Dissolving metals pyrroles

Reduction of isoindoles with dissolving metals or catalytically occurs in the pyrrole ring. Reduction of indolizine with hydrogen and a platinum catalyst gives an octahydro derivative. With a palladium catalyst in neutral solution, reduction occurs in the pyridine ring but in the presence of acid, reduction occurs in the five-membered ring (Scheme 38). Reductive metallation of 1,3-diphenylisobenzofuran results in stereoselective formation of the cw-1,3-dihydro derivative (Scheme 39) (80JOC3982). 

Apart from catalytic hydrogenation and dissolving metal methods, very few other techniques exist for the reduction of the pyrrole ring. However, one example is the improved use of hypophosphorus acid that has been described by Scott and coworkers in a reduction of pyrrole-2-carboxylic acid to the prolyl hydroxylase inhibitor (5)-3,4-dehydroproline (after resolution) (equation 10). r,—A i, HI, AcOH, H3PO2... 

Pyrrole is soluble in alcohol, benzene, and diethyl ether, but is only sparingly soluble in water and in aqueous alkaUes. It dissolves with decomposition in dilute acids. Pyrroles with substituents in the -position are usually less soluble in polar solvents than the corresponding a-substituted pyrroles. Pyrroles that have no substituent on nitrogen readily lose a proton to form the resonance-stabilized pyrrolyl anion, and alkaU metals react with it in hquid ammonia to form salts. However, pyrrole pK = ca 17.5) is a weaker acid than methanol (11). The acidity of the pyrrole hydrogen is gready increased by electron-withdrawing groups, eg, the pK of 2,5-dinitropyrrole [32602-96-3] is 3.6 (12,13). 

A 50-liter three-neck reaction flask containing 30 liters of propionic acid was mixed with a solution of pyrrole (6.0 mol) dissolved in 583 ml of toluene and 2-pyridinecar-boxaldehyde (6.0 mol) dissolved in 432 ml toluene and then refluxed for 1 hour. The dark red-brown mixture was then stirred for 18 hours at ambient temperature and then filtered and concentrated. The residue was diluted with 5 ml toluene and then reconcentrated, this process being repeated three times. The residue was then added to 5 ml ethyl acetate and stirred 18 hours, filtered, diluted in CH2CI2, and purified with flash column chromatography on silica gel using CF C /triethylamine, 98 2, respectively. Relevant fractions were combined and concentrated and a black granular solid isolated, which was diluted with 10% aqueous ammonium hydroxide, and then stirred for 2 hours and filtered. The washed solids were dried and the product isolated as a deep metallic purple solid in 2% yield. 

White, small crystals or cryst powder odorless and stable in air affected by Light. Poisonl One gram dissolves in 20 ml water, 5 ml boiling water, 300 ml alcohol practically insol in ether. Protect from light On adding NaOH to its aq soln a yellowish-white ppt forms which is reduced to metallic Hg by heat heated with zinc dust, pyrrole evolves which colors a pine splinter moistened with HCI red. The aq soln is not pptd by albumin. 

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