Reductive bromination of N, N-bis(4-tert-butylphenyl)hydroxylamine

Article abstract of DOI:10.1007/s11172-019-2556-6

Unlike most arenes, N, N-bis(4-tert-butylphenyl)hydroxylamine reacts with Br₂via the reductive bromination mechanism. Here, two hydrogens in ortho positions of benzene rings are substituted by Br₂ and provide two-electron reduction o

Full text of DOI:10.1007/s11172-019-2556-6

Russian Chemical Bulletin, International Edition, Vol. 68, No. 6, pp. 1293—1297, June, 2019
1293
Reductive bromination of N,N-bis(4-tert-butylphenyl)hydroxylamine
V. A. Golubeva and Yu. D. Kimb
аInstitute of Problems of Chemical Physics, Russian Academy of Sciences,
1
prosp. Akad. Semenova, 142432 Chernogolovka, Moscow Region, Russian Federation.
Fax: +7 (496) 515 5420. Е-mail: vgolubev@icp.ac.ru
b
M. V. Lomonosov Moscow State University,
1
Leninskie Gory, 119991 Moscow, Russian Federation.
Е-mail: yula.me.kim@gmail.com
Unlike most arenes, N,N-bis(4-tert-butylphenyl)hydroxylamine reacts with Br2 via the
reductive bromination mechanism. Here, two hydrogens in ortho positions of benzene rings are
substituted by Br and provide two-electron reduction of hydroxylamine to amine.
2
Key words: diarylhydroxylamines, halogenation, electrophilic substitution, reductive halo-
genation.
Most arenes react with halogens via the electrophilic
quinone imine-N-oxide or derivatives thereof. The reac-
substitution mechanism.1 A known exception comprises
,2
tion of bis(4-tert-butylphenyl)amineoxyl with Br yields
2
diarylnitroxyl radicals reacting with halogens via reductive
dibromoamine 3 and corresponding tribromoamine in
halogenation.3
—5
This process involves three-electron
comparable amounts. The authors of study supposed
that the reductive bromination of this radical involves
formation of intermediate bromohydroxylamine 2 and
dibromodiphenylaminyl radical.
4
4
reduction of the nitroxyl group and formation of corre-
sponding diarylamines. We found that the reductive
halogenation reaction involves not only radicals but dia-
magnetic diarylhydroxylamines as well. So, the reaction
of N,N-bis(4-tert-butylphenyl)hydroxylamine (1) with Br2
in the equimolar amounts produces dibromoamine 3 (yield
Being stoichiometrically simple, the reaction of hydr-
oxylamine 1 with Br is a convenient model reaction to
2
study the reductive bromination of arenes. The major goal
of our work is to reveal the mechanism of this unusual
reaction.
9
4±2ꢀ, Scheme 1) rather than bromohydroxylamine 2
and HBr.
The reductive halogenation mechanism of arenes has
3
not been fully revealed yet. So, the authors of study, which
Results and Discussion
describes the synthesis and properties of diphenylnitroxyl
radical, suppose that bromine reduces this radical to tri-
The structure of dibromoamine 3 was identified by IR,
UV, and NMR spectra. The spectra of the synthesized
compound are identical to those of dibromoamine 3, which
we obtained via bromination of bis(4-tert-butylphenyl)-
bromodiphenylamine, whose reaction with Br excess
2
yields final tetrabromodiphenylamine. The authors of
6
monograph suggest an alternative reductive bromination
4
mechanism for this radical. According to their hypothesis,
diphenylnitroxyl initially disproportionates into N-phenyl-
quinone imine-N-oxide and diphenylamine. The latter
amine (4) and corresponding nitroxyl radical. In relation
to hydroxylamine 1, bromine acts simultaneously as
a brominating and two-electron reducing agent. The re-
ductive bromination rate of hydroxylamine 1 is much
higher than that of its electrophilic bromination to bromo-
reacts with Br to yield tetrabromodiphenylamine. However,
2
such mechanism is not evidenced by releasing N-phenyl-
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1293—1297, June, 2019.
066-5285/19/6806-1293 © 2019 Springer Science+Business Media, Inc.
1

1294
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 6, June, 2019
Golubev and Kim
hydroxylamine 2. We did not detect the latter among the
reaction products. The conversion of hydroxylamine 1 to
dibromoamine 3 involves the intermediate complex A
forming via Scheme 2 immediately upon mixing the
reagents.
A
1
1
0
0
0
0
.2
.0
.8
.6
.4
.2
1
1
4
1
0
5
1
4
0
Scheme 2
0
1
1
0
3
00
Fig. 2. Absorption spectra of N,N-bis(4-tert-butylphenyl)hydr-
oxylamine (1) and products of its reaction with Br (1—10) in
350 λ/nm
2
–
4
–1
CCl . [Br ] = [1] = 7•10 mol L , 0.10 cm cuvette, reaction
4
2 0
0
The UV spectrum of complex A shows two absorption
bands in the range from 250 to 700 nm. The first band with
λmax = 406 nm (Fig. 1) accounts for the brown reddish
color of the reaction solution. The peak of this absorption
time, min: 0 (0), 0.8 (1), 1.8 (2), 2.6 (3), 4.3 (4), 11.3 (5), 18.7 (6),
2
3.7 (7), 31.8 (8), 39.5 (9), and 47 (10).
hydroxylamine 1 at λmax = 282 nm (Fig. 2). During the
reaction time (50 s), the absorption intensity of hydroxyl-
amine 1 at λ = 260 nm decreases by ca. 16ꢀ upon its
conversion to complex A. The extinction coefficient of
complex A in the absorption band at 308 nm was calculated
by the Lambert—Beer formula as ~81000 L mol ¹ cm ¹
that was 11 times higher than that of hydroxylamine 1.
Note that all the absorption curves of the reaction mixture,
aside from those corresponding to the starting period, pass
through the isosbestic point at λiso = 294 nm.
band is close to that of Br (422 nm). However, the extinc-
2
–
1
–1
tion coefficient (ε ~ 3600 L mol cm ) of this band of
the complex is 16 times higher than that of Br . The ab-
2
sorption of complex A almost completely masks that of
Br . The band intensity of the complex rapidly decreases
2
–
–
upon its conversion to dibromoamine 3. The half-life of this
–
3
–1
conversion is ~3.5 min at [1] = [Br ] = 2•10 mol L
0
2 0
and 25 °С.
The second band of complex A with λmax = 308 nm is
red-shifted by 26 nm in relation to the absorption band of
The reductive bromination mechanism of hydroxyl-
amine 1 principally differs from the known electrophilic
bromination mechanism of arenes via intermediate π- and
A
1
,2
σ-complexes.
The structures of these complexes are
2
1
1
1
1
1
0
0
0
0
.0
.8
.6
.4
.2
.0
.8
.6
.4
.2
7
,8
unambiguously determined by the X-ray structural data.
In π-complexes, Br molecules are arranged almost per-
2
1
1
2
pendicularly to the aromatic ring plane and coordinated
by С—С bonds with the highest electron density. At the
reaction rate determining step, π-complexes turn into
σ-complexes, which are brominated carbocations. The
3
4
5
25
–
latter react with Br anion to yield bromoarenes and HBr.
So bromination of arenes via electrophilic mechanism
consumes only a half of bromine amount for the synthesis
of bromoarenes. The electrophilic bromination is not
selective as it always yields a mixture of isomers.
1
6
Br2
Unlike common π-complexes, Br molecule in com-
2
2
5
plex A is apparently coordinated by two benzene rings of
hydroxylamine 1. In the reaction rate determining step,
two benzene hydrogens in ortho positions of the complex
are substituted by bromine atoms and transferred to NOH
group to reduce it to an amino group. Simultaneously,
formed dibromoamine 3 releases water. This mechanism
is evidenced with a high selectivity of reductive bromina-
tion yielding sole ortho-isomer of dibromoamine 3. More-
3
50
400
450 500
550
600
650 λ/nm
Fig. 1. Absorption spectra of Br and products of its reaction with
2
N,N-bis(4-tert-butylphenyl)hydroxylamine (1) in CCl at 25 °С.
4
–
3
–1
[
Br ] = [1] = 2•10 mol L , 1.00 cm cuvette, reaction time,
2 0 0
min: 0.7 (1), 1.06 (2), 1.41 (3), 1.77 (4), 2.12 (5), 2.47 (6),
2
5
4
.82 (7), 3.17 (8), 3.52 (9), 3.87 (10), 4.22 (11), 4.57 (12), 4.92 (13),
.27 (14), 5.62 (15), 10.8 (16), 16.7 (17), 22.7 (18), 30.7 (19),
0.7 (20), 50.7 (21), 62 (22), 73 (23), 121 (24), and 251 (25).

Bromination of (4-tert-BuC H ) NOH
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 6, June, 2019
1295
6
4 2
over, the presence of an isosbestic point in the absorption
curves evidences the direct conversion of complex A to
the final product. Unlike the electrophilic mechanism,
both bromine atoms are consumed for the synthesis of
bromoarenes via the reductive bromination.
The reaction of hydroxylamine 1 with Br yields, along
2
with dibromoamine 3, five by-products, which are HPLC
detectable. Three chromatographic peaks at Vret 355, 630,
and 755 μL are attributed to amine 4, bromoamine 5, and
tribromoamine 6, whose yield is 0.8, 0.3, and 0.8 mol.ꢀ,
respectively.
probably formed by bromination of dibromoamine 8,
which is a meta isomer of dibromoamine 3. As follows
from the yield ratio of dibromoamine 3 and tribromo-
amine 7, the rate of Br addition in ortho position of
2
benzene rings of hydroxylamine 1 is by ~500 times higher
than that in meta position.
The structure of quinone imine 9 is evidenced by the
mass, UV, and NMR spectra. The mass spectrum of this
compound shows a peak of protonated molecular ion at
m/z = 1027 and thirteen isotope peaks whose intensity
ratio is closed to the theoretical ratio of isotope peaks for
a molecule with six Br atoms. The UV spectrum of com-
pound 9 shows a band at λmax = 494 nm, which accounts
for its red color, as well as an intense band at λmax = 276 nm,
which is characteristic for phenylamines. The ¹Н NMR
spectrum of quinone imine 9 shows three overlapping
singlet signals at δ 1.25, 1.27, and 1.32 from four tert-
butyl groups and two singlet signals at δ 5.52 and 5.78 from
two protons of the quinone imine moiety. Quinone imine 9
comprises two different benzene moieties each having
three protons. See an assumable attribution of six signals
from benzene protons in the Experimental section.
Apparently, dye 9 results from dimerization of hydr-
oxylamine 1 to intermediate quinone imine B, which is
brominated to final quinone imine 9 according to Scheme 3.
A probable catalyst for dimerization of hydroxylamine
The structures of these substances were established on
the basis of the identity of their UV and NMR spectra and
those of the available samples.4 Amine 4 exists as an
impurity in the starting hydroxylamine 1. Apparently,
bromoamine 5 is formed via bromination of amine 4, while
tribromoamine 6 is formed by bromination of dibromo-
amine 3. The bromination mechanism of amines 3 and 4
is likely electrophilic substitution as it releases the equiv-
alent amount of HBr.
,8
Aside of these impurities, the reaction yields tribromo-
amine 7 and quinone imine 9 (0.2 and 1 mol.ꢀ, res-
pectively).
Tribromoamine 7 was detected chromatographically
at Vret = 720 μL and identified by ¹Н NMR. The spectrum
of the obtained compound shows a singlet signal of two
tert-butyl groups (δ 1.24) and a singlet signal of NH
(
δ 5.46). The benzene ring with one bromine atom shows
the signals of three protons. The doublet-doublet signal
at δ 6.77 (J = 1.8 and 8.2 Hz) is attributed to Н(6´), the
doublet signal at δ 6.42 (J = 8.2 Hz) is attributed to Н(5´),
and the doublet signal at δ 6.73 (J = 1.8 Hz) is attributed
to Н(2´). The benzene rings with two bromine atoms shows
two doublet signals of Н(2) and Н(6) at δ 6.66 and 6.93
9
1 is HBr. As was noted in study, when affected by acids,
hydroxylamine 1 does not only disproportionates but also
yields quinone imine dyes.
Therefore, the reaction of arenes with Br may occur
2
(
J = 2.0 Hz). Due to the steric hindrances caused by tert-
not only via the electrophilic substitution mechanism but
also via the reductive halogenation mechanism. To realize
the latter, arenes should comprise readily reducible sub-
stituents such as hydroxylamine or nitroxyl groups.
butyl groups, C—N bond twisting is complicated, Н(2)
and Н(6) atoms appear in different spatial environments
and have different chemical shifts. Tribromoamine 7 is

1296
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 6, June, 2019
Golubev and Kim
Scheme 3
(0.011 mmol, 3.3 mol.ꢀ of Br ). The solvent (CCl ) was evapo-
2 4
rated under reduced pressure to yield the solid reaction product
(
(
137 mg). HPLC, Vret/μL (Irel (ꢀ)): 355 (10) 4, 395 (2.1) 9, 630
5.6) 5, 720 (0.8) 7, 755 (2.4) 6, 1080 (100) 3. According to the
quantitative HPLC test, the product comprised dibromoamine
(130±3 mg, 0.296 mmol, 94±2ꢀ). The reaction product com-
3
position was also determined by the ¹Н NMR signal area ratio
in the range of 5.4 to 6.4 ppm. According to NMR data, the
product comprised dibromoamine 3 (96.5ꢀ, amine 4 (0.8ꢀ),
bromoamine 5 (0.3ꢀ), tribromoamine 6 (0.8ꢀ), tribromoamine
7
(0.2ꢀ), and quinone imine 9 (1ꢀ). The reaction product was
i
recrystallized from Pr OH to obtain dibromoamine 3 (106 mg,
7
7ꢀ). The mother liquor was evaporated to dry, the residue was
dissolved in hexane, then the solution was put on a column with
silica gel and eluated with hexane. The first zone (Vret 10—20 mL)
comprised primarily dibromoamine 3. The second zone
(
(
Vret 20—40 mL) was evaporated to yield a colorless product
5 mg) whose ¹Н NMR spectrum detected dibromide 3 (10ꢀ),
monobromide 5 (47ꢀ), tribromide 6 (37ꢀ), and tribromide 7
5ꢀ). The second zone TLC (silica gel, hexane eluent) yielded
monobromide 5 (m.p. 90 °С, 2 mg) and tribromide 6 (m.p.
82 °С, 1.5 mg). The third chromatographic zone (Vret 40—60 mL)
(
1
Experimental
comprised primarily amine 4. The fourth (red) zone was eluated
with a benzene—hexane (1 : 1) mixture, which evaporation
yielded quinone imine dye 9 (0.9 mg).
N,N-Bis(4-tert-butylphenyl)hydroxylamine (1) synthesized
9
according to the known technique and recrystallized from hex-
ane decomposed at 113—115 °С. According to ¹Н NMR, it
comprised 3ꢀ bis(4-tert-butylphenyl)amine (4). Bromine (pure
grade) was distilled under ambient pressure at b.p. 58 °С. Carbon
tetrachloride was distilled on a 50-cm column with glass spirals
at b.p. 76.5 °С.
Bis(2-bromo-4-tert-butylphenyl)amine (3). Colorless prism-
i
atic crystals, m.p. 163 °С (from Pr OH); cf. Ref. 4: m.p. 163 °С.
UV (EtOH), λmax/nm (ε): 287 (22700), 236 sh (9300), 208
–
(39900). IR (reflection), ν/cm ¹: 3389 (NH); 3038 (Ar); 2961,
2900, 2866 (СН ); 1601, 1519 (Ar), 1331, 1262, 1116, 1036, 882,
3
814, 712. ¹Н NMR, δ: 1.30 (s, 18 Н, С(СН ) ); 6.26 (s, 1 Н,
3
3
IR reflection spectra were recorded with a Spectrum 100
instrument. NMR spectra were recorded in chloroform-d with
NH); 7.21 (m, 4 H, H(5), H(6)); 7.56 (br. dd, 2 Н, Н(3),
J = 1.8 Hz, J = 0.7 Hz).
1
a Bruker AIII spectrometer (500 MHz). UV spectra were re-
corded with a Specord UV–VIS and a Specord 210 instruments.
ES mass spectra were recorded in a methanol solution with
a Shimadzu LCMS 2020 instrument at the ionizing voltage of
N-(2-Bromo-4-tert-butylphenyl)-N-(4´-tert-butylphenyl)-
amine (5). Colorless crystals, m.p. 90 °С (from MeCN); cf. Ref. 4:
m.p. 90 °С. UV (EtOH), λmax/nm (ε): 286 (21800), 238 sh (7530),
202 (40140). ¹Н NMR, δ: 1.28 (s, 9 H, C(4)(CH ) ); 1.32 (s, 9 H,
3
3
5
kV and temperature of 65 °С. The melting points were deter-
C(4´)(CH ) ); 5.93 (c, 1 H, NH); 7.07 (dm, 2 Н, Н(2´), H(6´),
3 3
mined on a РНМК warm table. The chromatographic tests were
carried out with a Millikhrom chromatograph, a UV detector at
J = 8.6 Hz); 7.17 (m, 2 Н, Н(5), H(6)); 7.32 (dm, 2 Н, Н(3´),
H(5´), J = 8.6 Hz); 7.51 (br. dd, 1 Н, Н(3), J = 1.5 Hz, J = 0.9 Hz).
N-(2,6-Dibromo-4-tert-butylphenyl)-N-(2´-bromo-4´-tert-
butylphenyl)amine (6). Colorless plate crystals, m.p. 182 °С (from
heptane); cf. Ref. 4: m.p. 182 °С. UV (EtOH), λmax/nm (ε): 286
(9380), 234 sh (18400), 208 (69300). ¹Н NMR, δ: 1.27 (s, 9 H,
2
9
90 nm (column 2×64 mm, Separon C18, 5 μm), and aqueous
0ꢀ MeCN eluent. The substance retention volumes (Vret/μL)
were as follows: 1080 (3), 355 (4), 630 (5), 755 (6), 720 (7), and
95 (9). The quantitative HPLC test was carried out by the peak
3
intensities of these substances. The calibration used the know-
ingly impurity-free substances. Further, the reaction product was
quantitatively tested by the amino group signal peak area ratio
in ¹Н NMR at δ 6.26 (3), 5.59 (4), 5.93 (5), 5.96 (6), 5.46 (7),
and 6.04 (unidentifiable substance). The thin-layer chromatog-
raphy used TLC Al Fluka plates with a 254 nm indicator. The
substances were preparatively separated on a 10×105-mm column
C(4´)(CH ) ); 1.32 (s, 9 H, C(4)(CH ) ); 5.96 (s, 1 H, NH);
3 3 3 3
6.29 (d, 1 H, H(6´), J = 8.5 Hz); 7.10 (dd, 1 H, H(5´), J = 8.5 Hz,
J =2.2 Hz); 7.52 (d, 1 Н, Н(3´), J = 2.2 Hz); 7.60 (s, 2 H, H(3),
H(5)).
N-(3,5-Dibromo-4-tert-butylphenyl)-N-(3´-bromo-4´-tert-
butylphenyl)amine (7). ¹Н NMR, δ: 1.24 (s, 18 H, C(CH ) ); 5.46
3
3
(s, 1 H, NH); 6.42 (d, 1 H, H(5´), J = 8.2 Hz); 6.66 (d, 1 H,
H(2), J = 2.0 Hz); 6.73 (d, 1 H, H(2´), J = 1.8 Hz); 6.77 (dd, 1 Н,
Н(6´), J = 8.2 Hz, J = 1.8 Hz); 6.93 (d, 1 Н, Н(6), J = 2.0 Hz).
N-(3´-Bromo-4´-tert-butylphenyl)-N´-(2´´-bromo-4´´-tert-
butylphenyl)-3,5,7,10-tetrabromo-4,9-di-tert-butyl-1,6-dipheno-
quinone diimine (9). Red deliquescing crystals. UV (MeCN), nm
(Аrel (ꢀ)): 494 (3.4), 298 (65), 276 (100), 253 (75), 241 (82), 206
(
Merck 9385 silica gel; 37—63 μm). The preparative TLC used
2
00×200-mm plates coated with silica gel (1.5-mm layer) com-
prising a fluorescent indicator.
Reaction of N,N-bis(4-tert-butylphenyl)hydroxylamine (1)
with Br . Bromine (53.4 mg, 0.334 mmol) solution in CCl
2
4
(
1 mL) was added to diarylhydroxylamine 1 (93.6 mg, 0.315 mmol)
solution in CCl (1 mL) at 22 °С. The reaction mixture imme-
(321). ¹Н NMR, δ: 1.25, 1.27 and 1.32 (all s, 36 H, C(CH ) );
4
3 3
diately became brown-red. The color weakened in time and
became pink in 20—30 min. The reaction solution was extracted
with water (2 mL), which potentiometric titration detected HBr
5.52 (s, 1 H, H(8)); 5.78 (s, 1 H, H(2)); 6.50 (d, 1 Н, Н(6ʺ),
J = 8.4 Hz); 6.93 (dd, 1 H, H(6´), J = 8.2 Hz, J = 2.1 Hz); 7.06
(d, 1 Н, Н(5´)), J = 8.2 Hz); 7.07 (br.s, 1 Н, Н(2´)); 7.13 (dd,

Bromination of (4-tert-BuC H ) NOH
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 6, June, 2019
1297
6
4 2
1
Н, Н(5ʺ), J = 8.4 Hz, J = 1.7 Hz); 7.50 (d, 1 Н, Н(3ʺ),
2. D. A. Klump, in Arene Chemistry. Reaction Mechanisms and
Methods for Aromatic Compounds, Ed. J. Mortier, Wiley, New
York, 2016, p. 1—32.
3. H. Wieland, M. Offenbächer, Ber. Deutsch. Chem. Ges., 1914,
47, 2111.
4. V. A. Golubev, V. D. Sen´, Russ. J. Org. Chem., 2013,
49, 1161. aaaaa
5. V. A. Golubev, V. D. Sen´, Russ. Chem. Bull., 2013,
62, 2074. aaaaa
+
J = 1.7 Hz). Mass spectrum, m/z (I (ꢀ)): 1027 [М + Н] (12),
rel
+
+
+
1
1
1
1
1
1
[
[
[
[
028 [М + 2] (7), 1029 [М + 3] (16), 1030 [М + 4] (22),
031 [М + 5] (45), 1032 [М + 6]+ (28), 1033 [М + 7] (100),
+
+
034 [М + 8] (72), 1035 [М + 9]+ (94), 1036 [М + 10] (54),
+
+
+
+
+
037 [М + 11] (46), 1038 [М + 12] (17), 1039 [М + 13] (15),
+
040 [М + 14] (9). С40Н44Br N . Calculated, m/z (I (ꢀ)):
6
2
rel
+
+
+
026 [М] (5), 1027 [М + 1]+ (2), 1028 [М + 2] (30), 1029
+
+
М + 3] (13), 1030 [М + 4] (75), 1031 [М + 5] (32), 1032
+
+
+
М + 6] (100), 1033 [М + 7]+ (42), 1034 [М + 8] (77), 1035
6. A. R. Forrester, J. M. Hay, R. H. Thomson, Organic Chemistry
of Stable Free Radicals, Academic Press, London, New York,
1968, 227.
+
+
М + 9] (32), 1036 [М + 10] (33), 1037 [М + 11] (13), 1038
М + 12] (7), 1039 [М + 13]+ (2).
+
7
8
. S. M. Hubig, J. K. Kochi, J. Org. Chem., 2000, 65, 6807.
. A. V. Vasilyev, S. V. Lindeman, J. K. Kochi, Chem. Commun.,
2001, 909.
This study was carried out under the State Order
No. 01201361874 with the equipment of the Analytical
Core Facilities Center, Institute of Problems of Chemical
Physics, Russian Academy of Sciences.
9. V. A. Golubev, V. V. Tkachev, V. D. Sen´, Russ. J. Org. Chem.,
2014, 50, 678.
References
Received December 6, 2018;
revised form January 31, 2019;
accepted February 25, 2019
1
. H. G. O. Becker, Einfürung in die Elektronentheorie Organisch —
Chemischer Reaktionen, Wissenschaften, Berlin, 1974.