3- hydroxy-, Kolbe reaction

Protected sugar derived acids, having no a-hydroxy substituent, have also been used in die mixed Kolbe reaction [106]. The Kolbe reaction is used to graft short functionalised alkyl chains onto poly(acryIic acid) [107],... 

The Kolbe reaction of 3-hydroxy-2-(trifluoromethyl)propanoic acid (9) affords the isomerized diols 10 in 95% yield, which are cyclized with phosphoric acid to form the 3,4-bis(tri-fluoromethyl)tetrahydrofurans 11. The electrolysis has been carried out under a constant current (2.0 A) at 5 C using a beaker-type undivided cell attached with platinum electrodes (40 cm X 40 mm). 

An easier method of production of p-anisic acid is methy-lation of p-hydroxy benzoic acid obtained as a co-product during manufacture of o-hydroxy benzoic acid (salicylic acid) via Kolbe reaction of phenol and CO2... 

The Kolbe-Schmitt reaction has been applied to the preparation of other o hydroxy benzoic acids Alkyl derivatives of phenol behave very much like phenol itself... 

Hydroxy-1-Naphthalenecarboxylic Acid. 2-Hydroxy-1-naphthoic acid is manufactured by a Kolbe-type process, ie, by reaction of the thoroughly dried potassium or sodium 2-naphthalenolate with CO2 at ca 115—130°C in an autoclave at ca 300—460 kPa (3.0—4.5 atm) for 10—16 h. It decarboxylates readily, eg, in water starting at ca 50°C. 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Non-Kolbe electrolysis of alicyclic p-hydroxy carboxylic acids offers interesting applications for the one-carbon ring extension of cyclic ketones (Eq. 35) [242c]. The starting compounds are easily available by Reformatsky reaction with cyclic ketones. Some examples are summarized in Table 13. Dimethylformamide as solvent and graphite as anode material appear to be optimal for this reaction. 

Non-Kolbe electrolysis of carboxylic acids can be directed towards a selective fragmentation, when the initially formed carbocation is better stabilized in the y-position by a hydroxy or trimethylsilyl group. In this way the reaction can be used for a three-carbon (Eq. 36) [335] (Table 14, No. 1) or four-carbon ring extension (Eq. 37) [27] (Table 14, Nos. 2-4). Furthermore it can be employed for the stereo-... 

The conventional synthesis of trans-2,5-dialkyl phospholanes starting from a chiral 1,4-diol is shown in Scheme 24.1. Originally, these 1,4-diols were obtained via electrochemical Kolbe coupling of single enantiomer a-hydroxy adds [25], but this method proved to be commercially impracticable and has since been replaced by more viable biocatalytic routes [26]. Reaction of the chiral 1,4-diol with thionyl chloride followed by ruthenium-catalyzed oxidation with so-... 

These reactions are notable because a-branched carboxylic acids usually do not undergo efficient Kolbe coupling. Similarly, Kubota et al. have achieved highly efficient homo and crossed coupling reactions using trifluoromethylated carboxylic acids as shown in Scheme 7.7 [77,78]. Notably, the protection of the hydroxy group of the acids 12 is not necessary. 

Hydroxy-3-naphthoic acid ( BONA or BON ) is prepared by heating the sodium salt of 2-hydroxynaphthalene with carbon dioxide in a pressure chamber at 240 to 250°C at a pressure of 15 bar (Kolbe synthesis). The reaction mixture is continuously agitated. Remaining 2-naphthol is separated and recycled ... 

Form Supplied in colorless oil commercially available. Analysis of Reagent Purity optical rotation NMR spectroscopy. Preparative Methods the preparation of (5, 5)-ethyl-DuPHOS is based on (3R,61 )-octane-3,6-diol as an enantiomerically pure starting compound. The latter is synthesized by a three-step procedure starting from methyl 3-oxopentanoate, which is transformed to methyl (l )-3-hydroxypentanoate (99% ee) by enantioselective hydrogenation with a Ru-(R)-BINAP catalyst, followed by hydrolysis to the hydroxy acid. The subsequent electrochemical Kolbe coupling reaction leads to (3R,6R)-octane-3,6-diol in a protocol that can be scaled up to multigram quantities (eq 1). ... 

In addition to these reactions in which the carbanions are supplied from carbonyl compounds, we will discuss in this chapter Grignard reactions, the benzilic acid rearrangement, the benzoin condensation, and the Kolbe synthesis of hydroxy aromatic acids. These reactions illustrate the addition of other kinds of carbanions to carbonyl groups. The benzilic acid rearrangement is an example of the intramolecular addition of a group with its pair of electrons to a carbonyl carbon atom. 

The new 23-hydroxy-epimers of cholesterol have been prepared by boro-hydride reduction of the 23-ketone, and Grignard reactions on the cyanohydrin of pregnenolone acetate have been used to prepare both epimers of 20a,22-dihydroxycholesterol. Using optically pure half-esters of methyl succinic acid in Kolbe electrolytic coupling reactions with various bile acids the corresponding 25-d- and 25-L-cholestanoic acids have been prepared. ... 

Hyttroxyisopbtbalic Acid. 4-Hydroxy-l,3-benz-enedicarboxylic acid. C,H405 mol wt 182.13. C 52,75%, H 3.32%, O 43.92%. Prepd by high pressure carbonation of potassium phenate (Kolbe -Schmitt reaction) Baine et aL. J. Org. Chem. 19, 510 (1954) or by boiling salicylic acid with carbon tetrachloride in alkaline medium in the presence of Cu powder Ger. pat. 258,887 (1913 to Zeltner. Landau) Chem. Zentr. 1913,1, 1641 Frdl. 11, 210. Major constituent of the brown dust residue from sublimation of salicylic acid Hunt et aL, Chem. Ind. (London) 1985, 417. 

A Kolbe cross-coupling electrolysis reaction of 170 with propionic acid (MeOH, Et N, 35 °C) furnishes methyl (iS)-2-hydroxypentanoate which, after protection (TBS-Cl, imidazole, DMF) and saponification (KOH, EtOH), gives the TBS-protected a-hydroxy acid 171 in 58% overall yield [60].This hydroxy acid supplies the 0-1 to C-3 fragment in the convergent synthesis of the antibiotic myxovirescine (172). 

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