Selenium chlorides in the domino process of the regiospecific allyl chlorination of betulin and diacetylbetulin

Article abstract of DOI:10.1080/17415993.2020.1714049

The interaction of betulin and diacetylbetulin with selenium chlorides occurs regiospecific with allylic chlorination of the substrate. Selenium chlorides are obtained by chlorination of selenium with sulfuryl chloride in the form of a mixture of SeCl

Full text of DOI:10.1080/17415993.2020.1714049

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: https://www.tandfonline.com/loi/gsrp20
Selenium chlorides in the domino process of the
regiospecific allyl chlorination of betulin and
diacetylbetulin
I. V. Bodrikov, Yu. A. Kurskii, A. A. Chiyanov, A. Yu. Subbotin, A. S. Shavirin &
N. V. Anderson
To cite this article: I. V. Bodrikov, Yu. A. Kurskii, A. A. Chiyanov, A. Yu. Subbotin, A.
S. Shavirin & N. V. Anderson (2020): Selenium chlorides in the domino process of the
regiospecific allyl chlorination of betulin and diacetylbetulin, Journal of Sulfur Chemistry, DOI:
10.1080/17415993.2020.1714049
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JOURNAL OF SULFUR CHEMISTRY
https://doi.org/10.1080/17415993.2020.1714049
Selenium chlorides in the domino process of the regiospecific
allyl chlorination of betulin and diacetylbetulin
a
a
b
a
c
I. V. Bodrikov , Yu. A. Kurskii , A. A. Chiyanov , A. Yu. Subbotin , A. S. Shavirin and
d
N. V. Anderson
a
b
R.E.Alekseev Nizhny Novgorod State Technical University, Nizhny Novgorod, Russia; N.I. Lobachevsky State
c
University of Nizhny Novgorod, Nizhny Novgorod, Russia; Razuvaev Institute of Organometallic Chemistry of
Russian Academy of Sciences, Nizhny Novgorod, Russia; Sciences Facilities, Baylor University, Waco, TX, USA
d
ABSTRACT
ARTICLE HISTORY
The interaction of betulin and diacetylbetulin with selenium chlo-
rides occurs regiospecific with allylic chlorination of the substrate.
Selenium chlorides are obtained by chlorination of selenium with
sulfuryl chloride in the form of a mixture of SeCl2 and Se2Cl2. An inter-
mediate product of the domino process, unsaturated allylic structure
chloroselenide, was detected by 77Se and H NMR. The rate of con-
version of selenide to allyl chloride was determined. According to the
results of quantum-chemical calculations, in the reactions of betulin
and diacetylbetulin with both SeCl2 and Se2Cl2, intermediates of
the episelenuran type are formed in the first stage. Further, these
intermediates are converted to unsaturated selenium chlorides by
eliminationofHCl. Accordingtothecalculationresults, thefinalstage
of the domino process – the formation of allyl chlorides is realized
due to the catalytic action of SeCl2 in the elimination of selenium.
Received 16 October 2019
Accepted 4 January 2020
KEYWORDS
Selenium chlorides; betulin;
intermediate; domino
reaction
1
1. Introduction
Selenium halides are widely used in preparative organic synthesis [1,2], including one-pot
synthesis options [3,4]. The selenium chlorides are used more often than other halogen
derivatives for reactions with unsaturated compounds and mainly exhibit the properties of
bielectrophils in these reactions. Two types of π-bonds are involved in the additive process
CONTACT A. A. Chiyanov
trips-25@yandex.ru; N. V. Anderson
natalia_anderson@baylor.edu
Supplemental data for this article can be accessed here. https://doi.org/10.1080/17415993.2020.1714049
2020 Informa UK Limited, trading as Taylor & Francis Group
©

2
I. V. BODRIKOV ET AL.
with selenium dihalides: dienes that are completed by heterocyclization [5], or two alkenes
with the formation of a dimer, where the alkenes are linked by selenium [6].
Recently, in a preliminary report [7], we described a new direction of the reaction
of selenium chlorides with betulin and diacetylbetulin demonstrating regiospecific allyl
chlorination of these substrates. According to our data [8], halogenation of betulin and
diacetylbetulin with N-chloro-, N-bromo-, and N-iodosuccinimides leads to a mixture of
vinylic and allylic isomers. Thus, when they are chlorinated with N-chlorosuccinimide or
tert-butyl hypochlorite, the main products are unsaturated vinylic chlorides of the Z- and
E-structures, and the content of the allylic isomer does not exceed 30% [8,9]. As confirmed
by X-ray analysis, allylic and vinylic isomers of diacetylbetulin crystallized jointly [9]. The
developing of selective methods for the synthesis of betulin derivatives is due to the com-
plexity of separating its isomers, since they have similar physical characteristics, as well as
the low content of the allylic isomer in the mixture.
Betulin and many of its derivatives have polyfunctional biological activity [10–12]. An
increase of biological activity is usually produced by modification of these bioactive com-
pounds [13–16]. To do this, the modified compounds are transformed into precursors by
the introduction of nucleofuge fragments, which can be easily replaced by target bioactive
synthons. Within the framework of this strategy, the found reaction of the regiospecific allyl
chlorination of unsaturated compounds is of interest as an effective method of preparing
such precursors for the targeted modification of bioactive unsaturated compounds. The
present work uses NMR spectroscopy and quantum chemistry to identify the structures
of the short-lived intermediates generated during the regiospecific halogenation of betulin
1a and diacetylbetulin 1b with selenium halides.
2. Results and discussion
2.1. NMR results
In the experiments, geminally substituted alkenes 1a,b and selenium chlorides were used.
The control over the initial components, detected intermediates and the final reaction
1
13
77
products, were identified by H, C and Se NMR spectroscopy. The NMR was chosen
1
as the main method of analysis, since H NMR signals of protons in the double bond of the
initial substrates, intermediates and final product are clearly different and are an analyti-
cal characteristic for quantitative analysis. To monitor changes in the components of the
reaction mixture during the process, part of the experiments were carried out directly in
an NMR spectrometer.
By the method of 77Se NMR, it was established that the selenium chlorides obtained
in CDCl consist of a mixture of SeCl (30–40% of the total amount of selenium) and
3
2
7
7
Se Cl (60–70%). In accordance with the data of [17,18], the Se NMR peak at 1275 ppm
2
2
is attributed to Se Cl , and a wider peak at 1761 ppm to SeCl .
2
2
2
We have shown for the first time that the reaction of diacetylbetulin 1b and the indicated
selenium chlorides lead to the formation of the product 2b by substitution of hydrogen
by selenium chloride in the allylic position and detected by NMR. Thus, signals δ 4.61,
H
1
5
.35 and 5.42 ppm belonging to intermediate 2b, appear in the H NMR spectrum of the
reaction mixture (Figure 1). In the Se NMR spectrum, taken immediately after mix-
7
7
ing the reactants, a δSe 571 ppm signal belonging to 2b was detected. According to the

JOURNAL OF SULFUR CHEMISTRY
3
1
Figure 1. The H NMR spectra (a, b fragments) of the reaction products of diacylbetulin with selenium
chlorides 400 MHz, in CDCl3. a – After mixing the components in a ratio of 1:2; b – in 20 min; c – NMR
spectrum of the reaction product after recrystallization.
proton-proton correlation (COSY) intermediate 2b has an allylic structure. The signal at
4
.61 ppm refers to the allylic protons of the H C(30)SeCl groups, and two singlets at 5.42
2
and 5.35 ppm (Figure 1a) to cis- and trans-vinylic H C(29)=C protons 2b. In the COSY
2
spectrum (Figure 2) taken during the reaction, an interaction is observed between the cis-
proton H C(29)=C δ 5.42 ppm (trans-position relative to the H C(30)SeCl group) and
2
H
2
the protons of the H C(30)SeCl group δ 4.61 ppm and between the cis-and trans-protons
2
H
of the H C(29)=C group 2b. These spin-spin interactions confirms that all these signals
2
belong to one molecule.
1
In the case of a large excess of substrate 1b, with respect to selenium chlorides in the H
NMR spectrum, additional signals appear at 4.82 and 4.88 ppm, which can be attributed to
vinylic protons of the chlorodiselenide 3b. Two allylic protons of the H C(30)Se Cl group
2
2
1
3
b appear in the H NMR spectrum as two doublets at δH 3.09 and 3.13 with the constant
J = 12.2 Hz characteristic of the geminal protons.
The accumulation of unsaturated selenides in the reaction mass proceeds very quickly
and produces a significant amount of red precipitate that falls out of solution and produces
hydrogen chloride gas. Simultaneously, the second stage of the reaction develops the trans-
formation of 2b into the unsaturated chloride of the allylic structure 4b. Signal intensity
2
b δ 4.61, 5.35 and 5.42 ppm gradually decreases with a simultaneous increase in the sig-
H
nals δH 3.99, 5.03 and 5.12 ppm, belonging to the final product of unsaturated chloride
b (Figure 1a,b). During the development of this stage, the slow precipitation of red sele-
nium from the reaction mass continues. The organoselenium intermediate 3b, as well as
4

4
I. V. BODRIKOV ET AL.
Figure 2. Two-dimensional proton-proton correlation spectrum (COSY) of the reaction mixture of
diacetylbetulin with selenium chlorides 400 MHz in CDCl3.
Scheme 1. General scheme of allylic chlorination of betulin (1a) and diacetylbetulin (1b) with selenium
chlorides.
2b, gradually transforms into allylic chloride 4b. After a relatively quick completion of the
first stage of the reaction (2–3 min), the second stage of the reaction lasts 5–9 h with the
quantitative conversion of the substitutive selenation products into allylic monochloride
4
b (Scheme 1).
In the reaction of betulin 1a, with selenium chlorides, the substitutive selenation prod-
ucts 2a and 3a are not detected by NMR spectroscopy, however, the results of quantum
chemical calculations indicate a greater likelihood of the participation of intermediates 2a

JOURNAL OF SULFUR CHEMISTRY
5
Scheme 2. The mechanism of formation of intermediate products of chlorination.
and 3a in the channel of betulin transformation into the product of allyl chlorination 4a.
Apparently, the intermediates 2a and 3a have low stability, which, together with the low sol-
ubility of 1a, does not allow them to reach a stationary concentration sufficient for NMR
detection.
Chlorine derivatives of selenium as carriers of chlorine emit selenium in a zero-valence
state. When chlorinating the released selenium with sulfuryl chloride (selenium oxidation),
selenium chlorides regain the original properties of the reactants and catalyst. Thus, a cyclic
process of regiospecific chlorination of betulin 1a and its derivative 1b can be organized.
2
.2. Quantum chemical calculations
According to the results of quantum chemical calculations, the interaction of betulin 1a
and diacetylbetulin 1b with selenium chlorides SeCl and Se Cl leads to the generation
2
2
2
of intermediates 5a, b and 6a, b (Scheme 2). The charges on the atoms of the reaction
center and adjacent fragments and the distance between the atoms are shown in Table 1.
In the intermediates, the selenium atom is located closer to the terminal methylene group
(
C29) than to the central carbon atom (C20). The dihedral angle between the vinylic methyl
group at C(30) and the polycyclic fragment in the intermediates is slightly deviated from
the flat state. Therefore, the intermediates responsible for substitutive selenation of betulin
and diacetylbetulin are close in structure to the asymmetric episelenurane. At the same
time, the bond order for the C(20)-C(29) of these episelenuranes is similar to the 1.5 bond
order in benzene. Symmetric episelenurane was obtained by the action of tolueneselenenyl
chloride on ethylene [19]. The formation of this type of cyclic intermediates was considered
in the reactions of electrophilic sulfur with alkenes [20,21].
2
The hybrid state of the carbon atom C(20) in 5a, b and 6a, b, is closer to the sp
state according to the dihedral angle and the length of the partial bond Se-C(20). A fur-
ther decrease in the dihedral angle is accompanied by a sharp increase in the energy of
the system due to the repulsive interaction of geminal substituents at the C(20) carbon
atom. Such an extreme increase in the energy of the repulsive interaction of bulky gemi-
nal substituents in the bromonium cation was revealed by the results of quantum chemical
calculations [22]. With such a significant interaction of geminal substituents in the asym-
metric episelenurane, the implementation of a nonadditive process such as the elimination
of the β-proton, becomes more advantageous. Elimination, in turn, provides an increase in

6
I. V. BODRIKOV ET AL.
Table 1. Charges, bond lengths and dihedral angles in the intermediates 5a, b and 6a, b. The results of
quantum chemical calculations.
Intermediate
5a
5b
6a
6b
Bond length, Å
C(20)-C(29)
C(29)-Se
C(20)-Se
C(19)
H(19)
C(20)
1.43
2.01
2.16
1.43
2.01
2.16
1.39
2.11
2.32
1.39
2.11
2.36
Charge
−0.16
+0.15
+0.26
−0.46
+0.20
−0.55
+0.20
+0.47
–
−0.16
+0.15
0.26
−0.46
+0.20
−0.55
+0.20
+0.47
–
−0.18
+0.15
+0.29
−0.47
+0.20
−0.56
+0.19
+0.25
+0.06
−0.38
−0.22
165°
−0.19
+0.15
+0.34
−0.50
+0.20
−0.57
+0.20
+0.24
+0.05
−0.35
−0.24
167°
C(29)
b
H (29)
C(30)
c
H (30)
Se
Se’
Cl
−0.41
−0.39
156°
−0.40
−0.38
155°
Cl’
Dihedral angleC(19)-C(20)-C(30)
Notes:a–theatomicnumbersoftheskeletonoftheintermediatescorrespondtotheatomicnumbersofthebetulinskeleton
Scheme 1); b – same charge on both hydrogen atoms; c – average charges of three hydrogen atoms.
(
the specified dihedral angle up to 180° and leads to a decrease in the repulsive interaction
of geminal substituents at the C(20) atom.
The formation of intermediate episelenuranes 5a, b and 6a proceeds without an energy
barrier. The studied domino reaction is a multi-stage process where the stage of formation
of episelenuran proceeds barrier-free or with a low energy barrier, since only one π-bond
breaks during the generation of this intermediate, and one and a half σ-bonds Se-C are
formed. In the reaction of 1b with Se Cl , the energy barrier of 1.4 kcal/mol is overcome.
2
2
The energy of 6b is reduced relative to the initial state by 10.2 kcal/mol. Next, the inter-
mediates 5a,b, 6a,b are transformed into allylic selenium chlorides due to the elimination
of HCl. The transformation of alkene intermediates 1a,b with SeCl into allylic selenium
2
chlorides 2a,b proceeds with an energy barrier of 11 kcal/mol. With that, the energy of the
system as compared with the energy of episelenurane decreases by 1.3 kcal/mol for 5a and
by 1.6 kcal/mol for 5b. The transformation of alkene intermediates with Se Cl into allylic
2
2
chlorodiselenides 3a,b occurs with energy barriers: 6.3 kcal/mol for 6a and 6.8 kcal/mol
for 6b. At the same time, the energy of 3a,b decreases by 6.0 and 6.3 kcal/mol compared
with the energies of episelenurane 6a and 6b respectively.
The results of quantum-chemical calculations show that intermediates of the type of
asymmetric episelenurane 5a,b, 6a,b are formed with subsequent elimination of HCl in
the first stage of the substitutive selenation of betulin and diacetylbetulin under the action
of SeCl and Se Cl . Realized stages are characterized by low energy barriers. In accordance
2
2
2
with the results of the calculations, the higher rate is predicted for the reaction of 1a,b with
Se Cl compared to the reaction with SeCl .
2
2
2
From the obtained experimental data it follows that the final products of the reactions of
betulin and diacetylbetulin with SeCl and Se Cl are only the corresponding allylic chlo-
2
2
2
rides 4a,b. Therefore, the fragments SeCl and Se Cl must be replaced by chlorine at the
2
next stage of transformation of the products of the substitutive selenation of betulin and
diacetylbetulin. Quantum chemical analysis was performed for two variants of intramolec-
ular substitution. The first one involved a chlorine attack of a carbon atom in the allylic
position containing a selenium fragment (allylic attack). The second variant of selenium

JOURNAL OF SULFUR CHEMISTRY
7
Scheme 3. Catalytic participation of SeCl2 in the substitution of SeCl nucleofuge.
fragment substitution concludes in attack of the terminal carbon atom at the double bond
vinylic attack) with the implementation of a cascade process, completed by the elimination
(
of the selenium fragment.
An analysis of the energy barriers of these intramolecular substitution channels shows
that replacing SeCl and Se Cl fragments with a chlorine atom by type of an S -process or
2
Ni
with the attack of a terminal double bond requires overcoming a high barrier (more than
5
0 kcal/mol). The occurrence of reactions with such a high energy barrier is unlikely.
Chloroselenium as a leaving group, apparently, does not possess sufficient nucleofugal-
ity. Therefore, to increase the nucleofugal activity of the introduced selenium fragments,
SeCl and Se Cl, we coordinated them with another SeCl molecule. This procedure is
2
2
implemented barrier-free or by overcoming the low energy barrier. The results of cal-
culations show that in the technique with an activated selenium fragment, the variant of
substituting this fragment with chlorine, with an attack of the allylic carbon atom, requires
overcoming a much larger barrier compared to the vinylic attack.
In accordance with this, in the present work, we present the results of the calculation
of the variant of replacing the selenium fragment with the chlorine attack of the terminal
carbon atom as an energetically more advantageous substitution channel. It should also
be noted that replacing SeCl as a catalyst in the substitution reaction with diselenium
2
dichloride (Se Cl ) does not provide the nucleofugal activity of the selenium fragment,
2
2
which is sufficient to form allylic chloride.
When SeCl acts on chloroselenide 2a, barrier-free coordination of the catalyst with
2
selenium, introduced as an electrophile, occurs with the formation of complex 7a. In the
subsequent procedure, the bond between terminal selenium and chlorine was forcibly
stretched with the orientation of chlorine to the methylene group at the double bond
(
vinylic attack). As a result of this procedure, in the complex 7a, when passing through
the energy barrier of 23.7 kcal/mol, the carbon–selenium bond is broken with the frag-
mentation of Se Cl . With that, the migration of the double bond with the formation of
2
2
allylic chloride 4a occurs (Scheme 3). The potential energy of the system is higher than the
energy of complex 7a by 4.8 kcal/mol.
To coordinate the unsaturated chloroselenium derivative of diacetylbetulin 2b with
a catalyst (SeCl ), it is necessary to overcome the energy barrier of 3.2 kcal/mol.
2
The energy of the obtained donor-acceptor complex 7b is 10.4 kcal/mol below the
energy of the chloroselenium derivative 2b. For the intramolecular substitution of the

8
I. V. BODRIKOV ET AL.
Scheme 4. Catalytic participation of SeCl2 in the substitution of Se2Cl nucleofuge.
trichlorodiselenium fragment by the attack of the terminal methylene group at the double
bond by chlorine of the terminal dichloroselenium fragment of complex 7b, it is necessary
to overcome the energy barrier of 19.9 kcal/mol. During the substitution, the carbon-
selenium bond is broken with the Se Cl fragmentation and the double bond is migrated
2
2
to form allylic chloride 4b (Scheme 3). The potential energy of the products is higher than
the energy of complex 7b by 4.6 kcal/mol.
Under the action of SeCl on the chlorodiselenide of betulin 3a, with an energy barrier
2
of 1.9 kcal/mol, donor-acceptor complex 8a is formed, in which the selenium atom of the
catalyst (SeCl ) is coordinated with selenium bonded to the carbon atom of betulin. At
2
the same time, complex 8a is 3.4 kcal/mol more stable than chlorodiselenide 3a. Then the
chlorine attack from the SeCl fragment also occurs at the double bond of the terminal
2
methylene group. As a result of this transformation, with an energy barrier of 23.7 kcal/mol,
Se Cl is eliminated and the double bond has a 1,2-shift to form allylic chloride 3a, which
3
2
is more stable than complex 8a by 1.6 kcal/mol.
Coordination of unsaturated chlorodiselenide 3b and SeCl , with an energy barrier of
0.8 kcal/mol, leads to the formation of donor-acceptor complex 8b, which is more stable
2
1
than product 3b by 8.6 kcal/mol (Scheme 4).
The implementation of the final stage proceeds along a route, involving an attack of a ter-
minal carbon atom at the double bond with chlorine. The attacking Cl(2) atom has a charge
of −0.279 and is coordinated with two selenium atoms. Both Se(1)–Cl(2) and Se(3)–Cl(2)
bonds are stretched to 2.42 Å. Overcoming the energy barrier of 28.3 kcal/mol, the reac-
tion leads to the elimination of Se Cl and 1,2-migration of the terminal double bond with
3
2
the formation of allylic chloride 4b. The total energy of the products of intramolecular
elimination of Se Cl is more than the energy of the donor – acceptor complex 8b by
3
2
4
kcal/mol.
2.3. Kinetic measurements
The overall domino process of the interaction of SeCl and Se Cl with the substrate 1b
2
2
2
involves a rapid stage the formation of organoselenium compounds 2b and 3b and a slow
intramolecular cascade replacement of the nucleofuge activated chloroselenium fragment
with chlorine to form allylic monochloride 4b. In such processes, it is possible to estimate
the ratio of the rates of formation of 2b and 3b, as well as to determine the rate constant

JOURNAL OF SULFUR CHEMISTRY
9
Scheme 5. Kinetic stages of chloroselenation of diacetylbetulin (1b).
Table 2. The primary products of SeCl2 and Se2Cl2 with betulin diacetate reaction.
The ratio of free and bound
betulin diacetate forms, %
The rate constant of 2b
transformation, k·10 s
4
−1
[Se]0/[1b]0*, %
2b
3b
Non-reacted DABT
3
4
6
9
1
1
2
2
3
3
2
1
2
02
49
00
00
00
13
17
28
45
49
13
13
9
5
6
74
70
63
50
45
28
∼ 2.0
1.5
1.4
1.6
1.6
1.7
3.2
3.4
3.6
72
100
100
100
*The initial mole relationship of reagent [Se]0 = [SeCl2]0 + 2[Se2Cl2]0 and substrate.
of the slow stages. The content of organoselenium intermediate products and non-reacted
diacetylbetulin 1b for the different initial ratios of total selenium and substrate 1b 5–10 min
after the start of the reaction is shown in Table 2. Despite the fact that the molar content
of selenium chlorides, SeCl and Se Cl , in the initial mixture is close to 50%, in the reac-
2
2
2
tion products the content of selenium chloride 2b is 9 times higher than the content of
diselenium chloride 3b (when a ratio of selenium in the reagent to the substrate 1:1). With
this ratio of reagent/substrate, all selenium chloride (both SeCl and Se Cl ) is consumed
2
2
2
completely in the fast stage, and the proportion of reacted 1b is only 55%. Consequently,
parallel to the main fast reactions 1b with SeCl and Se Cl , the process of additional con-
2
2
2
sumption of Se Cl must proceed. Apparently, this is the exchange reaction of diselenium
2
2
chloride 3b with Se Cl , which proceeds at a high rate (Scheme 5). The sum of rapid reac-
2
2
tions in the first stage leads to the release of HCl, precipitation of the initial amount of
selenium, and the formation of selenium chloride 2b for the most part.
A numerical simulation of the kinetics of the first stage of the process was carried out in
accordance with scheme 5. The calculations were performed for different rate constants, for
different initial ratios of selenium/substrate 1b and different contents of SeCl in a mixture
2
of selenium chlorides. The calculated reaction time was 100 s. The results of numerical
simulation (Table 3) are consistent with the experimental data (Table 2).
For Scheme 5, the amount of selenium precipitated at the first moment was calculated at
different initial molar ratios selenium/1b. For the ratios [Se] /[1b] 0.5, 1.5 and 2.5, the cal-
0
0
culated proportion of selenium precipitated is 27, 38 and 32% respectively (k = 2, k = 1,
1
2
k = 10, initial [SeCl ]/[Se] = 20%). This trend is consistent with the experimental data.
3
2
0

10
I. V. BODRIKOV ET AL.
Table 3. The calculated content of the primary products of SeCl2 and Se2Cl2 with betulin diacetate
reaction (Scheme 5).
The ratio of free and bound
betulin diacetate forms, %
Initial [Se]0/[1b]0, %
Model
2b
3b
Non-reacted DABT
Sediment [Se]/[Se]0, %
4
6
9
1
0
A
B
A
B
A
B
A
B
17.5
22.7
28.7
36.3
46.3
57.9
78.7
99.5
6.5
5.3
7.3
5.7
7.6
5.1
6.7
0.5
76
72
64
58
46.2
37
14.6
0
23.8
16.8
27.9
20.5
31.6
24.3
35.5
29.7
0
0
50
Model A: k1 = 0.1, k2 = 1, k3 = 10, initial [SeCl2]0/[Se]0 = 20%.
Model B: k1 = 2, k2 = 1, k3 = 10, [SeCl2]0/[Se]0 = 40%.
It was found that the proportion of initially released selenium goes through the maximum
with an increase in the ratio [Se] /[1b] . Thus, for the ratios [Se] /[1b] 0.5, 1, and 2, the
0
0
0
0
proportion of selenium precipitated 5 min after the start of the reaction is 23, 59, and 26%,
respectively.
The transformation of intermediate 2b to allylic chloride 4b proceeds by a first-order
−
4
−1
reaction. In this case, the effective reaction rate constant 1.6·10
s
does not change in
the range of selenium/substrate ratios from 0.3:1 to 1.5:1 (Table 2). The results of quan-
tum chemical calculations show that the transformation of 2b to allylic monochloride
4b is a catalytic process. Consequently, in this range of selenium/substrate 1b ratios, the
concentration of the catalyst is kept constant. It can be assumed, that at such ratios sele-
nium/1b in catalysis, soluble forms of red selenium are involved. The concentration of a
poorly soluble substance is determined only by its solubility product and does not depend
on the amount of selenium in the precipitate. With an increase in the selenium/1b ratio
over 1.5 and higher, the effective reaction rate constant increases with an increase in the
selenium/1b ratio (Table 2). Upon reaching the selenium/substrate 1b ratio 2 and more in
the system, non-reacted SeCl and Se Cl remain after rapid primary reactions. Accord-
2
2
2
ing to quantum chemical calculations, SeCl has a catalytic effect on the transformation of
2
intermediate 2b, therefore, the effective rate constant increases.
The rate constant for the slow transformation of chlorodiselenide 3b to the final product
−5
−1
4
b is ∼2·10
s
. The experimentally observed order of magnitude lower transformation
rate of 3b compared to 2b is consistent with the results of quantum chemical calcula-
tions. According to the calculated data, the energy barrier at the stage of transformation of
chlorodiselenide 3b to product 4b (28.3 kcal/mol) significantly exceeds the corresponding
energy barrier for selenium chloride 2b (19.7 kcal/mol).
The obtained experimental data and quantum chemical calculations are in agreement
with each other and complement each other.
3. Conclusion
We first discovered that such weak electrophiles as SeCl and Se Cl in reactions with
2
2
2
betulin and diacetylbetulin replace a hydrogen atom in the allylic position with the
formation of unsaturated selenium chlorides instead of attaching by a double bond. In the

JOURNAL OF SULFUR CHEMISTRY
11
reaction of diacetylbetulin with SeCl , unsaturated selenium chloride was first detected
2
by NMR as a short-lived intermediate. According to the data of quantum chemical cal-
culations, the indicated selenium chlorides are formed from unstable intermediates called
asymmetric episelenuranes. At the next stage of the reaction, the SeCl and Se Cl fragments
2
introduced as electrophiles form donor–acceptor complexes with selenium compounds
present in solution. The nucleofugal activity of the chloroselenium leaving groups (SeCl
and Se Cl) is increased due to coordination with SeCl . An energetically more advan-
2
2
tageous route for the reactions of all complex systems is the transfer of a chlorine atom
from selenium to a terminal carbon atom at the double bond. The process being imple-
mented includes the cascade formation of a C-Cl bond, elimination of selenium-containing
nucleofuge-activated fragments, and a shift of the double bond to the carbon atom released
from the chloroselenium fragment. The result of the domino process is the regiospecific
allyl chlorination of betulin and diacetylbetulin. Thus, chloroselenides in domino reactions
of allyl chlorination perform two functions: substitutive selenation reagents and catalysts
for intramolecular substitution of chloroselenium nucleofuge with the chlorine atom.
4. Experimental
Quantum chemical calculations were performed using the semi-empirical method PM6
accomplished by the Gaussian 09 software package [23]. The search of intermediate by
QST2 and TS procedures for the models studied in this article did not allow us to pre-
cisely establish such an intermediate with a single negative frequency. Therefore, analysis
of transformations was performed using the Scan procedure, not the IRC.
1
The H NMR spectrums were recorded on a Bruker DPX-200 (200 MHz) and a Brukier
1
3
Avance III (400 MHZ) spectrometers. The spectrums, C (100 MHz, 1024 scans, 30° pulse
7
7
width 15 μs) and Se (76.3 MHz, 512 scans, 90° pulse width 22.5 μs) were recorded on a
Brukier Avance III spectrometer. In all cases, the solvent was CDCl3.
To record reaction kinetics, the freshly prepared solution of selenium chlorides was
mixed with the solutions of 1a or 1b in the ratios given in Table 2 and the reaction mixture
1
was stirred at room temperature. Then, the samples were placed in NMR tubes and H
NMR spectrums were taken after 10 min.
Selenium chloride was prepared by chlorinating metal selenium with sulfuryl chloride.
To prepare a solution of SeCl to 0.45 g (5.7 mmol), finely dispersed Se was added to a solu-
2
tion of 0.77 g (5.7 mmol) of freshly distilled SO Cl in 3 ml of chloroform. The mixture was
2
2
rapidly stirred at room temperature until complete dissolution of selenium was observed.
The freshly prepared solution of selenium chlorides was mixed with the solutions of 1a or
1b and the reaction mixture was stirred at room temperature. The precipitated red sele-
nium was filtered off, the filtrate was washed with 10 ml of 3% sodium carbonate solution,
and then with water (3 × 10 ml). The solvent was evaporated on a rotary evaporator and
the precipitate was air dried.
30-Chlorolup-20(29)-ene-3β,28-diol. A solution of selenium chlorides (1.42 mmol)
was added to a solution of 0.42 g of 1a (0.95 mmol) in 30 ml of CHCl . Yield 4a 0.42 g
3
1
9
(
1
1
92%). NMR H (CDCl , 400 MHz): 0.64–0.71 (m, 1H, C H), 0.76, 0.82, 0.97, 0.99, and
3
.03 (all s, all 3H, CH ), 0.79–2.01 (m, CH and CH ), 2.12–2.23 (m, 1H, HCH), 2.39 (t,d,
3 2
1
9
3
H, C H, J = 11.1 Hz, J = 5.4 Hz), 3.12 (d,d, 1H, C HO, J = 11.2 Hz, J = 5.0 Hz), 3.33
2
8
2
30
2
and 3.80 (both d, both 1H, C H O, J = 10.8 Hz), 4.06 (s, 2H, C H Cl, J = 12.0 Hz),
2
2

12
I. V. BODRIKOV ET AL.
2
9
13
5
1
4
.02 and 5.09 (both s, both 1H, H C =C). NMR C (CDCl , 100 MHz): 14.9, 15.5, 16.1,
2
3
6.2, 18.4, 21.1, 27.13, 27.15 27.5, 28.1 (CH ), 29.4, 32.3, 33.8, 34.4, 37.28, 37.31, 38.8, 39.0,
1.1, 42.8, br. 43.5 (C H), 47.9, br. 48.5 (C H Cl), 50.1, 50.5, 55.4, 60.4 (H C OH), 79.1
3
1
9
30
28
2
2
3
29
20
(
HC OH), br. 112.6 (H C =C), 150.7 (C =CH ).
2
2
3
β,28-Di-O-acetyl-30-chlorolup-(20)29-ene. A solution of selenium chlorides (5.7
mmol) was added to a solution of 2 g of 1b (3.8 mmol) in 10 ml of CHCl . Yield 4b 1.88 g
3
1
9
(
88%). NMR H (CDCl , 400 MHz): 0.76–0.80 (m, 1H, C H), 0.83 (s, 3H, CH ), 0.85
3 3
(
2
s, 6H, 2 × CH ), 0.98 and 1.04 (both s, both 3H, CH ), 0.93–1.89 (m, CH and CH ),
3
3
2
1
9
.04 and 2.07 (both s, both 3H, CH CO ), 2.11–2.22 (m, 1H, HCH), 2.44 (t,d, 1H, C H,
3 2
2
8
2
J = 11.1 Hz, J = 5.5 Hz), 3.85 and 4.25 (both d, both 1H, H C OAc, J = 11.1 Hz), 4.05
2
3
0
2
3
(
s, 2H, C H Cl, J = 12.1 Hz), 4.45–4.49 (m, 1H, HC OAc), 5.02 and 5.10 (both s, both
29 13
2
1
2
3
6
1
H, H C =C). NMR C (CDCl , 100 MHz): 14.9, 12.2, 16.3 and 16.6 (all CH ), 18.3,
2
3
3
1.09, 21.14 and 21.4 (both CH CO ), 23.8, 27.12, 27.18, 28.1 (CH ), 30.0, 32.2, 34.3, 34.4,
3
2
3
1
9
30
7.2, 37.6, 37.9, 38.6, 41.1, 42.8, br. 43.4 (C H), 46.5, br. 48.5 (C H Cl), 50.2, 50.4, 55.5,
2
2
8
3
29
20
2.7 (H C OAc), 81.0 (HC OAc), br. 112.7 (H C =C), 150.5 (C =CH ), 171.1 and
2
2
2
71.7 (both C(O)O).
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
The study was carried out under the financial support of the Russian Foundation for Basic Research
RFBR) [grant number 19-03-00908].
(
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