Pyrrole-3-carboxylic acid, acidity

Grignard reagent from, acylation, 4, 237 nitration, 4, 211 reactivity, 4, 71-72 synthesis, 4, 149, 237, 341, 360 Pyrrole-3-carboxylic acids acidity, 4, 71 decarboxylation, 4, 286 esterification, 4, 287 esters... 

Pyrrole Carboxylic Acids and Esters. The acids are considerably less stable than benzoic acid and often decarboxylate readily on heating. However, electron-withdrawing substituents tend to stabilize them toward decarboxylation. The pyrrole esters are important synthetically because they stabilize the ring and may also act as protecting groups. Thus, the esters can be utilized synthetically and then hydrolyzed to the acid, which can be decarboxylated by heating. Often P-esters are hydrolyzed more easily than the a-esters. 

Figure 16 Principal mass spectrometric fragmentations for pyrrole carboxylic acids and esters...

In Table II the pK s of the 2- and 3-carboxylic acids of thiophene, furan, and pyrrole are reported. While pyrrole carboxylic acids, like the alkoxy- and amino-substituted benzoic acids, are weaker, thiophene- and furan carboxylic acids, like the chloro-and bromobenzoic acids, are stronger than unsubstituted benzoic acid. This behavior is confirmed by other side-chain reactivity data.41... 

Aminopyridones form diazo anhydrides (e.g., 758) (cf. aminophenols) which on irradiation give pyrrole carboxylic acids, e.g., 760 via 759. 

Preparation of A,-methyl-4-[(A, -methyl-4-nitro-pyrrolyl-2-yl)carbonylamino]-pyrrole-carboxylic acid chloride... 

As in the furan series, the loss of an OH or an -OR group is very favored in pyrrole carboxylic acids and esters, (53)->[51]. The presence of an N—H group in a-pyrrole carboxylic esters causes also the elimination of an ROH fragment,41 (53)->[54]. 

Basic hydrolysis of the l/7-pyrrole-2-carboxylate 1280, obtained in 71% yield by a procedure similar to described <2000JOC2479> (by alkylation of the corresponding NH-pyrrole with 3,4-dimethoxyphenethyl methanesulfonate (N2, NaH, DMF, 70 °C, 12 h)), with NaOH in aqueous EtOH produces the respective pyrrole carboxylic acid 1281 in 90% yield and in an analytically pure form (Scheme 246) <2003T207>. When the acid 1281 was heated with lead tetraacetate in refluxing ethyl acetate, a 52% yield of ningalin B hexamethyl ether 1282, the multidrug-resistant reversal agent, a marine natural product derivative, was obtained. 

The same reaction has been applied to a pyrrole carboxylic acid (35) and although some diazo compound (36) was formed the reaction... 

NonbasicCCR2 antagonists have also been reported. The 3-chlorobenzyl 2-pyrrole carboxylic acid (27)is a modest CCR2 antagonist... 

Triple bromination of A -TIPS-pyri ole (6) with NBS affords tribromopyrrole 12 (97%) [22], which can either be deprotected to afford the marine acorn worm metabolite 2,3,4-tribromoindole 13 [22,23] or lithiated selectively at C-2 to give, after quenching with carbon dioxide, pyrrole carboxylic acid 14 [24],... 

The results of earlier attempts - to assign a structural formula to the neuraminic acids were not substantiated by the chemical characteristics of the chromatographically homogeneous substances. The first clue to their true structure arose from the work of Hiyama and of Gottschalk -on the composition of the carbohydrate prosthetic group of homogeneous urinary and submaxillary sialoproteins. These workers isolated 2-pyrrole-carboxylic acid " in very small yield (0.05%) from alkaline hydrolyzates of the sialoproteins. 

Tripeptide 220 is prepared from amino pyrrole 218 and pyrrole carboxylic acid 219 using DEPC and NEt3.82... 

Methylpyrrole is used in excess to be sure that no butyllithium is present during the reaction with C02 the pentanoie acid formed from BuLi might give rise to difficulties in the purification of the pyrrole carboxylic acid. 

The most famous of the many alkaloids isolated so far is without any doubt batrachotoxin and its derivatives. Batrachotoxin has a LD50 of 2 ug per kg body weight (mouse, i.m.), thus being the most toxic nonprotein substance at all. Because of its special pharmacologic activity to keep open irreversably the sodium channels of nerve cells it has become an important tool in the studies of sodium channels. Chemically the batrachotoxins are esters of a 20-hydroxy steroid, batrachotoxinin A, with different pyrrol carboxylic acids. Although the activities of the different batrachotoxins is qualitatively the same, it differs quantitatively according to the acid part of the molecule (refs. 14, 15). 

Scheme 16.26. Coupling of pyrrole carboxylic acids with oligonucleotides.

Figure 4 Proposed mass spectral fragmentations of pyrrole carboxylic acids.

Intramolecular allylation with alkenyloxiranes offers a good method of macro-cyclization. In the total synthesis of roseophilin by Fiirstner, the alkenyloxirane 144 was cyclized smoothly to yield the 13-membered carbocycle 145 in high yield (85%) in the presence of two ligands DPPE and PPh3. Then Pd-catalyzed reaction of the allylic lactone 146 with benzylamine afforded the pyrrole carboxylic acid 147 cleanly in 70 % yield via regioselective allylation of benzylamine at the electron-deficient terminus of the allylic lactone 146 [52],... 

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