3,5-Di-tert-butyl-1,2-benzoquinone in the synthesis of quinolino[4,5-bc][1, 5]benzoxazepines, aminophenols, and phenoxazines

Article abstract of DOI:10.1134/S1070428009030178

Reaction of 3,5-di-tert-butyl-1,2-benzoquinone with 5-amino-4- chloroquinolines gave derivatives of a new fused heterocyclic system, substituted quinolino[4,5-bc][1,5]benzoxazepines. The molecular structure of 9,11-di-tert-butyl-2,4,6-trimethyl-7H-quinoli

Full text of DOI:10.1134/S1070428009030178

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 3, pp. 442–448. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © Zyong Ngia Bang, V.N. Komissarov, Yu.A. Sayapin, V.V. Tkachev, G.V. Shilov, S.M. Aldoshin, V.I. Minkin, 2009, published in
Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 3, pp. 452–457.
3,5-Di-tert-butyl-1,2-benzoquinone in the Synthesis
of Quinolino[4,5-bc][1,5]benzoxazepines, Aminophenols,
and Phenoxazines
Zyong Ngia Banga, V. N. Komissarova, Yu. A. Sayapina, V. V. Tkachevb, G. V. Shilovb,
S. M. Aldoshinb, and V. I. Minkina,c
a Institute of Physical and Organic Chemistry, Rostov State University, pr. Stachki 194/2, Rostov-on-Don, 344090, Russia
e-mail: bell@ipoc.rsu.ru
b Institute of Chemical Physics Problems, Russian Academy of Sciences,
pr. Akademika N.N. Semenova 1, Chernogolovka, Moscow oblast, 142432 Russia
e-mail: sma@icp.ac.ru
c Southern Research Center, Russian Academy of Sciences, ul. Chekhova 41, Rostov-on-Don, 344006 Russia
Received March 3, 2008
Abstract—Reaction of 3,5-di-tert-butyl-1,2-benzoquinone with 5-amino-4-chloroquinolines gave derivatives
of a new fused heterocyclic system, substituted quinolino[4,5-bc][1,5]benzoxazepines. The molecular structure
of 9,11-di-tert-butyl-2,4,6-trimethyl-7H-quinolino[4,5-bc][1,5]benzoxazepine was determined by X-ray anal-
ysis. 3,5-Di-tert-butyl-1,2-benzoquinone reacted with o-nitro-, o-acyl-, and o-methoxycarbonylanilines and
some amino-substituted nitrogen-containing heterocycles to form the corresponding sterically hindered N-aryl-
(hetaryl)-o-aminophenols. Di-tert-butyl-substituted phenoxazines were obtained as a result of thermal cycliza-
tion of intermediately formed quinone imines.
DOI: 10.1134/S1070428009030178
1,4(1,5)-Oxa(thia)zepine derivatives exhibit strong
biological activity and are extensively studied. In
particular, 10-[3-(dimethylamino)propyl]-2-nitrodiben-
zo[b,f][1,4]oxazepin-11(10H)-one (I) (Sintamil) is
known as efficient antidepressant [1]. Dilthiazem (II,
D-cis-3-acetoxy-2,3-dihydro-5-[2-(dimethylamino)-
ethyl]-2-(2-methoxyphenyl)-1,5-benzothiazepin-4(5H)-
one hydrochloride) is a benzothiazepine-type calcium
antagonist possessing antianginal, antiarrhythmic, and
hypotensive properties.
tives belong to novel so-called atypical antipsychotic
drugs that are effective in the treatment of psycho-
neurological disorders such as psychosis, depression,
and schizophrenia [5]. Unlike traditionally used drugs,
the above compounds more rarely cause extrapyrami-
dal side effects and are more effective in the treatment
of negative symptoms and treatment-resistant schizo-
phrenia. 2,3,4,5-Tetrahydrobenzo[f][1,4]oxazepine-5-
carboxamide showed a high inhibitory activity toward
γ-secretase in the treatment of Alzheimer disease [6].
Substituted 5,11-dihydrobenzo[b,e][1,4]oxazepines
exhibiting a lower anticholinergic activity [2–4] were
also tested as calcium antagonists of new generation.
Piperazinyldibenzo[b,f][1,4]oxa(thia)zepine deriva-
In the present article we describe a new procedure
for the synthesis of 1,5-benzoxazepine derivatives
fused to a heteroring. We have found that 3,5-di-tert-
butyl-1,2-benzoquinone (III) reacts with 5-amino-4-
O
Me2N
NMe2
OAc
O
N
N
· HCl
· HCl
S
O2N
MeO
O
I
II
442

3,5-DI-tert-BUTYL-1,2-BENZOQUINONE IN THE SYNTHESIS
443
Scheme 1.
Cl
Me
Bu-t
NH2 Cl
O
O
O
R1
R2
t-Bu
N
N
+
R1
Me
t-Bu
N
Me
R2
Me
Bu-t
III
IVa–IVd
A
Bu-t
Me
N
Bu-t
OH
OH
Cl
Me
OH
O
H
N
t-Bu
N
t-Bu
Me
–III
–HCl
t-Bu
N
H
R1
Me
R1
R2
Bu-t
R2
B
Va–Vd
R1 = R2 = H (a); R1 = H, R2 = Me (b); R1 = Me, R2 = H (c); R1 = Br, R2 = H (d).
chloroquinolines IVa–IVd in the presence of 3,5-di-
tert-butylbenzene-1,2-diol according to Scheme 1 to
form derivatives of a new fused heterocyclic system,
quinolino[4,5-bc][1,5]benzoxazepines Va–Vd. In
keeping with the assumed mechanism, initially formed
o-quinone imine A possesses pronounced oxidative
power, and, like other o-quinones, it acts as dehydro-
genating agent toward 3,5-di-tert-butylbenzene-1,2-di-
ol. As a result, quinolylaminophenol B is formed, and
it undergoes intramolecular cyclization to quinolino-
benzoxazepine V (yield 50–60%). Initial 3,5-di-tert-
butyl-1,2-benzoquinone (III) is regenerated by oxida-
tion of 3,5-di-tert-butylbenzene-1,2-diol with quinone
imine A. The reaction in the absence of reducing agent
is characterized by poor yields. Compounds V were
also isolated in poor yields (7–22%) when equimolar
amounts of quinone III and quinoline IV were heated
in o-xylene at 135–140°C or fused without a solvent.
reactions of quinone III with various aromatic and
heteroaromatic amines containing electron-withdraw-
ing groups (NO2, COPh, COOMe). In fact, fusion of
quinone III with amines VI gave aminophenol deriva-
C22
C23
C20
C13
C21
C24
C12
C14
C11
C19
C25
C15
C10
C26
N2
O1
C17
The structure of quinolinobenzoxazepines Va–Vd
was confirmed by the H NMR, IR, and mass spectra.
C5
1
C3
C6
C4
The molecular structure of compound Vc was deter-
mined by X-ray analysis (see figure). The central
seven-membered ring is folded along the line passing
through the O1 and N2 atoms. The dihedral angle be-
tween the corresponding planes is 38.8°, the C18 atom
deviates from the quinoline ring plane by 0.22 Å, and
the C19 and C20 atoms in the tert-butyl groups deviate
from the benzene ring plane in opposite directions by
0.25 and 0.23 Å, respectively.
C2
C1
C7
C9
C16
C8
C18
N1
Molecular structure of 9,11-di-tert-butyl-2,4,6-trimethyl-7H-
quinolino[4,5-bc][1,5]benzoxazepine (Vc) according to the
X-ray diffraction data (hydrogen atoms are not shown).
With a view to confirm intermediate formation of
quinone imines A and aminophenols B we examined
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 3 2009

ZYONG NGIA BANG et al.
444
Scheme 2.
Bu-t
Bu-t
R4
O
O
N
R3
R2
Δ
III
+
Ar(Het)NH2
Ar(Het)
N
t-Bu
t-Bu
R1
VI
VIIa–VIIe
Xa–Xe
Bu-t
OH
, Δ
R4 = H
t-Bu
OH
Bu-t
Bu-t
OH
O
R3
R2
Ar(Het)
t-Bu
N
t-Bu
N
H
H
R1
VIIIa–VIIIi
IXa–IXe
VIII, Ar = 2-O2NC6H4 (a), 2-O2N-4-MeC6H3 (b), 2-O2N-4-ClC6H3 (c), 2-PhCOC6H4 (d), 2-MeOCOC6H4 (e), 2-MeOCO-3,4-
(MeO)2C6H2 (f); Het = pyridin-2-yl (g), pyrimidin-2-yl (h), 4-methylpyrimidin-2-yl (i); IX, X, R1 = O2N, R2 = R3 = H (a); R2 = H,
R3 = Me (b); R2 = H, R3 = Cl (c); R1 = PhCO, R2 = R3 = H (d); R1 = MeOCO, R2 = R3 = MeO (e).
tives VIII and (in some cases) phenoxazines IX
(Scheme 2). When the reaction was performed in the
presence of 3,5-di-tert-butylbenzene-1,2-diol, the yield
of aminophenols VIII increased, while the formation
of phenoxazines IX was suppressed. Presumably,
phenoxazines IX are formed as a result of thermal
cyclization of intermediate o-quinone imines VII. To
verify this assumption, aminophenols VIIIa–VIIIe
were oxidized with lead(IV) oxide in benzene to the
corresponding o-quinone imines VIIa–VIIe. After
removal of the solvent and heating for 1–1.5 h at
135–140°C we obtained phenoxazines IXa–IXe in
30–40% yield.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Varian
Unity-300 spectrometer. The mass spectra were ob-
tained on a Finnigan MAT Incos 50 instrument. The IR
spectra were measured from samples dispersed in
mineral oil on a Specord 75IR spectrometer. Column
chromatography was performed on aluminum oxide of
activity grade II or III according to Brockmann. The
melting points were determined in glass capillaries and
were not corrected.
9,11-Di-tert-butyl-2,4-dimethyl-7H-quinolino-
[4,5-bc][1,5]benzoxazepine (Va). A solution of 1.1 g
(5 mmol) of 3,5-di-tert-butyl-1,2-benzoquinone (III),
1.1 g (5 mmol) of 3,5-di-tert-butylbenzene-1,2-diol,
and 1.03 g (5 mmol) of 4-chloro-2,8-dimethylquinolin-
5-amine (IVa) in 10 ml of acetic acid was heated for
2 h at 65–70°C. The mixture as cooled, diluted with
water, and extracted with chloroform. The extract was
evaporated, and the residue was subjected to column
chromatography on aluminum oxide using petroleum
ether–chloroform (1:1) as eluent. The second bright
yellow fraction was evaporated, and the residue was
recrystallized from propan-2-ol. Yield 1.05 g (56%),
light yellow crystals, mp 196–199°C. IR spectrum, ν,
cm–1: 3286 (NH), 1647, 1593, 1473, 1433, 1393, 1366,
Analogous transformations were studied previously
[7–9]. Sterically hindered o-quinone imines are stable
compounds which can be isolated as individual sub-
stances under certain conditions [8, 9]. Abakumov
et al. [8] described the reaction of quinone III with
2,6-dimethylaniline and 2,6-diisopropylaniline, which
led to the formation of chiral 4aH-phenoxazines Xf
and Xg (R1 = R2 = R3 = H; R4 = Me, i-Pr) as a result
of intramolecular cyclization of the corresponding
o-quinone imines VII. However, compounds Xa–Xe
having no substituent on the C4a atom (R4 = H) under-
went aromatization via 1,3-sigmatropic (C–N) hydro-
gen shift to give 6,8-di-tert-butyl-10H-phenoxazines
IXa–IXe (Scheme 2).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 3 2009

3,5-DI-tert-BUTYL-1,2-BENZOQUINONE IN THE SYNTHESIS
445
1353, 1326, 1233. 1H NMR spectrum (CDCl3), δ, ppm:
1.28 s (9H, 9-t-Bu), 1.50 s (9H, 11-t-Bu), 2.66 s (3H,
4-CH3), 2.71 s (3H, 2-CH3), 5.78 br.s (1H, NH), 6.74 d
(1H, 5-H, J = 7.6 Hz), 6.84 d (1H, 10-H, J = 2.38 Hz),
7.04 d (1H, 8-H, J = 2.38 Hz), 7.13 br.s (1H, 1-H),
7.33 d (1H, 6-H, J = 7.69 Hz). Mass spectrum, m/z
(Irel, %): 374 (100) [M]+, 359 (9), 303 (9), 259 (16),
187 (14), 128 (10), 115 (18), 91 (12), 77 (21), 63 (12),
57 (90), 41 (87). Found, %: C 80.15; H 7.99; N 7.42.
C25H30N2O. Calculated, %: C 80.17; H 8.07; N 7.48.
the residue was recrystallized from propan-2-ol. Yield
0.16 g (7%), colorless crystals, mp 139–141°C. IR
spectrum, ν, cm–1: 3353 (NH), 1593, 1567, 1460, 1433,
1
1393, 1367, 1313, 1233. H NMR spectrum (CDCl3),
δ, ppm: 1.29 s (9H, 9-t-Bu), 1.50 s (9H, 11-t-Bu), 2.63 s
(3H, 4-CH3), 2.68 s (3H, 2-CH3), 6.62 s (1H, NH),
6.91 d (1H, 10-H, J = 2.08 Hz), 7.07 d (1H, 8-H, J =
2.08 Hz), 7.16 s (1H, 1-H), 7.59 s (1H, 5-H). Found,
%: C 66.21; H 6.38; Br 17.59; N 6.12. C25H29BrN2O.
Calculated, %: C 66.22; H 6.45; Br 17.62; N 6.18.
4,6-Di-tert-butyl-2-(2-nitrophenylamino)phenol
(VIIIa) and 6,8-di-tert-butyl-1-nitrophenoxazine
(IXa). A mixture of 1.1 g (5 mmol) of 3,5-di-tert-
butyl-1,2-benzoquinone (III) and 0.69 g (5 mmol) of
2-nitroaniline (VIa) was heated for 1 h at 135–140°C.
The melt was cooled and dissolved in a 2:1 mixture of
petroleum ether with chloroform, and the solution was
passed through a column charged with Al2O3 (15×
750 mm) using the same solvent mixture as eluent.
Two fractions were collected. The first orange fraction
contained compound VIIIa, and the second violet
fraction, compound IXa. The solvent was distilled off
from each fraction, and the residue was recrystallized
from propan-2-ol.
9,11-Di-tert-butyl-2,4,5-trimethyl-7H-quinolino-
[4,5-bc][1,5]benzoxazepine (Vb) was synthesized in
a similar way from 1.102 g of compound IVb. Yield
0.98 g (51%), light yellow crystals, mp 166–168°C. IR
spectrum, ν, cm–1: 3350 (NH), 1633, 1606, 1667, 1473,
1
1447, 1380, 1353, 1313, 1233. H NMR spectrum
(CDCl3), δ, ppm: 1.28 s (9H, 9-t-Bu), 1.50 s (9H,
11-t-Bu), 2.40 s (3H, 5-CH3), 2.63 s (3H, 4-CH3),
2.70 s (3H, 2-CH3), 5.73 br.s (1H, NH), 6.70 s (1H,
6-H), 6.83 d (1H, 10-H, J = 2.2 Hz), 7.02 d (1H, 8-H,
J = 2.2 Hz), 7.07 s (1H, 1-H). Found, %: C 80.35;
H 8.27; N 7.18. C26H32N2O. Calculated, %: C 80.37;
H 8.30; N 7.21.
9,11-Di-tert-butyl-2,4,6-trimethyl-7H-quinolino-
[4,5-bc][1,5]benzoxazepine (Vc) was synthesized in
a similar way from 1.102 g of compound IVc. Yield
1.15 g (59%), light yellow crystals, mp 206–208°C. IR
spectrum, ν, cm–1: 3406 (NH), 1593, 1567, 1460, 1393,
Compound VIIIa. Yield 0.58 g (34%), yellow–
1
orange crystals, mp 105–107°C. H NMR spectrum
(CDCl3), δ, ppm: 1.26 s (9H, 4-t-Bu), 1.42 s (9H,
6-t-Bu), 5.77 s (1H, OH), 6.65 d (1H, 6′-H, J =
7.69 Hz), 6.80 t (1H, 5′-H, J = 7.24 Hz), 7.00 d (1H,
5-H, J = 2.38 Hz), 7.33 d (1H, 3-H, J = 2.38 Hz),
7.36 t (1H, 4′-H, J = 7.04 Hz), 8.22 d (1H, 3′-H, J =
7.14 Hz), 8.88 s (1H, NH). Found, %: C 70.12; H 7.58;
N 8.15. C20H26N2O3. Calculated, %: C 70.15; H 7.65;
N 8.18.
1
1433, 1367, 1313, 1233. H NMR spectrum, δ, ppm:
1.29 s (9H, 9-t-Bu), 1.50 s (9H, 11-t-Bu), 2.49 s (3H,
4-CH3), 2.64 s (3H, 6-CH3), 2.69 s (3H, 2-CH3), 5.81 s
(1H, NH), 6.83 d (1H, 10-H, J 2.28 Hz), 7.04 d (1H,
8-H, J = 2.28 Hz), 7.12 s (1H, 5-H), 7.29 s (1H, 1-H).
Mass spectrum, m/z (Irel, %): 398 (95) [M]+, 373 (5),
315 (6), 301 (6), 287 (5), 273 (14), 194 (13), 128 (11),
115 (19), 91 (16), 77 (20), 57 (98), 41 (100). Found,
%: C 80.36; H 8.25; N 7.18. C26H32N2O. Calculated,
%: C 80.37; H 8.30; N 7.21.
Compound IXa. Yield 0.07 g (4%), bright violet
1
crystals, mp 101–103°C. H NMR spectrum (CDCl3),
δ, ppm: 1.24 s (9H, 8-t-Bu), 1.36 s (9H, 6-t-Bu), 6.48 d
(1H, 7-H, J = 2.2 Hz), 6.56 t (1H, 3-H, J = 8.78 Hz),
6.80 d (1H, 4-H, J = 2.2 Hz), 6.82 d (1H, 2-H, J =
6.66 Hz), 7.58 d (1H, 4-H, J = 7.62 Hz), 8.91 br.s (1H,
NH). Found, %: C 70.55; H 7.04; N 8.20. C20H24N2O3.
Calculated, %: C 70.57; H 7.11; N 8.23.
6-Bromo-9,11-di-tert-butyl-2,4-dimethyl-7H-
quinolino[4,5-bc][1,5]benzoxazepine (Vd). A mixture
of 1.1 g (5 mmol) of 3,5-di-tert-butyl-1,2-benzoqui-
none (III), 1.43 g (5 mmol) of 5-amino-6-bromo-4-
chloro-2,8-dimethylquinoline (IVd), and 200 mg of
p-toluenesulfonic acid was heated for 30 min at 160–
170°C. The melt was cooled and dissolved in a 1:1
mixture of petroleum ether with chloroform, and the
solution was passed through a column charged with
Al2O3 (15×750 mm) using the same solvent mixture as
eluent. The first colorless fraction was evaporated, and
4,6-Di-tert-butyl-2-(4-methyl-2-nitrophenyl-
amino)phenol (VIIIb). A mixture of 1.1 g (5 mmol) of
3,5-di-tert-butyl)-1,2-benzoquinone (III), 0.69 g
(5 mmol) of 2-nitroaniline (VIa), and 0.56 g of 3,5-di-
tert-butylbenzene-1,2-diol was heated for 1 h at 135–
140°C. The melt was cooled and dissolved in a 2:1
mixture of petroleum ether with chloroform, and the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 3 2009

ZYONG NGIA BANG et al.
446
solution was passed through a column charged with
aluminum oxide (15×750 mm) using the same solvent
mixture as eluent. A light–orange fraction was col-
lected, the solvent was distilled off, and the residue
was recrystallized from propan-2-ol. Yield 0.68 g
(38%), orange crystals, mp 137–140°C. 1H NMR spec-
trum (CDCl3), δ, ppm: 1.28 s (9H, 4-t-Bu), 1.44 s (9H,
6-t-Bu), 2.30 s (3H, 4′-CH3), 5.84 s (1H, OH), 6.58 d
(1H, 5′-H, J = 8.64 Hz), 7.01 d (1H, 5-H, J = 2.27 Hz),
7.20 d (1H, 6′-H, J = 8.64 Hz), 7.30 d (1H, 3-H, J =
2.35 Hz), 8.04 br.s (1H, NH). Mass spectrum, m/z
(Irel, %): 356 (100) [M]+, 341 (4), 321 (13), 310 (20),
295 (12), 279 (10), 268 (11), 253 (12), 237 (18), 223
(11), 211 (10), 146 (20), 133 (10), 117 (10), 105 (12),
91 (25), 77 (22), 65 (15), 57 (87), 41 (72). Found, %:
C 70.74; H 7.88; N 7.85. C21H28N2O3. Calculated, %:
C 70.76; H 7.92; N 7.86.
7.98 d (1H, 3:-H, J = 6.52 Hz), 8.83 br.s (1H, NH).
Found, %: C 74.31; H 8.15; N 3.91. C22H29NO3. Cal-
culated, %: C 74.33; H 8.22; N 3.94.
Methyl 2-(3,5-di-tert-butyl-2-hydroxyphenyl-
amino)-4,5-dimethoxybenzoate (VIIIf) was synthe-
sized from 1.06 g of methyl 2-amino-4,5-dimethoxy-
benzoate. Yield 0.85 g (41%), colorless crystals,
1
mp 139–141°C. H NMR spectrum (CDCl3), δ, ppm:
1.27 s (9H, 5-t-Bu), 1.44 s (9H, 3-t-Bu), 3.65 s (3H,
4′-OCH3), 3.86 s (3H, 5′-OCH3), 3.91 s (3H, COO-
CH3), 6.06 d (1H, 3′-H, J = 7.55 Hz), 7.03 d (1H, 4-H,
J = 2.35 Hz), 7.21 d (1H, 6-H, J = 2.35 Hz), 7.26 s
(1H, 6′-H), 7.42 s (1H, OH), 8.85 br.s (1H, NH).
Found, %: C 69.34; H 7.93; N 3.31. C24H33NO5. Cal-
culated, %: C 69.37; H 8.00; N 3.37.
2,4-Di-tert-butyl-6-(pyridin-2-ylamino)phenol
(VIIIg). A mixture of 1.1 g (5 mmol) of 3,5-di-tert-
butyl-1,2-benzoquinone (III), 0.47 g (5 mmol) of pyri-
din-2-amine (VIg), and 0.55 g of 3,5-di-tert-butyl-
benzene-1,2-diol was heated for 1 h at 135–140°C. The
melt was cooled and dissolved in a 2:1 mixture of
petroleum ether with chloroform, and the solution was
passed through a column charged with aluminum
oxide (15×750 mm) using the same solvent mixture as
eluent. The first colorless fraction was collected, the
solvent was distilled off, and the residue was recrystal-
lized from methanol. Yield 0.43 g (29%), colorless
Compounds VIIIc–VIIIf were synthesized in
a similar way.
4,6-Di-tert-butyl-2-(4-chloro-2-nitrophenyl-
amino)phenol (VIIIc) was synthesized from 0.86 g of
4-chloro-2-nitroaniline. Yield 0.68 g (36%), orange
1
crystals, mp 123–125°C. H NMR spectrum (CDCl3),
δ, ppm: 1.26 s (9H, 4-t-Bu), 1.42 s (9H, 6-t-Bu), 5.67 s
(1H, OH), 6.63 d (1H, 6-H, J = 9.06 Hz), 7.00 d (1H,
5-H, J = 2.2 Hz), 7.30 t (1H, 5′-H, J = 2.93 Hz), 7.32 d
(1H, 6′-H, J = 2.48 Hz), 8.22 d (1H, 3-H, J = 2.47 Hz),
8.85 br.s (1H, NH). Found, %: C 63.72; H 6.63;
Cl 9.38; N 7.41. C20H25ClN2O3. Calculated, %:
C 63.74; H 6.69; Cl 9.41; N 7.43.
1
crystals, mp 133–135°C. H NMR spectrum (CDCl3),
δ, ppm: 1.27 s (9H, 4-t-Bu), 1.43 s (9H, 2-t-Bu), 6.59 t
(1H, 4′-H, J = 4.95 Hz), 6.88 d (1H, 3′-H, J =
5.92 Hz), 6.95 d (1H, 3-H, J = 2.37 Hz), 6.98 d (1H,
6′-H, J = 5.92 Hz), 7.47 t (1H, 5′-H, J = 4.86 Hz),
7.99 d (1H, 5-H, J = 2.37 Hz), 8.40 s (1H, OH),
10.38 br.s (1H, NH). Mass spectrum, m/z (Irel, %): 298
(94) [M]+, 283 (100), 255 (29), 227 (47), 143 (16), 123
(26), 105 (29), 91 (36), 78 (45), 57 (53), 41 (71).
Found, %: C 76.44; H 8.73; N 9.33. C19H26N2O. Cal-
culated, %: C 72.47; H 8.78; N 9.39.
[2-(3,5-Di-tert-butyl-2-hydroxyphenylamino)-
phenyl](phenyl)methanone (VIIId) was synthesized
from 0.99 g of 2-aminobenzophenone. Yield 0.64 g
(32%), yellow crystals, mp 107–109°C. 1H NMR spec-
trum (CDCl3), δ, ppm: 1.29 s (9H, 5-t-Bu), 1.45 s (9H,
3-t-Bu), 6.02 s (1H, OH), 6.61 d (1H, 6′-H, J =
8.51 Hz), 6.70 t (1H, 5′-H, J = 7.14 Hz), 7.06 d (1H,
4-H, J = 2.38 Hz), 7.24–7.70 m (8H, Harom), 9.46 br.s
(1H, NH). Found, %: C 80.74; H 7.71; N 3.41.
C27H31NO2. Calculated, %: C 80.76; H 7.78; N 3.49.
2,4-Di-tert-butyl-6-(pyrimidin-2-ylamino)phenol
(VIIIh) was synthesized from 0.48 g of pyrimidin-2-
amine as described above for compound VIIIg. Yield
0.46 g (31%), colorless crystals, mp 189–191°C.
1H NMR spectrum (CDCl3), δ, ppm: 1.30 s (9H,
4-t-Bu), 1.48 s (9H, 2-t-Bu), 6.70 t (1H, 5′-H, J =
4.90 Hz), 6.92 d (1H, 5-H, J = 2.35 Hz), 7.26 s (1H,
OH), 8.38 s (2H, 4′-H, 6′-H), 9.34 br.s (1H, NH). Mass
spectrum, m/z (Irel, %): 299 (97) [M]+, 284 (100), 256
(14), 242 (10), 228 (30), 135 (12), 115 (8), 96 (13), 79
(19), 57 (28), 41 (45). Found, %: C 72.19; H 8.35;
Methyl 2-(3,5-di-tert-butyl-2-hydroxyphenyl-
amino)benzoate (VIIIe) was synthesized from 0.76 g
of methyl 2-aminobenzoate. Yield 0.69 g (39%), color-
1
less crystals, mp 109–110°C. H NMR spectrum
(CDCl3), δ, ppm: 1.27 s (9H, 5-t-Bu), 1.44 s (9H,
3-t-Bu), 3.93 s (3H, COOCH3), 6.09 s (1H, OH),
6.52 d (1H, 6′-H, J = 8.28 Hz), 6.75 t (1H, 5′-H, J =
7.18 Hz), 7.02 d (1H, 4-H, J = 2.34 Hz), 7.24 t (1H,
4′-H, J = 4.47 Hz), 7.28 d (1H, 6-H, J = 2.34 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 3 2009

3,5-DI-tert-BUTYL-1,2-BENZOQUINONE IN THE SYNTHESIS
447
N 14.01. C18H25N3O. Calculated, %: C 72.21; H 8.42;
N 14.03.
6,8-Di-tert-butyl-3-chloro-1-nitro-10H-phenoxa-
zine (IXc) was synthesized from 0.57 g (0.15 mmol)
of compound VIIIc. Yield 0.09 g (14%), dark red
2,4-Di-tert-butyl-6-(4-methylpyrimidin-2-yl-
amino)phenol (VIIIi) was synthesized from 0.55 g of
4-methylpyrimidin-2-amine according to the procedure
described above for the synthesis of compound VIIIg.
Yield 0.28 g (18%), colorless crystals, mp 189–191°C
1
crystals, mp 171–173°C. H NMR spectrum (CDCl3),
δ, ppm: 1.24 s (9H, 8-t-Bu), 1.34 s (9H, 6-t-Bu), 6.48 d
(1H, 7-H, J = 2.05 Hz), 6.79 d (1H, 2-H, J = 1.98 Hz),
6.83 d (1H, 9-H, J = 2.05 Hz), 7.57 d (1H, 4-H, J =
2.2 Hz), 8.93 br.s (1H, NH) Found, %: C 64.05;
H 6.12; Cl 9.42; N 7.42. C20H23ClN2O3. Calculated, %:
C 64.08; H 6.18; Cl 9.46; N 7.47.
1
(from propan-2-ol). H NMR spectrum (CDCl3), δ,
ppm: 1.29 s (9H, 4-t-Bu), 1.49 s (9H, 2-t-Bu), 2.41 s
(3H, 4′-CH3), 6.56 d (1H, Harom, J = 5.15 Hz), 6.89 d
(1H, 3-H, J = 2.35 Hz), 7.10 s (1H, OH), 7.21 d (1H,
5-H, J = 2.35 Hz), 8.23 d (1H, Harom, J = 5.15 Hz),
9.85 br.s (1H, NH). Found, %: C 72.78; H 8.61;
N 14.37. C19H27N3O. Calculated, %: C 72.81; H 8.68;
N 14.41.
(6,8-di-tert-Butyl-10H-phenoxazin-1-yl)(phenyl)-
methanone (IXd) was synthesized from 0.6 g
(0.15 mmol) of compound VIIId. Yield 0.23 g (38%),
1
bright orange crystals, mp 129–132°C. H NMR spec-
trum (CDCl3), δ, ppm: 1.23 s (9H, 8-t-Bu), 1.38 s (9H,
6-t-Bu), 6.42 d (1H, 7-H, J = 2.02 Hz), 6.47 t (1H,
3-H, J = 7.6 Hz), 6.73 d (1H, 9-H, J = 2.02 Hz), 6.77 d
(1H, 2-H, J = 7.6 Hz), 6.98 d (1H, 4-H, J = 8.2 Hz),
7.41–7.63 m (5H, Harom), 9.41 br.s (1H, NH). Found,
%: C 81.16; H 7.27; N 3.46. C27H29NO2. Calculated,
%: C 81.17; H 7.32; N 3.51.
6,8-Di-tert-butyl-1-nitro-10H-phenoxazine (IXa).
Lead(IV) oxide, 4 g, was added to a solution of 0.52 g
(1.5 mmol) of 2,4-di-tert-butyl-6-(2-nitrophenyl-
amino)phenol (VIIIa) in 8 ml of benzene, and the
mixture was vigorously stirred for 2 h at room tem-
perature. The mixture was filtered, the filtrate was
evaporated, and the residue was heated for 1 h at 135–
140°C. The resulting melt was cooled and dissolved in
petroleum ether–chloroform (2:1), and the solution
was passed through a column charged with aluminum
oxide (15×550 mm) using the same solvent mixture as
eluent. A violet fraction was collected, the solvent was
distilled off, and the residue was recrystallized from
propan-2-ol. Yield 0.19 g (36%), bright violet crystals,
Methyl 6,8-di-tert-butyl-3,4-dimethoxy-10H-
phenoxazine-1-carboxylate (IXe) was synthesized
from 0.62 g (0.15 mmol) of compound VIIIf. Yield
0.17 g (27%), bright yellow crystals, mp 125–127°C.
1H NMR spectrum (CDCl3), δ, ppm: 1.28 s (9H,
8-t-Bu), 1.44 s (9H, 6-t-Bu), 3.78 s (3H, 3-OCH3),
3.85 s (3H, 4-OCH3), 3.90 s (3H, COOCH3), 6.48 d
(1H, 7-H, J = 1.35 Hz), 6.63 s (1H, 2-H), 6.83 d (1H,
9-H, J = 1.35 Hz), 8.55 br.s (1H, NH). Found, %:
C 69.68; H 7.48; N 3.32. C24H31NO5. Calculated, %:
C 69.71; H 7.56; N 3.39.
1
mp 101–103°C. H NMR spectrum (CDCl3), δ, ppm:
1.24 s (9H, 8-t-Bu), 1.36 s (9H, 6-t-Bu), 6.48 d (1H,
7-H, J = 2.2 Hz), 6.56 t (1H, 3-H, J = 8.78 Hz), 6.80 d
(1H, 9-H, J = 2.2 Hz), 6.82 d (1H, 2-H, J = 6.66 Hz),
7.58 d (1H, 4-H, J = 7.62 Hz), 8.91 br.s (1H, NH).
Found, %: C 70.55; H 7.04; N 8.20. C20H24N2O3. Cal-
culated, %: C 70.57; H 7.11; N 8.23.
This study was performed under financial support
by the Presidium of the Russian Academy of Sciences
(program no. 8, “Development of Methods for the Syn-
thesis of Chemical Substances and Creation of New
Materials,” subprogram “Development of Methodol-
ogy of Organic Synthesis and Design of Compounds
with Practically Important Properties”), by the prog-
ram for support of young scientists, and by the prog-
ram for support of leading scientific schools (project
no. NSh-4849.2006.3).
Compounds IXb–IXe were synthesized in a similar
way.
6,8-Di-tert-butyl-3-methyl-1-nitro-10H-phenoxa-
zine (IXb) was synthesized from 0.54 g (0.15 mmol)
of compound VIIIb. Yield 0.21 g (39%), dark red
1
crystals, mp 152–154°C. H NMR spectrum, δ, ppm:
REFERENCES
1.24 s (9H, 8-t-Bu), 1.36 s (9H, 6-t-Bu), 2.18 s (3H,
3-CH3), 6.47 d (1H, 7-H, J = 2.27 Hz), 6.68 d (1H,
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7.38 d (1H, 4-H, J = 1.83 Hz), 8.83 br.s (1H, NH).
Found, %: C 71.15; H 7.38; N 7.87. C21H26N2O3. Cal-
culated, %: C 71.16; H 7.39; N 7.90.
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