5- Methylpyrrole-2-aldehyde

Table 2 shows the relative quantities of component groups in the volatiles after heating mixtures of glucose or fructose with serine at 120°, 150° and 180° C. It shows optimal formation of furans and pyranones at 120° C, whereas furanones possess a maximum at 150° C. Compounds of the other groups are formed preferentially at 150° C, while the formation of pyrazines proceeds better the higher a reaction temperature was chosen. Also pyrroles need higher temperatures for their formation. So we could demonstrate that only acetylpyrrole and 5-methylpyrrole-2-aldehyde has been formed at 120° C whereas many additional pyrroles appear at 150° C or 180°C respectively (12). 

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 iV-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... 

Photochemical [2 + 2] cycloaddition is a powerful way to produce cyclobutanes, which, in turn, are reactive synthesis intermediates. N-Methylpyrrole adds aldehydes via [2 -I- 2] photocycloaddition to give transient oxetanes with high regioselectivity Ring-opening produces 3-(oi-hydroxyalkyl)pyrroles which are oxidized easily to 3-arylpyrroles, such as 3-BUTYROYL-l-METHYL-PYRROLE. With a special apparatus, ethylene is conveniently added to 3-methyl-... 

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. 

The formation of 3-pyrrolylcarbinols (280) from the photochemically induced reaction of pyrrole, or its 1-alkyl derivatives, with aliphatic aldehydes and ketones is thought to proceed via an oxetane intermediate (279) (79JOC2949). In contrast, the analogous reaction of 1 -phenylpyrrole with benzophenone leads to the formation of the diphenyl(2-pyrrolyl)car-binol, whilst the oxetane (281) has been isolated from the photoaddition of 1-benzoylpyrrole and benzophenone (76JHC1037, B-77MI30500). 2-Benzoyl-1-methylpyrrole undergoes a normal Paterno-Buchi photocyclization with 2,3-dimethylbut-2-ene, via the n -> v triplet... 

Pyrrole, like thiophene, does not react with benzophenone to give the corresponding oxetane. However, pyrrole reacts with aliphatic aldehydes and ketones to the corresponding 3-pyrryl carbinols. The alcohols derive from the cleavage of the corresponding oxetanes (Scheme 3.48) [94]. The yields increase when A -methylpyrrole is used as substrate, while the reactivity is depressed in the presence of substituents on the pyrrole ring. 

There are few references to dioxinopyrroles which are compounds which do lend themselves to systematic study. The lactam acetal of 1-methylpyrrole (288) reacts with aldehydes in anhydrous ether (or in the absence of solvent) at room temperature to give the tetrahydro-l,3-dioxino[4,5-6]pyrroles (289) (Scheme 21). These lose one molecule of aldehyde when treated with alcoholic potassium hydroxide to yield the benzhydrols (290) <83IJC(B)1079>. 

In addition to furan, other heterocycles have been examined." Thiophene undergoes efficient photocycloaddition with benzaldehyde to afford a single exo photoproduct (183) in 60% yield. As reported by Jones and coworkers,the photolysis of IV-methylpyrrole in the presence of aldehydes or ketones yields the corresponding 3-hydroxyalkyl derivative (184), even when the reaction mixture is free from any trace of acid. In order to use the pyrrole nucleus for stereoselective alkaloid synthesis (cf. caesalpinine, 185) in the fashion developed with the furan nucleus, pyrrole substituents that stabilize the presumed intermediate bicyclic oxetane must be discovered. 

Hydroxyalkylation at the 5-position of 2-formylthiophene results from exposure of the thiophene aldehyde and a second aldehyde, to samarium(II) iodide in the example shown below, the other aldehyde is 1 -methylpyrrole-2-carboxaldehyde. ... 

In their porphyrin syntheses Fischer and his co-workers955 made great use of the condensation of methylpyrroles with pyrrolecarbaldehyde. Methyl groups attached to aromatic condensed heterocycles can also be condensed with aldehydes in this way in the presence of zinc chloride, quinaldine hydrochloride and 2-ethylhexanal give 2-(3-ethyl-l-heptenyl)quinoline in 87% yield 956 and 9-methylacridine condenses with m- or / -nitrobenzaldehyde, giving the 9-styryl derivatives in good yield.957... 

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." ... 

Similar conditions were used to prepare pyrroles from both t-butyl and benzyl isocyanoacetate. <94JHC255, 94S170> The reaction was also effective for preparing some rather hindered 3-aryl-4-methylpyrrole-2-carboxylates. Several p-methylnitrostyrenes were prepared by condensation of an aromatic aldehyde with nitroethane. These nitrostyrenes condensed with ethyl or methyl isocyanoacetate. Even o,o -disubstituted... 

Both 1-methylpyrrole and 1-methylindole can be easily lithiated and the resulting intermediates have been used extensively in synthesis. The range of electrophiles which can be used with lithiated pyrroles and indoles is quite broad. Aldehydes and ketones give carbinols. A,A-Disubstituted formamides give aldehydes. Carbon dioxide and alkyl chloroformates have been used to make carboxylic acid derivatives. Alkyl halides, sulfates and sulfonates can be used to introduce alkyl groups. Interestingly, even t-butyl bromide has been used successfully for alkylation (see entry 3, Table 7). Some examples are given in Table 7. 

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