A Facile One-Pot Synthesis of 1,2,3-Tri- and 1,1,2,3-Tetrasubstituted Bis(guanidine)s from Bis(thiourea)s

Article abstract of DOI:10.1002/ejoc.201700782

A facile and efficient one-pot strategy for the preparation of 1,2,3-tri- and 1,1,2,3-tetrasubstituted bis(guanidine)s by starting from from readily available bis(thiourea)s has been successfully developed. The reaction provides products that contain a range of terminal and bridging groups. After a simple workup procedure, the products were obtained in analytically pure and in good to excellent yields.

Full text of DOI:10.1002/ejoc.201700782

A Journal of
Accepted Article
Title: A Facile One-Pot Synthesis of 1,2,3-Tri- and 1,1,2,3-
Tetrasubstituted Bis(guanidines) from Bis(thioureas)
Authors: Valentin Vass, Maximilian Dehmel, Florian Lehni, and Robert
Kretschmer
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using the Digital Object Identifier (DOI) given below. The VoR will be
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700782
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European Journal of Organic Chemistry
10.1002/ejoc.201700782
FULL PAPER
A Facile One-Pot Synthesis of 1,2,3-Tri- and 1,1,2,3-
Tetrasubstituted Bis(guanidines) from Bis(thioureas)
Valentin Vass, Maximilian Dehmel, Florian Lehni, and Robert Kretschmer*[a]
This work is dedicated to Prof. Dr. Rainer Beckert on the occasion of his 65th birthday.
formamidinium chlorides.[12,20] In contrast, less substituted
derivatives often require multi-step procedures.[18]
Abstract
A facile and efficient one-pot strategy for the preparation of 1,2,3-tri-
and 1,1,2,3-tetrasubstituted bis(guanidines) originating from readily
available bis(thioureas) has been successfully developed. The
reaction scope covers a range of terminal and bridging groups, and
after a simple work-up, the products are obtained analytically pure and
in good to excellent yields.
Introduction
Compounds containing several nitrogen atoms play a central role
in biological systems and in a wide range of industrial processes.
Over the last few decades, intensive research has been devoted
to improve currently employed synthetic methods for the
Scheme 1. Structures of guanidines (I), bis(guanidines) (II), bis(β-diketimines)
(III), and bis(amidines) (IV); L = linker group.
[
1]
production of this important class of substances. Among the
versatile class of multi-nitrogen compounds, guanidines[2]
1,1,2,3-tetrasubstituted bis(guanidines) are of particular interest
as they serve as interesting alternatives to bis(β-diketimines) III,[
bis(amidines) IV,[22] (Scheme 1), and the bridged-version of the
21]
I
(
Scheme 1) attracted significant attention since their first synthesis
by Strecker in 1861[ and are widely used as artificial
3]
ligand.[23]
amidoamine
In
addition,
1,2,3-trisubstituted
sweeteners,[ explosives,[5] and pharmaceuticals. In addition,
4]
[6]
bis(guanidines) offer the possibility to provide two dianionic
binding sites within one ligand. Thus, both 1,2,3-tri- and 1,1,2,3-
tetrasubstituted bis(guanidines) are promising frameworks for di-
and polynuclear complexes.[24] Unfortunately, synthetic
approaches towards these species usually involve several
reaction steps and are therefore associated with rather low
yields.[25,26] In addition, bis(carbodiimides), which are relatively
unstable and must be handled with care, often serve as
intermediates. Thus we envisaged a synthetic protocol, which
originates from easily available bis(thioureas) 1 and allows for the
synthesis of bis(guanidines) 2 via an one pot reaction avoiding the
isolation of bis(carbodiimides), Scheme 2.
guanidines, which have been categorized as superbases,[7] found
manifold applications either as organocatalysts[8] or as supports
for transition metals[9] and main group elements[10] giving rise to
guanidinate complexes. As a consequence of the broad interest,
synthetic routes towards guanidines have been developed to quite
some extent.[7,11] Bis(guanidines) II, i.e., compounds composed of
two guanidine moieties that are connected by a linker (L), have
recently received considerable interest.[12,13] Compared to their
mono(guanidine) counterparts, these species show enhanced
properties, e.g., in catalysis,[14] as ion sensors,[15] superbases,
[16]
and ligands in bioinorganic and coordination chemistry.[17]
However, protocols aiming for the synthesis of bis(guanidines)
strongly depend on the substitution pattern.[18] Persubstituted
bis(guanidines) are accessible either from the reaction of
N,N,N’,N’-tetrasubstituted
guanidines
with
a
dihalogen
compound[19] or by reacting diamines with tetrasubstituted chloro-
[
a]
V.Vass, M. Dehmel, F. Lehni, Dr. R. Kretschmer*
Institut für Anorganische Chemie
Universtität Regensburg
Universitätsstrasse 31, 93053 Regensburg, Germany
E-mail: robert.kretschmer@ur.de
http://www.ur.de/chemie-pharmazie/anorganische-chemie-
kretschmer/
Scheme 2. Synthesis of 1,2,3-tri- (R & R’’’ = H) and 1,1,2,3-tetrasubstituted (R’’’
= H) bis(guanidines) 2 from readily available bis(thioureas) 1. Noteworthy,
different tautomeric forms of 2 are possible depending on the nature of the
terminal group (R) and the linker (L), respectively; for the sake of clarity only one
form is shown.
Supporting information for this article is given via a link at the end of
the document.
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European Journal of Organic Chemistry
10.1002/ejoc.201700782
FULL PAPER
Table 2. Substrate scope with respect to the terminal groups R (entries 1-3) and
the linker L (entries 3-6), respectively. Different tautomers of 2 are observed
depending on the nature of L and R, respectively; for the sake of clarity only one
Results and Discussion
Table 1. Screening of desulfurization agents for the transformation of 1a to 2a in
the presence of pyrrolidine (Dipp = 2,6-Diisopropylphenyl).
F
form is shown (Dipp = 2,6-Diisopropylphenyl, Ph = Pentafluorophenyl).
#
1
2
3
4
5
6
R
L
Temp. & Time
100 °C / 16 h
100 °C / 16 h
50 °C / 48 h
50 °C / 16 h
100 °C / 88 h
100 °C / 16 h
Yield
98%
99%
89%
0%a
Product
2a
#
1
2
3
4
5
6
Reagent
CuCl
Solvent
acetonitrile/toluene
acetonitrile/water
toluene
Temp. & Time
80 °C / 64 h
r.t. / 64 h
Yield
45%
n.r.
Dipp
PhF
tBu
tBu
tBu
propylene
propylene
propylene
ethylene
2b
2c
KICl
2
HgO
PbO
100 °C / 16 h
100 °C / 16 h
100 °C / 16 h
60 °C / 96 h
98%
98%
98%
10%
m-phenylene
m-xylylene
73%
99%
2d
2e
toluene
Dipp
PbO
2
toluene
a) N-(tert-butyl)-4,5-dihydro-1H-imidazol-2-amine was formed instead of the desired bis(guanidine)
ZnO
ethanol
However, the reaction conditions are of crucial importance. The
transformation of bis(thioureas) bearing moderately and strong
electron-withdrawing substituents (entries 1 and 2) requires
temperatures of about 100 °C, while the tert-butyl substituted
derivative (entry 3) yielded complex reaction mixtures when
heated above 50 °C. However, when extending the reaction time
to 48 hours, a reaction temperature of 50 °C turned out to be
suitable to obtain the desired product 2c in 89% yield. Thus, it can
be concluded that the protocol is applicable to both electron-rich
and electron-deficient bis(thioureas), when choosing the proper
reaction conditions. Next, we became interested if the linker group
L limits the reaction scope. Indeed, we found that the ethylene-
bridged bis(thiourea) 1d (entry 4) does not yield the desired
bis(guanidine), but gives rise to N-(tert-butyl)-4,5-dihydro-1H-
imidazol-2-amine as the main product. Most likely, this is due to
an intermediary formation of the mixed carbodiimide thiourea
For guanidines, the use of thioureas as starting materials has
become a facile strategy[27] and the desulfurization can be
achieved by a variety of reagents such as copper(I) salts,[28]
mercury(II) oxide,[29] KICl ,[30] lead oxides,[31] or ZnO.[32] As we
2
assumed that these protocols may also be applicable for the
synthesis of multi-substituted bis(guanidines), we investigated the
applicability of the aforementioned procedures for transforming the
bis(thiourea) 1a and pyrrolidine into the related bis(guanidine) 2a
as summarized in Table 1. The protocol established by Wang et
al.[28] employing CuCl in a mixture of acetonitrile and toluene,
yielded the bis(guanidine) 2a in only 45% yield after 64 hours, and
2
using potassium dichloroiodate (KICl ), as mentioned by the group
of Costa,[ did not affect any conversion of the bis(thiourea) 1a.
However, using mercury(II), lead(II) and lead(IV) oxide,
respectively, affords 2a in nearly quantitative yield, while two
equivalents of zinc oxide give rise to only 10% of the desired
product despite the long reaction time of four days. Thus, HgO,
30]
species 3a, which undergoes
a subsequent intramolecular
cyclization yielding the imidazolidinecarbo-thioamide 3b (Scheme
3). Next, elimination of tert-butyl isothiocyanate gives rise to N-
(tert-butyl)-4,5-dihydro-1H-imidazol-2-amine. Note that N-aryl
substituted imidazolidine-carbothioamides have already been
isolated and structurally characterized, while no derivative bearing
strong electron donating substituents has been reported so far.[
In case of a longer alkyl chain, i.e., propylene, the desired
bis(guanidine) 2c is formed in 89% yield, as mentioned above.
Similar results are obtained for the 1,3-phenylene- and 1,3-
xylylene-bridged bis(thioureas) (entries 5 and 6), which allow for
2
PbO, and PbO turned out to perform best, not only with respect
to yields but also regarding a facile work-up. Here, the products
can be easily isolated by filtering-off the insoluble metal sulphides
and evaporating the solvent and residual pyrrolidine. Due to the
poor solubility of bis(thioureas) in toluene, potentially remaining
starting materials may also be separated as part of the remaining
residue. Although all three compounds are not plain sailing in
terms of eco(toxicity), lead(II) oxide is associated with the least
risks.[33] In addition, the formed lead(II) sulphide is easily converted
34]
to lead(II) oxide in a roasting process, which allows for its recycling. the isolation of the related bis(guanidines) 2d and 2e, respectively.
We thus employed PbO for further experiments. To obtain some
insight into the substrate scope of this reaction, we investigated
the effect of electron-donating and electron-withdrawing terminal
groups (R) as well as the impact of the linking group (L), Table 2.
Hence, reactions of bis(thioureas) bearing aryl and alkyl
substituents in terminal position were performed under standard
reaction conditions, i.e., using 2.1 and 20 equivalents of PbO and
Scheme 3. Proposed mechanism for the formation of N-(tert-butyl)-4,5-dihydro-
pyrrolidine, respectively, with toluene as solvent. For all of these
1H-imidazol-2-amine 3 from 1,1’-(1,2-ethylene)bis(3-tert-butylthiourea) 1d.
substrates, it was found that the related bis(guanidines) had been
formed in good to excellent yields.
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European Journal of Organic Chemistry
10.1002/ejoc.201700782
FULL PAPER
Table 3. Substrate scope with respect to secondary (entries 1-7) and primary
(entries 8-9) amines (Dipp
=
2,6-Diisopropylphenyl, 2,6-Dmpip
=
cis-2,6-
dimethylpiperidine).
#
Amine
R
R’
Yield
99%
77%
n.r.
Product
2e
1
2
3
4
5
6
7
8
9
pyrrolidine
morpholine
Pyr
Morph
2f
cis-2,6-dimethylpiperidine
diethylamine
2,6-Dmpip
Et
nPr
iPr
Cy
Cy
Ph
Et
nPr
iPr
Cy
H
99%
99%
n.r.
2g
2h
dipropylamine
(
1.3041(19) Å) and C4–N5 (1.2973(19) Å) bond lengths are close
diisopropylamine
dicyclohexylamine
cyclohexylamine
aniline
to typical values for C–N double bonds.
n.r.
96%
95%
2i
2j
Figure 1. Molecular structure of 2a (hydrogen atoms besides H1 and H2 and the
disorder in one iPr substituent are omitted for the sake of clarity). Thermal
ellipsoids display 50% probability of presence for each atom. Selected bond
lengths [Å] and angles [°]: C1-N1 1.3729(19), C1-N2 1.3041(19), C1-N3
1.3622(19), C2-N3 1.4491(20), C3-N4 1.4577(19), C4-N4 1.3708(19), C4-N5
1.2973(19), C4-N6 1.3637(19), N5-H1 2.0993(198); N1-C1-N2 125.11(13), N2-
C1-N3 120.54(13), C1-N3-C2 125.81(13),C1-N3-H1 119.53 (1.18), N3-H1-N5
H
Noteworthy, the formation of 2d requires longer reaction times and
is associated with the lowest yield in the whole series, most likely
due to steric reasons.
1
54.4 (16).
Having evaluated the impact of the terminal groups R and the
linker L, we then studied the utility of the protocol through the use
of a variety of amines, Table 3. Applying less-substituted cyclic
and acyclic secondary alkyl amines, the corresponding 1,1,2,3-
tetrasubstituted bis(guanidines) 2e-h are readily obtained (entries
The values of the other two sets of carbon nitrogen bonds, e.g.,
C1–N1 (1.3729(19) Å) and C1–N3 (1.3622(19) Å), are
intermediate between those of typical single (1.46 Å) and double
1, 2, 4, 5) in good to excellent yields. Higher substituted secondary
C–N bonds (1.27 Å),[37] indicating
a certain amount of
amines, i.e., cis-1,6-dimethylpiperidine, diisopropylamine as well
as dicyclohexylamine remained unreactive under the given
conditions (entries 3, 6, 7), presumably due to their steric bulk.
While limiting the scope of the reaction, this offers an advantage
in the reaction selectivity that can be obtained. Noteworthy, the
reaction with diisopropylamine was also conducted in the
delocalization. However, all bond distances are comparable to
values observed in other guanidine compounds (C–N1 1.355 Å,
C-N2 1.307 Å, C1–N3 1.333 Å), and electronic push-pull effects
have been identified to have a crucial impact on the geometry of
guanidine compounds.[39]
3
presence of catalytic amounts of a Lewis acid (AlCl ) and/or
In addition, 2a features an intramolecular hydrogen bond in the
solid state, i.e., N5–H1, of medium strength as suggested by both,
the N5–H1 distance (2.099(20) Å) and the N3–H1–N5 bond angle
of 154.4(16)°.[ The N3–H1 N5 hydrogen bond also effects the
geometry of the two guanidine groups in such a way, that the C4–
N5 (1.2973(19) Å) and C4–N6 (1.3637(19) Å) bonds are to some
extent shorter compared to their C1 counterparts (C1–N2
(1.3041(19) Å), C1–N1 (1.3729(19) Å)) and the increased bond
length of C4–N4 (1.3708(19) Å) versus C1–N3 (1.3622(19) Å). In
solution, however, only one set of signals is observed for the 2,6-
molecular sieves, which, however, does not facilitate the formation
of the desired bis(guanidine). Although less nucleophilic than
secondary amines, applying a primary aliphatic and an aromatic
amine (entries 8-9) afforded the corresponding 1,2,3-trisubstituted
bis(guanidines) 2i and 2j, respectively, in excellent yields.
Noteworthy, 1,2,3-trisubstituted bis(guanidines) having the same
38]
…
substituents at the terminal position are also accessible from
carbodiimides and diamines,[35] but examples for N,N’,N’’-
trisubstituted bis(guanidines) carrying three different substituents
remain rare and involve rather demanding reaction
sequences.[
26,36]
diisopropylphenyl groups, i.e., one methine septet and two methyl
1
doublets, in the H NMR spectra of 2a in CDCl
3
. This is indicative
for only one type of species, where the two guanidine sites are
The obtained bis(guanidines) are either solids (2a, 2b, 2d-f, 2i-j)
or highly viscous liquids (2c, 2g, 2h) at room temperature. To gain
insight into the solid-state structure of the bis(guanidines), 2a was
crystallized from a saturated acetonitrile solution. A single crystal
X-ray diffraction study revealed the molecular structure of 2a,
Figure 1. 2a crystallizes in the monoclinic space group P2 /c with
1
four independent molecules in the unit cell. As expected, the
hydrogen atoms reside on the more basic bridging nitrogen atoms
1
13
1
symmetrically related on the NMR time scale. While H and C{ H}
NMR data indicate that mirror symmetry is also maintained in
1
13
1
solution for the bisguanidines 2b and 2d-2j, the H and C{ H}
NMR spectra of the more basic bis(guanidine) 2c, however,
consist of two separated signal sets for the tert-butyl groups,
evidencing an asymmetric steric environment as expected if the
hydrogen bond remains intact in solution.
(
N3 and N4, respectively). In consequence, the terminal C1–N2
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European Journal of Organic Chemistry
10.1002/ejoc.201700782
FULL PAPER
Conclusions
NHCH
7
2
CH
2
CH
2
NH), 7.21 (d, 4H, 3JHH = 7.7 Hz, m-CHarom), 7.35 (t, 3JHH
=
.6 Hz, 2H, p-CHarom), 7.40 (s, 2H, NHCSNH). 13C{ H} NMR (101 MHz,
1
CDCl
3
):
δ
CH
=
CH
23.1 (CHCH
3
), 24.7 (CHCH
3 3
), 28.6 (CHCH ),
In summary, 1,2,3-tri- and 1,1,2,3-tetrasubstituted bis(guanidines)
could be obtained via a facile one-pot procedure using readily
available bis(thioureas). The protocol is applicable to terminal alkyl
30.2 (CH
2
2
2
), 40.7 (CH CH
2
2
CH ), 124.7 (m-CHarom), 129.9 (o-
2
-
1
CHarom), 130.1 (p-CHarom), 147.8 (i-CHarom), 181.7 (NHCSNH). IR [cm ]:
ν(NH) = 3265 and 3169, ν(CH) = 2960 and 2864, ν(CN) = 1532, ν(CCarom)=
(
t-butyl) and aryl (perfluorophenyl, 2,6-diisopropylphenyl) groups.
[M+H]+ 513.3086;
1502, ν(CS) = 1210. HR-ESI-MS: calcd. for C29
44 4 2
H N S
Various alkyl and aryl linker groups are tolerated, while the
ethylene-bridge remains a notable exception. In addition, less
sterically demanding cyclic and acyclic secondary alkyl amines are
applicable and primary aliphatic and aromatic amines give rise to
N,N’,N’’-trisubstituted bis(guanidines).
found 513.3062.
1,1’-(1,3-propylene)bis[3-(perfluorphenyl)thiourea] (1b): 350 mg (4.7
mmol) 1,3-diaminopropane were added to a stirred solution of 2.10 g (9.3
mmol) pentafluorophenylisothiocyanate in 30 ml of diethyl ether. The
solution was stirred for 72 hours. The volatiles were removed en vacuo and
the residue was purified by column chromatography (SiO
acetate: 3/2) yielding 1b in analytically pure form. Off-white solid, 930 mg,
.8 mmol, 38%. 1H NMR (400 MHz, DMSO-d
): δ = 1.82 (br, 2H,
), 8.24 (br, 2H, NHCH CH CH NH),
): 28.1
), 136.0 (m-CHarom), 138.5 (p-CHarom),
142.8 (o-CHarom), 145.2 (i-CHarom), 182.3 (NHCSNH). 19F-NMR (282 MHz,
DMSO-d ): -163.53 (quint, 22.0 Hz, 4F, m-CFarom), -157.10 (t, 22.3 Hz, 2F,
2
, n-pentane/ethyl
Experimental Section
1
CH
6
2
CH
2
CH
2
), 3.51 (br, 4H, CH
2
CH
CH
2 2
2
2
2
1
3
1
General Considerations. The solvents and starting materials were
purchased from ABCR, Sigma Aldrich or VWR and used as delivered. tert-
Butylisothiocyanate[40] and pentafluorophenylisothiocyanate[41] were
prepared as described elsewhere.
9.29 (br, 2H, NHCSNH). C{ H} NMR (101 MHz, DMSO-d
6
2 2 2 2 2 2
(CH CH CH ), 42.3 (CH CH CH
6
-
1
p-CFarom), -144.67 (d, 22.0 Hz, 4F, o-CFarom). IR [cm ]: ν(NH) = 3217 and
3043, ν(CH) = 2928, ν(CCarom) = 1704, 1615, 1480 and 984 ν(CN) = 1504,
ν(CS) = 1266. HR-ESI-MS: calcd. for C17H F N S
10 10 4 2
[M+H]+ 525.0266;
Characterization. The NMR spectra were recorded on Bruker Avance 300
and 400 spectrometers (T = 300 K) with δ (given in ppm) referenced to
external trimethylsilane ( H and 13C) and trichlorofluoromethane (19F). 1
1
H
found 525.0208.
and 13C NMR spectra were calibrated using the solvent residual peak (δ H
1
(
CHCl
3
) = 7.26 and δ 1H (CD
3
SOCD
2
H) = 2.50) and the solvent peak (δ
1,1’-(1,3-propylene)bis(3-tert-butylthiourea) (1c): 6.93 g (93.5 mmol)
1,3-diaminopropane were added to a stirred solution of 21.55 g (187.1
mmol) tert-butylisothiocyanate in 350 ml of diethyl ether. A suspension was
formed after a few minutes and stirring was continued for 16 h. Then, the
precipitates were filtered off, washed with diethyl ether and dried en vacuo
to yield 1c in analytically pure form. White solid, 19.60 g, 64.4 mmol, 69%.
1
3
1
13
1
3 3 2
C{ H} (CDCl ) = 77.16 and δ C{ H} ((CD ) SO) = 39.52), respectively.
The coupling constants J are given in Hertz [Hz]. IR spectra were recorded
with a Thermo Fisher Scientific FT-IR spectrometer Nicolet iS5 equipped
with an iD7 diamond ATR unit. High-resolution mass spectra were
measured by using a Waters LCT Micromass spectrometer.
1H NMR (300 MHz, CDCl
CH CH CH
), 3.74 (dt, 3JHH = 5.5 Hz, 3JHH = 6.2 Hz, 4H, CH
br, 2H, NHC(CH
MHz, CDCl ): δ = 29.5 (C(CH
), 180.7 (NHCSNH). IR [cm ]: ν(NH) = 3247 and 3050, ν(CH)
3
3 3
): δ = 1.41 (s, 18H, C(CH ) ), 1.82 (br, 2H,
Synthesis of 2,6-diisopropylphenylisothiocyanate
2
2
2
2
CH
2
CH
2
), 6.13
1
(
3
)
3
), 6.55 (t, 3JHH = 6.1 Hz, 2H, NHCH
), 30.6 (CH CH CH
2
). 13C{ H} NMR (101
3
3
)
3
2
2
2 2 2 2
), 41.9 (CH CH CH ),
6
8.50 g (900 mmol) of carbon disulphide were added dropwise to a stirred
solution of 139.50 g (708 mmol) of 2,6-diisopropylaniline (90% wt.) and
93.40 g (1.4 mol) K CO in 500 ml of H O. After the addition was complete
3 hours), the reaction mixture was stirred for 16 hours at room temperature
-
1
5
3 3
2.9 (C(CH )
=
2961, ν(CN) = 1536 ν(CS) = 1189. HR-ESI-MS: calcd. for C13
H N S
28 4 2
1
2
3
2
+
[M+H] 305.1833; found 305.1841.
(
before it was cooled to 0 °C and treated dropwise with a solution of 64.50
g (350 mmol) of 2,4,6-trichloro-1,3,5-triazine in 350 ml of dichloromethane
over the course of 3 hours. The resulting brown suspension was then
stirred for 4 hours at room temperature before it was basified to pH > 11 by
adding 700 mL of a sodium hydroxide solution (7 mol/L). After the addition
1,1’-(1,2-ethylene)bis(3-tert-butylthiourea) (1d): 3.00 g (50.0 mmol) 1,2-
ethylenediamine were added to a stirred solution of 11.50 g (100.0 mmol)
tert-butylisothiocyanate in 25 ml of methanol. The solution was stirred over
night at room temperature before the volatiles have been removed en
vacuo. The residue was suspended in water and treated with five drops of
conc. hydrochloric acid. The white precipitate was filtered off and dried en
vacuo to yield 1d in analytically pure form. White solid, 9.54 g, 32.8 mmol,
of 200 ml of dichloromethane and 500 ml of H
organic layer was separated, washed twice with water (200 ml each) and
dried using MgSO . The volatiles were removed en vacuo giving 2,6-
2
O, two layers appeared. The
4
66%. 1H NMR (300 MHz, DMSO-d
4H, (CH ), 7.11 (br, 2H, NHCH ), 7.29 (br, 2H, NHC(CH
): δ = 1.39 (s, 18H, C(CH
)
), 3.43 (s,
diisopropylphenylisothiocyanate as brown oil (105.45 g, 481 mmol, 68%).
The NMR spectra were in accordance with those reported in the
literature.[43]
6
3
3
), 13C{ H} NMR
1
2
)
2
2
3
)
3
(75 MHz, DMSO-d ): δ = 28.9 (C(CH ) ), 42.3 ((CH ) ), 52.2 (C(CH ) ),
6
3
3
2
2
3 3
-
1
1
81.4 (NHCSNH). IR [cm ]: ν(NH) = 3250 and 3056, ν(CH) = 2973 and
2
929, ν(CN) = 1532 ν(CS) = 1196. HR-ESI-MS: calcd. for C12
H N S
26 4 2
Synthesis of the bis(thioureas) 1a–f
+
[M+H] 291.1677; found 291.1710.
1
,1’-(1,3-propylene)bis[3-(2,6-diisopropylphenyl)thiourea] (1a): 5.56 g
1
,1’-(1,3-phenylene)bis(3-tert-butylthiourea) (1e): A mixture of 3.50 g
(75.0 mmol) 1,3-diaminopropane were added to a stirred solution of 32.90
(32.4 mmol) 1,3-diaminobenzene and 8.50
g
(73.8 mmol) tert-
g (150.0 mmol) 2,6-diisopropylphenylisothiocyanate in 200 ml of toluene. A
suspension was formed within a few hours and stirring was continued for
butylisothiocyanate in 10 ml of ethanol was stirred at 70 °C for 72 hours.
After cooling to room temperature, petrol ether was added (about 50 mL)
and the resulting precipitates were filtered off, washed with diethyl ether
and dried en vacuo to yield 1g in analytically pure form. White solid, 6.95 g,
20.5 mmol, 63%. H NMR (400 MHz, DMSO-d
7.13 (m, 2H, 4,6-CHarom), 7.21 (m, 1H, 5-CHarom), 7.34 (s, 2H,
CSNHC(CH
), 7.75 (t, 4JHH = 3.5 Hz, 1H, 2-CHarom), 9.34 (s, 2H,
6 3 3
CSNHCarom). C{ H} NMR (101 MHz, DMSO-d ): δ = 28.6 (C(CH ) ), 52.8
48 h. Then, the precipitates were filtered off, washed with n-hexane and
dried en vacuo to yield 1a in analytically pure form. White solid, 36.18 g,
1
): δ = 1.14 (d, 3
70.6 mmol, 94%. H NMR (300 MHz, CDCl
3
JHH = 6.8 Hz,
1
), 1.20 (d, 3JHH = 6.8 Hz, 12H, CHMe
), 3.05 (sept, JHH = 6.8 Hz, 4H, CHCH
6.1 Hz, 4H, CH
6
): δ = 1.49 (s, 18H, C(CH
3
)
3
),
12H, CHCH
3
2
), 1.59 (br, 2H,
3
), 3.53 (dt, 3JHH = 5.5 Hz,
), 6.22 (t, 3JHH
6.4 Hz, 2H,
CH
3JHH
2
CH
2
CH
2
3
3 3
)
13
=
CH CH
2 2 2
=
1
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700782
FULL PAPER
(
C(CH
3
)
3
), 117.1 (2-CHarom), 118.0 (4,6-CHarom), 128.4 (5-CHarom), 139.5
1,1’-(1,3-propylene)bis(N-tert-butylpyrrolidine-1-carboximidamide)
(2c): A mixture of 0.31 g (1.0 mmol) 1c, 1.48 g (20.0 mmol) pyrrolidine, and
0.11 g (5.0 mmol) PbO in 20 ml of toluene was stirred at 50 °C for 48 hours.
After cooling to room temperature, the solids were filtered off, washed with
toluene and the combined filtrates were concentrated en vacuo yielding 2c
-
1
(1,3-Carom), 179.1 (NHCSNH). IR [cm ]: ν(NH) = 3259 and 3058, ν(CHarom
)
=
1
2980, ν(CH) = 2916, ν(CCarom)= 1569 and 1479, ν(CN) = 1537, ν(CS) =
198. HR-ESI-MS: calcd. for C16
+
26 4 2
H N S [M+H] 339.1677; found 339.1621.
in analytically pure form. Orange viscous oil, 0.36 g, 0.9 mmol, 89%. 1
NMR (300 MHz, CDCl ): δ = 1.17 (s, 9H, C(CH ), 1.23 (s, 9H, C(CH
.69-1.77 (m, 8H, N(CH (CH ), 1.77-1.80 (m, 2H, CH
.23 (m, 8H, N(CH (CH ), 3.24-3.33 (m, 4H, CH CH
): δ = 21.9 (CH CH CH ), 25.0 (C(CH
), 26.0 (N(CH (CH ), 29.5 (C(CH ), 32.0 (C(CH
(CH ), 46.2 (N(CH (CH ), 50.2 (C(CH ), 53.3
), 56.4 (CH CH CH ), 144.8 (NHC(N)N), 145.4 (NHC(N)N). IR
H
) ),
3 3
), 3.13-
). 13C{ H}
1
,1’-(1,3-xylylene)bis[3-(2,6-diisopropylphenyl)thiourea] (1f): 10.22 g
3
3
)
3
(75.0 mmol) 1,3-bis(aminomethyl)benzene were added to a stirred solution
1
3
2
)
2
2
)
2
2
CH
2
CH
2
of 32.90 g (150.0 mmol) 2,6-diisopropylphenylisothiocyanate in 200 ml of
toluene. A suspension was formed within a few hours and stirring was
continued for 18 h. Then, the precipitates were filtered off, washed with n-
hexane and dried en vacuo to yield 1f in analytically pure form. White solid,
1
2
)
2
2
)
2
2
2
CH
2
NMR(101 MHz, CDCl
N(CH (CH
43.4 (N(CH
(C(CH
3
2
2
2
3
)
3
), 25.4
(
2
)
2
2
)
2
2
)
2
2
)
2
3
)
3
3 3
) ),
1
): δ = 1.07 (d, 3JHH
2
)
2
2
)
2
2
)
2
2
)
2
3 3
)
3
4.22 g, 59.5 mmol, 79%. H NMR (300 MHz, CDCl
.2 Hz, 12H, CH(CH
3
=
), 1.16 (d, 3JHH = 7.2 Hz, 12H, CH(CH
), 3.08 (sept,
), 4.77 (d, 3JHH = 5.8 Hz, 4H, CH
2
HH = 7.2 Hz, 12H, CH(CH NH), 5.54(br,
3
)
3
2
2
2
7
3
)
2
3
)
2
-
1
3
[cm ]: ν(NH) = 3420, ν(CH) = 2952 and 2854, ν(CN) = 1611. HR-ESI-MS:
J
3
)
2
+
calcd. for C21H N
42 6
[M+H] 379.3549; found 379.3566.
2
H, CH
2
NH), 7.05 - 7.22 (m, 8H, CHarom), 7.55 (br, 2H, p-CHarom), 8.07 (br,
H, NHCarom). 13C{ H} NMR (75 MHz, CDCl
1
): 23.2 (CH(CH
), 124.6 (m-CHarom), 127.0 (4,6-
CHarom), 129.1 (2-CHarom), 129.7 (i-Carom), 130.1 (p-CHarom), 138.1 (1,3-
2
3
3 2
) ), 24.7
(CH(CH
3
)
2
), 28.6 (CH(CH
3
)
2
), 48.8 (CH
2
1,1’-(1,3-phenylene)bis(N-tert-butylpyrrolidine-1-carboximidamide)
(2d): A mixture of 3.39 g (1.0 mmol) 1e, 1.42 g (20.0 mmol) pyrrolidine, and
0.45 g (6.0 mmol) PbO in 10 ml of toluene was stirred at 100 °C for 88
hours. After cooling to room temperature, the solids were filtered off,
washed with toluene and the combined filtrates were concentrated en
-
1
C
arom), 147.8 (o-CHarom), 181.6 (NHCSNH). IR [cm ]: ν(NH) = 3381 and
3123, ν(CHarom) = 2961, ν(CH) = 2924, ν(CN) = 1534, ν(CCarom)= 1499 and
+
1289, ν(CS) = 1210. HR-ESI-MS: calcd. for C29
H N S
44 4 2
[M+H] 513.3086;
found 513.3051.
vacuo yielding 2d in analytically pure form. Brown solid, 0.30 g, 0.7 mmol,
1
), 1.72 (dt, 3JHH
7
=
3%. H NMR (400 MHz, CDCl
6.2 Hz, 6.5 Hz, 8H, N(CH
3
): δ = 1.32 (s, 18H, C(CH
3
)
3
), 3.13 (t, 3JHH = 6.5 Hz, 8H,
2
)
2 2
(CH )
2
Synthesis of the bis(guanidines) 2a-j
3
N(CH
2
)
2
(CH
2
)
2
), 3.53 (s, 4H, CNHC), 6.13 (t, JHH = 1.9 Hz, 1H, 5-CHarom),
3
4
6
.24 (dd, JHH = 1.9 Hz, JHH = 7.8 Hz, 2H, 4,6-CHarom), 6.97 (t, 4JHH = 7.8
1,1’-(1,3-propylene)bis[N-(2,6-diisopropylphenyl)pyrrolidine-1-
13
1
Hz, 1H, 2-CHarom).
N(CH (CH ), 30.2 (C(CH
13.7 (4,6-CHarom), 115.4 (2-CHarom), 128.6 (1,3-CHarom), 129.2 (5-CHarom),
C{ H} NMR(101 MHz, CDCl
3
):
δ
=
25.4
carboximidamide] (2a): A mixture of 0.51 g (1.0 mmol) 1a, 1.42 g (20.0
mmol) pyrrolidine, and 0.45 g (2.1 mmol) PbO in 20 ml of toluene was
stirred at 100 °C for 16 hours. After cooling to room temperature, the solids
were filtered off, washed with toluene and the combined filtrates were
(
2
)
2
2
)
2
3
)
3
), 48.6 (N(CH (CH ), 51.9 (C(CH
2
)
2
2
)
2
3
)
3
),
1
1
-
1
51.7 (NHC(N)N). IR [cm ]: ν(NH) = 3362, ν(CH) = 2960 and 2869,
ν(CCarom)= 1607, 1505 and 1341 ν(CN) = 1559. HR-ESI-MS: calcd. for
concentrated en vacuo yielding 2a in analytically pure form. White solid,
+
1
): δ = 1.12 (d, 3JHH = 6.9
C H N
24 40 6
[M+H] 413.3393; found 413.3387.
0.58 g, 1.0 mmol, 98%. H NMR (400 MHz, CDCl
3
Hz, 12H, CH(CH
3JHH = 7.0 Hz, 2H, CH
3
)
2
), 1.14 (d, 3JHH = 6.9 Hz, 12H, CH(CH
3
)
2
), 1.52 (quint,
), 1.78 (dt, 3
1,1’-(1,3-xylylene)bis[N-(2,6-diisopropylphenyl)pyrrolidine-1-
2
CH
2
CH
2
J
HH = 5.6 Hz, 6.5 Hz, 8H,
), 3.03 (sept, 3JHH = 6.9 Hz, 4H, CH(CH
carboximidamide] (2e): A mixture of 0.85 g (1.0 mmol) 1f, 1.42 g (20.0
mmol) pyrrolidine, and 0.45 g (2.0 mmol) PbO in 20 ml of toluene was
stirred at 100 °C for 16 hours. After cooling to room temperature, the solids
were filtered off, washed with toluene and the combined filtrates were
2
N(CH )
2 2
(CH )
2
3
)
2
), 3.00 (br, 4H,
3
CH CH
2
2
CH
2
), 3.19 (t, JHH = 6.5 Hz, 8H, N(CH
2
)
2
2
(CH )
2
), 3.54 (br, CNHC),
.92 (t, JHH = 7.4Hz, 2H, p-CHarom), 7.03 (d, 3JHH = 7.4 Hz, 4H, m-CHarom).
3
6
1
3
1
C{ H} NMR(101 MHz, CDCl
(CH ), 28.0 (CH(CH
8.2 (N(CH (CH ), 121.6 (m-CHarom), 122.7 (p-CHarom), 140.2 (o-
3
): δ = 23.2 (CH(CH
3
)
2
), 23.7 (CH(CH
3
)
2
), 25.5
concentrated en vacuo yielding 2e in analytically pure form. White solid,
(
4
N(CH
2
)
2
2
)
2
3
)
2
), 31.5 (CH CH
2
2
CH ), 41.3 (CH CH
2
2
2
CH ),
2
1
): δ = 1.14 (d, 3JHH = 7.0
), 1.84 (dt, 3JHH
HH = 7.0 Hz, 4H,
2 2
) ), 3.81 (br, 2H, CNHC),
0
.66 g, 1.0 mmol, 99%. H NMR (400 MHz, CDCl
3
2
)
2
2 2
)
), 1.18 (d, 3JHH = 7.0 Hz, 12H, CH(CH
(CH
), 3.09 (sept, 3
(CH
-
1
Hz, 12H, CH(CH
5.2 Hz, 6.8 Hz, 8H, N(CH
CH(CH
), 3.29 (t, 3JHH = 6.8 Hz, 8H, N(CH
3
)
2
3 2
)
CHarom), 145.4 (i-CHarom), 151.0 (NHC(N)N). IR [cm ]: ν(NH) = 3236 , ν(CH)
=
2
)
2
2
)
2
J
=
2955 and 2922, ν(CCarom)= 1550, 1429 and 1327, ν(CN) = 1515. HR-ESI-
+
3
)
2
2
)
2
MS: calcd. for C37
H
60
N
6
[M+H] 588.4880; found 588.4842.
4
J
.26 (s, 4H, CH
C H
2 6 4
CH
2
), 6.93 (t, 3
J
HH = 7.8Hz, 2H, p-CHarom), 7.04 (d,
3
3
HH = 7.8 Hz, 4H, m-CHarom), 7.12 (d, JHH = 8.3 Hz, 2H, 4,6-CHarom), 7.13
m, 1H, 2-CHarom), 7.21 (t, 3JHH = 8.3 Hz, 1H, 5-CHarom). 13C{ H} NMR(101
1,1’-(1,3-propylene)bis[N-(perfluorphenyl)pyrrolidine-1-
1
(
carboximidamide] (2b): A mixture of 0.26 g (0.5 mmol) 1b, 0.71 g (10.0
mmol) pyrrolidine, and 0.22 g (1.0 mmol) PbO in 10 ml of toluene was
stirred at 100 °C for 16 hours. After cooling to room temperature, the solids
were filtered off, washed with toluene and the combined filtrates were
concentrated en vacuo yielding 2b in analytically pure form. Off-white waxy
MHz, CDCl
8.1 (CH(CH
CHarom), 122.8 (p-CHarom), 125.8 (4,6-CHarom), 128.8 (2-CHarom), 140.1 (o-
3
): δ = 23.2 (CH(CH
3
)
2
), 23.7 (CH(CH
3
)
2 2 2 2 2
), 25.5 (N(CH ) (CH ) ),
2
3
)
2
), 47.7 (CH
2
C
4
H
6
CH ), 48.4 (N(CH
2
2
)
2
(CH ), 121.8 (m-
2 2
)
-
1
CHarom), 140.3 (i-CHarom), 145.1 (1,3-CHarom), 151.0 (NHC(N)N). IR [cm ]:
solid,0.30 g, 0.5 mmol, 99%. 1H NMR (300 MHz, CDCl
3JHH = 5.8 Hz, 2H, CH ), 1.80 (dt, 3
CH CH HH = 6.0 Hz, 6.5 Hz, 8H,
N(CH (CH HH = 6.5 Hz, 8H, N(CH
), 3.07 (t, 3
3JHH = 5.8 Hz, CH
CH CH
CDCl ): δ = 25.5 (N(CH
7.8 (N(CH (CH ), 127.6 (m-CHarom), 136.7 (p-CHarom), 139.4 (o-
CHarom), 141.8 (i-CHarom), 155.1 (NHC(N)N). F NMR(282 MHz, CDCl
ν(NH) = 3449 and 3399, ν(CH) = 2954 and 2865, ν(CCarom)= 1611, 1503
3
): δ = 1.68 (quint,
+
and 1342, ν(CN) = 1580. HR-ESI-MS: calcd. for C42
H N
60 6
[M+H] 649.4958;
2
2
2
J
found 649.4975.
2
)
2
2
)
2
J
2
)
2
(CH
2
)
2
), 3.41 (q, 4H,
13
1
2
2
2
), 5.02 (br, 2H, CNHC). C{ H} NMR (101 MHz,
1,1’-(1,3- xylylene)bis[N-(2,6-diisopropylphenyl)morpholine-1-
3
2 2 2 2 2 2 2 2 2 2
) (CH ) ), 30.6 (CH CH CH ), 39.0 (CH CH CH ),
carboximidamide] (2f): A mixture of 0.27 g (0.5 mmol) 1f, 0.11 g (9.3
mmol) morpholine, and 0.23 g (1.0 mmol) PbO in 10 ml of toluene was
stirred at 100 °C for 16 hours. After cooling to room temperature, the
solids were filtered off, washed with toluene and the combined filtrates
4
2
)
2
2 2
)
19
3
): δ
171.83 (br, 2F, p-CFarom), -166.60 (t, 3JFF = 21.0 Hz, 4F, m-CFarom), -155.71
d, 3JFF = 21.0 Hz, 4F, o-CFarom). IR [cm ]: ν(NH) = 3272, ν(CH) = 2958 and
-
(
-1
were concentrated en vacuo yielding 2f in analytically pure form. White
2
867, ν(CCarom)= 1597, 1529 and 986, ν(CN) = 1498. HR-ESI-MS: calcd.
1
+
solid, 0.25 g, 0.4 mmol, 77%. H NMR (400 MHz, CDCl
3
): δ = 1.13 (d,
for C25
H F N
24 10 6
[M+H] 599.1981; found 599.1984.
3JHH = 6.9 Hz, 12H, CH(CH
.96 (sept, 3JHH = 6.9 Hz, 4H, CH(CH
N(CH (CH O), 3.69 (br, 2H, CNHC), 3.76 (br, 8H, N(CH
), 1.16 (d, 3JHH = 6.9 Hz, 12H, CH(CH
), 3.25 (t, 3JHH = 4.0 Hz, 8H,
2 2
(CH )
)
),
3
)
2
3
2
2
3 2
)
2
)
2
2
)
2
2
)
2
O),
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700782
FULL PAPER
), 6.86-7.27 (m, 10H, CHarom). 13C{ H} NMR(101
), 28.1 (CH(CH ), 49.0 (CH CH ),
(CH O), 123.0 (m-CHarom), 123.2
1
(NCH(CH
)
(CH
)
(CH
), 122.4 (m-CHarom), 123.1 (p-CHarom), 126.2 (4,6-
4
.17(s, 4H, CH
MHz, CDCl ): δ= 23.4 (CH(CH
7.8 (N(CH (CH O), 66.7 (N(CH
2
C
6
H
4
CH
2
2
2
2
2
2
3
3
)
2
3
)
2
C H
2 4 6
2
CHarom), 126.2 (5-CHarom), 128.9 (2-CHarom), 141.4 (o-CHarom), 141.5 (i-
CHarom), 144.0 (1,3-CHarom), 148.1 (NHC(N)N). IR [cm ]: ν(NH) = 3402,
-
1
5
2
)
2
2
)
2
2
)
2
2
)
2
(
(
p-CHarom), 125.1 (4,6-CHarom), 125.7 (2-CHarom), 129.2 (2-CHarom), 139.4
o-CHarom), 139.8 (i-CHarom), 143.6 (1,3-CHarom), 154.5 (NHC(N)N). IR [cm-
ν(CH) = 2925 and 2853, ν(CCarom)= 1630, 1441 and 1326, ν(CN) = 1584.
+
HR-ESI-MS: calcd. for C46
H N
68 6
[M+H] 705.5583; found 705.5592.
1
]
: ν (NH) = 3385, ν(CH) = 2956 and 2864, ν(CCarom)= 1629, 1446 and
60 6 2
324 and 1113, ν(CN) = 1586. HR-ESI-MS: calcd. for C42H N O
[M+H]+
1
6
1,1’-(1,3-xylylene)bis[3-phenyl-2-(2,6-diisopropylphenyl)guanidine]
81.4856; found 681.4863.
(2j): A mixture of 0.27 g (0.5 mmol) 1f, 0.87 g (9.3 mmol) aniline, and 0.23
g (1.0 mmol) PbO in 8 ml of toluene was stirred at 100 °C for 16 hours.
After cooling to room temperature, the solids were filtered off, washed with
toluene and the combined filtrates were concentrated en vacuo yielding 2j
in analytically pure form. Off-white solid, 0.31 g, 0.5 mmol, 95%. 1H NMR
1
,1’-(1,3-xylylene)bis[3,3-diethyl-2-(2,6-diisopropylphenyl)guanidine]
(2g): A mixture of 0.29 g (0.5 mmol) 1f, 0.73 g (10.0 mmol) diethylamine,
and 0.25 g (1.1 mmol) PbO in 10 ml of toluene was stirred at 100 °C for 16
hours. After cooling to room temperature, the solids were filtered off,
washed with toluene and the combined filtrates were concentrated en
vacuo yielding 2g in analytically pure form. Orange viscous oil, 0.29 g, 0.5
(400 MHz, CDCl
4.07-4.84 (m, 4H, CH
3
): δ = 1.18 (br, 24H, CH(CH
CH ), 5.41 (br, 2H, CNHC), 6.84-7.82 (m, 22H,
CHarom + CNHC). 13C{ H} NMR(101 MHz, CDCl
): δ= 23.8 (CH(CH ), 28.1
(CH(CH ), 45.5 (CH CH ), 122.1 (CHarom), 122.8 (CHarom), 123.8
3 2 3 2
) ), 3.20 (br, 4H, CH(CH ) ),
2
C
6
H
4
2
1
3
3 2
)
mmol, 99%. 1H NMR (400 MHz, CDCl
CH(CH HH = 7.0 Hz, 12H, CH(CH
), 1.17 (d, 3
N(CH (CH
, 3.02 (sept, 3JHH = 7.0 Hz, 4H, CH(CH
.1 Hz, 8H, N(CH
): δ = 1.13 (d, 3
), 1.10-1.19 (m, 12H,
), 3.26 (q, 3
J =
HH
J
HH = 7.0 Hz, 12H,
3
3
)
2
2
C
4
H
6
2
3
)
2
J
3
)
2
(CHarom), 124.9 (CHarom), 126.3 (CHarom), 127.0 (CHarom), 128.7 (CHarom),
129.5 (CHarom), 138.3 (CHarom), 140.1 (CHarom), 141.2 (CHarom), 143.9 (1,3-
2
)
2
3
)
2
3
)
2
-
1
7
2
)
2
(CH
2
)
2
), 3.63 (br, 2H, CNHC), 4.12 (s, 4H,
CHarom), 149.4 (NHC(N)N). IR [cm ]: ν(NH) = 3403, ν(CH) = 2958, 2925
CH
δ
4
C H
2 6 4
CH
12.9 (N(CH
2.6 ,0(N(CH (CH
CHarom), 125.1 (4,6-CHarom), 125.5 (5-CHarom), 129.0 (2-CHarom), 139.8 (o-
2
), 6.90-7.20 (m, 10H, CHarom). 13C{ H} NMR(101 MHz, CDCl
1
3
):
and 2865, ν(CCarom)= 1634, 1497, 1437 and 1256, ν(CN) = 1584. HR-ESI-
+
=
2
)
2 3
(CH )
2
), 23.6 (CH(CH
3
)
2
), 28.1 (CH(CH
3
)
2
),
MS: calcd. for C46H N
56 6
[M+H] 693.4645; found 693.4638.
2
)
2
3
)
2 2 4 6 2
), 48.5 (CH C H CH ), 122.5 (m-CHarom), 123.1 (p-
-
1
CHarom), 140.1 (i-CHarom), 144.6 (1,3-CHarom), 154.4 (NHC(N)N). IR [cm ]:
ν(NH) = 3383, ν(CH) = 2958 and 2866, ν(CCarom)= 1622, 1437, 1379 and
Acknowledgements
64 6
H N
[M+H]+ 653.5270;
1082, ν(CN) = 1585. HR-ESI-MS: calcd. for C42
The project was financially supported by the Fonds der Chemischen
Industrie, the Deutsche Forschungsgemeinschaft (DFG, KR4782/2-
found 653.5258.
1
), and the University of Regensburg. R.K. is grateful to the Stiftung
1
(
1
,1’-(1,3-xylylene)bis[3,3-di-n-propyl-2-
2,6-diisopropylphenyl)guanidine] (2h): A mixture of 0.45 g (0.8 mmol)
f, 1.62 g (16.0 mmol) dipropylamine, and 0.35 g (1.6 mmol) PbO in 20 ml
Stipendien-Fonds des Verbands der Chemischen Industrie for a
Liebig fellowship. Additionally, helpful discussions with Dr. Stefanie
Gärtner and generous support from Professor Manfred Scheer is
gratefully acknowledged.
of toluene was stirred at 100 °C for 16 hours. After cooling to room
temperature, the solids were filtered off, washed with toluene and the
combined filtrates were concentrated en vacuo yielding 2h in analytically
1
Keywords: bis(guanidine) • bis(thiourea) • desulfurization •
ditopic ligands • hydrogen bond
pure form. Orange viscous oil, 0.57 g, 0.8 mmol, 99%. H NMR (300 MHz,
CDCl (CH
): δ = 0.89 (t, 3JHH = 6.8 Hz, 12H, N(CH , 1.13 (d, 3JHH = 6.5
Hz, 12H, CH(CH
), 1.16 (d, 3JHH = 6.5 Hz, 12H, CH(CH
H, N(CH )(CH (CH ), 3.96 - 3.04 (m, 4H, CH(CH
Hz, 8H, N(CH (CH (CH ), 3.63 (br, 2H, CNHCH
Hz, 4H, CH
), 6.85 (br, 1H, 2-CHarom) 6.94 (t, 3JHH = 7.4 Hz, 2H, p-
3
2
)
4
3 2
)
3
)
2
3
)
2
), 1.50-1.71 (m,
3
8
2
2
)
2
3
)
2
3
)
2
), 3.18 (t, JHH = 6.8
), 4.10 (d, 3JHH = 6.7
2
)
2
2
)
2
3
)
2
2
Notes and references
2 6
C
H
4
CH
2
CHarom), 7.00 (d, JHH = 8.3 Hz, 2H, 4,6-CHarom), 7.06 (d, 3JHH = 7.3 Hz, 4H,
m-CHarom), 7.19 (br, 1H, 5-CHarom). 1 C{ H} NMR (101 MHz, CDCl
3
3
1
[1]
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): 11.5
), 28.0
3 2
) ), 122.4 (m-
(
(
N(CH
CH(CH
2
)
4
(CH
3
)
2
), 20.8 (N(CH
2
)
2
(CH
2
)
2
(CH
3
)
2
), 23.5 (CH(CH
3 2
)
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), 48.4 (CNHCH
2
), 50.1 (N(CH
2
)
2
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-
1
CHarom), 139.6 (o-CHarom), 140.1 (i-CHarom,) 154.8 (NHC(N)N). IR [cm ]:
ν(NH) = 3379, ν(CH) = 2959 and 2870, ν(CCarom)= 1625, 1459 and 1079,
2
013; e) J. Bariwal, E. Van der Eycken, Chem. Soc. Rev. 2013, 42,
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[M+H]+ 709.5897; found
ν(CN) = 1586. HR-ESI-MS: calcd. for C46H N
72 6
709.5905.
.
[
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,1’-(1,3-xylylene)bis[3-cyclohexyl-2-(2,6-
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.
diisopropylphenyl)guanidine] (2i): A mixture of 0.27 g (0.47 mmol) 1f,
.92 g (9.3 mmol) cyclohexylamine, and 0.23 g (1.0 mmol) PbO in 8 ml of
[
[
[
3]
4]
5]
A. Strecker, Liebigs Ann. Chem. 1861, 118, 151–177.
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0
toluene was stirred at 100 °C for 16 hours. After cooling to room
temperature, the solids were filtered off, washed with toluene and the
combined filtrates were concentrated en vacuo yielding 2i in analytically
pure form. Off-white solid, 0.32 g, 0.5 mmol, 96%. H NMR (300 MHz,
CDCl
A. Dippold, T. M. Klapötke, F. A. Martin, Z. Anorg. Allg. Chem. 2011
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37, 1181–1193.
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3.10 (br, 4H, CH(CH
3
)
2
), 3.44 (br, 2H, CNHC), 3.70-4.8 (m, 4H,
3
CH
7
2 6
C
H
4
CH
2
), 4.65 (br, 2H, CNHC), 6.99 (t, JHH = 7.0Hz, 2H, p-CHarom),
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1
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NMR(101 MHz, CDCl
3
): δ= 23.7 (CH(CH
(CH ) ), 25.1 (NCH(CH
), 34.3 (NCH(CH (CH (CH ), 45.7 (CH
3
)
2
), 24.9
&
.
(NCH(CH
2
)
2 2
(CH )
2
2
2
)
2
(CH
2
)
2
(CH
2
) ), 27.9
(
CH(CH
3
)
2
2
)
2
2
)
2
2
2
C
H
4 6
CH ), 50.8
2
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European Journal of Organic Chemistry
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FULL PAPER
FULL PAPER
V. Vass, M. Dehmel, F. Lehni, R.
Kretschmer*
Page No. – Page No.
A Facile One-Pot Synthesis of 1,2,3-
Tri- and 1,1,2,3-Tetrasubstituted
Bis(guanidines) from Bis(thioureas)
Using an efficient one-pot protocol, 1,2,3-tri- and 1,1,2,3-tetrasubstituted
bis(guanidines) are obtained from readily available bis(thioureas) in analytically
pure form and good to excellent yields. The facile strategy covers a range of
terminal and bridging groups. Less sterically demanding cyclic and acyclic
secondary alkyl amines are applicable as well as primary amines and anilines.
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