Pyrrolium cations

However, pyridine and pyrrole are significantly less basic than either of their saturated analogues. The pyridinium cation has pATa 5.2, making pyridine a much weaker base than piperidine, whereas the pyrrolium cation (pATa - 3.8) can be considered a very strong acid, and thus pyrrole is not at all basic. 

Thus, pyrrole and acetone react as shown above. This involves pyrrole acting as the nucleophile to attack the protonated ketone in an aldol-like reaction. This is followed by elimination of water, facilitated by the acidic conditions. This gives an intermediate alkylidene pyrrolium cation, a highly reactive electrophile that reacts with another molecule of nucleophilic pyrrole. We then have a repeat sequence of reactions, in which further acetone and pyrrole molecules are incorporated. The presence of the two methyl substituents from acetone forces the growing polymer to adopt a planar array, and this eventually leads to a cyclic tetramer, the terminal pyrrole attacking the alkylidene pyrrolium cation at the other end of the chain. 

Porphyrin rings are formed in nature by a process that is remarkably similar to that shown above. Though the sequence contains some rather unusual features, the coupling process also involves nucleophilic attack on to an alkylidene pyrrolium cation. This may be generated from the precursor porphobilinogen by elimination of ammonia. 

The linear tetrapyrrole has methylene bridges between the pyrrole rings we start from porphobilinogen that has either -H or -CH2NH2 as the ring substituents at these positions. Since the nitrogens are lost, we should consider an elimination, and this is assisted by the pyrrole nitrogen. We can consider protonation of the amine to facilitate the elimination. The product is an electrophilic methylidene pyrrolium cation. 

Pyrrole is very reactive towards electrophiles charge distribution from the nitrogen makes either C-2 (or C-3) electron rich. Thus, a second porphobilinogen acts as the nucleophile towards the methylidene pyrrolium cation in a conjugate addition reaction. It is now possible to see that two further identical steps will give us the required linear tetrapyrrole, and that one more time will then achieve ring formation. 

The 2H- and 3Af-pyrrolium cations are essentially iminium ions and as such are electrophilic they play the key role in polymerisation (see 16.1.8) and reduction (16.7) of pyrroles in acid. In the reaction of pyrroles with hydroxylamine hydrochloride, which produces ring-opened 1,4-dioximes, it is probably the more reactive 37f-pyrrolium cation that is the starter. Primary amines, RNH2, can be protected, by conversion into l-R-2,5-dimethylpyrroles (16.16.1.1), recovery of the amine being by way of this reaction with hydroxylamine." ... 

Condensations of pyrroles with aldehydes and ketones oceur easily by acid catalysis, but the resulting pyrrolyl-carbinols cannot usually be isolated, for under the reaction conditions proton-catalysed loss of water produces 2-alkylidene-pyrrolium cations that are themselves reactive electrophiles. Thus, in the case of pyrrole itself, reaction with aliphatic aldehydes in acid inevitably leads to resins, probably linear polymers. Reductive trapping of these cationic intermediates, producing alkylated pyrroles, can be synthetically useful, however all free positions react acyl and alkoxycarbonyl-substituents are unaffected. ... 

The mineral-acid-catalysed polymerisation of pyrrole involves a series of Mannich reactions, but under controlled conditions, pyrrole can be converted into an isolable trimer, which is probably an intermediate in the polymerisation. The key to understanding the formation of the observed trimer is that the less stable, therefore more reactive, P-protonated pyrrolium cation is the electrophile that initiates the sequence, attacking a second mole equivalent of the heterocycle. The dimer , an enamine, is too reactive to be isolable, however pyrrole trimer , relatively protected as its salt, reacts further only slowly. ... 

HOMO 1,2-dimethoxyacetylene comparable to the FMO changes for acetylene addition to pyrrole. As stated previously, the addition of acetylene to the pyrrolium ion should be examined separately because of its charge the full localization of double bonds on the pyrrole ring (an ideal diene for a Diels-Alder reaction), and the charge in the pyrrolium cation result in an exceptionally low LUMO energy. 

In solution, reversible proton addition occurs at all positions, being by far the fastest at the nitrogen, and about twice as fast at C-2 as at C-3. In the gas phase, mild acids like C4H9 and NH4 protonate pyrrole only on carbon and with a larger proton affinity at C-2 than at C-3. Thermodynamically the stablest cation, the 2H-pyrrolium ion, is that formed by protonation at C-2 and observed values for pyrroles are for these 2-protonated species. The weak A -basicity of pyrroles is the consequence of the absence of mesomeric delocalisation of charge in the H-pyrrolium cation. 

Scheme 13.16. The initial steps in the formation of an Af-methyl-A -pyrrolium cation. Pyridoxal phosphate-catalyzed decarboxylation of ornithine (ornithine decarboxylase, EC 4.1.1.17) yields bntane-1,4-diamine (pntresdne). Ar nine (Arg,R) also nndergoes pyridoxal phosphate-catalyzed decarboxylation (arginme [Arg,R] decarboxylase,EC4.1.1.19) to agma-tine and then hydrolytic loss of nrea (agmatinase, EC 3.5.3.11) to prodnce the same diamine. Methylation on nitrogen by 5 -adenosylmethionine is catalyzed by pntrescine N-methyltransferase (EC 2.1.1.53). EC nnmbers and some graphic materials provided in this scheme have been taken from appropriate links in a URL starting with http7/ www.chem.qmul.ac.uk/iubmb/enzyme/.

The reaction of nicotinic acid with the A-methyl-A -pyrrolium cation has been shown to involve exchange at C-6 as shown in Scheme 13.19. 

As recently pointed out, the joining of the two pieces (i.e., the A-methyl-A -pyrrolium cation to the pyridine ring) to produce nicotine occurs with the participation of enzymes whose nature remains poorly characterized. Indeed, the condensation process itself with labeled materials is not, even at this writing, as clean an experiment as is desirable. Nonetheless, it appears that it is widely accepted that a hydride source donates a hydrogen, with its pair, to C-6 of the nicotinic acid, and a (tritium) label originally placed there is lost as the condensation reaction is consummated. 

Scheme 13.19 A cartoon representation of a possible path to (-)-nicotine from a combina-tion of nicotinic acid with an A-methyl-A -pyrrolium cation. There is no evidence that the source of hydride is NADH or NAD(P)H, and it is shown to be so here only as a matter of convenience. As noted earlier, the enzymes involved are currently poorly characterized. ...

Scheme 13.20. Some indications of the pathways available for the conversion of Af-methyl-A -pyrrolium cation to tropine and pseudotropine ( r-tropine) by reaction with an acetate-derived representative fragment.

Although it is not easy to compare the electrochemical stabilities of different ILs, it is known, as described above, that the cations and anions of ILs have an impact on the electrochemical window. The cation species affect the reduction limit potential. l-Alkyl-3-methylimidazolium cations are easily reduced due to the presence of the hydrogen atom at the 2-position of the imidazole ring. When this position is substituted with an alkyl group, the reduchon stability is improved. The reduction stability of aliphatic quaternary ammonium and pyrrolium cations is higher than that of l-alkyl-3-methylimidazolium cations. The structure of the anion affects the oxidation potential. Some anions such as F2..3HF", N(CN)2, and C(CN)3 are easily oxidized, and other anions such as BF4, PFg, and N(CF3S02)2 have a relatively higher oxidation potential and present better oxidation stability. 

As far as regioselectivity and structure of the dihydropyrrolium cations 5 are concerned, the reactions of 2-substituted N-vinylpyrroles with HX (X=C1, Br) give the same ontcomes. This is confirmed by nearly complete concordance of their H NMR parameters including spin-spin coupling constants. The main distinction is that the addition of HBr is almost exhaustive, whereas for HCl, owing to weaker nucleophi-licity of chloride ion, the equilibrium is shifted toward pyrrolium cation 3. 

The reason for the different behaviors of 2-(2-furyl)pyrrolium cations in the superacidic medium and in the presence of hydrogen halides at temperature iuCTease is likely the higher stability of the cations in HSO3F and CF3COOH as compared to systems containing hydrogen halides. 

Selective protonation of the pyrrole ring at a low temperature can be considered as the kinetic result leading to thermodynamic nonequilibrium state with predominance of pyrrolium cations 12, the energy value of which is comparable with that of their furanium isomers 13. When temperature rises, the system reaches equilibrium and concentration of isomeric cations 12 and 13 levels off according to their energies. 

The low basicity of pyrrole is a consequence of the loss of aromaticity which accompanies protonation on the ring nitrogen or on carbon 2 or carbon 3 of the ring. The thermodynamically most stable cation is the 2H-pyrrolium ion, and the p/sTa for protonation at C-2 has been recorded as -3.8 the corresponding pK values for protonation at C-3 and at nitrogen are -5.9 and ca. -10 (Scheme 7). 

From the pyrrolinium-furanium ion equilibrium (Scheme 62) one can assume, in agreement with CTp values (—1.7 and —0.86 for 2-pyrrolyl and 2-furyl, respectively), that the pyrrole ring stabilizes the adjacent furanium cation better than vice versa. Thus, the selective pyrrole ring protonation at low temperature (—80 C) is most likely a kinetic result leading to the thermodynamically nonequilibrium state with the predominance of pyrrolium ions. 

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