FATTAKHOV et al.
1,3-dioxanes in the Prins reaction under kinetic control
1852
[9]. Furthermore, the formation of oxazinane 2a as
a result of transformation of intermediate 1,3-dioxane
was also confirmed by the extremal character of the
kinetic curve for the accumulation of 4-methyl-4-
phenyl-1,3-dioxane (3) (Fig. 2).
Thus, the reaction of α-methylstyrene with formal-
dehyde and methylamine yields 3,6-dimethyl-6-
phenyl-1,3-oxazinane (2a). It has been shown for the
first time that compound 2a is formed as a result of
transformation of intermediate 1,3-dioxane which is
the product of initial Prins reaction (Scheme 2).
3,6-Dimethyl-6-phenyl-1,3-oxazinane (2a) and
4-methyl-4-phenyl-1,3-dioxane (3). A solution of
3.38 g (0.05 mol) of methylamine hydrochloride and
3.00 g (0.1 mol) of paraformaldehyde in 5.25 mL of
water was purged with nitrogen over a period of 5 min,
and 6.4 mL (0.05 mol) of α-methylstyrene (1) was
added. The mixture was refluxed for 1 h with stirring,
cooled, treated with a saturated solution of sodium
hydrogen carbonate, and extracted with chloroform.
The extract was dried over magnesium sulfate, the
solvent was removed under reduced pressure, and the
yellow oily residue was subjected to chromatographic
separation in a column charged with silica gel (eluent
hexane– ethyl acetate, 10:1.5).
Fig. 1. HMBC and NOE correlations for 3,6-dimethyl-6-
phenyl-1,3-oxazinane (2a).
was 1 h, we isolated two products, oxazinane 2a and
4-methyl-4-phenyl-1,3-dioxane (3). Intermediate
formation of 1,3-dioxane 3 provides an additional
support to Scheme 2. Here, 1,3-dioxane 3 is a kineti-
cally controlled product, and oxazinane 2a is a ther-
modynamically controlled product, which is confirmed
by the calculations of the Gibbs free energies of the
reactions (ΔGr368) by the semiempirical RM1 method
[6, 7] in the AM1 approximation [8] which is more
accurate. The obtained data showed that the formation
of oxazinane 2a (ΔGr368 = –43.0 kJ/mol) is thermo-
dynamically more favorable than the formation of
1,3-dioxane 3 (ΔG3r 68 = –18.8 kJ/mol). This is very
consistent with published data on the formation of
Compound (2a). Yield 5.0 g (52%), colorless oily
1
liquid. H NMR spectrum, δ, ppm: 1.34 s (3H, CH3),
2.02 d.t (1H, 5-H, J = 4.0, 10.5 Hz), 2.10 d.t (1H, 5-H,
J = 4.0, 10.3 Hz), 2.28 s (3H, CH3N), 2.56 m and
2.73 m (1H each, 6-H), 3.96 d and 4.13 d (1H each,
2-H, J = 9.4 Hz), 7.30 m (5H, Harom). 13C NMR spec-
trum, δC, ppm: 30.47 (C5), 31.13 (CH3), 39.45 (NCH3),
48.98 (C4), 75.65 (C6), 81.05 (C2), 125.80 (Co), 126.74
(Cp), 128.52 (Cm), 144.65 (Ci). 15N NMR spectrum:
δN 36.25 ppm. Found, %: C 74.92; H 8.87; N 7.15.
C12H17NO. Calculated, %: C 75.35; H 8.96; N 7.32.
c, M
0.20
Compound (3). Yield 3.2 g (36%). The properties of
compound 3 were in agreement with the data of [10].
0.15
0.10
0.05
0.00
When the reaction time was 20 h, other conditions
being equal, we isolated 7.0 g (80%) of 2a as the only
product.
The NMR spectra were recorded on a Bruker
Avance III 500 spectrometer at 500.13 (1H), 125.73
(13C), and 50.68 MHz (15N); 5-mm QNP probe, 298 K;
solvent CDCl3, internal standard tetramethylsilane.
Gas chromatographic analysis was performed on
a Chrom-5 chromatograph equipped with a flame
ionization detector; injector and detector temperature
250°C, oven temperature 200°C; 2.0 m×2-mm column
0
50
100
150
τ, min
200
250
300
Fig. 2. Kinetic curve for the accumulation of 4-methyl-4-
phenyl-1,3-dioxane (3) in the reaction of α-methylstyrene
with formaldehyde and methylamine hydrochloride (100°C);
initial concentrations, M: [1] = 3.33, [MeNH2 ·HCl] = 3.33,
[CH2O] = 6.66.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 12 2018
Fattakhov, A. Kh.
