Tautomerism and stereodynamics of indophenols, amidines, their derivatives, and analogs: XIII. 1 intramolecular cyclization of 2,6-di-tert-butyl-4-(o-alkoxyphenylimino)-2,5-cyclohexadienones as a method of synthesis of spiro benzoxazines

Article abstract of DOI:10.1023/A:1012373722077

A new method was developed for synthesizing benzoxazine derivatives by O-alkylation of 2,6-di-tert-butyl-4-(o-hydroxyphenylirnino)-2,5-cyclohexadienones with allyl or benzyl halides and subsequent thermal heterocyclization of allyl or benzyl ethers thus f

Full text of DOI:10.1023/A:1012373722077

Russian Journal of General Chemistry, Vol. 71, No. 5, 2001, pp. 776 779. Translated from Zhurnal Obshchei Khimii, Vol. 71, No. 5, 2001,
pp. 828 832.
Original Russian Text Copyright
2001 by Kurbatov, Simakov, Vikrishchuk, Ruzhnikov, Zhdanov, Olekhnovich.
Tautomerism and Stereodynamics of Indophenols, Amidines,
Their Derivatives, and Analogs:
XIII.1 Intramolecular Cyclization of 2,6-Di-tert-butyl-4-
(o-alkoxyphenylimino)-2,5-cyclohexadienones as a Method
of Synthesis of Spiro Benzoxazines
S. V. Kurbatov, V. I. Simakov, N. I. Vikrishchuk, A. E. Ruzhnikov,
Yu. A. Zhdanov, and L. P. Olekhnovich
Rostov State University, Rostov-on-Don, 344104 Russia
Received September 27, 1999
Abstract A new method was developed for synthesizing benzoxazine derivatives by O-alkylation of 2,6-di-
tert-butyl-4-(o-hydroxyphenylimino)-2,5-cyclohexadienones with allyl or benzyl halides and subsequent
thermal heterocyclization of allyl or benzyl ethers thus formed. The cyclization of ethers derived from 2,6-di-
tert-butyl-4-(o-hydroxyphenylimino)-2,5-cyclohexadienones and phenacyl bromides or diethyl bromomalonate
is so fast that these compounds cannot be isolated.
We previously reported [2] on a new noncata-
lytic intramolecular rearrangement of allyl and ben-
zyl ethers I derived from 2,6-di-tert-butyl-4-(o-hy-
droxyphenylimino)-2,5-cyclohexadienones, which af-
forded the corresponding spiro benzoxazines II
(Scheme 1). The mechanism of this transformation
includes concerted [1,5]-C N sigmatropic proton
shift and electrocyclic formation of C C bond;
these processes are promoted by electronic polar-
ization of ethers I during Z/E topomerization via
rotation about the C N bond [3]. The kinetic and
activation parameters of the rearrangements I II
7
11
1
are as follows: k298 10 10
s , G298 108
1
130 kJ mol [2].
Scheme 1.
R = C6H4NO2-4, CH CH2; X = 3,5-(t-Bu)2, 4-NO2, 5-NO2.
For communication XII, see [1].
1070-3632/01/7105-0776$25.00 2001 MAIK Nauka/Interperiodica
1

TAUTOMERISM AND STEREODYNAMICS OF INDOPHENOLS, AMIDINES
777
The goal of the present study was to determine the
scope of application of the above method for building
up benzoxazine ring and to develop preparative proce-
dures for synthesizing previously inaccessible benz-
oxazine derivatives with a spiro-fused cyclohexadi-
enone fragment.
range from 100 to 180 C (perfluorotoluene, o-xylene,
chlorobenzene, o-dichlorobenzene, diphenyl ether).
The cyclization in higher-boiling solvents, e.g., in
diphenyl ether, was faster, but the yield of the prod-
uct was reduced because of appreciable tarring. In
lower-boiling solvents, the reaction takes much time
or does not occur at all (as in toluene). The optimal
conditions were heating in freshly distilled xylenes
under reflux for 2 5 h. The progress of the reaction
can be monitored visually, following the disappear-
ance of the original bright red color, or by thin-lay-
er chromatography on Al2O3 using petroleum ether
as eluent. The transformation I II can also be mon-
O
t-Bu
Bu-t
3
H
R
N4
5
H
2
1O
6
X
7
9
1
8
itored by H NMR spectroscopy: the CH2 signal at
4.5 ppm disappears, and NH and CH signals appear
III IX
at
5.1 and 6.5 ppm, respectively.
III, X = H, R = CH=CH2; IV, X = H, R = Ph; V, X = H,
R = 4-NO2C6H4; VI, X = 7-Cl, R = CH=CH2; VII, X =
7-Cl, R = Ph; VIII, X = 7-Br, R = CH=CH2; IX, X = 7-Br,
R = Ph.
The cyclization of p-nitrobenzyl ether X in boiling
p-xylene was accompanied by formation of a con-
siderable amount ( 30%) of phenoxazinone XI, pre-
sumably as a result of homolytic cleavage of the
O CH2 bond under severe conditions. The structure
of compound XI was established on the basis of its
1H NMR and mass spectra.
Compounds III IX were synthesized by heating
solutions of the corresponding 2,6-di-tert-butyl-4-
[o-allyloxy(or benzyloxy)phenylimino]-2,5-cyclohexa-
dienones [2] in solvents with boiling boints in the
O
O
t-Bu
Bu-t
t-Bu
Bu-t
O
N
O
CH2
NO2
N
NO2
NO2
X
XI
Taking into account that the key stage in the trans- cyclization kinetics. We have found that alkylation of
formation under study is proton transfer from the
active methylene group to the imino nitrogen atom,
it was interesting to examine the effects of different
electron-acceptor groups on the C N proton shift and
compound XII with phenacyl bromides (Scheme 2)
is accompanied by so fast cyclization into benzoxa-
zines XV and XVI that intermediate phenacyl ethers
XIII and XIV cannot be isolated or even detected.
Scheme 2.
O
N
O
N
O
t-Bu
Bu-t
t-Bu
Bu-t
t-Bu
Bu-t
O
O
R
Br CH2C
R
C
H
O
H N
K2CO3, acetone
H
O
CH2
O
C
O
R
XII
XV, XVI
XIII, XIV
XIII, XV, R = H; XIV, XVI, R = Br.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 5 2001

778
KURBATOV et al.
1
The H NMR spectra of benzoxazines XV and XVI
are characterized by isochronous signals from both
tert-butyl groups, as well as from protons in the
cyclohexadiene ring. Despite mild consitions of the
transformations XII XV and XII XVI, the yields
of the final products were considerably lower than
the yields of benzoxazines II IX in the thermal
cyclization of allyl and benzyl ethers. In this connec-
tion it seemed surprising that compounds XVII and
XVIII which were obtained by alkylation with ethyl
bromoacetate did not undergo cyclization into benz-
oxazines even on prolonged heating in boiling xylene
or o-dichlorobenzene.
By contrast, the reaction of 2,6-di-tert-butyl-4-
(o-hydroxyphenylimino)-2,5-cyclohexadienone with
diethyl bromomalonate, as with phenacyl bromides,
directly yielded spiro diester XIX (Scheme 3). The
structure of XIX is confirmed by the presence in the
1H NMR spectrum of isochronous signals from the
tert-butyl groups ( 1.39 ppm) and cyclohexadiene
ring protons ( 7.29 ppm).
O
t-Bu
Bu-t
O
C
N
2
O
1
CH2
OEt
3
6
R
4
5
Thus, the rearrangement of 2,6-di-tert-butyl-4-
(o-alkoxyphenylimino)-2,5-cyclohexadienones can be
regarded as a convenient method for preparation of
various spirobenzoxazine derivatives.
XVII, XVIII
XVII, R = 4-NO2; XVIII, R = 5-NO2.
Scheme 3.
O
O
O
t-Bu
Bu-t
t-Bu
Bu-t
t-Bu
Bu-t
COOEt
COOEt
Br CH
COOEt
COOEt
COOEt
COOEt
H N
K2CO3, acetone
N
OH
N
CH
O
O
XIX
EXPERIMENTAL
3 ,5 -Di-tert-butyl-2-vinyl-2,3-dihydro-1,4-benz-
oxazine-3-spiro-1 -cyclohexa-2 ,5 -dien-4 -one (III).
1
1
mp 126 C. Yield 75%. H NMR spectrum (CDCl3),
The H NMR spectra were obtained on a Bruker
DPX-250 instrument (250 MHz) at 25 C. The mass
spectrum of compound XI was recorded on a Perkin
Elmer Q-Mass 910 GC MS system. The elemental
compositions of compounds III XIX were consistent
with the calculated values.
, ppm: 1.18 s (9H), 1.20 s (9H), 3.88 s (1H), 5.30 m
(2H), 4.41 d (1H), 5.62 m (1H), 6.38 d (1H), 6.8 d
(1H), 6.69 d (1H), 6.76 d.d (1H), 6.86 d.d (1H),
6.91 d (1H).
3 ,5 -Di-tert-butyl-2-phenyl-2,3-dihydro-1,4-
benzoxazine-3-spiro-1 -cyclohexa-2 ,5 -dien-4 -one
(IV). mp 212 C. Yield 70%. 1H NMR spectrum
(acetone-d6), , ppm: 1.08 s (9H), 1.12 s (9H), 5.19 s
(1H), 5.77 s (1H), 6.70 m (3H), 6.85 m (3H), 7.27 m
(5H).
General procedure for synthesis of compounds
III IX. To a solution of 1 mmol of appropriate
2,6-di-tert-butyl-4-(o-hydroxyphenylimino)-2,5-cyclo-
hexadienone in 20 ml of acetone we added 1.5 mmol
of freshly calcined potassium carbonate and 1 mmol
of allyl bromide or benzyl halide. The progress of
the reaction was monitored by chromatography on
Al2O3 (eluent petroleum ether). When the reaction
was complete, the mixture was filtered, the filtrate
was evaporated to dryness, and the residue was recrys-
tallized from methanol. The product was refluxed in
o-xylene for 2 5 h, the solvent was removed under
reduced pressure, and the residue was recrystallized
from methanol or 2-propanol.
3 ,5 -Di-tert-butyl-2-p-nitrophenyl-2,3-dihydro-
1,4-benzoxazine-3-spiro-1 -cyclohexa-2 ,5 -dien-4 -
1
one (V). mp 198 C. Yield 65%. H NMR spectrum
(CDCl3), , ppm: 1.18 s (9H), 1.22 s (9H), 4.05 s
(1H), 4.56 s (1H), 6.33 d (1H), 6.49 d (1H), 6.75
8.86 m (4H), 7.35 d (2H), 8.00 d (2H).
3 ,5 -Di-tert-butyl-7-chloro-2-vinyl-2,3-dihydro-
1,4-benzoxazine-3-spiro-1 -cyclohexa-2 ,5 -dien-4 -
1
one (VI). mp 168 C. Yield 80%. H NMR spectrum
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 5 2001

TAUTOMERISM AND STEREODYNAMICS OF INDOPHENOLS, AMIDINES
779
(CDCl3), , ppm: 1.17 s (9H), 1.21 s (9H), 3.88 s
(1H), 4.39 d (1H), 5.28 m (2H), 5.57 m (1H), 6.31 d
(1H), 6.47 d (1H), 6.58 d (1H), 6.67 s (1H), 6.70 d
(1H).
Ethyl 2-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexa-
dienylidenamino)-4-nitrophenoxyacetate (XVII).
1
mp 120 C. Yield 60%. H NMR spectrum (CDCl3),
, ppm: 1.17 s (9H), 1.25 s (9H), 1.31 t (3H), 4.22 q
(2H), 4.72 s (2H), 6.61 d (1H), 6.85 d (1H), 7.06 d
(1H), 7.69 d (1H), 8.05, d. d (1H).
3 ,5 -Di-tert-butyl-7-chloro-2-phenyl-2,3-dihydro-
1,4-benzoxazine-3-spiro-1 -cyclohexa-2 ,5 -dien-4 -
1
one (VII). mp 223 C. Yield 80%. H NMR spectrum
Ethyl 2-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexa-
(CDCl3), , ppm: 1.07 s (9H), 1.08 s (9H), 4.07 s
(1H), 5.02 m (1H), 6.42 d (1H), 6.61 d (1H), 6.69 d
(1H), 6.73 d (1H), 6.87 d (1H), 7.20 m (5H).
dienylidenamino)-5-nitrophenoxyacetate (XVIII).
1
mp 118 C. Yield 55%. H NMR spectrum (CDCl3),
, ppm: 1.16 s (9H), 1.25 m (3H), 1.30 s (9H), 4.22 q
(2H), 4.52 s (2H), 6.54 d (1H), 6.86 d (1H), 7.05 d
(1H), 7.68 d (1H), 7.93 d.d (1H).
7-Bromo-3 ,5 -di-tert-butyl-2-vinyl-2,3-dihydro-
1,4-benzoxazine-3-spiro-1 -cyclohexa-2 ,5 -dien-4 -
1
one (VIII). mp 175 C. Yield 65%. H NMR spectrum
Diethyl 3 ,5 -di-tert-butyl-4 -oxo-2,3-dihydro-
1,4-benzoxazine-3-spiro-1 -cyclohexa-2 ,5 -diene-2,2-
dicarboxylate (XIX). To a solution of 0.31 g of
compound XII in 10 ml of acetone we added 0.5 g
of potassium carbonate and 0.34 g of diethyl bromo-
malonate [4], and the mixture was left overnight at
room temperature. It was then filtered, the filtrate
was evaporated, and the residue was purified by
column chromatography on Al2O3 (eluent chloroform),
followed by recrystallization from 2-propanol.
(CDCl3), , ppm: 1.17 s (9H), 1.21 s (9H), 3.93 s
(1H), 4.37 d (1H), 5.29 m (2H), 5.54 m (1H), 6.33 d
(1H), 6.49 d (1H), 6.78 m (3H).
7-Bromo-3 ,5 -di-tert-butyl-2-phenyl-2,3-dihydro-
1,4-benzoxazine-3-spiro-1 -cyclohexa-2 ,5 -dien-4 -
1
one (IX). mp 228 C. Yield 75%. H NMR spectrum
(CDCl3), , ppm: 1.07 s (9H), 1.09 s (9H), 4.01 s
(1H), 5.00 s (1H), 6.38 d (1H), 6.59 d (1H), 6.82 m
(3H), 7.19 m (5H).
1
mp 95 C. Yield 75%. H NMR spectrum (CDCl3),
2,4-Di-tert-butyl-7-nitrophenoxazin-3-one (XI).
1
, ppm: 1.08 m (6H), 1.39 s (18H), 4.08 4.17 m
(4H), 5.18 s (1H), 6.52 d.d (1H), 6.72 6.85 m (3H),
7.29 s (2H).
mp 95 C. Yield 25%. H NMR spectrum (CDCl3), ,
ppm: 1.33 s (9H), 1.49 s (9H), 7.11 s (1H), 7.76 d
(1H), 8.07 d.d (1H), 8.11 d. Mass spectrum: m/z 354
(M+).
ACKNOWLEDGMENTS
2-Benzoyl-3 ,5 -di-tert-butyl-2,3-dihydro-1,4-
benzoxazine-3-spiro-1 -cyclohexa-2 ,5 -dien-4 -one
(XV). To a solution of 0.14 g of compound XII in
10 ml of acetone we added 0.3 g of potassium carbo-
nate and 0.07 g of phenacyl bromide. The mixture
was refluxed for 1 2 min and was kept for 7 8 h at
room temperature. The solution was filtered, the fil-
trate was evaporated, and the residue was purified
by column chromatography on Al2O3 (eluent chloro-
form), followed by recrystallization from 2-propanol.
This study was financially supported by the Rus-
sian Foundation for Basic Research (project no. 98-
03-32903a) and by the Program Universities of
Russia Basic Research (project no. 5.3.1387).
REFERENCES
1. Olekhnovich, R.Ya., Korobov, M.S., Lyubchenko, S.N.,
Sukholenko, E.S., Nivorozhkin, L.E., Olekhnovich, L.P.,
and Minkin, V.I., Zh. Obshch. Khim., 1992, vol. 62,
no. 4, p. 901.
1
mp 179 C. Yield 45%. H NMR spectrum (CDCl3),
, ppm: 1.35 s (18H), 5.02 s (1H), 6.56 s (1H), 6.7
6.9 m (4H), 6.98 s (2H), 7.44 m (2H), 7.56 m (1H),
8.02 d (2H).
2. Olekhnovich, L.P., Simakov, V.I., Furmanova, N.G.,
Ivakhnenko, E.P., Rekhlova, O.Yu., Ryskina, T.A., and
Zhdanov, Yu.A., Zh. Obshch. Khim., 1992, vol. 62,
no. 4, pp. 885 900.
2-p-Bromobenzoyl-3 ,5 -di-tert-butyl-2,3-dihy-
dro-1,4-benzoxazine-3-spiro-1 -cyclohexa-2 ,5 -dien-
4 -one (XVI) was synthesized as described above for
compound XV by reaction of compound XII with
3. Olekhnovich, L.P., Ivakhnenko, E.P., Simakov, V.I.,
Lyubchenko, S.N., Ryskina, T.A., Zakharchenko, S.G.,
and Kogan, V.A., Zh. Obshch. Khim., 1990, vol. 60,
no. 7, pp. 1609 1617.
1
p-bromophenacyl bromide. mp 180 C. Yield 35%. H
NMR spectrum (CDCl3), , ppm: 1.36 s (18H), 5.07 s
(1H), 6.46 s (1H), 6.81 m (3H), 6.95 s (2H), 7.58 m
(3H), 7.88 d (2H).
4. Lieb, H. and Schoniger, W., Anleitung zur Darstellung
organischer Praparate mit kleinen Substanzmengen,
Wien: Springer, 1950. Translated under the title Sintez
organicheskikh preparatov iz malykh kolichestv
veshchestv, Leningrad: GNTIKhL, 1957, pp. 67 68.
Compounds XVII and XVIII were synthesized as
described above for compound III using ethyl bromo-
acetate as alkylating agent.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 5 2001