in 50 ml dry ether is added dropwise. The mixture is refluxed for 1 hr and after cooling to 0° poured into 100 ml of an aqueous ammonium chloride solution. The aqueous solution is extracted with ether, and the organic extract is washed with ammonium chloride solution and water, dried, and evaporated. The residue is chromatographed on 130 g alumina (activity III). Elution with petroleum ether-benzene (1 1) yields, after crystallization from acetone-hexane, 1.27 g (35%) 3j5-acetoxy-17a-ethoxyethynylandrost-5-en-17) -ol mp 138-139° Ho -122°. 

The reaction of 17-keto steroids with hydrogen cyanide (or acetone cyanohydrin) to form a mixture of the 17-cyano-17-hydroxy compounds, followed by dehydration and reaction with methyl Grignard reagent, is one of the earliest methods for the conversion of androstanes to pregnanes. 

The flask is cooled in a dry ice-acetone bath, and the Grignard reagent solution is added dropwise with rapid stirring at such a rate that the temperature of the reaction mixture remains between —25° and —30° with a bath temperature of —45° this addition requires about 1.5 hours. After the addition has been completed, the cooling bath is removed, and the mixture is allowed to warm to room temperature. Finally, the reaction mixture is heated to reflux with continuous stirring for 30 minutes. 

Alvernhe and Laurent first developed a procedure for conversion of Grignard reagents to primary amines using acetone oxime 6c and butanone oxime 6d (Scheme 55) 22 23 However, the yields were low. They expanded their study to investigate how well organo-lithiums perform in their reaction with 6c or 6d 23. Phenyllithium gave a 1 4 mixture of aniline and the addition product of phenyllithium to the imine (Scheme 53, path e product) in the reaction with 6c while aziridine was obtained in the reaction with 6d (Scheme 56). 

The reaction vessel should be cooled with an ice-salt bath (rather than an acetone-dry ice bath as specified in the published procedure) during the addition of the PSCI3 solution to the Grignard reagent. The reaction temperature should be monitored carefully. If it falls below -5°, the addition should be stopped and the reaction mixture cautiously rewarmed to 0-5° before addition is resumed. 

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