2- pyrrole derivatives

There are four parent isomeric indoloquinones the 4,5-dione (2), 5,6-dione (3), 6,7-dione (4), and 4,7-dione (5). In the isoindole series there are two isomers isoindole-4,5-dione (6) and -4,7-dione (7). There are many benzo, naphtho, and other extended analogs and they will be treated later. In the indole series, there are only a few representatives of systems 2-4 and the same holds for the isoindole series. However, there are many examples of 5. 

An adduct (9) could be isolated when Fremy s salt oxidation was applied to an analogous system. This intermediate, when treated with concentrated hydrochloric acid, is immediately transformed into the quinone 10 (59CB667). 

Indoloquinones of type 3 are rare. Although such quinonoid formulas were once the preferred ones for adrenochrome and related compounds. 

There are also few compounds corresponding to 4. 2,3-Diphenyl-6-hydroxyindole afforded the corresponding 6,7-dione upon oxidation with Fremy s salt (61JCS3516). Similarly, the 1,2-dione was obtained from 2-hydroxycarbazole (54CB1251). By a nonoxidative procedure, the quinone 

17 was obtained when 3-acetylamino-4-chloro-l,2-naphthoquinone was condensed with diethyl malonate (1899CB260). A related cyclohexyl analog was similarly prepared (85ZOR1315). In an uncommon reaction the aldehyde 

Sessler, J. L., Camiolo, S., Gale, P. A., Pyrrolic and polypyrrolic anion binding agents , Coord. Chem. Rev. 2003, 240, 17-55. 

While interesting neutral alternatives to the unsaturated expanded porphyrin derivatives, calix[n]pyrroles (n = 4, 5, 6, 8) are relatively limited in their scope for anion binding because of the constraints of the cavity size. Nevertheless pyrroles linked by an sp hybridised carbon atom are of considerable interest because of their resemblance to the anti-cancer agents the prodigiosins (Section 4.2.4), moreover pyrrole anion-receptor chemistry is synthetically versatile and hence a range of acyclic pyrroles and hybrid amidopyrroles such as 4.50-4.52 have been developed, particularly by the groups of 

There are four parent isomeric indoloquinones the 4,5-dione (2), 5,6-dione 

5- to 4,7-dione isomerization under different conditions has been observed. For example, the carbazoledione 11 is oxidized in dilute alkali into the p-quinone 12 (63JOC1169). Isomerization is possible also via reductive acetylation, hydrolysis, and subsequent oxidation with ferric chloride (79FES1062) or air, as in the case of conversion of 13 to 14 (65JOC4381). A mixture of the 4,5- (15) and 4,7-dione (16) was obtained in low yield after oxidation of 2,6-dimethyl-l-ethyl-4-hydroxyindole with Fremy s salt. The 

Basavaiah and Rao first disclosed that a MBH adduct bearing a nitro group can furnish y-lactams in good yields via a reductive cyclization. Treatment of the starting material 400 (2.0 mmol) with nitroethane (8.0 mmol) in the presence 

3-Aryl-3-hydroxypyrrolidin-2-ones have been found in many natural products such as chimonamidine and donaxaridine, and an efficient synthetic route for the preparation of such derivatives has been developed by Kim s group. Using isatins 415 as substrate, the reactions were carried out in the presence of benzylamine in MeOH at room temperature to give diastereomeric 

C02Me aniline (1.1 equiv) LICI04(1.2 equiv) MeCN, reflux, 24 h  

However, 2,5-dihydropyrroles 455 were completely deprotected to give the pyrrolines 457 as a hydrofluoride salt in quantitative yields, when they were used to react with neat hydrofluoric acid. Furthermore, hydrogenation of 455 with a Pd/C catalyst followed by HF-mediated deprotection of the resultant compound 458 yielded pyrrolidines 459 in excellent yields and good diaster-eomeric ratios. 

The same preparation procedure as the synthesis of compound 468 from compound 460 

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Prepared by heating ammonium mucate, or from butyne-l,4-diol and ammonia in the presence of an alumina catalyst. The pyrrole molecule is aromatic in character. It is not basic and the imino-hydrogen atom can be replaced by potassium. Many pyrrole derivatives occur naturally, e.g. proline, indican, haem and chlorophyll. 

The preparation of 2 4-dimethyl-3 5-dicarbethoxypyrrole (II) is an example of the Knorr synthesis of pyrrole derivatives, involving the reaction of an -aminoketone (or a derivative thereof) with a reactive methylene ketone (or a derivative thereof). The stages In the present synthesis from ethyl acetoacetate (I) may be represented as follows ... 

Pyrrole derivatives are prepared by the coupling and annulation of o-iodoa-nilines with internal alkynes[291]. The 4-amino-5-iodopyrimidine 428 reacts with the TMS-substituted propargyl alcohol 429 to form the heterocondensed pyrrole 430, and the TMS is removed[292]. Similarly, the tryptophane 434 is obtained by the reaction of o-iodoaniline (431) with the internal alkyne 432 and deprotection of the coupled product 433(293]. As an alternative method, the 2,3-disubstituted indole 436 is obtained directly by the coupling of the o-alky-nyltrifluoroacetanilide 435 with aryl and alkenyl halides or triflates(294]. 

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

See also g-Aminobutyric acid.) PYRROLE AND PYRROLE DERIVATIVES] (Vol 20)... 

Except for the pyrroHdinones (see Pyrrole and pyrrole derivatives), these products are discussed in the following. 

When heated with acidic oxide catalysts, mixtures of butynediol with ammonia or amines give pyrroles (66) (see Pyrrole AND PYRROLE DERIVATIVES). 

Photolysis of pyridazine IV-ethoxycarbonylimide results in the formation of the pyrrole derivative (56). The rearrangement is postulated to proceed via a diaziridine, followed by ring expansion to the corresponding 1,2,3-triazepine derivative and rearrangement to a triazabicycloheptadiene, from which finally a molecule of nitrogen is eliminated (Scheme 19) (80CPB2676). 

The oxidative coupling of 3,4-dimethyl-or 3,4-diphenyl-isoxazolin-5-one by activated Mn02 produced a 4,4 -bis(isoxazolinone) (519) and 2,4 -bis(isoxazolinone) (520). Hydrogenation of (519) over Pt02/H0Ac produced a pyrrole derivative while similar reaction of (520) produced an isomeric pyrrole (80JHC763). These reactions are shown in Scheme 152. 

Finally, the bimolecular cycloaddition of alkynes with 2-phenylazirines in the presence of molybdenum hexacarbonyl has been studied (79TL2983). The pyrrole derivatives (294) obtained appear to arise from an initial [2 + 2] cycloaddition followed by a ring opening reaction. 

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