РЕАКЦІЙНА ЗДАТНІСТЬ НУКЛЕОФІЛІВ І α-ЕФЕКТ У ПРОЦЕСАХ ЗАМІЩЕННЯ В ЕЛЕКТРОНОДЕФІЦИТНИХ ЦЕНТРАХ
The review analyzes issues related to the reactivity of nucleophiles and the manifestation of the α-effect in substitution processes at electron-deficient centers. The fundamental aspects of this phenomenon, as well as the possibilities and prospects of using α-nucleophiles in systems for the highly...
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| Дата: | 2020 |
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| Автори: | , , , |
| Формат: | Стаття |
| Мова: | Англійська |
| Опубліковано: |
V.I.Vernadsky Institute of General and Inorganic Chemistry
2020
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| Назва журналу: | Ukrainian Chemistry Journal |
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Репозитарії
Ukrainian Chemistry Journal| _version_ | 1871465480835825664 |
|---|---|
| author | Popov, Anatolii Kapitanov, Illia Serdyuk, Anna Sumeiko, Aleksandr |
| author_facet | Popov, Anatolii Kapitanov, Illia Serdyuk, Anna Sumeiko, Aleksandr |
| author_institution_txt_mv | [
{
"author": "Anatolii Popov",
"institution": "Институт физико-органической химии и углехимии им. Л.М.Литвиненко НАН Украины"
},
{
"author": "Illia Kapitanov",
"institution": "Институт физико-органической химии и углехимии им. Л.М.Литвиненко НАН Украины "
},
{
"author": "Anna Serdyuk",
"institution": "ganna.serdyuk@gmail.com"
},
{
"author": "Aleksandr Sumeiko",
"institution": "Институт физико-органической химии и углехимии им. Л.М.Литвиненко НАН Украины ––––– Институт органической химии НАН Украины"
}
] |
| author_sort | Popov, Anatolii |
| baseUrl_str | https://ucj.org.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-22T08:23:43Z |
| description | The review analyzes issues related to the reactivity of nucleophiles and the manifestation of the α-effect in substitution processes at electron-deficient centers. The fundamental aspects of this phenomenon, as well as the possibilities and prospects of using α-nucleophiles in systems for the highly efficient degradation of substrates - ecotoxicants of various natures, are discussed. In the first part of the review such aspects were observed: inorganic α-nucleophiles as the most effective class of reagents for the decomposition of organic phosphorus compounds, hydroxylamine, its N-alkyl derivatives, oximes, and hydroxamic acids, reactivity of the НОО– anion in the processes of acyl group transfer, reactivity of oximate ions, inorganic α-nucleophiles as the basis of formulations for the degradation of neurotoxins, vesicants, and organophosphorus pesticides, design of inhibited acetylcholinesterase reactivators based on hydroxylamine derivatives, ways of structural modification of α-nucleophiles and systems based on them. The data on the reactivity of typical inorganic α-nucleophiles in the cleavage of acyl-containing substrates, including phosphorus acid esters, which provide abnormally high reaction rates in comparison with other supernucleophiles, are analyzed. Various types of such α-nucleophiles, features of their structure and reactivity are considered. It was shown that an important feature of hydroxylamine, oximes, and hydroxamic acids is the presence of a fragment with adjacent O and N (–N – O – H) atoms containing one or more lone electron pairs, which determines their belonging to the class of α-nucleophiles. It has been shown that a many of factors can be responsible for the manifestation of the α-effect and its magnitude, the main of which is the destabilization of the ground state of the nucleophile due to repulsion of lone electron pairs, stabilization of the transition state, the unusual thermodynamic stability of reaction products, solvation effects of the solvent, type of hybridization of the electrophilic center, etc. |
| doi_str_mv | 10.33609/2708-129X.86.7.2020.3-31 |
| first_indexed | 2025-09-24T17:43:27Z |
| format | Article |
| fulltext |
3
UDC 541.124:541.183:547.288.4 doi: 10.33609/2708-129X.86.7.2020.3-31
REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION
PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
A. F. Popov1, I. V. Kapitanov1,3, A. A. Serdyuk1,3, A. E. Shumeiko1,2*
1Institute of Physical Organic Chemistry and Coal Chemistry, L.M. Litvinenko NAS of Ukraine; Kharkiv
highway 50, Kyiv 02160, Ukraine.
2Institute of Organic Chemistry, NAS of Ukraine; st. Murmanskaya 5, Kyiv 02660, Ukraine
3Center for Excellence in Green Chemistry, European Research Area. Department of Chemistry and Bio
technology, Faculty of Science, Tallinn University of Technology, Academia 15, 12618 Tallinn, Estonia
* E-mail: ashumeiko@ukr.net
The review analyzes issues related to the reactivity of nucleophiles and the manifestation of the
α-effect in substitution processes at electron-deficient centers. The fundamental aspects of this phe
nomenon, as well as the possibilities and prospects of using α-nucleophiles in systems for the highly
efficient degradation of substrates - ecotoxicants of various natures, are discussed. In the first part of the
review such aspects were observed: inorganic α-nucleophiles as the most effective class of reagents for
the decomposition of organic phosphorus compounds, hydroxylamine, its N-alkyl derivatives, oximes,
and hydroxamic acids, reactivity of the НОО– anion in the processes of acyl group transfer, reactivity of
oximate ions, inorganic α-nucleophiles as the basis of formulations for the degradation of neurotoxins,
vesicants, and organophosphorus pesticides, design of inhibited acetylcholinesterase reactivators based
on hydroxylamine derivatives, ways of structural modification of α-nucleophiles and systems based on
them. The data on the reactivity of typical inorganic α-nucleophiles in the cleavage of acyl-containing
substrates, including phosphorus acid esters, which provide abnormally high reaction rates in com
parison with other supernucleophiles, are analyzed. Various types of such α-nucleophiles, features of
their structure and reactivity are considered. It was shown that an important feature of hydroxylamine,
oximes, and hydroxamic acids is the presence of a fragment with adjacent O and N (–N – O – H) atoms
containing one or more lone electron pairs, which determines their belonging to the class of α-nucleo
philes. It has been shown that a many of factors can be responsible for the manifestation of the α-effect
and its magnitude, the main of which is the destabilization of the ground state of the nucleophile due
to repulsion of lone electron pairs, stabilization of the transition state, the unusual thermodynamic
stability of reaction products, solvation effects of the solvent, type of hybridization of the electrophilic
center, etc.
Key words: functionalized surfactants, α-nucleophiles, micellar systems, hydroxylamine, oximes,
amidoximes, hydroxamic acids, peroxides.
ORGANIC CHEMISTRY REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
4 ISSN 2708-129X. Укр. хім. журн., 2020
INTRODUCTION. The first publication re
lated to the phenomenon, which later became
known as the α-effect, dates to 1947. Only
15 years later, Edwards and Pearson [1], having
analyzed and generalized a significant amount
of experimental material, introduced this term
into physical organic chemistry. In its most
general form, the essence of the α-effect can
be represented as an abnormally high nucleop
hilic reactivity of a number of compounds,
which cannot be predicted from the Brønsted
dependence for “normal” oxygen-containing
nucleophilic reagents (arylate and alcoholate
ions). It was in [1] that compounds contain
ing an electronegative atom with one or more
lone pairs of electrons near the nucleophilic
center (in the α-position) were isolated from
the group of nucleophiles and were called
α-nucleophiles (supernucleophiles). Their ba
sic structure is schematically presented below:
.. ..
X–Y
Typical α-nucleophiles include hypochlo
rite, hydroperoxide anions, hydroxylamine
and its derivatives (oxymate, hydroxamate,
amidoximate ions), etc. [1, 2, 6, 9, 10, 12–15].
There are two equivalent approaches to assess
ing the magnitude of the α-effect: as the ratio of
the rate constants kα-nuc/knuc or as the difference
lg kα-nuc– lg knuc (kα-nuc к and knuc are, respectively,
rate constants characterizing the reactivity of
an α-nucleophile and a “normal” nucleophile)
at рКа
α-nuc ≈ рКа
nuc. Usually, on the Brønsted de
pendence, in reactions with electrophilic sub
strates, the points for such typical α-nucleop
hiles as ClO–and HOO– ions deviate upwards
by 2–3 logarithmic units [1, 2, 6, 9, 10, 15, 16].
In this regard, when creating reagents that ef
fectively break down ecotoxicants (mainly es
ters of phosphorus and sulfur acids), the main
efforts of researchers were focused on studying
the nature of the α-effect [1, 2, 6, 9 , 10, 12–15],
which remains one of the intriguing problems
of modern physical organic chemistry.
Numerous studies of the anomalously high
reactivity of α-nucleophiles indicate that there
is hardly a single reason for the realization of
the α-effect. At present, it is believed that α-ef
fect can be responsible for: a) destabilization of
the ground state of a nucleophile due to the re
pulsion of lone electron pairs [17], b) stabiliza
tion of the transition state [18, 19], c) unusual
thermodynamic stability of the reaction prod
ucts [20–23] and d) differentiating solvation ef
fects of the solvent [10, 24–27]. The magnitude
of the α-effect can be influenced by a number
of factors, including the nature of solvent [10,
24–28], the sensitivity of the standard series
reactivity (“normal” anionic nucleophiles) to
basicity (βnuc) [8–20, 23], type of hybridization
of the electrophilic center [16, 24, 29, 30].
As was demonstrated [10, 24–28], the role
of the solvent is extremely significant here.
Bunsel et al. [24] showed that in nucleophilic
substitution reactions involving p-nitrophenyl
acetate and related esters, the magnitude of the
α-effect strongly depends on the composition
of the solvent. The existence of the α-effect in
the gas phase was questioned from the begin
ning [25, 26], however, later works [31] made it
possible to demonstrate convincingly that the
α-effect in the gas phase nevertheless manifests
itself.
The βnuc value [18, 20–23] and the basicity of
the α-nucleophile [1, 4, 9, 10, 12, 27] also affect
the magnitude of the α-effect. The α-effect is
small or absent for reactions with low values of
βnuс [1–4, 9, 10–12, 27] or for reactions involv
ing highly basic α-nucleophiles [27, 31].
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
5https://ucj.org.ua
The type of hybridization of the electro
philic center can play a dominant role in the
magnitude of the α-effect. Thus, small (or
practically absent) α-effect usually occurs for
reactions at the sp3-hybridized carbon atom
[24, 29], while in reactions at the sp2-hybrid
ized carbon atom the reaction rate with partic
ipation of α-nucleophiles usually increases in ~
50–100 times [24]. At the same time, the mag
nitude of the α-effect is extremely high for re
actions in the sp-hybridized carbon atom. For
example, НОО– ion is (2 – 6).104 times more
reactive than, НО– anion with respect to the
sp-hybridized carbon atom of benzonitriles in
50% aqueous ethanol and water [24, 28].
The result of the study of the abnormal
ly high reactivity of α-nucleophiles was not
only the expansion of ideas about the factors
influencing the rate of reactions, but also the
discovery of a fairly wide field of practical ap
plication of these compounds as the basis of
formulations for the effective destruction of
ecotoxicants [4, 5, 7, 9, 12].
1. Inorganic α-nucleophiles – the most effec-
tive class of reagents for the decomposition of
organic phosphorus compounds (OPC)
Analysis of data on the reactivity of typical
inorganic α-nucleophiles in the processes of
degradation of acyl-containing substrates [1–7,
9, 12–14, 34–36], including esters of phospho
rus acids [4–7, 9, 12–14, 34–36], indicates that
inorganic anions – H2NO–, HOO–, ClO–, BrO–,
HCO4
–, CO4
2– – provide abnormally high reac
tion rates as compared to other supernucleo
1 The use of the k2
HOO–/k2
HO– ratio to estimate the magnitude of the α-effect is also due to the fact that, for most
substrates, there are no experimental data for standard reaction series (interaction with arylate and alcoholate ions).
philes. A special place among them belongs to
hydroperoxide anion, since it is on its basis that
highly effective “green” systems can be created
for the decomposition of ecotoxicants.
In the considered reaction series, the value
of the α-effect for the hydroperoxide ion, de
fined as the k2
HOO- / k2
HO- ratio, reaches 10 ÷ 103
times, however, it should be even higher, since
the acid ionization constant of hydrogen per
oxide (~ 11,5 – 11,6 [37]) is approximately 4
units lower than the basicity of Н2О (15.74 [38]),
and therefore the nucleophilicity of HOO– (in
the absence of the α-effect), calculated on the
basis of the Brønsted dependence, should be
102 – 103 times lower than the nucleophilici
ty of НО–. In this case, the magnitude of the
α-effect will be ~ 105 – 106 times1.
The nature of the ester’s acyl group has lit
tle effect on the α-effect magnitude of the hy
droperoxide ion. In the case of a carbonyl car
bon atom, the change in the electrophilicity of
the electron-deficient center under the influ
ence of the electronic effects of the acyl group
is satisfactorily compensated in the values of
k2
HOO- / k2
HO- ratio. For some acyl-contain
ing substrates such compensation is not ob
served, but the magnitude of the α-effect is
significantly higher. It should be noted that
for them, the change in k2
HOO- / k2
HO- ratio is
to a greater extent associated with the low
er rates of alkaline hydrolysis than would be
expected. A detailed study of nucleophilic
reactions with the participation of hydroper
oxide ion and 4-nitro- and 4-methylbenzo
ates demonstrated the important role of the
nature of the leaving group [33].With fair
ly easy leaving groups, the α-effect is clearly
ORGANIC CHEMISTRY REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
6 ISSN 2708-129X. Укр. хім. журн., 2020
manifested. With more complicatedly leaving
groups it sharply decreases, and in the case of
decomposition of 2-fluoroethyl and methyl
ethers it has a minimum value. Such a strong
dependence of the magnitude of the α-effect
on the substrate structure was interpreted by
the authors of [33] by differences in the po
sition of the transition state on the reaction
coordinate in accordance with Hammond’s
postulate (Fig. 1).
Fig. 1. The energy profile of the interaction of
α-nucleophile with substrates containing easily
(solid line) and complicatedly (dashed line) leaving
groups; Ο - speed determining the transition state
Hypohalogenated acids (HHalO) - a unique
class of reagents; depending on the acidity of
the medium, solutions of these acids contain
HHalO, hypohalogenite anion (HalO–.) or
HHalO / HalO–. In this case, hypohalogenite
ions are typical α-nucleophiles [1–7, 9, 12, 13],
and their conjugated acids are effective ox
idants. The attack of the hypochlorite ion on
the electron-deficient centers of the substrates
leads to the formation of acylhypohalogenites,
which rapidly hydrolyze to the corresponding
acids (Fig. 2).
Fig. 2. Reaction of hypochlorite ion with a num
ber of substrates
Consequently, in these reactions ClO– acts
as a nucleophilic catalyst [39]. Although the
magnitude of the α-effect is less than that for
the НОО– ion, nevertheless, taking into ac
count the difference in the basicities of hydrop
eroxide and hypochlorite ions, which reaches
~ 104 times (рКа
HClO = 7,2 ÷ 7,4 [12, 40]), hypo
chlorite ion should be classified as one of the
most effective α-nucleophiles.
2. Hydroxylamine, its N-alkyl derivatives,
oximes and hydroxamic acids
Hydroxylamine derivatives have found
wide application in various fields of chemistry,
including as cleaving agents in the destruction
of ecotoxicants and, first of all, organophos
phorus compounds [4, 10, 12, 19, 35, 43–46].
The structure of typical representatives of this
class of substances is shown in fig. 3.
Fig. 3. Hydroxylamine and its N-alkyl derivatives
Reaction coordinate
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
7https://ucj.org.ua
An important feature of hydroxylamine,
oximes and hydroxamic acids is the presence
of a fragment with adjacent O and N atoms
(–N–O–H) containing one or more lone pairs
of electrons, which determines their belonging
to the class of α-nucleophiles [4, 10, 12, 19, 35,
43–46].
In hydroxylamines (ambident nucleop
hiles), in nucleophilic substitution reactions at
electrophilic centers, both nitrogen and oxy
gen atoms can act as attacking atoms (left side
of fig. 4) [43, 44, 47].
In aqueous solutions, depending on the
acidity of the medium, hydroxylamine (like
its N-alkyl derivatives) can exist in the form of
four particles – NH2OH, +NH3O
–, NH2O
– and
+NH3OH, the first three of which are potential
nucleophilic reagents (fig. 4). Nevertheless, it
was considered generally accepted that in re
actions involving acid halides and esters of car
boxylic, phosphoric and phosphate acids, hy
droxylamine interacts with these substrates in
the neutral form [48]. However, if we proceed
from the definition of the α-effect [1, 2], the hy
droxylamine anion meets all the requirements
for α-nucleophiles: (i) a nucleophilic center is
a negatively charged atom of the second period
(an oxygen atom); (ii) there are no substituents
near the nucleophilic center that provide ster
ic obstacles to the attack on the electrophilic
center of the substrate; (iii) the nucleophile
contains a catalytically active group capable of
exerting a stabilizing effect on the transition
state of the reaction. Finally, in the hydroxy
lamine molecule there is an electronegative
nitrogen atom with a lone pair of electrons in
the α-position to the reaction center, which
can destabilize the initial state of the reagent
and stabilize the transition
state of the reaction. Indeed,
the authors of [12] were able
to demonstrate convincing
ly that the anionic form of
hydroxylamine is responsi
ble for a significant increase
in the rate of transfer of the
acyl group in alkaline media.
This point of view was fur
ther confirmed by studies of
reactions of bis (2,4-dinitro
phenyl)-phosphate [43, 44],
2,4-dinitrophenyl diethyl
phosphate with anionic forms of hydroxy
lamine, N-methylhydroxylamine and N, N-di
methylhydroxylamine, which appeared as typ
ical α-nucleophiles [35].
Even more unusual is the kinetic behavior
of the neutral form of hydroxylamine in re
actions of acyl group transfer. Points on the
corresponding graphs for NH2OH in reactions
with 4-nitrophenyl ether of diethylphosphoric
acid (NPDEP), 4-nitrophenyl ether of dieth
ylphosphonic acid (NPDEPS), 4-nitrophenyl
ether of toluene sulfonic acid (NPTS) and p-ni
tro-phenylacetate (NPA) significantly positive
ly deviate not only from the standard reaction
Fig. 4. Scheme of the reactivity of hydroxylamines
ORGANIC CHEMISTRY REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
8 ISSN 2708-129X. Укр. хім. журн., 2020
series (Δ = lg k2
NH2OH – lg k2
нукл. ≈ 9.0 (NPA),
Δ ≈ 6.0 (NPTS), Δ ≈ 6.0 (NPDEP), Δ ≈ 6.1
(NPDEPS)), but also on the Brønsted depend
ence for α-nucleophiles (Δ ≈ 3.4 (NPA), Δ ≈
1.6 (NPTS), Δ ≈ 1.6 (NPDEP) [12]. Obviously,
the neutral form of hydroxylamine exhibits an
abnormally high reactivity even among inor
ganic α-nucleophiles and reacts with the stud
ied substrates as a hypothetical α-nucleophile
with с рКа ≈ 1 – 5.
If we evaluate the value of the α-effect of the
neutral form of hydroxylamine by the ratio and
take into account that the basicity of the oxy
gen atom in NH2OH is unlikely to exceed that
for water, then the differences in basicities are
~ 16 orders of magnitude, and the α-effect for
NH2OH is one of the most important among
inorganic α-nucleophiles.
The data on the reactivity of the neutral
form of hydroxylamine indicate that the mech
anism of transfer of the acyl group on NH2OH
is fundamentally different from that for inor
ganic α-nucleophiles. However, there is still
no common point of view on the mechanism
of acylation of hydroxylamine. Based on the
analysis of kinetic isotope effects, the following
mechanism of the reaction of hydroxylamine
with NPA was proposed [47]. At the first equi
librium stage, subject to basic assistance from
the amino group of hydroxylamine, a tetrahe
dral intermediate adduct (I) is rapidly formed.
Then, at the rate of the determining stage, un
der the influence of total acidic catalysis, inter
mediate (I) slowly decomposes with the forma
tion of O-acetylhydroxylamine. The considered
mechanism of O-acylation remains controver
sial, since it cannot explain either the behavior
of N, N-dialkylhydroxylamines in this reaction,
or the existence of a single Bronsted depend
ence for the interaction of hydroxylamine and
its N-alkyl- and N, N-dialkyl derivatives with
NPA. Apparently, the transition states (II – IV)
are more preferable in comparison with (I),
and a necessary and sufficient condition for
this is the participation only of the hydrogen
atom of the OH group of hydroxylamine in the
formation of a hydrogen bond [12].
I II
III IV
The appearance in the transition states of
the anion-like form of hydroxylamine and the
presence of a general basic and general acidic
assistance should reduce the free energy bar
rier of the reaction and, therefore, ensure high
rates of transfer of the acyl group not only to
hydroxylamine, but also to its N-alkyl- and N,
N-dialkyl derivatives.
Jencks [40] proposed a different explanation
of the O-nucleophilic reactivity of the neutral
form of hydroxylamine, based on the possibil
ity of the formation of a bipolar ion NH3
+O–
(Fig. 4). Subsequently, the author considered
it unlikely that such particles in sufficient con
centrations would be generated in solution
[15]. Nevertheless, Kirby et al., based on the
formation of products corresponding to the
O-attack of electron-deficient centers (phos
phorus, carbon), crystallography data, and
quantum-chemical calculations, believe that
it is NH3
+O– form is responsible for the abnor
O
CO
N
H
OAr
H
H
O
CO
N
OAr
H
H
H
O
SO
N
OAr
O
H
H
H
O
PO
N
OAr
H
H
H
O
CO
N
H
OAr
H
H
O
CO
N
OAr
H
H
H
O
SO
N
OAr
O
H
H
H
O
PO
N
OAr
H
H
H
O
CO
N
H
OAr
H
H
O
CO
N
OAr
H
H
H
O
SO
N
OAr
O
H
H
H
O
PO
N
OAr
H
H
H
O
CO
N
H
OAr
H
H
O
CO
N
OAr
H
H
H
O
SO
N
OAr
O
H
H
H
O
PO
N
OAr
H
H
H
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
9https://ucj.org.ua
mally high nucleophilicity of hydroxylamine
in neutral media [35, 45, 46]. Nevertheless, at
the moment it is hardly possible to consider
as strictly proven the formation of NH3
+O– ––
ions in aqueous solutions and the supposed re
action mechanism.
In conclusion, it should be noted that hy
droxylamine is a unique α-nucleophile, and its
neutral and anionic forms cause high transfer
rates of the acyl group in a wide pH range, with
which none of the known α-nucleophiles can
compete.
3. Reactivity of the НОО– anion in the process-
es of acyl group transfer
The anomalously high reactivity of the
НОО– anion in the processes of acyl group
transfer is usually interpreted from the point
of view of the general acid catalysis [38, 40].
Stabilization of the V and VI transition states,
due to the formation of a hydrogen bond with
the equatorial oxygen atom of the acyl group,
will contribute to the rapid elimination of the
4-nitrophenolate ion.
V VI
The higher nucleophilicity of the НОО– ion
as compared to the CH3COO– anion in reac
tions with monoanionic forms of 4-nitrophenyl
sulfate k2
HOО- / k2
CH3COO-
≈ 30) [34] and 4-nitro
phenylmethyl phosphate (k2
HOО- / k2
CH3COO-
≈ 50)
[50], as well as with triacetylethylenediamine
(k2
HOО- / k2
CH3COO-)≈ 20) [51] is consistent with the
presence of a hydrogen bond in the transition
states of types I and II. However, in reactions
with aryl esters of carboxylic acids, the impor
tance of such an interaction is apparently small,
since the nucleophilicities of the ions НОО– and
CH3COO– differ only by a factor of ~ 3. There
fore, the presence or absence of general acid ca
talysis is hardly the only factor controlling the
supernucleophilic properties of the НОО– ion.
Indeed, НОО– ion reacts anomalously quickly
with alkyl halides [2, 6, 38], although this type
of catalysis does not play a significant role in the
reactions of alkyl group transfer. It is also unlike
ly that the high rates of acid-catalyzed addition
of the НОО– ion to aldehydes are a consequence
of the formation of an intramolecular hydrogen
bond in these processes [52]. It is possible that an
important role in the reactivity of the НОО– ion
is played by the stability of the reaction products
and the transition state, i.e. the nucleophilicity
of the НОО– ion is largely controlled by ther
modynamic factors. Apparently, the possibility
of implementing intramolecular acid catalysis
and the relatively high thermodynamic stabili
ty of the transition states are responsible for the
observed α-effect of the НОО– ion in the trans
fer of the acyl group.
The manifestation of the α-effect in the reac
tions of hypohalogenite ions with acyl-contain
ing substrates can be explained by the formation
of a transition state at the rate of the determin
ing stage, in which there is an interaction of the
oxygen of the acyl group with unoccupied d-or
bitals of the hypohalogenite ion (VII) [38, 40].
In fact, hypohalogenite ions, being Lewis acids,
can provide the same assistance in acyl transfer
reactions as Brønsted acids. Nevertheless, as in
the case of the hydroperox
ide anion, this factor is hard
ly the only one that provides
the α-effect of hypohalogen
ite ions. VII
ORGANIC CHEMISTRY REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
10 ISSN 2708-129X. Укр. хім. журн., 2020
Fig. 5. Brønsted dependences for the reaction of α-nucleophiles (●) and arylate ions (▲) with 4-nitro
phenyl acetate (a); 4-nitrophenyl diethyl phosphonate (b); 4-nitrophenyl diethyl phosphate (c); 4-nitro
phenyl tosylate (d) [12]; 2,4-dinitrophenyl diethyl phosphate (e) [35]2
2 Attention is drawn to the behavior of the fluorine anion, which, exhibiting an abnormally high affinity for the
electron-deficient phosphorus atom, behaves in nucleophilic substitution reactions like an α-nucleophile. One of the
possible explanations for this phenomenon is the successful overlap of the orbitals and the high electron-negativity
of fluorine, which makes it possible to form a “one and a half ” F P bond.
в
а
д
б
г
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
11https://ucj.org.ua
4. Reactivity of oximate ions
The particular interest that has been shown
for many years to the study of the nucleophilic
reactivity of oxymate ions (Ох–) is primari
ly due to the fact that it is among this class of
α-nucleophiles that effective antidotes have
been found – acetylcholinesterase reactivators
[10, 53–60], the search for and design of which
continues intensively at the present time. There
is no doubt that this property of oximate ions
is associated with their anomalously high re
activity, and therefore the establishment of the
factors controlling the α-effect of Ox– anions is
a rather urgent problem.
Extrathermodynamic analysis of the oxi
mate ions behavior in the transfer reactions of
aryl sulfonyl, acetyl, phosphoryl and other acyl
groups [10, 24, 61, 62] indicates that the sol
vation effects of water play an important role
here. Indeed, the reactivity of typical α-nu
cleophiles – oximate ions cannot be described
within the framework of a unified Brønsted
equation, and the existence of nonlinear Brøn
sted dependences (Fig. 6) for the transfer of
acyl groups is a consequence of energetically
unfavorable effects of solvent [10, 24, 61, 62].
Analysis of the Brønsted dependences for
reactions of oximate ions and standard reac
tion series (arylate and alcoholate ions) [10,
24, 61, 62] makes it possible to establish reg
ularities in the nature of the change in the k2
and α-effect values at varying the structure of
the oxime. First, Ох– ions in acyl group trans
fer reactions act as typical α-nucleophiles,
and the magnitude of the α-effect, defined as
the Ox
2k
−
/ ArO (RO )
2k
− −
ratio at
-Ox
apK ≈
-ArO (RO )
apK
−
,
significantly depends on the oxime structure.
As the acidity of the oxime decreases (≤ 9.0),
the α-effect, within the reaction series, persists
at ~ 102 - 103 times. Although a further increase
in the oxime basicity (≥ 9.0) leads to a slight
increase in the k2
Ox–values, the value of the
α-effect begins to decrease in this case (Fig. 6).
And, finally, oxymate ions with
-Ox
apK ≥ 12.0 in
terms of reactivity no longer exceed high-ba
sic alcoholate ions ( Ox
2k
−
/ RO
2k
−
≈ 1.0), i.e. the
α effect disappears. Moreover, they form one
Brønsted dependence with highly basic alcoho
late ions, i.e. for all substrates, regardless of the
nature of the electrophilic center, the limiting
reactivity of Ox– ions in water is comparable
to that for highly basic alcoholate ions [63, 64].
Particularly noteworthy is the effect of “leve
ling” the reactivity of Ox- ions, noted already
-Ox
apK ≥ 9.0, leading to a decrease in the value of
the α-effect with an increase in the basicity of
the oxime and, finally, to its disappearance (at
-Ox
apK ≥ 12.0 ). Secondly, for processes with the
participation of Ox- ions, an extremely early
break in the Brønsted dependence is observed,
which occurs at рKа ≈ 8.0 - 9.0, while for ar
ylate and alcoholate ions it occurs in the region
of рKа ≈ 12.5 - 13.0 [6
The curvature of the Brønsted dependence
for the reactions of anionic nucleophiles -
arylate, alcoholate, oximate ions, etc. [10, 24,
61–67] with substrates containing electron-de
ficient centers of carbon, sulfur and phospho
rus, can be associated not only with the ener
getically unfavorable solvation effects of the
solvent, the contribution of which becomes
more and more significant as the basicity of the
nucleophile increases [63, 65–67], but also with
a change in the structure of the transition state.
Nevertheless, it is unlikely that for the reaction
series under consideration, with an increase in
the basicity of Ox– ions, such a strong change
in the structure of the transition state occurs.
So, for example, for the reactions of NPA,
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12 ISSN 2708-129X. Укр. хім. журн., 2020
0
0,5
1
1,5
2
2,5
5 7 9 11 13 15
lg k2
pKa
а
0,6
1
1,4
1,8
7,5 8 8,5 9 9,5 10
lg k2
рКа
б
-1,4
-0,6
0,2
1
1,8
6 8 10 12 14 16
lg k2
рКа
в
-4,5
-3,5
-2,5
-1,5
6 8 10 12 14 16
lg k2
рКа
г
-6
-5
-4
-3
-2
-1
0
5 7 9 11 13 15 17
lg k2
рКа
д
-4
-3
-2
-1
0
5 7 9 11 13 15
lg k2
рКа
е
Fig. 6. Brønsted dependences for the reaction of oximate- (●) and arylate-(alcoholate-) ions (▲) with
4-nitrophenyl acetate (a), diisopropyl fluorophosphate (b), 2,4-dinitrophenyltosylate (c), 4-nitrophenyl
tosylate (d), 4-nitrophenyl diethyl phosphate (e), 4-nitrophenyl diethyl phosphonate (f) [61, 62].
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
13https://ucj.org.ua
DNPTS, NPTS, NPDEP and NPDEPS with
oximate ions, regardless of the nature of the
electron-deficient center of the substrate and
the leaving group, the sensitivity of the reac
tivity of a series of α-nucleophiles (in this case
oximes) to basicity (βN) varies from 0.5 – 0.6
(
-Ox
apK ≤ 9.0) tо 0.1 – 0.2 (
-Ox
apK ≥ 9.0), despite
the fact that the maximum difference in reac
tivity when passing from NPA to NPDEP is ~
105 times. In addition, a break in the correla
tion dependences occurs at рKа ≈ 8.0 - 9.0, and
its position is practically independent of the
structure and reactivity of the substrate. This
once again confirms that the nonlinear Brøn
sted dependences for reactions with Ох- ions
reflect rather the differences in the nature of
the solvation states of low-basic and high-basic
oximate ions in water, as it is interpreted for
the reactions of the transfer of the acyl group
to arylate and alcoholate ions [63–66], as well
as to neutral and anionic nitrogen-containing
reagents [67].
5. Inorganic α-nucleophiles – the basis of
formulations for the degradation of neurotoxins,
vesicants and organophosphorus pesticides
Inorganic α-nucleop
hiles – HOO– and ClO–
ions, exhibiting anom
alously high reactivity,
are of interest as the
basis of formulations for
the decomposition of
ecotoxicants. For quite
understandable reasons,
detailed studies of the
mechanism of reactions with the participation
of α-nucleophiles and the design of recipes
based on them have been carried out for chem
ical warfare agents [68–71].
In an alkaline medium, organic substances,
such as sarin (GB), are rapidly destroyed due
to the nucleophilic attack of the hydroperoxide
ion on the phosphorus atom with the forma
tion of peroxy acids, which quickly decompose
to the corresponding phosphonic acid (Fig. 7)
[5, 69–71].
Fig. 7. Scheme of GB degassing in an alkaline
medium by hydroperoxide ion
In this case, the reaction rate is ~ 50 times
higher than the rate of alkaline hydrolysis [32].
VX peroxyhydrolysis proceeds according to
the scheme in Fig. 8, with the formation of eth
ylmethylphosphonic acid. N-oxide of VX is an
other reaction product, which later, in a slower
stage, undergoes a nucleophilic attack with the
formation of an acid. In this case, the released
thiol undergoes oxidation to sulfonate [5].
O
P
F
O
O
P
O-
O
O
P
OO-
O+ HOO-
- F-
+ HO-
- O2
- F-
O
P
S
N
O
O
P
O-
O
-O3S
N
O
P
S
N
O
O
HOO-
H2O2
HOO-
O
P
F
O
O
P
O-
O
O
P
OO-
O+ HOO-
- F-
+ HO-
- O2
- F-
O
P
S
N
O
O
P
O-
O
-O3S
N
O
P
S
N
O
O
HOO-
H2O2
HOO-
Fig. 8. Scheme of VX degassing with peroxyhydroxide ion
ORGANIC CHEMISTRY REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
14 ISSN 2708-129X. Укр. хім. журн., 2020
The reaction of VX with НОО– anion pro
ceeds approximately 40 times faster than with
the more basic НО– ion ((τ1/2 = 45 s, 230С,
[HOO–] = 0.1 М), which allows to carry out ef
fectively the destruction of VX in alkaline me
dium by the nucleophilic mechanism. In neu
tral and acidic media, concentrated solutions of
hydrogen peroxide, exhibiting oxidizing prop
erties under these conditions, oxidize mustard
gas and V-gases. Since p a
H OK 2 2= 11.5 – 11.6,
then to ensure the decomposition of ecotox
icants by both the nucleophilic and oxidative
mechanisms, the pH of the medium will be of
great importance (and the optimal conditions
for carrying out these reactions are different),
and, therefore, hydrogen peroxide is hardly can
be considered a universal degassing substance.
Nevertheless, intensive studies of the reactivity
of hydrogen peroxide and its activators (car
bonates, molybdates, phthalates, etc.) have led
to the creation of universal formulations of the
nucleophilic-oxidative mechanism of action,
which are quite effective in relation to the main
types of organic substances [72, 73 ]. Thus,
the activation of Н2О2 by sodium bicarbonate
leads to the appearance in the reaction mix
ture in weakly alkaline media of НСО4
– anion,
which is a more powerful oxidizing agent than
Н2О2, and this makes it possible to destroy tox
ical agents not only of the GB and VX type, but
also HD (Fig. 9).
Fig. 9. Scheme of HD degassing using НСО4– anion
The use of potassium molybdate as an acti
vator of hydrogen peroxide in microemulsions
of the oil/water type makes it possible to de
sign universal systems for the destruction of
ecotoxicants of various nature [73]. The ad
vantage of this system is that the oxidation of
HD mainly leads to the formation of sulfoxide
(HDO) rather than the highly toxic sulfone
(HDO2) [73].
Chloric acid salts are widely used in the
decomposition of ecotoxicants [5]. Hypochlo
rites are universal degassing substances and
are used to detoxify human skin, equipment,
and territory [5]. In reactions of nucleophilic
substitution at the tetracoordinated atom
of phosphorus, the ClO- ion acts as a true
nucleophilic catalyst and decomposes the
GB type of subtanses to phosphonic acids
(Fig. 10).
Fig. 10. Scheme of GB degassing using hypo
chlorite anion
The high oxidative activity of hypochlorous
acid plays an important role in the degassing
of mustard gas, which in alkaline media un
dergoes destruction with the formation of a
number of oxidation and elimination products
(Fig. 11). It should be emphasized that at the
first stage of this rather complex process, sul
foxide is formed, which is subsequently con
verted into other products.
Cl
S
Cl
O
Cl
S
Cl
H2O2H2O
HCO4
-HCO3
-
O
P
F
O
O
P
O-
O
O
P
OCl
O+ ClO-
- F-
+ HO-
- ClO-
- F-
+ HO-
Cl
S
Cl
O
Cl
S
Cl
H2O2H2O
HCO4
-HCO3
-
O
P
F
O
O
P
O-
O
O
P
OCl
O+ ClO-
- F-
+ HO-
- ClO-
- F-
+ HO-
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
15https://ucj.org.ua
Hypochlorite solutions can also be used
for degassing of VX, especially in the low pH
range (Fig. 12). In this case, for the destruction
of 1 mole of VX, only 3 moles of “active” chlo
rine are consumed. For the oxidation of 1 mole
of VX in alkaline media, more than 10 moles of
“active” chlorine are required.
Despite the fact that hypochlorites are pro
duced on a large scale and are relatively inex
pensive, they, as degassing substances, have a
number of significant disadvantages: 1) low
stability during storage; 2) strong corrosive
action on the surface during storage and use;
3) relatively high toxicity, etc. Softer agents
for degassing of organic matter are N–Cl de
rivatives of ammonia, amines, amides, ureas,
hydantoins, urethanes, etc. [5], the so-called
chloramines, which can be considered as de
rivatives of perchloric acid amide (HClO and
R(R’) N–Cl). However, these compounds are
not devoid of certain disadvantages: 1) lack of
universality of action; 2) weaker action at low
temperatures; 3) high consumption of solvents
for non-water-soluble reagents, etc.
A brief analysis of data on the use of in
organic α-nucleophiles as the basis of for
mulations for the breakdown of ecotoxicants
allows us to draw an important conclusion:
the use of “green” systems hydrogen per
oxide - activator for the destruction of toxic
substrates on an industrial scale and treat
ment of surfaces of considerable area is un
doubtedly more preferable than systems con
taining “active” chlorine, since the former are
not toxic, are not corrosive and do not pose
a threat to the environment. As for minimiz
ing the consequences of emergency situations
and terrorist acts associated with the spill of
toxic agents, the most expedient is the use of
systems based on “active” halogen. These have
an extremely successful combination of oxi
dizing and nucleophilic properties, allowing
their use not only for the destruction of sub
strates of various chemical natures, but also
for the destruction of dangerous biological
objects (pathogenic bacteria and viruses), i.e.
using the same system to solve the problems
of chemical and biological protection.
O
P
S
N
O
O
P
O-
O
-O3S
N3 HOCl
3 Cl-
O
P
S
N
O
O
P
O-
O
-O3S
N3 HOCl
3 Cl-
Fig. 11. Scheme of mustard gas degassing using hypochlorite anion
Fig. 12. VX degassing scheme using hypochlorite anion
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16 ISSN 2708-129X. Укр. хім. журн., 2020
6. Design of inhibited acetylcholinesterase re
activators based on hydroxylamine derivatives
The fact that some phosphate esters have
insecticidal properties (found at the begin
ning of the twentieth century) opened up
broad prospects for the use of this class of
compounds and a
number of their ana
logs in agriculture to
control insect pests
[75, 76]. The high
toxicity in relation to
mammals, which was
discovered somewhat
later for many of
these substances, not
only made it necessary to take a more careful
approach to the selection of compounds rec
ommended for practical use, but also made it
possible to create a new generation of chem
ical weapons - neuroparalytic chemical war
fare agents [77, 78].
A detailed study of the nature of the biolog
ical activity of organophosphorus substances
of this group showed that all of them are in
hibitors of acetylcholinesterase (AChE), an en
zyme that plays a key role in the transmission
of neuronal signalings [75–78]. Inactivation of
AChE by these compounds occurs due to acy
lation of the HO-group of serine in the active
center of the enzyme [77, 78].
When searching for antidotes for these
acetylcholinesterase inhibitors, oxymates, as
well as hydroxylamines and hydroxamates,
have become of paramount importance, since
under mild conditions they can remove the
acetyl group from the active center of the en
zyme and thereby restore its activity [10, 55,
77, 78].
Modeling the process of oxime-induced re
activation inhibited by the organophosphorus
compound AChE using the Density Function
al Theory (DFT) approach [10, 54] showed
that of the two possible reactivation pathways
(A and B) shown in Fig. 13, preference should
be given to a two-stage mechanism (B):
It is important to note that the calculation
of the potential energy surface indicates that
the reactivation process proceeds easily, with
low energy barriers both in the gas phase and
in an aqueous solution [54]. This is consistent
with the results of the experimental study of
oximates as reactivators in the treatment of the
aftermath of poisoning with organophospho
rus neurotoxins [10].
The structures of the most commonly used
antidotes VIII - XXV, including pyridini
um aldoximes [10, 55, 61, 77–79], are given
below. It should be especially noted that for
X - XVI, the presence of a quaternized pyrid
inium fragment gives an advantage in solu
bility, and also reduces the pKa of the oxime,
which leads to a higher reactivity of such
antidotes under milder conditions (at low
pH values).
P
O
CH3O O-Ser-E
CH3
H2C=NO-
Фосф орилированный
ф ермент
P
O
CH3O
O-Ser-E
CH3
H2C=NO P
O
H2C=NO OCH3
CH3
+ E-Ser-O-
Фосф орилированный
оксим
Реактивированный
ф ермент
P
O
CH3O
O-Ser-E
CH3
H2C=NO P
O
CH3O
O-Ser-E
CH3
H2C=NOP
O-
CH3O
O-Ser-E
CH3
H2C=NO
A
B
Fig. 13. Scheme of the reactivation process of
acetylcholinesterase inhibited by organophospho
rus compound.
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
17https://ucj.org.ua
A similar series of reactivators of inhibited
AChE, which has some advantage over pyrid
inium derivatives, contains a diazolyl ring
XXVI - XXIX [80].
The literature contains data on the reactivi
ty of oximates with respect to various organo
phosphorus compounds, such as phosphinates,
phosphonates, phosphates and their thioan
alogues (4-nitrophenyl diphenylphosphinate
(NPDPP), bis-nitrophenyl methylphosphonate
(BNPMP), 4-nitrophenyl phosphonate NPP),
fenitrothion, etc.). [53–62, 80–88].
NPDPP
BNPMP
NPP
Fenitrothion
O NO2PPh
Ph
O
O2N O P
O
CH3
O NO2
OP
O
OH
OH
NO2
OP
S
NO2MeO
OMe
CH3
Fig. 14. Structures of the most commonly used antidotes VIII – XXV.
ORGANIC CHEMISTRY REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
18 ISSN 2708-129X. Укр. хім. журн., 2020
At the moment, the reactivators of inhibited
AChE (in combination with anticholinergics)
recommended for use make it possible to neu
tralize the effect of at least two lethal doses of
neuro paralytic agent [77–79]. Compounds VIII
- XXV and a number of their structural analogs
eliminate the symptoms of acute poisoning,
however, the level of their activity does not al
low us to consider the problem of searching for
new, more efficient reactivators as solved [55, 56,
61, 77]. Experiments carried out on animals and
humans have shown that in a number of cases
using VIII - XXV it is not enough to restore the
required level of enzyme activity, and this leads
to the development of undesirable consequenc
es in the coming months after poisoning [77,
89–93]. That is why the problem of searching
for new AChE reactivators remains in the center
of attention and, undoubtedly, the works aimed
at solving it are urgent [53 - 61; 92; 93].
7. Ways of structural modification of α-nu-
cleophiles and systems based on them
The fulfillment of the Brønsted dependenc
es for the reactions of inorganic α-nucleophiles
with electron-deficient substrates (eq. 1–6) [12]
indicates that the basicity of the α-nucleop
hile can serve as a characteristic on the basis
of which it is possible to predict the reactivity
new α-nucleophilic reagents
lg k2
NPA = – 2.2 + 0.5 pKа (1)
lg k2
NPTS = – 5.5 + 0.45 pKа (2)
lg k2
NPDMC = – 7.2 + 0.46 pKа (3)
lg k2
NPDEP = – 4.4 + 0.28 pKа (4)
lg k2
NPDEP = – 2.9 + 0.25 pKа (5)
lg k2
DNEP = – 6.1 + 0.41 pKа (6)
Another important conclusion following
from the analysis of the Brønsted dependences:
the NH2O
– anion is the most powerful accep
tor of the acyl group in the series of α-nucleop
hiles. Since
-
2NH O
apK ≈ 13.8 [12], it is difficult to
imagine the structure of α-nucleophile, which
in water has a basicity comparable to or high
er than the hydroxylamine anion. Therefore,
based on the basicity of the NH2O
– anion, it is
possible to postulate the value of the limiting
reactivity of inorganic α-nucleophiles in each
reaction series. Nevertheless, this fact does not
mean that the design of new α-nucleophiles or
their structural modification is not an urgent
problem. The focus of researchers is on the de
signing nucleophilic or universal systems that
are not only highly efficient in the decomposi
tion of ecotoxicants, but also have sufficient sta
bility during storage, are safe for storage, do not
pose a threat to the environment and etc. The
main ways to solve this problem are as follows:
1. Search for new activators of hydrogen
peroxide. The use of H2O2 activators, leading
to the generation of new nucleophilic and ox
idizing particles in the reaction system, allows
fast and irreversible splitting of eco-toxicants
of various chemical nature under milder con
ditions.
2. Creation of new sources of “active” hal
ogen. It seems promising in this direction to
obtain organocomplexes of tribromide ion [4],
the use of which should ensure overcoming a
number of disadvantages inherent in existing
systems based on “active” chlorine [5].
3. Obtaining low-basic oximes. As discussed
above, understanding the reaction mechanism
with the participation of oximate ions and the
patterns in their reactivity change makes it
possible to explain the nonlinear form of the
Brønsted dependence.
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
19https://ucj.org.ua
The Brønsted dependences for the reactions
of oximate and arylate ions with organophos
phorus organic substances - sarin, soman, and
diisopropyl fluorophosphate - have a charact
feristic feature: the reactivity of oximate ions
at
-Ox
apK ≥ 8.5 is straightening [61]. The same
kind of dependences was established earli
er for other acyl-containing substrates [12].
Obviously, the observed “saturation” effect, in
the case of organophosphorus poisonous sub
stances, is of great practical importance since
the detoxification process will be effective both
when using highly basic and relatively weakly
basic oximate ions. This factor determines the
ways of scientifically grounded modification of
the structure of oximes.
РЕАКЦІЙНА ЗДАТНІСТЬ НУКЛЕОФІЛІВ
І α-ЕФЕКТ У ПРОЦЕСАХ ЗАМІЩЕННЯ
В ЕЛЕКТРОНОДЕФІЦИТНИХ ЦЕНТРАХ
А. Ф. Попов1, I. В. Капiтанов1,3,
Г. О. Сердюк1,3, О. Є. Шумейко1,2*
1Інститут фізико-органічної хімії і вуг
лехімії ім. Л. М. Литвиненка НАН України;
вул. Харківське шосе 50, Київ 02160, Україна
2Інститут органічної хімії НАН України;
вул. Мурманська 5, Київ 02660, Україна
3Центр передового досвіду в галузі зе
леної хімії Європейського дослідницького
простору, відділення хімії та біотехнології,
факультет наук, Талліннський технічний
університет, Академія, 15, Таллінн, 12618,
Естонія
* E-mail: ashumeiko@ukr.net
В огляді проаналізовано питання, пов’я
зані з реактивністю нуклеофілів та проявом
α-ефекту в процесах заміщення в електро
недефіцитних центрах. Обговорено фун
даментальні аспекти цього явища, а також
можливості та перспективи використання
α-нуклеофілів у системах для високоефек
тивної деградації субстратів- екотоксикан
тів різної природи. У першій частині огляду
було розглянуто такі аспекти: неорганічні
α-нуклеофіли як найефективніший клас ре
агентів для розкладання органічних сполук
фосфору, гідроксиламіну, його N-алкіль
них похідних, оксимів та гідроксамових
кислот, реактивність НОО-аніона в проце
сах перенесення ацильної групи, реакцій
ної здатності оксиматних іонів, неорганіч
них α-нуклеофілів як основи рецептур для
деградації нейротоксинів, везикантів та ор
ганофосфорних пестицидів, проектуван
ня інгібіторних реактиваторів ацетилхо
лінестерази на основі похідних гідрокси
ламіну, способів структурної модифікації
α-нуклеофіли та системи на їхній основі.
Проаналізовано дані про реакційну здат
ність типових неорганічних α-нуклеофілів
при розщепленні ацилвмісних субстратів,
включаючи складні ефіри фосфорної кис
лоти, які забезпечують аномально високі
швидкості реакції порівняно з іншими над
нуклеофілами. Розглянуто різні типи таких
α-нуклеофілів, особливості їхньої структу
ри та реакційної здатності. Було показано,
що важливою особливістю гідроксиламіну,
оксимів та гідроксамових кислот є наяв
ність фрагмента з сусідніми атомами O та
N (–N - O - H), що містять одну чи більше
парних електронних пар, що визначає їхню
належність до класу α-нуклеофілів. Показа
но, що за прояв α-ефекту та його величини
ORGANIC CHEMISTRY REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
20 ISSN 2708-129X. Укр. хім. журн., 2020
може бути відповідальною низка факторів,
головний з яких дестабілізується основним
станом нуклеофіла за рахунок відштовху
вання самотніх пар електронів, стабілізації
перехідного стану, незвичайної термодина
мічної стійкості продуктів реакції, сольва
таційних ефектів розчинника, типу гібри
дизації електрофільного центру тощо.
Ключові слова: функціоналізовані ПАР,
α-нуклеофіли, міцелярні системи, гідро
ксиламін, оксими, амідоксими, гідроксамо
ві кислоти, пероксиди,
РЕАКЦИОННАЯ СПОСОБНОСТЬ
НУКЛЕОФИЛОВ И α-ЭФФЕКТ
В ПРОЦЕССАХ ЗАМЕЩЕНИЯ
У ЭЛЕКТРОНОДЕФИЦИТНЫХ
ЦЕНТРОВ
А. Ф. Попов1, И. В. Капитанов1,3,
А. А. Сердюк1,3, А. Е. Шумейко1,2
*
1 Институт физико-органической химии
и углехимии им. Л. М. Литвиненко НАН
Украины; ул. Харьковское шоссе 50, Киев
02160, Украина
2 Институт органической химии НАН
Украины; ул. Мурманская 5, Киев 02660,
Украина
3 Центр передового опыта в области зе
леной химии Европейского исследовате
льского пространства, Отделение химии
и биотехнологии, факультет наук, Таллин
нский технический университет, Акаде
мия, 15, Таллинн, 12618, Эстония
*E-mail: ashumeiko@ukr.net
В обзоре проанализированы вопросы,
связанные с реакционной способностью
нуклеофилов и проявлением α-эффекта
в процессах замещения у электронодефи
цитных центров. Обсуждены фундамен
тальные аспекты этого явления, а также
возможности и перспективы использова
ния α-нуклеофилов в системах для высоко
эффективного расщепления субстратов-э
котоксикантов различной природы.
Ключевые слова: функционализирован
ные ПАВ, α-нуклеофилы, мицеллярные си
стемы, гидроксиламин, оксимы, амидокси
мы, гидроксамовые кислоты, пероксиды.
ЛИТЕРАТУРА
1. John O., Edwards R., Pearson G. The Fac
tors Determining Nucleophilic Reactivities //
J. Am. Chem. Soc. – 1962. – 84, № 1. – P. 16–24.
2. Nick J., John O. Edwards R. The Alpha Effect.
Review // International J. Chem. kinetics. –
1973. – 5. – P. 1–26.
3. Попов А., Савелова В. Современные подходы
к конструированию высокоэффективных
нуклеофильных систем // Теорет. и
эксперим. химия. – 1999. – 35, № 1. –С. 1–16.
4. Popov A. Design of green microorganized sys
tems for decontamination of ecotoxicants //
Pure Appl. Chem. –2008. – 80, № 7. – P. 1381–
1397.
5. Decontamination of Chemical Warfare Agents /
Yu-Chu Y., James A., Baker J. Ward R. // Chem.
Rev. – 1992. – 92, № 8. – P. 1729–1743.
6. Греков А., Веселов В. α-Эффект в химии
органических соединений // Успехи
химии. – 1978. – 47, №.7. – С.1200–1230.
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
21https://ucj.org.ua
7. Décontamination chimique. I. Déphosphoryl
ation des composés organophosphorés / Séguès
B., Pérez E., Rico-Lattes I., Rivière M., Lattes A. //
Bull. Soc. Chim. Fr. –1996. – 133. – P. 925–937.
8. Применение организованных молекуляр
ных систем для химического разложения
боевых отравляющих веществ / А. Латт,
И. Рико-Латт, Є. Перез, В. Крутиков, Б. Ама
да // Журн. Рос. хим. об-ва им. Д. И. Менде
леева. – 2007. – 51, № 6. – С. 36–43.
9. Реакционная способность неорганических
α-нуклеофилов в процессах переноса фос
форильной и фосфонильной групп / А. По
пов, Т. Прокопьева, И. Супрун, Ю. Сима
ненко // Теорет. и эксперим. химия. – 2000. –
36, № 4. – С. 226–232.
10. Rappoport E., Liebmann J. The chemistry of
Hydroxylamines, Oximes and Hydroxamic Ac
ids. – England: John Wiley & Sons Ltd., 2009.
11. Morales-Rojas H., Moss R. Phosphorolytic Re
activity of o-Iodosylcarboxylates and Related
Nucleophiles // Chem. Rev. – 2002. – 102. –
P. 2497–2591.
12. Неоганические анионные кислородсодержа
щие α-нуклеофилы – эффективные акцепто
ры ацильной группы. Гидроксиламин – «ли
дер» в ряду α-нуклеофилов / Ю. Симаненко,
А. Попов, Т. Прокопьева, Е. Карпичев, В. Са
велова, И. Супрун, К. Бантон // Журн. орган.
химии. – 2002. – 38,№ 9. – С. 1341–1353.
13. The Reactivity of Some Active Nucleophilic
Reagents with Organophosphorus Anticho
linesterases / Green A., Sainsbury G., Saville B.,
Stansfield M. // J. Chem. Soc. –1958. – № 4. –
P. 1583–1587.
14. Kirby A., Younas M. The Reactivity of Phos
phate Esters. Reactions of Diesters with Nu
cleophiles // J. Chem. Soc. (B). –1970. – № 6. –
P. 1165–1172.
15. Jencks W., Gilchrist M. Nonlinear Struc
ture-Reactivity Correlations. The Reactivity of
Nucleophilic Reagents toward Esters // J. Am.
Chem. Soc. –1968. – 90, № 10. – P. 2622–2637.
16. The α-Effect in Benzyl Transfers from Benzyl
phenylmethyl Sulfonium Salts to N-Methylb
enzohydroxamate Anions / Fountain K.,
Tady D., Paul T., Golynskiy M., // J. Org.
Chem. – 1999. – 64, № 18. – P. 6547–6553.
17. Khairat M., John O., Edwards R. The Mech
anism of the Oxidation of Some Aromatic
Amines by Peroxyacetic Acid // J. Am. Chem.
Soc. –1962. – 84, № 5. – P. 763–768.
18. Buncel E., Wilson H., Chuaqui C. Reactivi
ty-selectivity correlations. 4. The α-effect in SN2
reactions at sp3 carbon. The reactions of hydro
gen peroxide anion with methyl phenyl sul
fates // J. Am. Chem. Soc. –1982. –104, № 18. –
P. 4896–4900.
19. Hoz S., Buncel E. Pitfalls in the determination
of the α-effect by a two-point analysis. The ef
fect of solvent on the α-effect // Tetrahedron
Lett. –1984. – 25, № 32. – P. 3411–3414.
20. Dixon J., Bruice T. Kinetic and thermodynamic
nature of the α-effect for amine nucleophiles // J.
Am. Chem. Soc. –1972. – 94, № 6. – P. 2052–2056.
21. Palling D., Jencks W. Nucleophilic reactivity
toward acetyl chloride in water // J. Am. Chem.
Soc. – 1984. – 106, № 17. – P. 4869–4876.
22. Jeffrey J., Page M. Buffer catalysis in the hydraz
inolysis of benzylpenicillin // J. Chem. Soc.,
Perkin Trans. 2. – 1980. – P. 220–224.
23. Kinetics of the Reactions of β-Methoxy-α-ni
trostilbene with Methoxyamine and N-Meth
ylmethoxyamine. Direct Observation of the
Intermediate in Nucleophilic Vinylic Substi
tution / Bernasconi C., Leyes A., Eventova I.,
Rappoport Z. // J. Am. Chem. Soc. – 1995. –
117, № 6. – P. 1703–1711.
24. Buncel E., Ik-Hwan Um. The α-effect and its
modulation by solvent // Tetrahedron Lett. –
2004. – 60, № 36. – P. 7801–7825.
25. Absence of an α-effect in the gas-phase nu
cleophilic reactions of hydroperoxide ion /
DePuy С., Della E., Filley J., Grabowski J., Bi
erbaum V. // J. Am. Chem. Soc. – 1983. – 105,
№ 8. – P. 2481–2482.
ORGANIC CHEMISTRY REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
22 ISSN 2708-129X. Укр. хім. журн., 2020
26. Theoretical studies of SN2 transition states, the
alpha effect / Saul W., Mitchel D., Schlegel B.,
Minot C., Eisenstein O. // Tetrahedron Lett. –
1982. – 23, № 6. – P. 615–618.
27. The α-Effect in SNAr Substitutions – Reaction
between Oximate Nucleophiles and 2,4-Dini
trofluorobenzene in Aqueous Solution / Mout
iers G., Guével E., Cannes C., Terrier F., Bun
cel E. // Europ. J. Org. Chem. – 2001. – № 17. –
P. 3279–3284.
28. The α-Effect in Reactions of sp-Hybridized Car
bon Atom: Michael-Type Reactions of 1-Aryl-
2-propyn-1-ones with Primary Amines / Ik-
Hwan Um, Eun-Ju Lee, Jin-Ah Seok, Kyung-
Hee Kim // J. Org. Chem. – 2005. – 70, № 19. –
P. 7530–7536.
29. The α-Effect in Methyl Transfers from
S-Methyldibenzothiophenium Fluoroborate
to Substituted N-Methylbenzohydroxamates /
Fountain K., Felkerson C., Driskell J., Lamp
B. // J. Org. Chem. – 2003. – 68, № 5. – P. 1810–
1814.
30. Patterson E., Fountain K. On Gas Phase α-Ef
fects. 1. The Gas-Phase Manifestation and Po
tential SET Character // J. Org. Chem. – 2006. –
71, № 21. – P. 8121–8125.
31. Aubort J., Hudson R. The α-effect of hydroxam
ic acids // J. Chem. Soc. D: Chem. Commun. –
1970. – № 15. – P. 938–939.
32. Effect of modification of the electrophilic center
on the α-effect / Ik-Hwan Um, Ji-Youn Lee,
Sun-Young Bae, Buncel E. // Can. J. Chem. –
2005. – 83. – P. 1365–1371.
33. Predominant role of basicity of leaving group
in α-effect for nucleophilic ester cleavage / No
mura Y., Kubozono T., Hidaka M., Horibe M.,
Mizushima N., Yamamoto N., Takahashi T.,
Romiyama M. // Bioorg. Chem. – 2004. – 32. –
P. 26–37.
34. Micellar effects of surfactants in cleavage of
4-nitrophenyl diethylphosphonate by hydrop
eroxide anion / Solomoichenko T., Sadovskii Y.,
Prokop’eva T., Karpichev V., Kapitanov I., Pis
kunova Zh., Savelova V., Popov A. // Theoret.
and Experim. Chem. –2006. – 42, №. 6. –
P. 364–370.
35. Peroxyhydrolysis of 4-nitrophenyl diethyl
phosphate in micellar systems based on imida
zolium gemini surfactants / Sadovskii Y., Solo
moichenko T., Turovskaya M., Kapitanov I.,
Piskunova Zh., Kostrikin M., Prokop’eva T.,
Popov A. // Theoret. and Experim. Chem. –
2012. – 48, № 2. – P. 122–128.
36. Reactivity of inorganic α-nucleophiles in acyl
group transfer processes in water and sufactant
micelles: I. Systems based on organic complexes
of tribromide anion / Turovskaya M., Mikhailov
V., Burakov N., Kapitanov I., Zubareva T., Lo
bachev V., Pan chenko B., Prokop’eva T. // Russ.
J. Org. Chem. – 2017. – 53, № 3. – P. 351–358.
37. Альберт Л., Сержент Е. Константы иониза
ции кислот и оснований. – М.: Химия, 1964.
38. Дженкс В. Катализ в химии и энзимоло
гии. – М.: Мир, 1972.
39. The Chlorine-catalyzed Hydrolysis of Isopropyl
Methylphosphonofluoride (Sarin) in Aqueous
Solution / Epstein J., Baver V., Saxe M., Demek
M. // J. Am. Chem. Soc. – 1956. – 78, № 8. –
P. 4068–4071.
40. Jencks W., Carriuolo J. Reactivity of Nucleop
hilic Reagents toward Esters // J. Am. Chem.
Soc. –1960. – 82, № 7–8. – P. 1778–1786.
41. The Oxibase Scale and Displacement Reac
tions. XVII. The Reaction of Nucleophiles with
Ethyl Tosylate and the Extension of the Oxi
base Skale / Davis R., Nehring R., Blume W.,
Chuang C. // J. Am. Chem. Soc. –1969. – 91,
№ 1. – P. 91–96.
42. Dixon E., Bruice C. α-Effect. IV. Additional
Observation on the α-Effect Employing Mala
chite Green as Substrate // J. Am. Chem. Soc. –
1971. – 93, № 24. – P. 6592–6597.
43. Mechanisms of Nucleophilic Substitution Re
actions of Methylated Hydroxylamines with
Bis(2,4-dinitrophenyl) phosphate. Mass Spec
trometric Identification of Key Intermediates /
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
23https://ucj.org.ua
Domingos J., Longhinotti E., Brandão T., Bun
ton C., Santos L., Eberlin M., Nome F. // J. Org.
Chem. – 2004. – 69, № 18. – P. 6024–6033.
44. Reactivity of N-alkyl derivatives of hydroxy
lamine in decomposition of 4-nitrophenyl di
ethylphosphonate in water and in cetyltrimeth
ylammonium bromide micelles / Zubareva T.,
Prokop’eva T., Kapitanov I., Belousova I., Ra
zumova N., Popov A. // Theoret. and Experim.
Chem. – 2007. – 43, №. 4. – P. 247–254.
45. Characteristic features of the change in reactiv
ity of supernucleophilic functional surfactants
in acyl group transfer processes / Prokop’eva
T., Karpichev E., Belousova I., Turovskaya M.,
Shumeiko A., Kostrykin M., Razumova N., Ka
pitanov I. Popov A. // Theoreret. and Experim.
Chem. – 2010. – 46, №. 2. – P. 94–101.
46. From α-nucleophiles to functionalized aggre
gates: exploring the reactivity of hydroxamate
ion towards esterolytic reactions in micelles /
Singh S., Karpichev Y., Sharma R., Sahu A., Sat
nami M., Ghosh K. // Org. Biomol. Chem. –
2015. – 13. – P. 2827–2848.
47. Hess R., Hengge A., Cleland W. Kinetic Isotope
Effects for Acyl Transfer from p-Nitrophenyl
Acetate to Hydroxylamine Show a pH-De
pendent Change in Mechanism // J. Am. Chem.
Soc. – 1997. – 119, № 30. – P. 6980–6983.
48. Брюс Т., Бенкович С. Механизмы биоорга
нических реакций. – М.: Мир, 1970. – 96 с.
49. Kirby A., Jencks W. The Reactivity of Nucleo
philic Reagents toward the p-Nitrophenyl
Phosphate Dianion // J. Am. Chem. Soc. –
1965. – 87, № 14. – P. 3209–3217.
50. Reactions of Phosphate Acid Esters with Nu
cleophiles. II. Survey of Nucleophiles React
ing with p-Nitrophenyl Methyl Phosphonate
Anion / Behrmann E., Biallas M., Brass H., Ed
wards J., Isaaks M. // J. Org. Chem. – 1970. –
35, № 9. – P. 3069–3070.
51. Davies D., Deary M. A convenient preparation
of aqueous methyl hydroperoxide and a com
parison of its reactivity towards triacetyleth
ylenediamine with that of other nucleophiles:
the mechanism of peroxide bleach activation //
J. Chem. Soc., Perkin Trans 2. – 1992. – № 4. –
P. 559–562.
52. Sander E., Jencks W. General acid and base ca
talysis of the reversible addition of hydrogen
peroxide to aldehydes // J. Am. Chem. Soc. –
1968. –90, № 16. –P. 4377 – 4386.
53. Cholinesterase Reactivation in Vivo with a Novel
Bis-Oxime Optimized by Computer-Aided De
sign / Hammond P., Kern C., Hong F., Kollme
yer T., Pang Y., Brimijoin S. // J. Pharmacol. Ex
perim. Therap. – 2003. – 307, № 1. – P. 190–196.
54. Oxime-Induced Reactivation of Sarin-Inhibi
ted AchE: A Theoretical Mechanisms Study /
Wang J, Gu J., Leszczynski J., Feliks M., Sokal
ski W. // J. Phys. Chem. B. – 2007. – 111, № 9. –
P. 2404–2408.
55. Progress in Synthesis of New Acetylcho
linesterase Reactivators During the Period
1990–2004 / Musilek K., Kuca K., Jun D.,
Dolezal M. // Current Org. Chem. – 2007. – 11,
№ 2. – P. 229–238.
56. The Development of New Structural Analogues
of Oximes for the Antidotal Treatment of Poi
soning by Nerve Agents and the Comparison
of Their Reactivating and Therapeutic Effica
cy with Currently Available Oximes / Kassa J.,
Kuca K., Bartosova L., Kunesova G. // Current
Org. Chem. – 2007. – 11, № 2. – P. 267–283.
57. Monooxime reactivators of acetylcholinester
ase with (E)-but-2-ene linker – Preparation and
reactivation of tabun- and paraoxon-inhibited
acetylcholinesterase / Musilek K., Holas O., Jun
G., Dohnal V., Gunn-Moore F., Opletalova V.,
Dolezal M., Kuca K. // Bioorg. Med. Chem. –
2007. – 15, № 21. – P. 6733–6741.
58. New oxime reactivators connected with
CH2O(CH2)n OCH2 linker and their reactiva
tion potency for organophosphorus agents-in
hibited acetylcholinesterase / Yang G., Oh
K., Park N., Jung Y. // Bioorg. Med. Chem. –
2007. – 15, № 24. – P. 7704–7710.
ORGANIC CHEMISTRY REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
24 ISSN 2708-129X. Укр. хім. журн., 2020
59. Monoquaternary pyridinium salts with mod
ified side chain–synthesis and evaluation
on model of tabun- and paraoxon-inhibited
acetylcholinesterase / Musilek K., Kucera J.,
Jun D., Dohnal V., Opletalova V., Kuca K. //
Bioorg. Med. Chem. – 2008. – 16, № 17. – P.
8218–8223.
60. Design of a Potent Reactivator of Tabun-Inhib
ited Acetylcholinesterase-Synthesis and Evalu
ation of (E)-1-(4-Carbamoylpyridinium)-4-(4-
hydroxyiminomethylpyridinium)-but-2-ene
Dibromide (K203) / Musilek K., Jun D., Cabal
J., Kassa J., Gunn-Moore F., Kuca K. // J. Med.
Chem. – 2007. – 50, № 22. – P. 5514–5518.
61. Revisiting the reactivity of oximate α-nucleo
philes with electrophilic phosphorus centers.
Relevance to detoxification of sarin, soman and
DFP under mild conditions / Terrier F., Rodri
guez-Dafonte P., Guével E., Moutiers G. // Org.
Biomol. Chem. – 2006. – 4, № 23. – P. 4352–
4363.
62. Нуклеофильное замещение у тетракоорди
нированного атома серы VI. Реакционная
способность оксимат-ионов / Прокопьева
Т., Симаненко Ю., Супрун И., Савелова В.,
Зубарева Т., Карпичев Е. // Журн. орган. хи
мии. – 2001. – 37, № 5. – С. 694–704.
63. Reactivity of functional detergents with a
pyridine ring and an α-nucleophile fragment
in the head group / Belousova I., Kapitanov
I., Shumeiko A., Mikhailov V., Razumova N.,
Prokop’eva T., Popov A. // Theoret. and Exper
im. Chem. – 2008. – 44, № 5. – P. 292–299.
64. Supernucleophilic systems based on function
alized surfactants in the decomposition of 4-ni
trophenyl esters derived from phosphorus and
sulfur acids: I. Reactivity of a hydroxyimino
derivative of gemini imidazolium surfactant /
Kapitanov I., Belousova I., Shumeiko A., Kost
rikin M., Prokop’eva T., Popov A. // Russ. J.
Org. Chem. – 49, № 9. P. 1291–1299.
65. Nonlinear Bronsted Correlations: The Roles
of Resonance, Solvation and Changing Tran
sion-State Structure / Jencks W., Brant S.,
Gandler J., Fendrich G., Nakamura C. // J. Am.
Chem. Soc. – 1982. – 104, № 25. – P. 7045–
7051.
66. Нуклеофильное замещение у тетракоорди
национного атома серы. III. Реакционная
способность анионных кислородсодержа
щих нуклеофилов – арилат – и алкоголят-
ионов / Симаненко Ю., Прокопьева Т., Са
велова В., Закаличная О., Белоусова И., По
пов А., Саккулин Г. // Реакц. способн. орган.
соедин. – 1989. – 26, №.1. – С. 30–54.
67. Нуклеофильное замещение у тетракоорди
нированного атома серы. IV. Реакционная
способность анионных азотсодержащих
нуклеофилов / Савелова В., Карпичев Е.,
Симаненко Ю., Прокопьева Т., Лобачев Л.,
Белоусова И. // Журн. орган. химии. –
1996. – 32, № 4. – С. 551–560.
68. Chemical Warfare Agent Degradation and De
contamination / Talmage S., Watson A., Haus
child V., Munro N., King J. // Current Org.
Chem. – 2007. – 11, № 3. – P. 285–298.
69. Decontamination of VX, GD, and HD on a
Surface Using Modified Vaporized Hydrogen
Peroxide / Wagner G., Sorrick D., Procell L.,
Brickhouse M., Mcvey I., Schwartz L. // Lang
muir. – 2007. – 23, № 3. – P. 1178–1186.
70. Destruction of Chemical Warfare Agents VX
and Soman by α-Nucleophiles as Oxidizing
Agents / Cassgne Т., Cristau H., Delmas G.,
Desgranges M., Lion G., Magnaud G., Tor
reilles T., Virieux D. // Heteroatom Chem. –
2001. – 12, № 6. – P. 485–490.
71. Wagner G., Yu-Chu Yang. Rapid Nucleophilic/
Oxidative Decontamination of Chemical War
fare Agents // Ind. Eng. Chem. Res. – 2002. –
41, № 8. – P. 1925–1928.
72. Пат. US 006245957 B1. Universal Decontami
nating Solution for Chemical Warfare Agents /
Wagner G., Yu-Chu Yang. – Опубл. 2001.
73. Пат. US 006723891 B1. Molybdate/Peroxide
Microemulsions useful for Decontamination
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
25https://ucj.org.ua
of Chemical Warfare Agents / Wagner G, Pro
cell L., Yu-Chu Yang and other. –Опубл. 2004.
74. Aubry J., Bouttemy S. Preparative Oxidation of
Organic Compounds in Microemulsions with
Singlet Oxygen Generated Chemically by the
Sodium Molybdate / Hydrogen Peroxide Sys
tem // J. Am. Chem. Soc. –1997. – 119, № 23. –
P. 5286–5294.
75. Acetylcholinesterase reactivators based on
oxime-functionalized biodegradable ionic liq
uids / Karpichev E., Kapitanov I., Gathergood
N., Soukup O., Hepnarova V., Jun D., Kuča K. //
Military Medical Science Letters. – 2018. – 87,
№ 1. – P. 87.
76. Marrs T., Ballantyne B. Pesticide Toxicology
and International Regulation. – England: John
Wiley & Sons, Ltd., 2004.
77. Marrs T., Maynard R., Sidell F. Chemical War
fare Agents: Toxicology and Treatment. – Eng
land: John Wiley & Sons Ltd., 2007.
78. Франке З. Химия отравляющих веществ. –
М.: Химия, 1973.
79. Машковский М. Лекарственные средства. –
М.: Медицина, 1998.
80. Nonquaternary cholinesterase reactivators. 2.
α-Heteroaromatic aldoximes and thiohydrox
imates as reactivators of ethyl methylphos
phonyl-acetylcholinesterase in vitro / Kenley
R., Bedford C., Dailey O. Howd J., Miller A. //
J. Med. Chem. – 1984. – 27, № 9. – P. 1201–
1211.
81. Tarkka R., Buncel E. Origin of the Bell-Shaped
α-Effect-Solvent Composition Plots. pKa-Sol
vent Dependence of the α-Effect at a Phospho
rus Center // J. Am. Chem. Soc. –1995. – 117,
№ 5. – P. 1503–1507.
82. The levelling effect of solvational imbalances
in the reactions of oximate –nucleophiles with
electrophilic phosphorus centers. Relevance
to detoxification of organophosphorus esters /
Terrier F., Guével E., Chatrousse A., Mouti
ers G., Buncel E. // Chem. Commun. – 2003.
№ 5. – P. 600–601.
83. Degorre F., Kiffer D., Terrier F. Sulfur deriva
tives of 2-oxopropanal oxime as reactivators of
organophosphateinhibied acetylcholinester
ase in vitro: synthesis and structure-reactivity
relationships // J. Med. Chem. – 1988. – 31,
№ 4. – P. 757–763.
84. Green A., Saville B. The reaction of oximes with
isopropyl methylphosphono-fluoridate (Sa
rin) // J. Chem. Soc. – 1956. – P. 3887–3892.
85. Degradation of the pesticide fenitrothion as
mediated by cationic surfactants and α-nu
cleophilic reagents / Han X., Balakrishnan V.,
Loon G., Buncel E. // Langmuir. – 2006. – 22,
№. 21 – P. 9009–9017.
86. Han X., Balakrishnan V., Buncel E. Alkaline
Degradation of the Organophosphorus Pes
ticide Fenitrothion as Mediated by Cationic
C12, C14, C16, and C18 Surfactants // Langmuir. –
2007. – 23, № 12. – P. 6519–6525.
87. Acceleration of Nucleophilic Attack on an
Organophosphorothioate Neurotoxin, Feni
trothion, by Reactive Counterion Cationic
Micelles. Regioselectivity as a Probe of Sub
strate Orientation within the Micelle / Balakr
ishnan М., Han X., Loon G., Dust J., Toullec J.,
Buncel E. // Langmuir. – 2004. – 20, № 16. –
P. 6586–6593.
88. Mechanisms of abiotic degradation and soil–
water interactions of pesticides and other hy
drophobic organic compounds. Part 3. Nu
cleophilic displacement at the phosphorrus
centre of the pesticide fenitrothion [O, O-di
methyl O-(3-methyl-4-nitrophenyl) phospho
rothioate] by oxygen nucleophiles in aqueous
solution: α-effect and mechanism / Omakor J.,
Onyido I., Loon G., Buncel E. // J. Chem. Soc.,
Perkin Trans. 2. – 2001. – № 3. – P. 324–330.
89. Sidell F., Groff W. The Reactivatibility of Cho
linesterase Inhibited by VX and Sarin in Man //
Toxicol. Appl. Pharmacol. –1974. – 27. –
P. 241–252.
90. Toxicity of Parathion, Systox, Octamethyl Py
rophosphoramide, and Methyl Parathion in
ORGANIC CHEMISTRY REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
26 ISSN 2708-129X. Укр. хім. журн., 2020
Man / Rider J., Moeller H., Puletti E., Swa
der J. // Toxicol. Appl. Pharmacol. – 1969. –
14. – P. 603–611.
91. Grossblatt N. Possible Long-Term Health
Effects of Short-Term Exposure to Chemi
cal Agents. –Washington: National Academy
Press. – 1982. 1. – 296 p. – 1984. – 2. – 330 c.
92. Analysis of inhibition, reactivation and aging
kinetics of highly toxic organophosphorus
compounds with human and pig acetylcho
linesterase / Aurbek N., Thiermann H., Szinicz
L., Eyer P., Worek V. // Toxicology. – 2006. –
224, № 1–2. – P. 91–99.
93. Reiner E., Simeon-Rudolf V. Pyridinium, im
idazolium and quinuclidinium compounds:
toxicity and antidotal effects against the nerve
agents tabun and soman // Arh. Hig. Rada Tox
icol. – 2006. – 57. – P. 171–179.
REFERENCES
1. John O., Edwards R., Pearson G. The Factors
Determining Nucleophilic Reactivities. J. Am.
Chem. Soc. 1962. 84 (1): 16.
2. Nick J., John O. Edwards R. The Alpha Effect.
Review. International J. Chem. kinetics. 1973.
5: 1.
3. Popov A., Savelova V. Modern approaches to
the design of highly efficient nucleophilic sys
tems. Theoret. and Experim. Chem. 1999. 35
(1): 1.
4. Popov A. Design of green microorganized sys
tems for decontamination of ecotoxicants. Pure
Appl. Chem. 2008. 80 (7): 1381.
5. Yu-Chu Y., James A., Baker J. Ward R. Decon
tamination of Chemical Warfare Agents. Chem.
Rev. 1992. 92 (8): 1729.
6. Grekov A., Veselov V. α-Effect in the chemis
try of organic compounds. Advances in Chem.
1978. 47 (7): 1200.
7. Séguès B., Pérez E., Rico-Lattes I., Rivière M.,
Lattes A. Décontamination chimique. I. Dé
phosphorylation des composés organophos
phorés. Bull. Soc. Chim. Fr. 1996. 133: 925.
8. Latt A., Rico-Latt I., Perez E., Krutikov V., Am
ada B. The use of organized molecular systems
for the chemical decomposition of chemical
warfare agents. J. Russ. Chem. Society to them
D. Mendeleev. 2007. 51 (6): 36.
9. Popov A., Prokopieva T., Suprun I., Simanen
ko Y. The reactivity of inorganic nucleophiles
in the transfer of phosphoryl and phosphonyl
groups. Theoret. and Experim. Chem. 2000.
36 (4): 226.
10. Rappoport E., Liebmann J. The chemistry of
Hydroxylamines, Oximes and Hydroxamic Ac
ids. (England: John Wiley & Sons Ltd., 2009).
11. Morales-Rojas H., Moss R. Phosphorolytic Re
activity of o-Iodosylcarboxylates and Related
Nucleophiles. Chem. Rev. 2002. 102: 2497.
12. Simanenko Y., Popov A., Prokopyeva T., Kar
pichev E., Savelova V., Suprun I., Banton K.
Neo-organic anionic oxygen-containing nu
cleophiles are effective acceptors of the acyl
group. Hydroxylamine – the «leader» in the
series of α-nucleophiles. Russ. J. Org. Chem.
2002. 38 (9): 1341.
13. Green A., Sainsbury G., Saville B., Stansfield M.
The Reactivity of Some Active Nucleophilic Re
agents with Organophosphorus Anticholinest
erases. J. Chem. Soc. 1958. (4): 1583.
14. Kirby A., Younas M. The Reactivity of Phos
phate Esters. Reactions of Diesters with Nu
cleophiles. J. Chem. Soc. (B). 1970. (6): 1165.
15. Jencks W., Gilchrist M. Nonlinear Struc
ture-Reactivity Correlations. The Reactivity of
Nucleophilic Reagents toward Esters. J. Am.
Chem. Soc. 1968. 90 (10): 2622.
16. Fountain K., Tady D., Paul T., Golynskiy M.
The α-Effect in Benzyl Transfers from Benzyl
phenylmethyl Sulfonium Salts to N-Methylb
enzohydroxamate Anions. J. Org. Chem. 1999.
64 (18): 6547.
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
27https://ucj.org.ua
17. Khairat M., John O., Edwards R. The Mech
anism of the Oxidation of Some Aromatic
Amines by Peroxyacetic Acid. J. Am. Chem.
Soc. 1962. 84 (5): 763.
18. Buncel E., Wilson H., Chuaqui C. Reactivi
ty-selectivity correlations. 4. The α-effect in
SN2 reactions at sp3 carbon. The reactions of
hydrogen peroxide anion with methyl phenyl
sulfates. J. Am. Chem. Soc. 1982. 104 (18): 4896.
19. Hoz S., Buncel E. Pitfalls in the determination
of the α-effect by a two-point analysis. The ef
fect of solvent on the α-effect. Tetrahedron Lett.
1984. 25 (32): 3411.
20. Dixon J., Bruice T. Kinetic and thermodynamic
nature of the α-effect for amine nucleophiles.
J. Am. Chem. Soc. 1972. 94 (6): 2052.
21. Palling D., Jencks W. Nucleophilic reactivity to
ward acetyl chloride in water. J. Am. Chem. Soc.
1984. 106 (17): 4869.
22. Jeffrey J., Page M. Buffer catalysis in the hydraz
inolysis of benzylpenicillin. J. Chem. Soc., Per-
kin Trans. 2. 1980. 220.
23. Bernasconi C., Leyes A., Eventova I., Rap
poport Z. Kinetics of the Reactions of β-Meth
oxy-α-nitrostilbene with Methoxyamine and
N-Methylmethoxyamine. Direct Observation
of the Intermediate in Nucleophilic Vinylic
Substitution. J. Am. Chem. Soc. 1995. 117 (6):
1703 .
24. Buncel E., Ik-Hwan Um. The α-effect and its
modulation by solvent. Tetrahedron Lett. 2004.
60 (36): 7801.
25. DePuy С., Della E., Filley J., Grabowski J., Bi
erbaum V. Absence of an α-effect in the gas-
phase nucleophilic reactions of hydroperoxide
ion. J. Am. Chem. Soc. 1983. 105 (8): 2481.
26. Saul W., Mitchel D., Schlegel B., Minot C.,
Eisenstein O. Theoretical studies of SN2 tran
sition states, the alpha effect. Tetrahedron Lett.
1982. 23 (6): 615.
27. Moutiers G., Guével E., Cannes C., Terrier F.,
Buncel E. The α-Effect in SNAr Substitutions –
Reaction between Oximate Nucleophiles and
2,4-Dinitrofluorobenzene in Aqueous Solu
tion. Europ. J. Org. Chem. 2001. (17): 3279.
28. Ik-Hwan Um, Eun-Ju Lee, Jin-Ah Seok, Kyung-
Hee Kim. The α-Effect in Reactions of sp-Hy
bridized Carbon Atom: Michael-Type Reac
tions of 1-Aryl-2-propyn-1-ones with Primary
Amines. J. Org. Chem. 2005. 70 (19): 7530.
29. Fountain K., Felkerson C., Driskell J., Lamp B.
The α-Effect in Methyl Transfers from S-Me
thyldibenzothiophenium Fluoroborate to Sub
stituted N-Methylbenzohydroxamates. J. Org.
Chem. 2003. 68 (5): 1810.
30. Patterson E., Fountain K. On Gas Phase α-Ef
fects. 1. The Gas-Phase Manifestation and
Potential SET Character. J. Org. Chem. 2006.
71 (21): 8121.
31. Aubort J., Hudson R. The α-effect of hydroxam
ic acids. J. Chem. Soc. D: Chem. Commun. 1970.
(15): 938.
32. Ik-Hwan Um, Ji-Youn Lee, Sun-Young Bae,
Buncel E. Effect of modification of the elec
trophilic center on the α-effect. Can. J. Chem.
2005. 83: 1365.
33. Nomura Y., Kubozono T., Hidaka M., Horibe
M., Mizushima N., Yamamoto N., Takahashi
T., Romiyama M. Predominant role of basicity
of leaving group in α-effect for nucleophilic es
ter cleavage. Bioorg. Chem. 2004. 32: 26.
34. Solomoichenko T., Sadovskii Y., Prokop’eva T.,
Karpichev Y., Kapitanov I., Piskunova Zh.,
Savelova V., Popov A. Micellar effects of sur
factants in cleavage of 4-nitrophenyl dieth
ylphosphonate by hydroperoxide anion. Theo-
ret. and Experim. Chem. 206. 42 (6): 364.
35. Sadovskii Y., Solomoichenko T., Turovskaya
M., Kapitanov I., Piskunova Zh., Kostrikin
M., Prokop’eva T., Popov A. Peroxyhydrolysis
of 4-nitrophenyl diethylphosphate in micellar
systems based on imidazolium gemini sur
factants. Theoret. and Experim. Chem. 2012.
48 (2): 122.
36. Turovskaya M., Mikhailov V., Burakov N., Kapi
tanov I., Zubareva T., Lobachev V., Panchenko B.,
ORGANIC CHEMISTRY REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
28 ISSN 2708-129X. Укр. хім. журн., 2020
Prokop’eva T. Reactivity of inorganic α-nucleo
philes in acylgroup transfer processes in water
and surfactant micelles: I. Systems based on
organic complexes of tribromide anion. Russ.
J. Org. Chem. 2017. 53 (3): 351.
37. Albert L., Sergeant E. Ionization constants of
acids and bases. (M.: Khimiya, 1964). [in Rus
sian].
38. Jenks W. Catalysis in chemistry and enzymolo
gy.. (М.: Мir, 1972). [in Russian].
39. Epstein J., Baver V., Saxe M., Demek M. The
Chlorine-catalyzed Hydrolysis of Isopropyl
Methylphosphonofluoride (Sarin) in Aqueous
Solution. J. Am. Chem. Soc. 1956. 78 (8): 4068.
40. Jencks W., Carriuolo J. Reactivity of Nucleop
hilic Reagents toward Esters. J. Am. Chem. Soc.
1960. 82 (7-8): 1778.
41. Davis R., Nehring R., Blume W., Chuang C. The
Oxibase Scale and Displacement Reactions.
XVII. The Reaction of Nucleophiles with Ethyl
Tosylate and the Extension of the Oxibase
Skale. J. Am. Chem. Soc. 1969. 91(1): 91.
42. Dixon E., Bruice C. α-Effect. IV. Additional
Observation on the α-Effect Employing Mal
achite Green as Substrate. J. Am. Chem. Soc.
1971. 93 (24): 6592.
43. Domingos J., Longhinotti E., Brandão T.,
Bunton C., Santos L., Eberlin M., Nome F.
Mechanisms of Nucleophilic Substitution Re
actions of Methylated Hydroxylamines with
Bis(2,4-dinitrophenyl) phosphate. Mass Spec
trometric Identification of Key Intermediates.
J. Org. Chem. 2004. 69 (18): 6024.
44. Zubareva T., Prokop’eva T., Kapitanov I., Bel
ousova I., Razumova N., Popov A. Reactivity
of N-alkyl derivatives of hydroxylamine in de
composition of 4-nitrophenyl diethylphospho
nate in water and in cetyltrimethylammonium
bromide micelles. Theoret. and Experim. Chem.
2007. 43 (4): 247.
45. Prokop’eva T., Karpichev E., Belousova I.,
Turovskaya M., Shumeiko A.,Kostrykin M.,
Razumova N., Kapitanov I. Popov A. Char
acteristic features of the change in reactivity
of supernucleophilic functional surfactants in
acyl group transfer proceses. Theoret. Theoret.
and Experim. Chem. 2010. 46 (2): 94.
46. Singh S., Karpichev Y., Sharma R., Sahu A.,
Satnami M., Ghosh K. From α-nucleophiles
to functionalized aggregates: exploring the re
activity of hydroxamate ion towards esterolyt
ic reactions in micelles. Org. Biomol. Chem.
2015. 13: 2827.
47. Hess R., Hengge A., Cleland W. Kinetic Isotope
Effects for Acyl Transfer from p-Nitrophenyl
Acetate to Hydroxylamine Show a pH-De
pendent Change in Mechanism. J. Am. Chem.
Soc. 1997. 119 (30): 6980.
48. Bruce T., Benkovich S. Mechanisms of bioor
ganic reactions. (М.: Mir, 1970). [in Russian].
49. Kirby A., Jencks W. The Reactivity of Nucleop
hilic Reagents toward the p-Nitrophenyl Phos
phate Dianion. J. Am. Chem. Soc. 1965. 87 (14):
3209.
50. Behrmann E., Biallas M., Brass H., Edwards J.,
Isaaks M. Reactions of Phosphate Acid Esters
with Nucleophiles. II. Survey of Nucleophiles
Reacting with p-Nitrophenyl Methyl Phospho
nate Anion. J. Org. Chem. 1970. 35 (9): 3069.
51. Davies D., Deary M. A convenient preparation
of aqueous methyl hydroperoxide and a com
parison of its reactivity towards triacetyleth
ylenediamine with that of other nucleophiles:
the mechanism of peroxide bleach activation.
J. Chem. Soc., Perkin Trans 2. 1992. (4): 559.
52. Sander E., Jencks W. General acid and base ca
talysis of the reversible addition of hydrogen
peroxide to aldehydes. J. Am. Chem. Soc. 1968.
90 (16): 4377.
53. Hammond P., Kern C., Hong F., Kollmeyer T.,
Pang Y., Brimijoin S. Cholinesterase Reacti
vation in Vivo with a Novel Bis-Oxime Opti
mized by Computer-Aided Design. J. Pharma-
col. Experim. Therap. 2003. 307 (1): 190.
54. Wang J, Gu J., Leszczynski J., Feliks M., Sokal
ski W. Oxime-Induced Reactivation of Sarin-
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
29https://ucj.org.ua
Inhibited AchE: A Theoretical Mechanisms
Study. J. Phys. Chem. B. 2007. 111 (9): 2404.
55. Musilek K., Kuca K., Jun D., Dolezal M. Pro
gress in Synthesis of New Acetylcholinesterase
Reactivators During the Period 1990-2004.
Current Org. Chem. 2007. 11 (2): 229.
56. Kassa J., Kuca K., Bartosova L., Kunesova G.
The Development of New Structural Analogues
of Oximes for the Antidotal Treatment of Poi
soning by Nerve Agents and the Comparison
of Their Reactivating and Therapeutic Efficacy
with Currently Available Oximes. Current Org.
Chem. 2007. 11 (2): 267.
57. Musilek K., Holas O., Jun G., Dohnal V., Gunn-
Moore F., Opletalova V., Dolezal M., Kuca K.
Monooxime reactivators of acetylcholinest
erase with (E)-but-2-ene linker – Preparation
and reactivation of tabun- and paraoxon-in
hibited acetylcholinesterase. Bioorg. Med.
Chem. 2007.15 (21): 6733.
58. Yang G., Oh K., Park N., Jung Y. New oxime
reactivators connected with CH2O(CH2)n
OCH2 linker and their reactivation potency
for organophosphorus agents-inhibited ace
tylcholinesterase. Bioorg. Med. Chem. 2007.
15 (24): 7704.
59. Musilek K., Kucera J., Jun D., Dohnal V., Oplet
alova V., Kuca K. Monoquaternary pyridinium
salts with modified side chain-synthesis and
evaluation on model of tabun- and paraox
on-inhibited acetylcholinesterase. Bioorg. Med.
Chem. 2008. 16 (17). 8218.
60. Musilek K., Jun D., Cabal J., Kassa J., Gunn-
Moore F., Kuca K. Design of a Potent Reacti
vator of Tabun-Inhibited Acetylcholinester
ase-Synthesis and Evaluation of (E)-1-(4-Car
bamoylpyridinium)-4-(4-hydroxyiminometh
ylpyridinium)-but-2-ene-dibromide (K203).
J. Med. Chem. 2007. 50 (22): 5514.
61. Terrier F., Rodriguez-Dafonte P., Guével E.,
Moutiers G. Revisiting the reactivity of oximate
α-nucleophiles with electrophilic phosphorus
centers. Relevance to detoxification of sarin,
soman and DFP under mild conditions. Org.
Biomol. Chem.2006. 4 (23): 4352.
62. Prokopyeva T., Simanenko Yu., Suprun I.,
Savelova V., Zubareva T., Karpichev E. Nu
cleophilic substitution at the tetracoordinated
sulfur atom VI. The reactivity of oximeate ions.
Russ. J. Org. Chem. 2001. 37 (5): 694.
63. Belousova I., Kapitanov I., Shumeiko A.,
Mikhailov V., Razumova N., Prokop’eva T.,
Popov A. Reactivity of functional detergents
with a pyridine ring and an α-nucleophile frag
ment in the head group. Theoret. and Experim.
Chem. 2008. 44 (5): 292.
64. Kapitanov I., Belousova I., Shumeiko A., Ko
strikin M., Prokop’eva T., Popov A. Supernu
cleophilic systems based on functionalized
surfactants in the decompositi on of hydrox
yimino derivative of gemini imidazolium sur
factant. Russ. J. Org. Chem. 2013. 49 (9): 1291.
65. Jencks W., Brant S., Gandler J., Fendrich G., Na
kamura C. Nonlinear Bronsted Correlations:
The Roles of Resonance, Solvation and Chang
ing Transion-State Structure. J. Am. Chem. Soc.
1982. 104 (25): 7045.
66. Simanenko Yu., Prokopyeva T., Savelova V.,
Zakalichnaya O., Belousova I., Popov A., Sak
kulin G. Nucleophilic substitution at the tetra
coordinating sulfur atom. III. Reactivity of an
ionic oxygen-containing nucleophiles – arylate
and alcoholate ions. Reakt. capable organ. con-
nection. 1989. 26 (1): 30.
67. Savelova V., Karpichev E., Simanenko Yu.,
Prokopyeva T., Lobachev L., Belousova I. Nu
cleophilic substitution at a tetracoordinated
sulfur atom. IV. The reactivity of anionic ni
trogen-containing nucleophiles. Russ. J. Org.
Chem. 1996. 32 (4): 551.
68. Talmage S., Watson A., Hauschild V., Mun
ro N., King J. Chemical Warfare Agent Deg
radation and Decontamination. Current Org.
Chem. 2007. 11 (3): 285.
69. Wagner G., Sorrick D., Procell L., Brickhouse M.,
Mcvey I., Schwartz L. Decontamination of VX,
ORGANIC CHEMISTRY REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS (Part 1)
30 ISSN 2708-129X. Укр. хім. журн., 2020
GD, and HD on a Surface Using Modified Va
porized Hydrogen Peroxide. Langmuir. 2007.
23 (3): 1178.
70. Cassgne Т., Cristau H., Delmas G., Desgranges
M., Lion G., Magnaud G., Torreilles T., Virieux
D. Destruction of Chemical Warfare Agents
VX and Soman by α-Nucleophiles as Oxidizing
Agents. Heteroatom Chem. – 2001. – 12, № 6. –
P. 485–490.
71. Wagner G., Yu-Chu Yang. Rapid Nucleophilic/
Oxidative Decontamination of Chemical War
fare Agents. Ind. Eng. Chem. Res. 2002. 41 (8).
1925.
72. Patent US 006245957 B1. Wagner G., Yu-Chu
Yang. Universal Decontaminating Solution for
Chemical Warfare Agents. 2001.
73. Patent US 006723891 B1. Wagner G, Procell L.,
Yu-Chu Yang and other. Molybdate/Peroxide
Microemulsions useful for Decontamination
of Chemical Warfare Agents. 2004.
74. Aubry J., Bouttemy S. Preparative Oxidation of
Organic Compounds in Microemulsions with
Singlet Oxygen Generated Chemically by the
Sodium Molybdate / Hydrogen Peroxide Sys
tem. J. Am. Chem. Soc. 1997. 119 (23): 5286.
75. Karpichev E., Kapitanov I., Gathergood N.,
Soukup O., Hepnarova V., Jun D., Kusa A.,
Acetylcholinesterase reactivators based on
oxime-functionalized biodegradable ionic liq
uids. Military Medical Science Letters. 2018.
87 (1): 87.
76. Marrs T., Ballantyne B. Pesticide Toxicology
and International Regulation. (England: John
Wiley & Sons Ltd., 2004).
77. Marrs T., Maynard R., Sidell F. Chemical War
fare Agents: Toxicology and Treatment. (Eng
land: John Wiley & Sons Ltd., 2007).
78. Franke Z. Chemistry of toxic substances. REF
ERENCES REFERENCES – М.: Khimiya,
1973). [in Russian].
79. Mashkovsky M. Drugs. – М.: Medicine, 1998.
[in Russian].
80. Kenley R., Bedford C., Dailey O. Howd J.,
Miller A. Nonquaternary cholinesterase reac
tivators. 2. α-Heteroaromatic aldoximes and
thiohydroximates as reactivators of ethyl meth
ylphosphonyl-acetylcholinesterase in vitro.
J. Med. Chem. 1984. 27 (9): 1201.
81. Tarkka R., Buncel E. Origin of the Bell-Shaped
α-Effect-Solvent Composition Plots. pKa-Sol
vent Dependence of the α-Effect at a Phospho
rus Center. J. Am. Chem. Soc. 1995. 117 (5):
1503.
82. Terrier F., Guével E., Chatrousse A., Mouti
ers G., Buncel E. The levelling effect of solva
tional imbalances in the reactions of oximate
–nucleophiles with electrophilic phosphorus
centers. Relevance to detoxification of organo
phosphorus esters. Chem. Commun. 2003. (5):
600.
83. Degorre F. Degorre F., Kiffer D., Terrier F. Sul
fur derivatives of 2-oxopropanal oxime as re
activators of organophosphate-inhibited ace
tylcholinesterase in vitro: synthesis and struc
ture-reactivity relationships. J. Med. Chem.
1988. 31 (4): 757.
84. Green A., Saville B. The reaction of oximes with
isopropyl methylphosphono-fluoridate (Sarin).
J. Chem. Soc. 1956. 3887.
85. Han X., Balakrishnan V., Loon G., Buncel E.
Degradation of the pesticide fenitrothion as
mediated by cationic surfactants and α-nu
cleophilic reagents. Langmuir. 2006. 22 (21):
9009.
86. Han X., Balakrishnan V., Buncel E. Alkaline
Degradation of the Organophosphorus Pesti
cide Fenitrothion as Mediated by Cationic C12,
C14, C16, and C18 Surfactants. Langmuir. 2007.
23 (12): 6519.
87. Balakrishnan М., Han X., Loon G., Dust J.,
Toullec J., Buncel E. Acceleration of Nucleo
philic Attack on an Organophosphorothioate
Neurotoxin, Fenitrothion, by Reactive Coun
terion Cationic Micelles. Regioselectivity as a
Probe of Substrate Orientation within the Mi
celle. Langmuir. 2004. 20 (16): 6586.
UCJ № 7 / Vol. 86A. F. Popov, I. V. Kapitanov, A. A. Serdyuk, A. E. Shumeiko
31https://ucj.org.ua
88. Omakor J., Onyido I., Loon G., Buncel E.
Mechanisms of abiotic degradation and soil–
water interactions of pesticides and other hy
drophobic organic compounds. Part 3. Nu
cleophilic displacement at the phosphorrus
centre of the pesticide fenitrothion [O,O-di
methyl O-(3-methyl-4-nitrophenyl) phospho
rothioate] by oxygen nucleophiles in aqueous
solution: α-effect and mechanism. J. Chem.
Soc., Perkin Trans. 2. 2001. (3): 324.
89. Sidell F., Groff W. The Reactivatibility of Cho
linesterase Inhibited by VX and Sarin in Man.
Toxicol. Appl. Pharmacol. 1974. 27: 241.
90. Rider J., Moeller H., Puletti E., Swader J. Tox
icity of Parathion, Systox, Octamethyl Pyroph
osphoramide, and Methyl Parathion in Man.
Toxicol. Appl. Pharmacol. 1969. 14: 603.
91. Grossblatt N. Possible Long-Term Health Ef
fects of Short-Term Exposure to Chemical
Agents. (Washington: National Academy Press,
1982. 1., 1984. 2 ).
92. Aurbek N., Thiermann H., Szinicz L., Eyer P.,
Worek V. Analysis of inhibition, reactivation
and aging kinetics of highly toxic organophos
phorus compounds with human and pig acetyl
cholinesterase. Toxicology. 2006. 224 (1–2): 91.
93. Reiner E., Simeon-Rudolf V. Pyridinium, im
idazolium and quinuclidinium compounds:
toxicity and antidotal effects against the nerve
agents tabun and soman. Arh. Hig. Rada Toxi-
col. 2006. 57: 171.
Статья направлена в редакцию «24» марта
2020 года.
|
| id | oai:ojs2.1444248.nisspano.web.hosting-test.net:article-194 |
| institution | Ukrainian Chemistry Journal |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-23T01:02:43Z |
| publishDate | 2020 |
| publisher | V.I.Vernadsky Institute of General and Inorganic Chemistry |
| record_format | ojs |
| resource_txt_mv | ucjorgua/47/caefaa03f4e873678d67b6a7cb577747.pdf |
| spelling | oai:ojs2.1444248.nisspano.web.hosting-test.net:article-1942026-07-22T08:23:43Z REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS РЕАКЦИОННАЯ СПОСОБНОСТЬ НУКЛЕОФИЛОВ И α-ЭФФЕКТ В ПРОЦЕССАХ ЗАМЕЩЕНИЯ У ЭЛЕКТРОНОДЕФИЦИТНЫХ ЦЕНТРОВ РЕАКЦІЙНА ЗДАТНІСТЬ НУКЛЕОФІЛІВ І α-ЕФЕКТ У ПРОЦЕСАХ ЗАМІЩЕННЯ В ЕЛЕКТРОНОДЕФІЦИТНИХ ЦЕНТРАХ Popov, Anatolii Kapitanov, Illia Serdyuk, Anna Sumeiko, Aleksandr functionalized surfactants, α-nucleophiles, micellar systems, hydroxylamine, oximes, amidoximes, hydroxamic acids, peroxides. The review analyzes issues related to the reactivity of nucleophiles and the manifestation of the α-effect in substitution processes at electron-deficient centers. The fundamental aspects of this phenomenon, as well as the possibilities and prospects of using α-nucleophiles in systems for the highly efficient degradation of substrates - ecotoxicants of various natures, are discussed. In the first part of the review such aspects were observed: inorganic α-nucleophiles as the most effective class of reagents for the decomposition of organic phosphorus compounds, hydroxylamine, its N-alkyl derivatives, oximes, and hydroxamic acids, reactivity of the НОО– anion in the processes of acyl group transfer, reactivity of oximate ions, inorganic α-nucleophiles as the basis of formulations for the degradation of neurotoxins, vesicants, and organophosphorus pesticides, design of inhibited acetylcholinesterase reactivators based on hydroxylamine derivatives, ways of structural modification of α-nucleophiles and systems based on them. The data on the reactivity of typical inorganic α-nucleophiles in the cleavage of acyl-containing substrates, including phosphorus acid esters, which provide abnormally high reaction rates in comparison with other supernucleophiles, are analyzed. Various types of such α-nucleophiles, features of their structure and reactivity are considered. It was shown that an important feature of hydroxylamine, oximes, and hydroxamic acids is the presence of a fragment with adjacent O and N (–N – O – H) atoms containing one or more lone electron pairs, which determines their belonging to the class of α-nucleophiles. It has been shown that a many of factors can be responsible for the manifestation of the α-effect and its magnitude, the main of which is the destabilization of the ground state of the nucleophile due to repulsion of lone electron pairs, stabilization of the transition state, the unusual thermodynamic stability of reaction products, solvation effects of the solvent, type of hybridization of the electrophilic center, etc. V.I.Vernadsky Institute of General and Inorganic Chemistry 2020-08-20 Article Article Organic chemistry Органическая xимия Органічна xімія application/pdf https://ucj.org.ua/index.php/journal/article/view/194 10.33609/2708-129X.86.7.2020.3-31 Ukrainian Chemistry Journal; Vol. 86 No. 7 (2020): Ukrainian Chemistry Journal; 3–31 Украинский химический журнал; ##issue.vol## 86 ##issue.no## 7 (2020): Украинский химический журнал; 3–31 Український хімічний журнал; Том 86 № 7 (2020): Український хімічний журнал; 3–31 2708-129X 2708-1281 en https://ucj.org.ua/index.php/journal/article/view/194/118 Copyright (c) 2020 Anatolii Popov, Illia Kapitanov, Anna Serdyuk, Aleksandr Sumeiko https://creativecommons.org/licenses/by-nc/4.0 |
| spellingShingle | Popov, Anatolii Kapitanov, Illia Serdyuk, Anna Sumeiko, Aleksandr РЕАКЦІЙНА ЗДАТНІСТЬ НУКЛЕОФІЛІВ І α-ЕФЕКТ У ПРОЦЕСАХ ЗАМІЩЕННЯ В ЕЛЕКТРОНОДЕФІЦИТНИХ ЦЕНТРАХ |
| title | РЕАКЦІЙНА ЗДАТНІСТЬ НУКЛЕОФІЛІВ І α-ЕФЕКТ У ПРОЦЕСАХ ЗАМІЩЕННЯ В ЕЛЕКТРОНОДЕФІЦИТНИХ ЦЕНТРАХ |
| title_alt | REACTIVITY OF NUCLEOPHILES AND α-EFFECT IN SUBSTITUTION PROCESSES AT ELECTRON - DEFICIENCY CENTERS РЕАКЦИОННАЯ СПОСОБНОСТЬ НУКЛЕОФИЛОВ И α-ЭФФЕКТ В ПРОЦЕССАХ ЗАМЕЩЕНИЯ У ЭЛЕКТРОНОДЕФИЦИТНЫХ ЦЕНТРОВ |
| title_full | РЕАКЦІЙНА ЗДАТНІСТЬ НУКЛЕОФІЛІВ І α-ЕФЕКТ У ПРОЦЕСАХ ЗАМІЩЕННЯ В ЕЛЕКТРОНОДЕФІЦИТНИХ ЦЕНТРАХ |
| title_fullStr | РЕАКЦІЙНА ЗДАТНІСТЬ НУКЛЕОФІЛІВ І α-ЕФЕКТ У ПРОЦЕСАХ ЗАМІЩЕННЯ В ЕЛЕКТРОНОДЕФІЦИТНИХ ЦЕНТРАХ |
| title_full_unstemmed | РЕАКЦІЙНА ЗДАТНІСТЬ НУКЛЕОФІЛІВ І α-ЕФЕКТ У ПРОЦЕСАХ ЗАМІЩЕННЯ В ЕЛЕКТРОНОДЕФІЦИТНИХ ЦЕНТРАХ |
| title_short | РЕАКЦІЙНА ЗДАТНІСТЬ НУКЛЕОФІЛІВ І α-ЕФЕКТ У ПРОЦЕСАХ ЗАМІЩЕННЯ В ЕЛЕКТРОНОДЕФІЦИТНИХ ЦЕНТРАХ |
| title_sort | реакційна здатність нуклеофілів і α-ефект у процесах заміщення в електронодефіцитних центрах |
| topic_facet | functionalized surfactants α-nucleophiles micellar systems hydroxylamine oximes amidoximes hydroxamic acids peroxides. |
| url | https://ucj.org.ua/index.php/journal/article/view/194 |
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