Pyrrole carboxylation

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. 

When haemin is reduced with hydriodic acid it yields a mixture of substituted pyrroles and pyrrole carboxylic adds, namely ... 

Methyl 2-pyrrole carboxylate was transformed in two steps into an N-pyrrolylalanine derivative which was converted into a pyrrolo[l,2-a]pyr-azine after heating under reflux in toluene. Five subsequent steps led to peramine (Scheme 50), a principal insect feeding deterrent, from Acremo-nium iolli (88CC978). 

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

Acid dissociation constants have also been measured for several pyrrole carboxylic acids238-243 (Table X) and attempts have been made, by taking the reaction constant p for ionization as unity, to extrapolate the a values obtained from the ionization constants of... 

A more recent development has been the synthesis of bisamidopyrrolylmethane based anion receptor systems (Figure 19).15 These receptors might be regarded as containing half a calix[4]pyrrole combined with die 2-amido appendages in common with the pyrrolic amide cleft. Compounds 19 and 20 were synthesized by reaction of diethyl-5,5 -methylenebis(4-ethyl-3-methyl-2-pyrrole) carboxylate with aniline or n-butylamine in the presence of trimethylaluminium in dry dichloromethane at 35°C in 40 and 43% respective yields. 

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... 

Physical and spectral properties of batrachotoxins are presented in Table I. Mass spectra have been presented and interpreted (3,13,14). The parent ion of batrachotoxin is virtually nondetectable by direct probe methods, and instead an apparent molecular ion of miz 399 is seen, probably because of pyrolytic elimination of the pyrrole carboxylate moiety. Batrachotoxin alkaloids do not chromatograph on capillary gas chromatographic columns, but a pyrolysis product has been detected at 280°C on the temperature-programmed, packed OV-1 columns used for analysis of other dendrobatid alkaloids (see Appendix). The pyrrole carboxylate moiety is responsible for major ions of C7H9N02 (m/z 139), C6H9N ... 

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. 

Substituted indoles are of biological interest and are not readily synthesized by conventional methods of indole chemistry. Annulation of a nuclear methyl and an a-ethoxyimine (or an imidate) under basic conditions is a promising procedure. The pyridine oxide ester (87.1) may be converted in high yields into two kinds of pyrrole carboxylic ester the potassium salt of the imidate, on heating in DMF, gives the 3-(2-oxocarboxylate) whereas dilute mineral acid leads to the 2-carboxylate ester. 

Birch reduction of pyrrole carboxylic esters and tertiary amides gives dihydro-derivatives the presence of an electron-withdrawing gronp on the nitrogen serves both to remove the acidic iV-hydrogen and also to rednce the electron density on the ring. Quenching the immediate reduced species - an enolate - with an alkyl halide produces alkylated dihydropyrroles. ... 

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