Acetaldehyde reaction with aniline

Primary aromatic amines react with aldehydes to form Schiff bases. Schiff bases formed from the reaction of lower aUphatic aldehydes, such as formaldehyde and acetaldehyde, with primary aromatic amines are often unstable and polymerize readily. Aniline reacts with formaldehyde in aqueous acid solutions to yield mixtures of a crystalline trimer of the Schiff base, methylenedianilines, and polymers. Reaction of aniline hydrochloride and formaldehyde also yields polymeric products and under certain conditions, the predominant product is 4,4 -methylenedianiline [101 -77-9] (26), an important intermediate for 4,4 -methylenebis(phenyhsocyanate) [101-68-8], or MDI (see Amines, aromatic amines, l thylenedianiline). 

In 1883, Bottinger described the reaction of aniline and pyruvic acid to yield a methylquinolinecarboxylic acid. He found that the compound decarboxylated and resulted in a methylquinoline, but made no effort to determine the position of either the carboxylic acid or methyl group. Four years later, Doebner established the first product as 2-methylquinoline-4-carboxylic acid (8) and the second product as 2- methylquinoline (9). Under the reaction conditions (refluxing ethanol), pyruvic acid partially decarboxylates to provide the required acetaldehyde in situ. By adding other aldehydes at the beginning of the reaction, Doebner found he was able to synthesize a variety of 2-substituted quinolines. While the Doebner reaction is most commonly associated with the preparation of 2-aryl quinolines, in this primary communication Doebner reported the successful use of several alkyl aldehydes in the quinoline synthesis. 

The Doebner reaction can provide the 4-carboxyl quinoline when the Pfitzinger reaction does not." Pfiztinger reaction of pinnacolone with isatin did not provide the desired quinoline. Doebner reaction of aniline with acetaldehyde and pyruvic acid did furnish the quinoline, albeit in only 8% yield. 

The arylation of acetaldehyde enolate by iodobenzene17-128 or p-iodoaniline73 failed, and the reduced products, benzene or aniline were obtained. In the reaction of aldehyde enolates with o-substituted derivatives, however, arylation does occur and in these cases subsequent cyclization reactions usually take place (see Section 2.2.4.2). The special effect of the o-substituents in facilitating reactions with aldehyde enolates is shown by the rare example of simple substitution (i.e. without concomitant cyclization) in equation (34).71... 

Reaction of a primary aromatic amine (such as aniline) with a carhonyl compound such as acetaldehyde, in the presence of acid, also generates a 2-alkylquinoline in the Doebner-Miller reaction. Reaction of aniline with acetaldehyde gave 262, but a subsequent aldol condensation with the imine derived from acetaldehyde (sec. 9.4.F.i) led to 263.1 Friedel-Crafts cyclization was followed by loss of aniline to give 264, and aromatization gave 2-methylquinoline (265). 

Two synthetic routes predicted by LHASA for the synthesis of quinoline (24) are shown in Scheme 7. LHASA S first synthetic route was to have 2-amino-benzaldehyde (25) condense with acetaldehyde (26) to yield quinoline and water, which is essentially equivalent to the known synthesis of quinoline from the reaction of aniline with acetaldehyde and formaldehyde (77). When this transform was removed from consideration, LIMS A suggested nucleophilic addition of aniline (27) to acrolein (28) to yield quinoline and water, which is identical to a known synthesis of quinoline (75). 

Quinoline was discovered in coal tar by Friedlieb Ferdinand Runge in 1834 it is present in concentrations of approximately 0.3%. Quinoline is recovered by extraction with sulfuric acid from the methylnaphthalene fraction of coal tar, followed by springing with ammonia and rectification of the crude base mixture. Quinoline can be synthesized by the Skraup method, by the reaction of aniline with glycerol (or acrolein produced from glycerol) and catalytic gas-phase reaction of aniline with acetaldehyde. Since the supply of the tar-derived material has been adequate for a long time, synthetic production is not warrented. 

When a mixture of aniline, hydrochloric acid and acetaldehyde is heated (in the absence of an oxidising agent), a vigorous reaction occurs with the pro duction of quinaldine. In these circumstances, the main reactions are undoubtedly, (i) the acetaldehyde undergoes the aldol condensation, and the... 

Dehydrogenation processes in particular have been studied, with conversions in most cases well beyond thermodynamic equihbrium Ethane to ethylene, propane to propylene, water-gas shirt reaction CO -I- H9O CO9 + H9, ethylbenzene to styrene, cyclohexane to benzene, and others. Some hydrogenations and oxidations also show improvement in yields in the presence of catalytic membranes, although it is not obvious why the yields should be better since no separation is involved hydrogenation of nitrobenzene to aniline, of cyclopentadiene to cyclopentene, of furfural to furfuryl alcohol, and so on oxidation of ethylene to acetaldehyde, of methanol to formaldehyde, and so on. 

In a reaction which is mechanistically related to the Skraup reaction an a,/ -unsaturated carbonyl compound, generated by way of an acid-catalysed aldol condensation, reacts with a primary aromatic amine in the presence of acid to yield a quinoline derivative (Doebner-Miller reaction). For example, when aniline is heated with paraldehyde (which depolymerises to acetaldehyde during the reaction) in the presence of hydrochloric acid the final product is 2-methyl-quinoline (101) (quinaldine, Expt 8.40). Retrosynthetic analysis for the 1,2-dihydroquinoline reveals crotonaldedhyde as the unsaturated carbonyl component which is in turn formed from acetaldehyde (see Section 5.18.2, p. 799). 

In this case the final dehydrogenation of 1,2-dihydroquinaldine to quinaldine is effected by anils formed by the condensation of aniline with either acetaldehyde or crotonaldehyde during the course of the reaction. This yields secondary amines as by-products these together with excess aniline are separated from the quinaldine by acetylation of the reaction mixture. The acetylated primary and secondary amines thus formed are less steam volatile than quinaldine which forms the basis of the isolation of the latter. 

The nse of polysnlfide complexes in catalysis has been discnssed. Two major classes of reactions are apparent (1) hydrogen activation and (2) electron transfers. For example, [CpMo(S)(SH)]2 catalyzes the conversion of nitrobenzene to aniline at room temperature, while (CpMo(S))2S2CH2 catalyzes a number of reactions snch as the conversion of bromoethylbenzene to ethylbenzene and the rednction of acetyl chloride, as well as the rednction of alkynes to the corresponding cw-alkenes. Electron transfer reactions see Electron Transfer in Coordination Compounds) have been studied because of their relevance to biological processes (in, for example, ferrodoxins), and these cluster compounds are dealt with in Iron-Sulfur Proteins. Other studies include the use of metal polysulfide complexes as catalysts for the photolytic reduction of water by THF and copper compounds for the hydration of acetylene to acetaldehyde. ... 

Ring Closure Reactions Several authors worked on the S5mthesis of 2-methyl and 4-methylquinolines. Thus, Campanati et al. performed the reaction of 2-ethylaniline with ethylene glycol using an acid-treated commercial montmorillonite K-10 catalyst to obtain mainly 2-methyl-8-ethylquinoline [137]. Brosius et al. reported the synthesis of both 2-methyl and 4-methylquinolines from aniline and acetaldehyde over BE A zeolite catalysts [138]. 

Three-component Mannich reactions of cyclohexanone and anilines with aromatic aldehydes, in the presence of HjO, have been promoted by amphiphilic isosteviol-proline organocatalysts with excellent de and eef DFT calculations indicate that the proline-catalysed single and double Mannich reactions between acetaldehyde and A-Boc imines, to give (5) and (5,5)-conformation products, respectively, are stereochemically controlled by hydrogen bonding." High enantioselectivity has been reported for L-proline-catalysed addition of aldehydes to 2-aryl-3//-indol-3-ones," ... 

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