To convert the epoxy derivatives 2a-j into the 7-carboxyphthalimidines 3a-i we used hydrochloric and
sulfuric acids at various concentrations, 85% phosphoric acid, and boron trifluoride etherate in boiling dioxane.
The largest yields of compounds 3 were obtained with BF3·Et2O, but from the practical standpoint it is better to
use 85% phosphoric acid in the range of 70-100°C. In spite of the fact that the yield of the desired products here
is reduced by 10-15% the procedure for the synthesis and the isolation of the isoindolones 3 is greatly
simplified.
It was not possible to select conditions for the aromatization of the N-furfuryl-substituted epoxide 2j.
During esterification of the acids 2a and 3a the corresponding monoesters 4 and 5 were obtained.
The mass spectra of compounds 2 and 3 (Tables 1 and 2) contain low-intensity peaks of molecular ions,
corresponding to their molecular formulas. The readily occurring elimination of a CO2 molecule and retrodiene
dissociation (in the case of the adducts 2) are the reason for the insufficient reliability of this method of obtaining
evidence for the structure of the synthesized substances.
In the IR spectra of the carboxylic acids 2a-j and 3a-i there are characteristic bands for the stretching
vibrations of the amide and carboxyl groups in the regions of 1610-1690 and 1705-1730 cm-1 respectively, and
there is also a broad band for the associated hydroxy in the region of 2280-2485 cm-1. In the IR spectra of the
esters 4 and 5 the band of the ester group appears at 1715-1725 cm-1.
The 1H NMR spectra of compounds 2a-j (Table 3) contain three characteristic signals for the interacting
protons 7-H, 8-H, and 9-H with chemical shifts of 4.96-5.35, 6.40-6.51, and 6.46-6.66 ppm respectively and
3
3
3
spin–spin coupling constants J78 = 1.3-1.8 and J89 = 5.5-5.9 Hz. The absence of the J67-exo spin–spin coupling
constant in the bicyclooxaheptene fragment of the molecule indicates unambiguously the endo arrangement of
the 5-H and 6-H protons (J56 = 9.0-9.3 Hz) and the exo arrangement of the carboxyl and amide substituents. The
protons of the 2-CH2 group in compounds (2a-j) are chemically nonequivalent and are observed in the spectrum
in the form of an AB system. Conversely, in the 1H NMR spectra of compounds 3a-e,g-i the signals of the 3-CH2
protons are equivalent and are observed in the form of a singlet at 4.63-5.25 ppm. Only in the case of the
magnetically anisotropic tetrahydrofuryl substituent R do these protons become nonequivalent and appear in the
form of an AB system (Table 4).
EXPERIMENTAL
The IR spectra were recorded on a Specord IR-75 spectrometer in tablets with potassium bromide. The
mass spectra were recorded on an HP MS 5988 mass spectrometer with direct injection of the sample into the ion
1
source with ionizing potential 70 eV. The H NMR spectra were recorded in deuterochloroform and DMSO-d6
solutions on Bruker WP-200 (200 MHz) or Bruker WH-400 (400 MHz) instruments with TMS as
internal standard. Silufol UV-254 plates were used for thin-layer chromatography (development with iodine
vapor).
3-R-4-Oxo-3-azatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic Acids (2a-j). A mixture of maleic
anhydride (0.1 mol) and N-R-furfurylamine 1a-j (0.1 mol) in benzene (100 ml) was stirred at 25°C for 2-3 days.
The precipitate was filtered off, washed with benzene, and dried at 90°C to constant weight. Compounds 2a-j
were obtained in the form of finely crystalline powders. The spectral data and physicochemical characteristics of
the tricyclic compounds 2a-j are given in Tables 1-3.
2-R-Carboxyisoindolin-1-ones (3a-i). The epoxyisoindolinones 2a-i (0.01 mole) were heated at
70-100°C for 1 h in 85% phosphoric acid (40 ml). The reaction mixture was cooled and poured into water. The
crystals that separated were filtered off, washed with water to a neutral reaction in the wash water, dried, and
recrystallized from a mixture of isopropyl alcohol and DMF. The spectral data and physicochemical
characteristics of the isoindolones 3a-i are given in Tables 1-3.
27
Varlamov
