5- dipyrromethane

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... 

Unsymmetrically substituted dipyrromethanes are obtained from n-unsubstitued pyrroles and fl(-(bromomethyl)pyiToIes in hot acetic acid within a few minutes. These reaction conditions are relatively mild and the o-unsubstituted pyrrole may even bear an electron withdrawing carboxylic ester function. It is still sufficiently nucleophilic to substitute bromine or acetoxy groups on an a-pyrrolic methyl group. Hetero atoms in this position are extremely reactive leaving groups since the a-pyrrolylmethenium( = azafulvenium ) cation formed as an intermediate is highly resonance-stabilized. 

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). 

New electrophilic substitution reaction methods for the preparation of dipyrromethanes have been reported. The condensation of IV-methylpyrrole with benzaldehyde leading to the corresponding dipyrromethane was promoted by the addition of the organic catalyst, pyrrolidinium tetrafluoroborate <06T12375>. The reaction between pyrrole and N-tosyl imines promoted by metal triflates gave dipyrromethanes whereas tripyrromethane byproducts were not observed <06T10130>. 

Iodopyrroles 199 can be conveniently deiodinated with formate as the hydride donor in the presence of Pd(0) [145]. This transformation is particularly important in the synthesis of dipyrromethanes for porphyrins and for linear pyrroles. Interestingly, no reaction occurs in refluxing THF. 

A detailed study of the electronic, vibrational, and e.s.r. spectra of a series of substituted dipyrromethane complexes of nickel(ii) has been reported." The reduction of the nickel(ii) 1,19-diethoxycarbonyltetradehydrocorrin cation with a sodium film in THF under high vacuum gives both one- and two-electron reduction products. The one-electron reduction product is a very stable free radical, and the other product is formulated as a Ni" species with the two extra electrons located in ligand n-orbitals. The structures of nickel-(ii)-octaethylporphin and nickel(ii)-deoxophylloerythrin methyl ester-1,2-... 

This enzyme [EC 4.3.1.8], also known as hydroxymethyl-bilane synthase, catalyzes the dipyrromethane-depen-dent reaction of four porphobilinogen molecules with water to produce hydroxymethylbilane and four molecules of ammonia. In the presence of a second enzyme, uroporphyrinogen-III synthase [EC 4.2.1.75], the product is cycUzed to form uroporphyrinogen-III. 

The oldest methods for synthesis involve the condensation-cyclization of trifluor-omethyl or fluoroalkyl pyrroles in the presence of a metal salt. These reactions afford tetrakis(fluoroalkyl) porphyrins. The electrophilic trifluoromethylation of porphyrins is selective and leads to /I-CF3 and meso-CVT, porphyrins. While condensation of meio-trifluoromethyl-dipyrromethane with an aldehyde in acidic medium is rather difficult, it proceeds with better yields and permits a selective introduction of trifluoromethyl groups in meso The Ruppert reagent (CF3TMS) has been used to... 

The first porphyrin containing fiiran and thiophene subunits adjacent to each other was accomplished by the 2+2 condensation of dipyrromethane and (meso-aryljfurylthienylmethane <99TL8879>. 

Daub, Grimme, and coworkers have reported chiroptical switches based on binaphthyl boron dipyrromethane (BDP) conjugates. It is known that BDP dyes with appropriate functionalization can be reversibly oxidized and reduced.58 The CD-spectroelectrochemical studies of R-56 show a decrease in the intensity of the Cotton effect at 501 nm by applying a reduction potential to the solution. The initial CD spectrum is restored completely after reoxidation thus, the CD signal intensity at 501 nm for R-56 can be switched on and off electrochemically.59... 

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. 

The ion (97), acting as an electrophilic reagent, can also attack another molecule of the heterocyclic compound. Thiophene with benzaldehyde or chloral gives the dinuclear product (100 R = Ph, CC13). Pyrrole and furan react with acetone to form tetranuclear derivatives of type (101 Z = NH, O). Pyrroles with a single free position react analogously to thiophene e.g. two molecules of 3-ethoxycarbonyl-2,4-dimethylpyrrole with formaldehyde afford the dipyrromethane (102). 

Monoazaporphyrins were first prepared using [2 4- 2] dipyrromethane condensation methods by Fischer et al.2 Later, Johnson et al. improved the yield to a moderate level ( 58%) by cyclization of 1,19-dibromobiladiene-a,c with NaN3.177 Syntheses of metallomonoazaporphyrins via oxophlorin intermediates have also been reported (Scheme 51),2,181... 

Cyclophanes are known to be efficient receptors for aromatic compounds in protic solvents. Thus, linking a cyclophane unit to a porphyrin, like in 193, provides an excellent way to study the oxidation of aromatic hydrocarbons [117]. The synthesis of 193 took advantage of an earlier protocol for the preparation of strapped porphyrins [118] using the bis-dipyrromethane 194 already linked to the cyclophane as a valuable precursor for an acid catalyzed condensation leading to the porphyrin in 9% yield (Fig. 32). 

Four different synthetic procedures have been examined for the preparation of the triphenyl derivative, the fourth one suggested by the synthetic conditions developed to obtain the diphenyl derivatives. In the first three procedures it has been impossible to isolate the triphenyl-dihydrobilin. Its formation has been demonstrated, however, by monitoring the electronic spectrum of the reaction mixture and the cyclization to corrole has been carried out in situ. The synthesis that gave the highest yield (20%) and that avoids tedious purification procedures is outlined in Fig. 10. It involved the acidic condensation of benzaldehyde with two equivalents of 3,3, 4,4 -tetramethyl-meso-phenyl-dipyrromethane-5,5 ... 

The synthesis of cobalt meso-diphenyl corrolates has also been reported [31]. The synthetic procedure involves the acidic condensation of 3,4-dimethyl-2-(a-hydroxybenzyl)pyrrole-5-carboxylic acid with 3,3, 4,4 -tetramethyl dipyrro-methane, followed by reaction with cobalt salts. The reaction afforded a mixture of two isomers Co(5,15-OMDPC)PPh3 and Co(5,10-OMDPC)PPh3. The formation of this latter isomer has been explained by the high tendency of self condensation of the starting pyrrole under the reaction conditions, 2-(a-hydroxybenzyl)meso-phenyl dipyrromethane can be formed. This species would afford the Co(5,10-OMDPC)PPh3 by further condensation with the dipyrromethane unit present in excess in the reaction mixture. 

Pyrrolidinium tetrafluoroborate (105) serves as an organocatalyst for the reaction of benzaldehyde with A-methyl pyrrole, to give the corresponding dipyrromethanes (106) under mild conditions.301 Initial formation of an iminium ion by condensation of the aldehyde with the catalyst is proposed. 

Alternative approaches for substituted porphyrins have been devised in which pre-functionalized dipyrromethane derivatives 3 are condensed with similar diformyl dipyrromethanes 4 through a "2+2" condensation to form meso-tetraarylporphyrins 5 (Scheme 3). Such condensations are usually catalyzed by acids and the intermediate porphyrinogens are oxidized by air to obtain porphyrins. In a similar "3+1" synthetic approach, tripyrranes 6 are condensed with 2,5-diformylpyrroles to form etioporphyrin 5 (1996CEJ1197). 

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