Homologation of acetic acid

Homologation of Acetic Acid-d4 Catalyst RuO2-10CH3I-d3... 

Syngas Homologation of Acetic Acid. To a N2-flushed liquid mix of acetic acid (50.0 gm) and methyl iodide (5.67 gm, 40 mmole), set in a glass liner is added 0.763 gm of ruthenium(IV) oxide, hydrate (4.0 mmole). The mixture is stirred to partially dissolve the ruthenium and the glass liner plus contents charged to a 450 ml rocking autoclave. The reactor is sealed, flushed... 

The homologation of acetic acid to higher carboxylic acids, especially to propionic acid, is also possible, e.g., with Ru/iodide catalysts. The reaction is thought to involve reduction and carbonylation steps, such as77... 

Acetic acid is quantitatively converted to acetic anhydride by reaction with ketene. Mixed anhydrides are formed when homologs of acetic acid or aromatic acids are used in the reaction. Upon distillation at atmospheric pressure, the mixed anhydrides disproportionate into acetic anhydride and the symmetrical anhydride corresponding to the carboxylic acid. Yields of propionic, n-butyric, and w-caproic anhydrides prepared by this method are in the range of 80% to 87%. ... 

The homologation of acetic acid to carboxylic acids in general and to propionic acid in particular is not a typical carbonylation reaction, in that the substrate is not treated with carbon monoxide gas but with synthesis gas. However, as outlined below, the homologation step itself is, within the sequence of consecutive reactions, a typical carbonylation reaction and, therefore, the reaction sequence will be dealt with here (cf. Sections 2.1.2.4 and 3.2.7). 

For both reactions a RhCl3/CH3l/TPO catalyst in acetic acid as reaction solvent affords propionic acid in more than 80 % yield according to the respective stoichiometries of Equations 12 and 13. Although acetic acid is present in excess in the reaction medium, it does not participate in the homologation as reactant. Only traces of propionic acid are produced in the absence of methyl acetate, ethyli-dene diacetate or acetic anhydride under our reaction conditions. Homologation of carboxylic acids has been reported by Knifton (10) to require more severe reaction conditions (220 °C, > 100 bar). 

Possible applications of ester-homologation reactions. The coproduction of acetic acid and ethyl acetate according to Reaction 4 may find some interesting applications ... 

Oxazolin-5-ones have also proven to be important intermediates in the homologation of carboxylic acids (71AG(E)655). The IV-acyl-DL-valine derivative (402), prepared from the acid chloride of the carboxylic acid and DL-valine by the Schotten-Baumann procedure, was treated with excess acetic anhydride to afford (403). Reaction of (403) with acrylonitrile and triethylamine led to (404) in good yield. Hydrolysis of (404) with dilute alkali or acid gave the y-keto nitrile or y-keto acid (Scheme 89). 

Hi) Carboxylic acids and derivatives. The haloform reaction on thienyl methyl ketones leads to thiophenecarboxylic acids, which can be treated with Raney nickel to produce the open-chain acids. This method has been used for the five-carbon homologation of carboxylic acids and to produce dicarboxylic acids (Scheme 51). Long-chain carboxylic acids may also be prepared by using dicarboxylic acid derivatives for the acylation of thiophenes (Scheme 52). In the synthesis of Queen substance, the precursor (213) has been generated by Raney nickel desulfurization of the appropriate thiophene-2-acetic acid derivative (79T329). 

In the first step of this one-carbon homologation, the diazomethane carbon is acylated by an acid chloride or mixed anhydride, to give an a-diazoketone. The excess diazomethane can be destroyed by addition of small amounts of acetic acid or vigourous stirring. Most a-diazoketones are stable and can be isolated and purified by column chromatography. 

Kolbe synthesis — The definition and use of the terms - Kolbe synthesis, K. reaction, K. electrolysis, and K. process are not very clearly distinguished and often bear different nuances of meaning. Kolbe electrolysis or synthesis mainly accounts for the anodic oxidation of carboxylic acids or carboxylates, followed by a decarboxylation step, when concentrated aqueous solutions of the respective carboxylates are electrolyzed. Kolbe picked up earlier results from -> Faraday on the electrolysis of acetic acid or acetate solutions to CO2 and ethane [i] and continued these experiments during 1843-1845 with further homologs as, e.g., valerianic acid [ii]. The carboxy-late R-COO- is anodically oxidized to form an unstable radical R-COO, which is stabilizing via a decarboxylation reaction, leaving radical rest R ... 

There are few reports on the use of rhodium for methanol homologation, although this metal is best suited for the related methanol carbonylation. The extreme selectivity of rhodium for carbonylation is noteworthy and even when a 1 1 H]/CO mixture Ls applied, selective formation of acetic acid occurs and virtually no hydrogenated by products, such as ethanol or acetaldehyde, arc detected [68],... 

In 1981, Texaco announced the rutheiuum/H2/CO-catalyzed homologation of carboxyhc acids. Homologation refers to a chain-extension reaction that increases the carbon number of the carboxyhc acid see Homologation Reactions). The particular reaction that was initially studied was the conversion of acetic acid to propioiuc acid. The proposed mechanism shown in Scheme 22 is based on a Ru /Ru cycle, similar to that suggested by Knifton and coworkers at Texaco. 

Direct chlorination of acetic acid in the presence of a small quantity of red phosphorus is a standard procedure for the preparation of chloro-acetic acid however, similar treatment of its straight-chain homologs gives complex mixtures of halogenated acids. Substitution by chlorine in a btanched-chain acid such as isovaleric acid occurs largely at the tertiary hydrogen. The peroxide-catalyzed chlorination of aliphatic acids... 

Dialkyl blsthioxooxalates are obtained if the sulfhydrolysis is performed in the presence of acetic acid (equation 50). The method also works successfully in the case of the homologous dicarboxylic acids (equation 51), 4 including the unsaturated fumaric acid. ° The preparation and further reaction of the appropriate imidates is not always straightforward. As Hartke and coworkers ° 4 have shown. 

Two short syntheses of racemic ipalbidine ( )-(842) are shown in Scheme 109. The synthesis by Jefford et al. commenced with conjugate addition between pyrrole and Ae atropate ester 849 followed by homologation of the acid 850 with diazomethane and rhodium-induced intramolecular carbene cyclization of the resulting diazoketone 851 (574). The bicyclic product 852 was converted into ( )-842 in a further four steps. The approach taken by Danishefsky and Vogel centered on acid-catalyzed cyclocondensation between the silyl ketene acetal 853 and A -pyrroline (854) to give indolizidinone 855 (575). Reduction of the lactam and cleavage of the aryl ether completed the synthesis of ( )-842. 

Mn(salen) CI2 complex 1 encapsulated in Zeolite-Y 2 catalyzed the homologation of methanol in presence of carbon monoxide and an iodide promoter at 30 atm CO and 150°C to give dimethyl ether and acetic acid as the main products. Esterification of acetic acid to methyl acetate is also observed with catalyt 2 under the same conditions. 

Homologation of methanol catalysed by 1 and 2 in presence of iodide promoter hydroiodic acid (entry Nos. 1 and 3), gave dimethyl ether selectively and while in the presence of water along with hydroiodic acid ( entry Nos. 2 and 4), both catalyst systems favoured the formation of acetic acid and dimethyl ether as the products. Catalyst 2 also gave methyl acetate a product of esterfication of acetic acid by methanol. Homogeneous catalyst 1 is at least two times more reactive than 2 in presence of water, however, catalyst 2 is more selective towards the formation of acetic acid (80%). 

On the other hand, from a qualitative standpoint, this value has always been, quite justifiably, linked to quality. Indeed, when an enologist tastes a wine and decides there is excessive volatile acidity, this derogatory assessment has a negative effect on the wine s value. This organoleptic characteristic is related to an abnormally high concentration of acetic acid, in particular, as well as a few homologous carboxylic acids. These compounds are distilled when wine is evaporated. Those which, on the contrary, remain in the residue constitute fixed acidity. 

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