Hydrogenated [1,2,4]triazolo[5,1ꢀb]quinazolines
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 2, February, 2006
349
lated (%): C, 78.50; H, 4.67; N, 13.08. IR, ν/cm–1: 3220—2680,
1660, 1608, 1572. H NMR, δ: 10.95 (br.s, 1 H, NH); 7.63 (s,
B. Sodium nitrite (0.21 g, 3 mmol) was added portionwise
(0.05 g) to a solution of compound 12 (0.4 g, 1 mmol) in AcOH
(5 mL). Once liberation of gaseous products ceased, the reacꢀ
tion mixture was poured into water and compound 14 was filꢀ
tered off. The yield was 0.21 g (53%).
7ꢀHydroxyꢀ5,6,8ꢀtriphenylꢀ6,7ꢀdihydro[1,2,4]triazoꢀ
lo[5,1ꢀb]quinazoline (15). Selenium dioxide (0.26 g, 2.5 mmol)
was added to a solution of compound 12 (0.8 g, 2 mmol) in
AcOH (10 mL). The reaction mixture was stirred at ~20 °C for
6 h and mixed with water (50 mL). An amorphous precipitate
was filtered off and recrystallized from a 1 : 20 PriOH—hexane
mixture. First, compound 15 was isolated in a yield of 0.21 g
(25%) with m.p. 275—278 °C, and then triazoloquinazoline 13
was isolated in a yield of 0.37 g (46%).
Compound 15. Found (%): C, 78.05; H, 4.86; N, 13.54.
C27H20N4O. Calculated (%): C, 77.88; H, 4.81; N, 13.46. IR,
ν/cm–1: 3148, 1612, 1600, 1532. 1H NMR, δ: 8.49 (s, 1 H,
C(2)H); 6.90—7.67 (m, 16 H, H arom.); 5.83 (d, 1 H, C(6)H,
J = 6.4 Hz); 4.79 (dd, 1 H, C(7)H, 3J = 6.4 Hz, 2J = 2.0 Hz);
4.44 (d, 1 H, C(7)OH, 2J = 2.0 Hz). MS (EI, 70 eV),
m/z (Irel (%)): 416 [M]+ (25).
10ꢀMethylꢀ5,6,8ꢀtriphenylꢀ5,6,7,10ꢀtetrahydro[1,2,4]triꢀ
azolo[5,1ꢀb]quinazoline (16). Compound 12 (0.4 g, 1 mmol) and
MeI (0.28 g, 2 mmol) were added to a 3% KOH solution in
PriOH. The reaction mixture was kept for 1 h and poured into
water. The precipitate that formed was filtered off. Compound
16 was obtained in a yield of 0.25 g (61%), m.p. 190—192 °C
(from PriOH). Found (%): C, 81.25; H, 5.83; N, 13.57.
C28H24N4. Calculated (%): C, 80.77; H, 5.77; N, 13.46. IR,
ν/cm–1: 3068, 3028, 1656, 1572. 1H NMR, δ: 7.60 (s, 1 H,
C(2)H); 6.81—6.89 (m, 11 H, H arom.); 7.25—7.42 (m, 5 H,
H arom.); 6.11 (s, 1 H, C(5)H); 3.66 (dd, 1 H, C(6)H, 3J =
8.3 Hz, 3J = 2.8 Hz); 3.15 (br.ddd, 1 H, C(7)H, 2J = –16.8 Hz,
3J = 8.3 Hz, 4J = 2.2 Hz); 2.63 (dd, 1 H, C(7)H, 2J = –16.8 Hz,
3J = 2.8 Hz); 3.59 (s, 3 H, Me). MS, m/z: 417 [M + H]+,
415 [M – H]–.
1
1 H, C(2)H); 6.98—7.62 (m, 17 H, H arom.); 6.87 (s, 1 H,
C(5)H). MS (EI, 70 eV), m/z (Irel (%)): 428 [M]+ (95).
After separation of quinazoline 7, the reaction mixture was
concentrated to oneꢀhalf of the initial volume. Dibenzoylethane
(8) was isolated from the residue. The yield was 32%, m.p.
142—143 °C (cf. lit. data21: m.p. 145 °C).
5,6,8ꢀTriphenylꢀ5,10ꢀdihydro[1,2,4]triazolo[5,1ꢀb]quinꢀ
azoline (10). A. Compound 10 was synthesized analogously to
compound 3a from azoloazine 1 and 2,3ꢀdibromoꢀ1,3ꢀdiꢀ
phenylpropanꢀ1ꢀone (9). The yield was 28%, m.p. 263—265 °C
(DMF—MeOH, 1 : 2).
B. Compound 10 was prepared analogously to compound 3a
from azoloazine 1 and 1,3ꢀdiphenylꢀ2ꢀpropynꢀ1ꢀone (11). The
yield was 43%.
C. A solution of Br2 (0.24 g, 1.5 mmol) in AcOH (3 mL) was
added to a solution of tetrahydrotriazoloquinazoline 12 (0.4 g,
1 mmol) in AcOH (3 mL). The reaction mixture was stirred for
1 h and poured into water. Compound 10 was filtered off. The
yield was 0.29 g (72%). Found (%): C, 80.67; H, 4.90; N, 14.25.
C27H20N4. Calculated (%): C, 81.00; H, 5.00; N, 14.00. IR,
1
ν/cm–1: 3376—2880, 1628, 1568. H NMR, δ: 10.67 (br.s, 1 H,
NH); 7.55 (s, 1 H, C(2)H); 6.54—7.67 (m, 17 H, H arom.); 6.63
(s, 1 H, C(5)H). MS, m/z: 401 [M + H]+, 399 [M – H]–.
5,6,8ꢀTriphenyl[1,2,4]triazolo[5,1ꢀb]quinazoline (13).
A. Tetrahydrotriazoloquinazoline 12 (0.4 g, 1 mmol) was reꢀ
fluxed in a 5% KOH solution in PriOH (10 mL) for 2 h. The
reaction mixture was neutralized with AcOH and poured into
water. The precipitate that formed was recrystallized from a 1 : 2
DMF—PriOH mixture. Yellow crystals of triazoloquinazoline
13 with m.p. 295—297 °C and compound 10 were successively
isolated in yields of 0.14 g (34%) and 0.25 g (63%), respectively.
Compound 13. Found (%): C, 81.54; H, 4.57; N, 14.15.
C27H18N4. Calculated (%): C, 81.41; H, 4.52; N, 14.07. IR,
ν/cm–1: 1596, 1576. 1H NMR, δ: 8.76 (s, 1 H, C(2)H);
7.07—8.35 (m, 17 H, H arom.). MS (EI, 70 eV), m/z (Irel (%)):
398 [M]+ (100).
10ꢀBenzylꢀ5,6,8ꢀtriphenylꢀ5,6,7,10ꢀtetrahydro[1,2,4]triꢀ
azolo[5,1ꢀb]quinazoline (17) was synthesized analogously to comꢀ
pound 16 from triazoloquinazoline 12 and benzyl chloride. The
yield was 53%, m.p. 180—183 °C (from PriOH). Found (%):
C, 83.02; H, 5.76; N, 11.51. C34H28N4. Calculated (%): C, 82.93;
H, 5.69; N, 11.38. IR, ν/cm–1: 3060, 3028, 2872, 1656, 1568.
1H NMR, δ: 7.63 (s, 1 H, C(2)H); 6.70—6.85 (m, 11 H,
H arom.); 7.15—7.47 (m, 10 H, H arom.); 6.15 (s, 1 H, C(5)H);
5.36 and 5.43 (both d, 1 H each, NCH2, 2J = –16.8 Hz); 3.66
B. A mixture of compound 12 (0.4 g, 1 mmol) and MeONa
(0.08 g, 1.5 mmol) in MeOH (10 mL) was refluxed for 1.5 h,
neutralized with AcOH, and poured into water. The precipitate
that formed was recrystallized from a 1 : 2 DMF—MeOH mixꢀ
ture. Triazoloquinazoline 13 and compound 10 were isolated in
yields of 0.19 g (48%) and 0.2 g (50%), respectively.
C. A solution of compound 12 (0.8 g, 2 mmol) was refluxed
in DMF (5 mL) for 1.5 h. Then MeOH (10 mL) was added.
Triazoloquinazoline 13 and compound 10 were successively isoꢀ
lated in yields of 0.22 g (54%) and 0.16 g (41%), respectively.
5,6,8ꢀTriphenylꢀ6,7ꢀdihydro[1,2,4]triazolo[5,1ꢀb]quinazoꢀ
line (14). A. A mixture of tetrahydrotriazoloquinazoline 12 (0.4 g,
1 mmol) and NBS (0.36 g, 2 mmol) in PriOH (10 mL) was
refluxed for 1.5 h and cooled. Compound 14 was isolated in a
yield of 0.3 g (76%), m.p. 220—223 °C. Found (%): C, 81.11;
H, 5.05; N, 14.12. C27H20N4. Calculated (%): C, 81.00; H, 5.00;
N, 14.00. IR, ν/cm–1: 3056, 1612, 1592, 1576. 1H NMR, δ: 8.43
(s, 1 H, C(2)H); 7.27—7.64 (m, 10 H, H arom.); 6.89—7.17 (m,
5 H, H arom.); 7.21 (dd, 1 H, C(9)H, 4J = 2.1 Hz, 4J = 0.7 Hz);
3
(dd, 1 H, C(6)H, J = 2.3 Hz, 3J = 8.0 Hz); 3.09 (br.ddd, 1 H,
2
3
4
C(7)H, J = –16.5 Hz, J = 8.1 Hz, J = 1.3 Hz); 2.62 (br.dd,
1 H, C(7)H, 2J = –16.5 Hz, 3J = 2.8 Hz). MS, m/z: 493
[M + H]+, 491 [M – H]–.
Xꢀray diffraction study of compound 15. Single crystals of
compound 15 were grown by crystallization from a 1 : 20
PriOH—hexane mixture. The unit cell parameters and intensiꢀ
ties of 3775 reflections (3703 independent reflections, Rint = 0.08)
were measured on an automated fourꢀcircle Siemens P3/PC
diffractometer (graphite monochromator, λ(MoꢀKα)
=
0.71073 Å, 20 °C, θ/2θꢀscanning technique, 2θmax = 50°). Crysꢀ
tals of 15 are monoclinic: a = 28.340(1) Å, b = 13.136(4) Å, c =
12.437(5) Å, β = 114.11(3)°, V = 4226(3) Å3, Mr = 416.47,
Z = 8, space group C2/c, dcalc = 1.309 g cm–3, µ(MoꢀKα) =
0.082 mm–1, F(000) = 1744. The structure was solved by direct
methods with the use of the SHELXTL program package.22 The
3
3
4.40 (dd, 1 H, C(6)H, J = 7.0 Hz, J = 0.2 Hz); 3.39 (br.ddd,
1 H, C(7)H, 2J = –17.6 Hz, 3J = 7.0 Hz, 4J = 2.1 Hz); 3.20
(br.dd, 1 H, C(7)H, 3J = 0.2 Hz, 4J = 0.7 Hz). MS, m/z: 401
[M + H]+, 399 [M – H]–.