Use of 1-halo derivatives of the 2,2,6,6-tetramethylpiperidine series as oxidants and halogenating agents

Article abstract of DOI:10.1023/B:RJAC.0000044124.36401.7e

1-Halo derivatives of the 2,2,6,6-tetramethylpiperidine series oxidize sterically hindered phenols to form dimers and p-quinones.

Full text of DOI:10.1023/B:RJAC.0000044124.36401.7e

Russian Journal of Applied Chemistry, Vol. 77, No. 6, 2004, pp. 964 967. Translated from Zhurnal Prikladnoi Khimii, Vol. 77, No. 6, 2004,
pp. 978 980.
Original Russian Text Copyright
2004 by Kashparova, Kagan, Zhukova, Ivakhnenko.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
Use of 1-Halo Derivatives of the 2,2,6,6-Tetramethylpiperidine
Series as Oxidants and Halogenating Agents
V. P. Kashparova, E. Sh. Kagan, I. Yu. Zhukova, and E. P. Ivakhnenko
South-Russian State Technical University, Novocherkassk, Rostov oblast, Russia
Research Institute of Physical and Organic Chemistry, Rostov-on-Don, Russia
Received February 3, 2004
Abstract 1-Halo derivatives of the 2,2,6,6-tetramethylpiperidine series oxidize sterically hindered phenols
to form dimers and p-quinones.
The capability of sterically shielded phenols to
undergo oxidation is well known [1] and is one of
the main characteristic properties of this class of com-
pounds, allowing their use as effective antioxidants
[2]. Diverse oxidation products are formed (phenoxyl
radicals, quinoid compounds, quinones), depending
on the structure of the phenols being oxidized and on
the oxidant chosen. For example, oxidation of 2,4,6-
tri-tert-butylphenol with PbO2 or MnO2 yields a sta-
ble phenoxyl radical, whereas oxidation with NaNO2
yields quinones [1].
OH
N Cl
O
O
II
IV
In an organic solvent, the dimerization apparently
occurs by the radical mechanism [1]. The reaction rate
depends on the rate of protonation of the 1-halo deriv-
ative. The possible pathway of dimer formation in the
oxidation of phenols with chloramines of the 2,2,6,6-
TMP series is shown in the scheme:
In this context, it seemed of interest to study the
oxidation of shielded phenols with 1-halo derivatives
of the 2,2,6,6-tetramethylpiperidine (TMP) series.
These agents have apparent advantages over other
N-haloalkylamines in that they show relatively high
stability and low nucleophilicity; these compounds can
be prepared in high yield from the available 2,2,6,6-
TMP derivatives [3 5].
OH
O
+
N
H
Cl
+
N Cl
O
+
H
Cl
+
N
The oxidation of sterically hindered phenols with
halo derivatives of the 2,2,6,6-TMP series is usually
performed in an organic solvent, e.g., benzene or meth-
ylene chloride. 2,6-di-tert-butyl-4-methylphenol I and
2,6-di-tert-butylphenol II are oxidized with 1-halo
derivatives of the 2,2,6,6-TMP series to form dimers:
3,3,5,5-tetra-tert-butylstilbenoquinone III and 3,3,5,5-
tetra-tert-butyldiphenoquinone IV, respectively:
H
Cl
N
2
N H + Cl
O
O
H
H
O
O
2
OH
H
O
N Cl
O
CH CH
O
2Cl
O
2HCl
CH3
I
III
1070-4272/04/7706-0964 2004 MAIK Nauka/Interperiodica

USE OF 1-HALO DERIVATIVES OF THE 2,2,6,6-TETRAMETHYLPIPERIDINE SERIES
965
The stability of the forming phenoxyl radical is
determined by the structural features of the initial
phenol molecule. For example, in oxidation of 2,4,6-
tri-tert-butylphenol V, we obtained 2,6-di-tert-butyl-
benzoquinone VI. 2,4,6-Tri-tert-butylphenol does not
undergo noticeable dimerization because of the high
stability of the forming 2,4,6-tri-tert-butylphenoxyl
radical [6]:
1-Bromo-4-hydroxy-2,2,6,6-TMP reacts with di-
methylphenylamine and diethylphenylamine in a weak-
ly acidic solution (pH 4 5) also to form the corre-
sponding p-bromo derivatives XIIIa and XIIIb:
N(R2)
N(R2)
N Br
OH
O
N Cl
Br
XIIIa, XIIIb
O
VI
where R = CH3 (XIIIa), C2H5 (XIIIb).
V
1-Chloro-2,2,6,6-TMP oxidizes hydroquinone VII
in an organic solvent to p-benzoquinone VIII in quan-
titative yield:
EXPERIMENTAL
3,3 ,5,5 -Tetra-tert-butylstilbenoquinone III. 2,6-
Di-tert-butyl-4-methylphenol (Ionol), 4.4 g (0.02 mol),
and 1-bromo-4-hydroxy-2,2,6,6-tetramethylpiperidine,
9.2 g (0.04 mol), were dissolved in 50 ml of benzene,
and the mixture was allowed to stand at 25 C for 4
5 days. After the disappearance of the starting Ionol
(TLC monitoring), the precipitate of 4-hydroxy-2,2,6,6-
tetramethylpiperidinium bromide was separated. The
solvent was distilled off under reduced pressure; 3.9 g
(90%) of 3,3 ,5,5 -tetra-tert-butylstilbenoquinone was
obtained; mp 304 305 C (from benzene).
OH
O
N Cl
O
OH
VIII
VII
Phenol IX in organic solvent reacts with 1-chloro
derivatives of the 2,2,6,6-TMP series to form 2,4,6-
trichlorophenol Xa and with 1-bromo derivatives to
form 2,4,6-tribromophenol Xb:
OH
OH
The reaction with 1-chloro-4-hydroxy-2,2,6,6-tetra-
methylpiperidine was performed similarly. The reac-
tion was slower, being complete in 6 7 days. Yield
of III 3.6 g (85%).
X
X
N X
X
3, 3 , 5, 5 -Tetra-tert-butyldiphenoquinone IV.
A mixture of 1 g (0.005 mol) of 2,6-di-tert-butyl-
phenol and 1.7 g (0.01 mol) of 1-chloro-4-hydroxy-
2,2,6,6-tetramethylpiperidine in 50 ml of benzene was
allowed to stand for 2 days. After the disappearance of
the starting phenol (TLC monitoring), the precipitate
of 4-hydroxy-2,2,6,6-tetramethylpiperidinium chlo-
ride was separated. The solvent was distilled off under
reduced pressure; 0.9 g (90%) of 3 ,3,5 ,5-tetra-tert-
butyldiphenoquinone was obtained; mp 240 242 C.
The isolated product was identified by comparison
with an authentic sample [5].
IX
Xa, Xb
where X = Cl (Xa), Br (Xb).
In acidic solutions, the reactions apparently occur
by the electrophilic mechanism, which is confirmed
by the formation of p-chloroacetanilide XII as the
only product in the reaction of acetanilide XI with
1-chloro-2,2,6,6-TMP:
H+
+ Cl+
+
N
N
N
H
H
Cl
Cl
2,6-Di-tert-butyl-p-benzoquinone VI. A mixture
of 2.6 g (0.01 mol) of 2,4,6-tri-tert-butylphenol and
3.4 g (0.02 mol) of 1-chloro-2,2,6,6-tetramethylpip-
eridine in 50 ml of benzene was placed in a flask
equipped with a reflux condenser and heated for 20 h
on a water bath kept at 60 C. The mixture was cooled,
the precipitated crystals of 2,2,6,6-tetramethylpiperi-
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 77 No. 6 2004

966
KASHPAROVA et al.
dinium chloride were filtered off, the solvent was
evaporated, and the residue was chromatographed on
a column (Al2O3, Brockmann grade II l = 20 cm, d =
3 cm, eluent hexane). The yellow fraction was col-
lected. The solvent was removed under reduced pres-
sure; 1.15 g (55%) of 2,6-di-tert-butyl-p-benzoqui-
none VI was obtained; mp 78 79 C (from hexane);
published data [6]: mp 78 80 C.
off. Yield of XII 3.2 g (92%); rhombic needles, mp
175 177 C; published data [10]: mp 177 178 C.
p-Bromoacetanilide was prepared similarly by the
reaction with 1-bromo-2,2,6,6-tetramethylpiperidine;
mp 167 168 C (from ethanol water, 1 : 1). The prod-
uct was identified by comparison with an authentic
sample [10].
p-Bromo-N,N-diethylaniline XIIIb. N,N-Diethyl-
aniline, 1.49 g (0.01 mol), was dissolved in 20 ml of
benzene, and a solution of 2.5 g (0.01 mol) of 1-bro-
mo-4-hydroxy-2,2,6,6-tetramethylpiperidine in 20 ml
of benzene was gradually added. The mixture was
heated on a water bath at 60 C for 40 45 min. Then
the mixture was cooled, and white crystals of 4-hy-
droxy-2,2,6,6-tetramethylpiperidine were filtered off.
The solvent was evaporated, and 2.1 g (90%) of
p-bromo-N,N-diethylaniline (white oily crystals) was
obtained; mp 31 33 C (from ethanol water, 1 : 1).
Mixing with an authentic sample gave no depression
of the melting point [10].
p-Benzoquinone VIII. A mixture of 2.2 g
(0.02 mol) of hydroquinone and 3.6 g (0.02 mol) of
1-chloro-2,2,6,6-tetramethylpiperidine in 20 ml of
methylene chloride was allowed to stand for 12 h.
The precipitate of 2,2,6,6-tetramethylpiperidinium
ch loride (3.5 g) was filtered off, and the solvent was
distilled off on a rotary evaporator; 1.72 g (80%) of
p-benzoquinone VIII was obtained, mp 116 C (from
water). The product was identified by comparison
with an authentic sample [7].
2,4,6-Trichlorophenol Xa. A mixture of 0.94 g
(0.01 mol) of phenol and 5.66 g (0.03 mol) of 1-chlo-
ro-4-hydroxy-2,2,6,6-tetramethylpiperidine in 50 ml
of benzene was allowed to stand for 24 h at room tem-
perature. The benzene solution was extracted with
10% NaOH, the organic layer was separated, and the
aqueous layer was acidified with HCl to pH 1. 2,4,6-
Trichlorophenol precipitated from the aqueous phase;
it was separated, washed with water, and dried in air.
Yield 1.78 g (91%); mp 63 65 C (from ethanol wa-
ter, 1 : 1); published data [8]: mp 64 65 C. 4-Hy-
droxy-2,2,6,6-tetramethylpiperidine was isolated from
p-Bromo-N,N-dimethylaniline XIIIa was prepared
similarly. Yield 85%; mp 54 56 C (from ethanol
water, 1 : 1); published data [10]: mp 55 56 C.
CONCLUSIONS
(1) 2,6-Di-tert-butyl-4-methylphenol and 2,6-di-
tert-butylphenol in an organic solvent are oxidized
by 1-halo derivatives of 2,2,6,6-tetramethylpiperidine
to form dimers.
the benzene layer; yield 4.2 g (90%), mp 130 132
(from ethyl acetate) [9].
C
(2) 1-Chloro-2, 2, 6, 6-tetramethylpiperidine oxi-
dizes in an organic solvent 2,4,6-tri-tert-butylphenol
and hydroquinone to 2,6-di-tert-butylbenzoquinone
and p-benzoquinone, respectively.
2,4,6-Tribromophenol Xb was prepared similarly,
by the reaction of phenol with 1-bromo-4-hydroxy-
2,2,6,6-tetramethylpiperidine. Yield 82%, mp 96
98 C (from ethanol water, 1 : 1). Mixing with an
authentic sample gave no depression of the melting
point [8].
(2) Phenol in an organic solvent and aromatic
amines in an acidic solution in the presence of 1-halo
derivatives of the 2,2,6,6-tetramethylpiperidine series
undergo halogenation.
p-Chloroacetanilide XII. Acetanilide, 2.7 g
(0.02 mol), and 1-chloro-2,2,6,6-tetramethylpiperi-
dine, 3.7 g (0.021 mol), were dissolved in 30 ml of
benzene, and 25 ml of 1 M HCl was added. The mix-
ture was stirred and heated on a water bath at 50
60 C for 15 20 min. The reaction progress was moni-
tored by TLC. After the reaction was complete, the
mixture was cooled, the organic layer was separated,
and the solvent was evaporated under reduced pres-
sure. The crystals of 4-chloroacetanilide were filtered
REFERENCES
1. Ershov, V.V., Nikiforov, G.A., and Volod’kin, A.A.,
Prostranstvenno-zatrudnennye
fenoly
(Sterically
Hindered Phenols), Moscow: Khimiya, 1972.
2. Roginskii, V.A., Fenoksil’nye antioksidanty (Phenoxyl
Antioxidants), Moscow: Nauka, 1988.
3. Zhukova, I.Yu., Pozhidaeva, S.A., Kagan, E.Sh., and
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 77 No. 6 2004

USE OF 1-HALO DERIVATIVES OF THE 2,2,6,6-TETRAMETHYLPIPERIDINE SERIES
967
Smirnov, V.A., Zh. Org. Khim., 1993, vol. 29, no. 4,
8. Rodionov, V.M., Bogoslovskii, B.M., and Fedoro-
pp. 751 757.
va, A.M., Laboratornoe rukovodstvo po khimii pro-
mezhutochnykh produktov i krasitelei (Laboratory
Manual on Chemistry of Intermediates and Dyes),
Moscow: Goskhimizdat, 1948.
4. Zhukova, I.Yu., Kashparova, V.P., and Kagan, E.Sh.,
Izv. Vyssh. Uchebn. Zaved., Sev.-Kavk. Region,
Estestv. Nauki, 2001, no. 2, pp. 44 45.
5. Neale, R.S., Synthesis, 1971, no. 1, pp. 1 15.
6. Condensation Monomers, Stille, J.K. and Camp-
9. Rozantsev, E.G., Svobodnye iminoksil’nye radika-
ly (Free Iminoxyl Radicals), Moscow: Khimiya,
1970.
bell, T.W., Eds., New York: Interscince, 1972.
10. Hickinbottom, W.J., Reaction of Organic Compounds,
7. Tolstikov, G.A., Reaktsii gidroperekisnogo okisleniya
(Hydroperoxide Oxidations), Moscow: Nauka, 1976.
London: Longmans, Green and co., 1936.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 77 No. 6 2004