Unusual Fries rearrangement of 7-acyloxyquinolin-2-ones– A new way to linear and angular furoquinolin-2-ones

Unusual temperature dependence of the Fries rearrangement of 7-acetoxy-4-methylquinolin-2-one has been established. The predominant content of 6-acetyl-7-hydroxy-4-methylquinolin-2-one in the final reaction mixture at higher temperature (155 o C) is due to a higher thermodynamic stability of this isomer in comparison to 8-acetyl-7-hydroxy-4-methylquinolin-2-one. The preferable formation of 8-acetyl-isomer at lower temperature (85 o C) seems to be due to the kinetically controlled reaction. By the AM1 calculations, the highest negative charge (by absolute value) at the position 8 has been found both in 7-hydroxy-4-methylquinolin-2-one and in its AlCl 3 -complex. Both 6-and 8-acetyl-7-hydroxy-4-methylquinolin-2-ones were smoothly transformed to the corresponding linear furo[3,2-g]quinolin-7-one and angular furo[2,3-h]quinolin-2-one.


Introduction
The Fries rearrangement of acyloxyarenes and acyloxyheteroarenes is a convenient way of corresponding o-hydroxyketones preparation.It goes smoothly also with acyloxycoumarins.We have previously found this reaction to be extremely useful in the syntheses of both linear and angular furocoumarins [1][2][3], well known as photochemotherapeutic medicines [4][5][6].
Quinolin-2-ones are nitrogen-containing analogs of coumarins.However, there are no in literature any data, concerned the Fries rearrangement of acyloxyquinolin-2-ones.Meanwhile, the resulted o-(hydroxy)acyl-derivatives seem to become rather useful in the furoquinolin-2-ones preparation, which show also a significant photobiochemical activity [7].
We have carried out the Fries rearrangement of 7-acetoxy-4-methylquinolin-2-one at different temperature and compared the results with those of the 7-acetoxy-4-methylcoumarin rearrangement.These results are quite different from those of the 7-acetoxy-4-methylcoumarin (5) Fries rearrangement (scheme 2) [3].The preferable formation of the 8-acetyl-isomer 3 at lower temperature (85 o C) seems to be due to the kinetically controlled Fries rearrangement of the compound 2. We have earlier found the Fries rearrangement to be an intermolecular reaction in the acylhydroxycoumarin series [3].

Results and Discussion
The same might be quite true for their acyloxyquinolin-2-one analogs.Therefore, the ratelimiting step of the compound 2 Fries rearrangement seems to be an electrophilic attack of acetyl cation on the compound 1 or its AlCl3-complex, since the reaction goes in the large excess of AlCl3.The highest negative charge (by absolute value) at the free positions of the substrate benzene ring will facilitate the rate of the reaction.The diagrams of the AM1 charges in the compound 1 and its AlCl3-complex 8 are shown below.
The position 8 is much more negatively charged in both structures and looks the more preferable one for the electrophilic attack when compared with the position 6.
Discussing the results of the compound 5 Fries rearrangement, the following AM1 calculation data should be kept in mind: thermodynamic stabilities of the isomers 6 and 7 are almost equal (Table 2); the highest negative charge (by absolute value) at the position 8 has been found by the AM1 calculations of both 7-hydroxy-4-methylcoumarin (9) and its AlCl3-complex (10); it can be seen on the diagrams shown below.Mass spectra were scanned on a SSQ-710 (Finnigan MAT) spectrometer at the energy of ionizing electrons equal to 70 ev.

7 -
Hydroxy-4-methylquinolin-2-one (1) has been prepared by heating of m-aminophenol and acetoacetic ester at 140-150 o C [8].This compound was then acetylated.Accordingly to the Fries rearrangement procedure, the resulted 7-acetoxy-4-methylquinolin-2-one (2) has been treated by excess of AlCl3 at different temperatures from 85 o C to 155 o C. The composition of the rearrangement products has been analyzed by the 1H NMR spectra.In general, two isomers: 8acetyl-4-methylquinolin-2-one (3) and 6-acetyl-4-methylquinolin-2-one (4) -have been detected in the reaction mixtures (scheme 1).The compositions of the final reaction mixtures and analytical chemical shifts for the compounds 1-4 are listed in the Scheme 2

1 H
As it was expected, acetylquinolin-2-ones 3 and 4 react easily with phenacylbromides.The corresponding both angular and linear furoquinolin-2-ones (11) and (12) have been isolated with a good yield.NMR spectra were recorded on a WP 200 (Bruker) spectrometer at 200 MHz in DMSO-d6 solutions using TMS as an internal standard.Chemical shifts are given in ppm.

. ISSN 1551-7004 Page 933  ARKAT USA, Inc The compound 3 predominates
in the reaction mixture when the rearrangement was carried out at 85 o C.Only traces of the compound 4 were detected in these conditions.Increase of the reaction temperature to 125 o C and then to 155 o C leads to a sharp decrease of the compound 3

Table 2 )
. The predominance of the isomer 4 at 155 o C seems to be due to its higher stability: it is more than 8 kcal/mol more stable than the isomer 3.