Of isobutyric acid

Dehydrogenation of Propionates. Oxidative dehydrogenation of propionates to acrylates employing vapor-phase reactions at high temperatures (400—700°C) and short contact times is possible. Although selective catalysts for the oxidative dehydrogenation of isobutyric acid to methacrylic acid have been developed in recent years (see Methacrylic ACID AND DERIVATIVES) and a route to methacrylic acid from propylene to isobutyric acid is under pilot-plant development in Europe, this route to acrylates is not presentiy of commercial interest because of the combination of low selectivity, high raw material costs, and purification difficulties. 

The oxidative dehydration of isobutyric acid [79-31-2] to methacrylic acid is most often carried out over iron—phosphoms or molybdenum—phosphoms based catalysts similar to those used in the oxidation of methacrolein to methacrylic acid. Conversions in excess of 95% and selectivity to methacrylic acid of 75—85% have been attained, resulting in single-pass yields of nearly 80%. The use of cesium-, copper-, and vanadium-doped catalysts are reported to be beneficial (96), as is the use of cesium in conjunction with quinoline (97). Generally the iron—phosphoms catalysts require temperatures in the vicinity of 400°C, in contrast to the molybdenum-based catalysts that exhibit comparable reactivity at 300°C (98). 

The distikative separation of methacrylic acid from unreacted isobutyric acid is problematic because the boiling points of isobutyric acid (155°C) and methacrylic acid (162°C) are quite close to one another. Alternatively, the cmde reaction mixture can be esterified, and the resultant methyl methacrylate (101°C) and methyl isobutyrate (92°C) can be separated. 

Although not commercialized, both Elf Atochem and Rn hm GmbH have pubUshed on development of hydrogen fluoride-catalyzed processes. Norsolor, since acquired by Elf Aquitaine, had been granted an exclusive European Hcense for the propylene-hydrogen fluoride technology of Ashland Oil (99). Rn hm has patented a process for the production of isobutyric acid in 98% yield via the isomerization of isopropyl formate in the presence of carbon monoxide and hydrofluoric acid (100). 

With stirring, 44.1 g of isobutyric acid is added to a mixture of 51.0 g of diisopropylamine, 23.2 g of a 57% sodium hydride dispersion in mineral oil, and 350 ml of tetrahydrofuran. When gas evolution subsides, the mixture is heated at reflux for 15 minutes, cooled to 0°C, and treated with 345 ml of a 1.45M solution of n-butyllithium in heptane. After 5 hr, the... 

A. Preparation of a-bromoisobutyryl bromide. To a mixture of 250 g. (2.85 moles) of isobutyric acid and 35 g. (1.13 moles) of red phosphorus in a 1-1. three-necked flask, fitted by ground-glass joints to a dropping funnel, mechanical stirrer, and reflux condenser, is added, dropwise with stirring, 880 g. (5.5 moles) of bromine. After the addition is complete, the solution is warmed to 100° over a period of 6 hours. The unreacted bromine and hydrogen bromide are removed under reduced pressure (30 mm.). The a-bromoisobutyryl bromide is decanted from the phosphorous acid and fractionated through a short helices-packed column. After a considerable fore-cut, the main fraction, 493-540 g. (75-83%), is collected at 91-98° (100 mm.). 

Actually one observes (Fig. 4) the formation of acetone and isopropanol, with only traces of isobutyric acid (reaction (9), both products being formed in amounts exceeding 80 % of the amount of DiPK decomposed as indicated by the initial rate of formation). 

In the presence of nitroxide I, diisopropyl ketone photooxidation takes a course differing considerably from that without this additive (Fig. 5). In this case high yields of isobutyric acid and acetone were obtained, presumably as products arising from the postulated peroxy radicals c and d. On the other hand, the formation of isopropanol is almost completely suppressed. 

If one takes into account not only the initial slope of the curves but also the part played by the formation of isobutyrate it can be seen that the amount of reaction products formed is almost equivalent to the loss of DiPK. In this case the formation of isobutyric acid represents the most important difference compared with irradiation without additive. It shows that in the presence of nitroxide the acyl radical may not only be captured by oxygen but can also react further as acyl-peroxy radical, without losing its carbonyl group in the process. 

The change in the product mixture in the presence of nitroxide I, i.e., formation of isobutyric acid instead of isopropanol, and... 

A second mechanism involving as intermediate step a stable hydroxylamine ether (isopropyl I-ether) is also a possibility (reaction (15)). In a second step the ether would undergo cleavage by the acylperoxy radical with formation of isobutyric acid and acetone and liberation of the nitroxide (reaction (16)) ... 

Irradiation of diisopropyl ketone under oxygen in the presence of the hindered piperidine II likewise results in formation of isobutyric acid, acetone and small amounts of isopropanol. At the same time the amine is quantitatively oxidized to the corresponding nitroxide I (Fig. 7, reaction (17)) ... 

The formation of isobutyric acid in the presence of the additives studied, and the results of additional studies (di-tert.-butyl peroxyoxalate/isobutyroal-dehyde/amine), point to the intermediate formation of acyl peroxy radicals. 

The decarboxylation via the peroxyl radical reaction with the carboxylic group was the main channel of C02 production (78-82%). The attack of the peroxyl radical on the CH2 group adds 18-22% of C02. However, in the case of isobutyric acid with a weak tertiary C—H bond, the attack on the C—H bond appeared to be the main reaction of decarboxylation. 

The isomerization is usually complete in 5 hours and can easily be followed by vapor-phase chromatography. Heating periods up to 20 hours are not detrimental. The only failure among numerous preparations occurred when tetramethyl-1,3-cyclobutanedione contaminated with 4% of isobutyric acid was used. In case of partial conversion after 5 hours, additional increments (0.5 g.) of aluminum chloride should be added to complete the reaction. 

ALIPHATIC CARBOXYLIC ACIDS The radiation chemistry of the simple aliphatic carboxylic acids has been widely investigated. The major products of gamma radiolysis of these compounds are typified by those found (1) for radiolysis of isobutyric acid at 273 K... 

Table I. Yields of volatile products for gamma radiolysis of isobutyric acid at 273 K...

The major radical intermediates formed following radiolysis of aliphatic carboxylic acids are also typified by those found following radiolysis of isobutyric acid (1). In Figure 1 are illustrated the ESR spectra found following radiolysis of this acid at 77 K and 195 K. 

Figure 1. ESR spectra of isobutyric acid following gamma radiolysis in the solid state at (A) 77 K (B) 195 K.

Radiolysis of isobutyric acid at 195 K results in the formation of only one radical intermediate, the hydrogen abstraction radical III. The decarboxylation radical and the anion radical are both unstable at this temperature and react forming the abstraction radical and other products. The hydrogen which is abstracted is generally that which is attached to the carbon atom a to the carboxyl group. 

Lithium diisopropylamide (LDA, Creger s base ) was introduced in 19677 in an important paper describing alkylations of the dianion of isobutyric acid in tetrahydrofuran-heptane (1 5), with acceptable yields. 

Isobutyramide has been prepared by the action of concentrated aqueous ammonia on isobutyryl chloride 3 or methyl isobutyrate 4 by distillation of ammonium isobutyrate 5 or a mixture of isobutyric acid and potassium thiocyanate.6 Hydrolysis of isobutyronitrile also results in the formation of isobutyramide. 7... 

The contrast between the two types is also found for organic reactions. The reduction of H3PM012O40 by dehydrogenation of isobutyric acid or cyclohexene belongs to the bulk type II classification, and the reduction by oxygenation of methacrolein or acetaldehyde is a surface reaction. For example, when H3PM012O40 is reduced by repeated pulses of isobutyric acid and methacrolein... 

The heteropoly catalyst is deactivated during a prolonged reaction period by the loss of Mo to form volatile Mo-containing species via the interaction of isobutyric acid and/or methacrylic acid with the catalyst (343). The deactivation was suppressed by presaturating the feed by flow over a bed of Mo03 (343). 

In the dehydrogenation of isobutyric acid, the by-products in addition to CO and C02 are propylene and acetone. Two reaction mechanisms were proposed (340, 341) and the latter is shown in Scheme 9 (340). The formation of methacrylic acid and acetone involves a common intermediate The El elimination of a proton from I yields the methacrylic acid while a nucleophilic SN1 attack of oxide ion produces C02 and acetone (344). On the other hand. 

It was reported in 1993 that reaction of Ar-(2-bromoethyl)phthalimide with the dianion of isobutyric acid gave the aroylaziridine 1, and that treatment of 1 with hydrazine in ethanol at 60°C gave the phthalazin-1 (2//)-one 2. Tentative mechanisms were suggested for the formation of 1 and 2. It was subsequently rapidly established, however, that while the condensation of the phthalimide with the dianion was fully reproducible (almost quantitative crude yield), the structure of the product was not 1 as claimed. It was shown that the correct structure for the... 

The potency of captopril (14) as an inhibitor of ACE depends critically on the configuration of the mercaptoalkanoyl moiety the compound with the S-configuration is about 100 times more active than its corresponding R-enantiomer [37], The required 3-mercapto-(25)-methylpropionic acid moiety has been prepared from microbially derived chiral 3-hydroxy-(2R)-methylpropionic acid, which is obtained by the hydroxylation of isobutyric acid [38-40],... 

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