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Russ.Chem.Bull., Int.Ed., Vol. 51, No. 5, May, 2002
Shklyaev and Nifontov
Table 2 (continued)
Comꢀ
pound
IR,
ν/cm–1
1H NMR, δ
H arom.
s, 6 H,
3,3ꢀMe2
s, 2 H,
4ꢀCH2
Other signals
7a*
7b
—
1.20
1.21
1.19
1.17
2.72
2.70
2.72
2.75
7.12—7.67 (w.m,
7 Н, 5ꢀН, 6ꢀН,
8ꢀН + 4 Н salicyl.)
2.25 (s, 3 Н, 7ꢀМе); 2.36 (s, 3 Н, 1ꢀМе);
12.45 (br.s, 1 Н, ОН phenolic)
1612; 1580
7.12 (d, 1 Н, 5ꢀН);
7.24 (d, 1 Н, 6ꢀН);
7.60 (s, 1 Н, 8ꢀН)
2.28 (s, 3 Н, 7ꢀМе);
2.36 (s, 3 Н, 1ꢀSМе)
7c
3290; 1735; 1600;
1580; 1500
7.15 (d, 1 Н, 5ꢀН);
7.20 (d, 1 Н, 6ꢀН);
7.58 (s, 1 Н, 8ꢀН)
1.25 (t, 3 Н, МеCH2); 2.27 (s, 3 Н, 7ꢀМе);
4.21 (q, 2 Н, ОСН2); 5.11 (s, 1 Н, СН=С);
9.87 (s, 1 Н, NH)
7d
3310; 3200; 1640;
1605; 1575
7.10 (d, 1 Н, 5ꢀН);
7.17 (d, 1 Н, 6ꢀН);
7.40 (s, 1 Н, 8ꢀН)
2.30 (s, 3 Н, 7ꢀМе); 5.15 (s, 1 Н, СН=С);
6.30 (s, 2 Н, NH2);
9.45 (s, 1 Н, NH)
* Identified as salicylate.
with 20 mL of Et2O, and crystallized from ethyl acetate. Physiꢀ
cochemical constants and spectroscopic data for compounds
1a—c and 2a—c are identical with those reported in Ref. 5.
Threeꢀcomponent synthesis of 1ꢀcarbamoylmethylideneꢀ3,3ꢀ
dimethylꢀ1,2,3,4ꢀtetrahydroisoquinolines (1d, 2d, and 5d—7d)
(general procedure). Cyanoacetamide (8.4 g, 0.1 mol) was disꢀ
solved in 50 mL of cold conc. H2SO4. A mixture of an arene
(0.1 mol) and isobutyraldehyde (0.1 mol) was added dropwise
with stirring over 15—20 min. The reaction mixture was stirred
for 30 min, poured into 300 mL of water, and washed with
50 mL of toluene. The organic layer was separated and the
aqueous layer was neutralized with ammonium carbonate to
pH 8—9. The precipitate that formed was filtered off, washed
with water, dried in air, and recrystallized.
though dimerization of two carbocations stabilized by
aryl radicals cannot be ruled out either.
Analogous products have been obtained earlier8 from
veratrole and isobutyraldehyde in the study of the Baeyer
reaction.
Experimental
IR spectra were recorded on a URꢀ20 spectrophotometer
1
(Nujol). H NMR spectra were recorded on a Bruker AMꢀ300
instrument (300.13 MHz) in DMSOꢀd6 with Me4Si as the inꢀ
ternal standard. Mass spectra were obtained on a Finnigan
MAT spectrometer.
Melting points were determined on a Kofler hot stage. The
course of the reactions and the purity of the compounds obꢀ
tained were monitored by TLC on Silufol UVꢀ254 plates in
chloroform—acetone (9 : 1) with detection by a 0.5% solution
of chloranil in toluene.
1,1ꢀBis(acylamino)ꢀ2ꢀmethylpropanes (8a—d). After the reꢀ
action mixtures obtained in the syntheses of compounds 7a—d
were diluted with water, the crystals that formed were filtered
off, washed with water, dried, and recrystallized. The physicoꢀ
chemical constants and spectroscopic data for compounds 8a—d
are given in Table 3.
Threeꢀcomponent synthesis of 1ꢀsubstituted 3,3ꢀdimethylꢀ
3,4ꢀdihydroisoquinolines (1a—c, 2a—c, 5a—c, 6a—c, and 7a—c)
(general procedure). A mixture of an arene (0.1 mol), isobutyrꢀ
aldehyde (0.1 mol), and a nitrile (0.1 mol) was added dropwise
at 0—5 °C over 15—20 min to conc. H2SO4 (50 mL) with
stirring. The reaction mixture was stirred for 30 min, poured
into 300 mL of water, and washed with 50 mL of toluene. The
organic layer was separated and the aqueous layer was neutralꢀ
ized with ammonium carbonate to pH 8—9. The precipitate
that formed was filtered off, washed with water, dried, and
recrystallized (5b,c and 6b,c) or extracted with CHCl3 (1a—c,
2a—c, 5a, 6a, and 7a—c). The solvent was evaporated on a
water bath and the residue was distilled in vacuo (1a—c, 2a—c,
and 7b,c) or converted into salicylate (5a, 6a, and 7a). In the
latter case, a solution of salicylic acid (1.38 g, 0.01 mol) in
20 mL of dry Et2O was added in one portion to a solution of
compound 5a, 6a, or 7a (0.1 mol) in 10 mL of dry Et2O. The
reaction mixture was stirred for 1 min and allowed to stand for
30 min. The precipitate that formed was filtered off, washed
2,2´ꢀ(Isopropyl)methylenebis(1,4ꢀdimethoxybenzene) (4a)
was extracted with toluene from the reaction mixtiure obtained
in the synthesis of compounds 2a—d. The extract was washed
with aqueous sodium carbonate and water to the neutral reacꢀ
tion and dried with MgSO4. The solvent was removed at a
reduced pressure and the residue was recrystallized from hexꢀ
ane. The yield of compound 4a was 7.6 g (23%) with respect to
pꢀdimethoxybenzene (in the reaction with acetonitrile), m.p.
83—84 °C (cf. Ref. 8: m.p. 86—87 °C (MeOH—light petroꢀ
leum)). Found (%): C, 72.90; H, 8.00. C20H26O4. Calcuꢀ
lated (%): C, 72.73; H, 7.88. IR, ν/cm–1: 1600; 1580. 1H NMR,
δ: 0.80 (d, 6 H, Me2CH); 2.45 (m, 1 H, CHMe2); 3.30
(d, 1 H, CHAr2); 3.68 (s, 6 H, 4ꢀOMe); 3.73 (s, 6 H,
1ꢀOMe); 6.80 (d, 2 H, 5ꢀH); 6.83 (d, 2 H, 6ꢀH); 6.93 (s,
2 H, 3ꢀH). MS (EI, 70 eV), m/z (Irel (%)): 330 [M]+ (10);
287 [M – Me2CH]+ (100).
4,4´ꢀ(Isopropyl)methylenebis(1,2ꢀdimethoxybenzene) (4b)
was isolated from the organic layer after workup of the reaction
Shklyaev, Yu. V.
