Month 2019
Novel Phthalazine Heterocycles
1
(
125 MHz, DMSO-d ): δ 158.4, 138.6, 134.7, 132.9, 132.3,
31.5, 131.0, 130.4, 129.2, 128.2, 127.5, 126.2, 123.3, 71.2,
1252 (C–O ether). H-NMR (300 MHz, DMSO-d6)
δppm: 8.38–7.35 (m, 9H, ArH), 4.41 (bs, 1H, J = 5.2,
OH, exchangeable with D O), 4.16 (t, 2H, CH O,
6
1
5
6
5.4, 48.4, 19.2. Anal. Calc. for C H ClN O (328): % C,
1
8
17
2
2
2
2
5.85; H, 5.21; N, 8.52; Found: C, 65.70; H, 5.27; N, 8.35.
Yield
54%), mp 124–126°C. IR (KBr, cm ): ν1245, 930 and
J = 6.6), 3.41 (t, 2H, NCH , J = 6.6 Hz), 2.10 (s, 2H,
PhCH ), 1.79 (m, 2H, CH ), 1.45 (m, 2H, CH ). MS, m/z
%): 310 [M ] (100.0%).
DMSO-d ): δ 170.0, 158.4, 141.1, 137.7, 132.9, 132.3,
2
1
-Benzyl-4-(oxiran-2-ylmethoxy) phthalazine (6).
2
2
2
ꢀ
1
.+
13
(
(
C-NMR (125 MHz,
1
8
30 (C–O epoxide). H-NMR (300 MHz, DMSO-d6)
6
δppm: 8.43–7.48 (m, 9H, ArH), 4.68–4.42 (dd, 2H,
1
31.5, 131.0, 130.4, 129.2 (2), 128.2, 127.5, 126.2, 123.3,
OCH , J = 5.52), 4.32–4.25 (m, 1H proton of oxirane
2
64.1, 56.7, 41.7. Anal. Calc. for C H N O (308): % C,
19 20 2 2
ring), 4.15–4.05 (2dd, 2H, CH of oxirane ring; J = 14.2,
74.00; H, 6.54; N, 9.08; Found: C, 74.12; H, 6.59; N 9.38.
2
.+
1
(
1.8 Hz), 2.38 (s, 2H, PhCH ). MS, m/z (%): 292 [M ]
100.0%). C-NMR (125 MHz, DMSO-d ): δ 158.4,
2-(((4-Benzylphthalazin-1-yl)oxy)methoxy)ethan-1-ol (10).
2
13
ꢀ1
Yield (75%), mp 121–123°C. IR (KBr, cm ): ν3465
6
1
1
(
38.9, 134.7, 132.9, 132.3, 131.5, 131.0, 130.4, 129.2
2), 128.2, 127.5, 126.2, 123.3, 55.4, 47.4, 43.1, 19.2.
Anal. Calc. for C H N O (292): % C, 73.95; H, 5.52;
(OH), 1261 (C–O ether). H-NMR (300 MHz, DMSO-d )
6
δppm: 8.53–7.63 (m, 9H, ArH), 4.89 (t, 1H, OH,
J = 6.9 Hz, exchangeable in D O), 5.34 (s, 2H, CH O),
1
8
16
2
2
2
2
N, 9.58; Found: C, 73.71; H, 5.37; N, 9.65.
Compounds 7 and 8. A mixture of 1 (0.01 mol), 4-
bromobutylacetate, and/or 2-(bromomethoxy)ethylacetate
3.52 (t, 2H, CH OCO, J = 5.5 Hz), 3.34 (t, 2H, OCH ,
2
2
.
J = 5.5 Hz), 2.23 (s, 2H, PhCH ). MS, m/z (%): 308 (M
2
+
13
,
100.0%). C-NMR (125 MHz, DMSO-d ): δ 168.2,
6
(
(
0.01 mol) in anhydrous K CO (0.01 mol)/dry DMF
30 mL) was stirred ultrasonically at room temperature
154.4, 138.1, 134.7, 132.9, 132.3, 131.5, 130.4, 129.2
2), 128.2, 127.5, 126.2, 123.3, 64.1, 56.7, 41.7, 40.5,
8.2. Anal. Calc. for C H N O (310): % C, 69.66; H,
2
3
(
3
for 1 h, then evaporated the excess solvent under reduced
pressure, and then diluted with water. The solid obtained
was recrystallized from ethanol.
18 18 2 3
5.85; N, 9.03; Found: C, 69.70; H, 5.73; N 9.10.
2-((4-Benzylphthalazin-1-yl)oxy)acetohydrazide (11).
A
4
-((4-Benzylphthalazin-1-yl)oxy)butyl acetate (7).
Yield
mixture of 1 (0.01 mol), 2-chloroacetic acid hydrazide
ꢀ
1
(
1
61%), mp 90–92°C. IR (KBr, cm ): ν1737 (CO ester),
256 (C–O ether). H-NMR (300 MHz, DMSO-d6)
δppm: 8.38–7.66 (m, 9H, ArH), 3.84 (t, 2H, CH OCO,
J = 6.6 Hz), 3.45 (t, 2H, OCH , J = 6.9 Hz), 2.36 (s, 2H,
PhCH ), 2.20 (s, 3H, CH CO), 1.93–1.89 (m, 4H, 2CH ).
MS, m/z (%): 352 [M ] (100.0%). C-NMR (125 MHz,
DMSO-d ): δ 170.0, 158.4, 138.2, 134.7, 132.9, 132.3,
(0.01 mol), and anhydrous K CO (0.01 mol) in dry DMF
2
3
1
(30 mL) was stirred ultrasonically at room temperature for
1 h. The excess solvent was evaporated under reduced
pressure, and the reaction mixture was diluted with water.
The solid obtained was recrystallized from ethanol.
2
2
2
3
2
.+
13
ꢀ1
Yield (75%), mp 154–156°C. IR (KBr, cm ): ν3378,
1
6
3267, 3159 (NH), 2956 (CH), 1252 (C–O ether). H-
131.5, 131.0, 130.4, 129.2 (2), 128.2, 127.5, 126.2,
NMR (300 MHz, DMSO-d ) δppm: 11.34 (bs, 1H, NH,
6
123.3, 87.4, 66.1, 63.7, 50.5, 39.1, 33.2. Anal. Calc. for
J = 8.3 Hz, exchangeable in D O), 8.53–7.63 (m, 9H,
2
C H N O (350): % C, 71.98; H, 6.33; N, 7.99; Found:
C, 71.89; H, 6.29; N, 7.90.
ArH), 5.52 (bs, 2H, NH , J = 5.5 Hz), 5.34 (s, 2H,
2
1
22
2
3
2
.
+
OCH ), 2.43 (s, 2H, PhCH ). MS, m/z (%): 308 [M ]
2 2
2
-(((4-Benzylphthalazin-1-yl)oxy)methoxy)ethylacetate
(100.0%). Anal. Calc. for C H N O (308): % C, 66.22;
17 16 4 2
H, 5.23; N, 18.17; Found: C, 66.18; H, 5.28; N, 18.20.
ꢀ
1
(
(
8). Yield (98%), mp 92–94°C. IR (KBr, cm ): ν1731
CO ester), 1252 (C–O ether). H-NMR (300 MHz,
DMSO-d ) δppm: 8.38–7.69 (m, 9H, ArH), 4.92 (s, 2H,
OCH O), 4.21–4.03 (m, 4H, 2OCH ), 2.38 (s, 2H,
PhCH ), 1.96 (s, 3H, CH CO). MS, m/z (%): 350 [M ]
100.0%). C-NMR (125 MHz, DMSO-d ): δ 170.0,
58.4, 138.1, 134.7, 132.9, 132.3, 131.5, 131.0, 130.4,
29.2 (2), 128.2, 127.5, 126.2, 123.3, 64.1, 56.7, 41.7,
0.5, 38.2. Anal. Calc. for C H N O (352): % C,
1
Compounds 12a and 12b. A mixture of 11 (0.01 mol)
and aromatic aldehydes, namely, 4-chlorobenzaldehyde
and N,N-dimethyl benzaldehyde (0.01 mol), in boiling
ethanol (30 mL) was stirred ultrasonically at 60°C for
6
2
2
.+
2
3
13
(
6
1
h. The excess solvent was evaporated under reduced
1
1
4
6
pressure, and the reaction mixture was diluted with water.
The solid obtained was recrystallized from ethanol.
2-((4-Benzylphthalazin-1-yl) oxy)-N′-(4-chlorobenzylidene)
2
0 20 2 4
8.17; H, 5.72; N, 7.95; Found: C, 65.20; H, 5.63; N, 7.81.
A mixture of 7 and/or 8
0.01 mol), triethylamine (1 mL), and few drops of water
in methanol (30 mL) was stirred at room temperature for
h and then left overnight. The excess solvent was
acetohydrazide (12a).
Yield (75%), mp 138–140°C. IR
ꢀ
1
Compounds 9 and 10.
(KBr, cm ): ν3313 (NH), 3064, 2956 (CH), 1252 (C–O
1
ether). H-NMR (300 MHz, DMSO-d ) δppm: 11.17 (bs,
(
6
1H, NH, J = 8.1 Hz, exchangeable in D
(m, 13H, ArH), 9.52 (s, 1H, CH), 5.34 (s, 2H, OCH
O), 8.43–7.28
),
.43 (s, 2H, PhCH ). MS, m/z (%): 432 [M +2] (15.0%),
2
1
2
.
+
2
evaporated under reduced pressure, and the formed
residue was recrystallized from ethanol.
2
.+
430 [M ] (100.0%). Anal. Calc. for C24H19ClN O
4 2
4
-((4-Benzylphthalazin-1-yl)oxy)butan-1-ol (9).
Yield
(430): % C, 66.90; H, 4.44; Cl, 8.23; N, 13.00; Found:
C, 66.88; H, 4.49; Cl, 8.29; N, 13.06.
ꢀ
1
(
75%), mp 114–115°C. IR (KBr, cm ): ν3445 (OH),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet