Bromo-3-methyl-2-butanone

Submitted by M. Gaudrv and A. Marqoet1 Checked by Diana Metzger and Richard E. Benson 

Caution This preparation must be carried out in an efficient hood. Bromomethyl ketones are highly lachrymatory and are skin irritants. 

To the solution is added 900 ml. of water, and the resulting mixture is washed with four 500-ml. portions of ether. The ether layers are combined and washed with 200 ml. of aqueous 10% potassium carbonate and then twice with 200-ml. portions of water (Note 9). The ether layer is dried for 1 hour over 200 g. of anhydrous calcium chloride (Note 10) and the solvent is removed on a rotary evaporator at room temperature to give 145-158 g. of crude product (Note 11). Distillation under reduced pressure through a Vigreux column gives 115-128 g. of a fraction, b.p. 83-86° (54 mm.), w22 d 1.4620-1.4640, containing 95% of l-bromo-3-methyl-2-butanone as established by proton magnetic resonance measurements (Note 11). 

The checkers used 3-methyl-2-butanone purchased from Eastman Organic Chemicals. One sample that gave a positive test for peroxides was purified by passage through a column of alumina before distillation. The material was distilled routinely before use. 

The methanol was distilled twice from magnesium turnings. Alternately, it was dried overnight over molecular sieves and then distilled. The checkers also found freshly opened reagent-grade methanol (purchased from Fisher Scientific Company) to be satisfactory. 

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The XH NMR spectrum of the major product, compound A, is consistent with the structure of 1 -bromo-3-methyl-2-butanone. The minor product B is identified as 3-bromo-3-methyl-2-butanone on the basis of its NMR spectrum. 

Exercise 18-14 Explain why decarboxylation of 2,2-dimethyl-3-oxobutanoic acid, CH3C0C(CH3)2C02H, in the presence of bromine gives 3-methyl-3-bromo-2-butanone, CH3COC(CH3)2Br. 

Chloroacetone, phenacylbromide, a-bromoisobutyrophenone, 3-bromo-3-methyl-2-butanone, 1 -alkylsulfonyl-3-bromo-2-propanone, and ethyl-y-chloroacetoacetate give with ammonium dithiocarbamate the corresponding 4-hydroxythiazolidine-2-thiones (177), which have a characteristic absorption between 273 and 279 nm. Dehydration by heating with dilute HCl can be followed by ultraviolet spectroscopy because the products formed (175) absorb at 315 to 340 nm. 

It is very important to add the bromine in a single portion. When it is added dropwise, a mixture containing significant amounts of 3-bromo-3-methyl-2-butanone is obtained. 

Butanone, 3-bromo-, 55, 129 2-BETANONE, l-bromo-3-methyl-, 55, 24 2-Butanone, 3-bromo-3-methyl-, 55, 25... 

The results of the olefin oxidation catalyzed by 19, 57, and 59-62 are summarized in Tables VI-VIII. Table VI shows that linear terminal olefins are selectively oxidized to 2-ketones, whereas cyclic olefins (cyclohexene and norbomene) are selectively oxidized to epoxides. Cyclopentene shows exceptional behavior, it is oxidized exclusively to cyclopentanone without any production of epoxypentane. This exception would be brought about by the more restrained and planar pen-tene ring, compared with other larger cyclic nonplanar olefins in Table VI, but the exact reason is not yet known. Linear inner olefin, 2-octene, is oxidized to both 2- and 3-octanones. 2-Methyl-2-butene is oxidized to 3-methyl-2-butanone, while ethyl vinyl ether is oxidized to acetaldehyde and ethyl alcohol. These products were identified by NMR, but could not be quantitatively determined because of the existence of overlapping small peaks in the GC chart. The last reaction corresponds to oxidative hydrolysis of ethyl vinyl ether. Those olefins having bulky (a-methylstyrene, j8-methylstyrene, and allylbenzene) or electon-withdrawing substituents (1-bromo-l-propene, 1-chloro-l-pro-pene, fumalonitrile, acrylonitrile, and methylacrylate) are not oxidized. 

Under a dinitrogen atmosphere, a 300-mL, two-necked, round-bottomed flask containing a magnetic stir bar and fitted with a pressure-equalizing dropping funnel and an inert gas inlet is charged with a solution of 2-aminopropane (10.6 g, 0.180 mol) in dry diethyl ether (70 mL). The flask and its contents are cooled in a dry ice—isopropanol bath to — 78°C then a solution of l-bromo-3-methyl-2-butanone (10.0 g, 0.0606 mol)1 in diethyl ether (20 mL) is added dropwise from the dropping funnel to the stirred solution of amine over 15 min. 

Caution. l-bromo-3-methyl-2-butanone is a severe lachrymator so all manipulations in this section should be performed in a good fume hood. 

Aston and Green burg 1 obtained hydroxyketals on treatment of 3-bromo-a-methyl-2-butanone and 2-bronjo-2-methyl-3-pentanorw with... 

C5H9Br trans-1-bromo-2-methyl-1-butene 54265-17-7 390.15 34.286 1,2 5066 C5H9CIO 3-chloro-3-methyl-2-butanone 5950-19-6 390.35 33.457 1,2... 

The aldehyde was then used in an aldol reaction with the anion from 3-isopropylbut-2-enolide. [The lactone was prepared in the following way bromination of 3-methyl-2-butanone under kinetic conditions (-15 °C) afforded the 1-bromo derivative. The bromine was displaced by acetate on refluxing a solution in acetone with anhydrous KOAc. Reaction of the resulting keto-acetate with the anion from triethylphosphonoacetate afforded the desired butenolide in 55% yield.] The anion was generated in tetrahydrofuran from the butenolide and lithium diisopropylamide and was cooled to -78 °C before addition of the aldehyde. The temperature was maintained below -70 °C for 5h and the reaction was quenched with ammonium chloride at this temperature. Under these conditions (kinetic) the 22R23R intermediate (3) was obtained in 65% yield (26). 

Acetic acid Acetone Methyl acetate 2-Butanone Acetone 2-Butanone 4-Methyl-2-pentanone Isopropyl ether Toluene 2-Bromo-propane 2-Bromo-propane Isopropyl formate 2-Butanone... 

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