Synthesis of 2-(2-hydroxybenzyl)phthalazin-1(2H)-ones

Full text of DOI:10.1007/s10593-011-0683-6

Chemistry of Heterocyclic Compounds, Vol. 46, No. 11, February, 2011 (Russian Original Vol. 46, No. 11, November, 2010)
SYNTHESIS OF 2-(2-HYDROXYBENZYL)PHTHALAZIN-
1(2H)-ONES
V. A. Osyanin1*, E. A. Ivleva1, and Yu. N. Klimochkin1
Keywords: 2-(2-hydroxybenzyl)phthalazin-1(2H)-ones, o-methylenequinones, salicyl alcohols, phthalazin-
1(2H)-one, Michael reaction.
It is known that reaction of naphthalene series o-methylenequinones, generated in situ from 1-dimethyl-
aminomethyl-2-naphthol, and phthalazin-1(2H)-ones form the Diels-Alder heteroreaction adducts 5,15a-dihydro-
6H,8H-naphtho[1',2':5,6]oxazino[2,3-a]phthalazin-5-ones [1]. At the same time, in the case of o-methylene-
quinones generated from the salicyl alcohols 1a-c, there are obtained, rather than the expected 6H,8H-phthala-
zino[1,2-b][1,3]benzoxazines, the products of Michael 1,4-addition, i.e. the 2-(2-hydroxybenzyl)phthalazin-
1(2H)-ones 2a-c.
OH
CH2
о-xylene,
145°C
O
OH
–H2O
R
R
1a–c
O
OH
R
O
N
N
NH
N
2a–c
O
N
O
N
R
H
a R = H, b R = Br, c R = COMe
The IR spectra of compounds 2a-c show the presence of carbonyl stretching bands for the heterocycle
fragments in the range 1628-1632 cm-1. The hydroxyl group corresponds to a broad absorption band in the range
2800-3300 cm-1. The retention of intense C=N stretching bands at 1582 cm-1 also provides an evidence about the
_______
* To whom correspondence should be addressed, e-mail: vosyanin@mail.ru.
1Samara State Technical University, Samara 443100, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1737-1739, November, 2010.
Original article submitted September 13, 2010.
0009-3122/11/4611-1413©2011 Springer Science+Business Media, Inc.
1413

1
formation of acyclic compounds. The H NMR spectra show the hydroxyl group proton at 9.52-10.32 ppm and
the proton on the carbon of the azomethine fragment as a singlet at 8.24-8.29 ppm [2].
1
IR spectra were recorded on a Shimadzu FTIR-8400S spectrometer for KBr tablets. H NMR spectra
were obtained on a Bruker AM-400 spectrometer (400 MHz) using TMS as internal standard and mass spectra
on a Finnigan Trace DSQ instrument with ionization energy 70 eV. Elemental analysis was carried out on a
Euro Vector EA-3000 CHNS autoanalyzer.
2-(2-Hydroxybenzyl)phthalazin-1(2H)-one (2a). A mixture of salicyl alcohol 1a (1 g, 8.1 mmol) and
phthalazin-1(2H)-one (1.18 g, 8.1 mmol) in o-xylene (30 ml) was refluxed with stirring for 40 h. Solvent was
removed in vacuo, the residue was purified by column chromatography on silica gel (eluent dichloromethane),
and then recrystallized from methanol. Compound 2a (0.93 g, 46%) was obtained as colorless crystals;
mp 157-158ºC. IR spectrum, , cm-1: 3300-2800 (OH), 1628 (C=O), 1582 (C=N), 1485, 1454, 1439, 1373,
1
1331, 1242, 1180, 1088, 764, 733, 687. H NMR spectrum, , ppm (J, Hz): 5.39 (2H, s, CH2); 6.89 (1H, dd,
J = 8.07, 7.34, H-5'); 7.00 (1H, d, J = 8.80, H-3'); 7.25 (1H, t, J = 8.07, H-4'); 7.49 (1H, d, J = 8.80, H-6'); 7.68
(1H, d, J = 8.07, H-5); 7.77-7.84 (2H, m, H-6,7); 8.24 (1H, s, H-4); 8.42 (1H, d, J = 8.07, H-8); 9.52 (1H, s,
OH). Mass spectrum (EI), m/z (Irel, %): 252 [M]+ (100), 235 [M-OH]+ (35), 207 [M-OH-CO]+ (17), 146
[C8H6N2O]+ (53), 132 [C8H6NO]+ (84), 121 [C7H7NO]+ (97), 118 [C7H6N2]+ (20), 107 [C7H7O]+ (25), 89 [C7H6]+
(72), 77 [C6H5]+ (44). Found, %: C 71.29; H 4.88; N 10.98. C15H12N2O2. Calculated, %: C 71.42; H 4.79;
N 11.10.
2-(5-Bromo-2-hydroxybenzyl)phthalazin-1(2H)-one (2b) was prepared similarly to compound 2a
from 5-bromosalicyl alcohol (1b) (1 g, 4.9 mmol) and phthalazin-1(2H)-one (0.72 g, 4.9 mmol) in o-xylene
(30 ml) to give colorless crystals (1.06 g, 65%); mp 186-187ºC (toluene). IR spectrum, , cm-1: 3300-2800
1
(OH), 1628 (C=O), 1605 (C=C), 1582 (C=N), 1481, 1443, 1373, 1331, 1242, 1169, 814, 764, 687. H NMR
spectrum, , ppm (J, Hz): 5.33 (2H, s, CH2); 6.86 (1H, d, J = 8.07, H-3'); 7.31 (1H, d, J = 8.07, H-4'); 7.60 (1H,
s, H-6'); 7.75-8.03 (3H, m, H-5,6,7); 8.29 (1H, s, H-4); 8.46 (1H, d, J =7.34, H-8); 9.65 (1H, s, OH). Mass
spectrum (EI, for 79Br isotope), m/z (Irel, %): 330 [M]+ (8), 313 [M-OH]+ (3), 285 [M-OH-CO]+ (2), 199
[C7H6BrNO]+ (27), 146 [C8H6N2O]+ (26), 132 [C8H6NO]+ (100), 118 [C7H6N2]+ (18), 104 (21), 89 [C7H6]+ (68),
77 [C6H5]+ (52). Found, %: C 54.52; H 3.30; N 8.41. C15H11BrN2O2. Calculated, %: C 54.40; H 3.35; N 8.46.
2-(5-Acetyl-2-hydroxybenzyl)phthalazin-1(2H)-one (2c) was prepared similarly to compound 2a from
5-acetylsalicyl alcohol (1c) (1 g, 6 mmol) and phthalazin-1(2H)-one (0.88 g, 6 mmol) in o-xylene (30 ml) to
give colorless crystals (1.04 g, 59%); mp 158-159ºC (ethanol). IR spectrum, , cm-1: 3300-2800 (OH), 1674
1
(C=O acetyl), 1632 (C=O), 1601 (C=C), 1582 (C=N), 1427, 1362, 1327, 1288, 1238, 1107, 841, 759, 690. H
NMR spectrum, , ppm (J, Hz): 2.53 (3H, s, CH3); 5.37 (2H, s, CH2); 6.96 (1H, d, J = 8.24, H-3'); 7.71 (1H, dd,
J = 7.33, J = 0.92, H-5); 7.79 (1H, td, J = 7.33, J = 1.83, H-7); 7.82 (1H, td, J = 7.33, J = 1.83, H-6); 7.84 (1H,
dd, J = 8.24, J = 2.29, H-4'); 8.10 (1H, d, J = 2.29, H-6'); 8.26 (1H, s, H-4); 8.40 (1H, dd, J = 7.79, J = 0.92,
H-8); 10.32 (1H, s, OH). Mass spectrum (EI), m/z (Irel, %): 294 [M]+ (22), 277 [M-OH]+ (4), 249 [M-OH-CO]+
(4), 163 [C9H9NO2]+ (40), 148 [C9H8O2]+ (36), 146 [C8H6N2O]+ (22), 133 (38), 132 [C8H6NO]+ (100), 118
[C7H6N2]+ (15), 105 (22), 89 [C7H6]+ (60), 77 [C6H6]+ (47). Found, %: C 69.46; H 4.66; N 9.42. C17H14N2O3.
Calculated, %: C 69.38; H 4.79; N 9.52.
REFERENCES
1.
2.
M. von Strandtmann, M. P. Cohen, and J. Shavel, Jr., US Pat. 3649626. Chem. Abstr., 76, 140844
(1972).
B. I. Buzykin, N. N. Bystrykh, A. P. Stolyarov, S. A. Flegontov, V. V. Zverev, and Yu. P. Kitaev, Khim.
Geterotsikl. Soedin., 402 (1976). [Chem. Heterocycl. Comp., 12, 342 (1976)].
1414