Propionic acid decarboxylation

Diethyl Ketone. Diethyl ketone [96-22-0] (3-pentanone) is isomeric with methyl / -propyl ketone (2-pentanone), which has similar solvent and physical properties. Diethyl ketone is produced by the decarboxylation of propionic acid over Mn02—alumina (165), Zr02 (166), or Zr02 or Th02 on Ti02 (167,168). Diethyl ketone can also be produced by the hydrocarbonylation of ethylene (169—171). It is used as a solvent and a reaction intermediate. 

This ester (70 g) and diethyl carbonate (250 mg) were stirred at 90°C to 100°C while a solution of sodium ethoxide [from sodium (7.8 g) and ethanol (1 54 ml)] was added over 1 hr. During addition, ethanol was allowed to distill and after addition distillation was continued until the column heat temperature reached 124°C. After cooling the solution to 90°C, dimethyl sulfate (33 ml) was followed by a further 85 ml of diethyl carbonate. This solution was stirred and refluxed for 1 hr and then, when Ice cool, was diluted with water and acetic acid (10 ml). The malonate was isolated in ether and fractionally distilled to yield a fraction boiling at 148°C to 153°C/0.075 mm, identified as the alpha-methyl malonate. This was hydrolyzed by refluxing for 1 hr at 2.5N sodium hydroxide (350 ml) and alcohol (175 ml), excess alcohol was distilled and the residual suspension of sodium salt was acidified with hydrochloric acid to give a precipitate of the alpha-methyl malonic acid. This was decarboxylated by heating at 180°C to 200°Cfor 30 minutes and recrystallized from petroleum ether (BP 80°C to 100°C) to give 2-(2-fluoro-4-biphenylyl)propionic acid, MP 110°C to 111°C. 

The malonic acid (9 g) was heated to 210° to 220°C in an oil bath for 20 minutes until decarboxylation had ceased. The propionic acid was cooled and recrystallized from light petroleum (BP 60° to 80°C). Two further recrystallizations from the same solvent gave colorless prisms of 2-(4-isobutylphenyl)propionic acid MP 75° to 77.5°C. (The procedure was reported in U.S. Patent 3,228,831.)... 

One example will show the manifold types of reactions studied by Mok et al. (1989). Lactic acid decomposes in supercritical water to give acetaldehyde, which then reacts further it can also undergo dehydration to give acrylic acid, which is either hydrogenated to give propionic acid or decarboxylated to give ethene (Fig. 7.4). 

Surprisingly, the partial reduction of quinone 137 is best achieved by refluxing in acetic or propionic acids (yield 67%). Thereby the acids suffer oxidative decarboxylation (82CL701 85BCJ515). Two further unexpected routes are based on the redox reaction with cycloheptatriene (85BCJ2072) and electrolysis under the conditions of the cyclic voltammetry measurements (87BCJ2497), respectively. 

Other than water, protein is the major constituent of meat averaging nearly 21% in heef or chicken meat, with fat varying fiom 4.6 to 11.0% in beef and fiom 2.7 to 12.6% in chickoi. The principal radiolytic reactions of aqueous solutions of aliphatic amino acids are reductive deamination and decarboxylation. Alanine yields NH3, pyruvic add, acetaldehyde, propionic acid, CO2, H2, and ethylamine (6). Sulfur-containing amino adds are espedally sensitive to ionizing radiation. Cysteine can be oxidized to cystine by the hydroxyl radical or it can react with the hydrated electron and produce... 

CeHgOs, Mr 128.13, was found in, e.g., fenugreek, coffee, sake, and flor-sherry. Its aroma characteristic changes from caramel-like at low concentrations to currylike at high concentrations. A method described for its preparation comprises condensation of ethyl propionate with diethyl oxalate and reaction of the intermediately formed diethyl oxalylpropionate with acetaldehyde. Acidic decarboxylation of the ethyl 4,5-dimethyl-2,3-dioxodihydrofuran-4-carboxylate gives the title compound [199]. 

Biotin enzymes are believed to function primarily in reversible carboxvlahon-decarboxylation reactions. For example, a biotin enzyme mediates the carboxylation of propionic acid to methylmalonic add, which is subsequently converted to succinic acid, a dtric acid cycle intermediate. A vitamin Bl2 coenzyme and coenzyme A are also essential to this overall reaction, again pointing out the interdependence of the B vitamin coenzymes. Another biotin enzyme-mediated reaction is the formation of malonyl-CoA by carboxylation of acetyl-CoA ( active acetate ). Malonyl-CoA is believed lo be a key intermediate in fatly add synthesis. 

Scheme 7 Alternative mechanism for asymmetric decarboxylation of 2-cyano-2-(6-methoxy-naphth-2-yl)propionic acid in the synthesis of Naproxen involving a pre-association mechanism.

Since Barton decarboxylation can be performed under mild conditions, thermal or photolytic treatment of the Barton ester (13) of propionic acid with TV-hydroxy-2-thiopyridone in the presence of chiral menthyl acrylates generates addition products (14). However, diastereoselectivity is rather poor, since the chiral menthyl center is too far away from the C-C bond-forming position, as shown in eq. 10.7. When the chiral center is adjacent to the reaction position, stereocontrol is significantly affected, as shown in eq. 10.8 [9-12]. 

A different approach was adopted in the synthesis by Justoni and Pessina (111). The Japp-Klingemann reaction of p-benzyloxyphenyl-hydrazine with cyclopentanone carboxylic ester gave the p-benzyloxy-phenylhydrazone of a-ketoadipic acid (XIV) Fischer cyclization of the corresponding dimethyl ester then yielded 5-benzyloxyindole-2-car-boxylic-3-jS-propionic acid (XV). Decarboxylation of XV followed by Curtius degradation and debenzylation eventually afforded 5-hydroxy-tryptamine. 

Indanones are very useful and versatile intermediates in the synthesis of metallocene catalysts. Scheme 1 has the synthetic scheme originally used for the preparation of 2-alkyl-4-aryl-substituted ansa metallocenes [9-11]. In the first part of this sequence, the biaryl unit is assembled and the missing carbon atoms are introduced as a side chain. The reaction of 2-phenylbenzyl bromide with malonic acid ethyl ester under basic conditions, followed by a decarboxylation, affords the 2-(2-phenylbenzyl)propionic acid. Chlorination and Friedel-Crafts acylation yields the 2-methyl-4-phenylindanone in 93 % yield. From here, only a few standard transformations are required to complete the synthesis, finally yielding the desired metallocene. 

Formic, oxalic and malonic acids were never detected during these oxidation experiments. It was verified that formic and oxalic acids were oxidized so rapidly, that they could not accumulate in the reaction mixture and be detected by HPLC. Malonic acid was decarboxylated very rapidly to yield acetic acid. On the other hand, as expected, acetic acid and propionic acid were much less reactive. The initial rates of TOC removal were 13 and 19 mol h mol, respectively, compared to 61 for succinic acid. After 6 h, TOC abatement was 65.9 and 68.5%, respectively. 

In addition to decarboxylation, the oxidation of acids yields hydro-peroxy, hydroxy, keto groups, lactones, and mono- and dicarboxylic acids of lower molecular weight. The mechanism of the oxidation of acids is similar to that for hydrocarbons. The reactivity of mono- [300] and dicarboxylic acids [216] with respect to cumylperoxy radicals was measured by oxidation in the presence of cumyl hydroperoxide as source of R02 (see Table 15). The reactivities of methylenic groups in mono- and dicarboxylic acids and in rc-paraffin acids are close. For example, at 100° C, feCH2 X 102 (1 mole-1 s-1) = 4.8 (n-decane), 10.0 (glutaric, sebacic, j3,7 groups), 6.4 (a-CH2 of dibasic acids), 8.0 (for monocarboxylic acids), and 11.0 (>CH2 for propionic acid). 

Koshima and his co-workers have studied the reactivity of co-crystals of acridine and 1-phenyIpropionic acid. This work is analogous to that described last year for the reactivity of acridine with diphenylacetic acid. The present study is summarized in Scheme 2. Again irradiation brings about decarboxylation of the propionic acid and the resulting radical bonds to the acridine. The yields of the compounds and their optical activities are shown below the appropriate structures. When acridine and the acid are irradiated in acetonitrile solution racemic (71) is formed along with the dimer (72). A review of the photochemistry in two-component and mixed crystals systems has been published. ... 

A time-resolved study of the photochemistry of aqueous 2-(3-benzoyIphenyl)-propionic acid reveals that the main pathway for decarboxylation is intramolecular electron transfer through triplet biradicals, and similar examination of the photoreactions of 6H-purine-6-thione (29) shows that ( 29 ) acts as an electron acceptor for tetramethylbenzidine and as an electron donor for />-dinitroben-zene. Rate constants for H-atom abstraction from benzenethiols, tocopherol,... 

---