Iodonium salts as efficient iodine(iii)-based noncovalent organocatalysts for Knorr-type reactions

Article abstract of DOI:10.1039/d0ra09640g

Hypervalent iodine(iii)-derivatives display higher catalytic activity than other aliphatic and aromatic iodine(i)- or bromine(i)-containing substrates for a Knorr-type reaction of N-acetyl hydrazides with acetyl acetone to give N-acyl pyrazoles. The highe

Full text of DOI:10.1039/d0ra09640g

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Iodonium salts as efficient iodine(III)-based
noncovalent organocatalysts for Knorr-type
Cite this: RSC Adv., 2021, 11, 4574
reactions†
a
Sevilya N. Yunusova,a Alexander S. Novikov,
Natalia S. Soldatova,a
b
a
*
Mikhail A. Vovk
and Dmitrii S. Bolotin
Hypervalent iodine(III)-derivatives display higher catalytic activity than other aliphatic and aromatic iodine(I)–
or bromine(I)-containing substrates for a Knorr-type reaction of N-acetyl hydrazides with acetyl acetone to
give N-acyl pyrazoles. The highest activity was observed for dibenziodolium triflate, for which 10 mol%
resulted in the generation of N-acyl pyrazole from acyl hydrazide and acetyl acetone typically at 50 ꢀC
for 3.5–6 h with up to 99% isolated yields. 1H NMR titration data and DFT calculations indicate that the
catalytic activity of the iodine(III) is caused by the binding with a ketone.
Received 12th November 2020
Accepted 5th January 2021
DOI: 10.1039/d0ra09640g
rsc.li/rsc-advances
that are based on iodine(I) derivatives, such as oligodentate 2-
iodoimidazolium species.45,46 Indeed, diaryliodonium salts
Introduction
exhibited a high catalytic activity in reactions in which a halide
abstraction occurred46 (including their application in living
cationic polymerization of olens;47 Fig. 1(i) and (ii)) and in the
synthetic transformations of carbonyl compounds, namely
In the past decade, organocatalysis has been the focus of
extensive studies owing to its signicant advantages over
catalysis by metal-containing species including lower toxicity,
reduced environmental footprint, and low to negligible sensi-
tivity to air and moisture.1,2 In general, these organocatalysts
can function either through a covalent or noncovalent bonding
activation. A covalent activation mode involves the formation of
covalent bond(s) between a substrate and catalyst (such as
amines,1–5 heterocyclic carbenes,1,6,7 or phosphines8), whereas
a noncovalent mode involves the activation of substrates
through noncovalent linkages to the catalyst.2,9–18
For noncovalent catalysis, an organic catalyst typically
interacts with a substrate through hydrogen bonding (HB), and
many important results were achieved for the reactions based
on such HB donors as ureas,2,19–24 squaramides,24–26 and other
Brønsted acids,27–31 whereas catalytic reactions involving
halogen (XB)9,10,15,32–35 or chalcogen bonding (ChB)34,36,37 are far
less explored. Although XB has been established as a valuable
tool in solid-state chemistry and crystal engineering,38–41 over
the last ve years XB has been studied in solution33–35,42–44 and
applied to homogeneous catalytic transformations.9,15,16,34,37
Recently Huber and coworkers reported that iodine(III)
derivatives such as diaryliodonium salts can serve as efficient
organocatalysts and utilize XBs for which the catalytic activity is
similar or even higher than other well-proven organocatalysts
aInstitute of Chemistry, Saint Petersburg State University, Universitetskaya Nab. 7/9,
Saint Petersburg, 199034, Russian Federation. E-mail: d.s.bolotin@spbu.ru
bCenter for Magnetic Resonance, Saint Petersburg State University, Universitetskii Pr.,
26, Saint Petersburg, 198504, Russian Federation
Fig. 1 Previously studied reactions catalyzed by diaryliodonium salts
and plausible modes of activation of substrates. s-hole is a region of
positive electrostatic potential on an atom.49
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d0ra09640g
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Diels–Alder cycloaddition46 (Fig. 1(iii)) and Mannich reaction48
(Fig. 1(iv)).
Considering the promising catalytic properties of diary-
liodonium salts and the small number of reported examples for
their application in homogeneous organocatalysis, further
studies are worthwhile. In this study, we report on the catalytic
activity of a series of diaryliodonium salts and provide
a comparison of their activity with other XB donors in a model
reaction that requires carbonyl activation. In agreement with
previous suggestions that the catalytic activity of diary-
liodonium salts is caused by the electrophilic activation of the
electrophile,46,47 their catalytic activity in the studied Knorr-type
cyclization is caused by binding with a ketone.
Results and discussion
Knorr-type syntheses50,51 conventionally proceed under mild
conditions even in the absence of a catalyst if amines and
carbonyl compounds are employed as the reactants.52 However,
for less nucleophilic hydrazine derivatives, e.g. 2-pyridine hydra-
zines50 or acyl hydrazides,53,54 a catalyst is desirable to conduct the
reaction under mild conditions. Thus, the reaction of N-acyl
hydrazides with 1,3-dicarbonyl compounds, which leads to N-acyl
pyrazoles, typically requires an additional activation and is usually
conducted in the presence of a Brønsted or a Lewis acid under
reux for several hours.55–57 This reaction was chosen as a model
to verify the catalytic effect of diaryliodonium salts.
Comparison of the catalytic activity for the halogen-
containing organic species
Benzoyl hydrazide (BH) was treated with acetyl acetone (AA) in
CD3OD (50 ꢀC, 5 h), which led to only a trace amount of the
corresponding N-benzoyl pyrazole 1 (Fig. 2 and Table 1, entry 1).
The addition of 1 equivalent (equiv.) of iodine(I)- or bromine(I)-
containing species A–E, which feature expressed s-holes at their
halogen atoms,58–60 resulted in negligible or no catalytic effect
(entries 1–6). In contrast, the utilization of the dibenziodolium
species F, G, and H led to a signicant acceleration and a half-
conversion was achieved aer approximately 70 min (entries 7–
9). Notably, other types of iodine(III) species (I and J) appeared to
be catalytically inactive in the model reaction (entries 10–11)
and the results obtained for the activity of F–I are fully consis-
tent with the recently reported relative Lewis acidity of the
iodine(III)-based XB donors.61
Having examined dibenziodolium triate H, whose catalytic
activity was the highest among all the studied halogen-
containing species, we further optimized the reaction condi-
tions. Based upon 1H NMR monitoring of the reaction per-
formed with various relative quantities of AA, we found that the
optimal quantity of the carbonyl reactant was 1.2 equiv. (Fig. 3;
Table 1, entries 9, 12, 13).
Fig. 2 Halogen-containing species tested as organocatalysts.
Table 1 Comparison of the catalytic activity of various halogen-
containing species
Catalyst load
(mol%)
AA
t
Entry
Catalyst
load (equiv.)
(min)
Yield (%)
1
2
3
4
5
6
7
8
None
A
B
C
D
E
—
1
1
1
1
1
1
1
1
1
1
1
1.5
1.2
1.2
1.2
300
300
300
300
300
300
70
70
70
70
70
Traces
32
Traces
Traces
30
29
50
46
52
100
100
100
100
100
100
100
100
100
100
100
100
50
F
G
H
I
9
10
11
12
13
14
15
3
J
Traces
98
95
98
98
H
H
H
H
70
70
100
220
10
The S-shape of the kinetic curves was caused by the initial
accumulation of the intermediate MeC(]NNHBz)CH2COMe in
the reaction mixture, which was then transformed to 1. The
overlap of the proton resonances of MeC(]NNHBz)CH2COMe
with those of the reactants and with the signals of 1 did not
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Fig. 3 1H NMR monitoring of the reaction of benzoyl hydrazide with
various amounts of acetylacetone in the presence of 1 equiv. H in
CD3OD at 50 ꢀC (entries 9, 12, 13). NMR yield of 1 is given on the y-axis.
allow the accurate calculation of its relative concentration;
therefore, the corresponding plot is not provided.
Next, the relative quantity of organocatalyst H was varied
(Fig. 4, Table 1, entries 1, 9, 14, 15) and we found that even
10 mol% of H effectively catalyzed the reaction and 1 could be
obtained within 1 d (Table 1, entry 15).
The optimal conditions for the studied reaction were
10 mol% of H, 1.2 equiv. of the 1,3-dicarbonyl component, and
50 ꢀC. Under these conditions the substrate scope was veried.
Fig. 5 The 1H NMR titration of H by benzoyl hydrazide.
Binding of H with the reaction substrates
(i)1H NMR titration. To conrm the binding of H with the
reactants, we performed a 1H NMR titration. In these experi-
ments, BH or AA (2, 4, 6, 8, or 10 equiv.) were added to 1 equiv.
of H in a CD3CN solution (0.038 M). The titration by BH (Fig. 5)
indicated a high-eld shi (approx. 0.5 ppm) of the 2-, 3-, and 4-
H resonances, whereas the 1-H resonances of H atoms located
in close proximity to the I atom indicated a low-eld shi by
approximately 0.5 ppm (Fig. 6). Based upon the changes in the
chemical shi of the 1-H protons, the H$BH binding constant
was estimated as 2.8(2) L molꢁ1. The opposite shi of the 1-H
protons might indicate the binding of H with benzyl hydrazide
in solution through XB as this would allow the ligated
nucleophile to directly interact with the atoms while the other H
atoms remain intact.
The titration of H by AA resulted in negligible changes in the
chemical shis (within 0.002 ppm) for the dibenziodolium
cation, even with an excess of AA up to 25-fold; therefore, the
corresponding binding constant could not be estimated. This
observation might indicate either a low value of the binding
constant or similar chemical shis of the H atoms in the H–AA
complex and separated substrates H and AA.
(ii) DFT calculations. Based on the 1H NMR titration data, we
performed DFT calculations to clarify the binding of H with BH
and AA in a MeOH solution. Initial calculations indicated that
Fig. 4 1H NMR monitoring of the reaction of benzoyl hydrazide with
acetylacetone with variable amount of H (CD3OD, 50 ꢀC; entries 1, 9, Fig. 6 The changes in chemical shifts of the H proton resonances
14, 15).
upon the titration.
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Table 2 The calculated Gibbs free energy (DG) and enthalpy change
(DH) for direct binding of H with the substrates in MeOH solutiona
DG
DH
Entry
Reaction
(kJ molꢁ1
)
(kJ molꢁ1
)
1
2
3
4
5
6
H + BH / H$BH (binding by O)
H + BH / H$BH (binding by N)
H + AA / H$AA
i
ii
iii
25.5
24.7
28.0
ꢁ1.3
1.7
ꢁ20.9
ꢁ25.1
ꢁ27.2
23.8
22.2
18.0
1.3
a
H – dibenziodolium triate; BH – benzoyl hydrazide; AA – acetyl
acetone.
the direct coupling of the reagents is thermodynamically
unfavorable in terms of the Gibbs free energy, which conicts
with the experimentally observed titration data at least for BH
(Table 2, entries 1–3).
Scheme 1 Model binding reactions.
Considering that the enthalpies of all the reactions are
negative, these results indicate the signicant impact of entropy
change in the model systems. Accordingly, we included MeOH
solvent molecules, which are the subject of substitution during
the binding of the substrates, in the explicit form in the model
systems (Scheme 1).
The obtained results (Table 2, entries 4–6) appeared to be
coherent with the titration data, i.e. the experimentally observed
small negative DG for the binding of BH (approx.
ꢁ2.5(5) kJ molꢁ1 within 3 st. dev. based on K ¼ 2.8(2) L molꢁ1 at
298 K) and the absence AA binding. Moreover, the theoretical
calculations indicated that the binding of the O atom in BH to
hydrazine derivatives, an additional molecule of a protic solvent
can be changed by a second molecule of the nucleophile.53
Next, three reaction paths for the proton transfer were
studied, i.e., the catalyzed route provided by the coupling of H
with AA (C to D via TS2), the non-catalyzed route (G to E via TS3),
and the coupling of H with the BH (G to H via TS4). The binding
of H with an electrophilic substrate (AA) resulted in stabilization
of the zwitterionic intermediate and reduced the Gibbs free
energy of activation for the reaction (Fig. 7, TS2). The binding of
H with BH (acting in this reaction as a nucleophile) resulted in
a decrease in the energy of the transition state TS4 in compare
with TS2 and TS3, but taking into account that cyclic interme-
diate I was not found, this reaction path was ruled out.
the I atom in H is more energetically favorable in MeOH than
3
coordination by the Nsp atom.
Based on the kinetic measurements, 1H NMR titration data,
and DFT calculations, the plausible mechanism of the studied
Theoretical study of the catalytic mechanism
To understand the catalytic mechanism of H in the studied
reaction (BH + AA / 1 + 2H2O), DFT calculations were per-
formed for the rst (and apparently rate-limiting) step. Initial
calculations indicated that the direct nucleophilic attack of the
Nsp3 atom in BH on the C atom in the carbonyl moiety of AA was
impossible in the absence of H. All attempts to x on the
potential energy surface of the zwitterionic intermediate PhC(]
O)NHN+H2C(–Oꢁ)MeCH2COMe and the corresponding transi-
tion state (TS) for a nucleophilic attack were unsuccessful in the
absence of bound H (the geometry optimization procedure
resulted in the collapse of the relevant model structures to the
initial reactants). Nevertheless, the zwitterionic intermediate
formation is possible then H is bound to AA (Scheme 2, a–c;
accordingly to the processes on Scheme 1, an additional four
MeOH solvent molecules were taken into account in the explicit
form).
reaction includes the binding of the organocatalyst H with AA
3
(Scheme 2, a), a nucleophilic attack of the Nsp atom on the C
atom of the carbonyl group of AA (b and c), incorporation of
a MeOH solvent molecule for the proton transfer (d and e), and
regeneration of H (f).
To better understand how organocatalyst H binds with the
reaction substrates, a theoretical estimation of the strength of
the hydrogen and halogen bonds in the optimized equilibrium
model structures was performed using the topological analysis
of the electron density distribution technique (QTAIM analysis,
see Table 1S in ESI for details†). The calculations indicated that
in all the structures, H forms typical noncovalent bonds with
ligands and the bond energies of H/O and I/O are 9.2–
15.8 kJ molꢁ1 and 19.6–35.7 kJ molꢁ1, respectively.
Investigation of covalent catalysis by H
For the proton transfer from the N atom to the O atom, the
inclusion of one MeOH solvent molecule in the reaction Another type of catalysis—through the formation of covalent
mechanism was realized (TS2, TS3, and TS4).62 Incorporation of bonds of the O atom of the AA carbonyl moiety—was also
the solvent molecule in the transition state of the rate-limiting checked theoretically. All attempts to x on the potential energy
reaction step was successfully employed by us in previous surface of the different kinds of minima for the Meisenheimer
theoretical studies.63 For aprotic solvents, at least in the case of complex-like intermediates were unsuccessful (Fig. 8). Thus,
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Scheme 2 Possible reaction paths.
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Fig. 7 The energy profile for the studied reaction paths.
Fig.
8 One of the five hypothetical Meisenheimer complex-like
intermediate.
geometry optimization for the appropriate model species ob-
tained through the formation of O–C–I, O–C–H1, O–C–H2, O–C–
H3, and O–C–H4 (accordingly to the numeration on Fig. 4) led
to the initial reactants, and these hypothetical structures were
excluded from consideration. These results excluded the
possibility of covalent catalysis.
Reaction scope
Dibenzidolium triate catalyzes the generation of N-acyl pyr-
azoles from AA and a series of aromatic and aliphatic acyl
hydrazides (Scheme 3). For the aromatic acyl hydrazides, the
reaction typically proceeded for 3.5 h, but for the substrates
featuring strong EWG NO2 functionality (5) or bulky Rs in the
ortho-position (6, 7, 10) heating for 6 h was required. The
reaction with the aliphatic acyl hydrazides also required a pro-
longed reaction time (12–15). In all studied cases, the reactions
initially were monitored by 1H NMR and each reaction was
stopped when the concentration of 1–15 was maximal, rather
Scheme 3 Substrate scope. Isolated yields are given.
than at the maximal conversion. This is caused by the slow
solvolysis of 1–15 under the reaction conditions to give 3,5-
dimethyl pyrazole and the corresponding RCO2Me. Our exper-
iments indicated that isolation of the products aer 24 h
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resulted in reduced yields of the pyrazoles by approximately
Preparation procedure for F
25% (except 15: isolated yield 53% aer 24 h).
2-Iodobiphenyl (0.898 mmol, 251.0 mg) and TFA (1.39 mL) were
dissolved in CH2Cl2 (5 mL) and CH2Cl2 was added until
a volume of 10 mL was reached. Then the reagent mixture was
pumped through an Oxone lled column with a syringe pump
(ow rate of 0.11 mL minꢁ1). Aer the addition of the reagent,
the syringe was immediately replaced with a syringe containing
CH2Cl2 (10 mL). CH2Cl2 was pumped for 30 min (ow rate of
0.11 mL minꢁ1) and then the ow rate was increased (0.5
mL minꢁ1) until no CH2Cl2 was le in the syringe. The solvent
was removed from the resulting solution in vacuo and the ob-
tained residue was diluted with water (5 mL). The product was
extracted with CH2Cl2 (3 ꢂ 5 mL). The organic layer was dried
over Na2SO4 and the solvent was removed in vacuo. Then Et2O (5
mL) was added to the residue and formation precipitate
formation was observed. The suspension was stirred for 10 min
and the product was ltered and washed with Et2O (5 mL) and
hexane (2 ꢂ 5 mL). The product was dried in vacuo. Diben-
zoiodonium triuoroacetate F (96% yield, 379 mg) was obtained
as a beige crystalline solid.
Conclusions
We found that dibenziodolium salts are convenient iodine(III)-
based noncovalent organocatalysts, which effectively catalyze
the Knorr-type reactions of N-acetyl hydrazides with AA to give
N-acyl pyrazoles. The reactivity of these salts only slightly
depends on the identity of the cation, but, as expected,61 the
reactivity of the triate appears to be higher than the other
studied salts. 1H NMR titration data and DFT calculations
provided collateral evidence that in MeOH, the catalyst binds to
the hydrazide species, which serve as a nucleophile, and this
binding proceeds through halogen and hydrogen bonds. Our
study indicates that for correct study of binding of iodonium
salts with substrates, solvent molecules should be taken into
account in the explicit form.
The catalytic effect of the iodonium salt is caused by binding
with the ketone, which is less energetically favorable than
binding with the hydrazide. Binding to the electrophile results
in the reduction of the Gibbs free energy of the transition state
of a rate-limiting step of the reaction and thus causes the
catalytic effect of the iodonium salt.
Preparation procedure for G
m-CPBA (77%, 0.736 g, 3.2 mmol) and a solution of HNTf2
(1.26 g, 4.5 mmol) in CH2Cl2 (5.0 mL) were added to a stirred
solution of 2-iodobiphenyl (0.56 g, 0.35 mL, 2.0 mmol) in
anhydrous CH2Cl2 (6.0 mL). The solution was stirred for 24 h at
room temperature, then the solvent was removed on a rotary
evaporator. Et2O (10 mL) was added to the remaining solid. The
mixture was stirred for 20 min, then ltered. The obtained solid
was washed with Et2O three times and dried in vacuo to produce
dibenziodolium bis(triuoromethane)sulfonimide G (0.84 g,
75%) as a pale-yellow solid.
Experimental section
Materials and instrumentation
Solvents and acetylacetone were obtained from commercial
sources and used as received. Acyl hydrazides64 and iodine(III)
derivatives65–67 were synthesized by the known methods. All
syntheses were conducted in air. Chromatographic separation
was carried out on Macherey-Nagel silica gel 60 M (0.063–0.2
mm). Analytical TLC was performed on unmodied Merck
ready-to-use plates (TLC silica gel 60 F254) with UV detection.
Melting points were measured on a Stuart SMP30 apparatus in
capillaries and are not corrected. Electrospray ionization mass-
spectra were obtained on a Bruker micrOTOF spectrometer
equipped with an electrospray ionization (ESI) source. The
instrument was operated in positive ion mode using an m/z
range 50–1200. The nebulizer gas ow was 1.0 bar and the
Preparation procedure for H
m-CPBA (77%, 0.736 g, 3.2 mol) and triic acid (0.57 mL, 6.5
mmol) were added to a stirred solution of 2-iodobiphenyl
(0.56 g, 0.35 mL, 2.0 mmol) in anhydrous CH2Cl2 (6 mL) and
stirred for 1 h at room temperature. Then CH2Cl2 was removed
in vacuo. Et2O (4 mL) was added to the remaining solid. The
mixture was stirred for 20 min and then ltered. The obtained
solid was washed with Et2O three times and dried in vacuo to
provide dibenziodolium triuoromethanesulfonate H (0.781 g,
91%) as a white solid.
drying gas ow 4.0 L minꢁ1
.
For HRESI+, the studied
compounds were dissolved in MeOH. 1H, 13C{1H} and 19F NMR
spectra were measured on a Bruker Avance 400 in CD3CN,
(CD3)2SO, or CD3OD at 298 K; the residual solvent signal was
used as the internal standard.
Preparation procedure for I
Mixture 1 was obtained by dissolving iodobenzene (0.898 mmol,
183 mg, 100 mL) and TFA (1.39 mL) to in CH2Cl2 to achieve
Preparation procedure for benzoyl hydrazide
A heterogeneous mixture of methyl benzoate (341 mg, 250 a total volume of 10 mL. Mixture 2 was obtained by dissolving
mmol) and hydrazine monohydrate (15.0 g, 300 mmol) was 1,3,5-trimethoxybenzene (1.037 mmol) and TFA (2.92 mL) in
reuxed for 18 h during which time a clear colorless solution CH2Cl2 to achieve a total volume of 11 mL.
was obtained. Aer cooling, all volatile components were
Mixture 1 was pumped through an Oxone-lled cartridge
evaporated in vacuo, and the resulting colorless crystalline solid using a syringe pump (ow rate of 0.11 mL minꢁ1). Aer
was dried at room temperature. Recrystallization from benzene/ 15.5 min, mixture 2 was added using a second syringe pump
ethanol (5 : 1) gave analytically pure benzohydrazide as color- (ow rate of 0.11 mL minꢁ1). Aer the addition of mixture 1, the
less needles (27.1 g, 79%).
syringe was immediately replaced with a syringe containing
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CH2Cl2 (10 mL) and pumped (ow rate of 0.11 mL minꢁ1) until with the previously published spectral data. The ESI† le
mixture 2 was completely added. Then the ow rate was contains characterization and spectra of the compounds 1–15.
increased (0.22 mL minꢁ1) for 5 min, then increased again (0.5
mL minꢁ1) until the syringe was empty. The solvent was
removed from the resulting solution in vacuo and the residue
was diluted with water (5 mL). The product was extracted using
CH2Cl2 (3 ꢂ 5 mL). The organic layer was dried over Na2SO4 and
the solvent was removed in vacuo. Then diethyl ether (5 mL) was
added to the residue and a precipitate was formed, the
suspension was stirred for 10 min, then the product was ltered
and washed with diethyl ether (5 mL) and hexane (10 mL). The
obtained product was dried in vacuo.
1H NMR monitoring
Optimization of acetylacetone amount (Fig. 3). Acetylacetone
(0.01, 0.012, 0.015 mmol) was added to the solution of acetyl
hydrazide (0.01 mmol) in CD3OD (0.3 mL), placed in an NMR
tube, whereupon catalyst (0.001 mmol) in CD3OD (0.3 mL) were
added to this mixture. The NMR tube was closed and the ob-
ꢀ
tained homogeneous solution was kept at 50 C for 70 min in
the NMR spectrometer. In this work the reaction was monitored
by measuring 1H NMR spectra every 10 min (for 0.012,
0.015 mmol of acetylacetone) and 5 min (for 0.01 mmol of
acetylacetone) (4 scans, repetition time 4 s) following the initial
Preparation procedure for J
Finely-crushed, solid 2-iodobenzoic acid (1.0 mmol) was mixed equilibration period of 5 min. The reaction was monitored by
with powdered Oxone (400 mg, 0.65 mmol) in a round- measuring the time-dependent integral intensity of the CH3
bottomed ask (50 mL) and stirred without a solvent for group signal for product of reaction (1).
5 min using a magnetic stirrer until a homogeneous reaction
Optimization of the catalyst amount (Fig. 4). Acetylacetone
mass was formed. Then the reaction mixture was cooled with (0.012 mmol) was added to the solution of acetyl hydrazide (0.01
ice to 5 ꢀC and, under magnetic stirring and pre-cooled H2SO4 mmol) in CD3OD (0.3 mL), placed in an NMR tube, whereupon
(5 ꢀC, total 0.8 mL) was added in four portions (0.2 mL) to the different amounts of H (0, 0.001, 0.005, 0.010 mmol) in CD3OD
center of the reaction mixture. Aer the addition of each (0.3 mL) were added to this mixture. The NMR tube was closed
ꢀ
portion, the reaction mass was mechanically shaken to achieve and the obtained homogeneous solution was kept at 50 C for
thorough mixing—the color of the resulting mass varied from 70–220 min in the NMR spectrometer. In this work the reaction
1
pale yellow to brown depending on the intensity of mixing. was monitored by measuring H NMR spectra every 10 min (4
Aer the addition of H2SO4, the reaction was continuously scans, repetition time 4 s) following the initial equilibration
stirred for 30 min at room temperature. The mixture was then period of 5 min. The reaction was monitored by measuring the
cooled to 5 ꢀC, CH2Cl2 (4 mL) and 1,3,5-trimethylbenzene (3.0 time-dependent integral intensity of the CH3 group signal for
mmol) were added, and was then continuously stirred at room the product of reaction (1).
1
temperature for 3 h. The reaction mixture was re-cooled to 5 ꢀC
The H NMR titration of H with benzoyl hydrazide (Fig. 5
and CH2Cl2 (5 mL) and a saturated aqueous solution of and 6). To a series of solutions of H (0.023 mmol) in CD3CN (0.3
NaHCO3 were added in small portions until pH 8.0 was mL) placed in an NMR tube a solution of acetyl hydrazide (0,
reached. The organic layer was separated, and the aqueous 0.046, 0.069, 0.092, 0.115 mmol) in CD3CN (0.3 mL) was added.
1
layer was extracted with CH2Cl2 (5 mL). The organic extracts The H NMR spectra were measured at 298 K.
were combined, dried with Na2SO4, the solvent evaporated,
and the crystalline product was dried in vacuo. Additional
purication of products can be performed by crystallization
from water.
Computational details
The full geometry optimization of all model structures in
methanol solution was carried out at the DFT level of theory
using the M06-2X functional74 with the help of Gaussian-09
program package.75 The quasi-relativistic pseudopotential
Syntheses of 1–15
Powder of a benzoyl hydrazide (1.0 mmol) was added to a solu- MWB46 (ref. 76) that described 46 core electrons and appro-
tion of the iodonium salt (0.1 mmol) in methanol (5 mL) placed priate contracted basis set were used for the iodine atom and
in a 10 mL round-bottomed ask, whereupon acetylacetone (1.2 standard 6-31G* basis sets were used for other atoms. The
mmol) was added to the mixture. The ask was closed and the solvent effects were taken into account using the SMD
obtained homogeneous solution (suspension for 12) was kept at (Solvation Model based on Density) continuum solvation
50 ꢀC for 3.5 h (for 1–8), 6 h (for 9–14), or 20 h (for 15). For 1–15, model suggested by Truhlar and coworkers.77 No symmetry
crude product was subjected to column chromatography on restrictions have been applied during the geometry optimiza-
silica gel (eluted with hexane : ethyl acetate ¼ 4 : 1, v/v) and tion procedure. The Hessian matrices were calculated analyt-
aer collection of the fracture with the product the solvent was ically for all optimized model structures to prove the location
evaporated in vacuo at 50 ꢀC. A light yellow oil (1–4, 6, 8–11, and of correct minimum or saddle point on the potential energy
13) and a colorless crystalline solid (5, 7, 12, 14, and 15) were surface (no imaginary frequencies or only one imaginary
obtained.
frequency, respectively) and to estimate the ꢀthermodynamic
1
Compounds 1–15 were characterized by HRESI+-MS, IR, H parameters, the latter being calculated at 25 C. The topolog-
13
and C{1H} NMR spectroscopies. N-Acyl pyrazoles 1–5,54,68–71 ical analysis of the electron density distribution (QTAIM
7,70 9,54 14,72 and 15 (ref. 73) were previously reported and the analysis)78 was performed by using the Multiwfn program
spectra of these species prepared by our procedure fully agree (version 3.7).79 The Cartesian atomic coordinates for all
© 2021 The Author(s). Published by the Royal Society of Chemistry
RSC Adv., 2021, 11, 4574–4583 | 4581

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optimized equilibrium model structures are presented in the 20 M. Puripat, R. Ramozzi, M. Hatanaka, W. Parasuk,
attached xyz-les.
V. Parasuk and K. Morokuma, J. Org. Chem., 2015, 80,
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Conflicts of interest
There are no conicts to declare.
23 O. V. Serdyuk, C. M. Heckel and S. B. Tsogoeva, Org. Biomol.
Chem., 2013, 11, 7051–7071.
24 F. E. Held and S. B. Tsogoeva, Catal. Sci. Technol., 2016, 6,
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25 X. Han, H. B. Zhou and C. Dong, Chem. Rec., 2016, 16, 897–
906.
26 B. L. Zhao, J. H. Li and D. M. Du, Chem. Rec., 2017, 17, 994–
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27 D. Parmar, E. Sugiono, S. Raja and M. Rueping, Chem. Rev.,
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28 T. Akiyama and K. Mori, Chem. Rev., 2015, 115, 9277–9306.
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Acknowledgements
This work was supported by the Russian Science Foundation
(grant 20-73-10013). Dr Pavel S. Postnikov and Prof. Dr Mekh-
man S. Yusubov (Tomsk Polytechnic University) are thanked for
their valuable advices on the syntheses of the iodine(III)
compounds conducted by N. S. S. Physicochemical studies were
performed at the Center for Magnetic Resonance, Center for X-
ray Diffraction Studies, Chemistry Educational Centre, and
Center for Chemical Analysis and Materials Research (all
belonging to Saint Petersburg State University).
30 J. Merad, C. Lalli, G. Bernadat, J. Maury and G. Masson,
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