Pyrrole, nitro derivatives

The syntheses shown in Scheme 26 (71CB1573) are based on dibenzo-/3-tropolone (108) and its enamines. Condensation of 108 and benzoin in the presence of ammonia affords pyrrole 109. The morpholino enamine gives pyrazole 110 via benzoylation, hydrolytic elimination of morpholine, and cyclization, whereas diazo-group transfer onto the anilino enamine leads to triazole 111. Dione 108 and p-nitrophenylazide in one step give predominantly the p-nitro derivative of 111 (92G249). 

In view of the ease with which nitrenes can be generated by the action of trivalent phosphorus reagents on nitro derivatives or by thermal decomposition of azido compounds, the suitable insertion of such nitrene intermediates leads to annelated pyrrole systems. For example, the action of triethyl phosphite on 2-nitro-3-styrylthiophenes (193) led to the thieno[2,3-6]pyrrole derivatives (194 Scheme 70). The isomeric thieno[3,2-6]pyrroles (196) were also prepared in a similar fashion from (195 Scheme 71) (73S313). 

The nitration of 1,2,3,5-tetraphenylpyrrole, using nitric acid acetic acid, gives the 4-nitro derivative (66MI1) as does 1-methyl-2,5-diphenyl-3-(2-pyridyl)pyrrole (9). The action of fuming nitric acid at 0°C on ethyl... 

The acid sensitivity of pyrrole dictates the use of acetyl nitrate as nitrating agent the main product is the 2-nitro derivative together with some of the 3-nitro compound. The nitration of N-substituted pyrroles yields relatively more -substituted product, and with electron-withdrawing groups such as acetyl or ethoxycarbonyl at the 2-position,... 

Extension166-166 to pyrrole- and selenophene-2-carboxylic acids gives a sequence of sensitivity in the order pyrrole, furan, selenophene, thiophene, benzene, the same order as that observed by Tirouflet et al.ul in the polaro-graphic reduction of nitro derivatives of these rings. A different sequence, however, which correlates better with ground state aromatic character , viz., furan, pyrrole, thiophene, benzene, has been observed in the gas-phase ionization process,168 but results for electrophilic substitution appear to be anomalous.169... 

The VNS is the reaction of choice for incorporation of a-sulfonylalkyl substituents into nitroarenes and their heteroanalogues. Particularly accessible and useful are nitroarylmethyl phenyl sulfones and their heteroanalogues that are efficiently produced in the VNS reactions of carbanions of chloromethyl aryl sulfones with a great variety of nitroarenes and nitroheteroarenes. Nitro derivatives of heterocycles, such as pyrrole [54,55], furan [54], thiophene [54], imidazole [106, 112, 113], pyrazole [114], pyridine [57], indole [115], indazole [116, 117], benzimidazole [118], benzotriazole [119], benzofuroxan [120], quinoline [121], and porphyrins [122, 123], have been shown to enter this reaction. 

Nitro derivatives of ary [porphyrins, which contain the nitro group in the pyrrole rings, enter the VNS reaction with carbanions bearing a leaving group at a-position, thus giving the expected substitution products in good yields (Scheme 43) [123]. 

Mercury(II) acetate tends to mercurate all the free nuclear positions in pyrrole, furan and thiophene to give derivatives of type (74). The acetoxymercuration of thiophene has been estimated to proceed ca. 10 times faster than that of benzene. Mercuration of rings with deactivating substituents such as ethoxycarbonyl and nitro is still possible with this reagent, as shown by the formation of compounds (75) and (76). Mercury(II) chloride is a milder mercurating agent, as illustrated by the chloromercuration of thiophene to give either the 2- or 2,5-disubstituted product (Scheme 25). 

Nitro ilkenes derived from galdctose or other carbohydrates are converted directly into pyrroles siibsdnited v/ith such carbohydrates at the fi-posidon. They are important precursors for water-soluble porphyrins fEq. 10.29. Such kmds of porphyrins are good candidates for photodynamic therapy of cancer and have been extensively snithed. 

In another series of experiments, the nitroporphyrin 6 (M = H2) or its metal derivatives 6 (M = Cu, Ni) have been used to attach heterocyclic rings to the nitro-substituted pyrrole ring of the macrotetracycle.112,113... 

As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as useful starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, and pyrrolidines, are frequently prepared from nitro compounds. Syntheses of heterocyclic compounds using nitro compounds are described partially in Chapters 4, 6 and 9. This chapter focuses on synthesis of hetero-aromatics (mainly pyrroles and indoles) and saturated nitrogen heterocycles such as pyrrolidines and their derivatives. 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

Ketoester 208 derived from l-(2-nitrophenyl)-lH-pyrrole and ethyl oxalyl chloride can be selectively reduced at the keto group with zinc iodide and sodium cyanoborohydride. Further reduction of the nitro group and cyclization to lactam 209 has been accomplished by treatment with stannous chloride in refluxing ethanol (Scheme 43 (2003BMCL2195)). 

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