Synthesis of 4‐(Monoalkylamino)‐coumarins

Convenient Replacement of the Hydroxy by an Amino Group in 4 Hydroxycoumarin and 4-Hydroxy-6-methyl-2-pyrone under Microwave Irradiation

“…The pressure reaction tube used for these experiments was equipped with a Teflon ring to firmly close the tube and to permit longer irradiation at 850 W. Optimum irradiation times were precisely determined by TLC control (Merck silica gel pre-coated Alsheets) at 60, 75, 90, 105 and 120 seconds. Most yields obtained by this simple procedure were almost quantitative (Table 1), with the exception of the corresponding N-cyclohexyl derivative 3c (40 %; previously 20 % [3]). However, the reaction failed under the described conditions with volatile primary amines (methylamine, ethylamine, propylamine) as well as with the following primary amines: 3-amino-and 4-aminopyridine, 2-aminoethanol, and 1,2-ethanediamine.…”

“…The action of primary aromatic, arylaliphatic and aliphatic amines on 4-hydroxycoumarin (1) (Scheme 1) results in the formation of N-substituted 4-aminocoumarins [2][3][4]. The latter compounds have also been prepared by the reaction of 4-halogenocoumarins with amines together with (o-hydroxyphenyl)propiolamide by-products formed by opening of the α-pyrone ring followed by elimination of hydrogen halogenide [5].…”

“…Some of the prepared compounds of type 3 showed antimicrobial activity [2]. It was recently reported that refluxing 1 in glacial acetic acid with an excess of primary amine prevented lactone ring opening and increased the yield [3]. Disadvantages of this procedure are the long reaction times (10-20 h) needed for the preparation of the N-(monoalkyl)-substituted products of type 3.…”

“…Disadvantages of this procedure are the long reaction times (10-20 h) needed for the preparation of the N-(monoalkyl)-substituted products of type 3. The reaction of 1 with secondary amines was reported to fail [3]. All known methods require considerable excess of the amine, e.g.…”

Design, Synthesis and Evaluation of Cytotoxicity of Novel Chromeno[4,3‐b]quinoline Derivatives

“…4‐Aminocoumarin was obtained in 90% yield by melting 4‐hydroxycoumarin in the presence of excess ammonium acetate for 30 min. This method compared to the ones using boiling acetic acid or ethoxyethanol has more yields and needs less time 26–29. It seems 4‐aminocoumarin was converted to 4‐hydroxycoumarin in the presence of both solvents and heating, making to decrease yield.…”