Pyrroles nitration

Since concentrated mineral acids polymerize pyrroles (pp. 59, 83), ordinary nitration methods cannot be used in the series unless deactivating groups are present. It is possible to nitrate pyrrole carboxylic acids and their esters i 121 and nitropyrroles273 with concentrated nitric acid. 

Even less dangerous in this respeet are the nitrating systems using alkyl nitrates and sodium ethoxide. Noteworthy examples of the use of these less acidic or basic nitrating systems are found in the pyrrole series. 

Silver fluorocomplexes are also used ia the separation of olefin—paraffin mixtures (33), nitration (qv) of aromatic compounds (34), ia the synthesis of (9-bridged bicycHcs (35), pyrroles (36), cyclo-addition of vinylbromides to olefins (37), and ia the generation of thioben2oyl cations (38). 

Nitration of pyrroles by the usual methods leads to extensive degradation. However, nitration can be achieved with an equimolar nitric acid—acetic anhydride mixture at low temperatures. In the case of pyrrole, the reaction leads predominandy to substitution at the -position (34), ie, in the following 51% 3-nitropyrrole [5930-94-9] (21) and 13% 2-nitropyrrole [5919-26-6] (22). 

The high reactivity of pyrroles to electrophiles is similar to that of arylamines and is a reflection of the mesomeric release of electrons from nitrogen to ring carbons. Reactions with electrophilic reagents may result in addition rather than substitution. Thus furan reacts with acetyl nitrate to give a 2,5-adduct (33) and in a similar fashion an adduct (34) is obtained from the reaction of ethyl vinyl ether with hydrogen bromide. 

Frontier orbital theory predicts that electrophilic substitution of pyrroles with soft electrophiles will be frontier controlled and occur at the 2-position, whereas electrophilic substitution with hard electrophiles will be charge controlled and occur at the 3-position. These predictions may be illustrated by the substitution behaviour of 1-benzenesulfonylpyr-role. Nitration and Friedel-Crafts acylation of this substrate occurs at the 3-position, whereas the softer electrophiles generated in the Mannich reaction (R2N=CH2), in formylation under Vilsmeier conditions (R2N=CHC1) or in formylation with dichloromethyl methyl ether and aluminum chloride (MeO=CHCl) effect substitution mainly in the 2-position (81TL4899, 81TL4901). Formylation of 2-methoxycarbonyl-l-methylpyrrole with... 

The range of preparatively useful electrophilic substitution reactions is often limited by the acid sensitivity of the substrates. Whereas thiophene can be successfully sulfonated in 95% sulfuric acid at room temperature, such strongly acidic conditions cannot be used for the sulfonation of furan or pyrrole. Attempts to nitrate thiophene, furan or pyrrole under conditions used to nitrate benzene and its derivatives invariably result in failure. In the... 

Thiophene is much more easily nitrated than benzene and it is therefore possible to use mild nitrating agents such as acetyl or benzoyl nitrate. Like pyrrole and furan the principal nitration product is the 2-derivative. The a selectivity decreases with increasing vigour of the reagent and up to 15% of the 3-isomer has been obtained. 

The general discussion (Section 4.02.1.4.1) on reactivity and orientation in azoles should be consulted as some of the conclusions reported therein are germane to this discussion. Pyrazole is less reactive towards electrophiles than pyrrole. As a neutral molecule it reacts as readily as benzene and, as an anion, as readily as phenol (diazo coupling, nitrosation, etc.). Pyrazole cations, formed in strong acidic media, show a pronounced deactivation (nitration, sulfonation, Friedel-Crafts reactions, etc.). For the same reasons quaternary pyrazolium salts normally do not react with electrophiles. 

Pyrrole, 3,4-dialkyl-2-ethyl-5-methyl-benzoylation, 4, 220 Pyrrole, 1,2-diamino-reactions, 4, 300 Pyrrole, 2,5-diamino-tautomerism, 4, 200, 299 Pyrrole, 2,4-diaryl-nitration, 4, 210 Pyrrole, 2,5-diaryl-synthesis, 4, 343 Pyrrole, 3,4-diaryl-synthesis, 4, 343 Pyrrole, di-t-butyl-protonation, 4, 47 Pyrrole, 2,5-dichloro-synthesis, 4, 368... 

Pyrrole, 2-methyoxycarbonyl-1 -methyl-formylation, 4, 45 Pyrrole, nitro-rearrangement, 4, 297 Pyrrole, 2-nitro-nitration, 4, 211 photolysis, 4, 203 radical methylation, 4, 260 synthesis, 4, 210, 362 Pyrrole, 3-nitro- N NMR, 4, 13 nitration, 4, 211 synthesis, 4, 49, 210, 362 Pyrrole, nitroso-rearrangement, 4, 297 Pyrrole, 2-nitroso-reactions... 

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... 

The chemistry of pyrrole is similar to that of activated benzene rings. In general, however, the heterocycles are more reactive toward electrophiles than benzene rings are, and low temperatures are often necessary to control the reactions. Halogenation, nitration, sulfonation, and Friedel-Crafts acylation can all be accomplished. For example ... 

Figure 24.6 Electrophilic nitration of pyrrole. The intermediate produced by reaction at C2 is more stable than that produced by reaction at C3.

Selective oxidation of methyl pyrroles 65 possessing an a-carboxylic ester and sensitive p-substituents can be accomplished using cerium triflate in methanol <96TL315>. Moreover, the resultant a-methoxymethylpyrroles 66 may be converted to dipyrrylmethanes 67 in a "one-pot" sequence by treatment with 48% HBr. The dipyrrylmethanes, in turn, can be further oxidized to dipyrryl ketones by ceric ammonium nitrate <96JHC221>. 

Nitration of the surface of polypyrrole and the subsequent reduction of the nitrate groups has been reported [244] and Bidan et al. [306, 307] have investigated the electrochemistry of a number of polymers based on pyrroles with /V-substituents which are themselves electrochemically active. Polypyrrole has also been successfully deposited onto polymeric films of ruthenium complexes [387], and has been used as an electrode for the deposition and stripping of mercury [388], As with most conducting polymers, several papers have also appeared on the use of polypyrrole in battery systems (e.g. [327, 389] and Ref. therein). 

Complex (21), a Con-cyclam analogue, is very active for the reduction of N02 and NH2OH intermediates and catalyzes the complex electrochemical conversion of N03 to NH3 325 Gold electrodes modified with cobalt-cyclam incorporated in Nafion films,324 or by electropolymerization of the pyrrole-substituted cobalt cyclam (22)326 have shown catalytic activity for the reduction of nitrate in strongly basic media. 

An oxidative radical coupling promoted by tetra-ra-butylammonium cerium(IV) nitrate (TB ACN) between P-aminocinnamate 22 and enamine 23 provided pyrrole-3,4-dicarboxylate 24 <06T2235>. Dimerization of the P-aminocinnamates provided symmetrical pyrroles. 

Pyrrolines and pyrroles can be readily prepared from the rearrangement of a-aminoallenes. Optically enriched a-aminoallene 137 is rearranged to pyrroline 138 by catalytic silver nitrate (Eq. 13.45) [53], The yield of the reaction is high and the cyclization occurs with high levels of asymmetry transfer. Annulated 3-pyrroline 140 is the product of rearrangement of allenyl pyrrolidine 139 (Eq. 13.46) [53]. 

The cydization can also be carried out on a-tosylaminoallenes, in which case the choice of reaction conditions determines whether the product is the N-tosyl-3-pyrro-line or whether elimination of toluenesulfonic acid acid gives the pyrrole. For example, in the presence of catalytic silver nitrate, allene 141 (Eq. 13.47) rearranges to N-tosylpyrroline 142 in excellent yield, whereas when 141 is treated with potassium tert-butoxide in DMSO, pyrrole 143 is formed in 71% yield [54]. Warming the lithium salt of 141 in DMSO also leads to 143. The rearrangement of 141 to 143 may be mechanistically related to the conversion of 130 to 131 (Eq. 13.42). 

Changes in intramolecular selectivity in the bromination and nitration of alkyl-benzenes in acidic media have been attributed to changes in medium polarity or changes in electrophile solvation. Mass spectrometric studies of the first stage in the gas-phase reactions of halobenzenes, furan, thiophene and pyrrole with alkyl cations have been rationalized in terms of co-existing a- and tt-complexes. The extent of... 

Typical electrophilic reactions, such as nitration, halogenation with a Lewis acid (as a carrier ), Friedel-Crafts C-alkylation and -acylation, that work well with benzene, cannot be applied to pyrrole, because heating with strong acids, or a Lewis acid, destroys the heterocycle. However,... 

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