Pyrroles, 2- - derivatives

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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