Gold-Catalyzed Functionalization of Semicarbazides with Terminal Alkynes to Achieve Substituted Semicarbazones

Article abstract of DOI:10.1002/ejoc.201901108

Gold-catalyzed functionalization of semicarbazides (ArNHCONHNH₂) with various terminal alkynes R²C≡CH (R² = Alk or Ar) in the presence of Ph₃PAuNTf₂ (3 mol-%) grants a range of substituted semicarbazo

Full text of DOI:10.1002/ejoc.201901108

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Accepted Article
Title: Gold-catalyzed Functionalization of Semicarbazides with
Terminal Alkynes to Achieve Substituted Semicarbazones
Authors: Dmitry P. Zimin, Dmitry V. Dar’in, Anastasiya A. Eliseeva,
Alexander S. Novikov, Valentin A. Rassadin, and Vadim
Yurievich Kukushkin
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10.1002/ejoc.201901108
European Journal of Organic Chemistry
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Gold-catalyzed Functionalization of Semicarbazides with
Terminal Alkynes to Achieve Substituted Semicarbazones
Dmitry P. Zimin,[a] Dmitry V. Dar’in,[a] Anastasiya A. Eliseeva,[a] Alexander S. Novikov,[a]
Valentin A. Rassadin,*[a] Vadim Yu. Kukushkin*[a]
Abstract: Gold-catalyzed functionalization of semicarbazides
(ArNHCONHNH2) with various terminal alkynes R2C≡CH (R2 = Alk or
Ar) in the presence of Ph3PAuNTf2 (3 mol %) grants a range of
substituted semicarbazones (16 examples; 93−64%). This novel
metal-catalyzed coupling proceeds under mild conditions (PhCl,
60 °C) and demonstrates a high functional group tolerance; the
reaction is sensitive to the electronic effects of the substituents in
terminal alkynes. Inspection of XRD solid-state structures of three
obtained semicarbazones proved their dimerization via weak to
moderate strength hydrogen bonding. The structures of the
semicarbazones in solutions were studied by concentration
dependent 1H NMR and 2D NMR and these experiments proved the
presence of H-bonds between two molecules. The nature and
energy of H-bonding (3.8–5.1 kcal/mol), degree of electron density
delocalization, and rotational barriers via various bonds in the
equilibrium model structures were studied by DFT calculations at the
M06-2X/6-311++G** level of theory.
particular, cationic gold complexes were widely used for the
synthesis of heterocyclic compounds[12–23] and in the total
synthesis of natural products.[24–26]
It is noteworthy that in the raw of multiple carbon-carbon
bonds, gold has an especially strong affinity to alkynes and
studies focused on reactions of alkynes with various
nucleophiles under homogeneous gold-catalyzed conditions
comprise one of the cutting edge topics of organic catalytic
reactions. In most cases, a key step of the nucleophilic addition
includes activation of unreactive alkynes by a gold(I) center that
makes them sensible toward broad range of nucleophiles, even
weak (Scheme 1).
1. Introduction
Conventionally gold, as a representative of the Noble
metals family, was perceived as chemically inactive, but in the
past decades, these views have been completely changed.
Nowadays it is well known that multiple carbon-carbon bonds
lose a substantial part of their π-electron density after ligation to
a gold center, but their geometry undergoes a minimal change.
This electrophilic activation of alkenes, allenes, or alkynes
determines enhancement of their reactivity toward various
nucleophiles. Another reactivity mode of gold-based catalysts
includes gold-carbenes, which are stabilized by π back bonding
and this property makes them suitable candidates for the
development of chemo- or regioselective reactions. Design of
highly efficient and easily available gold catalysts (for instance,
Ph3PAuNTf2[1]) with excellent activity additionally pushed this
field of chemistry toward new frontiers. As a result, over past two
decades gold-catalyzed organic transformation found numerous
impressive applications in modern synthetic chemistry.[2–11] In
Scheme 1. Mechanism of nucleophilic addition to gold(I)-activated alkynes.
If a nucleophile features an active hydrogen atom(s),
intermediate B undergoes a rapid proton migration to give C that
originates from the formal addition of NuH to the triple bond and
to regenerate the catalyst. In the cases of O-nucleophiles such
as water,[27–33] carboxylic acids,[34–37] and alcohols,[38–40] the
addition proceeds smoothly and target products are very often
formed in excellent yields. However, the addition of N-
nucleophiles proceeds differently, viz. primary- and secondary[41–
44]
amines react smoothly and selectively, whereas ammonia
and hydrazines, instead of the addition to target substrates,
reduce gold(I) to colloid gold thus preventing the planned
reaction. To avoid the poisoning of the catalyst via the reduction,
usage of specifically designed ligands is required.[45–47] By this
reason for a number of N-nucleophiles their reactions with gold-
activated alkynes are unknown. However, based on the data
obtained by cyclic voltammetry reducing ability of
semicarbazides (like hydrazides[48]) severely limited by the
presence of the carbonyl group next to the nitrogen center (E =
0.18, 0.60, and 0.68 V (Ag/Ag+; our CVA data for PhNHNH2,
PhNHCONHNH2, and PhCONHNH2, respectively); this makes
semicarbazides attractive substrates for hitherto unexplored
gold-catalyzed nucleophilic additions.
[a]
Dmitry P. Zimin, Dr. Dmitry V. Dar’in, Dr. Anastasiya A. Eliseeva,
Dr. Alexander S. Novikov, Dr. Valentin A. Rassadin,*
Prof. Dr. Vadim Yu. Kukushkin*
Institute of Chemistry, Saint Petersburg State University
Universitetskaya Nab. 7/9, 199034 Saint Petersburg,
Russian Federation
E-mail: vrassadin@clickchemistrytools.com
E-mail: v.kukushkin@spbu.ru
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/ejoc.201901108
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Here we report on new functionalization of semicarbazides
with terminal alkynes that proceeds in the presence of catalytic
carrying out the reaction using 3 mol % of Ph3PAuNTf2 in
chlorobenzene at 60 °C for 5 h leads to the best synthetic results.
To verify the scope and limitations of the developed approach,
series of alkynes and semicarbazides were tested (Scheme 2).
Commercially unavailable alkynes 2f and 2g were
previously synthesized in our group from the corresponding aryl
amount of the Gagosz catalyst, Ph3PAuNTf2.[1]
This
functionalization has never been reported as metal-free or
metal-catalyzed protocols. Our interest in the synthesis of
semicarbazones was additionally motivated by the available
evidence that they can act as urease inhibitor,[49,50] used as
insecticides,[51] and demonstrate antifungal,[52] anticonvulsant,[53]
antimicrobial,[54] antiproliferative[55] and antitumor[56] activities.
halides
and
trimethylsilylacetylene.[48]
2-Ethynyl-1,3,5-
trimethylbenzene (2h) was obtained from appropriate aldehydes
via the Bestmann–Ohira protocol[57] (for more details see the
Supporting information). Semicarbazides 1b–d were prepared
from commercially available isocyanates and hydrazine hydrate
in accord with the reported procedure.[58]
2. Results and Discussion
Phenylacetylene (2a) and its derivatives bearing moderate-
(4-Me 2b, 4-t-Bu 2c) and strong electron donating (4-MeO 2d)
groups reacted smoothly and, in all cases, semicarbazones
3aa–ad were isolated in excellent yields (85–90%). At the same
time, in case of alkynes bearing even weak electron withdrawing
group target products were isolated in lower yields. Thus, the
semicarbazone 3ae (2-F) was obtained in a moderate yield
(64%), whereas semicarbazones 3af (4-NC) and 3ag (4-O2N)
featuring strong EWGs were isolated in only 43 and 32% yields,
respectively, when the reactions conducted under the optimized
conditions. We overcame this problem by using 5 mol % of
Ph3PAuNTf2 and the larger amount of the catalyst significantly
affected the synthetic results and target 3af and 3ag were
obtained in 65 and 74% yields, correspondingly. Surprisingly
that alkynes 2h featuring the bulky substituent 2,4,6-Me3 next to
the reaction center reacted smoothly and 3ah was isolated in
excellent yield (87%). Terminal aliphatic alkynes reacted similar
to substituted phenylacetylenes with electron donating groups.
In the cases of 1-heptyne (2i) and 1-octyne (2j), 3ai and 3aj
were isolated as a mixture of E/Z isomers (see part Solution
structure of the semicarbazones for more information) in 88 and
86% yields, respectively.
As the next step, we tested several semicarbazides 1b–d
bearing chlorine atoms at different positions of the benzene ring
(4-Cl, 5-Cl, 2,5-Cl) and found that all these species were slightly
less reactive than N-phenylhydrazinecarboxamide (1a).
However, in all cases desired products 3ba–da were obtained in
good yields (72–78%).
To demonstrate the advantage of the developed gold(I)-
catalyzed functionalization reaction, we synthesized 2-(1-(4-
acetylphenyl)ethylidene)-N-phenylhydrazine-1-carboxamide
(3ak), which is difficult-to-obtain via the conventional
approach[59] (Scheme 3).
2.1. Gold-catalyzed integration of semicarbazides and
alkynes
Initially, functionalization of 4-phenylsemicarbazide (1a)
with phenylacetylene (2a) was carried out employing equimolar
ratio of the reagents in the presence of 6 mol % of Ph3PAuNTf2
in ethanol at 60 °C for 2 h. In the attempted reaction, target
semicarbazone 3aa was isolated in only 25% yield (Table 1,
entry 1). In order to find better conditions and to improve the
yield, we tested various solvents, temperature, amount of the
catalyst, and reaction time.
Table 1. Optimization of the reaction conditions.
Conditions [a]
[Au] mol %
Yield, % [b]
Solvent
EtOH
CHCl3
PhCl
time, h
2 h
1
2
3
4
5
6
7
8
6 mol %
6 mol %
6 mol %
3 mol %
3 mol %
3 mol %
3 mol %
3 mol %
25%
77%
98%
63%
79%
93%
93%
86% [c]
2 h
2 h
PhCl
2 h
PhCl
3 h
PhCl
5 h
PhCl
18 h
2 h
PhCl
[a] Equimolar ratios of 1a:2a was used, the reactions were performed at
60 °C; [b] Isolated yield; [c] The reaction was performed at 90 °C.
Employment of chloroform significantly improve the yield of
3aa (77%; Table 1, entry 2), whereas conductance of the
reaction in chlorobenzene led to the full conversion of
semicarbazide 1a as well as alkyne 2a; target 3aa was isolated
in 98% yield (Table 1, entry 3). On the next step, we halved the
amount of the catalyst and found that performance of the
reaction at a longer reaction time led to almost the same
synthetic results (Table 1, entries 4–7). The best yield (93%)
was achieved when the functionalization reaction was run for 5
h. We also demonstrated that keeping the reaction mixture for
18 h instead of 5 h did not improve the yield of the target
product. Running the reaction at a higher temperature (90 ºC)
insignificantly improved the yield of 3aa (Table 1, entry 8). To
summarize optimization of the reaction conditions, we found that
Scheme 3. Synthetic opportunities of the functionalization.
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10.1002/ejoc.201901108
European Journal of Organic Chemistry
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[a] 5 mol % of Ph3PAuNTf2 were used.
Scheme 2. Reaction scope with various terminal alkynes and semicarbazides.
Carbonyl group in 1-(4-ethynylphenyl)ethan-1-one (2k)
was protected with ethylene glycol to generate corresponding
The satisfactory results obtained for semicarbazides as
well as for oxoacetamide prove that the developed protocol is
common for substrates bearing the CONHNH2 moiety and, in
vast majority of cases, the desired products could be obtained in
good to excellent yield.
1,3-dioxalane,
which
was
then
treated
with
N-
phenylhydrazinecarboxamide (1a) in presence of the gold-
catalyst under the optimized conditions.
Finally, the protective group was easily removed under
acidic condition to furnish 3ak in 20% yield over the three steps.
Notably, the deprotection should be done rapidly (1 min)
otherwise the yield of final product drop off substantially because
of the instability of 3ak in the presence of acids.
To prove versatility of the gold-catalyzed integration of
semicarbazides and alkynes, we tested N-benzyl-2-hydrazinyl-2-
oxoacetamide (4) and found that the corresponding derivative of
oxalic acid 5 was formed in good yield (Scheme 4).
2.2. Structures of the obtained semicarbazones
Although semicarbazones are of considerable interest due
to a broad spectrum of their biomedical applications,[49–56]
structural data for these species are quite scarce and desultory.
Our processing of the Cambridge Structural Database (CSD; the
Supporting Information; Figure S2) revealed only 8 relevant XRD
structures.[60–66]
Having
the
substantial
number
of
semicarbazones at hands and being interested in further
developing of their chemistry, we conducted XRD studies of 3aa
(CCDC: 1921761), 3ad (CCDC: 1921796), and 3af (CCDC:
1921762), verified particular features of the solid-state structures,
whereupon we performed the Hirshfeld surface analysis, and
appropriate DFT calculations supporting our structural
conclusions (section 2.2.1) studied their structure in the solution
(section 2.2.2). All these data are consistently described below.
Scheme 4. The reaction of phenylacetylene with N-benzyl-2-hydrazinyl-2-
oxoacetamide.
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2.2.1. The X-ray diffraction and computational studies. The
crystal data, data collection parameters, and structure
refinement data of 3aa (Figure 1), 3ad (Figure S3), and 3af
(Figure S4) are summarized in Table S1 (the Supporting
Information); comments on molecular structure features of these
compounds are also given in the Supporting Information. The
bond distances and angles for the three compounds are in a
good agreement with values reported for similar XRD structures
found in CSD (Figure S5, Tables S2–S3).[60–66]
In the crystal structures of 3aa, 3ad, and 3af, the
semicarbazones are linked to each other through various types
of HBs, viz. C–H···O, C–H···N, and N–H···O. We carried out the
Hirshfeld surface analysis for all X-ray structures to understand
what kind of intermolecular contacts gives the largest
contributions in crystal packing (Table S5).
For the visualization, we have used a mapping of the
normalized contact distance (dnorm); its negative value enables
identification of molecular regions of substantial importance for
detection of short contacts. Figure S9 depicts the Hirshfeld
surfaces for the studied structures.
Since the N–H•••O HBs are the shortest identified
intermolecular contacts, which lead to the dimers (Figure 2), we
provide their parameters (Table 3), whereas all bond distances
and angles for C–H···O and C–H···N contacts are given in the
Supporting Information (Tables S6–S7, Figures S6–S8).
Figure 1. Dimer 3aa formed by N–H···O HBs. The contacts shorter Bondi vdW
radii[67] sums are given by dotted lines. Thermal ellipsoids are shown with the
50% probability. Similar molecular structures of 3ad and 3af are given on
Figures S3–S4.
Figure 2. Schematic representation of dimeric cluster held by N–H···O HBs
involving 3aa, 3ad, and 3af.
The shortest N–H···O contact (d(H···O) = 2.0218(18) Å)
was observed in 3af (Figure S4, Table 4) and it comprises 74%
from the sum of Bondi vdW radii[67] (RvdW(H) + RvdW(O) = 2.72 Å),
whereas the longest N–H···O HB was found in 3ad (d(H···O) =
2.123(2) Å; however, it is still less than Bondi vdW radii sum and
it is formed between the N–H and C=O groups (Figure S3, Table
4). It is noteworthy that in all structures the N···O distances are
also shorter than the sum of Bondi vdW radii[67] (RvdW(N) +
RvdW(O) = 3.07 Å; Table 3).
In order to confirm or disprove the hypothesis on the
existence of N–H···O HBs in semicarbazones, and quantify their
energies from theoretical viewpoint, we carried out DFT
calculations and performed topological analysis of the electron
density distribution within the framework of Bader’s theory
(QTAIM method)[69] for model supramolecular dimeric associates
(Table S9). This approach has already been successfully used
by us upon studies of various types HBs (see refs.[70–72] and
references therein). Results are summarized in Table 4, the
contour line diagram of the Laplacian distribution 2(r), bond
paths, and selected zero-flux surfaces as well as reduced
density gradient (RDG) isosurface[73] referring to hydrogen
bonding N–H···O in supramolecular structure of 3aa are shown
in Figure 3.
We have theoretically estimated the degree of electron
density delocalization in the optimized equilibrium model
structures of 3aa, 3ad, and 3af (M06-2X/6-311++G** level of
theory). The calculated Wiberg bond indices computed by using
the Natural Bond Orbital (NBO) partitioning scheme[68] for selected
bonds in the C1=N1–N2(H)–C2(O1)–N3(H)–C moieties
(Figure S5) of optimized equilibrium model structures of 3aa,
3ad, and 3af are given in Table 2. In this fragment, the electron
density is slightly delocalized. Thus, formal single bonds (N1–N2,
N2–C2, C2–N3, and N3–C) are only insignificantly deviate from
the theoretically expected orders, whereas the C1=N1 and
C2=O1 distances can be classified as one-and-a half chemical
bonds. These statements agree well with the calculated
hybridizations of the C, N, and O atoms in the C1=N1–N2(H)–
C2(O1)–N3(H)–C fragment (Table S8). The Cartesian atomic
coordinates for all optimized equilibrium model structures are
presented in Table S4.
Table 2. Calculated Wiberg bond indices for selected bonds in the C1=N1–
N2(H)–C2(=O1)–N3(H)–C moieties of optimized equilibrium model structures
of 3aa, 3ad, and 3af.
Bond
C1=N1
N1–N2
N2–C2
C2=O1
C2–N3
N3–C
3aa
1.74
1.11
1.05
1.63
1.12
1.04
3ad
1.74
1.10
1.05
1.63
1.12
1.04
3af
1.73
1.12
1.04
1.64
1.13
1.04
The QTAIM analysis performed for model dimeric
associates demonstrates the presence of appropriate bond
critical points (3, –1) (BCPs) for all non-covalent interactions
listed in Table 4. The low magnitude of the electron density
(0.017–0.020 a.u.), positive values of the Laplacian (0.074–
0.093 a.u.), and close to zero positive energy density (0.003–
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0.004 a.u.) in these BCPs are typical for hydrogen bonds.[74–76]
We have defined energies for these weak contacts according to
procedures proposed by Espinosa et al.[77] and Vener et al.,[78]
and one can state that these noncovalent interactions can be
formally classified as HBs of weak to moderate strength (3.8−5.1
kcal/mol) mainly due to electrostatics following the classification
of Jeffrey (“strong” HB, 40−15 kcal/mol; “moderate” HB, 15−4
kcal/mol; “weak” HB, <4 kcal/mol).[79] The balance between the
Lagrangian kinetic energy G(r) and potential energy density V(r)
at the BCPs reveals that a covalent contribution is absent in all
supramolecular contacts listed in Table 4.[80]
Table 3. Parameters of N–H···O HBs in 3aa, 3ad, and 3af.
d(N···O), Å
2.913(2)
2.860(4)
2.889(3)
2.866(3)
2.905(3)
R[a]
0.76
Structure
3aa
N–H···O
N2–H2···O1
d(H···O), Å
2.0767(16)
∠(N–H···O),°
163.76(12)
143.7(2)
3ad
N2A–H2A···O1
N2–H2···O1A
N30–H30···O11
N2–H2···O1A
Comparison [b]
2.121(3)
0.78
0.78
0.74
0.76
1.00
2.123(2)
148.2(2)
3af
2.0218(18)
2.0750(18)
2.72 (H···O)
166.73(16)
162.20 (16)
110<∠<180
[a] R is interatomic distance to vdW sum ratio, the sum of Bondi vdW radii[67] is RvdW(H) + RvdW(O) = 2.72 Å. [b] Comparison with the sum of Bondi vdW radii[67] and
with the typical HB angles.
Table 4. Values of the density of all electrons – (r), Laplacian of electron density – 2(r), energy density – Hb, potential energy density – V(r), and Lagrangian
kinetic energy – G(r) (a.u.) at the bond critical points (3, –1), corresponding to N–H···O HBs in supramolecular structures of 3aa, 3ad and 3af, bond lengths – l (Å),
as well as energies for these contacts Eint (kcal/mol), defined by two approaches.
[a]
[b]
Contact
Hb
3aa
0.004
3ad
V(r)
G(r)
Eint
Eint
(r)
2(r)
l
N2–H2···O1
0.018
0.081
–0.013
0.017
4.1
4.6
2.077
N2–H2···O1A
0.017
0.017
0.074
0.077
0.003
0.003
–0.012
–0.013
0.015
0.016
3.8
4.1
4.0
4.3
2.123
2.121
N2A–H2A···O1
3af
N30–H30···O11
N2–H2···O1A
0.020
0.018
0.093
0.082
0.004
0.004
–0.016
–0.013
0.019
0.017
5.0
4.1
5.1
4.6
2.022
2.075
[a] Eint = –V(r)/2[77]. [b] Eint = 0.429G(r)[78]
Figure 3. Contour line diagram of the Laplacian distribution 2(r), bond paths and selected zero-flux surfaces (left) and RDG isosurface (right) referring to
hydrogen bonding N–H···O in supramolecular structure of 3aa. Bond critical points (3, –1) are shown in blue, nuclear critical points (3, –3) – in pale brown, ring
critical points (3, +1) – in orange. Length units – Å, RDG isosurface values are given in a.u.
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2.2.2. Solution structure of the semicarbazones. Generally,
the semicarbazones were formed as a single stereoisomer.
However, when aliphatic alkynes 2i and 2j were used for the
functionalization, a mixture of E/Z isomers was detected; a pure
major isomer was isolated after column chromatography. To
verify the stereochemistry of the obtained compounds we
recorded 2D NMR of 3aj (derived from hept-1-yne and 4-
phenylsemicarbazide) in dimethyl sulfoxide-d6. In the 2D NOESY
spectra (the Supporting information) of 3aj for major isomer of
3aj, we observed cross-peaks between the NH and CH3 groups
and consequently we assigned the E-configuration of the double
bond.
We found that the chemical shift of 1 out of 2 protons on
nitrogen strongly depends on concentration; the peak shifted
from 9.44 to 8.28 ppm when the sample solution was diluted by
8 times. This experiment confirms the presence of HBs in
solutions. To assign signals of the NH groups we measured the
NOESY spectra and figured out that H atom from the NHN
moiety is involved in the formation of HBs. This result is
coherent the data obtained from the solid-state XRD study that
indicates that the same H atom forms HB (section 2.2.1).
3. Concluding Remarks
In the NMR spectra of all obtained semicarbazones, we
found only one set of signals, which indicates that single bond
rotational barrier is relatively low. These data agree well with the
calculated Wiberg bond indices and hybridizations of the C, N,
and O atoms in the C1=N1–N2(H)–C2(O1)–N3(H)–C moieties of
the optimized equilibrium model structures of 3aa, 3ad, and 3af
(Tables 2, S8). For 3aa, we theoretically estimated values of the
rotation barriers via C1=N1, C1–Ph, C1–Me, N2–C2, and C2–N3
bonds using the relaxed potential energy surface scan at the
M06-2X/6-311++G** level of theory. Based on the obtained
optimized equilibrium geometry of 3aa, we define appropriate
dihedral angles to be scanned in the range of 180° by
increments of 5°, assuming that the energy barriers associated
with the rotation by these dihedral angles can be estimated as
the difference between the obtained minimum and maximum
values of the calculated total energies. The values of rotation
barriers via N2–C2 and C2–N3 bonds calculated by this
technique are 13.6 and 14.1 kcal/mol, respectively, which is
noticeably higher than almost barrier-free rotations via C1–Ph
and C1–Me bonds (3.5 and 1.3 kcal/mol, respectively), but
slightly lower than the rotation barrier of the N–C bond in DMF
(19.4 kcal/mol).[81]
In conclusion, we have developed a new highly effective
general approach toward substituted semicarbazones based on
the gold-catalyzed integration between terminal alkynes and
semicarbazides. The observed high-yielding reaction utilizes
easily accessible substrates, proceeds under mild conditions,
demonstrates broad scope and substantial functional group
tolerance, and can be used in industry. The structure of the
obtained semicarbazones in solution was evaluated employing
concentration dependent 1H NMR and 2D NMR technique. Solid
state structure was studied using X-ray crystallography. The
Hirshfeld surface analysis performed for the obtained XRD data
shows that crystal packing in all cases is determined primarily by
intermolecular contacts involving H atoms. Results of DFT
calculations followed by the topological analysis of the electron
density distribution within the framework of Bader’s theory
(QTAIM method) reveal that the shortest identified
intermolecular contacts N–H•••O in the solid state leading to the
formation of dimers can be formally classified as hydrogen
bonds of weak to moderate strength (3.8–5.1 kcal/mol).
Acknowledgements
In order to identify the H-bond in the solution structures,
we measured 1H NMR spectra of 3aa at variable concentrations.
These measurements were conducted in a mixture of CCl4 and
CDCl3 (1:1, v/v); this solvent system was used due to the
differences of chemical shift of protons next to the N atom was
higher than in either CDCl3, or CD2Cl2 (Figure 4).
We gratefully acknowledge the support of the Russian
Foundation of Basic Research (synthetic part: grant 18-33-
00277 mol_a; theoretical part: grant 19-03-000444). A.A.E. is
grateful to Saint Petersburg State University for postdoctoral
fellowship. We thank Dr. A.Yu. Ivanov for the NMR experiments
and valuable suggestions. All physicochemical measurements
were performed at the Center for Magnetic Resonance, Center
for Chemical Analysis and Material Research, Center for X-ray
Diffraction Methods, and Educational Center of Chemistry (all
belonging to Saint Petersburg State University).
Keywords: Gold catalysis • Alkynes • Semicarbazone • X-ray •
Hydrogen bond • DFT calculations
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Gold catalysis
Dmitry P. Zimin, Dmitry V. Dar’in,
Anastasiya A. Eliseeva, Alexander S.
Novikov, Valentin A. Rassadin,*
Vadim Yu. Kukushkin*
Page No. – Page No.
Gold-catalyzed functionalization of semicarbazides with various terminal alkynes
grants a wide range of semicarbazones. Inspection of XRD solid-state structures of
the obtained semicarbazones proved their dimerization via weak to moderate
strength hydrogen bonding. The nature and energy of this H-bonding, degree of
electron density delocalization, and rotational barriers of various bonds were
studied by DFT calculations at the M06-2X/6-311++G** level of theory.
Gold-catalyzed Functionalization of
Semicarbazides with Terminal
Alkynes to Achieve Substituted
Semicarbazones
This article is protected by copyright. All rights reserved.