3-Nitro-5- pyrroles, preparation

Amino-pyrroles have been very little studied because they are relatively unstable and difficult to prepare. Simple 2-amino-pyrroles can be prepared, but must be stored in acidic solution. An alternative is to reduce nitro-pyrroles over Pd/C in the presence of anhydrides, which produces amides of the otherwise unstable amino-pyrroles. Another trapping procedure employs a 1,4-dione and thus engenders another pyrrole ring (cf. 16.16.1.1). ... 

As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as usefid starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, ind 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-aromadcs fmainly pyrroles ind indolesi ind saturated nitrogen heterocycles such as pyrrolidines ind their derivadves. 

Benzyl isocyanoacetate is a nsefnl reagent for the preparadon of benzyl 5-nnsnbsdnited pyrrole-2-carboxylates, which are widely used In the synthesis of porphyrins." Ono and coworkers have prepared pyrroles snbsdnited with various snbsdnients at the fi-posidons."" Because the reqidsite fi-nitro acetates for nitroalkenesi are readily available by the Henry... 

Many other biologically active pyrroles have been prepared by this reaction. 3-Cyano-3,4-disubsdnited pyrroles are prepared by thereacdon ofisocyanoacetonitnie v/ithfi-nitro acetates. 

In 1988, Ono and Maruyama reported a very simple synthesis of octaethylporphyrin (OEP) from 3,4-diethylpyrrole-2-carboxylate, as shown in Eq. 10.44 49 Reduction of this pyrrole with LiAlH4 gives 2-hydroxyethylpyrrole, which is converted into OEP on treatment with acid and an oxidizing agent. This route is very convenient for synthesis of porphyrins. This method is now used extensively for synthesis of P-substituted porphyrins.50 For example, a highly conjugated porphyrin, shown in Eq. 10.45, has been prepared by this route.51 The requisite pyrroles are prepared from nitro compounds or sulfones thus, various substituents are readily introduced into porphyrins. 

The dipolarophile was prepared in a short (three-step) sequence from methyl phenyl sulfone (38% overall yield) and ethyl trifluoroacetate. Desulfonation, followed by reductive N-0 cleavage afforded the syn aminoalcohols [246]. Conjugate additions to the sulfone were described some years earlier [247] more recently, trifluoromethyl pyrroles have been synthesised from the nitro-propene [248]. 

Nitro-substituted pyrroles have usually been prepared by electrophilic substitution on preconstructed pyrrole rings. Like other electrophilic substitutions, nitration gives primarily... 

In contrast to carbenes, nitrene attacks only the carbon and never the sulfur atom of thiophene the only exception to this is discussed in Section 3.14.3.5. Unsubstituted thieno[3,2-/>]pyrrole and thieno[2,3-6]pyrrole have been prepared by thermolysis of the corresponding vinyl azides (Scheme 68) (81IJC(B)27l). A bis-cyclization of this type has also been reported (73CR(C)(277)1149>. Similarly, in the benzo[Z>jthiophene series the nitrene (252), generated either by thermolysis of the azide or by P(OEt)3 induced deoxygenation of the nitro compound, gives only the condensed indole (253) (79AG(E)900). 

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). 

Fused pyrroles have been prepared by the condensation of an amino group with a suitably positioned carbonyl function. Thus, reduction of ethyl (3-nitro-2-thienyl)pyruvate (226) with tin(IV) chloride gave 5-ethoxycarbonyl thieno[3,2-6]pyrrole (47), by the spontaneous cyclization of the intermediate amino derivative (227 Scheme 76) (64JOC2160). The formation of indolo[3,2-6]indole (229), a dibenzannelated pyrrolopyrrole, by the cyclization of (228) with tin(IV) chloride (Scheme 77) is an example of a case where reduction of the imino function in the starting material is necessary before cyclization will occur (78AHC(22)183). 

Pyrrole synthesis. A new route to pyrroles1,2 is based on a base-catalyzed Michael addition of an alkyl isocyanoacetate to a nitroalkene to give an intermediate that cyclizes to a pyrrole. The nitroalkene is generally obtained from a P-acetoxy nitroalkane (1), prepared by a nitro aldol reaction of an aldehyde with a nitroalkane. The synthesis of ethyl 3,4-diethylpyrrole-2-carboxylate (2) is typical. 

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

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