Hydroxylation of 4-arylimino-5-hydroxy-1,4-dihydronaphthalen-1-ones

Article abstract of DOI:10.1007/s11178-005-0006-4

Heating of 4-arylimino-5-hydroxy-1,4-dihydronaphthalen-1-ones with sodium hydroxide in the presence of K₃Fe(CN)₆ gives the corresponding 2,5-dihydroxy derivatives, while in the reaction with FeCl ₃·6H₂O 4-arylim

Full text of DOI:10.1007/s11178-005-0006-4

Russian Journal of Organic Chemistry, Vol. 40, No. 9, 2004, pp. 1284–1287. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 9, 2004,
pp. 1334–1336.
Original Russian Text Copyright © 2004 by Bukhtoyarova, Ektova.
Hydroxylation of 4-Arylimino-5-hydroxy-
1,4-dihydronaphthalen-1-ones
A. D. Bukhtoyarova and L. V. Ektova
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. Akademika
Lavrent’eva 9, Novosibirsk, 630090 Russia
Received February 14, 2004
Abstract—Heating of 4-arylimino-5-hydroxy-1,4-dihydronaphthalen-1-ones with sodium hydroxide in the
presence of K3Fe(CN)6 gives the corresponding 2,5-dihydroxy derivatives, while in the reaction with
FeCl3 ·6H2O 4-arylimino-3,5-dihydroxy-1,4-dihydronaphthalen-1-ones are formed.
Extensive studies in the field of naphthoquinon-
imines originate from their high reactivity which
makes them convenient starting compounds for the
synthesis of various classes of organic compounds [1].
In addition, naphthoquinonimine derivatives are used
as dyes for optical data storage systems [2] and color
photography [3] and as anticarcinogenic agents [4].
Taking into account that some hydroxy-1,4-naphtho-
quinones are natural compounds possessing a high
biological activity [5], we anticipated that combination
of a hydroxynaphthoquinone and N-arylmonoquinon-
imine fragments in a single molecule will give rise
to new useful properties. The main procedures for
introduction of a hydroxy group into N-arylquinon-
imines are based on hydrolysis of the corresponding
amino derivatives and oxidation of quinonimines in
alkaline medium [1]. A number of 4-arylimino-2-hy-
droxy-1,4-dihydronaphthalen-1-ones exhibiting anti-
tuberculous activity were synthesized by reaction of
1,2-dioxo-1,2-dihydronaphthalene-4-sulfonic acid
potassium salt with the corresponding arylamines [6].
imino- and 5-hydroxy-4-(2,4,6-trimethylphenylimino)-
1,4-dihydronaphthalen-1-ones Ia and Ib were oxidized
with K3Fe(CN)6 only in aqueous alkali, and the prod-
ucts were the corresponding 2,5-dihydroxy derivatives
IIa and IIb (Scheme 1). Compound IIa was also
obtained by acid hydrolysis of 5-hydroxy-4-phenyl-
2-phenylamino-1,4-dihydronaphthalen-1-one (III) in
dilute sulfuric acid.
By oxidation of naphthoquinonimine Ia with
FeCl3·6H2O in DMF we obtained 3,5-dihydroxy-4-
phenyl-1,4-dihydronaphthalen-1-one (IVa) which is
isomeric to IIa. Compound Ib failed to react under
analogous conditions, while N-(4-methylphenyl)-,
N-(4-butoxycarbonylphenyl)-, and N-(4-methoxy-
phenyl)-4-imino-5-hydroxy-1,4-dihydronaphthalen-1-
ones Ic–Ie were converted into 3,5-dihydroxy deriva-
tives IVc–IVe (Scheme 2). It should be noted that
neither 2- nor 3-hydroxy derivatives were formed in
reactions of naphthoquinonimines Ia–Ie with such
oxidants as K2S2O8, (NH4)Ce(NO3)6, or NaIO4 in
neutral medium.
In the present work we studied hydroxylation of
4-arylimino-5-hydroxy-1,4-dihydronaphthalen-1-ones
Ia–Ie under different conditions. 5-Hydroxy-4-phenyl-
The position of the newly introduced hydroxy
group in the naphthalene ring was confirmed by the
Scheme 1.
Scheme 2.
O
O
O
O
OH
NaOH, K3Fe(CN)6
FeCl3 ·6H2O
OH
OH
NAr
OH
NAr
OH
NAr
OH
NAr
Ia, Ib
IIa, IIb
Ia, Ic–Ie
IVa, IVc–IVe
Ar = Ph (a), 2,4,6-Me3C6H2 (b).
Ar = Ph (a), 4-MeC6H4 (c), 4-BuOCOC6H4 (d), 4-MeOC6H4 (e).
1070-4280/04/4009-1284 © 2004 MAIK “Nauka/Interperiodica”

HYDROXYLATION OF 4-ARYLIMINO-5-HYDROXY-1,4-DIHYDRONAPHTHALEN-1-ONES
1285
fact that the reaction of 2,5-dihydroxy derivative IIa
with o-phenylenediamine afforded 5-phenylimino-5H-
benzo[a]phenazin-4-ol (V) (Scheme 3). 3,5-Dihydroxy
isomers IVa and IVc–IVe failed to react with
o-phenylenediamine. Isomeric 2,5- and 3,5-dihydroxy-
substituted compounds IIa and IVa can also be dis-
4853, and Beckmann DU-8 spectrophotometers from
solutions in EtOH. The 1H NMR spectra were obtained
on a Bruker WP-200SY spectrometer using CDCl3 or
DMSO-d6 as solvent. The molecular weights and
elemental compositions were determined from the
precise m/z values of the molecular ions in the mass
spectra which were run on Finnigan MAT-8200 and
Finnigan AEI MS-900 mass spectrometers. The prog-
ress of reactions and the purity of products were
monitored by thin-layer chromatography on Silufol
plates using chloroform as eluent.
1
tinguished by spectral data. In the H NMR spectrum
of 2,5-dihydroxy derivative IIa, the signal from
the 5-OH proton is located in a weaker field (δ∆ =
0.81 ppm) relative to the corresponding signal of initial
compound Ia (δ 13.76 ppm [7]). By contrast, the 5-OH
signal in the spectrum of 3,5-dihydroxy isomer IVa is
displaced upfield (δ∆ = 2.22 ppm). Analogous effect of
the introduced hydroxy group on the position of the
downfield signal was observed for 2- and 3-hydroxy-
juglones [8]: the corresponding δ∆ values were +0.41
and –0.83 ppm, respectively.
2,5-Dihydroxy-4-phenylimino-1,4-dihydronaph-
thalen-1-one (IIa) and 2,5-dihydroxy-4-(2,4,6-tri-
methylphenylimino)-1,4-dihydronaphthalen-1-one
(IIb). A mixture of 0.5 mmol of compound Ia or Ib in
10 ml of ethanol and 6 mmol of NaOH and 1 mmol of
K3Fe(CN)6 in 5 ml of H2O was heated for 30 min at
70–75°C. The mixture was poured into water and
neutralized with 5% hydrochloric acid, the precipitate
was filtered off, the filtrate was extracted with CHCl3
(3×20 ml), and the extract was dried over CaCl2 and
evaporated to dryness. The residue was combined with
the precipitate and dissolved in CHCl3, and the solu-
tion was applied to a column charged with silica gel.
Traces of the initial compound were washed off with
chloroform, and the subsequent elution with acetone
afforded compound IIa or IIb. Yield of IIa 76%,
mp 221–222°C (from benzene–hexane, 1:5). IR spec-
trum, ν, cm–1: 1620 (C=N), 1645 (C=O), 3292 (OH).
1H NMR spectrum (CDCl3), δ, ppm: 6.61 s (1H, 3-H),
7.03 d (2H, 2'-H, 6'-H, J = 10 Hz), 7.27–7.57 m (6H,
3'-H, 4'-H, 5'-H, 6-H, 7-H, OH), 7.78 d.d (1H, 8-H,
Jortho = 9.0, Jmeta = 1.5 Hz), 14.57 s (1H, OH). UV
spectrum, λmax, nm (ε×10–4 l mol–1 cm–1): 423 (0.75).
Found: [M]+ 265.07360. C16H11NO3. Calculated:
M 265.07389.
Scheme 3.
O
OH
NH2
NH2
+
OH
NAr
IIa
2
1
3
4
11
12N
10
9
OH
5
7
N
H
NPh
6
8
V
The reasons for the different directions of oxidative
hydroxylation of 4-arylimino-5-hydroxy-1,4-dihydro-
naphthalen-1-ones are not clear so far. Presumably,
2,5-dihydroxy derivatives IIa and IIb are formed via
1,4-addition of NaOH, followed by oxidation of the
adduct with K3Fe(CN)6 in a way similar to reactions of
4-imino-1,4-dihydronaphthalen-1-ones with other nu-
cleophiles (which usually lead to 2-substituted deriva-
tives [1]). The only example of formation of 3-tert-
butoxy-4-phenylimino-1,4-dihydronaphthalen-1-one in
the oxidation of N-phenyl-1-naphthylamine with tert-
butyl hydroperoxide was reported in [9].
Yield of IIb 62%, mp 297–299°C (from hexane).
IR spectrum, ν, cm–1: 1647 (C=N), 1664 (C=O), 3333
(OH). 1H NMR spectrum (CDCl3), δ, ppm: 2.03 s (6H,
2CH3), 2.30 s (3H, CH3), 6.16 s (1H, 3-H), 6.92 s (2H,
3'-H, 5'-H), 7.34 d (1H, 6-H, J = 8.0 Hz), 7.51 t (1H,
7-H, J = 8.0 Hz), 7.74 d (1H, 8-H, J = 8.0 Hz), 14.70 s
(1H, OH). UV spectrum, λmax, nm (ε×10–4 l mol–1 cm–1):
392 (0.47). Found: [M]+ 307.12035. C19H17NO3. Cal-
culated: M 307.12083.
EXPERIMENTAL
Hydrolysis of 5-hydroxy-2-phenylamino-4-
phenylimino-1,4-dihydronaphthalen-1-one (III).
A solution of 0.3 mmol of compound III in 5 ml of
50% sulfuric acid was heated for 15 min at 125°C. The
The IR spectra were recorded in KBr on UR-20 and
Vector-22 instruments. The electron absorption spectra
were measured on Specord UV-Vis, Hewlett–Packard
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 9 2004

BUKHTOYAROVA, EKTOVA
1286
mixture was cooled and poured into water, and the
precipitate was filtered off and dried. Yield of IIa 51%.
spectrum (CDCl3), δ, ppm: 3.81 s (3H, OCH3), 6.15 s
(1H, 2-H), 6.92 d.d (2H, 2'-H, 6'-H, Jortho = 8.0, Jmeta
=
2.0 Hz), 7.13–7.19 m (3H, 3'-H, 5'-H, 6-H), 7.39 br.s
(1H, OH), 7.59–7.62 m (2H, 7-H, 8-H), 11.55 s (1H,
OH). UV spectrum, λmax, nm (ε×10–4 l mol–1 cm–1):
414 (0.66), 503 (0.46). Found: [M]+ 295.08486.
C17H13NO4. Calculated: M 295.08443.
Reaction of 5-hydroxy-4-arylimino-1,4-dihydro-
naphthalen-1-ones Ia and Ic–Ie with iron(III)
chloride. A mixture of 1 mmol of 5-hydroxy-4-aryl-
imino-1,4-dihydronaphthalen-1-one Ia or Ic–Ie in
15 ml of DMF and 10 mmol of FeCl3·6H2O was
stirred for 3 h at 80–90°C. The mixture was poured
into water, 5 ml of 5% hydrochloric acid was added,
and the precipitate of compound IVa or IVc–IVe was
filtered off, dried in air, and purified by column chrom-
atography on silica gel using chloroform as eluent.
Reaction of 5-hydroxy-4-(2,4,6-trimethylphenyl-
imino)-1,4-dihydronaphthalen-1-one (Ib) with
FeCl3·6H2O. A mixture of 1 mmol of compound Ib,
10 mmol of FeCl3 ·6H2O, and 15 ml of DMF was
heated for 5 h at 85–90°C. The mixture was treated as
described above to isolate 69% of initial compound Ib.
A zone containing tarry products remained in the
chromatographic column.
3,5-Dihydroxy-4-phenylimino-1,4-dihydronaph-
thalen-1-one (IVa). Yield 74%, mp 229–230°C (from
benzene). IR spectrum, ν, cm–1: 1627 (C=N), 1645
1
(C=O), 3280 (OH). H NMR spectrum (CDCl3), δ,
Reaction of 2,5-dihydroxy-4-phenylimino-1,4-
dihydronaphthalen-1-one (IIa) with o-phenylene-
diamine. A mixture of 1.3 mmol of 2,5-dihydroxy-
4-phenylimino-1,4-dihydronaphthalen-1-one (IIa),
2.8 mmol of o-phenylenediamine, and 30 ml of acetic
acid was stirred for 30 min at 80°C. The mixture
was cooled, poured into water, and neutralized with
aqueous potassium hydroxide, and the precipitate was
filtered off, washed with water, and dried. The product
was 5-phenylimino-5H-benzo[a]phenazin-4-ol (V).
Yield quantitative. The product was purified by repre-
cipitation with benzene from acetone, mp 260°C
(decomp.). IR spectrum, ν, cm–1: 1624 (C=N), 3334
ppm: 6.35 s (1H, 2-H), 7.10–7.70 m (9H, 2'-H, 3'-H,
4'-H, 5'-H, 6-H, 6-H, 7-H, 8-H, OH), 11.54 s (1H, OH).
UV spectrum, λmax, nm (ε×10–4 l mol–1 cm–1): 415
(0.65), 486 (0.44). Found: [M]+ 265.07360. C16H11NO3.
Calculated: M 265.073889.
3,5-Dihydroxy-4-(4-methylphenylimino)-1,4-di-
hydronaphthalen-1-one (IVc). Yield 78%, mp 203–
205°C (from benzene–hexane, 1:5). IR spectrum, ν,
1
cm–1: 1627 (C=N), 1635 (C=O), 3289 (OH). H NMR
spectrum (CDCl3), δ, ppm: 2.33 s (3H, CH3), 6.27 s
(1H, 2-H), 7.09–7.21 m (4H, 2'-H, 3'-H, 5'-H, 6'-H),
7.47 br.s (1H, OH), 7.57–7.61 m (3H, 6-H, 7-H, 8-H),
11.53 s (1H, OH). UV spectrum, λmax, nm (ε×
10–4 l mol–1 cm–1): 414 (0.75), 500 (0.53). Found:
[M]+ 279.09020. C17H13NO3. Calculated: M 279.08954.
1
(NH). H NMR spectrum (DMSO-d6), δ, ppm: 6.97 s
(1H, 6-H), 7.10–7.82 m (9H, 2-H, 3-H, 9-H, 10-H,
C6H5), 7.90 d (1H, 8-H, J = 8.0 Hz), 8.12 d (1H, 11-H,
J = 8.0 Hz), 8.76 d (1H, 1-H, 8.0 Hz) (signals from
the NH and OH protons were not observed due to
exchange with water present in the solvent). UV
spectrum, λmax, nm (ε×10–4 l mol–1 cm–1): 507 (1.07).
Found: [M]+ 337.12140. C22H15N3O. Calculated:
M 337.12150.
Butyl 4-[2,8-dihydroxy-4-oxonaphthalen-1(4H)-
ylideneamino]benzoate (IVd). Yield 84%, mp 159–
160°C (from benzene–hexane, 1:5). IR spectrum, ν,
cm–1: 1613 (C=N), 1634 (C=O), 1699 (COO–), 3317
(OH). 1H NMR spectrum (CDCl3), δ, ppm: 0.96 t (3H,
CH3, J = 7.0 Hz), 1.48 m (2H, CH2), 1.75 m (2H,
CH2), 4.31 t (2H, CH2, J = 7.0 Hz), 6.50 s (1H, 2-H),
7.18 d.d (1H, 6-H, Jortho = 8.0, Jmeta = 2.0 Hz), 7.28 d
(2H, 2'-H, 6'-H, J = 8.0 Hz), 7.60–7.65 m (2H, 7-H,
8-H), 7.67 br.s (1H, OH), 8.07 d (2H, 3'-H, 5'-H, J =
8.0 Hz), 11.48 s (1H, OH). UV spectrum, λmax, nm
(ε×10–4 l mol–1 cm–1): 423 (0.76), 500 (0.46). Found:
[M]+ 365.12585. C21H19NO5. Calculated: M 365.12631.
Reaction of 3,5-dihydroxy-4-arylimino-1,4-di-
hydronaphthalen-1-ones IVa and IVc–IVe with
o-phenylenediamine. A mixture of 1.3 mmol of com-
pound IVa or IVc–IVe, 2.8 mmol of o-phenylene-
diamine, and 30 ml of acetic acid was stirred for
30 min at 80°C. The mixture was treated as described
above to isolate ~90% of the initial compound.
3,5-Dihydroxy-4-(4-methoxyphenylimino)-1,4-di-
hydronaphthalen-1-one (IVe). Yield 61%, mp 215–
217°C (from CHCl3–hexane, 1:10). IR spectrum, ν,
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