Acetyl ketene aminals in Nenitzescu reaction

Abstract

Nenitzescu reaction of acetyl ketene aminals (N,N-acetals) was investigated. The interaction of 2-acetyl-l-amino-l-anilinoethene with benzoquinone gave 3-acetyl-2-amino-7a-hydroxy-l-phenyl-5,7a-dihydro-IH-indol-5-one, which was then transformed into 3-aeetyl-2-amino-6-chloro-5-hydroxy-l-phenylindole. The reaction of benzoquinone with 2-acetyi-lamino-l-benzoylaminoethene led to the corresponding hydroquinone-adduct which was oxidized to 4-acetylamino-5-(2,5-dihydroxyphenyl)-2-phenyloxazole.

The first example of the synthesis of 1-aminoindole derivatives by the Nenitzescu reaction

“…21,22 Appar ently, the same scheme is valid in the formation of indole 8 from compound 7 (rather than from compound 5 as we assumed earlier 11 ). Such rearrangements were reported earlier.…”

Synthesis of 3-EWG-Substituted 2-Amino-5-hydroxyindoles via Nenitzescu Reaction

“…1 H NMR spectra: Bruker AM 360 spectrometer at 360 MHz. 13 C NMR spectra: Bruker AC 250 spectrometer at 250 MHz. NMR spectra were measured in DMSO-d 6 or CDCl 3 , using TMS as internal standard.…”

“…In the literature only a second example is reported in which a primary/secondary acetylketene aminal is reacted with 1,4-benzoquinone (1). 13 According to our outlined strategy we report here on the Nenitzescu reaction of primary EWG-substituted ketene aminals 2 with 1,4-benzoquinone (1). This procedure affords new 2-amino-5-hydroxyindoles 3 with EWGgroups in position 3, suitable for pyrimidine ring closure reactions.…”

“…The required primary ketene aminals 2a-e were prepared according to literature procedures. [14][15][16][17][18] In order to calculate the enaminic (nucleophilic) properties of ketene aminal ethyl 3,3-diaminoacrylate (2a), we compared the 13 C NMR value of C-2 with the value of the standard enamine of the Nenitzescu reaction, ethyl (Z)-3aminocrotonate (5) (Figure 1). It turned out that in 5 the value for C-2 is 81.3 ppm and in 2a 62.9 ppm, indicating an enhanced nucleophilicity of 2a compared to 5 and a proposed good reactivity with the enone substructure of 1,4-benzoquinone (1).…”

“…Spectroscopic data ( 1 H, 13 C NMR, IR, UV) showed, that ethyl 2-amino-5-hydroxyindole-3-carboxylate (3a) had been formed in 49% yield. Structural proof of 3a as a 5hydroxyindole derivative was done by means of HMBC and HSQC experiments.…”