New Straightforward Quinoline Synthesis from the Mannich Reaction of α‐Ketohydrazones

Abstract

The addition of a-ketohydrazones to 2-acetamidobenzaldehyde proceeds efficiently in the presence of N-benzylpiperazine to afford in good to high yields the expected Mannich adducts; these are easily converted to quinoline derivatives under acidic conditions in a new Azo-Friedländer reaction.

Recent Advances in the Friedländer Reaction

“…Under these conditions, deprotection, cyclization, and elimination of the N-benzyl piperazine took place in a single step giving the 2,3-disubstituted quinoline (eq 14). 71 N-Acetylated 2-amino benzaldehydes have been combined with amides to give 2-amino-3-hydroxy quinoline derivatives in moderate yields. 72 The base-catalyzed intramolecular condensation of 2-acetamido aceto or benzophenones is known as the Camps quinoline synthesis.…”

“…82 The use of R-ketohydrazones, which are essentially azosubstituted ketones, has been already discussed in the context of an azo-Friedla ¨nder reaction based on the reaction with 2-acetamido benzaldehyde derivatives (eq 14). 71 A major limitation of the Friedla ¨nder reaction is the lack of regioselectivity when using unsymmetrical ketones. For example, it has been observed that the usual base-catalyzed Friedla ¨nder reaction conditions employing 2-amino nicotinaldehyde and 2-alkanones, such as 2-pentanone, give roughly a 1:2 mixture of 2-monosubstituted 1,8-naphthyridines (15) to 2,3-disubstituted ones (16) (Scheme 4).…”

“…Deprotection of the N -acetyl group was easily carried out in hot aqueous hydrochloric acid solutions. Under these conditions, deprotection, cyclization, and elimination of the N -benzyl piperazine took place in a single step giving the 2,3-disubstituted quinoline (eq ) …”

“…The use of α-ketohydrazones, which are essentially azo-substituted ketones, has been already discussed in the context of an azo-Friedländer reaction based on the reaction with 2-acetamido benzaldehyde derivatives (eq ) …”

C−S Bond Activation of Two Novel Asymmetric α-azo-Ketenedithioacetals Using Fe2(CO)9

“…Although, the literature describes that aldehydic arylhydrazones can be considered enamine analogues and that they, in appropriate conditions, promote the formation of arylazo compounds, only a few examples of these compounds are reported. , Recently, L. El Kaïm et al have reported the synthesis of several heterocyclic compounds via unstable azoalkenes trapped in situ by various nucleophiles …”