Addressing Hydrogen Bonding Motifs by Suited Substitution of Thioureas

Article abstract of DOI:10.1002/zaac.201600126

The possibility to form hydrogen bonds with different motifs is an interesting aspect of the chemistry of thioureas especially regarding catalysis. We present nine new thioureas with different unsymmetric substitution patterns involving aromatic and aliph

Full text of DOI:10.1002/zaac.201600126

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Zeitschrift für anorganische und allgemeine Chemie
DOI: 10.1002/zaac.201600126
Addressing Hydrogen Bonding Motifs by Suited Substitution of Thioureas
Katharina Hollmann,[a] Alexander Oppermann,[a] Maike Amen,[b] Ulrich Flörke,[b]
Hans Egold,[b] Alexander Hoffmann,[a] Sonja Herres-Pawlis,*[a] and Gerald Henkel[b]
Keywords: Thiourea; Hydrogen bonds; Molecular structure; Density functional calculations; NRT
Abstract. The possibility to form hydrogen bonds with different motifs
is an interesting aspect of the chemistry of thioureas especially regard-
ing catalysis. We present nine new thioureas with different unsymmet-
ric substitution patterns involving aromatic and aliphatic substituents
including the structural characterization of four of them. Herein, three
different hydrogen bond patterns could be realized. Moreover, DFT
calculations were performed to investigate the strength of the hydrogen
bonds. Hereby, we show that we can selectively address different
hydrogen bonding motifs by the choice of substituents. This enables a
correlation of the molecular structure and the bonding motifs. Ad-
ditionally, by natural resonance theory, we show that the contribution
of the thiolate resonance form dominates the electronic structure,
which is important for coordination chemistry.
applications ranging from organic catalysis to textile manufac-
turing and also extraction of metals.[18] Through different opti-
mization studies, the thiourea derivative and its closely related
analogues could be identified as universal and very effective
catalysts in Strecker reactions.[15,16] Moreover, a diverse spec-
trum of reactions[11,14,19–25] is catalyzed by thiourea deriva-
tives, e.g. Diels-Alder,[26] Michael addition,[27–30] Aza-
Henry,[27,29] Morita-Baylis-Hillman,[13,17,31,32] and the ring-
opening polymerization of lactide.[33–35]
Besides organocatalysis, thiourea based compounds such as
antithyroid drugs are useful in the medical field. They have
influence on the thyroid hormone, which controls the protein,
fat, and carbohydrate metabolism of the human body.[36]
In addition, thiourea serves as a source of sulfide in organic
transformations, e.g. for converting alkyl halides to thiols.[37]
It has a high industrial potential: in the textile industry it is
used as a reductive bleaching agent in combination with
hydrogen peroxide.[38] Additionally, thiourea derivatives have
also various agricultural applications as herbicides, fungicides
and rodenticides.[39]
Herein, we report on nine new thioureas with different sub-
stitution patterns involving aromatic and aliphatic residues. By
means of molecular structures and theoretical analyses, we
show that we can selectively address different hydrogen bond-
ing motifs by the choice of substituents. This enables a corre-
lation of the molecular structure and the bonding motifs with-
out the requirement of a moleculare structure. This is sup-
plemented through theoretical studies e.g. natural resonance
theory (NRT), which shows large contribution of the thiolate
form.
Introduction
Thioureas are important organocatalysts and also ligands for
coordination chemistry. Organocatalysts had a large impact on
modern chemistry for the last few decades and they are a part
of an intensively investigated research field since then.[1–4]
They can be environmentally friendly, of only minor toxicity,
and cheap.[2,4,5] In many cases, these catalysts offer an easy
way to produce asymmetric compounds in an enantiopure
manner.[1,6] Here, thiourea derivatives have found to be highly
useful. Because of their hydrogen-bonding interactions with
other organic molecules they are well-suited for organocata-
lysis.[7] The hydrogen-bonding mediated catalysis received
wide acceptance and is nowadays involved in many enantiose-
lective transformation reactions.[8,9]
Today, different kinds of thiourea catalysts (chiral or achiral,
mono- and bifunctional) are known. The growing interest on
the hydrogen bonding of thiourea began in the 1970’s when
Coiro et al. analyzed the intermolecular hydrogen bonds of
N,NЈ-dicyclohexylurea.[10] Since 2001 several potential achi-
ral/chiral mono- and bifunctional thiourea and urea derivatives
have been synthesized and characterized by many research
groups for example by Schreiner et al.[11] and other research
groups.[8,12,13–17] One of the first remarkable catalysts of this
kind was published in 1998 by Jacobsen et al.[15] They have
synthesized a variety of chiral Schiff base thioureas with broad
* Prof. Dr. S. Herres-Pawlis
E-Mail: sonja.herres-pawlis@ac.rwth-aachen.de
[a] Institut für Anorganische Chemie
RWTH Aachen University
Landoltweg 1
52074 Aachen, Germany
[b] Universität Paderborn
Warburger Str. 100
Results and Discussion
33098 Paderborn, Germany
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/zaac.201600126 or from the au-
thor.
We synthesized nine new unsymmetrically substituted thio-
ureas 1–9 analogous to the research group of Kong et al.[40]
Z. Anorg. Allg. Chem. 2016, 642, (9-10), 660–669
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Figure 1. Overview of the new thiourea derivatives.
The desired thiourea derivative is produced by reaction of the
The thioureas are synthesized in very good yields in the
corresponding primary amine with an isothiocyanate in aceto- range of 60–95%. Various attempts to purify the respective
nitrile (general procedure in Scheme 1).
products revealed that it is beneficial to perform the syntheses
with an excess of the primary amine. Hereby the starting mate-
rials and the product can be better separated from each other.
In order to simplify the following discussions of the unsym-
metric substitution pattern of the thioureas, the N atom arising
from the amine is called Na and the other one generated from
the isothiocyanate is labelled NIC, respectively.
In the following section we present the molecular structures
of the thioureas 1, 3, 4, and 6 in the solid state and the results
of the performed DFT calculations. The compounds 1, 3, 4,
and 6 were characterized with single-crystal X-ray structure
analysis. All structures display a hydrogen-bonding network
but with different motifs. The molecular structures show three
different motifs. These motifs are displayed in Figure 2. The
dimeric motif A, which is formed by compound 1 and 3, con-
tains two N–H···S interactions. The motif B consists of an infi-
nite chain with a bifurcated pattern of the hydrogen bonds.
Scheme 1. General reaction scheme of the synthesis of thioureas (Na
indicates the nitrogen atom from the amine source, whereas NIC indi-
cates the isothiocyanate side).
The synthesized thioureas are shown in Figure 1. The used
starting compounds contain three different isothiocyanates and
four primary amines. All of these thiourea derivatives exhibit
a characteristic resonance in the 13C NMR spectrum of the
quaternary carbon atom of the thiourea group at approximately
180 ppm (Table 1). As expected, the two NH protons have dif-
ferent chemical shifts because of the unsymmetric substitution
pattern. NH protons in close proximity to aromatic systems
appear in low field (ca. 8–9 ppm) and those, which are close
to an aliphatic system are found at a higher field (ca. 6–7 ppm)
in the NMR spectra. The largest differences appear in mol-
ecules with an aromatic and aliphatic residue e.g. compound 2
with signals at 6.70 (aliphatic side) and 8.51 ppm (aromatic
side). In most cases the difference is about one ppm as found
in compound 1.
Table 1. Positions of the NH and quaternary carbon signals /ppm of
the functional groups.
1
Ligand
Yield /%
Key position H (NH)
Key position 13C
1
2
3
4
5
6
7
8
9
75
63
76
58
94
60
87
68
63
8.27
6.70
6.97
6.69
8.76
6.75
6.68
9.22
6.72
9.23
8.51
8.14
8.47
8.85
7.09
6.80
9.53
8.56
178.4
180.5
180.3
180.2
180.0
182.0
182.1
179.1
181.1
Figure 2. Hydrogen bonding motifs.
Both (N)H functions of one molecule, which form this motif
B, are connected to the thiourea sulfur of a neighboring mol-
Z. Anorg. Allg. Chem. 2016, 660–669
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ecule of 4. The third motif C shows hydrogen bonds that do
not involve the thiourea sulfur atom. They form a motif with
molecules connected to infinite chains via additional S and N
donor functions.
The molecular structure of 1 is shown in Figure 3. The sub-
stituent of the nitrogen atom NIC of this compound is a phenyl
ring and Na is bound to the tert-butyl(phenyl)sulfide residue.
The molecular structure exhibits N1–H1···S1# hydrogen bond-
ing motifs with N–H···S of 2.48 Å that connect molecules into
non-crystallographic centrosymmetric dimers.
Figure 5. Unsubstituted thiourea (black hydrogen bonds = motif
A / blue hydrogen bonds = motif B).[41]
Table 2. Selected bond lengths /Å and angles /° of 1, 3, 4, and 6 (IC
= side of the isothiocyanate residue, a = side of the amine residue).
Figure 3. Molecular structure of 1. Intermolecular hydrogen bonds are
shown as dashed lines (motif A).
1
3
4
6
C=S
NIC–C(1)
1.685(1)
1.353(1)
1.358(1)
1.699(2)
1.349(3)
1.342(3)
118.6(2)
119.8(2)
121.6(2)
1.691(2)
1.335(3)
1.361(3)
114.2(1)
121.0(2)
124.8(2)
1.690(1)
1.348(2)
1.344(2)
114.9(2)
121.6(2)
123.6(1)
The substituents of 4 are a tert-butyl(phenyl)sulfide on one
side and a methyl(propyl)sulfide on the other side of the mol- Na–C(1)
Na–C(1)–NIC 115.2(1)
S–C(1)–NIC
S–C(1)–Na
ecule. In compound 4 hydrogen bonding motif B is found. It
is an infinite chain in the crystal where the units are perpendic-
ular to each other (89.9°) (Figure 4).
118.3(1)
126.5(1)
Figure 4. Molecular structure of 4. Intermolecular hydrogen bonds are
shown as dashed lines (motif B).
Figure 6. Molecular structure of 3. Intermolecular hydrogen bonds are
shown as dashed lines (motif A).
The involved two N–H···S hydrogen bonds are different
with 2.35 and 2.77 Å and related C–S···H angles of 95.1° and
107.3°. These two bonding motifs coexist in unsubstituted
thiourea (see Figure 5).[41,42]
This compound also represents the hydrogen bonding motif
Its dimeric structure is highlighted with black hydrogen A as 1, but with a shorter N–H···S# interaction of 2.37 Å. The
bonds and the infinite chain through blue hydrogen bonds. Se- molecular structure of compound 6 is shown in Figure 7. It
lected bond lengths and angles of all molecular structures are comprises the same [(ethylthio)methyl]pyridine residue as 3
shown in Table 2.
but has a methyl-(propyl)sulfide at Na. In contrast to the other
In addition to 1, compound 3 also forms a dimeric structure structures, the N–H···S bond involves the sulfur of the func-
via hydrogen bonds (Figure 6). The molecular structure has a tional group. Additionally, an N–H···N(py) interaction occurs
2-[(ethylthio)-methyl]pyridine residue at Na and a phenyl ring at the pyridine. Similar to 4, the hydrogen bonds connect the
at NIC.
molecules into infinite chains.
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the same level as compound 3, where the hydrogen bond
length is well predicted (exp. 2.37 Å and calcd. 2.38 Å). The
hydrogen bonds of compounds 4 and 6, which could be de-
scribed as infinite chains, feature a similar accordance with the
molecular structure as 1. The S···H bond lengths of 4 and 6
are displayed too long in the DFT calculations. The second
hydrogen bond of 6 (N···H) is well described by the theoretical
approach. The angles of all compounds are determined well
by the used DFT methods. Remarkable is that the symmetry
of compound 1, 4, and 6 is broken in the calculations with the
PCM model which is identified through slightly unsymmetric
atom distances and charge transfer energies. The differences
between the atom distances and angles of these compounds are
not very large but noticeable. The charge transfer energies of
the hydrogen bonding interactions of the dimers are reported
in Table 3.
Figure 7. Molecular structure of 6. Intermolecular hydrogen bonds are
shown as dashed lines (motif C).
Table 3. Selected bond lengths /Å, angles /° and hydrogen bonding
energy /kcal·mol–1 of DFT calculations of 1, 3, 4, and 6 [TPSSh/6-
311++G(d,p) with PCM for acetonitrile] (IC = side of the isothio-
cyanate residue, a = side of the amine residue).
A recent review discusses various hydrogen bonding pat-
terns of (substituted) thioureas[42] and the role of substituents
in the structures of thioureas are also described.[43] The results
exhibit the possibility for selectively addressing different
hydrogen bonding motifs through unsymmetrical substitution
patterns at the nitrogen donor atom. Both dimeric structures 1
and 3 have aromatic rings substituted on the nitrogen atom.
The infinite chain 4 has one pure aliphatic residue. The
hydrogen bonding motif C of thiourea 6 is an infinite chain as
well and it is constructed with a similar pattern, but it has
different hydrogen bonds (Figure 7). This could be one aspect
for a directed hydrogen bonding motif and a further step
1
3
4
6
C=S
1.701
1.702
1.357
1.356
1.360
1.360
2.389
2.388
–
1.710
1.697
1.701
1.347
1.348
1.374
1.368
2.472
1.709
1.703
1.355
1.350
1.351
1.357
–
NIC–C(1)
NA–C(1)
S···H(1)
S···H(2)
1.357
1.345
2.381
–
–
–
3.008
–
–
113.32
113.37
121.76
121.02
124.90
125.58
103.19
–
towards a selective synthesis of specific hydrogen bonding mo- Ste···H(1)
–
–
2.952
1.965
114.57
115.61
122.27
121.65
123.16
122.74
–
tifs for organocatalysis.[8,9,12–17,19–35]
To further investigate these bonding patterns and to clarify
the question for the thione or thiolate character of the thiourea,
DFT calculations were performed. In the past, large basis sets
with diffusion and polarization functions have been found use-
ful for the description of hydrogen bonding systems. Scheiner
et al. used larger basis set in MP2/aug-cc-pVDZ calculations
to describe the interactions between thioureas and imines.[44]
Npy···H(1)
Na–C(1)–Nic
115.29
115.43
119.61
119.53
125.04
124.99
109.63
109.52
–
117.69
Stu–C(1)–Nic
119.93
122.38
109.09
Stu–C(1)–Na
C(1)–Stu···H(1)
C(1)–Stu···H(2)
–
–
122.60
–
–
In this work, the calculations were carried out with the triple- C(1)–Ste···H(1)
–
90.65
122.57
113.44
127.64
–
zeta basis set 6-311++G(d,p) and the hybrid functional TPSSh
in various solvents and with or without empirical dispersion
correction (results are shown in the Tables S1 and S2, Support-
ing Information).
In contrast to the expensive MP2 method, our method is
comparatively efficient. Since the computational costs in-
crease, the DFT offers a good alternative to these methods.[45]
The results of the calculations based on two molecules of the
C–Nic···H(1)
–
–
–
Energy Stu···H–NIC 14.80
Stu···H–Na
Ste···H–NIc
NPy···H(1)–Na
15.60
15.60
–
11.55
–
1.22
–
15.54
–
–
–
1.64
11.69
–
Except the hydrogen bonds with atom distances of more
respective compounds with the PCM solvent model for aceto- than 3 Å, the energy of the hydrogen bonds in these thioureas
nitrile without dispersion correction are shown in Table 3. The amounts to 11.5–16 kcal·mol–1. These energy values are in a
results of this theoretical description show the best overall good agreement with the results from Scheiner et al. (ca. 16–
agreement with the experimental data of the X-ray analysis. 18 kcal·mol–1).[44] Besides this, NRT (natural resonance
The C=S bond lengths are predicted slightly too long (ca. theory) calculations were performed to predict the relative con-
0.02 Å), but the C–N bonds are well described. Differences are tributions of different resonance structures of 1, 3, 4, and 6 to
observed in the hydrogen bond lengths of the dimeric struc- investigate the principle character of the synthesized thioureas,
tures of compounds 1 and 3. The molecular structure of 1 whether they have a thiolate or thione character. We focus on
shows the hydrogen bond length with a length of 2.48 Å, but the percentage distribution of the resonance forms with regard
in the calculations it is significantly smaller (2.38 Å) and is on to the domination of the thione or thiolate form. Because of
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Figure 8. Resonance structures of the compounds 1, 3, 4, and 6 (calculated by NRT).
this, the NRT percentage distributions for all aromatic reso- urea derivatives. With NRT calculations, we investigated the
nance forms of the same basic structure have been com- relative contributions of the different resonance structures. The
bined.[46] The results are shown in Figure 8. The contribution results show a strong preference to the thiolate forms of the
of the thione form is predicted with 34.4 to 36.3% for the compounds, which is an important aspect for coordination
corresponding compounds. The dominant form is the combina- chemistry.
tion of the two thiolate forms A and B with in total ca. 60%.
Further investigations will be focused on the variation of
Similar results have been obtained for unsubstituted thio- the thiourea derivatives to confirm the possibility of directed
ureas.[47] As shown in Figure 8, the A and B forms are not hydrogen bond modification.
predicted equally. The form with the highest contribution is
the thiolate form A of 3. Generally, the dominant form between
Experimental Section
these two thiolate forms is the one with the positive charge on
the nitrogen atom with an aliphatic group. In compound 6,
with aliphatic groups on both nitrogen atoms, the differences
of the distribution is smaller (31.2% and 32.4%) as in the
other compounds. The preference for the thiolate form is an
General Methods: All reactions were carried out in a nitrogen atmo-
sphere. Nitrogen was dried by passage through P2O5. NMR spectra
were recorded with a Bruker Avance 500-spectrometer at 30 °C. 1H
and 13C NMR chemical shifts are given relative to TMS (0 ppm).
important aspect with regard to their potential coordination Assignment of NMR signals was done with the help of additional 2D
experiments (DEPT-135, DEPT-Q, HMBC, HMQC, COSY). Mass
spectra data were measured in acetonitrile with a Synapt 2G from
Waters (ESI pos/neg; 3 kV; source-T 120 °C; con gas flow 30 L·h–1
nitrogen; solvation gas flow 650 L·h–1 nitrogen). IR spectra were re-
corded with a Bruker Vertex 70 FT-IR Spectrometer with ATR tech-
nique. CHN analyses were measured with an Elemental Analyzer
Modell 240 of PERKIN-ELMER. All chemicals were purchased from
properties.
Conclusions
The possibility to form hydrogen bonds with different motifs
is an interesting aspect of the chemistry of thioureas especially
regarding catalysis. We have presented nine new substituted Fluka, Sigma Aldrich, Acros Organics, abcr and Merck. All primary
amines were synthesized according to literature or analogue to
them.[48–50] The solvents were purified by standard literature pro-
cedures.[24]
thioureas including the structural characterization of four of
them. Herein, three different hydrogen bond patterns could be
realized. The results show a distinct relation between the sub-
stitution pattern and the corresponding bonding motifs. We
have found that the substitution of a phenyl group on one of
the NH groups results in the dimeric structure motif A of 1
and 3. With a substitution of the aliphatic residue the motif
changes to an infinite chain with different types even among
Crystal Structure Analyses: Crystal data for compounds 1, 3, 4, and
6 are presented in Table 4. Data were collected with a Bruker-AXS
SMART[51] APEX CCD, using Mo-Kα radiation (λ = 0.71073 Å) and
a graphite monochromator. Data reduction and absorption correction
were done with SAINT and SADABS.[51] The structures were solved
themselves [4 (B) and 6 (C)]. We can selectively address dif- by direct and conventional Fourier methods and all non-hydrogen
atoms refined anisotropically with full-matrix least-squares based on
F2 (SHELXTL[51]). Hydrogen atoms were derived from difference
Fourier maps and placed at idealized positions, riding on their parent
C atoms, with isotropic displacement parameters Uiso(H) = 1.2Ueq(C)
and 1.5Ueq(C methyl). All methyl groups were allowed to rotate but
not to tip.
ferent hydrogen bonding motifs by the unsymmetrical substitu-
tion pattern. The molecular structures are well described by
DFT calculations with the triple-zeta basis set 6-311++G(d,p)
and the hybrid functional TPSSh in various solvents and with
and without dispersion correction. Remarkable is that the sym-
metry of the molecular structure is broken in most cases. Fur-
ther investigations of the charge transfer energies of the
hydrogen bonds show that their energies lie in a range of 11.5
Crystallographic data (excluding structure factors) for the structures
reported in this study have been deposited with the Cambridge Crystal-
to 16 kcal·mol–1 independent of the bonding motif of the thio- lographic Data Centre, CCDC, 12 Union Road, Cambridge CB21EZ,
Z. Anorg. Allg. Chem. 2016, 660–669
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Table 4. Crystallographic data and parameters of 1, 3, 4, and 6.
1
3
4
6
Empirical formula
C17H20N2S2
316.47
C15H17N3S2
303.44
C15H24N2S3
328.54
C13H21N3S3
315.51
Formula mass /g·mol–1
Crystal size /mm
T /K
0.50ϫ0.38ϫ0.32
130(2)
0.20ϫ0.08ϫ0.04
130(2)
0.49ϫ0.18ϫ0.11
130(2)
0.47ϫ0.19ϫ0.10
130(2)
Crystal system
Space group
triclinic
P1
monoclinic
C2/c
monoclinic
P21/c
orthorhombic
Aba2
¯
a /Å
b /Å
c /Å
α /°
9.3283(11)
9.8195(12)
9.8608(12)
74.937(2)
66.329(2)
82.522(2)
798.48(17)
2
19.574(5)
7.8292(19)
20.210(5)
90
100.525(7)
90
3045.0(13)
8
1.324
19.453(5)
10.019(2)
8.885(2)
90
101.916(5)
90
1694.4(7)
4
1.288
15.8792(18)
20.732(3)
9.5760(11)
90
90
90
3152.5(7)
8
1.330
β /°
γ /°
V /Å3
Z
ρcalc. /mg·m–3
1.316
0.328
μ /mm–1
0.343
0.430
0.461
λ /Å
F(000)
0.71073
336
0.71073
1280
0.71073
704
0.71073
1344
hkl range
–12/12; –9/12; –12/12 –25/22; –10/10; –26/26 –24/25; –13/13; –11/11 –20/20; –22/27; –12/12
Reflections collected
Independent reflections
Rint.
Reflections observed
Number of parameters
R1 [I Ն 2σ(I)]
wR2 (all data)
Goodness-of-fit
Largest diff. peak, hole /e·Å–3
7571
3766
0.0124
3766
190
0.0300
0.0832
1.019
14034
3633
0.0651
3633
181
0.0460
0.1073
1.006
15049
4028
0.0832
4028
193
0.0449
0.0906
0.881
12634
3755
0.0390
3755
173
0.0330
0.0738
1.044
0.353 and –0.325
0.323 and –0.279
0.402 and –0.362
0.298 and –0.177
UK. Copies of the data can be obtained free of charge on quoting Synthesis of [2-(tert-Butylthio)phenyl]-3-phenylthiourea (1): Analo-
the depository numbers CCDC-1434770 (1), CCDC-1434772 (3), gous to the general procedure, amine A1[48] (2.17 g, 12 mmol) and
CCDC-1434771 (4), and CCDC-1434773 (6) (Fax: +44-1223-336-
033; E-Mail: deposit@ccdc.cam.ac.uk, http://www.ccdc.cam.ac.uk).
phenylisothiocyanate (1.3 mL, 10.9 mmol) were added to anhydrous
acetonitrile (120 mL). The reaction mixture was stirred for 3 h at room
temperature and the solvent was removed under reduced pressure. The
residue was washed with Et2O and dried under vacuum. The product
is a white solid (2.57 g, 8.14 mmol, 74.6%). Single crystals suitable
for X-ray diffraction were obtained through recrystallization from
acetonitrile.
Computational Details: Density functional theory (DFT) calculations
were performed with the program suite Gaussian 09.[52] The geome-
tries of the complexes were optimized using the nonlocal hybrid meta
GGA TPSSh functional[53] and the triple-zeta basis set 6-311++G(d,p)
as implemented in Gaussian on all atoms. The starting geometries for
the complexes were generated from the molecular structures. Fre-
quency calculations did not show imaginary values verifying local mi-
nima on the potential surface. NBO calculations for the complexes
were accomplished by use of the program suite NBO 6.0 (includ-
ingNRT calculations).[54] As dispersion correction, we used Grimme
D3[55] dispersion correction as implemented in Gaussian, Revision
D.01 with Becke-Johnson damping factors[56] for TPSSh.
General Solution-phase Synthesis of N/NЈ-Thiourea: The general
synthesis proceeds comparable to the procedure of Kong et al.[40] The
corresponding primary amine (12.0 mmol) (depending on the product)
was dissolved in anhydrous acetonitrile (120 mL). To this solution the
corresponding isothiocyanate (10.9 mmol) was added and the reaction
mixture was stirred for 3 h at room temperature. The solvent was re-
moved under reduced pressure. The purification of the crude product
is specified at the compound. These purification steps differ from the
synthesis protocol of Kong et al.[40]
1H NMR (500 MHz, CDCl3, 30 °C, ppm): δ = 1.06 (s, 9 H, H15);
3
4
7.08 (ddd, 1 H, H11, JHH = 7.5, JHH = 1.4 Hz); 7.35–7.43 (m, 4 H,
3
4
H1, H3, H10); 7.46 (dd, 1 H, H12, JHH = 7.6, JHH = 1.6 Hz); 7.49
3
(m, 2 H, H2); 8.27 (br. s, 1 H, H5); 8.84 (dd, 1 H, H9, JHH = 8.2,
4JHH = 0.9 Hz); 9.23 (br. s, 1 H, H7). 13C NMR (125 MHz, CDCl3,
30 °C, ppm): δ = 30.5 (CH3, C15); 48.0 (Cq, C14); 122.3 (CH, C9);
123.0 (Cq, C13); 124.3 (CH, C11); 126.6 (CH, C1); 128.0 (CH, C3);
129.8 (CH, C10); 130.2 (CH, C2); 136.0 (Cq, C4); 138.5 (CH, C12);
141.9 (Cq, C8); 178.4 (Cq, C6). IR (ATR): ν˜ = 606 (vw), 627 (w), 658
(m), 696 (m), 735 (m), 760 (s), 773 (m), 808 (vw), 837 (vw), 910 (w),
Synthesis of the Starting Material: The primary amines 2-(tert-
butylthio)aniline (A1),[48] 2-[(2-aminoethyl)thio]-N,N-dimethylethan- 939 (m), 1003 (w), 1024 (vw), 1035 (w), 1072 (m), 1120 (m), 1165
amine (A2),[49] 2-[(pyridin-2-ylmethyl)thio]ethanamine (A3)[50] and 2- (m), 1176 (s), 1254 (m), 1288 (m), 1308 (m), 1360 (m), 1390 (vw),
[(pyridin-2-ylmethyl)thio]aniline (A4)[50] were synthesized according
1437 (m), 1448 (m), 1471 (m), 1487 (m), 1512 (s, NH, δ), 1531 (vs,
to the literature. The isothiocyanates were purchased from Aldrich and CN, ν), 1577 (m), 2860 (vw), 2896 (vw), 2922 (vw), 2937 (vw), 2958
directly used.
(w), 2975 (w), 3033 (vw), 3062 (vw), 3089 (vw), 3186 (w), 3242 (w)
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Zeitschrift für anorganische und allgemeine Chemie
cm–1. MS-ESI: [m/z (%)]: 317.11 (100) [M+]; 261.05 (21) [M+–tBu]; ppm): δ = 31.4 (CH2, C7); 37.7 (CH2, C6); 44.4 (CH2, C8); 122.0
182.10 (52) [M+–PhNCS]; 126.03 (73) [M+–tBu, PhNCS]; CHN:
calcd. 64.5% C, 8.9% N, 6.4% H, 20.3% S; found: 64.6% C, 8.9%
N, 6.3% H, 20.5% S.
(CH, C3); 123.1 (CH, C1); 125.2 (CH, C13); 127.2 (CH, C15); 130.0
(CH, C14); 137.0 (CH, C2); 136.4 (Cq, C12); 149.4 (Cq, C4); 158.5
(Cq, C5); 180.3 (Cq, C10). IR (ATR): ν˜ = 601 (w), 615 (w), 629 (w),
644 (m), 692 (vs), 729 (s), 739 (s), 754 (s), 812 (w), 827 (vw), 842
(vw), 874 (m), 897 (w), 918 (w), 962 (vw), 999 (m), 1024 (w), 1051
(w), 1072 (m), 1086 (m), 1105 (m), 1138 (w), 1155 (m), 1165 (m),
1244 (s), 1294 (m), 1317 (m), 1344 (m), 1384 (w), 1415 (m), 1434
(s), 1448 (m), 1473 (s), 1492 (m, NH, δ), 1529 (vs, CN, ν), 1569 (w),
1589 (m), 2908 (w), 2935 (w), 2953 (w), 2976 (w), 3003 (m), 3018
(m), 3058 (w), 3101 (w), 3159 (m) cm–1. MS-ESI: m/z (%): 304.09
(42) [M+]; 211.03 (100) [M+–PyCH3]; 124.02 (21) [M+–PhNHCSNH-
(CH2)2]. CHN: calcd. 59.4% C, 13.9% N, 5.7% H, 21.1% S; found:
59.3% C, 13.7% N, 5.7% H, 20.8% S.
Synthesis of 1-[2-((2-(Dimethylamino)ethyl)thio)ethyl]-3-phen-
ylthio-urea (2): Amine A2[49] (1.77 g, 12 mmol) and phenylisothiocy-
anate (1.3 mL, 10.9 mmol) were added to anhydrous acetonitrile
(120 mL). After 3 h stirring at room temperature the solvent was re-
moved in vacuo. The residue was a pale yellow oil that was poured
into water (20 mL) and extracted with DCM (3ϫ30 mL). The organic
layer was dried with Na2SO4, evaporation of the solvent and washing
with Et2O resulted in the product as pale yellow solid 2 (2.17 g,
6.84 mmol, 62.7%).
Synthesis of 1-[2-(tert-Butylthio)phenyl]-3-[3-(methylthio)propyl]-
thiourea (4): Amine A1[48] (1.7 g, 9.4 mmol) and 3-(methylthio)prop-
ylisothiocyanate (0.8 mL, 6.7 mmol) were added to anhydrous aceto-
nitrile (40 mL). After 3 h stirring at room temperature the solvent was
removed in vacuo. The residue was a colorless oil. Petroleum ether
(60–95 °C) was added to the oil and stirred for 1 h at room tempera-
ture. The product 4 precipitated as white solid (1.28 g, 3.91 mmol,
58.3%).
1H NMR (500 MHz, CDCl3, 30 °C, ppm): δ = 2.16 (s, 6 H, H1); 2.44
3
3
(t, 2 H, H2, JHH = 7.3 Hz); 2.57 (t, 2 H, H3, JHH = 7.2 Hz); 2.74 (t,
3
3
2 H, H4, JHH = 6.4 Hz); 3.77 (dd, 2 H, H5, JHH = 6.0 Hz); 6.70 (br.
s, 1H, H6/H8); 7.22 (m, 3H, H10+H12); 7.36 (m, 2H, H11); 8.51 (br.
s, 1H, H6/H8). 13C NMR (125 MHz, CDCl3, 30 °C, ppm): δ = 29.4
(CH2, C3); 31.5 (CH2, C4); 44.2 (CH2, C5); 45.2 (CH3, C1); 59.2
(CH2, C2); 125.0 (CH, C10/C12); 127.0 (CH, C10/C12); 130.0 (CH,
C11); 136.5 (Cq, C9); 180.5 (Cq, C7). IR (ATR): ν˜ = 603 (w), 638
(m), 690 (s), 709 (m), 731 (m), 742 (m), 758 (m), 775 (w), 814 (m),
841 (m), 903 (vw), 918 (vw), 968 (m), 1006 (s), 1031 (s), 1051 (m),
1070 (m), 1093 (s), 1138 (m), 1161 (s), 1195 (m), 1247 (m), 1288 (m),
1315 (s), 1334 (s), 1377 (m), 1408 (m), 1429 (m), 1448 (m), 1458
(m), 1467 (m), 1492 (vs, NH, δ), 1521 (vs, CN, ν), 1593 (m) 2711
(vw), 2777 (m), 2819 (m), 2825 (m), 2862 (m), 2944 (m), 2983 (m),
2993(m), 3058 (w), 3147 (m) cm–1. MS-ESI: [m/z (%)]: 312.15 (8);
284.12 (100) [M+]; 211.04 (9); 179.06 (24). CHN: calcd. 55.0% C,
14.8% N, 7.5% H, 22.6% S; found: 55.0% C, 13.8% N, 7.2% H,
21.6% S.
1H NMR (500 MHz, CDCl3, 30 °C, ppm): δ = 1.26 (s, 9 H, H15);
3
1.92 (tt, 2 H, H3, JHH = 7.7 Hz); 2.04 (s, 3 H, H1); 2.53 (t, 2 H, H2,
3
3JHH = 7.9 Hz); 3.73 (d, 2 H, H4, JHH = 5.4 Hz); 6.69 (br. s, 1 H,
3
H5); 7.12 (dd, 1 H, H11 / H12, JHH = 8.2 Hz); 7.39 (dd, 1 H, H11 /
H12, 3JHH = 8.6 Hz); 7.57 (d, 2 H, H10/H13, 3JHH = 7.3 Hz); 8.47 (br.
s, 1H, H7). 13C NMR (125 MHz, CDCl3, 30 °C, ppm): δ = 15.5 (CH3,
C1); 27.7 (CH2, C3); 30.8 (CH3, C 15; 31.8 (CH2, C2); 44.4 (CH2,
C4); 48.0 (Cq, C14); 122.7 (CH, C10 / C13); 125.1 (CH, C11 / C12);
130.5 (CH, C11 / C12); 139.9 (CH, C10 / C13); 140.9 (Cq, C8, C9);
180.2 (Cq, C6). IR (ATR): ν˜ = 648 (w), 692 (s), 719 (w), 737 (m),
752 (s), 858 (vw), 870 (w), 933 (vw), 956 (w), 1039 (m), 1103 (w),
1126 (w), 1145 (m), 1165 (s), 1207 (m), 1224 (m), 1263 (s), 1294 (s),
1315 (s), 1336 (m), 1359 (w), 1379 (vw), 1443 (m), 1456 (m, NH, δ),
1471 (w), 1531 (vs, CN, ν), 1583 (m), 2860 (vw), 2914 (w), 2937
(vw), 2974 (w), 3120 (vw), 3191 (w), 3246 (w) cm–1. MS-ESI: m/z
(%) 329.11 [M+] (40), 182.10 (51) [M+–PhNCS]; 126.03 (100)
[M+–tBu, PhNCS]. CHN: calcd. 54.8% C, 8.5% N, 7.4% H, 29.3%
S; found: 55.0% C, 8.6% N, 7.2% H, 29.1% S.
Synthesis of 1-Phenyl-3-[2-((pyridin-2-ylmethyl)thio)ethyl]-thio-
urea (3): Amine A4[50] (1.98 g, 11.7 mmol) and phenylisothiocyanate
(1.3 mL, 10.9 mmol) were added to anhydrous acetonitrile (120 mL).
After 3 h stirring at room temperature the solvent was removed in
vacuo. The residue was a green oil. Petroleum ether (60–95 °C) was
added to the oil and stirred for 1 h at room temperature. The product
3 precipitated as a grey solid (2.54 g, 8.32 mmol, 76.3%).
Synthesis of 1-Phenyl-3-[2-((pyridin-2-ylmethyl)thio)phenyl]-thio-
urea (5): Amine A3[50] (2.59 g, 12 mmol) and phenylisothiocyanate
(1.3 mL, 10.9 mmol) were added to anhydrous acetonitrile (120 mL).
After 3 h stirring at room temperature the solvent was removed in
vacuo. The residue was a yellow oil. Cold Et2O was added to the
oil and product 5 precipitated as a yellow solid (3.6 g, 10.21 mmol,
93.7%).
3
1H NMR (500 MHz, CDCl3, 30 °C, ppm): δ = 2.77 (t, 2 H, H7, JHH
3
= 7.2); 3.79 (s, 2 H, H6); 3.83 (dt, 2 H, H8, JHH = 6.9 Hz); 6.97 (br.
3
4
s, 1 H, H9); 7.08 (ddd, 1 H, H3, JHH = 7.3, JHH = 1.0 Hz); 7.23–
3
7.25 (m, 4 H, H1+H13+H15); 7.35 (dd, 2 H, H14, JHH = 7.4 Hz);
7.58 (ddd, 1 H, H2, 3JHH = 7.9, 4JHH = 1.9 Hz); 8.14 (br. s, 1 H, H11);
8.27 (d, 1H, H4, JHH = 4.6 Hz). 13C NMR (125 MHz, CDCl3, 30 °C,
3
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1H NMR (500 MHz, CDCl3, 30 °C, ppm): δ = 4.04 (s, 2 H, H6); 7.02–
added to anhydrous acetonitrile (120 mL). After 3 h stirring at room
7.13 (m, 2 H, H1–3/ H8–11/ H17–19); 7.21–7.44 (m, 8 H, H1–3/ H8–
11/ H17–19); 7.48–7.52 (m, 1 H, H1–3/ H8–11/ H17–19); 8.03 (d, 1
H, H1–3/ H8–11/ H17–19); 8.35 (dd, 1 H, H4); 8.76 (br. s, 1 H, H15);
8.85 (br. s, 1 H, H13). 13C NMR (125 MHz, CDCl3, 30 °C, ppm): δ
= 41.3 (CH2, C4); 122.2 (CH, C1–3/ C8–11/ C17–19); 123.2 (CH, C1–
3/ C8–11/ C17–19); 125.4 (CH, C1–3/ C8–11/ C17–19); 125.8 (CH,
C1–3/ C8–11/ C17–19); 126.3 (CH, C1–3/ C8–11/ C17–19); 127.0
(CH, C1–3/ C8–11/ C17–19); 128.7 (Cq, C7); 128.8 (CH, C1–3/ C8–
11/ C17–19); 129.6 (CH, C1–3/ C8–11/ C17–19); 134.4 (CH, C1–3/
C8–11/ C17–19); 136.8 (CH, C1–3/ C8–11/ C17–19); 137.2 (Cq, C16);
139.6 (Cq, C12); 149.1 (CH, C4), 156.9 (Cq, C5); 179.9 (Cq, C14). IR
(ATR): ν˜ = 613 (w), 627 (m), 656 (m), 669 (m), 696 (s), 719 (s), 742
(vs), 758 (m), 783 (vw), 796 (w), 841 (w), 864 (vw), 900 (vw), 926
(m), 943 (vw), 960 (vw), 979 (w), 995 (w), 1022 (m), 1035 (w), 1049
(w), 1070 (m), 1130 (m), 1153 (m), 1172 (m), 1199 (m), 1222 (s),
1247 (m), 1272 (m), 1292 (m), 1311 (m), 1357 (m), 1433 (s), 1446
(s), 1468 (s), 1498 (s, NH, δ), 1531 (s, CN, ν), 1568 (m), 1591 (m),
1624 (m), 2858 (vw), 2893 (vw), 2937 (w), 2958 (w), 3002 (w), 3057
(w), 3103 (vw), 3132 (w), 3193 (m), 3244 (w) cm–1. MS-ESI: m/z
(%) 352.09 [M+] (70), 259.03 (51) [M+–PhNH2]; 227.06 (100) [M+–
Py-MeSH]. CHN: calcd. 64.9% C, 12.0% N, 4.9% H, 18.3% S;
found: 65.6% C, 11.9% N, 5.0% H, 18.4% S.
temperature the solvent was removed in vacuo. The residue was a
brown oil that was poured into water (20 mL) and extracted with DCM
(3ϫ30 mL). The organic layer was dried over Na2SO4, evaporation
of the solvent and washing with Et2O resulted in the product as brown
oil 7 (1.40 g, 9.42 mmol, 86.5%).
1H NMR (500 MHz, CDCl3, 30 °C, ppm): δ = 1.82 (tt, 2 H, H10, 3JHH
= 6.8 Hz); 2.02 (s, 3 H, H12); 2.18 (s, 6 H, H1); 2.46 (m, 2 H, H2);
3
2.49 (t, 2 H, H3 / H11, JHH = 6.9 Hz); 2.59 (m, 2 H, H4), 2.70 (t, 2
3
H, H3 / H11, JHH = 7.1 Hz); 3.64 (m, 4 H, H5, H9); 6.68 (br. s, 1 H,
H6 / H8); 6.80 (br. s, 1 H, H6 / H8). 13C NMR (125 MHz, CDCl3,
30 °C, ppm): δ = 15.4 (CH3, C12); 28.1 (CH2, C10); 29.6 (CH2, C4);
31.5 (CH2, C3, C11); 43.8 (CH2, C5, C9); 45.2 (CH3, C1); 59.0 (CH2,
C2); 182.1 (Cq, C7). IR (ATR): ν˜ = 665 (w), 692 (w), 735 (w), 767
(w), 850 (w), 896 (vw), 958 (w), 1007 (m), 1039 (m), 1053 (m), 1097
(m), 1132 (m), 1170 (m), 1226 (m), 1267 (s), 1292 (m), 1342 (m),
1383 (m), 1435 (m), 1460 (m, NH, δ), 1543 (vs, CN, ν), 2102 (vw),
2179 (vw), 2362 (vw), 2721 (w), 2779 (m), 2821 (m), 2860 (w), 2919
(m), 3062 (vw), 3255 (m) cm–1. ESI-MS (m/z (%)): 296.12 (63) [M+];
191.06 (100) [M+–NH-(CH2)3SCH3)]]; 223.03 (41) [M+–
(CH2)2N(CH3)2]; 143.06 (37). CHN: calcd. 44.7% C, 14.2% N, 8.5%
H, 32.6% S; found: 43.6% C, 13.4% N, 8.2% H, 32.2% S.
Synthesis of 1-[3-(Methylthio)propyl]-3-[2-((pyridin-2-ylmethyl)-
thio)-ethyl]thiourea (6): Amine A4[50] (2.03 g, 12 mmol) and 3-
(methylthio)propylisothiocyanate (1.45 mL, 10.9 mmol) were added to
anhydrous acetonitrile (120 mL). After 3 h stirring at room temperature
the solvent was removed in vacuo. The residue was a pale yellow oil.
The crude product was dissolved in a few mL of MeOH and cooled
down in an ice bath. The product 6 precipitated as a yellow solid and
was washed with n-pentane (2.07 g, 6.56 mmol, 60.2%).
Synthesis of 1,1Ј-(1,4-Phenylene)bis[3-(2-(tert-butylthio)phenyl)-
thio-urea] (8): Amine A1[48] (1.80 g, 12 mmol) and 1,4-diisothiocyan-
atobenzene (0.86 g, 4.5 mmol) were added to anhydrous acetonitrile
(100 mL). After 3 h stirring at room temperature the solvent was re-
moved in vacuo. The residue was a pale yellow solid 8 (1.70 g,
3.06 mmol, 68.1%).
1H NMR (500 MHz, CDCl3, 30 °C, ppm): δ = 1.86 (tt, 2 H, H13, 3JHH
3
= 6.9 Hz); 2.03 (s, 3 H, H15); 2.51 (t, 2 H, H14, JHH = 7.5 Hz); 2.71
3
(t, 2 H, H7, JHH = 7.5 Hz); 3.54 (s, 2 H, H12); 3.69 (s, 2 H, H8);
3.82 (s, 2 H, H6); 6.75 (br. s, 1 H, H11); 7.09 (br. s, 1 H, H9); 7.16
3
4
3
(ddd, 1 H, H3, JHH = 7.6, JHH = 0.9 Hz); 7.31 (d, 1 H, H1, JHH
=
3
4
7.9 Hz); 7.64 (ddd, 1 H, H2, JHH = 7.8, JHH = 1.7 Hz); 8.47 (m, 1
H, H4). 13C NMR (125 MHz, CDCl3, 30 °C, ppm): δ = 15.5 (CH3,
C15); 28.2 (CH2, C13); 31.1 (CH2, C7); 31.6 (CH2, C14); 37.5 (CH2,
C6); 44.1 (CH2, C8, C12); 122.3 (CH, C3); 123.5 (CH, C1); 137.3
(CH, C2); 149.1 (CH, C4); 158.6 (Cq, C5); 182.0 (Cq, C10). IR (ATR):
ν˜ = 628 (m), 686 (s), 713 (m), 734 (s), 748 (s), 765 (m), 788 (m), 831
(w), 864 (w), 898 (w), 962 (m), 991 (m), 1003 (m), 1051 (m), 1066
(m), 1086 (m), 1136 (m), 1147 (m), 1176 (m), 1192 (m), 1213 (m),
1224 (m), 1265 (m), 1280 (s), 1319 (s), 1342 (m), 1369 (m), 1412
(m), 1435 (m), 1450 (m), 1473 (m, NH, δ), 1525 (vs, CN, ν), 1568
(m), 1589 (m), 2860 (w), 2916 (m), 2929 (m), 2964 (w), 3022 (m),
3207 (m), 3325 (m) cm–1. ESI-MS (m/z (%)): 316.09 (100) [M+];
223.04 (61) [M+– Py-CH3]; 211.03 (57) [M+–NH-(CH2)3SCH3];
124.02 (24) [M+- (CH2)2-NHCSNH-(CH2)3SCH3)]. CHN: calcd.
49.5% C, 13.3% N, 6.7% H, 30.5% S; found: 49.3% C, 13.3% N,
6.4% H, 31.4% S.
1H NMR (500 MHz, [D8]THF, 30 °C, ppm): δ = 1.23 (s, 18 H, H1);
3
4
7.08 (ddd, 1 H, H5, JHH = 7.5, JHH = 1.1 Hz); 7.39 (dd, 2 H, H7,
4
3
4
3JHH = 7.8, JHH = 1.5 Hz); 7.52 (dd, 2 H, H4, JHH = 7.4, JHH
=
1.4 Hz); 7.60 (s, 4 H, H13); 8.76 (m, 2 H, H6); 9.22 (br. s, 2 H, H11);
9.53 (br. s, 2 H, H9). 13C NMR (125 MHz, [D8]THF, 30 °C, ppm): δ
= 30.1 (CH3, C1); 47.3 (Cq, C2); 122.9 (Cq, C3); 123.4 (CH, C5);
123.4 (CH, C6); 125.6 (CH, C13); 129.2 (CH, C7); 136.1 (Cq, C12);
138.4 (CH, C4); 143.0 (Cq, C8); 179.1 (Cq, C10). IR (ATR): ν˜ = 624
(m), 651 (m), 690 (m), 740 (m), 750 (m), 762 (w), 798, 624 (w), 651
(w), 690 (w), 740 (w), 750 (s), 762 (m), 798 (w), 854 (w), 868 (vw),
937 (w), 953 (vw), 979 (vw), 1022 (m), 1033 (w), 1059 (w), 1093
(m), 1117 (m), 1165 (s), 1190 (s), 1215 (m), 1244 (s), 1288 (m), 1362
(s), 1390 (vw), 1435 (m), 1458 (m), 1469 (m), 1506 (vs, NH, δ), 1533
Synthesis
of
1-[2-((2-(Dimethylamino)ethyl)thio)ethyl]-3-[3- (s, CN, ν), 1573 (m), 2860 (vw), 2898 (vw), 2922 (w), 2949 (w), 2960
(methyl-thio)propyl]thiourea (7): Amine A2[49] (1.77 g, 12 mmol)
(m), 3130 (m), 3306 (vw) cm–1. MS-ESI: m/z (%) 555.17 (58) [M+];
465.12 (17) [M+–tBuSH];259.03 (100); 195.05 (18) [tBuSPhNHCH3];
and 3-(methylthio)propylisothiocyanate (1.45 mL, 10.9 mmol) were
Z. Anorg. Allg. Chem. 2016, 660–669
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ARTICLE
Zeitschrift für anorganische und allgemeine Chemie
[5] Enantioselective Organocatalysis. Reactions and Experimental
227.06 (53) [tBuSPhNHCH3SH]. CHN: calcd. 60.6% C, 10.10% N,
6.2% H, 23.1% S; found: 60.5% C, 9.9% N, 6.2% H, 22.5% S.
Procedures (Ed.: P. I. Dalko), Wiley-VCH, John Wiley,
Weinheim, Chichester, 2007.
[6] M. Benaglia, A. Puglisi, F. Cozzi, Chem. Rev. 2003, 103, 3401–
3429.
[7] T. Akiyama, J. Itoh, K. Fuchibe, Adv. Synth. Catal. 2006, 348,
Synthesis of 1-[3-(Methylthio)propyl]-3-[2-((pyridin-2-ylmethyl)-
thio)-phenyl]thiourea (9): Amine A3[50] (2.59 g, 12 mmol) and 3-
(methylthio)propylisothiocyanate (1.45 mL, 10.9 mmol) were added to
anhydrous acetonitrile (120 mL). The reaction mixture was stirred
overnight at room temperature and the solvent was removed in vacuo.
The residue was dissolved in acetone and precipitated with petroleum
ether (30–70 °C). The product was a pale yellow solid 9 (2.50 g,
6.89 mmol, 63.3%).
999–1010.
[8] M. S. Taylor, E. N. Jacobsen, Angew. Chem. 2006, 118, 1550–
1573; Angew. Chem. Int. Ed. 2006, 45, 1520–1543.
[9] A. G. Doyle, E. N. Jacobsen, Chem. Rev. 2007, 107, 5713–5743.
[10] V. M. Coiro, P. Giacomello, E. Giglio, Acta Crystallogr., Sect. B
1971, 27, 2112–2119.
[11] a) K. M. Lippert, K. Hof, D. Gerbig, D. Ley, H. Hausmann, S.
Guenther, P. R. Schreiner, Eur. J. Org. Chem. 2012, 5919–5927;
b) N. Mittal, K. M. Lippert, C. Kanta De, E. G. Klauber, T. J.
Emge, P. R. Schreiner, D. Seidel, J. Am. Chem. Soc. 2015, 137,
5748–5758.
[12] a) A. Berkessel, S. Mukherjee, T. N. Müller, F. Cleemann, K.
Roland, M. Brandenburg, J.-M. Neudörfl, J. Lex, Org. Biomol.
Chem. 2006, 4, 4319–4330; b) C. S. Yeung, R. E. Ziegler, J. A.
Porco, E. N. Jacobsen, J. Am. Chem. Soc. 2014, 136, 13614–
13617; c) T. Inokuma, Y. Hoashi, Y. Takemoto, J. Am. Chem. Soc.
2006, 128, 9413–9419; d) Y. Takemoto, Chem. Pharm. Bull.
2010, 58, 593–601; e) Y. Takemoto, T. Inokuma, Asymmetric Syn-
thesis II, Wiley-VCH, Weinheim, 2012.
[13] A. Berkessel, K. Roland, J. M. Neudörfl, Org. Lett. 2006, 8,
4195–4198.
[14] S. H. McCooey, S. J. Connon, Angew. Chem. 2005, 117, 6525–
6528; Angew. Chem. Int. Ed. 2005, 44, 6367–6370.
[15] M. S. Sigman, E. N. Jacobsen, J. Am. Chem. Soc. 1998, 120,
4901–4902.
[16] M. S. Sigman, P. Vachal, E. N. Jacobsen, Angew. Chem. 2006,
118, 1336–1338; Angew. Chem. Int. Ed. 2000, 39, 1279–1281.
[17] Y. Sohtome, A. Tanatani, Y. Hashimoto, K. Nagasawa, Tetrahe-
dron Lett. 2004, 45, 5589–5592.
[18] Ullmann’s Encyclopedia of Industrial Chemistry, Wiley-VCH,
Weinheim, 2011.
[19] K. Liu, H.-F. Cui, J. Nie, K.-Y. Dong, X.-J. Li, J.-A. Ma, Org.
Lett. 2007, 9, 923–925.
[20] R. P. Herrera, V. Sgarzani, L. Bernardi, A. Ricci, Angew. Chem.
2005, 117, 8189–92; Angew. Chem. Int. Ed. 2005, 44, 6576–6579.
[21] M. Kotke, P. Schreiner, Synthesis 2007, 2007, 779–790.
[22] Y. Sohtome, Y. Hashimoto, K. Nagasawa, Adv. Synth. Catal.
2005, 347, 1643–1648.
1H NMR (500 MHz, CDCl3, 30 °C, ppm): δ = 1.88 (tt, 2 H, H17, 3JHH
3
= 7.0 Hz); 1.98 (s, 3 H, H19); 2.49 (t, 2 H, H18, JHH = 7.0 Hz); 3.69
(dt, 2 H, H16, 3JHH = 6.2 Hz); 4.11 (s, 2 H, H6); 6.72 (br. t, 1 H, H15,
3JHH = 5.1 Hz); 7.05–7.10 (m, 2 H, H3+11); 7.22–7.24 (m, 2 H,
3
4
H1+H9; 7.37 (dd, 1 H, H10, JHH = 7.8, JHH = 1.4 Hz); 7.49 (dd, 1
3
4
3
H, H8, JHH = 7.7, JHH = 1.8 Hz); 7.56 (dd, 1 H, H2, JHH = 7.8,
3
4
4JHH = 1.7 Hz); 8.46 (dd, 1 H, H4, JHH = 4.9, JHH = 0.9 Hz), 8.56
(br. s, 1 H, H13). 13C NMR (125 MHz, CDCl3, 30 °C, ppm): δ = 15.4
(CH3, C19); 27.9 (CH2, C17); 31.8 (CH2, C18); 40.5 (CH2, C6); 44.4
(CH2, C16); 122.3 (CH, C11); 123.5 (CH, C1/C9); 126.4 (CH, C8+12);
127.5 (CH, C3); 128.5 (CH, C1/C9); 130.2 (Cq, C7/12); 133.3 (CH,
C10); 136.4 (Cq, C7/12); 136.9 (CH, C2); 149.4 (CH, C4); 156.9 (Cq,
C5); 181.1 (Cq, C14). IR (ATR): ν˜ = 607 (m), 632 (s), 685 (w), 713
(m), 723 (m), 742 (vs), 762 (w), 785 (w), 812 (m), 843 (w), 885 (vw),
903 (w), 962 (w), 989 (w), 1003 (m), 1024 (m), 1037 (m), 1060 (m),
1085 (m), 1107 (m), 1134 (m), 1151 (m), 1166 (m), 1193 (m), 1207
(m), 1244 (vs), 1273 (m), 1288 (m), 1303 (m), 1315 (m), 1357 (m),
1390 (m), 1421 (m), 1432 (s), 1465 (m), 1477 (m, NH, δ), 1510 (vs,
CN, ν), 1540 (m), 1569 (m), 1589 (m), 2912 (m), 2937 (m), 2952 (m),
2983 (m), 3051 (m), 3128 (m) cm–1. MS-ESI: m/z (%) 364.09 (28)
[M+]; 265.14 (100); 259.03 (67) [M+–NH2(CH2)3SCH3]. CHN: calcd.
56.2% C, 11.6% N, 5.8% H, 26.5% S; found: 56.0% C, 11.5% N,
5.8% H, 26.9% S.
[23] B. Vakulya, S. Varga, A. Csámpai, T. Soós, Org. Lett. 2005, 7,
1967–1969.
[24] Y. Lee, R. S. Klausen, E. N. Jacobsen, Org. Lett. 2011, 13, 5564–
5567.
[25] J. Y. Kang, R. G. Carter, Org. Lett. 2012, 14, 3178–3181.
[26] A. Wittkopp, P. R. Schreiner, Chem. Eur. J. 2003, 9, 407–414.
[27] T. Okino, Y. Hoashi, Y. Takemoto, J. Am. Chem. Soc. 2003, 125,
12672–12673.
Supporting Information (see footnote on the first page of this article):
Structural results of the DFT calculations, NBO charges, and NMR
spectra.
[28] C.-L. Cao, M.-C. Ye, X.-L. Sun, Y. Tang, Org. Lett. 2006, 8,
2901–2904.
Acknowledgments
[29] H. Miyabe, S. Tuchida, M. Yamauchi, Y. Takemoto, Synthesis
2006, 2006, 3295–3300.
[30] X.-J. Li, K. Liu, H. Ma, J. Nie, J.-A. Ma, Synlett 2008, 2008,
Financial support by the Deutsche Forschungsgemeinschaft (DFG-
FOR1405) is gratefully acknowledged. Calculation time is gratefully
acknowledged from the OCuLUS Cluster at the PC2 Paderborn.
3242–3246.
[31] J. Wang, H. Li, X. Yu, L. Zu, W. Wang, Org. Lett. 2005, 7, 4293–
4296.
[32] L. Wanka, C. Cabrele, M. Vanejews, P. R. Schreiner, Eur. J. Org.
Chem. 2007, 1474–1490.
[33] R. Todd, G. Rubio, D. J. Hall, S. Tempelaar, A. P. Dove, Chem.
Sci. 2013, 4, 1092–1097.
[34] J.-B. Zhu, E. Y.-X. Chen, J. Am. Chem. Soc. 2015, 137, 12506–
12509.
[35] S. S. Spink, O. I. Kazakov, E. T. Kiesewetter, M. K. Kiesewetter,
Macromolecules 2015, 48, 6127–6131.
References
[1] P. I. Dalko, L. Moisan, Angew. Chem. 2001, 113, 3840–3864; An-
gew. Chem. Int. Ed. 2001, 40, 3726–3748.
[2] P. I. Dalko, L. Moisan, Angew. Chem. 2004, 116, 5248–5286; An-
gew. Chem. Int. Ed. 2004, 43, 5138–5175.
[3] a) K. N. Houk, B. List, Acc. Chem. Res. 2004, 37, 487; b) B. List,
Chem. Rev. 2007, 107, 5413–5415.
[4] J. Seayad, B. List, Org. Biomol. Chem. 2005, 3, 719–724.
[36] a) D. Manna, G. Roy, G. Mugesh, Acc. Chem. Res. 2013, 46,
2706–2715; b) B. Solomon, D. Glinoer, R. Lagasse, L. Wartofsky,
Z. Anorg. Allg. Chem. 2016, 660–669
668
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Journal of Inorganic and General Chemistry
www.zaac.wiley-vch.de
ARTICLE
Zeitschrift für anorganische und allgemeine Chemie
J. Clin. Endocrinol. Metab. 1990, 70, 1518–1524; c) D. S. Coo- [52] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.
per, N. Engl. J. Med. 2005, 352, 905–917.
[37] A. J. Speziale, Org. Synth. 1950, 30, 35–36.
[38] M. A. Arifoglu, W. N. Marmer, R. B. Dudley, Textile Res. J. 1992,
62, 94–100.
[39] a) W. Kaim, B. Schwederski, Bioanorganische Chemie. Zur Funk-
tion chemischer Elemente in Lebensprozessen, Vieweg+Teubner,
Wiesbaden, 2010; b) Q. Lin, H. Yao, T.-B. Wei, Y.-M. Zhang,
Indian J. Chem. 2009, 48, 124–127.
Robb, J. R. Cheeseman, G.Scalmani, V. Barone, B. Mennucci,
G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian,
A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada,
M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Mont-
gomery Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E.
Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Norm-
and, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J.
Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox,
J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts,
R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli,
J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski,
G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D.
Daniels, Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, and
D. J. Fox, Gaussian 09, Revision D.01, Gaussian Inc., Wall-
ingford, CT, USA, 2013.
[40] K. H. Kong, C. K. Tan, X. Lin, Y. Lam, Chem. Eur. J. 2012, 18,
1476–1486.
[41] M. M. Elcombe, J. C. Taylor, Acta Crystallogr., Sect. A 1968, 24,
410–420.
[42] A. Saeed, U. Flörke, M. F. Erben, J. Sulfur Chem. 2013, 35, 318–
355.
[43] A. Saeed, U. Flörke, M. F. Erben, J. Mol. Struct. 2014, 1065–
1066, 150–159.
[44] V. de Paul, N. Nziko, S. Scheiner, J. Org. Chem. 2015, 80, 10334– [53] J. Tao, J. P. Perdew, V. N. Staroverov, G. E. Scuseria, Phys. Rev.
10341.
Lett. 2003, 90–91, 146401–1-146401–4.
[45] a) L. Rao, H. Ke, G. Fu, X. Xu, Y. Yan, J. Chem. Theory Comput.
2009, 5, 86–96; b) S. F. Sousa, P. A. Fernandes, M. J. Ramos, J.
Phys. Chem. A 2007, 111, 10439–10452.
[46] R. J. Thatcher, D. G. Johnson, J. M. Slattery, R. E. Douthwaite,
Chem. Eur. J. 2012, 18, 4329–4336.
[47] N. A. Sanina, S. M. Aldoshin, N. Y. Shmatko, D. V. Korchagin,
G. V. Shilov, N. S. Ovanesyan, A. V. Kulikov, Inorg. Chem. Com-
mun. 2014, 49, 44–47.
[48] A. Courtin, H.-R. von Tobel, G. Auerbach, Helv. Chim. Acta
1980, 63, 1412–1419.
[54] a) F. Weinhold, C. R. Landis, Valency and Bonding. A Natural
Bond and Orbital Donor-Acceptor Perspective, Cambridge Uni-
versity Press, Cambridge, 2005; b) E. D. Glendening, C. R. Lan-
dis, F. Weinhold, J. Comput. Chem. 2013, 34, 1429–1437; c) E. D.
Glendening, J. K. Badenhoop, A. E. Reed, J. E. Carpenter, J. A.
Bohmann, C. M. Morales, C. R. Landis, F. Weinhold, NBO 6.0,
University of Wisconsin, Madison, WI, USA, 2013.
[55] a) S. Grimme, J. Antony, S. Ehrlich, H. Krieg, J. Chem. Phys.
2010, 132, 154104–154119; b) L. Goerigk, S. Grimme, Phys.
Chem. Chem. Phys. 2011, 13, 6670–6688.
[49] R. O. Clinton, U. J. Salvador, S. C. Laskowski, C. M. Suter, J.
Am. Chem. Soc. 1948, 70, 950–955.
[50] L. F. Lindoy, S. E. Livingstone, Inorg. Chem. 1968, 7, 1149–1154.
[51] Bruker SMART (Version 5.62), SAINT (Version 6.02), SHELXTL
(Version 6.10) and SADABS (Version 2.03), Bruker AXS Inc.,
Madison, WI, USA, 2002.
[56] a) S. Grimme, S. Ehrlich, L. Goerigk, J. Comput. Chem. 2011,
32, 1456–1465; b) A. Hoffmann, R. Grunzke, S. Herres-Pawlis,
J. Comput. Chem. 2014, 35, 1943–1950.
Received: April 10, 2016
Published Online: May 27, 2016
Z. Anorg. Allg. Chem. 2016, 660–669
669
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim