Dipyrromethenes dipyrromethanes

The synthetic world of porphyrins is extremely rich and its history began in the middle of 1930s. An enormous number of synthetic procedures have been reported until now, and the reason can be easily understood analysing the porphyrin skeleton. In principle, there are many chemical strategies to synthesized porphyrins, involving different building blocks, like pyrroles, aldehydes, dipyrromethanes, dipyrromethenes, tripyrranes and linear tetrapyrroles. 

Naturally occurring porphyrins are usually symmetrically substituted about the 15-methine bridge. These porphyrins can be synthesized by the condensation of two dipyrroiic intermediates. Typical dipyrroiic intermediates in current use arc the dipyrromethanes and the dipyrromethenes. Both methods will shortly be described. This again is a highly specialized... 

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. 

The pyridine-like nitrogen of the 2H-pyrrol-2-yiidene unit tends to withdraw electrons from the conjugated system and deactivates it in reactions with electrophiles. The add-catalyzed condensations described above for pyrroles and dipyrromethanes therefore do not occur with dipyrromethenes. Vilsmeier formylation, for example, is only successful with pyrroles and dipyrromethanes but not with dipyrromethenes. 

This reaction sequence is much less prone to difficulties with isomerizations since the pyridine-like carbons of dipyrromethenes do not add protons. Yields are often low, however, since the intermediates do not survive the high temperatures. The more reactive, faster but less reliable system is certainly provided by the dipyrromethanes, in which the reactivity of the pyrrole units is comparable to activated benzene derivatives such as phenol or aniline. The situation is comparable with that found in peptide synthesis where the slow azide method gives cleaner products than the fast DCC-promoted condensations (see p. 234). 

Aromatic species include the neutral molecules pyrrole, furan and thiophene (1 Z = NH, O, S) and the pyrrole anion (2). The radicals derived from these rings are named pyrryl, furyl and thienyl. The 2-furylmethyl radical is called furfuryl. Compounds in which two pyrrole nuclei are joined by a CH2 group are called dipyrromethanes when the linkage is by a CH group, they are named dipyrromethenes . The 2- (3) and 3-pyrrolenines (4) are isomeric with the pyrroles, but are nonaromatic as the ring conjugation is broken by an. s/r -hybridized carbon atom. 

Pure individual porphyrins such as (4)-(7) can, however, be synthesized using dipyrroles, and these approaches will be briefly discussed later in this section. If two dipyrrole units (8) and (9) with an appropriate future meso-carbon are reacted together with the intention of preparing porphyrin (10), there is actually a maximum of three possible products, (10) (12) (Scheme 3). This is because the two dipyrroles can either react with themselves, or (as required) with each other. If the dipyrroles do not possess attached (future) meso-carbon atoms (e.g., (13) and (14)) and also bear an unsymmetrical arrangement of substituents (indicated by the A and B labels on each pyrrole— oxidation levels, i.e., dipyrromethene or dipyrromethane, not defined), even greater mixtures can occur—in this case, porphyrins (15)-(20) (Scheme 4). Such symmetry problems are common with all so-called [2 + 2] syntheses. However, if a porphyrin synthesis involving two dipyrroles is to be attempted, the symmetry problems can often be overcome if one of the two dipyrroles is symmetrical about its interpyrrolic (5-) carbon atom (e.g., synthesis of (6) from (21) and (22), Scheme 5). 

The two most common dipyrroles used in porphyrin syntheses are the dipyrromethanes (39) and dipyrromethenes (40) the latter are usually handled as their highly crystalline hydrohalide salts (e.g., (41)) (Scheme 10). Collectively, such syntheses of porphyrins using dipyrroles are know as [2 + 2] approaches. 

It is also possible to self-condense 1,9-diunsubstituted dipyrromethanes in the presence of a one-carbon unit (formaldehyde, orthoformic ester). Because of the non-nucleophilicity of protonated dipyrromethenes (e.g., (41)) this approach only works well for dipyrromethanes. Using this methodology, and with trimethyl orthoformate as the one-carbon unit and trichloroacetic acid as the catalyst, coproporphyrin-II tetramethyl ester (71) can be obtained in good yield from the dipyrromethane-1,9-dicarboxylic acid (72) (Scheme 21) 45... 

The presence of an a-free pyrrole attached to the native HMBS was also demonstrated, both in Cambridge and Southampton, by treatment with Ehrlich s reagent, acidic p-dimethylaminobenzaldehyde [30, 33]. This initially gave the UV/visible absorbance at 564 nm, typical of the Ehrlich product from an a-free pyrrole, but the spectrum then changed to one at 495 nm, typical of a dipyrromethene, indicating that the cofactor is in fact a dipyrromethane (e. g. 32), as shown in Scheme 11 and tautomerisation of the initial product 33 occurs to give 34. 

Dioxane, 2-oxo-, 321 Diphenimide, methylation of, 255 Dipyrromethanes, 5,5 -dihydroxy-, tautomerism of, 13 Dipyrromethenes, 4 Diskatoles, 303 Diskatyl, 303... 

The reaction comprises the following steps reduction of 2-trifluoroacetylpyrroles, condensation of the alcohols formed with pyrroles to dipyrromethanes (Scheme 2.187, Table 2.18), their oxidation to dipyrromethenes, and complex formation of the latter with boron trifluoride. The last two stages proceed in a one-pot manner. 

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