Benzoic acid product isolation

The von Richter reaction, also known as the von Richter rearrangement, was first disclosed in 1871 and the results were revised in 1875 to reflect the correct regiochemistry of the benzoic acid products. The reaction was largely ignored until the mid-20 century "when it was further examined in a series of critical experiments that lead to a fuller understanding of the scope and ultimate elucidation of the mechanism. The reaction has been of limited synthetic value due to the low isolated yield of the products. 

The synthetic utility of the von Richter reaction has been limited due to the low isolated yields of the benzoic acid products. The reported yields starting from nitroarenes range from 0.5-50%, though in some cases unreacted starting material can also be recovered. The low overall conversion is believed to be due, at least in part, to competing hydrolysis of the cyanide reagent in the reaction medium and often improved conversion is observed with greater excess of cyanide salts. ... 

The aqueous phase was rendered acid with concentrated hydrochloric acid (weak Congo red and the separated acid taken up in ether. The isolated crude acid was recrystallized from dibutyl ether, yielding colorless crystals of 4-[(2-methvl-1,2-dicarbobenzoxy-hvdra-zino)-methyl] -benzoic acid, which melted at 112°C. The so-obtained product was sufficiently pure for further reaction. 

Hydroxyphenylpyruvic acid plays an important role in the biogenesis of compounds with a phenylpropane skeleton, and it has been used as substrate in several enzyme studies. Published procedures for its preparation are unsatisfactory in many ways. The alkaline hydrolysis of the azlactone of a-bcnzoylamino- -acetoxycinnamic acid 7 makes necessary a tedious separation of the resulting benzoic acid, and the yield is only 34% based on -hydroxybenzaldehyde. The hydrolysis of 5- ( -hydroxybenzal)-3-phenylhydantoin 9 requires a separation of phenylurea. Finally, the two-step cleavage of the azlactone of a-acetamino- -acetoxycinnamic acid 8 does not proceed easily, and impure products are obtained. In applying this procedure to the synthesis of a carboxyl-labeled -hydroxyphenylpyruvic acid, the overall yield was only 9%.u It must be kept in mind that any prolonged isolation procedure will cause some decomposition of this sensitive compound. 

The regioselectivity of a Rhodococcus rhodochrous nitrilase has been demonstrated for the conversion of 5-fluoro-l,3-dicyanobenzene to 5-fluoro-3-cyano-benzoic acid [62]. The nitrilase was expressed in an Escherichia coli transformant, and a cell-free extract was employed as catalyst (0.14wt% cell-free extract) in 0.1m sodium phosphate buffer (pH 7.2) at 25 °C containing 0.18 m 5-fluoro-l,3-dicyanobenzene. After 72 h, the conversion was >98% and the reaction was stopped by addition of phosphoric acid (pH 2.4) to yield 5-fluoro-3-cyano-benzoic acid as a crystalline product (97% isolated yield). 

Heating of isopropanol under conventional reflux conditions, with 2,4,6-trimethyl-benzoic acid and a catalytic amount of sulfuric acid, afforded the corresponding isopropyl ester in only 2% conversion after 28 h. With the MBR, the product was isolated in 56% yield after 1 h at 148°C[26] (Scheme 2.1 - please note that in all schemes herein, the use of a double headed arrow does not imply a balanced equation). 

Buchanan and coworkers113c investigated the reaction of 2,3,5-tri-O-benzyl-D-ribofuranose with (ethoxycarbonylmethylene)triphenyl-phosphine in anhydrous 1,2-dimethoxyethane in the presence of a catalytic amount of benzoic acid. The alkenic products were isolated in high yield, and each was converted into an anomeric mix-... 

Figure 1. Optical photomicrographs of benzoic acid, obtained at a magnification of lOOX, for product isolated from (a) acetone-water, (b) methanol-water, and (c) water.

The oxidation of benzaldoxime with perchloryl fluoride (FClOj) has been reported [29 a) to give a complex mixture in which benzaldoxime benzoate and diphenyl oxadiazole are the main products. Sodium nitrohydroxamate [Na2(02NN0)] has been reported [99b) to oxidize benzyl chloride to a mixture of compounds from which benzyl alcohol, benzaldehyde, benzoic acid, 3,4,5-triphenylisoxazole, benzyl-ethyl-ether, phenylnitromethane and diphenyloxadiazole have been isolated. 

In a similar way, chiral, nonracemic 5-alkyl-4-imidazolidinones 8 can be prepared from chiral, nonracemic a-ami no acids 53. The enantiomerically pure starting material is transformed into the intermediate imine 6, which is cyclized with acid, then A -acylated. The major diastereomer, the more stable /ram-isomer, is obtained enantiomerically pure. The minor, enantiomerically pure ci.s-isomer can also be isolated from this product mixture3. Alternatively, the civ-isomer can be prepared by heating the imine 6 with benzoic acid anhydride, which results in a good yield and d.r. However, due to some raeemization during the reaction, the ee is <100%. 

A reactor was charged with a benzoic acid-acrylic ether derivative (81 mmol), 2,5-dihydroxybenzaldehyde (37 mmol), 4-dimethylaminopyridine (22 mmol), and 200 ml of CH2CI2 and then treated with the dropwise addition of 1,3-dichlorohexylcarbodi-mide (81 mmol) dissolved in 100 ml of CH2CI2. After the addition the mixture was stirred at ambient temperature for 10 hours and a precipitate formed that was removed and the organic layer was washed with water, dried with MgSOzt, and concentrated. The residue was purified by column chromatography, recrystallized from ethanol, and 27 mmol of product isolated. 

To a solution of 2.00 grams (0.00454 mole) of K[Cr(HO-A)2] in 200 ml. of water, cooled to 6° C., were added 12.8 grams of benzoyl chloride and a solution of 2.00 grams of potassium bicarbonate in 20 ml. of water. This mixture was stirred in an ice bath for 30 minutes and then for an additional hour out of the bath. The solution was acidified with concentrated nitric acid, and then filtered to remove benzoic acid. From the filtrate only starting material (infrared spectrum ) and its decomposition products could be isolated. 

Bromination of l,2-dihydro-l-methylbenzo[d][l,2,3]diazaborine (188 X = Y = H) gave substitution in the 4-position to give (188 X = Br, Y = H). Oxidation of the brominated product with potassium permanganate led to the isolation of 2-bromobenzoic acid, which was erroneously taken as evidence for bromination in the 5-position. However, a more careful oxidation gave benzoic acid, suggesting that the original procedure oxidized the bromine atom to elemental bromine, which then carried out a deboronating bromination. 

Pyrimido[4,5-d]pyridazine derivatives are readily cleaved under both acidic and basic conditions. Reaction of 2-phenyl-5,8-dimorpholinopyrimido[4,5-hydrochloric acid gives a mixture of four isolated products 2-phenyl-8-morpholinopyrimido[4,5-d]pyridazin-5(6//)-one (96), 4-hydroxy-6-morpholinopyridazin-3(2jy>one (97), 4-amino-5-formyl-3,6-dimorpholinopyridazine (98) and benzoic acid (99). 

After reaction of 6-14C-DON with glutaminase, glutamic acid (1 equivalent) and I4C-methanol (0.75 equivalent) were isolated from the reaction mixture. The initial product formed from the C-6 atom appears to be diazomethane Ha). If relatively high concentrations of a benzoic acid-benzoate buffer are included in the reaction mixture, labeled methyl benzoate is formed in addition to the methanol. Further, the relative... 

Flash vacuum pyrolysis of cocaine 1 at 550°C results in complete conversion to thermal degradation products. The major products isolated were benzoic acid (100%), N-methylpyrrole (74%) and methyl 3-butenoate (60%). 

There is no standard, universal, procedure for the Birch reduction. Experiment 7.19 illustrates some of the variants which have been reported in the literature. The original Birch procedure is to add small pieces of sodium metal to a solution of the aromatic compound in a mixture of liquid ammonia and the proton source (ethanol).18 After completion of the reaction, which is usually indicated by the disappearance of the blue colour, it is quenched by the addition of ammonium chloride and the ammonia allowed to evaporate before the cautious addition of water, and isolation of the product by ether extraction. In a modified procedure a co-solvent (ether, tetrahydrofuran, etc.) is initially added to the solution of aromatic compound/liquid ammonia prior to the addition of metal lithium metal is often used in place of sodium.19a,b In general these latter procedures are used for substrates which are more difficult to reduce. Redistilled liquid ammonia is found to be beneficial since the common contaminant iron, in collodial form or in the form of its salts, has a deleterious effect on the reaction.20 A representative selection of procedures is given in Expt 7.19 for the reduction of o-xylene, anisole, benzoic acid, and 3,4,5-trimethoxybenzoic acid. 

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