Tuning a robust system: N,O zinc guanidine catalysts for the ROP of lactide

Article abstract of DOI:10.1039/c8dt04938f

Non-toxic, highly active and robust complexes are the holy grail as ideal green catalysts for the polymerisation of biorenewable and biodegradable polylactide. Four new zinc guanidine complexes [ZnCl₂(TMG4NMe₂asme)], [ZnCl₂(TMG5Clasme)], [ZnCl₂(TMG5Measme)] and [ZnCl₂(TMG5NMe₂asme)] with different electron-donating and electron-withdrawing groups on the ligand's aromatic backbone have been synthesised. Ligands are derived from low-cost commercially available compounds and have been converted by a three- or four-step synthesis process into the desired ligand in good yields. The compounds have been fully characterised and tested in the ROP of rac-LA under industrially relevant conditions. The complexes are based on the recently published structure [ZnCl₂(TMGasme)] which has shown high activity in the polymerisation of lactide at 150 °C. Different substituents in the para-position of the guanidine moiety significantly increase the polymerisation rate whereas positioning substituents in the meta-position causes no change in the reaction rate. With molecular weights over 71000 g mol^-1 being achievable, the best system produces polymers for multiple industrial applications and its polymerisation rate approaches that of Sn(Oct)₂. The robust systems are able to polymerise non-purified lactide. The initiation of the polymerisation is suggested to occur due to impurities in the monomer.

Full text of DOI:10.1039/c8dt04938f

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P. M. Schäfer, P. McKeown, M. Fuchs, R. D. Rittinghaus, A. Hermann, J. Henkel, S. Seidel, C. Roitzheim, A.
N. Ksiazkiewicz, A. Hoffmann, A. Pich and M. Jones, Dalton Trans., 2019, DOI: 10.1039/C8DT04938F.
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DOI: 10.1039/C8DT04938F
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Tuning a robust system: N,O Zinc Guanidine Catalysts for the ROP
of Lactide
a
b
a
a
a
Pascal M. Schäfer, Paul McKeown, Martin Fuchs, Ruth D. Rittinghaus, Alina Hermann, Johanna
Received 00th January 20xx,
Accepted 00th January 20xx
Henkel,a Sebastian Seidel, Christoph Roitzheim, Agnieszka N. Ksiazkiewicz,
Hoffmann, Andrij Pich, Matthew D. Jones and Sonja Herres-Pawlis*
a
a
c,d
Alexander
a
c,d
b
a
DOI: 10.1039/x0xx00000x
www.rsc.org/
Non-toxic, highly-active and robust complexes are the holy grail as ideal green catalysts for the polymerisation of
biorenewable and biodegrable polylactide. Four new zinc guanidine complexes [ZnCl (TMG4NMe asme)],
ZnCl (TMG5Clasme)], [ZnCl (TMG5Measme)] and [ZnCl (TMG5NMe asme)] with different electron-donating and electron-
2
2
[
2
2
2
2
withdrawing groups on the ligand’s aromatic backbone have been synthesised. Ligands are derived from low-cost
commercially available compounds and have been converted in a three- or four-step synthesis into the desired ligand in
good yields. The compounds have been fully characterised and tested in the ROP of rac-LA under industrially relevant
conditions. The complexes are based on the recently published structure [ZnCl (TMGasme)] which has shown high activity
2
in the polymerisation of lactide at 150 °C. Different substituents in the para-position of the guanidine moiety significantly
increase the polymerisation rate whereas positioning substituents in meta-position causes no change in the reaction rate.
With molecular weights over 71 000 g mol-1 achievable, the best system produces polymer for multiple industrial
2
applications and its polymerisation rate approaches that of Sn(Oct) . The robust systems are able to polymerise non-purified
lactide. The initiation of the polymerisation is suggested to occur due to impurities in the monomer.
bioplastics. These macromolecules are characterised by their
Introduction
bio-based monomers and / or the biodegradability of the
polymer. These criteria apply to plastics such as starch plastics,
th
Since the middle of the 20 century, the production of plastics
has increased enormously. Due to their diverse material
properties, they are used in all areas of life and have
contributed to a tremendous progress of everyday life.1-3
Commodity plastics like PE, PP, PS, PVC and PET are produced
from petrochemicals. The scarcity of oil and the long lifetime of
plastics, leading to a waste problem, which possess new
challenges for society. Every year millions of tons of plastic
waste are released into the oceans, contaminating landscapes,
cellulose
poly(hydroxyalkanolate) (PHA).
acetate,
poly(lactic
acid)
(PLA)
and
5-7
Currently, polylactide is the
most widely produced biodegradable bioplastic. This polyester
has similar mechanical and physical properties in comparison
with PP and PET. Therefore, PLA can be used as a substitute in
many areas of everyday life, e.g. in the packaging industry. PLA
is also used as material for implants and sutures in the medical
3, 8-11
field.
The polymerisation to PLA occurs via a ring opening
polymerisation (ROP) of lactide, the cyclic dimer of lactic acid.
The most common mechanism for a controlled polymerisation
4
flora and fauna. A potential solution for this problem are
12
is the coordination insertion mechanism. In the literature a
considerable amount of catalysts for the ring opening
polymerisation are reported. Depending on the design of the
catalyst and choice of the monomer, tacticity and molar masses
of the polymer can be controlled. Highly active catalysts
containing aluminium, magnesium, titanium, tin, rare earth
metals and zinc have been presented in literature.13 Zinc
complexes from Tolman et al. feature aminophenolate
a.
P.M. Schäfer, M. Fuchs, R.D. Rittinghaus, A. Hermann, J. Henkel, S. Seidel, C.
Roitzheim, Dr. A. Hoffmann, Prof. Dr. S. Herres-Pawlis
Institut für Anorganische Chemie
RWTH Aachen University
Landoltweg 1, 52074 Aachen (Germany)
E-mail: sonja.herres-pawlis@ac.rwth-aachen.de
Dr. P. McKeown, Dr. M.D. Jones
b.
Department of Chemistry
University of Bath
Claverton Down, Bath BA2 7AY (UK)
A.N. Ksiazkiewicz, Prof. Dr. A. Pich
14
15
c.
ligands, whereas Coates et al. have used
-diiminates. Work
Institute of Technical and Macromolecular Chemistry
RWTH Aachen University
Worringerweg 2, 52074 Aachen (Germany)
A.N. Ksiazkiewicz, Prof. Dr. A. Pich
DWI – Leibniz Institute for Interactive Materials e.V.,
by Jones et al. is concerned with salan complexes using
16, 17
zirconium, titanium or hafnium
as well as Schiff bases with
d.
18
magnesium and zinc. Ketoiminate complexes have been
19, 20
presented by Schulz et al.
Williams et al. introduced in 2016
Forckenbeckstr. 50, 52074 Aachen (Germany)
Electronic Supplementary Information (ESI) available. See DOI: 10.1039/x0xx00000x
a dinuclear zinc complex as the fastest catalyst for lactide
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polymerisation in solution to date.21 The disadvantage of the technical grade lactide.45-52 In 2017 we presented four robust
View Article Online
DOI: 10.1039/C8DT04938F
majority of known catalysts is that the polymerisation of lactide N,O donor zinc guanidine catalysts with high activity in the
has not be reported with as-received lactide and/or in melt. polymerisation of lactide under industrial conditions.53 Though
However, for industry application the catalyst needs to be the catalysts are robust, they could not reach the high activity
active with technical grade lactide and under melt conditions.22 demonstrated by Sn(Oct)
. To address this, the systematic
In industry the most commonly used catalyst is tin(II) 2- exchange of substituents on the aromatic ring has been
ethylhexanoate {Sn(Oct) } better known as tin octanoate. conducted to analyse the influence of electronic effects on the
Several studies with this system have been reported by activity of the zinc chlorido complexes. The systems have been
2
2
23-26
Pennings and Kricheldorf et al.
This catalyst is highly active tested for the polymerisation in melt and kinetics have been
for the polymerisation of lactide at high temperatures studied using in situ Raman and IR spectroscopy. Herein, we
producing colourless polymers with high molar masses. In show that the activity can be enhanced by suited substitution in
addition, the catalyst maintains its activity at low catalyst para-position.
concentrations. However, after the polymerisation the catalyst
remains in the polymer matrix and can accumulate in the soil
after decomposition of the biodegradable PLA. Despite
Results and Discussion
approval of the catalyst from the FDA, tin octanoate has been
reported as toxic for cells.
Synthesis
27, 28
To investigate the electronic effect of different substituents in
the catalytic ROP of lactide, both electron-donating and
electron-withdrawing substituents on the aromatic backbone of
the TMGasme system were chosen. The substituents were
introduced in para- and meta-position to the guanidine moiety
on the aromatic system. The substituents used were the
electron-withdrawing chloro group and the electron-donating
substituents methyl and dimethylamine. For the guanidine
synthesis, the corresponding primary amines were prepared in
a two- or three-step synthesis (Scheme 1). The starting
carboxylic acids were purchased at low cost and converted to
the amine by esterification, substitution at the aromatic ring
and hydrogenation in high yields and under facile conditions.
Zinc complexes with neutral ligands represent an extremely
promising alternative to the existing catalyst for PLA
production. On one hand zinc is non-toxic and, on the other
hand, the complexes proved to be moisture-stable when using
29, 30
neutral ligands.
zinc(II) complexes.
Hayes et al. employed phosphinimine based
31-33
Carbene zinc complexes have been
reported by Tolman and co-workers.34 Zinc catalysts with bis-
camphoryldiimine ligands and pyrrolidine amines have been
35-37
described by Jeong et al.
Nevertheless, these catalysts
require purified lactide for a controlled polymerisation. In
contrast, zinc guanidine complexes are very robust catalysts for
the ROP of lactide and are able to polymerise non-purified
technical grade lactide which contains water and lactic acid
residues. Due to the high basicity of the nitrogen imine of the
guanidine, this ligand class can form copper complexes which
The four guanidines TMG4NMe
TMG5Measme (L3) and TMG5NMe
synthesised by treating the respective primary amine with the
2
asme (L1), TMG5Clasme (L2),
2
asme (L4) have been
3
8, 39
are active for the ATRP of styrene
, as modelling system of
54, 55
vilsmeier salt (TMG).
All ligands were characterised by NMR
4
0
tyrosinase complexes to activate oxygen and the entatic
and IR spectroscopy, as well as HR-MS spectrometry. Zinc
chlorido complexes with all four ligands have been prepared in
41-44
state.
Over the last few years several zinc guanidine
complexes have been reported as active catalysts in the ROP of
Scheme 1. Synthesis of TMG4NMe
2 2
asme (L1), TMG5Clasme (L2), TMG5Measme (L3) and TMG5NMe asme (L4) ligands.
a, R1 = NMe , R = H
2
1b, R1 = H, R2 = NMe2
4
2
R2
NO2
R2
R1
NO2
O
O
R1
OH
O
substitution
R2
esterification
substitution
hydrogenation
N
N
O
R2
R2
R1
guanidine
synthesis
NO2
NH2
NO2
esterification
hydrogenation
R2
N
O
O
O
O
R1
R1
R1
O
O
OH
, R1 = H, R2 = Cl
, R1 = Cl, R2 = H
, R1 = Me, R2 = H
, R1 = Cl, R2 = H
1a, R1 = H, R2 = Cl
2a, R1 = Cl, R2 = H
3a, R1 = Me, R2 = H
1c, R1 = H, R2 = NMe2
2b, R1 = Cl, R2 = H
3b, R1 = Me, R2 = H
L1, R1 = H, R2 = NMe2
L2, R1 = Cl, R2 = H
L3, R1 = Me, R2 = H
L4, R1 = NMe2, R2 = H
1
2
3
4
4b, R1 = NMe , R = H
2
4c, R1 = NMe , R = H
2
2
2
2
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View Article Online
DOI: 10.1039/C8DT04938F
Figure 2. Raman spectra of PLA and LA (spectrum every 10 s, excitation at 785 nm).
substituents in para- and meta-position to the guanidine
moiety.
In C4, the Zn‒O bond length is 2.091(2) Å, which is slightly
longer than in complex C3 with a value of 2.064(1)
delocalisation of the electrons in the guanidine moiety is
described by the parameter . The values of 0.99 (C3) and 1.00
C1 C2 C4) indicate full delocalisation within the guanidine
moiety. The guanidine twist allows an estimation of the ability
of the methyl groups on the nitrogen amine in the guanidine
moiety to rotate. The values are listed in Table 1 and show that
the twist is lowest for C3 (28.9°) and highest for C4 (32.1°). The
complexes C1‒C4 do not differ from the values of the
Å. The

Figure 1. Molecular structures of C1‒C4 in the solid state. H atoms are omitted for
clarity.
(
,
,
57
THF. The complexes [ZnCl
2
(TMG4NMe
(TMG5Measme)] (C3) and
asme)] (C4) have been synthesised with good
2
asme)]
(C1),
[
[
ZnCl
ZnCl
2
(TMG5Clasme)] (C2), [ZnCl
(TMG5NMe
2
2
2
yields. Single crystals of each compound have been analysed by
X-ray crystallography (Figure 1). The complexes C1 C4 (Table 1)
are four-coordinate by two chlorides, the carbonyl oxygen atom
carbonyl) and the guanidine imine atom (Nimine). With a value
of 0.86‒0.89, all complexes have the same preference towards
unsubstituted complex [ZnCl
lengths Zn‒O. With a value of 2.038(3) Å, the Zn‒O bond length
for [ZnCl (TMGasme)] is much shorter.
2
(TMGasme)] except for the bond
‒
2
(O

4
Polymerisation
5
6
the tetrahedral geometry. This observation is supported by
the plane angles ZnNO and ZnCl with a range of 81.8(1)‒
6.1(1)°. The bond lengths Zn‒Ngua are the same for all
All complexes (C1‒C4) have been tested in the polymerisation
2
of lactide under solvent free conditions (Table 2). Non-purified
technical grade lactide has been used to test the systems under
industrial relevant conditions at 150 °C. To compare the
8
complexes despite the different electronically influencing
Table 1. Selected bond lengths [Å] and angles [°].[a]
complex
Zn‒Ngua
Zn‒O
1.988(2) 2.076(2) 2.215(1)
.225(1)
1.999(1) 2.072(1) 2.212(1)
.212(1)
1.992(1) 2.064(1) 2.213(1)
.216(1)
1.981(3) 2.091(2) 2.214(1)
.221(1)
(TMGasme)]53 1.998(4) 2.038(3) 2.224(1)
.212(2)
Zn‒Cl
N‒Zn‒O
88.3(1)
(ZnCl
2
, ZnNO)
[b]

4
[c]
guanidine twist[d]
35.1(2)
C1
85.4(1)
84.0(1)
86.1(1)
81.8(1)
86.5(1)
1.00 0.89
1.00 0.86
0.99 0.87
1.00 0.86
1.00 0.85
2
27.1(1)
31.6(1)
26.6(1)
26.0(1)
31.7(1)
27.5(1)
36.7(2)
28.6
C2
C3
C4
87.2(1)
87.1(1)
86.8(1)
90.2(1)
2
2
2
[ZnCl
2
2
2
푎
[
a] Standard deviations are given in parentheses. [b]

= (
with a = d/(Cgua-Ngua) and b and c = d/(Cgua-Namine). [c]
푏+푐)
3
60°−(+)

4 =
. [d] The angles between the planes are represented by Ngua, Namine, Namine and Cgua, Camine, Camine. Two twist angles
1
41°
for each moiety.
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position to the guanidine moiety. The introduction of a chloro
View Article Online
DOI: 10.1039/C8DT04938F
substituent in para-position to the guanidine (C2) achieves an
increase in activity for the catalytic process. With a rate
-4 -1
constant kapp = 2.39
 0.005 x 10 s ([M]/[I] = 500:1), complex
C2 shows twice the activity in the ROP of lactide than the
unsubstituted analogue. The use of withdrawing groups has
been suggested to make the metal more Lewis acidic and
5
8
accelerates the polymerisation activity. Having a methyl group
as electron donating group in para-position to the guanidine
moiety (C3) doubles the activity compared to the previous
system (C2). Complex C3 affords a rate constant of
-
4 -1
k
app = 4.92 x 10 s ([M]/[I] = 500:1) and is four times faster
than [ZnCl
constant k
2
(TMGasme)]. For this system the propagation
has been determined by plotting various rate
p
Figure 3. Plot of kapp versus [init.] for C4. Conditions: rac-LA, 150 °C, 260 rpm, non-
purified lactide; [M]/[I] = 500:1, 625:1, 1000:1, 2000:1.
constants kapp against their initiator concentrations using the
slope of linear fit. The rate constant k allows a comparison
p
between different catalysts which have been tested in melt
independently of the initiator concentrations. C4 showed the
highest activity of the tested complexes. The complex bears a
dimethylamine group in para-position to the Ngua and seems to
have the highest influence on the polymerisation rate. With
k = 6.10 x 10 L mol s (Figure 3) the complex is six times
p
faster than the unsubstituted analogue. Even under our
laboratory conditions, where mass transport can be a challenge
systems in terms of the electronic influence of the different
substituents and positions to the aromatic ring, the apparent
polymerisation rate constants kapp
(C1‒C4) and the propagation
rate constants k C3 C4) have been determined. The
p
(
,
polymerisation using C1 as catalyst was performed in Schlenk
tubes at 150 °C under stirring (260 rpm). The polymerisation
was tested with a monomer-to-initiator ratio ([M]/[I]) of 500:1.
-2
-1 -1
k
app was determined by carrying out multiple batch reactions
1
n
at high conversions and M values, rac-lactide can be converted
with varying times. The conversion was determined by H NMR
spectroscopy, through examination of the methyl group
resonances for LA and PLA respectively. The polymers were
into PLA by up to 81%. The effect of the substituents might be
explained by the electron-donor strength of the different
substituents. Analysis of the bond lengths of the four crystals
structures, unfortunately, does give a clear answer. Since the
Zn- Ngua bond lengths are equal, therefore an effect of the donor
strength is not obvious. It is striking, that the most active
catalyst C4 has the longest Zn‒O bond length compared to other
complexes. The fastest complex C4 is the most favoured system
precipitated from ethanol, dried and the molecular weight (M
n
,
w
M ) analysed via GPC (gel permeation chromatography). By
plotting the natural-logarithmic lactide concentration versus
time, kapp was determined from the slope of the linear fit. For
complexes C2‒C4 the polymerisation was performed in a
reactor and followed by in situ Raman (Figure 2) or in situ IR
spectroscopy (500:1, C4) measurements (150 °C, 260 rpm).
The polymerisation results for complex C1 are listed in Table 2
to substitute Sn(Oct)
2
. The industrial used catalyst has a k
p
of
-2
-1 -1
1
6.7 x 10 L mol s (under analogous conditions, ESI) and is
-
5
-1
just three times faster than C4. So, finally, our catalyst come
close to the speed of the industrial system. Adding a co-initiator
to the polymerisation using C4 as catalyst at ratio of 625:1:1
shows that the rate constant doubles (ESI).
Considering the molar masses of polymers synthesised in
differently catalysed polymerisation runs, it becomes clear that
the measured masses are higher than the theoretical ones.
Since we used no external initiator, we calculated our
and present a kapp value of 6.7 x 10 s ([M]/[I] = 500:1). After
0 min the complex with a dimethylamine group in meta-
position to the guanidine achieved 48% conversion. In
comparison to the unsubstituted complex [ZnCl (TMGasme)]
0.10 x 10 s ([M]/[I] = 500:1) complex C1
9
2
-
4
-1
with a kapp = 1.09

with an electron-donating group in meta-position to the
guanidine has a similar activity. Therefore, the influence of an
electron-withdrawing group has been tested in the para-
Table 2. Polymerisation data for rac-LA with catalysts C1-C4 and the complex [ZnCl
2
(TMGasme)].[a]
-
1
-1 [b]
-1 [c]
conv. [%][d]
n,theo [g mol-
[g mol-1][f]
init.
k
p
[L mol s ]
k
app [s ]
time
M
M
n
PD
1
][e]
C1
C2
C3
C4
6.7 x 10-5
90 min
53 min
36 min
2 h
48
25
68
81
33 800
18 000
49 000
58 300
34 600
43 900
85 500
71 000
1.4
1.4
1.5
1.4
-4
2.39

0.005 x 10
4.11 x 10-2
4.92 x 10
-4
6.10
2

0.34 x 10- 8.82

0.16 x 10-4
[
ZnCl
2
(TMGasme)] 9.48 x 10-3
1.09

0.1 x 10-4
90 min
52
37 400
35 000
1.4
[
a] Conditions: 150 °C, solvent free, non-purified technical grade rac-LA. [b] Determined by plotting kapp versus [init.].
k
5
p
[I] [M] = kapp [M]; k
p
= kapp/[I]. [c] Determined from the slope of the plots of ln([LA]
0
/[LA]
t
) versus time for a ratio of [M]/[I] =
1
00:1. [d] As determined by H NMR spectroscopy. [e] Calculated assuming that every complex propagates one chain at a ratio
-1
of [M]/[I] = 500:1. [f] Determined by GPC (in THF), Mn,theo: 72 000 g mol for 100% conversion at a ratio of [M]/[I] = 500:1.
4
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theoretical molecular weights assuming that every complex
propagates one chain. However, with molar masses more than
Conclusions
View Article Online
DOI: 10.1039/C8DT04938F
Four different guanidine ligands with a N,O donor system have
been prepared and used in the synthesis of zinc chloride
complexes. The guanidines bear different electron-donating or
electron-withdrawing groups in para- and meta-position to the
guanidine moiety. The complexes have been successfully tested
in the ring opening polymerisation of non-purified technical
grade rac-lactide in melt. In situ IR & Raman measurements
have been used to determine the rate constant kapp at several
-1
4
0 000 g mol , industrial applicability is given. For the
polymerisation with catalyst C4, molar masses are in this case
-1
7
1 000 g mol . To further investigate the polymerisation
behaviour of this ligand class, polymerisation experiments with
the fastest catalyst C4 were carried out. For this purpose, the
catalytic activity of the complex in the polymerisation of
recrystallised and sublimed rac-LA was investigated. For the
polymerisation using recrystallised rac-LA at
a
ratio
[
M]/[I] ratios. While the meta-position has no influence on the
-4 -1
[
M]/[I] = 500:1, a kapp = 7.92 x 10 s was observed and with
reactivity in the ROP of rac-LA, a substitution in the para-
position by a chloro, a methyl or a dimethylamine group
increases the polymerisation rate. The dimethylamine group
has the strongest influence on the reaction rate with
-4 -1
sublimed monomer a kapp = 7.93 x 10 s was determined.
Thus, the two reaction rates are identical to the polymerisation
with non-purified technical grade lactide. It is noticeable,
however, that with increasing quality of the lactide higher molar
masses are obtained, as expected with removal of impurities
capable of initiating the polymerisation. Impurities like residual
water or free lactic acid hydrolyse or protonate the guanidine
-2
-1 -1
k
p
= 6.10 x 10 L mol s
unsubstituted complex [ZnCl
commonly used Sn(Oct) the tuned guanidine zinc complex C4 is
six times higher than the
2
(TMGasme)]. Compared to the
2
just three times slower. In addition, the robust catalyst
produces atactic polymers with high molar masses of more than
and lead to deactivation of the catalyst. Molar masses of
M
n
= 98 000 g mol- with recrystallised lactide and molar
1
-1
7
1 000 g mol , making it a viable alternative in industrial
masses of M
obtained, compared to M
lactide. In contrast, polymerisation experiments with low
M]/[I]-ratios (10:1 and 30:1; ESI) also achieved high molar
n
= 101 000 g mol-1 with sublimed lactide can be
= 71 000 g mol-1 with non-purified
applications. Polymerisation studies with different lactide
qualities and using different [M]/[I] ratios show, that the
catalyst uses impurities in the monomer to open the lactide. The
addition of a co-initiator leads to a control of the molar masses.
The results bear high potential to substitute toxic tin catalysts
in industrial production of PLA by guanidine zinc complexes with
N,O donor units.
n
[
masses and were therefore not applicable for MALDI-ToF
measurements. These results suggest that monomer impurities
and coordinated ligand are able to initiate polymerisation in the
presence of the zinc catalyst. We have observed similar
behaviour for the parent TMGasme system.53 By adding a co-
initiator (3,5-bis(trifluoromethyl)benzyl alcohol) at a ratio of
Experimental Section
General
1
M
00:1:1 ([M]/[I]/[alcohol]) predictable molar masses of
= 17 000 g mol-1 are achieved (ESI). This is close to the
n
-1
All steps were performed under nitrogen (99.996%) dried with
P O10 granulate using Schlenk techniques. Solvents were
4
theoretical value of M
ability of this complex to control the M
n
= 14 000 g mol and demonstrates the
with exogenous alcohol.
n
1
19
purified according to literature procedures and also kept under
nitrogen. All chemicals were purchased from Sigma‒Aldrich
GmbH, TCI GmbH, ABCR GmbH and Acros Organics and were
used as received without further purification. rac-LA (Total
Corbion) was not purified but stored in a nitrogen filled
MALDI and NMR experiments ( H and F NMR) show evidence
of the polymer chain ends being either complex, alcohol and, to
a lesser extent, the ligand (ESI). This complex is a highly active
robust catalyst which polymerises rac-lactide with high molar
masses without any addition of co-initiator. The tacticity
analysis revealed that all catalysts produce atactic polymer
glovebox. N,N,N′,N′-tetramethylchloroformamidinium chloride
TMG-VS) was synthesised as described in the literature.5
4, 55
(
(
ESI). To confirm the stability of the complex at high
temperature, TGA measurement was performed (ESI). At
50 °C, there is no mass loss over the entire measurement
period, which proves the thermal stability. To clarify that the Mass spectra were obtained with a ThermoFisher Scientific
complex is the active species and not the guanidine acts as Finnigan MAT 95 mass spectrometer for HR-EI (L1 L4) and a
organocatalyst, two polymerisation experiments with and ThermoFisher Scientific LTQ-Orbitrap XLSpectrometer for HR-
without a co-initiator and the guanidine TMG5NMe
asme were ESI (C1 C4). The source voltage was 4.49 kV, and the capillary
Physical Methods
1
‒
‒
2
carried out (ESI). The results show that for both conditions a temperature was 299.54 °C. The tube lens voltage was between
conversion of 9% PLA can be achieved after 90 min. However, 100 and 130 V. Acetonitrile or tetrahydrofuran were used as
no polymer was precipitated. During the reaction, the solvent.
formation of meso-lactide was observed. Therefore, the
guanidine is able to polymerise lactide, but does not show the Elemental analysis was conducted with an elementar varioEL
high activity as the corresponding zinc chlorido complex.
and an elementar varioEL cube. FTIR spectra were measured
with a Thermo Scientific Nicolet Avatar 380 spectrometer with
-1
a resolution of 2 cm or on a Shimadzu IRTracer 100 using a CsI
beam in combination with an ATR unit (Quest model from
Specac utilising a robust monolithic crystalline diamond) in a
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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Pleas De ad l too nn oT tr aa nd sj au cs t ti omn sa rgins
Page 6 of 13
ARTICLE
Journal Name
-
1
resolution of 2 cm . The samples were prepared as KBr pellets using a GPC from Agilent. The system was referenced against 11
View Article Online
or as a film between NaCl plates. NMR spectra were recorded narrow molecular weight standards polysDtyOrIe: 1n0e.10st3a9n/Cd8aDrTd0s4w93i8thF
at room temperature on a Bruker Avance II (400 MHz) or a detection via refractive index response. A correction factor of
Bruker Avance III (400 MHz). The NMR signals were calibrated 0.58 was applied to measured values.
to the residual signals of the deuterated solvent [

H
(CDCl
) = 77.16 ppm,
-DMSO) = 39.52 ppm] Data for H NMR are reported as
ppm) (multiplicity, coupling constants
Hz), integration). Couplings are expressed by: s = singlet, Raman spectra were obtained under process conditions using a
d = doublet, m = multiplet or combinations thereof. RXN1 spectrometer from Kaiser Optical Systems. Ten
3
) =
7
.26 ppm,
(d
H 6 C 3
 (d -DMSO) = 2.50 ppm,  (CDCl
1
Reaction monitoring

C
6
follows: chemical shift (

(
1
3
1
C{ H} NMR spectra are also expressed in parts per million accumulated measurements with 0.5 seconds measuring time
ppm) and reported as aforementioned. Various 2D NMR were subsumed to one spectrum. The laser was used at a
experiments (COSY, HSQC, HMBC, DEPT135) were used to wavelength 785 nm and 459 mW through an immersion probe
(
1
13
1
assign the H and C{ H} NMR spectra.
with a short-focus sapphire lens (d = 0.1 mm). The resulting
time-resolved data was processed with the PEAXACT 4.0
Software. The boundaries for the lactide integration were
X-Ray diffraction analysis
-1
6
27 – 713 cm .
The single crystal diffraction data for C1 to C4 are presented in IR kinetic measurements were recorded using a Bruker Matrix-
Table 3. The data for C1‒C4 were collected on a Bruker D8 MF FTIR spectrometer equipped with a diamond ATR probe
goniometer with an APEX CCD detector. An Incoatec (IN350 T) suitable for Mid-IR in situ reaction monitoring was
microsource with MoK
temperature control was achieved with an Oxford Cryostream
00. Crystals were mounted with grease on glass fibres and data
were collected at 100 K in
-scan mode. Data were integrated Polymerisation
with SAINT and corrected for absorption by multiscan

radiation ( = 0.71073 Å) was used and used.
7

5
9
5
9
methods with SADABS.
The polymerisations with complex C2 ([M]/[I] = 500:1) and the
The structures were solved by direct and conventional Fourier fastest complex C4 ([M]/[I] = 500:1 and 2000:1) have been
methods and all non-hydrogen atoms were refined investigated twice.
2
anisotropically with full-matrix least-squares based on F
(
6
0
61
62
XPREP, SHELXS, and ShelXle ). Hydrogen atoms were Technical grade rac-lactide: rac-LA from Corbion was used for
derived from difference Fourier maps and placed at idealised the polymerisations. Therefore, ᴅ- and ʟ-lactide were mixed in
positions, riding on their parent C atoms, with isotropic a ratio of 1:1. Both ᴅ- and ʟ-lactide consisted of maximum free
displacement parameters Uiso(H) = 1.2Ueq(C) and 1.5Ueq(C acids of 3 meq kg-1 and maximum water residues of 0.01%.
methyl). All methyl groups were allowed to rotate but not to tip.
Full crystallographic data (excluding structure factors) have Polymerisation in Schlenk tubes: In a nitrogen filled glovebox
been deposited with the Cambridge Crystallographic Data the catalyst (0.059 mmol) and rac-LA (3,6-dimethyl-1,4-
Centre as supplementary no. CCDC – 1880806 for C1, CCDC – dioxane-2,5-dione, 4.25 g, 29.5 mmol) were weighed
1
880807 for C2, CCDC – 1880808 for C3 and CCDC – 1880809 separately. The catalyst and the lactide were homogenised
for C4. Copies of the data can be obtained free of charge on completely in a agate mortar and portioned into eight Schlenk
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK flasks, each containing approximately 500 mg. The tubes,
(
fax: (+44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
containing a stirring bar (15 x 4.5 mm, stirring speed: 260 rpm),
were heated up in an oil bath at 150 °C. The polymerisation
started when the stirred mixture was melted entirely. Cooling
down the flask under running water stopped the reaction. For
Gel permeation chromatography
The average molecular masses and the mass distributions of the determination of the conversion, the sample was dissolved in
1
obtained polylactide samples were determined by GPC in THF 2 mL of DCM and a H NMR spectrum was measured.
-1
as the mobile phase at a flow rate of 1 mL min . The utilised Afterwards, the solved polymer was precipitated in ethanol (RT)
GPCmax VE-2001 from Viscotek was a combination of an HPLC and the collected polymer dried under high vacuum. All
pump, two Malvern Viscotek T columns (porous styrene polymers catalysed with C1
divinylbenzene copolymer) with a maximum pore size of 500 polymers with C4 were yellow coloured.
and 5000 , a refractive index detector (VE-3580), and a
viscometer (Viscotek 270 Dual Detector). Universal calibration Polymerisation followed by Raman spectroscopy: In a nitrogen
–C3 were colourless. Synthesised
Å
was applied to evaluate the chromatographic results.
filled glovebox, the catalyst and rac-LA (3,6-dimethyl-1,4-
dioxane-2,5-dione, 8.0 g, 55.5 mmol) were weighed separately.
°C with The catalyst and the lactide were homogenised completely in
-1
Some GPC samples were carried out at 1 ml min at 35
a THF eluent using a PLgel 5 μm MIXED-D 300 × 7.5 mm column an agate mortar and the mixture filled in a glass vial. The steel
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 13
Pleas De ad l too nn oT tr aa nd sj au cs t ti omn sa rgins
Journal Name
ARTICLE
+
+
reactor was heated at 150 °C under vacuum and flashed three m/z (%): 215.2 (23) [C
8
H
6
ClNO
4
] , 184.2 (100) [C
7
H
3
ClNO
3
] ,
View Article Online
+
+
DOI: 10.1039/C8DT04938F
times with argon. For polymerisation, the reaction mixture was 169.2 (3) [C
8
H ClO
6
2
+
] , 155.2 (3), 138.2 (5) [C
H Cl] , 98.2 (2), 75.3 (14) [C H ] .
6 3 6 3
7 3
H
ClO] , 126.2 (11),
+
filled in a steel reactor under argon conditions (99.998% purity). 110.2 (13) [C
The reactor was closed with a shaft drive stirrer with agitator
speed control (“minisprint”, premex reactor AG, Switzerland) Methyl 4-(dimethylamino)-2-nitrobenzoate (1b).
and the sample collection started after the reaction mixture (M = 224.22 g mol ). A round-bottom pressure flask with a PTFE
insertion as soon as the reactor was closed. The Raman probe front-seal plug was charged with 1a (1.79 g, 8.3 mmol, 1 equiv.)
10 12 2 4
C H N O
-1
was installed close to the stirrer. The shaft drive stirrer with and
agitator speed control was used to stir the reaction at 260 rpm. Tris(dibenzylideneacetone)palladium [Pd
Cs
2
CO
3
.
(8.14 g,
25.0 mmol, 3.0 equiv.)
3
(dba) ] (381.9 mg,
2
The reaction mixture was removed from the reactor and a 0.415 mmol, 0.05 equiv.), 2-dicyclohexylphosphino-2′-(N,N-
1
H NMR was collected to determine the conversion. The dimethylamino)biphenyl (DavePhos) (489.9 mg, 1.245 mmol,
reaction mixture was dissolved in an appropriate amount of 0.15 equiv.) and dimethylamine hydrochloride (830.0 mg,
DCM, the polymer was precipitated in ethanol (r.t.), dried in 10.2 mmol, 1.2 equiv.) were added. The solids were suspended
vacuo and characterised via GPC.
under stirring in dry dimethoxyethane (DME) (16.6 mL) and
heated up to 100 °C for 20 h. After cooling down to r.t., the
blood-red solution was suspended with diethyl ether (60 mL)
Polymerisation with co-initiator
For polymerisations with a co-initiator, we used the same and washed with water (80 mL). The aqueous phase was
method as mentioned above, but solid co-initiator (3,5- extracted with diethyl ether (3 x 20 mL) and dried over MgSO
bis(trifluoromethyl)benzyl alcohol) was weighed and also added The organic solution was purified by adding charcoal, filtered
4
.
to the mixture.
over celite and concentrated in vacuo. After purification by
column chromatography (n-hexane/ethyl acetate 7:1) the title
compound yielded in 41% as a yellow solid (0.77 g, 3.43 mmol,
Ligand synthesis
lit.: 68%). R
The following syntheses towards the primary amines have been ṽ = 3449 (w), 2956 [w,
conducted as reported in the literature. The syntheses of 1c 3b 1616 [vs, (C=Carom.)], 1538 [vs,
and 4c have been performed in an alternative way, but 1433 (m), 1420 (w), 1385 [m,
compared with the analytics from literature. The following O)], 1277 [vs, (C‒O)], 1236 (w), 1193 (m), 1134 (m), 1069 (w),
resynthesised compunds agree with the analytics from 973 (w), 965 (w), 881 (w), 848 [w, (C‒Harom.)], 820 [m, (C‒
f
= 0.16 (n-hexane/ethyl acetate 3:1); IR (KBr):
(CHaliph.)], 2918 (w), 1710 [s, (C=O)],
(C=Carom.)], 1485 (w), 1458 (w),
(CH )], 1335 (w), 1294 [vs, (C‒


,



3




6
3-65
-1
1
literature.
H
arom.)], 780 (w), 769 (m), 697 (w), 593 (w) cm ; H NMR
3
(
400 MHz, CDCl
J
3
):

= 7.77 (d, JH,H = 8.8 Hz, 1H; CHarom.), 6.77 (d,
H,H = 2.6 Hz, 1H; CHarom.), 6.79 (dd, 3JH,H = 8.9 Hz, 4JH,H = 2.6 Hz,
), 3.07 (s, 6H; CH ) ppm;
4
Methyl
(
4
4-chloro-2-nitrobenzoate
(1a).
8
C H
6
ClNO
4
-1
M = 215.59 g mol ). 4-Chloro-2-nitrobenzoic acid (8.06 g, 1H; CHarom.), 3.83 (s, 3H; CH
0.0 mmol, 1 equiv.) was suspended in dry methanol (200 mL).
3
3
13
1
3
C{ H} NMR (101 MHz, CDCl ):  = 165.0 (Ccarbonyl), 152.8
The solution was cooled down to 0 °C and thionyl chloride (Carom.), 152.4 (Carom.), 132.5 (CHarom.), 112.8 (CHarom.), 110.4
(
14.6 mL, 200.0 mmol, 5 equiv.) was added dropwise. The (Carom.), 105.6 (CHarom.), 52.5 (CH
3
), 40.3 (CH
3
) ppm; HRMS (EI):
+
solution was allowed to warm up to r.t., heated up to 50 °C and m/z (%): calcd.: 224.0797, found: 224.0795 [C10
stirred for 24 h. The solvent was removed under vacuo and the (EI): m/z (%): 224.1 (71) [C10
H
12
N
2
O
4
] ; MS
+
H
12
N
4
2
O
4
] , 205.2 (37), 193.1 (15)
+
+
+
concentrated solution was dissolved in aqueous saturated [C
NaHCO
ethyl acetate (3 x 60 mL) and the combined organic layers dried [C
over MgSO . After reducing the solvent under reduced
pressure, the compound yielded in colourless crystals to 67% Methyl 2-amino-4-(dimethylamino)benzoate (1c).
9
H
9
N
2
O
3
] , 180.1 (46) [C
8
H
6
NO
] , 178.1 (16) [C10
H
12NO
2
] ,
+
+
3
solution (100 mL). The solution was extracted with 150.1 (100) [C
7
H
N
6 2
O
2
] , 148.1 (27) [C
N] , 77.1 (28) [C
9
H10NO] , 119.1 (21)
+
+
+
H
8 9
N] , 105.1 (11) [C
H
7 7
6
H
6
] .
4
10 14 2 2
C H N O
-1
(5.75 g, 26.7 mmol, lit.: 93%). IR (KBr): ṽ = 3752 (vw), 3435 (w), (M = 194.23 g mol ). To a solution of 1b (0.77 g, 3.43 mmol,
3
2
091 (m), 3075 (m), 3054 [w,
963 (w) 2893 (w), 1727 [vs,
(C=Carom.)], 1536 [vs,
s), 1367 [s, (CH )], 1301 [s,

(CHaliph.)], 3039 [w,
(C=Carom.)], 1569 1.7 mmol, 5 mol%) was added. The hydrogenation was
)], 1483 (m), 1452 (m), 1431 performed at r.t. under atmospheric pressure and stirring
(C‒O)], 1281 [vs, (C‒O)], 1259 overnight. The reaction mixture was filtered over celite and the
 (CHaliph.)], 1 equiv.) in dry methanol (40 mL) palladium on carbon (0.183 g,


(C=O)], 1602 [s,
(NO


[
(
(
m,

2

3

s), 1191 (m), 1151 (m), 1130 (s), 1108 (s), 1066 (m), 974 (w), solvent removed under reduced pressure. The resulting
1
9
52 (m), 902 (m), 892 (m), 849 (m), 830 [m,

(C‒Harom.)], 777 brownish solid yielded in 99% (0.659 g, 3.40 mmol). H NMR
3
(m), 767 (m), 738 (m), 689 (w), 661 (vw), 621 (w), 534 (w), 508 (400 MHz, CDCl
3
):

= 7.71 (d, JH,H = 9.1 Hz, 1H; CHarom.), 6.08
-1
1
3
4
(
w), 449 (vw) cm ; H NMR (400 MHz, CDCl
J
3
):

= 7.86 (d, (dd,
J
H,H = 9.1 Hz,
J
H,H = 2.5 Hz, 1H; CHarom.), 5.82 (d,
3
), 2.98 (s, 6H; CH )
4
3
4
H,H = 2.0 Hz, 1H; CHarom.), 7.74 (d, JH,H = 8.3 Hz, 1H; CHarom.),
J
H,H = 2.2 Hz, 1H; CHarom.), 3.81 (s, 3H; CH
3
.64 (dd, 3JH,H = 8.3 Hz, JH,H = 2.0 Hz, 1H; CHarom.), 3.92 (s, 3H; ppm; C{ H} NMR (101 MHz, CDCl
4
13
1

= 168.7 (Ccarbonyl), 154.4
7
CH
3
):
), ppm; 13C{ H} NMR (101 MHz, CDCl
1

= 164.9 (Ccarbonyl), (Carom.), 152.1 (Carom.), 132.7 (CHarom.), 102.6 (CHarom.), 100.7
3
3
):
1
1
3 3
49.2 (Carom.), 138.3 (Carom.), 133.0 (CHarom.), 131.4 (CHarom.), (Carom.), 97.0 (CHarom.), 51.1 (CH ), 40.1 (CH ) ppm.
25.5 (Carom.), 124.3 (CHarom.), 53.6 (CH
3
) ppm; HRMS (EI): m/z
+
(%): calcd.: 214.9985, found: 214.9979 [C
8
H
6
ClNO
4
] ; MS (EI):
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
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Pleas De ad l too nn oT tr aa nd sj au cs t ti omn sa rgins
Page 8 of 13
ARTICLE
Methyl
Journal Name
-
1
5-chloro-2-nitrobenzoate
(2a).
8
C H
6
ClNO
4
9 9 4
View Article Online
5-Methyl-2-nitrobenzoate (3a). C H NO (M = 195.17 g mol ).
-1
DOI: 10.1039/C8DT04938F
3a (6.82 g, 35.0 mmol) was
(M = 215.59 g mol ). 5-chloro-2-nitrobenzoic acid (6.07 g, Using the same procedure as 2a
,
3
0.1 mmol, 1 equiv.) was suspended in methanol (25 mL). obtained from 5-methyl-2-nitrobenzoic acid (7.25 g, 40.0 mmol)
Concentrated sulphuric acid (8.8 mL) was added dropwise to as a colourless solid with a yield of 87%. IR (ATR, neat): ṽ = 1723
the ice cooled stirred suspension. Afterwards, the reaction [vs, (C=O)], 1540 [m, (N=O)], 1442 (m), 1380 [m, (CH )],
mixture was stirred under reflux for 20 h. The solution was 1293 (vs), 1209 (s), 1138 (m), 1069 (s), 973 (m), 904 (w), 785 [s,
cooled down to r.t. and toluene (95 mL) was added. Further, an (C‒Harom.)], 743 (m), 707 (m), 671 (w), 619 (m), 582 (m), 407



3

-
1
1
aqueous solution of sodium hydroxide was added thereto. The (m) cm ; H NMR (400 MHz,
d
6
-DMSO):
 = 7.99 (d,
3
H,H = 8.3 Hz, 1H; CHarom.), 7.65 (d, 4JH,H = 1.9 Hz, 1H; CHarom.),
aqueous solution was extracted with toluene (3 x 45 mL), the
J
3
combined organic phases dried over MgSO
4
and the solvent 7.60 (dd, JH,H = 8.3 Hz, 4JH,H = 1.9 Hz, 1H; CHarom.), 3.84 (s, 3H;
) ppm; 13C{ H} NMR (101 MHz, d
1
evaporated in vacuo. To the resulting colourless crystals hexane CH
70 mL) was added and the solution was stored in a fridge
3
), 2.45 (s, 3H; CH
= 165.5 (Ccarbonyl), 145.2 (Carom.), 145.0 (Carom.), 132.6 (CHarom.),
3
6
-DMSO):
(

overnight. Filtration of the yellow crystals with hexane (35 mL) 129.9 (CHarom.), 126.8 (Carom.), 124.2 (CHarom.), 53.1 (CH
3
), 20.7
+
yields the title compound to 89% (6.24 g, 28.9 mmol). IR (KBr): (CH
3
) ppm; MS (EI): m/z (%): 195.0 (100) [C
9
H
9
NO
4
] , 166.0 (4)
+
+
+
ṽ = 2959 [m,

(CHaliph.)], 1740 [s,

(C=O)], 1613 (m), 1570 [m,
(C‒Harom.)], 1347 [s,


[C
(10) [C
7
H
4
NO
4
] , 164.0 (54) [C
8
H
6
NO
3
+
] , 149.0 (11) [C
9
H
9
O
2
] , 134.0
+
+
(
(
(
N=O)], 1537 [m,
CH )], 1284 [vs,
s), 834 (s), 758 [m,

(C=Carom.)], 1431 [m,

8
+
H
6
O
2
] , 118.0 (6) [C
8
H
6
O] , 106.0 (20) [C
H
7 6
O] , 91.1 (46)
+
3

(C‒Harom.)], 1258 (s), 1131 (s), 1104 (vs), 1071 [C
7
H
7
] , 78.1 (18) [C
6
6
H ] .
-

(C‒Harom.)], 740 (m), 687 (w), 529 (m) cm
1
1
3
;
H NMR (400 MHz, CDCl
3
):

= 7.91 (d,
J
H,H = 8.7 Hz, 1H; Methyl
2-amino-5-methylbenzoate
(3b)
.
C
9
H
11NO
2
4
-1
CHarom.), 7.69 (d,
J
H,H = 2.3 Hz, 1H; CHarom.), 7.59 (dd, (M = 165.19 g mol ). Using the same procedure as 1c
,
3b
3
H,H = 8.7 Hz, 4JH,H = 2.3 Hz, 1H; CHarom.), 3.94 (s, 3H; CH
C{ H} NMR (101 MHz, CDCl
J
3
) ppm; (5.48 g, 33.0 mmol) was obtained from 3a (6.82 g, 35.0 mmol)
= 164.9 (Ccarbonyl), 146.3 as a beige solid with a yield of 95%. IR (ATR, neat): ṽ = 3474 (m),
(C=O)], 1627 (m), 1577 [m, (N=O)], 1560
(N=O)], 1503 (m), 1440 (s), 1350 [w, (CH )], 1295 (s), 1237
13
1
3
):

(
(
(
[
[
C
arom.), 139.9 (Carom.), 131.7 (CHarom.), 130.0 (CHarom.), 129.6 3367 (m), 1683 [vs,


Carom.), 125.6 (CHarom.), 53.7 (CH
3
) ppm; MS (EI): m/z (%): 215.1 [s,


3
+
+
31) [C
C
C
8
H
6
+
ClNO
4
] , 184.1 (100) [C
7
H
3
ClNO
3
] , 169.1 (2) (vs), 1203 (vs), 1187 (s), 1164 (s), 1092 (s), 1006 (m), 969 (w),
+
8
H
H
6
ClO
2
] , 154.1 (5) [C
7
H
3
ClO
2
] , 126.1 (13) [C
7
H
7
Cl], 110.1 (17) 898 (w), 827 (vs), 793 [vs,

(C‒Harom.)], 768 (m), 705 (m), 680
-
1
1
6
3
Cl], 75.2 (25) [C
6
3
H ].
(m), 533 (s), 517 (m), 472 (m) cm ; H NMR (400 MHz, d
6
-
4
DMSO):

= 7.50 (d,
JH,H = 2.0 Hz, 1H; CHarom.), 7.09 (dd,
3
H,H = 8.6 Hz, JH,H = 2.0 Hz, 1H; CHarom.), 6.69 (d, 3JH,H = 8.4 Hz,
4
Methyl
(
2-amino-5-chlorobenzoate
(2b).
C
8
H ClNO
8
2
J
-1
M = 185.61 g mol ). To an ice-cooled solution of 2a (3.22 g, 1H; CHarom.), 6.44 (bs, 2H, NH
2
), 3.78 (s, 3H; CH
3
), 2.15 (s, 3H;
= 167.8
13
1
1
4.94 mmol, 1 equiv.) and conc. HCl (14 mL) in ethanol (7 mL), CH
3
) ppm;
C{ H} NMR (101 MHz, d -DMSO): 
6
a solution of tin(II) chloride (8.494 g, 44.8 mmol, 3 equiv.) in (Ccarbonyl), 149.2 (Carom.), 135.1 (CHarom.), 130.0 (CHarom.), 123.1
ethanol (14 mL) was added dropwise over 35 minutes. After (Carom.), 116.7 (CHarom.), 108.5 (Carom.), 51.2 (CH ), 19.8 (CH
3
+
3
)
completing of the addition, the mixture was stirred over 95 h ppm; MS (EI): m/z (%): 165.0 (61) [C
9
H
11NO
2
] , 134.0 (25)
+
+
+
and turned from yellow to red. The solution was poured into [C
ice-water and changed from red to a murky brown-yellow [C
8
H
H
8
NO] , 133 (100) [C
8
H
5
2
O ] , 106.1 (27) [C
7
H
8
N] , 91.1 (2)
+
+
7
7 6 6
] , 78.1 (15) [C H ] .
solution. By the addition of 1
ᴍ NaOH the pH value was adjusted
to 8‒9 the solution and turned to a flaky milky-white solution. 5-(Dimethylamino)-2-nitrobenzoic acid (4a)
.
9 10 2 4
C H N O
-1
The solution was extracted with dichloromethane (3 x 150 mL) (M = 210.19 g mol ). 5-Chloro-2-nitrobenzoic acid (9.07 g,
and the combined organic layers dried over MgSO . The solvent 45.0 mmol, 1 equiv.) was added to a solution of 40 wt% aqueous
was removed in vacuo and a brown solid with a yield of 83% dimethylamine (28.5 mL, 225.0 mmol, 5 equiv.) in an autoclave.
4
(
[
(
1
(
1
2.674 g, 12.4 mmol, lit.: 89%) was obtained. IR (KBr): ṽ = 3458 After 25 h and a temperature of 70 °C the autoclave was
s, (NH )], 3362 [s, (NH )], 2950 [m, allowed to cool down to r.t. The reaction mixture was diluted in
C=O)], 1631 (m), 1587 (m), 1484 (m), 1430 [m, (C‒Harom.)], water (10 mL) and neutralised by adding conc. HCl (15.1 mL).
303 [vs, (N‒H)], 1239 [vs, (C‒O)], 1189 (m), 1152 (m), 1129 During the neutralisation a yellow solid precipitated from the
m), 1088 (m), 970 (m), 827 (m), 787 (m), 715 (w), 654 (w) cm ; red solution. The crystallisation was completed after adding

2

2
 (CHaliph.)], 1690 [s, 



-
1
4
H NMR (400 MHz, CDCl
3
):

4
= 7.82 (d,
J
H,H = 2.6 Hz, 1H; additional water (40 mL) and storage at 8 °C overnight. The
3
CHarom.), 7.21 (dd, JH,H = 8.7 Hz, JH,H = 2.5 Hz, 1H; CHarom.), 6.61 crystalline solution was filtered and the yellow crystalline solid
(
1
d, 3JH,H = 8.8 Hz, 1H; CHarom.), 3.87 (s, 3H; CH
3
) ppm; dried under vacuum yielding in 99% (9.35 g, 44.5 mmol, lit.:
= 167.7 (Ccarbonyl), 149.1 99%). IR (KBr): ṽ = 3434 [m, (O‒H)], 2924 [m,
(C=O)], 1604 [s, (C=Carom.)], 1578 [m,
(N=O)], 1522 (w), 1471 (m), 1437 (w), 1420 (w), 1384 [m,
)], 1318 (vs), 1274 (m), 1232 w, 1194 (w), 1175 (w), 1146
ClN] , (w), 1063 (m), 909 (w), 871 (w), 849 (w), 833 [w,
818 [m, (C‒Harom.)], 756 (w), 734 (vw), 658 (vw), 602 (vw), 565
w), 469 (vw) cm ; H NMR (400 MHz, d
3
1
C{ H} NMR (101 MHz, CDCl
3
):


 (CHaliph.)], 2661
(
(
(
[
C
arom.), 134.2 (CHarom.), 130.6 (CHarom.), 120.9 (Carom.), 118.2 (w), 2560 (w), 1710 [s,


CHarom.), 111.7 (Carom.), 51.9 (CH
80) [C
3
) ppm; MS (EI): m/z (%): 185.2


]+, 155.1 (34) [C
H
6
ClNO] , 154.1 (27) (CH
+
8
H
8
+
ClNO
2
7
+
3
+
C
7
H
5
ClNO] , 153.1 (100) [C
7
H
4
ClNO] , 126.1 (26) [C
6
H
5
 (C‒Harom.)],
9
9.2 (11), 90.2 (12), 73.2 (3).

-1 1
(
3
6
-DMSO):

= 7.98 (d,
3
4
J
H,H = 9.4 Hz, 1H; CHarom.), 6.79 (dd, JH,H = 9.4 Hz, JH,H = 2.9 Hz,
8
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 9 of 13
Pleas De ad l too nn oT tr aa nd sj au cs t ti omn sa rgins
Journal Name
ARTICLE
H; CHarom.), 6.71 (d, 4JH,H = 2.9 Hz, 1H; CHarom.), 3.09 (s, 6H; CH
(M = 292.38 g mol ). To an ice-cooled solution of 1c (668 mg,
-1
1
3
)
View Article Online
DOI: 10.1039/C8DT04938F
13
1
ppm; C{ H} NMR (101 MHz, d
6
-DMSO):  = 168.2 (Ccarbonyl), 3.43 mmol, 1.0 equiv.), triethylamine (0.48 ml, 3.43 mmol,
1
53.5 (Carom.), 133.6 (Carom.), 132.5 (Carom.), 126.6 (CHarom.), 111.1 1.0 equiv.), and dry CH
3
CN (10 mL) a solution of TMG-VS
CN (10 mL) was
(CHarom.), 109.4 (CHarom.), 39.9 (CH
3
) ppm; MS (EI): m/z (%): 210.0 (648 mg, 3.77 mmol, 1.1 equiv.) in dry CH
3
+
+
]+, added dropwise under stirring. The mixture was heated at reflux
for 3.5 h and cooled down to room temperature. An aqueous
(100) [C
H N
9 10 2
O
4
] , 180.0 (8) [C
7
H
4
N
2
O
4
] , 166.0 (3) [C
7
H
4
NO
4
+
+
+
1
36.1 (34) [C
6
H
4
N
2
O
2
] , 119.1 (11) [C
8
9
H N] , 77.1 (5) [C
6
6
H ] .
solution of NaOH (140 mg, 3.43 mmol, 1 equiv. in 3 mL H
added and the solvent and the triethylamine were evaporated
4b under reduced pressure. The guanidine hydrochloride was
7.36 g, 32.8 mmol) was obtained from 4a (9.35 g, 44.5 mmol) deprotonated by the addition of KOH (4.5 mL, 50 wt%). The free
CN (3 x 10 mL) and dried over
. After removing the solvent under reduced pressure, the
(C=Carom.)], guanidine was dried under high vacuum and yielded in a brown
(N=O)], 1478 (m), 1443 (m), oil with 75% (750 mg, 2.55 mmol). IR (NaCl): ṽ = 3460 (w), 3359
)], 1310 (vs), 1284 [vs, (C‒O)], 1266 (w), 3087 (w), 2943 [m,
(C‒O)], 1229 (s), 1192 (m), 1173 (m), 1134 (m), 1063 (s), [m,
76 (m), 950 (w), 863 (m), 839 [m, (C‒Harom.)], 810 [m, (C‒ (C=Ngua)], 1537 [vs,
arom.)], 780 (m), 755 (m), 699 (w), 665 (w), 640 (w), 602 (w), 562 (s), 1433 (s), 1379 [s,
2
O) was
12 2 4
Methyl 5-(dimethylamino)-2-nitrobenzoate (4b). C10H N O
-1
(M = 224.22 g mol ). Using the same procedure as 2a,
(
as yellow crystals with a yield of 82%. IR (KBr): ṽ = 3449 (w), guanidine was extracted with CH
3
3
2
1
1
080 (w), 3011 (w), 2958 [w,
573 (vw), 2341 (vw), 1742 [s,


(CHaliph.)], 2818 (w), 2689 (w), Na
(C=O)], 1603 [vs,

2 4
SO

577 [s,

(C=Carom.)], 1524 [m,
(CH
421 (m), 1384 [m,

3



(CHaliph.)], 2919 [m,
(CHaliph.)], 1704 [s,
(C=Carom.)], 1506 [s,
(CH
(C‒Harom.)], 809 [w,
 (CHaliph.)], 2889
(C=O)], 1578 [vs,
 (C=Carom.)], 1476
)], 1144 (s), 1085 (s), 1024 (m), 978
(C‒Harom.)], 772 (m),
[
vs,


(CHaliph.)], 2807 [m,

9





H
3
-1 1
(
w), 463 (vw) cm ; H NMR (400 MHz, d
6
-DMSO):

= 8.03 (d, (m), 895 (w), 844 [m,


3
3
4
-1
1
J
H,H = 9.4 Hz, 1H; CHarom.), 6.85 (dd, JH,H = 9.5 Hz, JH,H = 2.8 Hz, 714 (w), 699 (w), 659 (vw) cm ; H NMR (400 MHz, CDCl
3
):
3
1
3

1
H; CHarom.), 6.79 (d, 4JH,H = 2.9 Hz, 1H; CHarom.), 3.83 (s, 3H; CH
3
),

= 7.70 (d, JH,H = 9.4 Hz, 1H; CHarom.), 6.24‒6.22 (m, 2H; H-1,
.10 (s, 6H; CH
= 167.8 (Ccarbonyl), 154.1 (Carom.), 132.9 (Carom.), 132.5 (Carom.),
27.4 (CHarom.), 112.0 (CHarom.), 110.2 (CHarom.), 53.3 (CH
3
) ppm; 13C{ H} NMR (101 MHz, d
1
6
-DMSO): CHarom.), 3.72 (s, 3H; CH
3
), 2.97 (s, 6H; CH
C{ H} NMR (101 MHz, CDCl ):
), 40.7 156.4 (Carom.), 154.0 (Carom.), 133.0 (CHarom.), 109.6 (Carom.), 107.6
) ppm; HRMS (EI): m/z (%): calcd.: 224.0797, found: (CHarom.), 104.6 (Carom.), 50.8 (CH ), 40.2 (CH ), 39.3 (CH ) ppm;
3 3
), 2.69 (s, 12H; CH );
3
 = 168.1 (Ccarbonyl), 160.3 (Cgua.),
13
1
3
(CH
3
3
3
3
+
2
[
1
[
24.0792 [C10
C
78.5 (2) [C10
H
12
N
2
O
4
] ; MS (EI): m/z (%): 224.5 (100) HRMS (EI): m/z (%): calcd.: 292.1899, found: 292.1892
+
+
+
+
+
10
H
12
N
2
O
4
] , 194.5 (23) [C
8
H
6
N
2
O
4
] , 193.5 (4) [C
9
H
N
9 2
O
3
] , [C15
H
24
N
4
O
2
] ; MS (EI): m/z (%): 292.2 (24) [C15
H
2
24
+
N
4
O
2
] , 277.2
+
+
+
H
12NO
2
] , 148.4 (3) [C
9
H
10NO] , 120.5 (21) (2) [C14
H
21
+
N
4
2
O ] , 248.2 (18) [C13
H
18
N
3
O
] , 233.2 (54)
+
+
+
+
+
8
C H10N] , 105.4 (6) [C
7
H
7
N] , 77.4 (5) [C
6
H
6
] .
[C13H
21
N
4
] , 194.2 (56) [C10
H
14
N
2
O
2
] , 189.1 (50) [C11
H
15
N
3
] ,
+
+
1
75.2 (12) [C10
H
13
N
3
] , 163.2 (32) [C
9
H
11
N
2
O] , 162.2 (34)
+
+
+
Methyl 2-amino-5-(dimethylamino)benzoate (4c). C10
H
14
N
2
O
2
[C
4c (33) [C
5.60 g, 28.8 mmol) was obtained from 4b (7.02 g, 31.3 mmol)
H N
9 10 2
O] , 135.2 (14) [C
8
H
11
N
2
] , 133.2 (14) [C
8
H
9
N
2
] , 116.2
-1
]+, 72.2 (100) [C
+
(
M = 194.23 g mol ). Using the same procedure as 1c
,
5
H
14
N
3
2
H
6 3
N
] .
(
as a green-brownish solid with a yield of 92%. IR (KBr): ṽ = 3436 Methyl
s), 3327 (m), 3082 (w), 3040 (w), 2951 [m, (CHaliph.)], 2882 (w), chlorobenzoate
(C=O)], 1619 [m, (C=Carom.)], (M = 283.76 g mol ). Using the same procedure as L1
(N‒H)], 1568 (m), 1503 (s), 1438 [m, (CH )], 1384 (1.60 g, 5.6 mmol) was obtained after 16 h reflux from 2b
)], 1355 [w, (CH )], 1317 (m), 1292 (s), 1244 (vs), (2.67 g, 12.4 mmol) as a yellow viscous oil with a yield of 46%.
221 (vs), 1168 (m), 1132 (m), 1102 (m), 1061 (m), 984 (w), 956 IR (NaCl): ṽ = 2927 [m,
2-((bis(dimethylamino)methylene)amino)-5-
(
2
1

(TMG5Clasme, L2)
.
13 3 2
C H18ClN O
-1
843 (w), 2791 (m), 1686 [vs,
583 [m,
(CH


, L2

3

3
[
m,


3
1

(CHaliph.)], 2890 [m,
(C=Ngua)], 1505 [s,
(CH
 (CHaliph.)], 1723 [s,
(w), 873 (w), 857 [vw,

(C‒Harom.)], 809 [m,

(C‒Harom.)], 783

H
(C=O)], 1570 [vs,


(C=C)], 1434 [s,

(C‒
-
1 1
(w), 742 (w), 673 (w), 558 (w), 450 (w) cm ; H NMR (400 MHz,
arom.)], 1384 [s,

3
)], 1295 (s), 1219 (s), 1140 (s), 1102 (m),
4
d
6
-DMSO):

= 7.05 (d,
J
H,H = 3.0 Hz, 1H; CHarom.), 7.00 (dd, 1076 (m), 1020 (s), 972 (m), 922 (w), 894 (w), 835 [m,

(C‒
3
H,H = 9.0 Hz, JH,H = 3.0 Hz, 1H; CHarom.), 6.72 (d, 3JH,H = 8.9 Hz,
4
-
J
H
1
arom.)], 790 (m), 757 (m), 737 (w), 714 (w), 685 (w), 648 (m) cm
; H NMR (400 MHz, CDCl
= 167.9 (Ccarbonyl), CHarom.), 7.26 (dd, JH,H = 8.7 Hz, JH,H = 2.6 Hz, 1H; CHarom.), 6.83
44.3 (Carom.), 141.4 (Carom.), 123.5 (CHarom.), 117.9 (CHarom.), (d, JH,H = 8.7 Hz, 1H; CHarom.), 3.77 (s, 3H; CH
1
4
1
H; CHarom.), 6.09 (s, 2H; NH
2
), 3.78 (s, 3H; CH
3
), 2.72 (s, 6H; CH
3
)
3
):

4
= 7.67 (d, JH,H = 2.6 Hz, 1H;
13
1
3
ppm; C{ H} NMR (101 MHz, d -DMSO):
1
1
6

3
3
), 2.66 (s, 12H; CH
3
)
13
1
13.5 (CHarom.), 108.8 (Carom.), 51.3 (CH
3
), 41.7 (CH
3
) ppm; HRMS ppm; C{ H} NMR (101 MHz, CDCl
] ; (Cgua.), 152.0 (Carom.), 132.6 (CHarom.), 130.6 (CHarom.), 126.7
] , 179.5 (8) (CHarom.), 124.0 (Carom.), 122.4 (Carom.), 51.5 (CH
3
):

= 167.3 (Ccarbonyl), 160.6
+
(EI): m/z (%): calcd.: 194.1055, found: 194.1049 [C10
H
12
N
2
O
4
+
MS (EI): m/z (%): 194.5 (100) [C10
H
14
N
2
O
2
3
), 39.3 (CH
3
)
+
+
+
[
(
C
H N
9 11 2
O
2
] , 135.5 (19) [C
N] , 71.5 (52).
8
H
N
11 2
] , 134.5 (60) [C
8
H
6
O
2
] ,119.4 ppm; HRMS (EI): m/z (%): calcd.: 283.1088, found: 283.1083
+
35
+
+
20) [C
8
H
9
[C13
H
18 ClN
68.2 (9) [C12
12ClN
3
O
2
] ; MS (EI): m/z (%): 283.3 (31) [C13
H
18ClN
3
O
2
] ,
+
2
H
15ClN
3
O
2
] , 252.2 (9) [C12
H15ClN
3
O], 239.2 (38)
[
C
11
H
2
O
2
], 224.2 (40) [C11
H15ClN
3
], 212.2 (21), 193.1 (15),
Synthesis of guanidine hybrid ligands
180.1 (36) [C H ClN ]
2
, 166.1 (10), 124.1 (14), 116.2 (15), 100.2
+
9
9
(15), 72.3 (100).
Methyl 2-((bis(dimethylamino)methylene)amino)-4-(dimethyl
amino)benzoate (TMG4NMe asme, L1)
2
.
15 24 4 2
C H N O
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
Please do not adjust margins

Pleas De ad l too nn oT tr aa nd sj au cs t ti omn sa rgins
Page 10 of 13
ARTICLE
Methyl 2-((bis(dimethylamino)methylene)amino)-5-methyl [ZnCl
Journal Name
2
(TMG4NMe
2
-1
asme)]
(
C1):
15 2 4 2
View Article Online
C H24Cl N O Zn
DOI: 10.1039/C8DT04938F
-1
benzoate (TMG5Measme, L3). C14
H
21
N
3
O
2
(M = 263.34 g mol ). (M = 428.66 g mol ). Colourless crystals, yield: 72%. Calc. (%)
Using the same procedure as L1
,
L3 (3.36 g, 12.7 mmol) was for C15 Zn; C 42.03, H 5.64, N 13.07; Found (%);
H
2 4 2
24Cl N O
obtained after 4 h reflux from 3c (2.19 g, 13.0 mmol) as C 41.65, H 5.48, N 12.93. IR (KBr): ṽ = 2953 [w,
colourless solid with a yield of 96%. IR (ATR, neat): ṽ = 2921 (w), [w, (C=O)], 1596 [s, (C=O)], 1573 (m),
(C=Ngua)], 1466 (w), 1421 (m), 1410 (m), 1398 (m),
)], 1300 (m), 1239 (m), 1196 1293 (m), 1192 (m), 1163 (m), 1121 (m), 1100 (m), 1067 (m),
(C‒Harom.)], 1034 (m), 999 (w), 953 (w), 852 (w), 819 [m,
 (CHaliph.)], 2921

(CHaliph.)], 1620 [m,


2
1
872 [w,
506 (m), 1482 (s), 1376 [s,

(CHaliph.)], 1717 [m,

(C=O)], 1574 [vs,

(C=Ngua)], 1529 [s,


(CH
3
(
7
1
vs), 1137 (vs), 1077 (s), 1017 (s), 896 (w), 832 [m,


(C‒Harom.)], 772
-
1
-1
1
3
94 (m), 777 (m), 750 (w), 720 (w), 693 (w), 595 (w) cm ; (m), 690 (w) cm . H NMR (400 MHz, CDCl ):  = 7.84 (d,
4
3
3
4
H NMR (400 MHz, CDCl
3
):

= 7.53 (d,
4
J
H,H = 1.8 Hz, 1H;
J
H,H = 9.2 Hz, 1H; CHarom.), 6.33 (d, JH,H = 9.2 Hz, JH,H = 2.5 Hz,
3
4
CHarom.), 7.17 (dd, JH,H = 8.2 Hz, JH,H = 1.8 Hz, 1H; CHarom.), 6.96 1H; CHarom.), 5.48 (d, JH,H = 2.4 Hz, 1H; CHarom.), 3.95 (s, 3H; CH
3
),
(
d, 3JH,H = 7.6 Hz, 1H; CHarom.), 3.77 (s, 3H; CH
3
), 2.69 (s, 12H; 3.00 (s, 6H; CH
3
), 2.94 (s, 6H; CH
), 2.79 (br s, 6H; CH ) ppm.
3 3
C{ H} NMR (101 MHz, CDCl ):  = 172.5 (Ccarbonyl), 166.3 (Cgua.),
CH
3
), 2.27 (s, 3H; CH
3
) ppm; 13C{ H} NMR (101 MHz, CDCl
1
3
):
13
1
3

1
= 168.3 (Ccarbonyl), 160.3 (Cgua.), 133.9 (CHarom.), 131.2 (CHarom.), 155.1 (Carom.), 153.5 (Carom.), 134.5 (CHarom.), 106.8 (CHarom.),
3 3 3
29.8 (Carom.), 125.4 (CHarom.), 121.3 (Carom.), 51.4 (CH ), 39.4 105.4 (Carom.), 104.2 (CHarom.), 53.8 (CH ), 41.3 (CH ), 40.1 (CH ),
3
(
CH
3
), 20.6 (CH
3
) ppm; HRMS (EI): m/z (%): calcd.: 263.1634, 40.0 (CH
3
) ppm. HRMS (ESI+, MeCN): m/z (%): calcd.: 391.0879,
+
+
found: 263.1630 [C14
[
2
1
H
21
N
3
O
H
2
] ; MS (EI): m/z (%): 263.0 (55) found: 391.0880 [C15
H
24ClN
4
O
2
Zn] .
+
+
+
C
14
H
21
N
3
O
2
] , 248.0 (14) [C13
18
N
3
O
2
] , 232.0 (14) [C13
H
18
N
3
O] ,
+
+
Zn (M = 420.04 g mol-
Zn;
19.0 (63) [C12
79.0 (27), 165.0 (17) [C
H
15
N
2
O
2
] , 204.0 (83) [C12
H
18
N
3
] , 192.0 (36), [ZnCl
2
(TMG5Clasme)]
3 3 2
(C2): C13H18Cl N O
+
+
1
9
+
H
11NO
2
] , 160.0 (61) [C10
12
H N
2
] , 146.0
). Colourless crystals, yield: 79%. Calc. (%) for C13H18Cl N O
3 3 2
+
+
(30), 133 (100) [C
8
H
5
O
2
] , 106.0 (11) [C
7
H
8
N] , 91.0 (23) [C
7
H
7
] , C 37.17, H 4.32, N 10.00; Found (%); C 37.51, H 4.30, N 9.91. IR
+
7
8.1 (11) [C
6
H
6
] .
(KBr): ṽ = 2955 [m,
649 [vs, (C=O)], 1585 (s), 1548 [m,
Methyl 2-((bis(dimethylamino)methylene)amino)-5-(dimethyl (C=Ngua)], 1505 [s, (C=Carom.)], 1465 (s), 1414 [m,
amino)benzoate (TMG5NMe asme, L4) 1330 [s, (CH )], 1283 (m), 1250 (vs), 1206 (m), 1169 (m), 1151
M = 292.38 g mol ). Using the same procedure as L1 L4 (m), 1111 (m), 1084 (m), 1070 (w), 1062 (w), 1038 (m), 952 (m),
7.17 g, 24.7 mmol) was obtained after 15 h reflux from 4c 927 (m), 897 (m), 860 [m, (C‒Harom.)], 841 (m), 806 (m), 788

(CHaliph.)], 2936 [w,

(CHaliph.)], 1721 (w),
(C=Ngua)], 1527 [s,
(C‒Harom.)],
1





2
.
C
15
H
24
N
,
O
4 2

3
-1
(
(
(
(

-
1 1
5.60 g, 28.7 mmol) as yellow crystals with a yield of 86%. IR (m), 753 (m), 709 (m), 685 (w), 660 (m) cm . H NMR (400 MHz,
KBr): ṽ = 3441 (m), 3020 (w), 2996 (w), 2946 (m), 2926 (m), CDCl
4
3
):

= 8.01 (d,
JH,H = 2.6 Hz, 1H; CHarom.), 7.42 (dd,
3
H,H = 8.7 Hz, JH,H = 2.6 Hz, 1H; CHarom.), 6.43 (d, 3JH,H = 8.7 Hz,
4
2
1
1
871 [m,
704 [vs,

(CHaliph.)], 2844 [m,

(CHaliph.)], 2792 [m,


(CHaliph.)],
J

(C=O)], 1611 [m,

(C=Ngua)], 1585 [vs,
(C=Ngua)], 1H; CHarom.), 4.07 (s, 3H; CH
3
), 2.98 (s, 6H; CH
ppm. C{ H} NMR (101 MHz, CDCl ):
)], 1345 (m), 1282 (m), 1247 (m), 1203 (m), (Cgua.), 150.5 (Carom.), 135.9 (CHarom.), 132.4 (CHarom.), 127.4
167 (m), 1136 (m), 1109 (w), 1086 (m), 1061 (m), 1017 (m), 989 (Carom.), 124.9 (CHarom.), 118.5 (Carom.), 55.1 (CH ), 41.3 (CH ),
3 3
), 2. 82 (s, 6H; CH )
13
1
495 (s), 1459 (m), 1451 (m), 1434 (s), 1423 (m), 1408 [m,
)], 1371 [s, (CH

3
 = 171.7 (Ccarbonyl), 166.3
(CH
3

3
1
3
3
(
m), 947 (w), 924 (w), 876 (w), 861 [w,

(C‒Harom.)], 860 [m,

40.2 (CH
3
) ppm. HRMS (ESI+, MeCN): m/z (%): calcd.: 382.0068,
+
(C‒Harom.)], 787 (w), 764 (w), 743 (w), 694 (w), 664 (w), 617 (w), found: 382.0067 [C13
H
18Cl
2
N
3
O
2
Zn] .
-1 1
5
2
6
87 (w) cm ; H NMR (400 MHz, d -DMSO):  = 6.89‒6.85 (m,
H; CHarom.), 6.64‒6.61 (m, 1H; CHarom.), 3.67 (s, 3H; CH
3
), 2.80 [ZnCl
2
(TMG5Measme)]
(C3):
14 2 3 2
C H21Cl N O Zn
); 13C{ H} NMR (101 MHz, d
1
(M = 420.04 g mol ). Colourless crystals, yield: 85%. Calc. (%)
-1
(s, 6H; CH
3
), 2.54 (s, 12H; CH
3
6
-
DMSO):
2 3 2
 = 168.2 (Ccarbonyl), 158.4 (Cgua.), 143.8 (Carom.), 143.1 for C14H21Cl N O Zn; C 42.08, H 5.30, N 10.52; Found (%);
(
(
(
Carom.), 124.7 (CHarom.), 121.7 (Carom.), 118.5 (CHarom.), 113.5 C 42.24, H 5.50, N 10.45. IR (ATR, neat): ṽ = 2957 [w,  (CHaliph.)],
CHarom.), 51.0 (CH
%): calcd.: 292.1899, found: 292.1889 [C15
3
), 40.9 (CH
3
), 38.7 (CH
3
) ppm; HRMS (EI): m/z 1637 [vs,

(C=O)], 1529 [vs,

(C=Ngua)], 1484 (m), 1441 (s), 1423
)], 1250 (vs), 1168 (m), 1091 (m),
+
H
24
N
4
O
2
] ; MS (EI): (m), 1400 (vs), 1329 [s,

(CH
3
+
+
m/z (%): 292.3 (39) [C15
2
H
24
N
4 2
O
] , 277.3 (14) [C14
H N
21 4
O
2
] , 1064 (m), 1039 (s), 958 (m), 860 (m), 842 [m,

(C‒Harom.)], 808
+
+
-1 1
48.3 (6) [C13
H
18
N
3
O
2
] , 233.2 (27) [C13
H
21
N
4
] , 189.2 (18) (m), 789 (s), 714 (m), 695 (m), 676 (m), 438 (s) cm . H NMR
+
+
+
4
[
(
11
C H
15
N
3
] , 175.2 (10) [C10
H
13
N
3
] , 116.2 (40) [C
5
H
14
N
3
] , 72.3 (400 MHz, CDCl
3
):

= 7.81 (d, JH,H = 1.8 Hz, 1H; CHarom.), 7.27
JH,H = 1.8 Hz, 1H; CHarom.), 6.38 (d,
+
3
4
100) [C
2
H
6 3
N ] , 71.3 (77).
(dd,
J
H,H = 8.4 Hz,
3
J
H,H = 8.4 Hz, 1H; CHarom.), 4.04 (s, 3H; CH
3
), 2.94 (s, 6H; CH
) ppm. C{ H} NMR (101 MHz,
3
),
1
3
1
General synthesis of zinc complexes with guanidine hybrid 2.78 (s, 6H; CH
ligands CDCl ):
A hot solution of the ligand (0.1 mmol) was dissolved in dry THF (CHarom.), 132.9 (CHarom.), 132.0 (Carom.), 123.7 (CHarom.), 117.5
3
), 2.30 (s, 3H; CH
3
3
 = 172.8 (Ccarbonyl), 166.2 (Cgua.), 149.3 (Carom.), 136.9
3 3 3 3
(0.5 mL) and added to a hot solution of dissolved zinc chloride (Carom.), 54.6 (CH ), 41.2 (CH ), 40.1 (CH ) 20.6 (CH ) ppm. HRMS
(
0.1 mmol) in dry THF. The solution was cooled down to room (ESI+, THF): m/z (%): calcd.: 362.0614, found: 362.0198
+
temperature and crystals were obtained after 30 min. For C2 [C14
and C3 the crystals have been recrystallised in dry MeCN or THF
to obtain suitable single crystals for X-ray measurement.
H
21ClN
3
2
O Zn] .
1
0 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 11 of 13
Pleas De ad l too nn oT tr aa nd sj au cs t ti omn sa rgins
Journal Name
ARTICLE
[
(
ZnCl
M = 428.66 g mol ). Yellow crystals, yield: 75%. Calc. (%) for
Zn; C 42.03, H 5.64, N 13.07; Found (%); C 41.91,
H 5.52, N 12.95. IR (KBr): ṽ = 3442 (s), 3013 (w), 2995 [m,
2
(TMG5NMe
2
asme)]
(
C4):
C
15
H
24Cl
2
4
N O
2
Zn 9.
R. E. Drumright, P. R. Gruber and D. E. HentonV,ieAwdAvrt.icMle aOtnelirn.e,
2000, 12, 1841-1846.
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and R. Auras, Adv. Drug Delivery Rev., 2016, 107, 333-366.
A. P. Dove, Chem. Commun., 2008, 6446-6470.
-1
DOI: 10.1039/C8DT04938F
1
1
0.
1.
15 2 4 2
C H24Cl N O

(CHaliph.)], 2955 [m,

(CHaliph.)], 2891 [m,

(CHaliph.)], 2812 (w),
1
1
2.
3.
1
717 (w), 1646 [s,

(C=O)], 1607 [vs,
(C=Ngua)], 1500 [s,
454 (s), 1445 (s), 1436 (m), 1421 (s), 1405 (s), 1398 (s), 1385

(C=Carom.)], 1571 [vs, 
Y. Sarazin and J.-F. Carpentier, Chem. Rev., 2015, 115,
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
 (C=Ngua)], 1473 (m),
3
564-3614.
1
(
1
1
H
14.
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m), 1360 (m), 1331 (s), 1286 (s), 1256 (s), 1235 (vs), 1195 (m),
164 (m), 1145 (m), 1122 (w), 1083 (m), 1066 (m), 1037 (m),
105 (w), 982 (w), 949 (w), 932 (w), 882 (w), 860 [w,
(C‒ 15.
arom.)], 851 (w), 833 [w, (C‒Harom.)], 804 (w), 786 (w), 771 (w),

B. M. Chamberlain, M. Cheng, D. R. Moore, T. M. Ovitt, E.
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
-
1 1
6
96 (w), 609 (vw), 563 (w), 445 (w) cm . H NMR (400 MHz, d
6
-
3
16.
DMSO):
1
CH

= 6.95‒6.91 (m, 2H; CHarom.), 6.79 (d, JH,H = 6.2 Hz,
H; CHarom.), 3.73 (s, 3H; CH
3
), 2.84 (s, 6H; CH
3
), 2.63 (s, 12H;
= 167.7
13
1
3
) ppm.
C{ H} NMR (101 MHz, d -DMSO): 
6
17.
(
(
(
C
carbonyl), 158.8 (Cgua.), 145.3 (Carom.), 137.7 (Carom.), 125.2
CHarom.), 122.3 (Carom.), 118.0 (CHarom.), 113.5 (CHarom.), 51.5
CH
3
), 40.6 (CH
3
), 39.0 (CH
3
) ppm. HRMS (ESI+, MeCN): m/z (%):
18.
19.
20.
+
calcd.: 391.0879, found: 391.0868 [C15
4
H24ClN O
2
Zn] .
Conflicts of interest
There are no conflicts to declare.
21.
Acknowledgements
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Technology CPT, which was supported by the EU and the federal
state of North Rhine-Westphalia (Grant EFRE 30 00 88302).
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