Acetophenone, carboxylation

When an alkyl aryl ketone is heated with yellow ammonium polysulphide solution at an elevated temperature, an aryl substituted aliphatic acid amide is foimed the product actually isolated is the amide of the ci-aryl carboxylic acid together with a smaller amount of the corresponding ammonium salt of the oarboxylio acid. Thus acetophenone affords phenylacetamide (50 per cent.) and ammonium phenylacetate (13 per cent.) ... 

Ethers of benzenepentol have been obtained by Dakin oxidation of the appropriately substituted acetophenone. Thus, the oxidation of 2-hydroxy-3,4,6-ttimethoxyacetophenone and 2-hydroxy-3,4,5-ttimethoxyacetophenone with hydrogen peroxide ia the presence of alkali gives l,2-dihydroxy-3,4,6-ttimethoxybenzene and l,2-dihydroxy-3,4,5-ttimethoxybenzene, respectively further methylation of these ethers yields the pentamethyl ether of benzenepentol (mp 58—59 degC) (253). The one-step aromatization of myoinositol to produce esters of pentahydroxybenzene is achieved by treatment with carboxylic acid anhydrides ia DMSO and ia the presence of pyridine (254) (see Vitamins). 6-Alkyl- or... 

Lemiere and coworkers synthesized the antipicomavirus agent 3-0-Methylquercetin (76). A key transformation was the conversion of acetophenone 61a to 3-methoxyflavone 79. In the event, 61a and 3,4-dibenzyloxybenzoic anhydride (77) were allowed to react at 160 C in the presence of sodium carboxylate 78 to deliver the penultimate intermediate in 78% yield. Debenzylation of 79 in the presence of Pearlman s catalyst delivered the natural product in 99% yield. 

This procedure appears to be general and has been successfully applied to the following examples ethyl acetoacetate from acetone (68 %) ethyl benzoylacetate from acetophenone (74%) ethyl a-propionylpropionate from diethyl ketone (81%) ethyl 2-methylcyclohexanone-6-carboxylate from 2-methylcyclohexanone (67%). 

The carboxylation of ketones is carried out essentially as in the preceding experiment, but at slightly higher temperatures (requiring an oil bath or mantle). Thus, acetophenone (6 g, 0.05 mole) in 100 ml of approx. 2 M MMC is stirred and heated at 110-120° for 1 hour. After cooling, hydrolysis in the acid-ice mixture, and isolation from ether, benzoylacetic acid, mp 99-100°, is obtained in 68% yield. Similarly, 1-indanone gives l-indanone-2-carboxylic acid, mp 100-101°, in 91 % yield. 

In the hydrogenation, 200 g of acetophenone azine, 1000 ml of EtOAc and 5 g of 10% Pd-on-C was shaken at 30-50 psig for 10 h. Hydrogen absorption had ceased. About 7.6 g of phenylethylamine, formed by cleavage of the N—N bond, was obtained as a by-product. Oxidation of hydrazines can be done catalytically. Ethyl 2-arylhydrazine carboxylates were oxidized easily by bubbling air at 25 "C through a toluene or dioxane solution in the presence of Pd or Pt (5d). 

Just as an aromatic ring is alkylated by reaction with an alkyl chloride, it is acylated by reaction with a carboxylic acid chloride, RCOC1, in the presence of AICI3. That is, an acyl group (-COR pronounced a-sil) is substituted onto the aromatic ring. For example, reaction of benzene with acetyl chloride yields the ketone, acetophenone. 

Methyl 2-phenylsulfmylacetate 96 and /S-ketosulfoxides have been used for the syntheses of various ketones and derivatives of carboxylic acids131"133. For example, cu-(methylsulfinyl)acetophenone 97 have been converted to the corresponding ketone or to y- and <5-ketoesters134. 

Carbanions derived from optically active sulfoxides react with esters, affording generally optically active )S-ketoesters ° . Kunieda and coworkers revealed that treatment of (-t-)-(R)-methyl p-tolyl sulfoxide 107 with n-butyllithium or dimethy-lamine afforded the corresponding carbanion, which upon further reaction with ethyl benzoate gave (-l-)-(R)-a-(p-tolylsulfinyl)acetophenone 108. They also found that the reaction between chiral esters of carboxylic acids (R COOR ) and a-lithio aryl methyl sulfoxides gave optically active 3-ketosulfoxides The stereoselectivity was found to be markedly influenced by the size of the R group of the esters and the optical purity reached to 70.3% when R was a t-butyl group. 

Electrochemical carboxylation of acetophenone with CO2 coupled with nitrite reduction proceeds by the controlled-potential electrolysis of CO2-saturated acetonitrile containing [Fe4S4 (SPh)4] , N02, PhCOCH3, and a dehydration... 

Phenacyl esters of benzoic acid, of amino acid derivatives, and of gib-berillin A3 undergo photolytic cleavage at >313 nm, giving, in each case, the free carboxylic acid and the corresponding acetophenone (see Scheme 29) 84,85 -pijg yjeijs Qf free carboxylic acids (33-96%) vary considerably,... 

Compound (B), being an oxidation product of a ketone should be a carboxylic acid. The molecular formula of (B) Indicates that it should be benzoic acid and compound (A) should, therefore, be a monosubstituted aromatic methyl ketone. The molecular formula of (A) indicates that it should be phenyl methyl ketone (acetophenone). Reactions are as follows ... 

In 2003, Banerjee et al. designed an efficient photoremovable protecting group for the release of carboxylic acids based on similar p-elimination from photoenols (Scheme 14). They showed that o-alkyl acetophenone derivatives with various ester groups in the p-position release their ester moiety in high chemical yields. The authors proposed that the photorelease took place as shown in Scheme 14 but did not support the mechanism with transient spectroscopy. Formation of 21, which is expected to be the major product in the reaction, was not confirmed, and thus, the authors speculated that 21 undergoes polymerization to yield oligomers. 

The reagents RuCl3/Na(Br03) /aq. M Naj(C03) and RuCl3/K3(S30j)/aq. M KOH oxidised activated primary alkyl halides RX to carboxylic acids and secondary alkyl halides to ketones, e.g. 1-bromophenylethane to acetophenone [213]. Stoicheiometrically fran -Ba[Ru(OH)2(0)3]/CF3COOH/(bpy)/CH3Cl3 oxidised alkanes (e.g. cyclohexane, adamantane, n-hexane, ethane) to ketones or acids, perhaps via Ru (0) (bpy)(CF C(O)O) [550]. 

Formerly, benzoic acid was produced by the decarboxylation of phthalic anhydride. Oxidation of acetophenon, benzyl bromide, and toluene with sulfur and water has been described in the literature, but are not commercially feasible routes of synthesis. Carboxylation of benzene with carbon dioxide is not practical due to the instability of benzoic acid at the required reaction conditions [8]. 

The geometric isomers 464 and 467 of 5(47/)-oxazolones prepared from acetophenones can be separated. Alternatively, the mixture can be isomerized under the appropriate reaction conditions to obtain the pure of (Z) or ) isomer. Each isomer can be converted to a pair of enantiomers 466 and 469 (only one enantiomer shown) (Scheme 7.152). The p-methyl phenylalanine analogues thus obtained are constrained phenylalanines and the effect of incorporation of a p-MePhe or p-MeTyr residue on the biological properties of H-Tyr-Tic-Phe-Phe-NH2 (TIPP, where Tic = l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) a delta opioid receptor antagonist, has been studied. ... 

The Friedlander condensation of 2,6-diaminopyridine-3,5-dicarbaldehyde (393) with various ketones has been reported (77JOC3410). Reaction of the aldehyde with acetophenone, with deoxybenzoin and with a-tetralone generates the 5,10-dihydro-l,9,10-anthyridine derivatives (394 R = H), (394 R = Ph) and (395) respectively, whilst with acenaphthenone the nonacyclic anthyridine (396) is obtained. The condensation between 2-amino-3-ethoxy-carbonyI-l,8-naphthyridine (225) and alkyl carboxylates under basic conditions produces 4-hydroxy-1,9,10-anthyridin-2-ones (397) (79BAP571). 

Methyl thieno[3,2-r/][l,2,3]thiadiazole-6-carboxylate (MTTC) 50 has been shown to deactivate the P450 enzyme-catalyzed oxidation of 1-phenylethanol to acetophenone <1997B7209>. It was postulated that this was due to preferential enzymatic oxidization of MTTC. GC-MS analysis of the enzymatic oxidation products of compound 50 showed the major product to have a molecular mass of 188. Compounds 51 or 52 are possible structures assigned to this molecular mass although no other analytical method had been used for confirmation. 

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