Porphyrin from pyrrole

This apparently extremely simple synthesis of symmetrical porphyrins from aldehydes and pyrrole has also been used to produce porphyrins with interesting stereochemical proper-... 

A mild procedure which does not involve strong adds, has to be used in the synthesis of pure isomers of unsymmetrically substituted porphyrins from dipyrromethanes. The best procedure having been applied, e.g. in unequivocal syntheses of uroporphyrins II, III, and IV (see p. 251f.), is the condensation of 5,5 -diformyldipyrromethanes with 5,5 -unsubstituted dipyrromethanes in a very dilute solution of hydriodic add in acetic acid (A.H. Jackson, 1973). The electron-withdrawing formyl groups disfavor protonation of the pyrrole and therefore isomerization. The porphodimethene that is formed during short reaction times isomerizes only very slowly, since the pyrrole units are part of a dipyrromethene chromophore (see below). Furthermore, it can be oxidized immediately after its synthesis to give stable porphyrins. 

It is conceivable that related ligands, e.g. dehydrocorrins, could be obtained from pyrrolic units using pathways similar to those used for porphyrins and could be hydrogenated to corrins. This has indeed been achieved (I.D. Dicker, 1971), but it is, of course, impossible to introduce the nine chiral centres of cobyrinic acid by such procedures. 

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>. 

In terms of synthetic strategy, approaches to porphyrins from open-chain tetrapyrroles are the only truly general routes. The principle is to construct, in a stepwise manner, an open-chain tetrapyrrole bearing a pre-determined arrangement of peripheral substituents. Cyclization to produce a porphyrin, or an immediate precursor, under mild conditions which do not cause redistribution of the pyrrole rings, should be accomplished after full characterization of the open-chain intermediate. 

Dih symmetrical porphyrins such as porphin itself,7 H2TPP and H2OEP9 are conveniently prepared from pyrrole and aldehyde by cyclocondensations (Scheme 1). Addition of Zn11 ion often improves the yield.10 The product is often contaminated with chlorin by-product, which can be converted to porphyrin by oxidants such as DDQ,10 or separated by chromatography.11 Bulky substituents tend to lower the yield, and meso o-substituted phenyl groups give rise to atrope isomers. 

Reynolds et al. (1985, 1987) examined petroleum porphyrin and nonporphyrin metals independently with EPR after methanol extraction of porphyrins from the petroleum. Table IV shows the EPR-derived coordination spheres of vanadyl nonporphyrin fractions of various crudes. The Ni and V coordinated to four nitrogens (N4 type) could be petropor-phyrin precursors and derivatives as previously discussed or tetradentate-mixed ligands in which N does not necessarily come from a pyrrole group. Considerable variability in the vanadyl coordination among different crude oils is evident. Figure 4 illustrates some proposed metal complexes that may exist in petroleum (Yen, 1975). 

The reactive part of haemoglobin is a porphyrin. These are aromatic molecules with 18 electrons around a conjugated ring formed from four molecules of a five-membered nitrogen heterocycle. Chemically, symmetrical porphyrins are easily made from pyrrole and an aldehyde. 

The free base 5,10,15,20-tetraphenyl-21 A/,23//-porphine (H2tpp) may be prepared from pyrrole and benzaldehyde4 or purchased from Strem Chemicals, P.O. Box 108, Newbury Port, MA 01950 or Aldrich Chemical Co., 940 St. Paul Ave., Milwaukee, WI 53233. The material should be chlorin free, which can be effected either by dry column chromatography using alumina and chloroform or by oxidation of the chlorin to porphyrin using 2,3-dichloro-5,6-dicyano-... 

A variation of this method that removes the water produced in the pyrrole/aldehyde or hydrated aldehyde condensation has been used to produce meso-tetrakis(perfluoroalkyl)porphyrins. Lindsey s laboratory has also reported a rational synthesis of weyo-substituted porphyrins bearing one nitrogen heterocyclic group that can readily be used for preparing other mono-functionalized porphyrins, methods for minimi zing scrambling in the synthesisof tran -porphyrins from dipyrromethanes and aldehydes, and a rational synthesis of porphyrins bearing up to four different meso substituents. ... 

Woodward has pointed out that porphyrins contain pyrrole units that are on average one half of an electron away from a stable 6-ji-electron configuration [Woodward (214)]. From the presumed tendency to become aromatic pyrrole units one can deduce a metalloporphyrin resonance structure like (VIII), where the methine bridge carbons have lost n-... 

By careful choice of conditions, the simplest dipyrromethane, bis(pyrrol-2-yl)methane, can be obtained directly from pyrrole with aqueous formalin in acetic acid reaction in the presence of potassium carbonate allows 2,5-bis-hydroxymethylpyrrole to be isolated. This diol reacts with pyrrole in dilute acid to give tripyrrane and from this, reaction with 2,5-bis(hydroxymethyl)pyrrole gives porphyrinogen, which can be oxidised with chloranil (2,3,5,6-tetrachloro-p-benzoquinone) to porphine, the simplest porphyrin. 

The colours of life. An introduction to die chemistry of porphyrins and related confounds , Milgram, L. R., Oxford University Press, Oxford, 1997. The synthesis of 3-substituted pyrroles from pyrrole , Anderson, H. J. and Loader, C. E., Synthesis, 1985, 353. 

The limiting factor for practical use may be the expensive synthesis and often low yield of vinylporphyrins. (35) was prepared in a three step synthesis from pyrrol and benzaldehyde/p-nitrobenzaldehyd in an overall yield of 2%78). The picket fence porphyrin (36) is obtained in a yield of only 5%78. (35) is synthesized from the expensive protoporphyrin-IX-dimethylester (7f) with 45% yield80. ... 

Because of the occurrence of isomers, the synthesis from pyrroles is only useful for porphyrins with eight identical /8-pyrrolic and four identical methine bridge substituents. Famous examples are the syntheses of chloroform-soluble /8-octaethyl-porphyrin and meso-tetraphenylporphyrin which have been used in innumerable studies on porphyrin reactivity (K.M. Smith, 1975). Porphyrins with four long meso-alkyl side-chains can be obtained by use of analogous reactions. These porphyrins have melting points below 100 °C and are readily soluble in petroleum ether. Sulfonation of olefinic double bonds leads to highly charged, water soluble porphyrins (J.-H. Fuhrhop, 197 ). 

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