New functionalized sterically hindered o-aminophenols: Reversible intramolecular cyclization

Full text of DOI:10.1134/S001250081302002X

ISSN 0012ꢀ5008, Doklady Chemistry, 2013, Vol. 448, Part 2, pp. 44–48. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © V.K. Cherkasov, N.O. Druzhkov, T.N. Kocherova, E.N. Egorova, A.S. Shavyrin, 2013, published in Doklady Akademii Nauk, 2013, Vol. 448, No. 4,
pp. 422–426.
CHEMISTRY
New Functionalized Sterically Hindered oꢀAminophenols:
Reversible Intramolecular Cyclization
Corresponding Member of the RAS V. K. Cherkasov, N. O. Druzhkov,
T. N. Kocherova, E. N. Egorova, and A. S. Shavyrin
Received July 16, 2012
DOI: 10.1134/S001250081302002X
NꢀSubstituted
oꢀaminophenols exhibit redox [7]. Some Nꢀsubstituted oꢀaminophenols do not exist
in the aminophenol form but are isolated as isomeric
benzoxazoles [8, 9].
This study is aimed at synthesizing new sterically
hindered oꢀaminophenols derived from acetylꢀsubstiꢀ
isomerism when bound in a complex with a metal. The
introduction of additional coordinating groups
increases not only the ligand denticity but also the
number of redox states, which considerably enhances
the possibility of using the ligand in coordination tuted heterocyclic compounds and 3ꢀ(2,6ꢀdiisopropylꢀ
phenylimino)butanꢀ2ꢀone (ImKet) [10].
NꢀSubstituted ꢀaminophenols ( and
obtained by the reaction of 2ꢀaminoꢀ4,6ꢀdiꢀtert
butylphenol with ꢀacetyl derivatives of pyridine and
chemistry [1–4]. One of the methods to obtain such
derivatives consists in the condensation of sterically
o
1
2) were
hindered
oꢀaminophenols with different (aliphatic,
ꢀ
aromatic) aldehydes and ketones [5, 6] and the 1,2ꢀ
α
addition of amines to substituted
oꢀbenzoquinones thiophene (Scheme 1).
tꢀBu
tꢀBu
OH
N C
OH
100–140°C
O
+
–H2O
C
N
S
S
N
tꢀBu
H3C
tꢀBu
NH2
CH3
1 (65%)
2 (86%)
Scheme 1.
Isolated compounds
1
and
2
are yellow solids soluꢀ 1.44 ppm), methyl (
δ
1
.87–2.51 ppm), and hydroxy
.51–6.47 ppm), and a set of sigꢀ
nals of the aromatic protons of the aminophenol
ble in organic solvents and slowly oxidized in air. Their
composition was confirmed by elemental analysis
while the structure was established by NMR spectrosꢀ
copy.
group protons ( 5
δ
moiety and pyridine (thiophene) substituent (
8.55 ppm).
δ
6.70–
1H NMR spectra of compounds
narrow intense singlets of the tertꢀbutyl (
1
and
2
δ
show
1.26–
The reaction of 2ꢀaminoꢀ4,6ꢀdiꢀtertꢀbutylphenol
with ImKet led to a colorless crystalline solid identiꢀ
13
fied by spectral methods (1H, C NMR) and nitroꢀ
gen–proton correlation procedure (NHCORR) as
Razuvaev Institute of Organometallic Chemistry,
Russian Academy of Sciences, ul. Tropinina 49,
Nizhni Novgorod, 603950 Russia
dihydrobenzoxazole
3 rather than Nꢀsubstituted oꢀ
aminophenol (Scheme 2).
44

NEW FUNCTIONALIZED STERICALLY HINDERED
o
ꢀAMINOPHENOLS
45
tꢀBu
H3C
O
CH
N
3 iꢀPr
OH
+
tꢀBu
NH2
iꢀPr
ImKet
tꢀBu
tꢀBu
OH
CH3
O
CH
3 N
CH3
iꢀPr
3 iꢀPr
N
N
tꢀBu
CH
N
H
tꢀBu
iꢀPr
3 (85%)
iꢀPr
Scheme 2.
exhibits characterisꢀ
The IR spectrum of compound
3
It is known from the literature [8, 9] that two isoꢀ
ꢀsubstituted ꢀaminophenols
exist in equilibrium: open ( ꢀaminophenol) and cyclic
(benzoxazole). To reveal whether such an equilibrium
occurs for the obtained compounds, we conducted an
experiment with the use of different solvents (C6D6,
DMSO, CD3CN, CD3OD).
tic absorption bands of stretching vibrations of imine meric forms of certain
ν C=N 1666 cm–1) and amine (ν N–H 3291 cm–1) groups.
The 1H NMR spectrum of compound
shows the
signals of the tertꢀbutyl protons ( 1.26 and 1.36 ppm)
and a multiplet of aromatic protons of the aminopheꢀ
nol and ꢀaryl rings ( .74–7.14 ppm). The spectrum
also displays the doublets of methyl groups of the isoꢀ
propyl substituents ( .79–0.83 ppm, = 6.88 Hz), sepꢀ
tets of methyne protons ( 2.23 and 2.64 ppm,
6.88 Hz), and narrow singlets of nonequivalent methyl
groups ( 1.80 and 1.86 ppm).
The structure of compound
N
o
o
(
3
δ
N
δ
6
The 1H NMR spectra of compounds
1–3 immediꢀ
ately after dissolution in CD3OD were found to correꢀ
spond completely to the expected spectra. However,
the integrated intensity of the signal of the methyl
δ
0
J
δ
J =
δ
group at the imine carbon atom in compounds
and the quaternary carbon atom in compound
1
3
and
conꢀ
2
3
was confirmed by the
data of Xꢀray diffraction study (Fig. 1).
siderably decreases within 3–5 min, while new broadꢀ
ened signals shifted upfield appear at the same time
(Fig. 2).
Crystals for Xꢀray diffraction analysis were
obtained from CH3CN. The Xꢀray diffraction study
was performed on a Smart APEX automated diffractoꢀ
meter (graphite monochromator, Mo
K
radiation, –
ω
α
ϕ
scanning, exposure of 10 s/frame). The structure was
solved by direct methods and refined by least squares
on in anisotropic approximation for all nonꢀ
hydrogen atoms. Hydrogen atoms were located from
difference electron density maps and refined isotropiꢀ
cally. All computations were carried out with the use of
the SHELXTL v. 6.10.1x software package.
O1
C2
Fh2kl
C1
C3
N1
C4
The crystallographic data for compound
C30H44N2O, triclinic crystal system, space group Р1,
3:
N2
unit cell parameters
= 18.5268(1)
= 109.440(2)
1.072 g cm–3,
а
α
= 11.2464(9)
= 102.754(2)
Å
,
b
β
= 15.8609(1)
= 107.317(2)
= 4,
(000) = 984, R1
Å
,
c
γ
Å
°
;
;
°,
°
,
V
= 2781.0(4) Å3
,
Z
d
=
=
μ
= 0.064 mm–1
,
F
0.0667, wR2 = 0.1528. The crystallographic data were
deposited with the Cambridge Structural Database
(CCDC 890194), deposit@ccdc.cam.ac.uk, http://www.
ccdc.cam.ac.uk.
Fig. 1. Molecular structure of compound 3. Hydrogen atꢀ
oms are omitted except for the proton of the amino group.
The main bond distances (Å): O1–C2, 1.393(3); O1–C1,
1.464(3); N1–C1, 1.464(3); N2–C4, 1.277(3).
DOKLADY CHEMISTRY Vol. 448
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2013

46
CHERKASOV et al.
These changes indicate the exchange of hydrogen
After recrystallization of compound 3 from
CD3OD, a 2H NMR spectrum in CDCl3 was obtained.
The spectrum shows a signal with chemical shift of
1.8 ppm corresponding to the chemical shift of the
atoms of the methyl group for deuterium. In spite of
the fact that the exchange of hydrogen atoms in OH or
NH groups for deuterium in CD3OD is widely known,
the selective deuteration of methyl group under these
conditions is unusual.
Nonetheless such an exchange can be explained by
the existence of cyclization–decyclization equilibrium
in solution that proceeds through the enamine form
methyl protons in compound
3 (1.83 ppm). This is
direct evidence for the reaction proposed by us. The
intensity of 2H signals due to the CHD2 and H2D groups
located in proximity to the main peak is substantially
lower; taking into account the reaction conditions, we
may affirm that the deuteration results mainly in a prodꢀ
uct containing the completely deuterated CD3 group.
containing OH group (1*–3*), which is readily deuꢀ
terated with CD3OD (Scheme 3). Subsequently, deuꢀ
terium from the resulting OD group comes to the
methyl group. In the presence of a CD3OD excess, the
methyl hydrogen atoms are gradually replaced by deuꢀ
terium to give completely deuterated CD3 groups and
partially deuterated CHD2 and CH2D groups.
13
The C NMR spectrum of compound
2 shows a
multiplet at 16 ppm resulting from a superposition of
the septet of CD3 group and the signals of CHD2 and
CH2D groups (
J(C–D) = 0.19 Hz), Fig. 3.
tꢀBu
tꢀBu
tꢀBu
H
CH2
OD
OH
CH2
O
CD3OD
CH3
CH3
CH2
CH3
N Ar
N Ar
N
H
N Ar
N
H
tꢀBu
N
H
tꢀBu
tꢀBu
3
3*
tꢀBu
tꢀBu
O
CH3
CH2D
O
CH3
CD3
…
N Ar
N Ar
N
H
N
D
tꢀBu
tꢀBu
(Ar = 2,6ꢀdiisopropylphenyl
)
tꢀBu
tꢀBu
tꢀBu
tꢀBu
OH
CH3
OH
CH3
O
OH
CH2
CD3OD
CD3
C
C
R
C
C
R
N
R
N
N
H
tꢀBu
tꢀBu
tꢀBu
R
N
tꢀBu
H
1, 2
1*, 2*
⎛
⎜
⎜
⎜
⎝
⎞
⎟
⎟
⎟
⎠
ꢀꢀꢀꢀꢀ
Rꢀꢀꢀꢀꢀ=ꢀ
;
S
N
Scheme 3.
The oxidation of compounds 1–3 with alkaline solution of potassium ferricyanide leads to substituted benzꢀ
oxazines (Scheme 4).
⎛
⎜
⎜
⎞
⎟
⎟
⎟
⎟
⎟
⎟
⎠
iꢀPr
tꢀBu
CH3
N
;
;
R =
⎜
⎜
⎜
⎜
⎝
O
N
S
CH2
K3Fe(CN)6, KOH
N
1–3
C
R
tꢀBu
4 (48%)
5 (45%)
6 (48%)
iꢀPr
Scheme 4.
DOKLADY CHEMISTRY Vol. 448
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NEW FUNCTIONALIZED STERICALLY HINDERED
ꢀBu
o
ꢀAMINOPHENOLS
(СН3)3С
47
t
(СН3)3С
tꢀBu
(a)
CH3
(СН3)3С
(СН3)3С
(b)
СD3
2.5
1.5
0.5
, ppm
δ
35
33
31 28 17 16 15
, ppm
δ
1
Fig. 2. Fragments of H NMR spectra of compound
2
2
in
in
13
CD OD: (a) immediately after dissolution of
CD OD, (b) 10 min later.
Fig. 3. A fragment of C NMR spectrum of compound
2
3
3
in CD OD.
3
The 1H NMR spectra of compounds
4
and
5
show
ized by the presence of equilibrium between amiꢀ
nophenol and cyclic (benzoxazole) forms that occurs
through formation of isomeric enamine species. The
existence of this equilibrium is responsible for the
complete exchange of the methyl in close proximity to
the benzoxazole ring for deuterium in a CD3OD
the narrow intense singlets of the tertꢀbutyl protons
(1.33–1.41 ppm) and the signals of the protons of
resultant CH2 groups (4.91–5.24 ppm). The spectral
region of aromatic protons displays the multiplets of
protons of aminophenol and pyridine (thiophene)
substituents (7.13–8.65 ppm).
medium. The oxidation of compounds
to benzoxazine structures.
1–3 gives rise
1
The H NMR spectrum of compound
6 exhibits
intense singlets of protons of the tertꢀbutyl (1.33–
1.41 ppm) and methyl (2.07 ppm) groups, a septet of
ACKNOWLEDGMENTS
methyne protons (2.64 ppm,
blets of methyl protons of isopropyl substituents (1.14
and 1.15 ppm, = 6.88 Hz), and a multiplet of aroꢀ
matic protons (7.08–7.34 ppm). Moreover, a proton
peak of the CH2 group of compound is present. The
structure of compound was also confirmed by C
J = 6.88 Hz), two douꢀ
This work was supported by the Council for
Grants of the President of the Russian Federation for
Support of Leading Scientific Schools (grant
no. NSh 1113.2012.3), the Russian Foundation for Basic
Research (project nos. 11–03–97041ꢀr_povolzh’e_a
and 12–03–31348\12_mol), and the Ministry of Educaꢀ
tion and Science of the Russian Federation (the Federal
Target Program “Scientific and ScientificꢀPedagogical
Personnel of the Innovative Russia in 2009–2013,” State
Contract no. 8465).
J
6
13
6
NMR and DEPT (61.2 ppm) data.
The formation of products of methyl groups dehyꢀ
dration
4–6 upon oxidation of compounds 1–3 can
be also explained by the existence in solution of
enamine species
moiety.
1*–3* containing the methylene
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DOKLADY CHEMISTRY Vol. 448
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2013

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