spectral data) out of the two possible diastereomeric 3-methyl-1-(2,4-dimethylphenyl)-1-phenyl-1,3-
dihydroisobenzofurans (3c), which is evidence for stereospecificity of the reaction.
We assume that cyclization of iodomethylates 2a-c occurs as an intramolecular nucleophilic substitution
according to an SN2 mechanism, i.e., with inversion of the configuration of the site that is attacked (the chiral
center of the starting amine, which had an (S)-configuration). Thus in the phthalanes 3a-c obtained, the C-3 atom
should have an (R)-configuration. In the literature, (+)-3-methyl-1,3-dihydroisobenzofuran is described [5], for
which an (R)-configuration has been established. The positive rotation we observed ([α]D 131°) for phthalane 3a
may be confirmation for the (R)-configuration of the C-3 atom in this compound and consequently for the
proposed mechanism. It is also likely that phthalanes 3b,c are formed with inversion of the configuration of the
center.
The increase in the reaction rate in the presence of salts and NaOH may be explained by the fact that the
anions, having properties of bases, to some extent promote ionization of the hydroxyl group and its conversion
to a good nucleophile, which intramolecularly attacks the benzyl carbon atom on the side opposite to the leaving
trimethylammonium group.
We also isolate a small amount of the corresponding amino alcohol 1a-c from the reaction mixture
(1-2%, if the reaction is carried out in the presence of salts; and 10% in the absence of salts), the formation of
which may be assumed to be the result of nucleophilic attack on the methyl group.
The 1H NMR spectra were taken on a Varian XL-400 (400 MHz) in CDCl3, internal standard TMS.
3-Methyl-1,1-diphenyl-1,3-dihydroisobenzofuran (3a). MeI (0.02 mmol) at 0°C was added to a
solution of amino alcohol 1a (5 mmol) in dry acetone (50 ml). The precipitated iodomethylate 2a was filtered
out and washed with dry ether; mp 232°C (decomposes). [α]D -84° (c 1, ethanol).
A mixture of iodomethylate 2a (5 mmol), sodium acetate (25 mmol) in freshly distilled DMF (20 ml)
was refluxed for 5 h and then the DMF was driven off under vacuum; the residue was dissolved in water,
alkalinized to pH 10-11, and extracted with ether. The ether extracts were washed with 1 N HCl solution and
dried with MgSO4. The ether was distilled off and the phthalane 3a obtained (98% yield) was recrystallized from
alcohol; mp 92°C, [α]D 131° (c 1, ethanol). 1H NMR spectrum, δ, ppm: 1.62 (3H, d, CH3–CH); 5.30 (1H, q, CH–
CH3); 7.10-7.40 (14H, m, arom.). Found, %: C 87.79; H 6.43. C21H18O. Calculated, %: C 88.08; H 6.33.
3'-Methyl-3'-H-spiro[cyclohexane-1,1'-isobenzofuran] (3b) was obtained similarly from
iodomethylate 2b; mp 204°C (decomposes), [α]D 10° (c 1, ethanol), and was purified chromatographically on a
column with silica gel (Silica gel 60) in a benzene–acetone system, 10:1, Rf 0.8. Yield 50%. [α]D -8° (c 2,
1
ethanol). H NMR spectrum, δ, ppm: 1.50 (3H, d, CH3–CH); 1.60-1.90 (10H, m, C6H10); 5.28 (1H, q,
CH–CH3); 7.08-7.30 (4H, m, arom.).
3-Methyl-1-(2,4-dimethylphenyl)-1-phenyl-1,3-dihydroisobenzofuran (3c) was obtained similarly
from the corresponding iodomethylate 2c; mp 232°C (decomposes); [α]D 33° (c 1, ethanol), yield 70%;
mp 75°C; [α]D -257° (c 1, ethanol). 1H NMR spectrum, δ, ppm: 1.38 (3H, d, CH3–CH); 1.95 (3H, s, p-CH3); 2.30
(3H, s, o-CH3); 5.45 (1H, q, CH–CH3); 6.75-7.30 (12H, m, arom.).
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