Acidity continued indole

Indole-3-Acetic Acid. Dissolve 21.6 g of phenylhydrazine in 300 ml 0.3 N sulfuric acid. To this solution add 9.8 g of coned sulfuric acid. With stirring and heating to 100°, add dropwise 11.6 g of methyl-beta-formyl-propionate in 300 ml of 0.3 N sulfuric acid. Continue the heating and gentle stirring for 6 hours to get about 14 g of indole-3-acetic acid. This is from CA, 72, 66815 (1970). 

Lanthanide based Lewis acids continue to play pivotal roles in expediting electrophilic substitution reactions of both pyrroles and indoles vide infra). To the point, pyrroles (e.g., 63) have been found to undergo efficient conjugate addition with electron deficient olefins 66 in the presence of a catalytic amount of indium trichloride to afford the Michael adducts 67 <01TL8063>. 

To 21.6 g phenylhydrazine dissolved in 300 ml 0.3N sulfuric acid, add 9.8 g concentrated sulfuric acid. Add dropwise with stirring and heating at 100°, 11.6 g methyl-beta-formyl-propionate in 300 ml 0.3 N sulfuric acid and continue heating six hours to get 14 g indole-3-acetic acid. Convert to the dialkyltryptamine as already described. 

Due to the biological significance of some azoles (pyrrole, indole, imidazole, benzimidazole) and the consequences of acid-base equilibria in their functions, a continuous interest in the behavior in water is to be expected. To quote a significant approach, imidazole is being used to determine the intra- and extracellular acidity by H-NMR (82MI4 86UP13). 

To a stirred suspension of 4.6 g (13.8 mmoles) of the (S)-3-(2-hydroxyethyl)-5-(2-oxo-l,3-oxazolidin-4- ylmethyl)-lH-indol-2-carboxylic acid ethyl ester in 42 ml of dichloromethane were added 4.2 ml of pyridine, 3.9 g (20.7 mmoles) oftosyl chloride and 170 mg (1.38 mmoles) of dimethylaminopyridine and the stirring continued at room temperature for 20 hours. The reaction mixture was poured over 20 ml of 3 N, HCI precooled to 0°C and extracted twice with dichlormethane. The organic phases were washed with brine, dried on anhydrous sodium sulphate and the solvent evaporated to dryness. The evaporated solid was crystallised with isopropyl alcohol to give 6.4 g (95%) of the title compound as a white crystalline solid. Melting point 166.4°-168.2°C. 

SYNTHESIS To a 50 °C warmed mixture of 60 mL glacial acetic acid and IS mL acetic anhydride, there was added 66 g crystalline ammonium acetate, and stirring continued until solution was complete (20 min). To this there was added a solution of 87 g indole 3-carboxaldehyde (see under a-MT for preparation) and 300 mL nitropropane in 360 mL acetic acid. The mixture was held at reflux temperature for... 

SYNTHESIS To a well-stirred, ice cold solution of 5.0 g indole in 75 mL TBME, there was added a solution of 6.35 g oxalyl chloride in 25 mL CH2CI2. dropwise, over the course of 15 min. Stirring was continued for an additional 10 min, and the resulting solids were removed by filtration and washed with 15 mL cold TBME. This solid amide was, in turn, added portionwise over a period of 10 min to a well-stirred, ice cold solution of 15 mL N-buty 1-N-methyl amine in 100 mL CH2CI2. The clear, red solution that resulted was stirred for a few additional minutes, washed in sequence with H2O, % aqueous hydrochloric acid, and then H2O. Following... 

The isomerization proceeds via an intermediate compound that is symmetrical at the C-8 position and that exhibits a continuous conjugated system of double bonds stretching from the enol double bond up to the indole system. Thus, isomerization of dihydrolysergic acids, in... 

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