Pyrrole-2-aldehyde

Under conditions more similar to those of the Reimer-Tiemann reaction 3-bromopyridine was obtained from pyrrole and bromo-form. Treatment of pyrrole with chloroform and aqueous alkali gave pyrrole-2-aldehyde curiously, the formation of 3-chloropyridine under these conditions does not appear to have been reported, in spite of being frequently quoted. However, indole gave both indole-3-aldehyde and 3-chloroquinoline under these conditions [Eq. (10)]. 

A similar synthesis starting with l-(2-nitrobenzyl)pyrrol-2-aldehyde used ethanol-ethyl acetate as solvent (62). Indoles are prepared in excellent yield by hydrogenation of o-nitrobenzyl ketones over Pd-on-C (i). Azaindoles are correspondingly prepared from nitropyridines (97). 

The anion from pyrrole-2-aldehyde adds sequentially to the salt (146), resulting in the pyrrolizine137 (147) (Scheme 7). 

The Fe " " complex of the linear hexadentate A, A, 5 ,iS ,A, A -coordinating ligand derived from l,8-diamino-3,6-dithiaoctane and pyrrole-2-aldehyde has been synthesized and characterized, especially by Mossbauer spectroscopy.The hexadentate tripodal NsSs-donor triazamacrocyclic ligands (196) and (197) give brown-violet and green black Fe complexes, respectively the former is predominantly high-spin, the latter predominantly low-spin. In the complex of (1 the Fe—N bond distances are between 2.06 A and 2.08 A, Fe—S between 2.269(3) A and 2.288(3) A. ... 

Pyrrolo[ l, 2 -3,4]pyrimido[2,l,6-a/]pyrrolizine (40a) was obtained in 10% yield by a reaction of the sodium salt of pyrrole-2-aldehyde with vinylene-l,2-bistriphenylphosphonium iodide (39)in boiling toluene. The intermediate (yields shown in Scheme 1) were isolated from a reaction in boiling benzene. Compound 40a is diatropic and on refluxing in acetic anhydride it gives 40b. The position of substitution is in accordance with HMO calculations.44... 

Wittig reactions with pyrrole-2-aldehyde led to the esters (79) which were cyclisized to 3a-azaazulen-4-ones (80).104,105 4-Methylene-3a-aza-azulenes (81) have been obtained from 80 with stabilized phos-phoranes.36 Reaction of dimethyl acetylenedicarboxylate with 81 could not be achieved. A similar cycloaddition was successful in the synthesis of cycl[3,3,3]azines (2) (Section V). 

The carbonyl reactivity of pyrrole-, furan-, thiophene- and selenophene-2- and -3-carbaldehydes is very similar to that of benzaldehyde. A quantitative study of the reaction of Af-methylpyrrole-2-carbaldehyde, furan-2-carbaldehyde and thiophene-2-carbaldehyde with hydroxide ions showed that the difference in reactivity between furan- and thiophene-2-carbaldehydes was small but that both of these aldehydes were considerably more reactive to hydroxide addition at the carbonyl carbon than A-methylpyrrole-2-carbaldehyde (76JOC1952). Pyrrole-2-aldehydes fail to undergo Cannizzaro and benzoin reactions, which is attributed to mesomerism involving the ring nitrogen (see 366). They yield 2-hydroxymethylpyrroles (by NaBH4 reduction) and 2-methylpyrroles (Wolff-Kishner reduction). The IR spectrum of the hydrochloride of 2-formylpyrrole indicates that protonation occurs mainly at the carbonyl oxygen atom and only to a limited extent at C-5. 

Pyrrolo[l, 2 3,4]pyrimido[2,l,6-crf]pyrrolizines (182), as well as pyrrolizines (183) and (184), have been obtained from a one-pot reaction of the anion of pyrrole-2-aldehyde with l,2-bis(hetero) substituted ethylenes (181) in a route given in Scheme 24 (80CB614,81UP30801). 

H. Kato and M. Fujimaki, Formation of V-substituted pyrrole-2-aldehydes in the browning reaction between D-xylose and amino compounds, J. FoodSci., 1968, 33, 445. 

Species of marine sponge of the genus Laxosuberites contain several pyrrole-2-aldehydes with a long side-chain at position 5. Their structures (1), (2), and (3) have been settled by spectral study and by chemical degradation. One, (3), proved to be a cyanhydrin of unusual stability.3... 

J. F. Liebman and R. M. Pollack, in The Chemistry of Enones (Eds. S. Patai and Z. Rappoport), Wiley, Chichester, 1989. Buried enones in this chapter included pyrrole-2-aldehyde, 4-pyridone, 2-aminotropone, p-dimethylaminobenzaldehyde, indigotin and both methylphaeo-phorbide a and b. These compounds may also be recognized as buried enamines. 

A further example is the synthesis of 3H-pyrrolizine from the reagent and pyrrole-2-aldehyde (Eastman) in ether with sodium hydride as condensing agent. 

Kato Hiromichi (1967) Chemical studies on amino carbonyl reactions. III. Formation of substituted pyrrole-2-aldehydes by reaction of aldoses with alkylamines, Agric. Biol Chem. 31, 1086-90. 

Nitrogen Systems. - Monoaza-Compounds. Gas-phase pyrolysis of the condensation product (532) of pyrrole-2-aldehyde with Meldrum s acid gives pyrrolizin-3-one (533). The acid chloride (535) is produced by the action of phosphorus pentachloride on the pyrrole derivative (534). Treatment of the enamine (536) with dimethyl acetylenedicarboxylate in methanol yields, inter alia, the diester (537). A -Dehydropyrrolizidine undergoes dimerization to yield mainly compound (538), The pyrroloindoloquinone (540) is produced by irradiation of the benzoquinone derivative (539). ° ... 

The preparation of the dihydropyrrolo 4,2-a azepinone (553) from pyrrole-2-aldehyde and methyl vinyl ketone has been described.Irradiation of the indo-... 

The chiral auxiliary (188) was obtained from the anion of pyrrol-2-aldehyde and phosphonate (189) and used in asymmetric synthesis <92TA1515>. 

Diaza-compounds. Phenacyl bromide reacts with 2-aminopyridine 1-oxide to yield 2-phenylimidazo[l,2-a]pyridin-3-ol (769) another derivative of this ring system, compound (771), is produced by the action of diphenylketen on the sulphilimide (770), dimethyl sulphide being eliminated.(6-Methyl-2-pyri-dyl)acetyl azide (772) forms the dihydroimidazo[3,4-a]pyridinone (773) on heating." Whereas l-methylpyrrole-2-aldehyde and other heterocyclic aldehydes react with tosylmethyl isocyanide to give oxazoles, e.g. (774), pyrrole-2-aldehyde affords the 6-azaindolizine (775). The action of potassium amide on the derivative (776) of 3-bromopyridine furnishes the pyrrolo[3,4-c]pyridine (777) by cyclization of an intermediate pyridyne." ... 

Coordination compounds of the Schiff bases of pyrrole-2-aldehyde and its analogues... 

Why is pyrrole-2-aldehyde less reactive than benzaldehyde as an electrophile ... 

In a copper-catalyzed cyclocondensation reaction, pyrrole-2-aldehyde and 2-iodoaniline (X) are heated in NMP as solvent at 130°C in the presence of K3PO4 and Cul/sparteine as catalyst. After workup, a product A is isolated in 83% yield. 

When pyrrole-2-aldehyde is reacted with phenacyl bromide and diethyl acetylenedi-carboxylate (three-component MCR process) in DMF in the presence of K2CO3 at 50 °C, a product A is obtained in 85% yield. 

For preparative purposes the Gattermann reaction is much more useful. It was first usedS5 to prepare ethyl 2-formyl-3,5-dimethyl- and ethyl 3-formyl-2,5-dimethyl-pyrrole-4-carboxylate, by means of hydrogen cyanide and hydrogen chloride in ether. Later applications sometimes involved minor changes such as the use of chloroform as solvent, or of Adams modification of the reaction . Formylation generally occurs at an a-position, but if none is open there is usually no difficulty in jS-substitution. Pyrrole-2-aldehyde cannot be made this way, for it reacts further to form dyestuffs, but several 1-alkylpyrroles have been satisfactorily formylated . The initial... 

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