Butanone oxidation

Liquid-phase MPVO reactions were performed in 25 ml isopropanol (reductions) or 25 ml 2-butanone (oxidations) at 85 °C using 2.5 mmol of the appropriate substrate 4-r-butylcyclohexanone (4-Bu-ONE), 4-methylcyclohexanone (4-Me-ONE) or 4-t-butylcyclohexanol (4-Bu-OL, cis/trans mixture) 0.5 g zeolite or 0.25 mmol aluminium isopropoxide as the catalyst and 1,3,5-tri-f-butylbenzene as the internal standard. Samples were taken at regular intervals and analyzed by GC on a Carbowax CP-52 column and GC/MS. 

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). 

Various 4-, 5-, or 4,5-disubstituted 2-aryIamino thiazoles (124), R, = QH4R with R = 0-, m-, or p-Me, HO C, Cl, Br, H N, NHAc, NR2, OH, OR, or OjN, were obtained by condensing the corresponding N-arylthiourea with chloroacetone (81, 86, 423), dichloroacetone (510, 618), phenacyichloride or its p-substituted methyl, f-butyl, n-dodecyl or undecyl (653), or 2-chlorocyclohexanone (653) (Method A) or with 2-butanone (423), acetophenone or its p-substituted derivatives (399, 439), ethyl acetate (400), ethyl acetyl propionate (621), a- or 3-unsaturated ketones (691), benzylidene acetone, furfurylidene acetone, and mesityl oxide in the presence of Btj or Ij as condensing agent (Method B) (Table 11-17). 

Butane-Naphtha Catalytic Liquid-Phase Oxidation. Direct Hquid-phase oxidation ofbutane and/or naphtha [8030-30-6] was once the most favored worldwide route to acetic acid because of the low cost of these hydrocarbons. Butane [106-97-8] in the presence of metallic ions, eg, cobalt, chromium, or manganese, undergoes simple air oxidation in acetic acid solvent (48). The peroxidic intermediates are decomposed by high temperature, by mechanical agitation, and by action of the metallic catalysts, to form acetic acid and a comparatively small suite of other compounds (49). Ethyl acetate and butanone are produced, and the process can be altered to provide larger quantities of these valuable materials. Ethanol is thought to be an important intermediate (50) acetone forms through a minor pathway from isobutane present in the hydrocarbon feed. Formic acid, propionic acid, and minor quantities of butyric acid are also formed. 

Another attractive commercial route to MEK is via direct oxidation of / -butenes (34—39) in a reaction analogous to the Wacker-Hoechst process for acetaldehyde production via ethylene oxidation. In the Wacker-Hoechst process the oxidation of olefins is conducted in an aqueous solution containing palladium and copper chlorides. However, unlike acetaldehyde production, / -butene oxidation has not proved commercially successflil because chlorinated butanones and butyraldehyde by-products form which both reduce yields and compHcate product purification, and also because titanium-lined equipment is required to withstand chloride corrosion. 

Methyl vinyl ketone can be produced by the reactions of acetone and formaldehyde to form 4-hydroxy-2-butanone, followed by dehydration to the product (267,268). Methyl vinyl ketone can also be produced by the Mannich reaction of acetone, formaldehyde, and diethylamine (269). Preparation via the oxidation of saturated alcohols or ketones such as 2-butanol and methyl ethyl ketone is also known (270), and older patents report the synthesis of methyl vinyl ketone by the hydration of vinylacetylene (271,272). 

Acetaldehyde can be used as an oxidation-promoter in place of bromine. The absence of bromine means that titanium metallurgy is not required. Eastman Chemical Co. has used such a process, with cobalt as the only catalyst metal. In that process, acetaldehyde is converted to acetic acid at the rate of 0.55—1.1 kg/kg of terephthahc acid produced. The acetic acid is recycled as the solvent and can be isolated as a by-product. Reaction temperatures can be low, 120—140°C, and residence times tend to be high, with values of two hours or more (55). Recovery of dry terephthahc acid follows steps similar to those in the Amoco process. Eastman has abandoned this process in favor of a bromine promoter (56). Another oxidation promoter which has been used is paraldehyde (57), employed by Toray Industries. This leads to the coproduction of acetic acid. 2-Butanone has been used by Mobil Chemical Co. (58). 

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 mixture of 26 g (0.1 mol) of 0 -(4-pyridyl)-benzhydrol, 1.5 g of platinum oxide, and 250 ml of glacial acetic acid is shaken at 50°-60°C under hydrogen at a pressure of 40-50 Ib/in. The hydrogenation is complete in 2 to 3 hours. The solution is filtered and the filtrate evap-rated under reduced pressure. The residue is dissolved in a mixture of equal parts of methanol and butanone and 0.1 mol of concentrated hydrochloric acid is added. The mixture is cooled and filtered to give about 30 g of 0 -(4-piperldyl)-benzhydrol hydrochloride, MP 283°-285°C, as a white, crystalline substance. 

Methyl ethyl ketone MEK (2-butanone) is a colorless liquid similar to acetone, but its boiling point is higher (79.5°C). The production of MEK from n-butenes is a liquid-phase oxidation process similar to that used to... 

Since the transition state for alcohol oxidation and ketone reduction must be identical, the product distribution (under kinetic control) for reducing 2-butanone and 2-pentanone is also predictable. Thus, one would expect to isolate (R)-2-butanol if the temperature of the reaction was above 26 °C. On the contrary, if the temperature is less than 26 °C, (S)-2-butanol should result in fact, the reduction of... 

The Oppenauer Oxidation. When a ketone in the presence of base is used as the oxidizing agent (it is reduced to a secondary alcohol), the reaction is known as the Oppenauer oxidation. This is the reverse of the Meerwein-Ponndorf-Verley reaction (16-23), and the mechanism is also the reverse. The ketones most commonly used are acetone, butanone, and cyclohexanone. The most common base is aluminum r r/-butoxide. The chief advantage of the method is its high selectivity. Although the method is most often used for the... 

Starting from n-butane, 2-butoxides that rapidly convert to 2-butanone are found over MgCr204 [24]. However, the further oxidation of adsorbed 2-butanone only gives rise to the acetate species, while starting from n-butane, formate species are also observed. This can be explained assuming that sec-butoxides can partly isomerize to rert-butoxides before further oxidation. This implies that the C-O bond formed is partly ionic and the alkyl moiety has the... 

The effect of the nitric acid/hydrogen peroxide mixture on acetone when it is hot gives rise to an explosive oxidation, especially when the medium is confined. This situation also applies to a large number of ketones, and in particular, cyclic ketones. Cyclic di- and triperoxides form compounds that detonate, if there is no strict and very delicate thermal control. Accidents have been reported with butanone, 3-pentanone, cyclopentanone, cyclohexanone and methylcyclo-hexanones. 

Distillation to small volume of a small sample of a 4-year-old mixture of the alcohol with 0.5% of the ketone led to a violent explosion, and the presence of peroxides was subsequently confirmed [1]. Pure alcohols which can form stable radicals (secondary branched structures) may slowly peroxidise to a limited extent under normal storage conditions (isopropanol to 0.0015 M in brown bottle, subdued light during 6 months to 0.0009 M in dark during 5 years) [2], The presence of ketones markedly increases the possibility of peroxidation by sensitising photochemical oxidation of the alcohol. Acetone (produced during autoxidation of isopropanol) is not a good sensitiser, but the presence of even traces of 2-butanone in isopropanol would be expected to accelerate markedly peroxidation of the latter. Treatment of any mixture or old sample of a secondary alcohol with tin(II) chloride and then lime before distillation is recommended [3], The product of photosensitised oxidation is 2-hydroperoxy-2-propanol [4]. 

The hexahydro-2-methyl-477-[l,4]oxazino[3,4-3][l,3]oxazin 4-one 393 was prepared in excellent yield by electrochemical oxidation and cyclization of the 3-hydroxy-l-(morpholin 4-yl)butanone 392 (Equation 44). The oxazino[3,4+][l,3]oxazin-4-one 393 is one of a series of compounds obtained by utilization of electrochemistry in parallel and combinatorial syntheses <2000JC0545>. 

Due to high activity in reactions with free radicals, ozone undergoes the chain decomposition in solutions also. The chain reaction of ozone decomposition was evidenced in 1973 in the kinetic study of cyclohexane and butanone-2 oxidation by a mixture of 02 and 03 [146-151], It was observed that the rate of ozone consumption obeys the equation [112] ... 

Since the reactants (R02 ketone) and the transition state have a polar character, they are solvated in a polar solvent. Hence polar solvents influence the rate constants of the chain propagation and termination reactions. This problem was studied for reactions of oxidized butanone-2 by Zaikov [81-86]. It was observed that kp slightly varies from one solvent to another. On the contrary, kt changes more than ten times from one solvent to another. The solvent influences the activation energy and pre-exponential factor of these two reactions (see Table 8.16). 

Similar results on the influence of hydrogen bonding on chain propagation and chain termination were obtained in the study of butanone-2 oxidation [83,89,90], In addition to reactions discussed above, chain termination by the following reactions were added. 

Ketones are resistant to oxidation by dioxygen in aqueous solutions at T= 300-350 K. Transition metal ions and complexes catalyze their oxidation under mild conditions. The detailed kinetic study of butanone-2 oxidation catalyzed by ferric, cupric, and manganese complexes proved the important role of ketone enolization and one-electron transfer reactions with metal ions in the catalytic oxidation of ketones [190-194],... 

The oxidation of butanone-2, catalyzed by complexes of pyridine with cupric salts, appeared to be similar in its main features [191]. Butanone-2 catalytically oxidizes to acetic acid and acetaldehyde. The reaction proceeds through the enolization of ketone. Pyridine catalyzes the enolization of ketone. Enole is oxidized by complexes of Cu(II) with pyridine. The complexes Cu(II).Py with n = 2,3 are the most reactive. Similar results were provided by the study of butanone-2 catalytic oxidation with o-phenanthroline complexes, where Fe(III) and Mn(II) were used as catalysts [192-194],... 

In reactions carried out for 24 h at room temperature, a 95% yield of cyclo-hexanol from cyclohexanone was obtained. Other ketones and aldehydes were also hydrogenated under identical conditions, but with slower rates (38% conversion for hydrogenation of 2-hexanone, 25% conversion of acetophenone, 45% for 3-methyl-2-butanone). Insertion of the C=0 bond of the ketone or aldehyde into the Cr-H bond was proposed as the first step, producing a chromium alk-oxide complex that reacts with acid to generate the alcohol product. The anionic chromium hydride [(COJsCrH]- is regenerated from the formate complex by... 

Because the direct electrochemical oxidation of NAD(P)H has to take place at an anode potential of + 900 mV vs NHE or more, only rather oxidation-stable substrates can be transformed without loss of selectivity—thus limiting the applicability of this method. The electron transfer between NADH and the anode may be accellerated by the use of a mediator. At the same time, electrode fouling which is often observed in the anodic oxidation of NADH can be prevented. Synthetic applications have been described for the oxidation of 2-hexene-l-ol and 2-butanol to 2-hexenal and 2-butanone catalyzed by yeast alcohol dehydrogenase (YADH) and the alcohol dehydrogenase from Thermoanaerobium brockii (TBADH) repectively with indirect electrochemical... 

Titanium enolates.1 This Fischer carbene converts epoxides into titanium enolates. In the case of cyclohexene oxide, the product is a titanium enolate of cyclohexanone. But the enolates formed by reaction with 1,2-epoxybutane (equation I) or 2,3-epoxy butane differ from those formed from 2-butanone (Equation II). Apparently the reaction with epoxides does not involve rearrangement to the ketone but complexation of the epoxide oxygen to the metal and transfer of hydrogen from the substrate to the methylene group. 

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. 

---