Preparation benzoic acids from

Nickel(O) triphenylphosphine can be used to couple aryl halides and alkenes to synthesize substituted olefins [149], 1,2-bis[(di-2-propylphosphino)benzene]nick-el(0) can be used to couple aryl halides [150], and l,2-bis[(diphenylphos-phino)ethane]nickel(0) can be used to prepare benzoic acid from bromobenzene in the presence of carbon dioxide [151]. 

Nitrodienes are conveniendy prepared by eliminadon of benzoic acid from fi-nitro-fi- Tcy-clopentenyl-ct-benzoyloxyethane They undergo the Diels-Alder reacdon with methyl actylate fEq 8 17 ... 

The following example illustrates in detail the preparation of amino benzoic acids from the hot reaction product obtained by the oxidation of a xylene and containing a mixture of salt, amide salt and diamide of a phthalic acid. 

Nitrodienes are conveniently prepared by elimination of benzoic acid from P-nitro-P-l-cy-clopentenyl-a-benzoyloxyethane. They undergo the Diels-Alder reaction with methyl acrylate (Eq. 8.17).28... 

Zelenay etal. have applied CV and radiotracer technique to study adsorption of benzoic acid from 0.1 M HCIO4 solution on a pc-Au electrode prepared by electroplating [286]. Chemisorption occurred within the entire potential range... 

Initial efforts to prepare benzoic acid 28 from methyl or ethyl 4-aminobenzoate and biphenyl-2-carboxylic acid (27) afforded poor yields of 28 (48% and 7%, respectively). However, acylation of 4-aminobenzoic acid with biphenyl-2-carbonyl chloride was found to provide 28 in excellent yield (95%) when DMAP was employed as a base. Selective acylation of the anilinic nitrogen of 26 with benzoic acid 28 was accomplished in analogy with the first-generation process synthesis by conversion of 28 to the corresponding acid chloride (SOCl2, CH3CN) followed by acylation of 26 in acetonitrile. Subsequent addition of ethanolic hydrogen chloride to the reaction mixture resulted in the precipitation of conivaptan HCl (1), which was isolated in 90% yield. 

A halo acid, p-(/S-bromoethyl)-benzoic acid (87%), a hydroxy acid, yS-hydroxyisovaleric acid (9%), and an acetylated amino acid, p-(/3-acetyl-aminoethyl)4>enzoic acid (78%), have been made by this method. Attempts to prepare 3-nitro- and 4-hydroxy-benzoic acids from the corresponding acetophenones have failed. Oxidation of the methylene group of 2-acetylfluorene occurs during the reaction to give fluorenone-2-car-boxylic acid (60%). ... 

A one step approach to heteroaryl benzoic acids from readily accessible heteroaryl halides and 4-carboxybenzene boronic acid was described by Gong and Pauls. Pyrazinylbenzoic acid (74) was prepared via the Suzuki coupling of 4-carboxybenzene boronic acid with 2-chloropyrazine in the presence of Pd(PPh3)4 in high yield [44]. 

Another active principle soon extracted from plants was salicylic acid. Salicin, extracted from the willow tree, has been launched in 1876 by a Scottish physician, Thomas John McLogan It was in extensive competition with Cinchona bark and quinine and never became a very popular treatment for fever or rheumatic symptoms. The Italian chemist Raffaele Piria, after having isolated salicylalde-hyde (1839) in Spireae species, prepared salicylic acid from salicin in Dumas laboratory in the Sorbonne, Paris. This acid was easier to use and was an ideal step before future syntheses. Its structure was closely related to benzoic acid, an effective preservative useful as an intestinal antiseptic for instance in typhoid fever. Acetylsalicylic acid has been first synthesized by Charles Frederic Gerhardt in 1853 and then, in a purer form, by Johann Kraut (1869). Acetylsalicylic acid synthesis with carbolic acid and carbon dioxide was improved by Hermann Kolbe in1874, but in fact nobody noticed its pharmacological interest. 

Preparation and Separation of Benzoic Acid from Phthalic Anhydride... 

A resin with mixed carbonic-carboxylic anhydride function has been prepared and used as acylating reagent [144], Thus, the supported chloroformate 140 was obtained by reaction of hydroxymethylated polystyrene with phosgene in benzene (Scheme 7.43). Further treatment with benzoic acid in the presence of triethyl-amine in benzene gave rise to the supported mixed anhydride 141. This polymer has been used in the benzoylation of several amines, although variable amounts of benzoic acid from attack to the internal carbonyl were obtained when using aromatic amines. 

Preparation of the corresponding cA-16a,17a-diol relies on the known propensity of many inorganic oxidizing agents to produce cA-diols. The sequence for synthesizing that isomer starts with heat-induced elimination of the elements of benzoic acid from estradiol 17-benzoate. The resulting 16-dehydro compound, 31-2, is then treated with osmium tetraoxide (Scheme 3.31). The stereochemistry of that transformation can be rationalized by positing the intermediacy of a complex such as that depicted in 31-3. The overall result is the formation of the c -diol 16a-hydroxy-a-estradiol (31-4). 

Albert and Magrath24 give the preparation of / -(aminomethyl)benzoic acid from / -cyanobenzoic acid as example of the reduction of a nitrile in the presence of ammonia under atmospheric conditions (Raney nickel). Pressure hydrogenation in the presence of ammonia is carried out as follows ... 

Benzoic acid and its salts may be determined by titration with sodium hydroxide after extraction of the benzoic acid from an aqueous food suspension into chloroform, and evaporation of the chloroform and any acetic acid present (AOAC method 963.19). Vanillin interferes with this determination and a more selective method involves the determination of benzoic acid in an ether extract by UV absorption at 272 nm, as described in AOAC method 960.38. An alternative method of isolating benzoic acid from food involves the use of steam distillation and TLC separation. These sample preparation techniques are used in AOAC method 967.15 prior to the determination of benzoic acid by UV absorption. 

Grignard reagents react with CO2 to give carboxylic acids—thus, an acid can be disconnected to a Grignard reagent and hence a halide. The disconnection in Figure 19.37 was used to prepare benzoic acid labeled with using labeled CO2 produced from acid on labeled barium carbonate. 

Prepare a mixture of 30 ml, of aniline, 8 g. of o-chloro-benzoic acid, 8 g. of anhydrous potassium carbonate and 0 4 g. of copper oxide in a 500 ml. round-bottomed flask fitted with an air-condenser, and then boil the mixture under reflux for 1 5 hours the mixture tends to foam during the earlier part of the heating owing to the evolution of carbon dioxide, and hence the large flask is used. When the heating has been completed, fit the flask with a steam-distillation head, and stcam-distil the crude product until all the excess of aniline has been removed. The residual solution now contains the potassium. V-phenylanthrani-late add ca. 2 g. of animal charcoal to this solution, boil for about 5 minutes, and filter hot. Add dilute hydrochloric acid (1 1 by volume) to the filtrate until no further precipitation occurs, and then cool in ice-water with stirring. Filter otT the. V-phcnylanthranilic acid at the pump, wash with water, drain and dry. Yield, 9-9 5 g. I he acid may be recrystallised from aqueous ethanol, or methylated spirit, with addition of charcoal if necessary, and is obtained as colourless crystals, m.p. 185-186°. 

The isocoumarin 151 is prepared by the intramolecular reaction of 2-(2-propenyDbenzoic acid (149) with one equivalent of PdCbjMeCN) . However, the (Z)-phthalide 150 is obtained from the same acid with a catalytic amount of PdjOAc) under 1 atm of Oi in DMSO, alone is remarkably efficient in reoxidizing Pd(0) in DMSO. The isocoumarin 151 is obtained by the reaction of 2-(l-propenyl)benzoic acid (152) under the same conditions[4], 2-Vinylbenzoic acid (153) is also converted into the isocoumarin 154, but not to the five-membered lactone) 167,170],... 

In 1825 Michael Faraday isolated a new hydrocarbon from illuminating gas which he called bicarburet of hydrogen Nine years later Eilhardt Mitscherlich of the University of Berlin prepared the same substance by heating benzoic acid with lime and found it to be a hydrocarbon having the empirical formula C H ... 

Benzoic acid [65-85-0] C H COOH, the simplest member of the aromatic carboxyHc acid family, was first described in 1618 by a French physician, but it was not until 1832 that its stmcture was deterrnined by Wn b1er and Liebig. In the nineteenth century benzoic acid was used extensively as a medicinal substance and was prepared from gum benzoin. Benzoic acid was first produced synthetically by the hydrolysis of benzotrichloride. Various other processes such as the nitric acid oxidation of toluene were used until the 1930s when the decarboxylation of phthaUc acid became the dominant commercial process. During World War II in Germany the batchwise Hquid-phase air oxidation of toluene became an important process. 

Pyrogallol monomethyl ether has been prepared by the methylation of pyrogallol with dimethyl sulfate or methyl iodide by the decarboxylation of 2,3-dihj droxy-4-methoxy-benzoic acid and by the methylation of pyrogallol carbonate with diazomethane and subsequent hydrolysis. The method described is taken from the improved procedure of Baker and Savage for the preparation of pyrogallol monomethyl ether from o-vanillin by oxidation with hydrogen peroxide. 

Zincon disodium salt (o-[l-(2-bydroxy-5-sulfo)-3-pbenyl-5-formazono]-benzoic acid di-Na salt) [135-52-4, 56484-13-0] M 484.4, m -250-260 (dec). Zincon soln is prepared by dissolving 0.13g of the powder in aqueous N NaOH (2mL diluted to lOOmL with H2O). This gives a deep red colour which is stable for one week. It is a good reagent for zinc ions but also forms stable complexes with transition metal ions. [UV-VIS Bush and Yoe Anal Chem 26 1345 1954 Hunter and Roberts J Chem Soc 820 1941 Platte and Marcy Anal Chem 31 1226 1959] The free acid has been recrystd from dilute H2SO4. [Fichter and Scheiss Chem Ber 33 751 1900.]... 

Bromoresorcinol has been prepared by the monobromination of resorcinol monobenzoate and subsequent hydrolysis, from 2-bromo-5-aminophenol by the diazo reaction, by treating resorcinol with dichlorourea and potassium bromide, and by the bromination of 2,4-dihydroxy benzoic acid followed by decarboxylation. The above procedure is based particularly upon the observations of Rice. ... 

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