Pyrroles chlorination

Treatment of pyrrole, 1-methyl-, 1-benzyl- and 1-phenyl-pyrrole with one mole of A -bromosuccinimide in THF results in the regiospecific formation of 2-bromopyrroles. Chlorination with IV-chlorosuccinimide is less selective (8UOC2221). Bromination of pyrrole with bromine in acetic acid gives 2,3,4,5-tetrabromopyrrole and iodination with iodine in aqueous potassium iodide yields the corresponding tetraiodo compound. 

In the pyrrole series, ester groups a to nitrogen are more readily hydrolyzed by alkali, but those in a /3 position more readily by acid. A methoxycarbonyl group in the 2-positlon is meta directing thus bromination yields mainly 4-bromo-2-methoxycarbonylpyrrole. Free radical chlorination with f-butylhypochlorite gives the 5-chloro derivative. 

Reduction of indolenines with sodium and ethanol gives indolines. The pentachloropyr-role, obtained by chlorination of pyrrole with sulfuryl chloride at room temperature in anhydrous ether, was shown by spectroscopic methods to have an a-pyrrolenine (2H-pyrrole) structure (222). It is necessary, however, to postulate that it is in equilibrium with small but finite amounts of the isomeric /3-pyrrolenine form (3//-pyrrole 223), since pentachloropyrrole functions as a 2-aza- rather than as a 1-aza-butadiene in forming a cycloadduct (224) with styrene (80JOC435). Pentachloropyrrole acts as a dienophile in its reaction with cyclopentadiene via its ene moiety (81JOC3036). 

Ethylene, /3-(dimethylamino)-nitro-in pyrrole synthesis, 4, 334 Ethylene, dithienyl-in photochromic processes, 1, 387 Ethylene, furyl-2-nitro-dipole moments, 4, 555 Ethylene, l-(3-indolyl)-2-(pyridyl)-photocyclization, 4, 285 Ethylene, l-(2-methyl-3-indolyl)-l,2-diphenyl-synthesis, 4, 232 Ethylene, (phenylthio)-photocyclization thiophenes from, 4, 880 Ethylene carbonate C NMR, 6, 754 microwave spectroscopy, 6, 751 photochemical chlorination, 6, 769 synthesis, 6, 780 Ethylene oxide as pharmaceutical, 1, 157 thiophene synthesis from, 4, 899 Ethylene sulfate — see 2,2-dioxide under 1,3,2-Dioxathiolane... 

Pyrrole-3-carboxylic acid, l-benzoyl-5-bromo-2,4-dimethyl-ethyl ester chlorination, 4, 271... 

Battersby and coworkers have developed selective methods for total synthesis of chlorins on a model system, as shown in Scheme 10.15, in which the Michael addition of 5-f3-nittoethyl pyrrole to enone and reductive cyclizadon are used as key steps. "... 

Chlorophyll a, the green photosynthesis pigment, is the prototype of the chlorin (2,3-dihydro-porphyrin) class of products. It was first isolated by Willstatter1 at the turn of the century. The common structural unit in this class is the chlorin framework named after chlorophyll. The chromophore with a partially saturated pyrrole ring, which is formally derived from the completely unsaturated porphyrin, is less symmetric than the latter and systematically named according to IUPAC nomenclature as 2,3-dihydroporphyrin. 

In numerous synthetic studies4 1 b chlorins have been obtained from completely unsaturated porphyrins by reactions that occur on the periphery of the porphyrin chromophore. The main problem in these methods is the lack of regioselecttvity because each of the four pyrrole subunits... 

The formal addition of a methane molecule to a ft-pyrrolic C — C double bond can be achieved when bishydroxytin(IV) octaethylporphyrin 17 is first treated with a chloroform/aluminum tribromide mixture to give 18 which can subsequently be reduced with sodium borohydride and dcmctalated with acid to give the methylated chlorin 19.23... 

Benzoisobacteriochlorin 14 can be prepared from nickel(II) chlorin 12 by vinylogous Vilsmeier reaction to give 13 and subsequent acid-induced cyclization.22 The chlorin 12 is, as expected, alkylated in a meso position adjacent to the reduced pyrrole ring. 

As with the pyrroles, N-chloroamides have been widely employed in indole chlorination [66JOC2627 80H( 14)867 81JOC2054]. Chloroindolen-ines may be isolated under controlled conditions [80H( 14)867 81JOC2054], 2-Phenyl-, l-methyl-2-phenyl-and 3-methyl-2-phenyl-indoles were converted by 1-chloroisatin (NCI) into the 3-chloro derivatives... 

At high copper(II) chloride indole ratios the pyrrole ring of 2-methylindole was chlorinated in yields approaching 92%. This reaction is believed to involve radical cations of indoles formed in an electron-transfer process. At low copper(ll) chloride indole ratios dimers were formed [86JCS(P 1)2305]. 

Bis complexes of pyrrole-A -carbodithiolate (L) with Pt(II), Pd(II), and Co(II), as well as Cu(II), have been reported. A mixed chlorine-ligand complex of Pt(IV), [PtCl2L2], was also prepared. Infrared spectra of these complexes indicated an exocyclic single C-N bond, as opposed to similar complexes containing other dithiocarbamate ligands (407). 

In a similar way to the above, azidopropenoylfuro[3,2- ]pyrroles such as 27 can be thermolyzed in a mixture of diphenyl ether and tributylamine to give the 8-oxo-7,8-dihydropyrrolo[2, 3 4,5]furo[3,2-r]pyridines 28, again via the intermediate isocyanates. The lactam 28 can be chlorinated and reduced using standard methods (POCI3 then Zn/AcOH) to give the pyrrolo[2, 3 4,5]furo[3,2-r]pyridines 29 <1995M753> (Scheme 8). 

Subsequently, other publications have appeared involving the DA reactions of porphyrins with other dienes. For instance, the reaction of meso-tetrakis(pentafluorophenyl)porphyrin Id with the diene generated from pyrrole-fused 3-sulfolene gave rise to the isoindole-fused chlorin derivative 8 accompanied by a mixture of stereoisomeric bacteriochlorins 9 (Scheme 2) <98CC2355>. 

When a larger excess of the azomethine ylide precursors was used and the reflux was prolonged for 40 hours, the reaction afforded isobacteriochlorin 63 as the major adduct together with a small amount of bacteriochlorin 64 (Figure 5). This result demonstrates that the attack of the second azomethine ylide species to the chlorin macrocycle occurs preferentially at the adjacent P-pyrrolic double bond, yielding the isobacteriochlorin with high site selectivity. 

The large scale preparation of orthogonally protected pyrrole tricarboxylic acid derivatives (i.e., 92) was reported. A key step was the selective a-chlorination of a 2,4-dimethylpyrrole intermediate that was derived from the Knorr pyrrole synthesis. 

---