Synthesis of 2‐amino‐3‐carbethoxy‐1‐hydroxyindoles

Abstract

A general method is described for the synthesis of 2‐amino‐3‐carbethoxy‐l‐hydroxyindoles by the reductive cyclization of 2‐nitrophenylcyanoacetates using zinc and acetic acid at temperatures of 15–28°.

o-Nitrophenylacetonitrile Michael additions and cyclocondensations: a novel quinoline synthesis

“…However, drying of the K2CO3 (overnight 400 °C) and ethanol (over freshly activated sieves for >24 h) had no bearing on the outcome of the reaction, which raises the possibility that carbonate is the nucleophile that ring-opens intermediate 26 in these instances. In contrast to the two-step synthesis of 28 (Table 2 and Scheme 3), heating 1, diethyl maleate (12) and K2CO3 from the outset gave a complex mixture of products, suggesting that, with some electrophiles, one-pot annulations of this type may best be carried out with a room-temperature Michael-addition step prior to heating to induce the cyclocondensation reaction.…”

“…o-Nitrophenylacetonitriles, e.g., the parent 1, are valuable and versatile precursors to a variety of benzo-fused heterocycles, including indoles 2, 1-10 N-hydroxyindoles 3, [11][12][13][14][15] quinoline-N-oxides 4, [16][17][18][19][20][21] quinolines 5, [22][23][24][25][26] cinnoline-1-oxides 6, [27][28][29] and 2,1-benzisoxazoles (anthranils) 7 20,30,31 (Figure 1). As part of efforts to achieve the total synthesis of the marine pyrroloacridine natural product alpkinidine, [32][33][34] we investigated Michael addition of 1 to quinones.…”

Syntheses of New Multisubstituted 1-Acyloxyindole Compounds

“…In particular, Granchi et al discovered that 1-hydroxyindole derivatives inhibited lactate dehydrogenase isoform A (LDH-A) at low micromolar concentration [ 12 ] and thus were considered as potential compounds for cancer treatment [ 16 ]. Furthermore, these derivatives were employed as intermediates for synthesis of potent anticonvulsant and antiarrhythmic agents [ 17 ]. Despite their various biological activities, few studies on 1-hydroxy, 1-alkoxy, and 1-acyloxyindole derivatives have been conducted.…”

“…Other groups employed Zn/NH 4 Cl [ 2 ], tin chloride (SnCl 2 ) [ 21 , 22 , 23 ], or Pd/triethylammonium formate (TEAF) [ 24 ] for reductive cyclization to produce 1-hydroxyindole moiety, and 1-Alkoxyindole compounds were also synthesized by alkylation of 1-hydroxyindoles [ 25 ] or intramolecular cyclization of methoxime structure [ 26 ]. Although a few simple 1-acyloxyindole derivatives were synthesized by acylation of 1-hydroxyindoles [ 17 , 27 , 28 , 29 , 30 ], the generated 1-acyloxyindoles were unstable and easily hydrolyzed to afford 1-hydroxyindoles [ 31 ]. Consequently, these compounds suffer from chemical instabilities and difficult manipulation.…”

Synthesis of 2-Aminoindole-3-carboxylic Acid Derivatives by the Copper(I) Iodide Catalyzed Reaction of N-(2-Iodophenyl)formamides with Malononitrile or Cyanoacetates

“…Ethyl 2-Aminoindole-3-carboxylate (3b) 12,13Beige solid; mp 179-181 °C (hexane-THF) (Lit 12. mp 178-180 °C).…”