Pyrrole ring system

This synthesis of the pyrrole ring system, due to Knorr, consists in the condensation of an a-aminoketone with a 1,3-diketone or the ester of a p-keto-acid, a-Aminoketones are unstable in the free state, readily undergoing self-condensation consequently they must be prepared, by the reduction of an a-nitroso (or oximino) ketone, in the presence of the 1,3-diketone or p-ketoester, to ensure rapid interaction. 

Phthalocyanines. The pyrrole ring system is also the fundamental stmctural unit of the important group of blue and blue-green pigments known as the phthalocyanines (see Phthalocyanine compounds). 

Pyrrole is one of the most prominent heterocycles, having been known for more than 150 years, and it is the structural skeleton of several natural products, synthetic pharmaceuticals, and electrically conducting materials. A simple access to the pyrrole ring system involves the conversion of cyclic anhydrides into five-membered imides. Mortoni and coworkers have described the conversion of 2-methylquinoline-3,4-dicarboxylic acid anhydride to a quinoline-3,4-dicarboximide library by treatment of the anhydride with a diverse set of primary amines under microwave conditions (Scheme 6.180) [341]. The authors studied a range of different conditions, including dry media protocols (see Section 4.1) whereby the starting materials were adsorbed onto an inorganic support and then irradiated with microwaves. For the transforma-... 

The first step is formation of a pyrrole ring system from two identical aminoketones. It is actually a Knorr pyrrole synthesis, but we do not need to identify it as such, just approach it logically. In fact, if we look back at the Knorr pyrrole synthesis, we shall see that, under chemical conditions, the reagents used here are not sufficiently reactive for the pyrrole synthesis we need a more activated compound, like ethyl acetoacetate. Furthermore, we could not possibly proceed without masking the carboxyls as esters. This underlines how a biosynthetic sequence might differ somewhat from a purely chemical synthesis. 

The idea of employing the reaction of a nitroarene or nitroheterocycle with a mtinchnone to synthesize a fused pyrrole ring system has been developed by two groups. Nesi et al. (109) found that mtinchnone 38 reacts with 3-methyl-4-nitroisoxazole (196) and 4-nitro-3-phenylisoxazole (197) to give the corresponding 5//-pyrrolo[3,4-tf]isoxazoles 198 and 199, respectively, in good yield. Presumably loss of carbon dioxide in a retro-Diels-Alder reaction follows loss of nitrous acid. 

The crystal structure of ethyl 4//-thieno[3,2-3]pyrrole-5-carboxylate 55 indicates an ethoxycarbonyl group attached to a planar thieno[3,2-/)]pyrrole ring system <2004AXE2493>. 

The first synthesis of the parent compound of the benzo[4,5]thieno[2,3-f]pyrrole ring system 387 <2003T1477> and its derivatives was accomplished using the same synthetic sequence (Scheme 42). Starting with 2-methyl-benzo[ ]thiophene-3-carbaldehyde 388, an intermediate 389 was obtained. Treatment of bromo compound 389 with sodium azide in ethanol led to the stable triazoline 390. 1,3-Dipolar cycloreversion of 390 was induced by a catalytic amount of />-TsOH to give the parent 2//-benzo[4,5]thieno[2,3-c]pyrrole 387. Alternatively, direct treatment of bromo compound 389 with excess ammonia furnished 387 in one step. Compound 387 was treated with di-/-butyl dicarbonate and 4-dimethylaminopyridine (DMAP) to give iV-BOC derivative 391. Reaction of 389 with... 

The simplest members of this group are those in which X is a monocyclic residue, such as furan, thiophene, and pyrrole ring systems. Color may then be produced in the usual way by attaching auxochromes to the 5- and/or 8-positions. Few dyes of this type have been suggested for textile applications, presumably... 

Moskalev, N. V. Gribble, G. W. Synthesis and Diels—Alder reactions of the furo[3,4-b]pyrrole ring system. A new indole ring synthesis. Tetrahedron Lett. 2002, 43, 197—201. 

In the case of atorvastatin, a lH-pyrrole ring system was selected [3], The synthetic 2-(4-fluoro-phenyl)-5-isopropyl derivative (Fig. 4.5) inhibited [uC]-acetate conversion to cholesterol in a crude rat liver homogenate. A optimization of its 3,4-disubstituted analogues resulted in atorvastatin. 

The fused pyrrole ring system (204) has been obtained by the reaction of 17/3-hydroxy-17-methylandrosta-l,4-dien-3-one with tosylmethyl isocyanide in the presence of sodium hydride in DMSO,92 and 17/3-hydroxy-17-methyl-7-oxa-5o -androstano-[3,2-c]- (205) or -[2,3-d]-isoxazoles (206 X = O) have been prepared by treating 7-oxa-2-(hydroxymethylene)-17/3 -hydroxy-17-methyl-5 a -androstan-3-one with hydroxylamine hydrochloride.93 In the presence of pyridine, the isox-azole (206 X = O) is formed, but when the reaction is catalysed by sodium acetate in acetic acid the isomeric steroid (205) results. Cycloaddition of hydrazine hydrate to the same 2-hydroxymethylene-7-oxa-steroid results in the [3,2-c]pyrazole (206 X = NH). A similar addition is encountered in the reactions between 3/3-hydroxy-16-(hydroxymethylene)-5a-androstan-17-one and the substituted hydrazines RNHNH2 (R = H, o-COC6H4NH2, or p-COQHUNH ,) when the corresponding [17,16-c]pyrazoles (207) are formed after cyclization of the intermediate hydrazones.94... 

The involvement of the nitrogen lone pair in the aromatic sextet means that the nitrogen of pyrrole is non-basic. When the pyrrole ring system is protonated. addition takes place at C-2 (Scheme 4.30a). Electrophilic attack on pyrrole is rapid and also takes place at C-2. Reaction at C-3 is less favoured (Scheme 4.30b). 

The proposed reaction pathway leading to these products is depicted in figure 5. The electron-rich pyrrole ring system is oxidized to the reactive arene oxide (structure 32) which rearranges to the zwitterionic species... 

Three classes of pyrroles have been identified (Scheme 1) the familiar aromatic 1//-pyrroles and the less familiar 2H- and 3i/-pyrroles. The latter two classes, described in the early literature both as isopyrroles and as pyrrolenines, are nonaromatic due to the tetrahedral carbon atom in the ring, and their chemical properties are thus expected to be very different from those of their 1H counterparts. The 2H- and 3//-pyrrole ring systems... 

Scheme 4.30 BTMG (2) catalysed formation of pyrrole ring system...

Construction of the phosphole ring, with one useful exception, is accomplished by methods that are quite different from those employed for the N, S, O ring systems. Because of fundamental differences in the chemistry of phosphines versus amines, none of the familiar carbonyl condensation processes are known to be applicable to phosphole synthesis. Thus an attempt to use the Paal-Knorr condensation of 1,4-dicarbonyl compounds with PhPH2 <65JCS2184> and with PH3 <88ZOB783> failed to give phospholes. The only successful method known to the present that is common to both the phosphole and pyrrole ring systems is the condensation of 1,3-diynes with primary phosphines... 

As is consistent with the high reactivity of pyrroles toward electrophiles, the coupling reaction with diazonium ions is well known for the pyrrole ring system. The highly colored azo product, e.g., 7.3, is useful as a precursor of aminopyrroles, which can be formed with reducing agents such as stannous chloride (Scheme 7.12). 

A new class of long-wavelength photosensitizers (738-798 nm) named verdinochlorins 100 were recently reported by Pandey and coworkers. These compounds were obtained by the reaction of 13 -oxopyropheophorbide a 99 with diazomethane which produces the isomeric verdinochlorins 100 via expansion of the cyclopentanedione ring E (Scheme 28). These long-wavelength photosensitizers represent the first example of verdins with a reduced pyrrolic-ring system. 

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