Urea-and thiourea-catalyzed aminolysis of carbonates

Article abstract of DOI:10.1002/cssc.201600778

The aminolysis of (poly)carbonates by (poly)amines provides access to non-isocyanate polyurethanes (NIPUs) that are toxicreagent-free analogues of polyurethanes (PUs). Owing to their low reactivity, the ring opening of cyclic carbonates requires the use of a catalyst. Herein, we report that the more available and cheaper ureas could advantageously be used for catalyzing the formation of NIPUs at the expense of the thiourea analogues. In addition, we demonstrate a medium-range pK_a of the (thio)urea and an unqeual substitution pattern is critical for controlling the efficiency of the carbonate opening.

Full text of DOI:10.1002/cssc.201600778

DOI: 10.1002/cssc.201600778
Full Papers
Very Important Paper
Urea- and Thiourea-Catalyzed Aminolysis of Carbonates
[
a, b]
[c]
[a]
[b]
Marine Blain,
Honman Yau, Ludivine Jean-Gꢀrard, Rꢀmi Auvergne,
[d]
[c]
[b]
[a]
Dominique Benazet, Peter R. Schreiner, Sylvain Caillol,* and Bruno Andrioletti*
The aminolysis of (poly)carbonates by (poly)amines provides
access to non-isocyanate polyurethanes (NIPUs) that are toxic-
reagent-free analogues of polyurethanes (PUs). Owing to their
low reactivity, the ring opening of cyclic carbonates requires
the use of a catalyst. Herein, we report that the more available
and cheaper ureas could advantageously be used for catalyz-
ing the formation of NIPUs at the expense of the thiourea ana-
logues. In addition, we demonstrate a medium-range pK of
a
the (thio)urea and an unqeual substitution pattern is critical for
controlling the efficiency of the carbonate opening.
Introduction
th
Polyurethanes (PUs) are the 6 most widely used
[
1]
polymers, but the use of the toxic isocyanates for
their syntheses raises increasing health and environ-
[
2]
mental concerns. For this reason, the development
of isocyanate-free alternatives to PUs is currently in-
tensely investigated. While the long-known aminoly-
sis of carbonates allows the preparation of non-isocy-
anate polyurethanes (NIPUs) whose properties may
[
3–8]
match those of PUs in many cases,
the limited re-
Scheme 1. TBD or thiourea-catalyzed carbonate aminolysis.
activity of amines towards carbonates requires the
use of catalysts for activating the amine and/or the
carbonate. As a consequence, the aminolysis of car-
[
9–18]
bonates has been investigated thoroughly.
In par-
ticular, it has been reported that 1,5,7-triazabicyclo[4.4.0]dec-5-
as substituted ureas are generally more readily available than
the corresponding thiourea derivatives, we have also screened
a series of urea derivatives to evaluate their catalytic activity in
the aminolysis of carbonates. The results of this study as well
as the rationalization of the observations are presented and
discussed in this article.
ene (TBD) and the cyclohexylphenyl thiourea 1a allow the effi-
[
9,17]
cient preparation of NIPUs (Scheme 1).
Interestingly, at low
catalyst loading, 1a outperformed TBD, hence allowing for the
large scale preparation of NIPUs. However, the problem with
the use of 1a as catalyst lies in 1) its price and 2) the absence
of commercial sources that may hamper its broad use.
About a decade ago, Wittkopp and Schreiner reported that
substituted thioureas are able to catalyze Diels–Alder reactions
via “Lewis acid-type catalysis” and that the catalytic activity de-
On the basis of this observation, we investigated the possi-
bility of using more affordable thiourea catalysts. In addition,
[19]
pends on the substitution pattern.
In particular, it was
shown that the 3,5-bis(trifluoromethyl)phenyl group is among
the best substituent not only because of the electron with-
[
a] Dr. M. Blain, Dr. L. Jean-Gꢀrard, Prof. B. Andrioletti
Universitꢀ de Lyon, Universitꢀ Claude Bernard-Lyon 1
ICBMS-UMR CNRS 5246 Campus LyonTech la Doua - Bꢁt. Curien/CPE
drawing effect of the CF substituents, but also because of ad-
3
[20]
4
3 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex (France)
ditional interactions involving the ortho-protons.
E-mail: bruno.andrioletti@univ-lyon1.fr
To ascertain this hypothesis in the (thio)urea catalyzed ami-
nolysis of carbonates, we synthesized a series of thiourea deriv-
atives and their urea analogues (Table 1) bearing cyclohexyl,
phenyl, and bis(trifluoromethyl)phenyl groups, and evaluated
their performance towards the ring opening of propylene car-
bonate (PC) with cyclohexylamine. The choice of the two part-
ners relies on earlier studies that demonstrated that the limited
reactivity of cyclohexylamine was most appropriate for reveal-
[
b] Dr. M. Blain, Dr. R. Auvergne, Dr. S. Caillol
Ingꢀnierie Architecture Macromolꢀculaire
Institut Charles Gerhardt UMR 5253 – CNRS, UM, ENSCM
8
, Rue Ecole Normale, 34296 Montpellier (France)
[
c] Dr. H. Yau, Prof. P. R. Schreiner
Institute of Organic Chemistry
Justus-Liebig University
Heinrich-Buff-Ring 17, 35392 Giessen (Germany)
[
d] D. Benazet
[9]
ing catalytic efficacy.
Juxta, 5 rue de la Jalesie,
BP 71039, 25401 Audincourt cedex (France)
Supporting Information for this article can be found under:
http://dx.doi.org/10.1002/cssc.201600778.
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as the other thioureas and ureas were insoluble in CDCl the
3
Table 1. Substitution pattern of the thiourea (a) and urea (b) derivatives
used in the study and association constants (K) with propylene carbon-
ate.
association cannot be measured in more competitive (H-bond-
ing) solvents.
Upon adding various amounts (x equiv.) of PC to a solution
1
of 1 equivalent catalyst in CDCl , H NMR titrations followed by
3
nonlinear regression were carried out and allowed the calcula-
tion of the association constants. The detailed calculations are
provided in the Supporting Information.
[
a]
[a]
À1
Substituents
(Thio)urea
pK
a
K
[M
]
1
R =3,5-(CF
3
)
2
C
6
H
3
1a
1b
13.2
17.8
12
The addition of increasing amounts of PC to a solution of
2
R =cyclohexyl
nd
0.67
1
5
a in CDCl induces significant peak shifts in the H NMR spec-
3
1
2
trum with an important downfield shift of the NH urea protons
R =R =cyclohexyl
2a
20.3
nd
(
Dd=0.91 ppm) and a moderate downfield shift for the ortho-
2
b
0
1
2
R =R =Ph
3a
13.4
18.7
nd
nd
3
b
1
2
R =R =3-(CF
3
)C
6
H
4
4a
10.9
16.1
1.4
nd
4
b
1
2
R =R =3,5-(CF
3
)
2
C
6
H
3
5a
8.5
13.8
121
nd
5
b
1
R =3,5-(CF
3
)
2
C
6
H
3
6a
6b
10.7
16.1
nd
nd
2
R =Ph
[a] The pKa values were calculated according to the method developed
by Schreiner and co-workers. nd=not determined.
Results and Discussion
Synthetic procedures
Urea derivatives 1b–6b were synthesized in a one-step proce-
dure by reacting the commercially available isocyanate with
the corresponding amine. The symmetrical thiourea derivatives
2
a–5a were readily prepared by condensation of two equiva-
lents of the appropriate amine with thiophosgene. The non-
symmetrically substituted thioureas 1a and 6a were synthe-
sized according to a two-step process. The first step involved
the synthesis of the thiocyanate by reaction of the amine and
thiophosgene before the second amine was added. The experi-
mental details are available in the Supporting Information.
1
Figure 1. H NMR titration of 5a with increasing amounts of PC in CDCl
3
.
The pK values of the organocatalysts screened in this study
a
were determined using the method developed by Schreiner
[
21,22]
and coworkers.
The pK values found for the new organo-
and para-protons with Dd=0.23 and 0.11 ppm, respectively
(Figure 1). Similar changes had already been observed by
Schreiner and coworkers upon studying the complexation of
a
catalysts investigated in this study are in agreement with the
trend determined earlier. As expected, the pK value of 4b
pK =16.1) matches with the expectations because the contri-
a
[20]
(
g-valerolactone with 5a; 5a is the only catalyst for which
a shift of the para-protons is observed. For the other thiourea
derivatives (2a, 4a, and 6a), only the NH chemical shift was
sensitive to complexation. As for 1a, the chemical shifts of
both the NH and ortho-protons underwent a noticeable
change in the chemical shifts. For the thiourea derivatives in-
vestigated, the affinity constants were moderate but varied
a
butions of the CF groups to the pK are additive regardless
3
a
[
21]
their position. For this reason, similar pK values were deter-
a
mined for 4b and 6b. The pK values of 1a and 1b differ by
.6 units. This observation is consistent with the electronic
a
4
effect of S versus O that was shown to induce a pK change of
a
[
21]
4
to 6 pK units.
a
À1
In parallel with the pK determinations, an attempt to esti-
with the highest K value for the most acidic 5a (K=121m )
a
À1
mate the association constants between the (thio)ureas and
the model carbonate was undertaken (Table 1). Unfortunately,
the NMR titration method used for the calculation of the affini-
ty constants (K) was only possible for 1a, 2a, 4a, 5a, and 2b,
and the lowest K value (K=0.67m ) for the least acidic 2a.
1
Hence, H NMR titrations provide a useful tool to confirm the
pK determination obtained by titration, so as to predict cata-
a
[23]
lytic activity.
&
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Catalysis and correlation with pKa values
The catalysis experimentswere carried out at 258C for 10 h. As
[
9]
established previously, cyclohexylamine and propylene car-
bonate were chosen for this study as they are virtually unreac-
tivein the absence of catalyst (conv.<9% after 1 h). Cyclohex-
ylamine and PC were mixedtogether in a 1:1 ratio before the
organocatalyst (5 mol%) was added. The progress of the reac-
tion was monitored by GC–MS analyses (PC conversion,
Table 2).
Table 2. Thiourea (a) and urea (b) catalyzed aminolysis of CP.
a
Figure 2. Evolution of the conversion of PC after 1 h versus pK .
more basic (thio)ureas afforded lower conversions. Indeed, the
cyclohexylamine is capable of deprotonating the most “acidic”
(
Thio)urea
(Thio)urea
Conv. [%]
t=0.5 h
[24]
substituents
t=1 h
(
thio)urea derivatives [pK (cyclohexylamine)=11.5 at 258C].
a
none
1a
1b
5
55
42
9
66
48
Consequently, the deprotonated catalyst is not able to activate
the carbonate. Conversely, the less acidic catalysts do not acti-
vate the carbonyl strongly enough to allow nucleophilic attack
of the amine. A more striking observation concerns the sym-
metry of the catalysts. Indeed, when two couples of catalysts
1
R =3,5-(CF
3
)
2
C
6
H
3
,
2
R =cyclohexyl
1
2
R =R =cyclohexyl
2a
17
5
26
21
2
b
with the same pK are compared, the non-symmetrical cata-
a
1
2
R =R =Ph
3a
44
47
51
53
lysts afford higher conversions. Hence, thioureas 4a and 6a ex-
3
b
hibit similar pK values (10.9 and 10.7, respectively), but the
a
1
2
R =R =3-(CF
3
) C
6
H
4
4a
40
60
52
67
symmetrical 4a organocatalyst afforded a medium 52% con-
version while the non-symmetrical catalyst 6a gave 64%. A
similar trend was noticed when comparing the ureas 4b and
4
b
1
2
R =R =3,5-(CF
3
)
2
C
6
H
3
5a
28
65
41
70
6
b even if the difference is minor. However, it appears that the
5
b
substitution effect is more pronounced with thioureas than
with ureas.
1
R =3,5-(CF
3
)
2
C
6
H
3
6a
6b
55
65
64
71
2
R =Ph
Similar trends were established when comparing the conver-
sion and the K values (Figure 3). The calculated association
constants are low for most of the thioureas with K <2 (2a, 4a,
6a). In addition, although 5a displays the highest association
constant it was not the best catalyst for the aminolysis of car-
Monitoring of the reaction was performed after 0.5 and 1 h
respectively. After 1 h, the conversion slows down and reaches
a plateau. Using a thiourea catalyst, the highest conversions
were obtained with catalysts 1a and 6a (66 and 64%, respec-
tively). Hence, non-symmetrical thioureas afford the best con-
versions. Slightly lower conversions of 51, 52, and 41% were
obtained with 3a, 4a, and 5a. Remarkably, the bis-cyclohexyl-
substituted thiourea 2a afforded much lower conversion with
only 26% after 1 h. More interestingly, the urea catalysts also
appeared to be excellent candidates for catalyzing the carbon-
ate aminolysis reaction. Indeed, ureas 4b, 5b, and 6b afforded
the expected carbamates in 67, 70, and 71% conversion after
bonates. The low pK of 5a probably explains this observation.
a
1
h, respectively. Hence, all the aromatic ureas investigated in
our study proved more active catalysts than their thiourea
counterparts. Owing to the large variety of commercially avail-
able ureas and isocyanate precursors, this unprecedented ob-
servation opens new perspectives in the catalyzed aminolysis
of carbonates for the large scale synthesis of NIPUs. Figure 2
reveals that an optimal pK ranging between 14 and 16 is re-
a
Figure 3. Evolution of the conversion of PC after 1 h versus the binding con-
stant K.
quired for obtaining the highest PC conversion. More acidic or
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Therefore, the conversion after 1 h detailed in Figure 3 is only
1% for 5a versus 66% for 6a that displays a 10ꢂ lower asso-
support. H.M.Y. was supported by the Alexander-von-Humboldt
Foundation (fellowship with P.R.S.).
4
ciation constant. The highest conversions are obtained with as-
sociation constants ranging between 1 and 12. Interestingly,
the association constants between the carbonate and 4a and
Keywords: aminolysis · catalysis · polyurethanes · pka
reactivity
·
6
a are the same. Therefore, the CF groups need not be neces-
3
sarily located on the same aryl group to enhance the associa-
tion constant value. A similar observation had already been
[
21]
made for the determination of the pK values.
a
Although the catalytic binding event of the (thio)urea for
the aminolysis of the carbonate reaction involves an interac-
tion between the NH (thio)urea groups and the carbonyl of
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This study demonstrates that readily available and affordable
urea derivatives may advantageously replace thiourea deriva-
tives or 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) in the aminoly-
sis of carbonate reactions. This observation renders the non-
isocyanate polyurethane (NIPU) synthesis more appealing as
equally performant but cheaper catalysts may be used. The
choice of the substitution pattern of the catalyst is mainly gov-
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the catalyst and the carbonate as well as the relative positions
of the substituents do not influence conversion much. Hence,
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gler, P. R. Schreiner, J. Am. Chem. Soc. 2011, 133, 7624–7627.
The Association Nationale de la Recherche et de la Technologie
Received: June 10, 2016
(ANRT) and Juxta are deeply acknowledged for their financial
Published online on && &&, 0000
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FULL PAPERS
M. Blain, H. Yau, L. Jean-Gꢀrard,
R. Auvergne, D. Benazet, P. R. Schreiner,
S. Caillol,* B. Andrioletti*
&& – &&
Urea- and Thiourea-Catalyzed
Aminolysis of Carbonates
Catalyst substituted: Appropriately
substituted ureas advantageously sub-
stitute thiourea catalysts in the ring
opening of carbonates to afford non-
isocyanate polyurethanes. A medium-
range pK of the (thio)urea and an un-
a
equal substitution pattern is critical for
controlling the efficiency of the carbon-
ate opening
ChemSusChem 2016, 9, 1 – 5
www.chemsuschem.org
5
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
These are not the final page numbers! ÞÞ