1 - -2-methyl-1 -butanone

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

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. 

Ketones may also be named using functional class lUPAC nomenclature by citing the two groups attached to the carbonyl m alphabetical order followed by the word ketone Thus 3 methyl 2 butanone (substitutive) becomes isopropyl methyl ketone (functional class)... 

Ethyl acetoacetate may also be subjected to double alkylation Show how you could prepare 3 methyl 2 butanone by double alkylation of ethyl acetoacetate ... 

Methyl Isopropyl Ketone. Methyl isopropyl ketone [563-80-4] (3-methyl-2-butanone) is a colorless Hquid with a characteristic odor of lower ketones. It can be produced by hydrating isoprene over an acidic catalyst at 200—300°C (150,151) or by acid-catalyzed condensation of methyl ethyl ketone and formaldehyde to 2-methyl-l-buten-3-one, foUowed by hydrogenation to the product (152). Other patented preparations are known (155,156). Methyl isopropyl ketone is used as an intermediate in the production of pharmaceuticals and fragrances (see Perfumes), and as a solvent (157). It is domestically available from Eastman (Longview, Texas) (47). 

Methyl-2-butanone (methyl isopropyl ketone) [563-80-4] M 86.1, b 93-94 /752mm, d 0.818, n 1.410, pK -7.1 (aq H2SO4). Refluxed with a little KMn04. Fractionated on a spinning-band column, dried with CaS04 and distd. 

The idea of kinetic versus thermodynamic control can be illustrated by discussing briefly the case of formation of enolate anions from unsymmetrical ketones. This is a very important matter for synthesis and will be discussed more fully in Chapter 1 of Part B. Most ketones, highly symmetric ones being the exception, can give rise to more than one enolate. Many studies have shown tiiat the ratio among the possible enolates that are formed depends on the reaction conditions. This can be illustrated for the case of 3-methyl-2-butanone. If the base chosen is a strong, sterically hindered one and the solvent is aptotic, the major enolate formed is 3. If a protic solvent is used or if a weaker base (one comparable in basicity to the ketone enolate) is used, the dominant enolate is 2. Enolate 3 is the kinetic enolate whereas 2 is the thermodynamically favored enolate. 

Enamines of several methyl ketones have been prepared and their isomer content estimated by NMR spectroscopy (13,39,43). The reaction of Ti[N(CH3)2l4 as the amine source and 3-methyl-2-butanone gave only 26 (Ri = Rj = CH3), which could be isomerized by prolonged heating to a 1 1 mixture ofthatenamine and enamine 27 (R, = Rj = CH3)(39). The reaction of morpholine and 3-methyl-2-butanone in benzene with a trace of acetic... 

Acetone, 2-butanone, 3-methyl-2-butanone, 2-pentanone, 3,3-dimethyl-2-butanone, cyclopentanone, 3-heptanone. 4-methyl-cyclohexanone, 2-octanone, and acetophenone 2 m Porapak Q column, 100-200° at 107min. 

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. 

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. 

On the other hand, as mentioned in the preceding subsection, a preparative-scale enzymic synthesis of 1-deoxy-D-r/ireo-pentulose can be achieved, according to Reaction 1, in the presence of an extract of B. pumilus. Obviously, this raises the question of the relevance of Eq. 1 to the production of the pentulose in microorganisms. Acetoin in Reaction 1 could be replaced by 3-hydroxy-3-methyl-2-butanone (then the by-product is acetone). More interestingly, it can be also replaced by pyruvate, then the pentulose is synthesized according to Reaction 3 ... 

A rapid and efficient one-pot synthesis of substituted 2(5H)-furanones has been reported starting from 3-hydroxy-3-methyl-2-butanone 88 and ethyl... 

Methyl-2-butanone was purchased from Eastman Organic Chemicals and distilled before use. 

The equilibrium ratios of enolates for several ketone-enolate systems are also shown in Scheme 1.1. Equilibrium among the various enolates of a ketone can be established by the presence of an excess of ketone, which permits reversible proton transfer. Equilibration is also favored by the presence of dissociating additives such as HMPA. The composition of the equilibrium enolate mixture is usually more closely balanced than for kinetically controlled conditions. In general, the more highly substituted enolate is the preferred isomer, but if the alkyl groups are sufficiently branched as to interfere with solvation, there can be exceptions. This factor, along with CH3/CH3 steric repulsion, presumably accounts for the stability of the less-substituted enolate from 3-methyl-2-butanone (Entry 3). 

Alpine-Hydrideab 3 - methyl-2-butanone 62 S Hydride-Donor Reagents... 

---