2ꢀPolyfluoroalkylꢀ4Hꢀchromenꢀ4ꢀimines
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 2, February, 2004
391
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1615, 1575 (C=N, arom.). H NMR (CDCl3), δ: 2.53 (s, 3 H,
2 mL of an ammonium acetate solution prepared by mixing
glacial AcOH (8 mL), water (2 mL), and 25% NH3 (3 mL). The
reaction mixture was thoroughly stirred for 30 min and then
diluted with 5 mL of water. The colorless precipitate of amino
enone 2 that formed was filtered off, washed with H2O, and
dried. The yields of amino enones 2a,d were 90 and 97%, reꢀ
spectively.
Me); 3.73 (t, 2 H, CH2N, J = 5.2 Hz); 3.95 (s, 3 H, MeO); 4.02
(t, 2 H, CH2O, J = 5.2 Hz); 4.03 (s, 3 H, MeO); 6.77 (d, 1 H,
H(3), J = 2.3 Hz); 7.42 (d, 1 H, H(2), J = 2.3 Hz). (Nonꢀ
recrystallized imine 9 contains 17% khellinone (1H NMR data).
1H NMR (CDCl3), δ: 2.73 (s, 3 H, Me); 4.04 (s, 3 H, MeO);
4.14 (s, 3 H, MeO); 6.90 (d, 1 H, H(3), J = 2.3 Hz); 7.51 (d,
1 H, H(2), J = 2.3 Hz)).
Synthesis of thiocyanates 6a,b,d (general procedure). Potasꢀ
sium thiocyanate (0.40 g, 4.1 mmol) and chromenimines 4a,d
(0.66 mmol) were triturated in 2 mL of AcOH—water (2 : 1) for
5 min (for 4b, in 2.5 mL of Me2CO—AcOH—water (2 : 2 : 1)).
The reaction mixture was diluted with 10 mL of water and the
precipitate that formed was filtered off, dried, and recrystallized
from toluene (see Table 3). Acid hydrolysis of thiocyanates 6a,b,d
under the conditions described for compounds 2a,b,d and 4a,b,d
gave chromanones 5a,d in 71 and 65% yields, respectively.
5ꢀ[4,4,4ꢀTrifluoroꢀ3ꢀ(2ꢀhydroxyethylamino)ꢀ1ꢀoxobutꢀ2ꢀ
enyl]ꢀ6ꢀhydroxyꢀ4,7ꢀdimethoxybenzofuran (8a). Trifluorokhellin
7a (0.19 g, 0.60 mmol) and 2ꢀaminoethanol (0.06 g, 1.0 mmol)
were dissolved in 1.5 mL of ethanol, stirred at ≈20 °C for 24 h,
and then diluted with 10 mL of water. The precipitate that
formed within 4 h was filtered off, washed with water, dried, and
recrystallized from toluene—hexane (1 : 1). The yield of 8a was
0.06 g (26%); orange crystals, m.p. 134 °C. Found (%): C, 51.32;
H, 4.50; N, 3.52. C16H16F3NO6. Calculated (%): C, 51.21;
H, 4.30; N, 3.73. IR, ν/cm–1: 3480 (OH), 3170 (CH=), 1640
Synthesis of 3ꢀalkylaminoꢀ3ꢀ(2ꢀhydroxyaryl)ꢀ1ꢀpolyfluoroꢀ
alkylpropꢀ2ꢀenꢀ1ꢀones 2a—i and 10 (general procedure). Anꢀ
hydrous THF (20 mL), finely ground LiH (0.50 g, 0.063 mol),
CF3CO2Et (3.2 mL, 3.8 g, 0.027 mol), and the corresponding
imine (0.018 mol) were placed in a roundꢀbottom threeꢀneck
flask fitted with a mechanical stirrer and a reflux condenser. The
stirred reaction mixture was refluxed for 4 h, whereupon the
solvent was removed in vacuo. The residue was treated with
7% AcOH and the product (white powder) was filtered off,
washed with water, dried, and recrystallized from an appropriꢀ
ate solvent (see Table 3).
Synthesis of 2ꢀpolyfluoroalkylꢀ4Hꢀchromenꢀ4ꢀimines 4a—i
(general procedure). Amino enone 2 (0.0125 mol) was dissolved
in 16 mL of ethanol saturated with HCl. The mixture was left at
≈20 °C for 2 h and then mixed with cold water (150 mL). Then,
aqueous 25% NH3 (16 mL) was added in one portion to the
stirred solution. The precipitate of chromenimine 4 that formed
was filtered off, washed with water, dried, and recrystallized
from hexane (the hot solution was filtered to remove an impuꢀ
rity of amino enone 2, which is insoluble in nonpolar solvents)
(see Table 3). Chromenimines 4 are storageꢀstable colorless
needleꢀlike crystals.
Nꢀ(2ꢀHydroxyethyl)ꢀ6ꢀmethylꢀ2ꢀtrifluoromethylꢀ4Hꢀ
chromenꢀ4ꢀimine hydrochloride (3e). Amino enone 2e (0.30 g,
1.0 mmol) was dissolved in 1.5 mL of ethanol saturated with
HCl. The resulting solution was kept at ≈0 °C for 2 h and mixed
with EtOH (2 mL) and Et2O (7 mL). The precipitate that formed
was filtered off, washed with Et2O, and dried (see Table 3).
Hydrolysis of amino enones 2a,b,d and chromenimines 4a,b,d.
Amino enone 2 or chromenimine 4 (0.65 mmol) was heated
with 65% AcOH (2 mL) at 80 °C for 1 h. The reaction mixture
was allowed to cool and diluted with 10 mL of water. The colorꢀ
less precipitate of chromanone 5 that formed was filtered off,
washed with H2O, and dried.
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(NH), 1620 (C=O), 1550 (C=C). H NMR (CDCl3), δ: amino
enone form (50%): 3.6—3.7 (m, 3 H, CH2N, OH); 3.90 (t, 2 H,
CH2O, J = 5.3 Hz); 3.98 (s, 3 H, MeO); 4.07 (s, 3 H, MeO);
6.84 (s, 1 H, CH=); 6.83 (d, 1 H, H(3), J = 2.1 Hz); 7.49 (d,
1 H, H(2), J = 2.1 Hz); 10.6 (br.s, 1 H, NH); 12.9 (br.s, 1 H,
phenolic OH); oxazolidine form (50%): 3.06 (d, 1 H, CHH,
JAX = 14.7 Hz); 3.1—3.4 (m, 2 H, CH2N); 3.6—4.0 (m, 2 H,
CH2O); 4.05 (s, 3 H, MeO); 4.18 (s, 3 H, MeO); 4.40 (d, 1 H,
CHH, JAX = 14.7 Hz); 6.91 (d, 1 H, H(3), J = 2.4 Hz); 7.52 (d,
1 H, H(2), J = 2.4 Hz); 12.4 (br.s, 1 H, OH). 1H NMR
(DMSOꢀd6), δ: 3.47 (q, 2 H, CH2N, J = 5.3 Hz); 3.63 (q, 2 H,
CH2O, J = 5.1 Hz); 3.89 (s, 3 H, MeO); 3.95 (s, 3 H, MeO);
5.10 (t, 1 H, OH, J = 4.9 Hz); 6.21 (s, 1 H, CH=); 7.10 (d, 1 H,
H(3), J = 2.4 Hz); 7.87 (d, 1 H, H(2), J = 2.4 Hz); 10.4 (br.s,
1 H, NH); 11.2 (s, 1 H, phenolic OH).
6ꢀHydroxyꢀ5ꢀ[3ꢀ(2ꢀhydroxyethylamino)ꢀ1ꢀoxobutꢀ2ꢀenyl]ꢀ
4,7ꢀdimethoxybenzofuran (8b). Khellin 7b (0.25 g, 0.96 mmol)
was thoroughly triturated with 2ꢀaminoethanol (0.12 g,
2.0 mmol). The resulting mixture was left for six days and then
mixed with water (10 mL). The precipitate that formed was
filtered off, washed with water, dried, and recrystallized from
toluene. The yield of 8b was 0.28 g (90%); yellow crystals, m.p.
146 °C. Found (%): C, 59.84; H, 6.14; N, 4.21. C16H19NO6.
Calculated (%): C, 59.81; H, 5.96; N, 4.36. IR, ν/cm–1: 3480
(OH), 1635 (NH), 1590, 1570, 1545, 1510 (C=O, C=C, arom.).
1H NMR (CDCl3), δ: 2.11 (s, 3 H, Me); 2.33 (br.s, 1 H, OH);
3.52 (q, 2 H, CH2N, J = 5.6 Hz); 3.85 (br.s, 2 H, CH2O); 3.91
(s, 3 H, MeO); 4.06 (s, 3 H, MeO); 6.20 (d, 1 H, CH=); 6.78 (d,
1 H, H(3), J = 2.1 Hz); 7.44 (d, 1 H, H(2), J = 2.1 Hz); 11.2
(br.s, 1 H, NH); 13.5 (br.s, 1 H, phenolic OH).
2ꢀHydroxyꢀ2ꢀtrifluoromethylchromanꢀ4ꢀone (5a) was obꢀ
tained upon hydrolysis of amino enones 2a,b and chromenimines
4a,b in 70—72 and 60—65% yields, respectively; colorless crysꢀ
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tals, m.p. 153—154 °C (Ref. 24: m.p. 151—153 °C). H NMR
(CDCl3), δ: 3.04 (d, 1 H, CHH, JAB = 16.7 Hz); 3.10 (d, 1 H,
CHH, JAB = 16.7 Hz); 3.61 (s, 1 H, OH); 7.07 (dd, 1 H, H(8),
Jo = 8.3 Hz, Jm = 1.0 Hz); 7.15 (ddd, 1 H, H(6), Jo = 7.8 and
7.3 Hz, Jm = 1.0 Hz); 7.58 (ddd, 1 H, H(7), Jo = 8.3 and 7.3 Hz,
Jm = 1.7 Hz); 7.93 (dd, 1 H, H(5), Jo = 7.8 Hz, Jm = 1.7 Hz).
2ꢀHydroxyꢀ6ꢀmethylꢀ2ꢀtrifluoromethylchromanꢀ4ꢀone (5d)
was obtained upon hydrolysis of amino enone 2d and chromenꢀ
imine 4d in 60 and 62% yields, respectively; colorless needles,
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m.p. 158—159 °C (Ref. 25: m.p. 157 °C). H NMR (CDCl3), δ:
2.33 (s, 3 H, Me); 3.00 (d, 1 H, CHH, JAB = 16.7 Hz); 3.07 (d,
1 H, CHH, JAB = 16.7 Hz); 3.60 (s, 1 H, OH); 6.96 (d, 1 H,
5ꢀ[4,4,4ꢀTrifluoroꢀ1ꢀ(2ꢀhydroxyethylamino)ꢀ3ꢀoxobutꢀ1ꢀ
enyl]ꢀ6ꢀhydroxyꢀ4,7ꢀdimethoxybenzofuran (10) was obtained as
described for amino enones 2. The yield of 10 was 58%; colorless
crystals, m.p. 169—170 °C (toluene). Found (%): C, 51.43;
H, 4.31; N, 3.74. C16H16F3NO6. Calculated (%): C, 51.21;
H(8), Jo = 8.4 Hz); 7.38 (dd, 1 H, H(7), Jo = 8.4 Hz, Jm
2.2 Hz); 7.71 (d, 1 H, H(5), Jm = 2.2 Hz).
=
Synthesis of amino enones 2a,d from chromenimines 4a,d
(general procedure). Chromenimine 4 (0.65 mmol) was added to