Kinetics of N-oxyl Radicals' Decay

Article abstract of DOI:10.1021/acs.joc.0c00506

N-oxyl radicals of various structures were generated by oxidation of corresponding N-hydroxy compounds with iodobenzene diacetate, [bis(trifluoroacetoxy)]iodobenzene, and ammonium cerium(IV) nitrate in acetonitrile. The decay rate of N-oxyl radicals follows first-order kinetics and depends on the structure of N-oxyl radicals, reaction conditions, and the nature of the solvent and oxidant. The values of the self-decay constants change within 1.4 × 10-4 s-1 for the 3,4,5,6-tetraphenylphthalimide-N-oxyl radical to 1.4 × 10-2 s-1 for the 1-benzotriazole-N-oxyl radical. It was shown that the rate constants of the phthalimide-N-oxyl radicalsê? self-decay with different electron-withdrawing or-donor substituents in the benzene ring are higher than that of the unsubstituted phthalimide-N-oxyl radical in most cases. The solvent effect on the process of phthalimide-N-oxyl radical self-decomposition was investigated. The dependence of the rate constants on the Gutmann donor numbers was shown.

Full text of DOI:10.1021/acs.joc.0c00506

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Article
KINETI#S OF N-OXYL RADICALS# DECAY
Olga V. Kushch, Iryna O. Hordieieva, Katerina V. Novikova, Yurii E. Litvinov,
Mykhailo O. Kompanets, Alexander N. Shendrik, and Iosip A. Opeida
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00506 • Publication Date (Web): 15 May 2020
Downloaded from pubs.acs.org on May 16, 2020
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The Journal of Organic Chemistry
KINETIСS OF N-OXYL RADICALSʼ DECAY
Olga Kushcha,b*, Iryna Hordieievab, Katerina Novikovaa,
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Yurii Litvinova, Mykhailo Kompanetsa,c, Alexander Shendrikb, Iosip Opeidab,d
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a L.M. Litvinenko Institute of Physico-Organic Chemistry and Coal Chemistry, National
Academy of Sciences of Ukraine, Kyiv, 02660 Ukraine
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bFaculty of Chemistry, Biology and Biotechnologies, Vasyl' Stus Donetsk National University,
Vinnytsia, 21021 Ukraine
c National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute”, Kyiv,
03056 Ukraine
d Department of Physical Chemistry of Fossil Fuels InPOCC, National Academy of Sciences of
Ukraine, Lviv, 79053 Ukraine
ABSTRACT
N-oxyl radicals of various structure were generated by oxidation of corresponding
N-hydroxyimides with iodobenzene diacetate, [bis(trifluoroacetoxy)]iodobenzene and ammonium
cerium (IV) nitrate in acetonitrile. The decay rate of imide-N-oxyl radicals follows first-order
kinetics and depends on the structure of N-oxyl radicals, reaction conditions, the nature of the
solvent and oxidant. The values of the self-decay constants change within 1.4·10-4 s-1 for
3,4,5,6-tetraphenylphthalimide-N-oxyl radical to 1.4·10-2 s-1 for 1-benzotriazole-N-oxyl radical. It
was shown that the rate constants of the phthalimide-N-oxyl radicalsʼ self-decay with different
electron withdrawing or donor substituents in the benzene ring are higher than that of
unsubstituted phthalimide-N-oxyl radical in most cases. The solvent effect on the process of
phthalimide-N-oxyl radical self-decomposition was investigated. It was shown the dependence of
the rate constants on the Gutmann donor numbers.
INTRODUCTION
Oxidation of organic compounds with molecular oxygen is an important environmentally
friendly method to produce various oxygen-containing products.1, 2 The selectivity of these
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processes is difficult to achieve without the use of catalysts.3 It is known that
N-hydroxyphthalimide (NHPI) exhibits high catalytic activity and selectivity in the oxidation of
organic compounds with molecular oxygen under mild conditions.4 One of the main drawbacks,
which limits its use, is the spontaneous decay of phthalimide-N-oxyl radical (PINO), formed in situ
from NHPI. The PINO radicals are the key intermediates in oxidation processes. To maintain their
high concentration in the reaction mixture, the oxidation of organic compounds is carried out at
high concentrations (10-20 mole %) of NHPI.5 This fact poses problems when developing
commercially acceptable technologies with participation of NHPI.
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The catalytic cycle promoted by the NHPI / PINO system is presented in Scheme 1. PINO
is formed in initiation stage (Ri) by oxidation of NHPI with transition metal salts and complexes,
enzymes, quinones, aldehydes, and traditional radical initiators as azo-compounds or peroxides.6
PINO abstracts the H-atom from the C-H bond of organic molecule (kH) with formation of alkyl
radical and regeneration of NHPI. Formed C-centered radical readily reacts with molecular oxygen
to give peroxyl radical, which abstracts the H-atom from RH (kp) (classical propagation reaction)
or NHPI (kf) to form the hydroperoxide as primary product. PINO radicals do not terminate chains
by reaction with ROO• or by dimerization,7 therefore chain termination in catalytic process occurs
through the reaction of peroxyl radicals with each other (kt). kd in Scheme 1 is the self-decay rate
constant of N-oxyl radicals.
Scheme 1. Mechanism of catalytic oxidation of organic compounds RH with
molecular oxygen in the presence of NHPI.
As shown in Scheme 1 the N-oxyl radicals work as mediators that efficiently transfer
H-atoms from the substrates to the ROO• radicals. Obviously, the efficiency of such chain radical
process depends on the stability of the NHPI catalyst and its PINO radical, since recyclability of
NHPI will significantly affect the selectivity of the process.
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The Journal of Organic Chemistry
Kinetic studies of PINO decay have been carried out by various research groups.8 But the
current views on the mechanism and kinetics of this process are contradictory. Depending on the
solvent and the radical generation method, different constants of the PINO self-decay are given.
Masui et al.8d have reported the results of investigation of PINO stability when radical was
generated via electrochemical oxidation of NHPI in acetonitrile in the presence of pyridine and
NaClO4. The self-decomposition of PINO obeyed second-order kinetics with a kd = 24.1 M-1s-1 at
25 ℃. It was shown that the reaction rate depends little on temperature, concentration of dissolved
oxygen, water, or added base. Trimer 4 (71 %) was identified as the main product of the PINO
self-decay (Scheme 2). Masui8d has concluded that the PINO decay proceeds through the radical
disproportionation, including the formation of NHPI molecule and N-oxonium cation 1, which
transforms to acyl radical 2. Then NHPI as nucleophile attacks radical 2 to give dimer 3. Trimer 4
is a reaction product of NHPI with dimer 3, as shown in Scheme 2. In addition to the trimer phthalic
acid (2.5 %), phthalic anhydride (8 %), phthalimide (trace), and NHPI (3.5 %) were found among
the products.
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Espenson et al.8a have generated PINO by oxidation of NHPI with Pb(OAc)4 and obtained
the same value for the second-order constant of PINO decay in both acetic acid and acetonitrile
(0.6 M 1s-1), which is significantly less than that reported by Masui et al.8d As per opinion of
Espenson, the PINO decay acceleration in acetonitrile in the experiments by Masui8d could be
attributed to the addition of pyridine. The constants presented by Espenson8a were confirmed by
Baciocchi,9 which obtained values of kd 0.4, 4 and 0.9 M-1s-1 in acetonitrile, CCl4 and 1,1,1,3,3,3-
hexafluoro-2-propanol, respectively. However, Pedulli et al. reported the first-order of the PINO
self-decomposition rate constant kd = 0.1 s-1 8c using EPR method. In this case radical was produced
photochemically from NHPI in the presence of dicumyl peroxide (20 % by weigth) in benzene
solutions containing 10 % acetonitrile. Recupero and Punta4b believe that a reason for different
observations by Masui8d, Espenson8a, Baciocchi9 and Pedulli8c is the different experimental
conditions. At low concentrations of PINO, such as in the Pedulliʼs case8c, radical undergoes a
first-order decay. In contrast, when radical was generated at high concentrations like in the works
of Masui8d, Espenson8a and Baciocchi9, PINO decay occurs by second-order kinetics.
Scheme 2 illustrates the possible ways of PINO transformations with the cleavage at one
of the C-N bonds with formation of acyl radical 2. Thus, in both processes, proposed by Pedulli8c
(first-order kinetics, kd1) and Masui8d (second-order kinetics, kd2) identical products can be formed:
Scheme 2. The PINO self-decay reaction following a first- and second-order kinetics
with the formation of dimer 3 and trimer 4.
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Considering such a mechanism of radical decay, it is necessary to take into account that
under the aerobic oxidation, the resulting acyl radical 2 may turn into highly reactive peroxyacyl
radicals, which can participate in the chain propagation stage.
Unlike initiator radicals involved only in the initial stages of radical-chain process, PINO
take part in propagation stage (see Sheme 1) and its structure have a significant impact on the
oxidation process. For example, the introduction of various electron-withdrawing or donor
substituents into the benzene ring affects the persistence8b and reactivity of PINO radicals.10
Nevertheless, as far as we know, systematic study of the influence of the PINO radicals’ structure
on their persistence8b has not been carried out. The investigation of decay of N-oxyl radicals is
important for the design of new structures, expand the structural diversity of N-oxyl radical
catalysts for their potential use in selective functionalization of aliphatic C-H bonds. In this study,
we present new kinetic data of self-decomposition reactions of various N-oxyl radicals.
RESULTS AND DISCUSSION
The structures of N-hydroxy compounds under study are presented in the Scheme 3:
N, N-dihydroxypyromellitimide (NDHPI)
NHPI (R1=R2=R3=R4= H)
Ph4-PINO (R1=R2=R3=R4= Ph)
3-CH3-NHPI (R1=CH3, R2=R3=R4= H)
4-CH3-NHPI (R2=CH3, R1=R3=R4= H)
N-hydroxynaphthalimide (NHNI)
3-F-NHPI (R1=F, R2= R3=R4= H)
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4-F-NHPI (R2=F, R1= R3=R4= H)
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3-I-NHPI (R1=I, R2= R3=R4= H)
4-I-NHPI (R2=I, R1= R3=R4= H)
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3-Br-NHPI (R1=Br, R2=R3=R4= H)
4-Br-NHPI (R2=Br, R1=R3=R4= H)
3-Cl-NHPI (R1=Cl, R2=R3=R4= H)
4-Cl-NHPI (R2=Cl, R1=R3=R4= H)
4-CH3O-NHPI (R2=CH3O, R1= R3=R4= H)
4,5-diCl-NHPI (R1= R4= H, R2=R3=Cl)
4-HOOC-NHPI (R2=COOH, R1= R3=R4= H)
Cl4-NHPI (R1= R2=R3=R4= Cl)
1-hydroxybenzotriazole (1-HBT)
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N-hydroxyquinolinimide (NHQI)
F4-NHPI (R1= R2=R3=R4= F)
Br4-NHPI (R1= R2=R3=R4= Br)
Scheme 3. The structures of N-hydroxy compounds.
The kinetic studies of N-oxyl radical reactions require а reliable, efficient and simple
methods for producing radicals. N-oxyl radicals can be generated from their parents N-hydroxy
compounds in oxidation processes by different ways6 including photoactivation,11
electrochemical,10a, 12 and chemical methods with inorganic,13 organic and enzymatic oxidants.14
In recent years special attention was paid to nonmetallic methods for generating N-oxyl radicals.4b,
4c, 15
In this study we have used effective method for the generation of N-oxyl radicals from the
corresponding N-hydroxy compounds (Scheme 4) with the metal-free oxidant
(diacetoxyiodo)benzene PhI(OAc)2 (PIDA), which is stable and readily soluble in organic
solvents. The method allows us to produce high concentrations of PINO at room temperature.
PIDA has the mild and highly selective oxidizing properties and was used for the C–O and C–C
bond formation in the presence of NHPI,16, 17 and also for the NHPI-mediated oxidation of
sulfonamides to N-sulfonylimines.18 Previously we have successfully used this method for
recording the EPR spectra of the imide-N-oxyl radicals19 and also for determining of the rate
constants of the H-abstraction from the C-H bonds20, 21 of organic compounds by PINO.
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Scheme 4. Generation of PINO from NHPI using PIDA.
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When PIDA is added to the N-hydroxy compounds solutions, the absorption bands appear
in the region of 350 – 600 nm with λmax, depending on the structure of N-hydroxy compounds.
This result indicates the formation of N-oxyl radicals (Figure 1 and Figure S1-S2 in the SI). We
used a stoichiometric excess of N-hydroxy compounds to minimize the effect of the oxidant on the
radical decay. The N-oxyl radical bands do not overlap with the absorption region of oxidant
(Figure S3 in the SI), as well as of iodobenzene and acetic acid, formed from oxidant (see Scheme
4). N-hydroxy compounds absorb in the UV region, and the bands of radicals are usually in the
visible region. This allows us to correctly carry out kinetic measurements using UV/Vis
spectroscopy.
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Figure 1. UV/Vis spectra of N-oxyl radicals generated by oxidation of N-hydroxy compounds
(3.0 mM) with PIDA (0.3 mM) in CH3CN, t = 30 ℃. A) 4-Br-PINO (1), 4,5-diCl-PINO (2),
4-Cl-PINO (3), PINO (4), Ph4-PINO (5), 4-CH3O-PINO (6). B) Br4-PINO (1), Cl4-PINO (2),
F4-PINO (3).
During the oxidation of N-hydroxy compounds with PIDA, the formation of N-oxyl
radicals can be observed by increasing the absorption at max of the corresponding radicals. Over
time, the absorbance of the solutions decreases, which indicates decay of the radicals (Figure 2).
The point corresponding to the maximum on the absorption−time curve is taken as start of the
radical decay process. N-oxyl radicals decompose slowly, they are reasonably persistent to record
accurate UV/Vis spectra.
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Figure 2. Absorption−time curves for the generation and decay of N-oxyl radicals in CH3CN at
corresponding max. [N-hydroxy compound]o = 3.0 mM; [PIDA]o = 0.3 mM; 4-CH3O-PINO (1)
at 494 nm, 4,5-diCl-PINO (2) at 409 nm, quinolineimide-N-oxyl radical (QINO) (3) at 382 nm,
pyromellitimide-N-oxyl radical (NDNO) (4) at 398 nm, 30 оС.
The decay reaction of N-oxyl radicals follows first order kinetics. The initial sections of
kinetic curves of radical decay (Figure 2) are nicely described by equation 1. A plots of
ln(At-AꝎ)/(A0-A∞) versus time give a straight line.
(1)
where kd is the first-order rate constant for spontaneous decay, A0, A and At are the absorbances
at t = 0, ∞, and t, respectively.
The first-order rate constants for the self-decay of N-oxyl radicals (kd) were obtained from
the slopes of the linear plots (Figure 3 and Figure S4 – S20 in the SI), using equation 1.
As per Figures 2, 3 and Figures 4-20 in SI, after the period of the radical accumulation and
reaching the maximum absorbance, the kinetic curves of the radical decay consist of two parts.
The first part could be attributed to the fast decay, which follows well the first-order kinetics. The
second part describes the slow reaction (with about the same rate for the many radicals studied)
(Figure 2). This type of kinetic traces, in our opinion, is explained by the complex mechanism of
the decay. Obviously, based on principle of valency conservation, a monomolecular elementary
act of PINO transformation into a stable molecular product is impossible. This process can only
be a staged one. In particular, Pedulli8c and Masui8d proposed two alternative routes, as shown in
Scheme 2. This is a bimolecular reaction between two PINO radicals; and a monomolecular
process with a cleavage of C-N bond of PINO and subsequent bimolecular interaction of the
resulting acyl radical and PINO. Since the final molecular product is the same for both routes, it is
impossible to carry out their kinetic differentiation by product and we cannot expect that the
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kinetics of the process of PINO spontaneous decay will be simple and to strictly follow the kinetics
of the first or second order for a long period of time. The kinetics of the overall process will be
described by a first-order equation if the first stage of the PINO transformation to an acyl radical
is limiting.
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We have used initial segments of the kinetic curves for the determination of the reaction
rate constants, which under standard conditions are best described by a first-order equation. And
it is these constants that we have chosen as a parameter to compare the radical stability.
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Figure3. Absorption−time curves for the generation and decay of N-oxyl radicals. Inset:
first-order plots for the self-decomposition of N-oxyl radicals. [N-hydroxy compound]o = 3.0 mM;
[PIDA]o= 0.3 mM, 30 ℃. A) benzotriazole-N-oxyl radical (ВТNO) at 476 nm; B) 4,5-diCl-PINO
at 409 nm; C) 3-I-PINO at 383 nm; D) 4-CH3-PINO at 396 nm.
[Bis(trifluoroacetoxy)]iodobenzene (PIFA) is also effective oxidant for generation of
N-oxyl radicals at room temperature. Hypervalent iodine compounds as PIDA and PIFA are
efficient alternatives to toxic heavy metal-based oxidants in many organic transformations.22
As can be seen in Figure 4 rates of radical accumulation and decomposition when using
hypervalent iodine compounds and ammonium сerium (IV) nitrate (CAN) as oxidants are
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different. This indicates an effect of the oxidant nature on the process; therefore, the measured rate
constants do not relate to elementary reaction. Under oxidation by CAN, radical accumulation
occurs immediately. On the contrary, during the oxidation of N-hydroxy compounds with PIDA
or PIFA, the radical buildup can be observed.
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Figure4. Absorption−time curves for the generation and decay of N-oxyl radicals using
different oxidants. Conditions: [N-hydroxy compound]o = 3.0 mM; [oxidant]o= 0.3 mM (1–
CAN; 2–PIFA; 3–PIDA), 30 ℃. A) QINO at 382 nm; B) NDNO at 398 nm.
The rate constants of N-oxyl radical self-decomposition were calculated using equation 1.
In Table 1 wavelengths of maximum absorbance of radicals as well as the first-order rate constants
for radical decay kd are presented. All reactions were run at 30 °C under same conditions ([NHI]o
= 3.0 mM; [PIDA]o= 0.3 mM), as described in “Experimental Section”. All rate constants were
determined from several experimental runs with typical error 10 %.
Table 1. The wavelengths of maximum absorbance of the N-oxyl radicals and the decay
rate constants (kd)

max (nm)
kd104 (s-1)

max (nm) kd104 (s-1)
N-oxyl radical
N-oxyl radical
4-CH3-PINO
4-Br-PINO
435
1.4
396
394
9.5
10
Ph4-PINO
383
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8
3-I-PINO
3-CH3-PINO
4-CH3O-PINO
F4-PINO
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494
374
382
382
422
387
409
2.4
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399
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406
370
398
415
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86
3-Cl-PINO
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2.7
4.1
5.0
5.3
5.9
7.3
7.3
NINO
4-Cl-PINO
PINO
4-HOOC-PINO
QINO
Cl4-PINO
3-F-PINO
NDNO
4-I-PINO
4-F-PINO
4,5-diCl-PINO
Br4-PINO
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7.6
476
140
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BTNO
3-Br-PINO
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It can be observed from Table 1 that the values of constants of N-oxyl radicals’ decay vary
within two orders of magnitude from 1.4·10-4 s-1 for Ph4-PINO to 1.4·10-2 s-1 for BTNO (Table 1).
Only five of them, within experimental error, decompose slower than PINO. A shift of the
absorption maxima in the long-wave region for 4-substituted NHPI compared with 3-substituted
NHPI is observed.
For most of the radicals presented in Table 1, the decay constants were measured for the
first time, however catalytic activity of their N-hydroxy compounds precursors in aerobic
oxidation of organic compounds was studied earlier. In some cases, the catalytic behavior of
N-hydroxy compounds was interpreted in terms of stability of the corresponding N-oxyl radicals.
Espenson et al.23 investigated NHPI and its derivatives, such as 3-F-NHPI, 4-CH3-NHPI, NDHPI
and NHPI, in the presence of cocatalyst Co(OAc)2 for the autoxidation of p-xylene and other
methyl arenes. The activity of the substituted NHPIs shows an increase in the following order:
4-CH3-NHPI < 3-F-NHPI < NHPI. Cai et al. reported8b that the self-decomposition of PINO
radicals obeys second-order kinetics in benzene and the radical decay rate follows the order
4-CH3-PINO < 3-F-PINO < PINO, consistent with the reactivity of the NHPIs in the catalytic
cycle.23
Xu et al.24 also considered the reactivity of tetra-halogen substituted NHPIs from the point
of view of radical stability. The authors showed that F4-NHPI in combination with
4-diamino-2,3-dichloroanthraquinone in the oxidation of ethylbenzene exhibited an abnormally
lower catalytic activity compared with Cl4-NHPI and Br4-NHPI. The reason may be that four
strongest electron-withdrawing fluoro-groups in F4-NHPI decrease the stability of the
corresponding PINO radical, which leads to a lower efficiency in catalysis. We have generated
corresponding N-oxyl radicals from halogen substituted NHPIs using PIFA and measured the
decay rate constants (Table 1), which increase in the order F4-PINO ˂ Cl4-PINO ˂ Br4-PINO. The
obtained results show that the instability of the F4-PINO radical is not the main reason of its lower
efficiency in the oxidation of ethylbenzene.
Many aspects of the catalytic behavior of NHPI were studied in detail, and it was shown
that the catalyst activity depends on many parameters.10b, 25 However, the discussion about the
influence of various factors on the oxidation of organic compounds in the presence of NHPI is still
open in the literature.
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The investigations of NHPI derivatives for the functionalization of organic molecules have
been presented in many reports. For example, 3-CH3O-NHPI,26, 27 4-CH3O-NHPI,10a, 26, 27, 28
4-CH3-NHPI,26, 27, 28 3-F-NHPI,26, 27, 28 4-Cl-NHPI,10a 4,5-diCl-NHPI, F4-NHPI10a successfully
tested in the processes of oxidation of alcohols under aerobic26, laccase-catalyzed27, 28 and
electrochemical oxidation conditions10a, 12b. Cl4-NHPI demonstrated a high potential as catalyst for
electrochemical C–H oxidation of allylic compounds,12b primary and secondary alcohols.10a, 29 The
observed electrochemical reactivity of NHPI catalysts is determined by their redox potential and
does not correlate with their reactivity under conditions of aerobic catalytic or laccase oxidation.
The decomposition of the electro-generated PINO radical is the limiting factor in development of
electrochemical oxidation processes12c.
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Study of various N-hydroxy compounds facilitates the development of new methods and
strategies for the functionalization of organic molecules, opens up new possibilities for new and
well-known structures of NHPI-type catalysts. For example, recently the groups of Brown30 and
Liu31 demonstrated that Сl4-NHPI and 4-CH3O-NHPI can be used as components of catalytic
systems for enantioselective synthesis.
The effect of the N-hydroxy compounds structure in the oxidation of n-butylbenzene was
studied by Boaz et al.32 The authors used a catalyst system consisting of ammonium iodate with
an NHPI-type catalyst and showed that yield of the main product 1-phenylbutyl acetate slightly
decreased in the presence of 4-CH3-NHPI (76 %), F4-NHPI (76 %), Br4-NHPI (73 %), NDHPI
(81 %), NHNI (67 %) compared with unsubstituted NHPI (86 %).
Lanzalunga et al.33 reported the oxidation of cyclohexane, toluene, ethylbenzene and
triphenylmethane by the nonheme iron (IV)−oxo complex [(N4Py)FeIV=O]2+ using NHPI,
4-FNHPI, 3-CH3-NHPI and 3-CH3O-NHPI as mediators. It was found a slight decrease in the
mediation efficiency for 4-CH3−NHPI and 4-CH3O−NHPI compared with NHPI and 4-F-NHPI.
The effect of substitution in the aromatic ring of NHPI on the oxidation of ethylbenzene using
3-CH3-NHPI, 4-CH3-NHPI, 3-F-NHPI, 3-CH3O-NHPI and 4-CH3O-NHPI in combination with
cobalt (II) acetate was studied by Nolte et al.34 It was shown that NHPIs with electron-withdrawing
substituents accelerate the oxidation of ethylbenzene. Xu35 and Lanzalunga13b, 26 observed similar
effects in the oxidation of other substrates. For example, Xu et al.35 reported that the catalytic
activity of system NHQI / metal salts in acetonitrile in the aerobic oxidation of toluene is
significantly higher than that of NHPI through an electron-withdrawing effect of N-heteroaromatic
ring containing N-hydroxy compound. The combination of СuСl2 with NHQI showed the best
activity in toluene oxidation. Substrate was transformed with 70.9 % conversion and 93.5 %
selectivity to benzoic acid at 90 ℃ within 2 h. Later Lanzalunga,13b demonstrated an increase in
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the reactivity of QINO compared with PINO in the reaction of the H-abstraction due to the
presence of the N-heteroaromatic ring in QINO.
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On the other hand, Marcadal-Abbadi reported36 that NHPIs with electron-donating
substituents such as 4-CH3O-NHPI and Ph4-NHPI show high activity in the oxidation of
ethylbenzene in the presence of CuCl. Catalysts with electron-withdrawing substituents
4-Cl-NHPI, 4,5-diCl-NHPI, Cl4-NHPI, F4-PINO and NHQI are less effective. For example, a very
low efficiency of the NHQI / CuCl system was observed for the oxidation of ethylbenzene in
acetonitrile at 25 ℃.36 The conversion of the substrate was only 10 % with 5 % acetophenone
yield. Earlier we have shown that NHPI is much more effective than 4-HOOC-NHPI with an
electron-withdrawing substituent in the cumene oxidation when using cocatalysts CuCl, CuBr10g
and Co(OAc)2.10i, 37 Li et al. successfully used 4-HООC-NHPI in combination with NHQI for the
aerobic oxidation of ethylbenzene,38 but it was shown that 4-HOOC-NHPI alone is an ineffective
catalyst in the allylic oxidation of cholesteryl acetate.39 Thus, the high reactivity of N-oxyl radicals
with electron-withdrawing substituents in H-abstraction does not always correlate with overall
catalytic activity. A strong O-H bond of N-hydroxy compounds with electron-withdrawing
substituents facilitates the H-abstraction from substrates by corresponding N-oxyl radicals, but
simultaneously decreases quasi stationary concentration of N-oxyl radicals formed in situ as a
result of the reaction (ROO + NHPI  ROOH + PINO, kf) 10i, 34 (see Scheme 1).
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The data in Table 1 demonstrate, that the NDNO, BTNO, NINO radicals decompose with
high rates, but in many cases the high catalytic efficiency of corresponding N-hydroxy compounds
was observed. NHNI demonstrated high catalytic performance in aerobic oxidation of
ethylbenzene40 and p-xylene compared with NHPI.41 On the other hand, NHNI exhibited a very
low catalytic effect in the process of cumene oxidation in the presence of Cu (I) salts.10i
NDHPI has two NOH groups in the molecule and provides efficient catalysis in various
oxidation processes,36, 42 although a low conversion of substrates was obtained in the presence of
NDHPI for both the aerobic oxidation of cumene10i, 43 and electrochemical C–H oxidation of allylic
compounds.12b Besides, NDHPI along with 4-HOOC-NHPI is effective in the processes of
stereospecific radical polymerization of methyl methacrylate.44
BTNO radical is not stable and quickly decomposes with a half-lifetime of 49 s and a
first-order rate constant kd = 6.310-3 s-1 at 25 ℃.45 We have generated BTNO using PIDA and
PIFA and observed the decay of radical with rate constants 14.010-3 s-1 and 6.710-3 s-1,
respectively. Despite the low stability of the BTNO radical, its 1-HBT precursor is well-known as
mediator of laccase oxidation of benzyl alcohols,46 the laccase oxidative degradation of dyes47 and
as catalyst for the electrochemical oxidation of allylic C–H bonds.12b
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The smallest rate constant of self-decay is observed for Ph4-PINO radical (Table 1). It is
known that Ph4-NHPI is more soluble than NHPI in most of the classical solvents and it is one of
the most successful organic catalysts of aerobic oxidation. Einhorn et al.48 found that Ph4-NHPI with
CuCl in the oxidation of benzylic compounds shows good catalytic activity, even better than
NHPI / CuCl. We have also showed, that system Ph4-NHPI / CuCl is effective in the oxidation of
cumene10g and system Ph4-NHPI / Cu(NO3)2 successfully used for the mild oxidation of
5-hydroxymethylfurfural to 2,5-diformylfuran with molecular oxygen.49 However, the oxidation
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rate of cumene in acetic acid in the presence of the Ph4-PINO/Co(OAc)2 system is lower
compared with the oxidation catalyzed by NHPI. This is explained by steric hindrances during the
interaction of cobalt ions and a bulk Ph4-PINO molecule in the internal coordination sphere of the
metal. Stahl et al.50 also reported a lower activity of Ph4-NHPI compared with NHPI during
electrochemical iodination of methylarenes.
Comparative kinetic study of degradation of PINO and Ph4-PINO indicated the steric factor
importance. The introduction of four bulky phenyl substituents in the Ph4-PINO radical limits the
opening of the five-membered ring by breaking the C-N bond and increases the radical stability. Such
results are consistent with the data discussed by Vanel51 and Jacq.52 Various polyaromatic catalysts
analogous to NHPI were synthesized with the aim of tuning the catalyst performances in aerobic
oxidation. It was shown that half-life of catalysts with polyaromatic structures is longer than that of
PINO. Einhorn et al.48 investigated the processes of generation and self-decomposition of the
corresponding radicals in acetonitrile at 35 ℃. High kinetic stability of the corresponding radicals
allows using such catalysts with low loading in aerobic oxidation of various substrates.
The presented analysis shows, despite that the decay of radicals is an important reaction
responsible for deactivation of the catalyst, that there is no simple correlation between the rate of
decomposition of radicals and the catalytic activity of N-hydroxy compounds. A complex catalytic
oxidation process involves several stages with different radicals. The rates of reactions depend on
the process conditions, the presence of cocatalysts, the structure of the N-hydroxy compounds,
substrates and reaction intermediates. In addition, radicals with increased stability are often
inactive in the key stage of oxidation process such H-atom transfer reaction. Thus, effective
catalysis involving N-hydroxy compounds suggests a favorable balance between reactivity and
stability of the resulting radicals.
Another factor that can significantly affect the decay rate of PINO is medium effect. The
solvent is an important component and active participant of the reaction system; it can significantly
affect the transformations of PINO and its reactivity. Numerous researchers discussed the solvent
effect on the NHPI-catalyzed process of aerobic oxidation of organic compounds.8c, 25c, 37, 53 It was
shown, that the conversion of the substrate and the yield of the products can be controlled by
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solvent properties. For example, catalytic activity of NHPI changes in polar protic solvents due to
the formation of hydrogen bonds between solvent molecules and NHPI.54 This effect is not
observed in non-polar solvents, but their use is limited due to the poor solubility of NHPI.
Unfortunately, data on the solvent effects on the radical decay rate are limited to reports from
Espenson8a and Baciocchi.9 Rafiee and co-workers examined the effect of solution pH on PINO
decomposition rates and showed55 that the rate increases with the basicity of the medium (0.18,
0.37, 1.4, and 6.2 s-1 at pH 2.5, 4.7, 7.2 and 8.3 respectively). The instability of electrogenerated
PINO at increasing pH could be explained in terms of occurrence of some side reactions in aqueous
solution.
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To investigate the kinetic solvent effect, the rate constants of the PINO decay were
determined in series of solvents. In Table 2 the values of the obtained constants are given, PINO
was generated by oxidation of NHPI with PIDA.
Table 2. Rate constants kd for the PINO decay and solvent properties. [NHPI]o =
3.0 mM; [PIDA]o= 0.3 mM; monitored wavelength, 382 nm; temperature, 30 ℃.
Solvent
Acetonitrile
Ethyl acetate
Acetic acid
εa
37.5
6
DNb (kcal/mol)
ANc (kcal/mol)
H d
kd103(s-1)
0.5
2
14.1
17.1
20.0
11.9
2.7
18.9
9.3
0.09
0.7
0.8
6.2
52.9
15.5
20.5
0.55
0.12
–
Benzonitrile
Nitromethane
Chlorobenzene
(PhCl) / Acetonitrile
(2:1)
20.0
38.0
25.2
38.6
2.6 (for
PhCl)
11.0
3.3(for PhCl)
–
athe dielectric constant. bGutmann donor number; ref 56. cGutmann acceptor number; ref
56. dAbraham’s value; ref 57.
The lowest decay rate of PINO is observed in acetonitrile, which is in good agreement with
the results of effective oxidation of various organic compounds in the presence of NHPI in
acetonitrile.8c, 10g, 10i, 25c, 49, 58 As can be seen from the data in Table 2, the rate of PINO decay varies
little in solvents, which differ greatly in their ability as hydrogen bond donors, as confirmed by
Abraham’s 2H values.57 These results are in agreement with the observations by Espenson8a and
Baciocchi.9
The data in Table 2 allow us to trace the dependence of the rate constants on the Gutmann
donor numbers, which characterize the nucleophilic properties of solvents.59 The rate constants of
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radical decay are low in the solvents with a high donor numbers such as acetonitrile, ethyl acetate
and acetic acid, but in benzonitrile and nitromethane, which have a low donor numbers, the decay
rate constants are sharply increasing. We can assume the formation of molecular complexes
(solvates) between PINO radical and solvent molecule. Their formation will be facilitated by the
large dipole moment of PINO and its elecrtrophilic character.9, 20, 25c, 60 The higher the value of the
solvent donor number, the larger the degree of the PINO solvation, that prevents its spontaneous
decay.
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CONCLUSIONS
Aerobic oxidation of organic compounds in the presence of NHPI-type catalysts is a
complex multi-stage process. N-hydroxy compounds simultaneously participate in several
reactions and their catalytic activity in such processes is determined by a complex of factors. One
of the main reasons for limiting the use of N-hydroxy compounds as catalysts for industrial
oxidation processes is non-persistence of derived radicals. We have found that the kinetics of N-
oxyl radicals’ decay strongly depends on the solvent, oxidant, reaction conditions, and the structure
of radicals. Our experimental observations showed that different substituents of NHPI can impact
the kinetic stability of corresponding radicals. However, substituted PINO radicals both with
electron-donating and with electron-withdrawing substituents, within experimental error, have
lower kinetic stability than unsubstituted PINO, except for 3-CH3-, 3-I-, 4-CH3O-, F4- and Ph4-
PINO. The introduction of bulky phenyl substituents into the aromatic ring of the NHPI molecule
contributes to the stability of the corresponding radical. It can be assumed that steric hindrances
will affect the rate of radical decomposition. In this case, one might expect the slow decay of
radicals formed from NDHPI and NHNI, but, on contrary, we have observed high rates of self-
decomposition. Perhaps such complex structures decompose by another mechanism.
The presented study does not yet give an unambiguous answer to the question of how the
radical structure affects their stability, but we hope that it adds valuable information for
understanding the mechanisms of catalysis in the presence of N-hydroxy compounds. To establish
a quantitative relationship between the structure and stability of radicals, additional studies are
needed, which are carried out by our research group and will be published later.
EXPERIMENTAL SECTION
Materials.
(Diacetoxyiodo)benzene,
[bis(trifluoroacetoxy)]iodobenzene,
N-
hydroxyphthalimide, 1-hydroxybenzotriazole hydrate, ammonium сerium (IV) nitrate
(NH4)2Ce(NO3)6 were commercial reagents and used without purification. CH3CN used "HPLC
gradient grade" without additional purification.
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Instrumentation. Spectrophotometric measurements were performed on UV/Vis
spectrophotometer Analytic Jena SPECORD 50 using a quartz cuvette (10 mm path length)
equipped with a thermostated cell holder. IR spectra were recorded on Perkin-Elmer Spectrum BX
using a KBr pellets. NMR spectra were recorded on a Bruker BioSpin 400 using DMSO-d6 as
solvent with tetramethylsilane as an internal reference. Elemental analysis was performed using
Vario EL III. MS analysis was performed on an LCMS instrument (Agilent 1100) with chemical
ionization.
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Spectrophotometric Kinetic Studies. N-oxyl radicals were generated in a 3-mL
spectrophotometric quartz cuvette by quickly mixing N-hydroxy compounds (3.0 mM) with PIDA,
PIFA or CAN (0.3 mM) in deoxygenated acetonitrile at 30 ℃. All kinetic experiments were carried
out by using freshly prepared samples.
Synthesis of N-hydroxyimides. N-hydroxyimides were synthesized by the reaction of
corresponding phthalic anhydride with hydroxylamine hydrochloride according to the modified
literature procedures and characterized by elemental analysis, 1H NMR, 13C NMR,
IR-spectroscopy and HPLC/MS analysis (Figures 21-24 in SI).
The general approach to the synthesis of substituted NHPI can be shown by 3-methyl-N-
hydroxyphthalimide synthesis34. 2.01 g. (30 mmol) of hydroxylamine hydrochloride were
dissolved in 50 ml pyridine in ambient conditions under constant stirring. Stirring continued for
another 20 min until complete dissolution of solid. Then, 4,48 g (27,6 mmol) finely ground 3-
methylphthalic anhydride were added. The resulted solution was refluxed for 8 hours. After
cooling to the room temperature, 100 ml of distilled water were added to formed yellow solution.
pH was adjusted to the 2-3 by slowly adding 3 M. HCl solution. The target compound was formed
as white powder, which was washed with cold water, filtered and dried in vacuum over P2O5 (45 °С
/ 10 torr).
1
3-Methyl-N-hydroxyphthalimide (3-CH3-NHPI):19, 34 yield: 2.54 g, 52%, m.p. 223 ℃. H
NMR (400 MHz, DMSO-d6) δ 10.72 (s, 1H), 7.73–7.58 (m, 3H), 2.60 (s, 3H). 13C{1H} NMR (75
MHz, DMSO-d6) δ 164.8, 163.9, 137.0, 136.6, 133.9, 129.1, 125.3,120.5. IR (KBr), cm−1: 3221,
2935, 2829, 1774, 1674, 1604. Anal. Calcd for C9H7O3N: C 61.01; H 3.95; N 7.91. Found: C,
61.86; H, 3.71; N, 7.75.
1
4-Methyl-N-hydroxyphthalimide (4-CH3-NHPI):19, 34 yield: 1.56 g, 43%, m.p. 202 ℃. H
NMR (400 MHz, DMSO-d6) δ 10.72 (s, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.65 (s, 1H), 7.62 (d, J =
13
7.6 Hz, 1H), 2.46 (s, 3H). C{1H} NMR (101 MHz, DMSO-d6) δ 164.7, 164.6, 145.9, 135.3,
129.5, 126.5, 123.9, 123.4, 21.9. IR (KBr), cm−1: 3120, 2925, 2840, 1750, 1690,1604. Anal. Calcd
for C9H7O3N: C, 61.01; H, 3.95; N, 7.91. Found: С, 60.89; Н, 4.11; N, 8.21.
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N-hydroxynaphthalimide (NHNI):61, 62 yield: 1.17 g, 68%, m.p. 299°С. 1H NMR (400 MHz,
DMSO-d6) δ 10.76 (s, 1H), 8.52 (d, J = 7.2 Hz, 2H), 8.48 (d, J = 8.2 Hz, 2H), 7.89 (t, J = 7.7, 7.7
Hz, 2H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 160.9, 134.6, 131.4, 130.9, 127.4, 126.3, 122.4.
IR (KBr), cm−1: 3107, 2925, 1716, 1584, 1496. Anal. Calcd for С12H7O3N: С, 67.61; Н, 3.31;
N, 6.57. Found: C, 67.81; H, 3.28; N, 6.90.
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4-Methoxy-N-hydroxyphthalimide (4-CH3O-NHPI):19, 34 yield: 2.76 g, 65%, m.p 222 ℃.
1H NMR (300 MHz, DMSO-d6) δ 10.70 (s, 1H), 7.76 (d, J = 8.3 Hz, 1H), 7.36 (d, J = 2.3 Hz, 1H),
7.29 (dd, J = 8.3, 2.3 Hz, 1H), 3.91 (s, 3H). 13C{1H} NMR (75 MHz, DMSO-d6) δ 164.4, 164.0,
163.8, 131.4, 125.1, 120.3, 119.5, 108.7, 56.3. IR (KBr), cm−1: 3138, 2942, 2829, 1778, 1688,
1608. Anal. Calcd for C9H7O4N: C, 55.96; H, 3.65; N, 7.25. Found: C, 56.02; H, 3.72; N, 7.29.
4-Carboxy-N-hydroxyphthalimide (4-HOOC-NHPI):19, 63 yield: 5.21 g, 70%, m.p 239 –
242 ℃ 1H NMR (400 MHz, DMSO-d6) δ 13.09 (br s, 1H), 11.01 (br s, 1H), 8.35 (d, J = 7.7 Hz,
1H), 8.18 (s, 1H), 7.95 (d, J = 7.7 Hz, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 165.8, 163.4,
136.2, 135.3, 132.2, 129.3, 123.3, 122.9. IR (KBr), cm−1: 3451, 2758, 1767, 1672. Anal. Calcd for
C9H5O5N: C, 52.19; H, 2.43; N, 6.76. Found: C, 52.11; H, 2.49; N, 6.69.
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3,4,5,6-Tetraphenyl-N-hydroxyphthalimide (Ph4-NHPI):64 yield: 2.81g, 70%, m.p 295 –
1
296 ℃. H NMR (400 MHz, CDCl3) δ 7.25–7.15 (m, 6H), 7.14–7.09 (m, 4H), 6.95–6.88 (m,
6H), 6.77–6.72 (m, 4H). 13C{1H} NMR (101 MHz, CDCl3) δ 163.1, 148.1, 139.7, 137.8, 135.1,
130.7, 129.9, 127.5, 127.4, 127.1, 126.4, 125.1. IR (KBr), cm−1: 3255, 3061, 1777, 1731, 1444,
1092. Anal. Calcd for С32H21O3N: С, 82.23; Н, 4.5; N, 2.99. Found: С, 82.34; Н, 4.34; N, 3.21.
48
4,5-Dichloro-N-hydroxyphthalimide (4,5-diCl-NHPI):19,
yield: 2 g, 72%, m.p.
13
202−205 ℃. 1H NMR (400 MHz, DMSO-d6) δ 11.05 (br s, 1H), 8.12 (s, 2H). C{1H} NMR
(101 MHz, DMSO-d6) δ 162.4, 137.2, 128.8, 125.2. IR (KBr), cm−1: 3362, 2907, 1774, 1716.
Anal. Calcd for C8H3Cl2NO3: C, 41.41; H, 1.30; N, 6.04. Found: C, 41.50; H, 1.39; N, 5.99.
1
N,N-dihydroxypyromellitimide (NDHPI):23 yield: 2.39 g, 50 %, m. p. 330 ℃ (dec). H
NMR (400 MHz, DMSO-d6) δ 11.18 (s, 2H), 8.13 (s, 2H). 13C{1H} NMR (101 MHz, DMSO-d6)
δ 162.6, 134.3, 117.0. Anal. Calcd for C10H4O6N2: C, 42.27; H, 2.84; N, 9.86. Found: С 42.5; Н
2.70; N 9.91.
3,4,5,6-Tetrachloro-N-hydroxyphthalimide (Сl4-NHPI):24 yield: 2.11 g, 68 %, m. p. 253°C.
1H NMR (400 MHz, DMSO-d6) δ 11.25 (s, 1H). 13C{1H} NMR (101 MHz, DMSO- d6) δ 172.3,
167.2, 140.1, 128.0, 125.8. IR (KBr), cm-1: 3578, 3495, 3254, 2921, 1774, 1724, 1363, 1159, 1040.
Anal. Calcd for C8HCl4NO3: C, 31.93; H, 0.33; N, 4.65. Found: C, 32.03; H, 0.41; N, 4.78.
3,4,5,6-Tetrafluoro-N-hydroxyphthalimide (F4-NHPI):24 yield: 2.41 g, 41 %, m. p. 165°C.
1H NMR (400 MHz, DMSO-d6) δ 11.31 (s, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 172.7,
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167.7, 142.1, 126.4, 121.8. IR (KBr), cm−1: 3389, 3188, 1798, 1734, 1512, 1412, 1330, 1165, 1074.
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Anal. Calcd for C8HF4NO3: C, 40.87; H, 0.43; N, 5.96. Found: С 41.05; Н 0.52; N 5.81.
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3,4,5,6-Tetrabromo-N-hydroxyphthalimide (Br4-NHPI):24 yield: 2.86 g, 55 %, H NMR
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(400 MHz, DMSO-d6) δ 11.25 (s, 1H). C{1H} NMR (101 MHz, DMSO-d6) δ 168.4, 163.2,
138.1, 128.0, 124.3. IR (KBr), cm−1: 3242, 3074, 1778, 1728, 1543, 1333, 1150, 1024. Anal. Calcd
8
9
for C8HBr4NO3: C, 20.07; H, 0.21; N, 2.93. Found: С 20.15; Н 0.32; N 2.81.
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4-Iodo-N-hydroxyphthalimide (4-I-NHPI):65 yield: 2.35 g, 73 %, m.p. 205 ℃ (dec). Н
NMR (400 MHz, DMSO-d6) δ 10.89 (s, 1H), 8.19 (d, J = 7.4 Hz, 1H), 8.13 (s, 1H), 7.59 (d, J =
6.3 Hz, 1H). 13С{1H} NMR (101 MHz, DMSO-d6) 162.9, 143.0, 131.2, 130.2, 127.9, 124.5, 102.1.
IR (KBr), cm−1: 3136, 2943, 2843, 1766, 1702. Anal. Calcd for С8H4IO3N: С, 33.32; Н, 1.28; N,
4.92. Found: С, 33.25; Н, 1.39; N, 4.85.
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3-Iodo-N-hydroxyphthalimide (3-I-NHPI):65 yield: 2.84 g,68 %, m.p. 272–273 °С. Н
NMR (400 MHz, DMSO-d6) δ 10.90 (br s, 1H), 8.18 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 7.2 Hz, 1H),
7.51 (t, J = 7.7, 7.7 Hz, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 163.8, 162.9, 145.5, 135.9,
131.5, 130.1, 123.3, 90.3. IR (KBr), cm−1: 3114, 2945, 2841, 1776, 1707. Anal. Calcd for
С8H4IO3N: С, 33.25; Н, 1.39; N, 4.85. Found: С, 33.12; Н, 1.45; N, 4.96.
3-Chloro-N-hydroxyphthalimide (3-Cl-NHPI):66, 67, 68 yield: 3.24 g, 52 %, m.p. 234−237 ℃
(dec.). 1H NMR (300 MHz, DMSO-d6) δ 10.91 (br s, 1H), 7.88−7.73 (m, 3H). 13C{1H} NMR (75
MHz, DMSO-d6) δ 162.7, 161.9, 135.9, 135.6, 131.1,129.2, 124.7, 121.8. IR (KBr), cm−1: 3362,
2907, 1774, 1716. Anal. Calcd for C8H4O3NCl: C, 48.63; H, 2.04; N, 7.09. Found: C, 48.77; H,
2.00; N, 7.13.
4-Chloro-N-hydroxyphthalimide (4-Cl-NHPI):19 yield: 2.27 g, 73 %, m.p. 209 ℃. 1H NMR
(400 MHz, DMSO-d6) δ 10.94 (s, 1H), 7.98–7.81 (m, 3H). 13C{1H} NMR (75 MHz, DMSO-d6) δ
163.3, 162.9, 139.2, 134.2, 130.8, 127.4, 124.7, 123.1. IR (KBr), cm−1: 3110, 2914, 1774, 1694.
Anal. Calcd for C8H4O3NCl: C, 48.63; H, 2.04; N, 7.09. Found: C, 48.71; H, 1.98; N, 7.11.
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4-Fluoro-N-hydroxyphthalimide (4-F-NHPI): yield: 2.54 g, 52 %, m.p. 183-185 ℃. H
NMR (400 MHz, DMSO-d6) δ δ 10.93 (s, 1H), 7.91 (dd, J = 8.1, 4.6 Hz, 1H), 7.79–7.73 (m, 1H),
13
7.70–7.61 (m, 1H). C{1H} NMR (101 MHz, DMSO-d6) δ 167.0, 164.5, 163.3, 162.9, 131.9,
131.8, 125.9, 125.8, 121.2, 121.0, 117.4, 117.2, 111.4, 111.1. IR (KBr), сm-1: 3115, 2920, 1781,
1689. Anal. Calcd for C8H4O3NF: С, 53.05; Н, 2.33; N, 7.73. Found: С, 53.19; Н, 2.32; N, 7.85.
3-Fluoro-N-hydroxyphthalimide (3-F-NHPI):34, 69 yield: 2 g, 79 %, m.p. 216 ℃. 1H NMR
(400 MHz, DMSO-d6) δ 10.94 (s, 1H), 7.92–7.84 (m, 1H), 7.71–7.61 (m, 2H). 13C{1H} NMR
(101 MHz, DMSO-d6) δ 161.7, 158.2, 155.6, 138.1, 138.0, 131.5, 123.4, 123.2, 120.1.IR (KBr),
сm-1: 3523, 3435, 3063, 2910, 2707, 1744, 1709, 1600. Anal. Calcd for C8H4O3NF: С, 53.05; Н,
2.33; N, 7.73. Found: С, 52.99; Н, 2.42; N, 7.69.
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3-Bromo-N-hydroxyphthalimide (3-Br-NHPI):68 yield: 1.82 g, 84 %, m.p. 251–253 ℃. 1Н
NMR (400 MHz, DMSO-d6) δ 10.91 (br s, 1H), 7.98 (d, J = 8.1 Hz, 1H), 7.82 (d, J = 7.2 Hz, 1H),
7.71 (t, J = 7.7, 7.7 Hz, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 162.6, 162.4, 138.7, 135.8,
131.4, 126.5, 122.3, 117.1. IR (KBr), сm-1: 3354, 3118, 2909, 2836, 1780, 1719, 1694. Anal. Calcd
for С8H4BrNO3: С, 39.70; Н, 1.67; N, 5.79. Found: С, 39.81; Н, 1.73; N, 5.82.
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4-Bromo-N-hydroxyphthalimide (4-Br-NHPI): yield: 2.95 g, 75 %, m.p. 215 ℃. 1H NMR
(400 MHz, DMSO-d6) δ 10.95 (s, 1H), 8.05–7.99 (m, 2H), 7.75 (d, J = 8.4 Hz, 1H). 13C{1H} NMR
(101 MHz, DMSO-d6) δ 164.1, 163.5, 137.7, 131.3, 128.5, 128.3, 126.4, 125.4. IR (KBr), сm-1:
3360, 2903, 1777, 1674. Anal. Calcd for С8H4BrNO3: С, 39.70; Н, 1.67; N, 5.79. Found: С, 39.91;
Н, 1.82; N, 5.69.
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N-hydroxyquinolinimide (NHQI):35, 70 yield: 3.13 g, 40 %, m.p. 163-165 ℃. H NMR (400
MHz, DMSO-d6) δ 10.76 (s, 1H), 8.89-8.84 (m, 1H), 8.24-8.19 (m, 1H), 7.34-7.27 (m, 1H).
13C{1H} NMR (101 MHz, DMSO-d6) δ 163.3, 162.1, 151.1, 139.9, 126.7, 124.9, 123.9. IR (KBr),
сm-1: 3513, 3086, 2548, 1749, 1724, 1607, 1385, 1155, 1101. Anal. Calcd for C7H4N2O3: C, 51.23;
H, 2.46; N, 17.07. Found: C, 51.38; H, 2.31; N, 17.21.
ASSOCIATED CONTENT
Supporting Information
UV/Vis spectra of N-oxyl radicals in CH3CN, absorption-time curves for the generation
and decay of N-oxyl radicals, the first-order plots for the self-decomposition of N-oxyl radicals,
HPLC/MS analyses of N-hydroxyimides (PDF).
AUTHOR INFORMATION
Corresponding Authors
*E-mail: kusch.o@donnu.edu.ua
ORCID
Olga Kushch: https://orcid.org/0000-0002-7740-173X
Mikhail Kompanets: https://orcid.org/0000-0003-1890-7367
Alexander Shendrik: https://orcid.org/0000-0002-5518-1019
Iosyp Opeida: https://orcid.org/0000-0001-8591-0537
Iryna Hordieieva: https://orcid.org/0000-0002-5923-4683
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
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This work was supported by the Vasyl’ Stus Donetsk National University, Vinnytsia,
Ukraine. The study was carried out within the Fundamental/Applied Research Programme funded
by the Ministry of Education and Science of Ukraine, Project (No 0117 U002361).
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