Sustainable synthesis routes towards urazole compounds

Article abstract of DOI:10.1039/c7gc02027a

Sustainable synthesis routes towards urazoles, the precursor molecules for triazolinediones, are reported. Not only is the use of isocyanates avoided, but the applied synthetic procedures are also mostly solvent-free, high yielding and performed in an equimolar manner. Two complementary synthesis routes have been developed starting from a wide range of amines, both based on the use of diphenyl carbonate. The first method, which is particularly suitable for the synthesis of bulk urazoles, such as butyl, cyclohexyl or benzyl urazole, is performed in bulk in a one-pot fashion and generally results in yields between 87% and 96%. The second synthesis route, with yields up to 95%, focusses on the implementation of functionalities in the urazole structure and offers the possibility to generate bifunctional urazole compounds.

Full text of DOI:10.1039/c7gc02027a

View Article Online
View Journal
Green
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: L. Vlaminck, B.
Van de Voorde and F. Du Prez, Green Chem., 2017, DOI: 10.1039/C7GC02027A.
Volume 18 Number
7
7
April 2016 Pages 1821–2242
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Green
Chemistry
Cutting-edge research for a greener sustainable future
www.rsc.org/greenchem
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1463-9262
CRITICAL REVIEW
G. Chatel et al.
Heterogeneous catalytic oxidation for lignin valorization into valuable
chemicals: what results? What limitations? What trends?
rsc.li/green-chem

Page 1 of 7
Pleas Ge rdeo e nn o Ct ah de j mu si ts mt r ya rgins
View Article Online
DOI: 10.1039/C7GC02027A
Green Chemistry
ARTICLE
Sustainable Synthesis Routes towards Urazole Compounds
a
a
a,†
Received 00th January 20xx,
Accepted 00th January 20xx
Laetitia Vlaminck , Babs Van de Voorde and Filip E. Du Prez
Sustainable synthesis routes towards urazoles, the precursor molecules for triazolinediones, are reported. Not only is the
use of isocyanates avoided, but the applied synthetic procedures are also mostly solvent-free, high yielding and performed
in an equimolar manner. Two complementary synthesis routes have been developed starting from a wide range of amines,
both based on the use of diphenyl carbonate. The first method, which is particularly suitable for the synthesis of bulk
urazoles, such as butyl, cyclohexyl or benzyl urazole, is performed in bulk in a one-pot fashion and generally results in
yields between 87 % and 96%. The second synthesis route, with yields up to 95%, focusses on the implementation of
functionalities in the urazole structure and offers the possibility to generate bifunctional urazole compounds.
DOI: 10.1039/x0xx00000x
www.rsc.org/
1
4
crosslinkers was shown to be efficient and subsequently, TAD
modification of ADMET based polymers was described on fatty
1
5
16
Introduction
acid- and phosphoester-based structures. Furthermore,
sustainable applications in thermoplastic elastomers based on
Urazoles (Figure 1) have been known since 1887, when Pinner
reported the first synthesis of phenyl urazole from
1
phenylhydrazine and urea. Nowadays, urazoles serve
1
7
18
plant oils and in shape memory materials can be found.
The main drawback of all above described reports is that the
applied TADs are not synthesized via a sustainable synthesis
route. The general synthesis method towards urazoles starts
from the corresponding isocyanate, as described by Cookson in
different uses as building blocks in organic synthesis. For
example, the pharmaceutical sector has incorporated urazoles
2
in anti-inflammatory agents or applied it as a scaffold to
1
9
3
1
971. Cookson further developed the synthesis that was
generate libraries for inhibitors of thrombin.
2
0
proposed by Zinner and Deucker in 1961. The Cookson-
method combines an isocyanate with ethyl carbazate to form
the corresponding semicarbazide, which is subsequently
cyclized under aqueous basic conditions (Figure 2a).
Upon oxidation of urazoles, 1,2,4-triazolinediones (TADs) are
generated. These reactive species are known as one of the
most electron deficient species, making them extremely
4
reactive in Diels-Alder and Alder-ene reactions (Figure 1). This
During many decades, solutions were sought-after to avoid the
use of isocyanates. This search was not driven by the toxicity
of isocyanates, but rather by the limited structural variety that
can be found in commercially available isocyanates. Thus,
carboxylic acids were proposed as a substitute, as the
corresponding isocyanate could be created in situ, avoiding the
isolation and purification of hazardous intermediates. The
most applied reaction path converts the carboxylic acid in the
acyl azide, for example by making use of diphenylphosphoryl
azide (DPPA), which can undergo a Curtius rearrangement
upon heating with the formation of the corresponding
was already discovered in the 1970s and ‘80s when TADs were
repeatedly utilized for the modification and crosslinking of
5
-7
polybutadiene structures.
Although the exceptional
reactivity of TAD has been proven multiple times, the
application window has been narrow, as the commercial
availability of the TAD building blocks is limited.
The number of reports making use of TAD compounds has
been rising since 2014, after our first article describing a
8
powerful “click” and “trans-click” chemistry platform. Since
then, several articles were published, reporting the use of TAD
9
in the field of polymer-polymer coupling,
0-12
surface
13
crosslinking of α,ω-oleyl-PCL-structures and
2
1-23
1
isocyanate.
modification,
more. Next to the above described applications, reports on the
use of TAD in the field of polymer materials from renewable
resources have been published. First, the direct crosslinking of
commercially available plant oils via bifunctional TAD
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Pleas Ge rdeo e nn o Ct ah de j mu si ts mt r ya rgins
Page 2 of 7
View Article Online
DOI: 10.1039/C7GC02027A
ARTICLE
Journal Name
3
6, 37
Figure 1 - The basic cyclization of a functional semicarbazide, followed by the oxidation of dimethyl carbonate (DMC) with phenol (Figure 3b),
the
of a urazole to a 1,2,4-triazoline-3,5-dione (TAD) and the subsequent Diels-Alder (top) oxidative carbonylation of phenol (Figure 3c) is an often used
3
8, 39
or Alder-ene (bottom) reaction.
methodology.
Although both reactions need the use of a catalyst and yields
3
are strongly dependent on the catalyst system, these
5
Figure 2 - (a) Cookson-method for the synthesis of 1,2,4-triazoline-3,5-diones (TADs) (b)
In situ generation of an isocyanate for the generation of semicarbazides via the Curtius
rearrangement. (c)+(d) The synthesis of semicarbazides from amines in a isocyanate-
Figure 3 - (a) Oxidative carbonylation of methanol, (b) transesterification of DMC with
phenol and (c) direct oxidative carbonylation of phenol.
2
4
25
Ph, Et. R’’ = Ph, p-NO
26
27
free reaction pathway. R' = NO
2
2
Ph.
synthetic routes, which can incorporate the recycled phenol,
are highly promising.
Subsequently, ethyl carbazate can be added in a one-pot It is clear from the above paragraphs that synthetic routes for
fashion to obtain the semicarbazide (Figure 2b). Although this urazole compounds starting from amines still show significant
reaction pathway avoids the direct use of isocyanates, the drawbacks. Indeed, the use of chloroformates and the need
toxicity and price of DPPA is a main drawback of this synthesis for purification still limits the sustainability of the processes.
route.
On the other hand, the use of diphenyl carbonate could offer a
Also amines or anilines were suggested as alternative starting solution to the challenging synthesis. We will report on
compounds. Amines are abundant in nature and are generally sustainable urazole synthesis routes. Our aim was not only to
less toxic and expensive compared to their isocyanate avoid the use of isocyanates, chloroformates and solvents but
counterpart. Next to the synthesis route in which amines are also to apply equimolar amounts. Two different pathways are
converted in situ in the corresponding isocyanate using proposed, depending on the starting compound and the
2
8-30
(tri/di)phosgene,
two main reaction paths can be described desired functionality of the urazole or corresponding TAD
starting from amines or anilines. The first method was compound.
2
4, 25
investigated by Mallakpour et al.
and closely resembles
the Cookson-strategy, as activated carbamates are used as the
alternative to isocyanates (Figure 2c). These activated
Results and Discussion
carbamates are synthesized using chloroformates and are The replacement of chloroformates by DPC in the two
subsequently converted to the corresponding semicarbazide previously mentioned protocols, to synthesize urazoles
using ethyl carbazate. This one-pot procedure was recently starting from amines (Figure 2c-d), resulted in two separate
optimized by Barbas and co-workers, who make use of an reaction pathways to obtain the semicarbazide from the free
3
1-33
excess of chloroformate and ethylcarbazate.
amine. The semicarbazide was subsequently cyclized in a
The second methodology involves the use of a reactive thermal or basic fashion, as is visualised in Figure 4. All
intermediate, which is made from a chloroformate and ethyl reaction routes will be discussed in detail below.
carbazate, which can subsequently react with a range of
amines under mild conditions (Figure 2d). Breton introduced
Reaction route A
this methodology in 2014, with the formation of ethyl phenyl
2
6
Figure 5 summarizes the first reaction route, in which an
activated carbamate is formed via an addition-elimination step
of the corresponding amine to DPC. Subsequently, the
semicarbazide is formed via reaction with ethyl carbazate at
hydrazine-1,2-dicarboxylate (R’’ = Ph).
was suggested by Adamo and co-workers, who applied p-
nitrophenyl chloroformate (R’’ = p-NO Ph) to afford a more
A similar pathway
2
3
4
reactive intermediate. However, this did not result in higher
yields. It should be noted that both protocols use an excess of
amine and therefore require a purification step before
cyclization can be performed.
Recently, diphenyl carbonate (DPC) has drawn a lot of
attention as a sustainable alternative of phosgene in organic
3
5
synthesis.
Environmentally friendly processes for the
synthesis of DPC without the use of phosgene have been
developed in the past decades. Besides the transesterification
2
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 7
Pleas Ge rdeo e nn o Ct ah de j mu si ts mt r ya rgins
View Article Online
DOI: 10.1039/C7GC02027A
Journal Name
ARTICLE
which included an increase in temperature and thus an
increase in reaction rate, was started after this reaction time.
The last step included the thermal cyclization of the
4
0
triazolinedione as described earlier by Paquette et al. This
step was performed at 250°C under gentle nitrogen flow to
remove
Figure 4 - The different reaction pathways for sustainable synthesis of urazole
compounds. (1A) Formation of the reactive carbamate and subsequent addition of
ethyl carbazate (EC) or (1B) direct conversion of the amine to the semicarbazide using
ethyl phenyl hydrazine dicarboxylate, followed by (2A) thermal or (2B) basic cyclization.
Figure 6 - A side reaction was observed during the first reaction step, as a second amine
1
addition leads to the urea rather than the carbamate. H-NMR analysis showed that
this side product can be avoided when an excess of DPC is used.
the produced phenol, which can easily be recuperated in
industrial processes to regenerate the DPC.
1
Kinetic analysis via H-NMR showed that all semicarbazide was
transformed in the corresponding urazole after 30 minutes.
Furthermore, the urea side product got thermally removed
from the reaction mixture. The reaction mixture was kept at
2
50°C for one hour in order to remove all traces of phenol. An
important advantage of this method is that there is no need
for work-up, which makes the method fast and avoids the
unnecessary use of solvents.
The above described methodology was applied to a range of
amines (Table 1). The yield of the complete process varies
Figure 5 - A one-pot isocyanate- and solvent-free reaction path towards urazoles. The
activated carbamate, formed in the first step, reacts further towards the corresponding
semicarbazide, which leads to the urazole via thermal ring closure.
1
between 89% and 96%. LC-MS, HR-MS and H-NMR proved the
1
purity of the compounds, Figure S2 shows the complete H-
NMR analysis of the synthesis of butyl urazole via this method.
It should be noted that, in certain cases, minor phenol-
1
impurities are still visible in the H-NMR spectra.
elevated temperature. In a final step, the semicarbazide is
transformed towards a urazole via a thermal cyclization step.
All steps were optimized via a kinetic study.
Furthermore, it should however be noted that difficulties arise
upon incorporation of different functional groups. As phenyl-
TAD (PhTAD) is a well-known TAD compound, it is interesting
to investigate the synthesis of its urazole counterpart via the
above described synthesis with the use of aniline. However,
because of the reduced nucleophilicity of aniline, the
carbamate could not be formed during the first reaction step.
Although
The first step was performed in bulk at 80°C, the melting
temperature of DPC, which proved to be instantaneous via a
1
kinetic H-NMR analysis. As a guideline, a reaction time of 10
minutes is applied, to provide optimal mixing. Because of the
speed of reaction, a side product was observed when an
equimolar ratio of amine and DPC was applied. Although the
majority of the desired product was formed, a minor urea side
product (5-10%) appeared, both in NMR and LC-MS, resulting
from double amine-addition to the DPC (Figure 6).
Optimisation showed that the urea was the only product
formed upon addition of a twofold excess of amine, while no
urea was formed upon addition of two equivalents of DPC
4
1
Harada et al. obtained the activated carbamate with the use
of isobutyric acid as catalyst and an excess of aniline, the pure
carbamate can only be obtained after intermediate column
chromatography, which limits the sustainability of the process.
Furthermore, 3-amino-1-propanol was investigated as starting
compound in order to obtain an alcohol-functionalized
urazole. However, in this case, a mixture of carbamates and
carbonates was obtained. LC-MS analysis proved that the
mixture was too complex for purification, as can be seen from
the list of reaction products in Figure S3. Moreover, in order to
obtain a bis-urazole, ethylenediamine was investigated as
starting product. Again, a range of side products was formed
upon addition of two equivalents DPC to one equivalent of
ethylenediamine (Figure S4). The high reactivity of the amine
towards DPC results in the formation of these side products.
The above described synthesis has significantly increased the
sustainability in comparison to the synthesis as described by
(Figure S1). However, as the urea was removed automatically
during the thermal cyclization, the first step was kept under
equimolar conditions.
In the second reaction step, ethyl carbazate (EC) was added to
the reaction mixture and the temperature was increased
towards 140°C. This resulted in the formation of the
semicarbazide as the only product. The urea side product from
the first reaction step was shown to be unreactive towards the
ethyl carbazate and persisted in the reaction mixture. The
kinetics of this reaction were tested and it was shown that the
reaction slowed down after reaching approx. 80% conversion
in about 150 minutes (Figure 7). Therefore, the next step,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Pleas Ge rdeo e nn o Ct ah de j mu si ts mt r ya rgins
Page 4 of 7
View Article Online
DOI: 10.1039/C7GC02027A
ARTICLE
Journal Name
2
4, 25
Mallakpour et al.
It would, however, be beneficial if DPC step to obtain the semicarbazide directly from the amine. In
could be replaced by the more environmentally friendly order to synthesize EPHD, Breton et al. make use of phenyl
alternatives such as dimethyl carbonate (DMC) or diethyl chloroformate, which is labelled as toxic and corrosive.
1
00
80
60
40
20
0
0
30
60
90
120
150
180
210
240
Time (min)
Figure 7 - Kinetics of the semicarbazide formation in the second step.
Table 1 - Overview of the amines used for urazole synthesis via the two described
Figure 8 – The urazole is obtained in a one-pot fashion via the direct formation of
the semicarbazide, which is cyclized via thermal or basic conditions.
a
reaction routes and the respective yields of those reactions (in %). Thermal The sustainability of the process was improved by combining
b
cyclization, basic cyclization, n.s.: not successful.
DPC with EC for the synthesis of EPHD. The bulk reaction
between equimolar amounts of DPC and EC at 90 °C for 2
Amine
Butylamine
Route A
86
Route B
a
hours resulted in a conversion of 73 %. To further optimize the
reaction, TBD and DBU were tested as catalysts and the
temperature was increased to 100 °C and 110 °C. However,
kinetic analysis showed no significant improvement in
conversion upon variation of catalyst and reaction
temperature (Figure S5). Furthermore, upon increase in
reaction time, only 14% increase in conversion was obtained
after overnight reaction, which is limited in correlation to the
extra energy input. In a final test, a twofold excess of EC was
applied, which resulted in complete conversion. The reaction
temperature could even be lowered to 80°C. The excess of EC
and the produced phenol can be removed by precipitation in
water and could in principle be recuperated for next reactions.
Figure 9 summarizes the optimized reaction conditions, in
which a yield of 76 % was obtained.
89
a
Octylamine
96
95
a
Benzylamine
87
85
b
Tetrahydrofurfurylamine
Oleylamine
87
90
a
96
95
a
Allylamine
89
84
a
Cyclohexanemethylamine
93
95
b
3
-Amino-1-propanol
Ethylene diamine
Aniline
n.s.
n.s.
n.s.
78
a
92
n.s.
carbonate (DEC). This would not only avoid the synthesis of
DPC but would also release methanol or ethanol, respectively,
instead of their aromatic counterpart, phenol. However, it was
shown that the replacement of DPC by DMC could not provide
a more sustainable alternative. Indeed, as the leaving group
capacity of the methoxy-group is limited, this resulted in
prolonged reaction times up to 24 hours to reach full
conversion in the first reaction step, while no reaction at all
could be observed for the semicarbazide formation in the
second step. This was further investigated by an increase in
temperature towards 160°C and the use of catalysts such as
TBD and DBU, but no improvement was observed. In
conclusion, the use of DMC does not offer more promising
results than the proposed DPC pathway.
As can be seen in Figure 8, the first reaction step towards the
semicarbazide was performed in bulk at 80°C, the melting
1
temperature of EPHD. H-NMR analysis showed that full
conversion was reached after 5 minutes, which demonstrates
the high reactivity of the activated intermediate. A reaction
time of 10 minutes was applied to ensure complete reaction.
Cyclization towards the urazole was performed thermally for
non-functional semicarbazides, as this is
a fast and
straightforward method that effectively removes the produced
phenol. As no urea side product was formed, basic cyclization
was also possible without the need for intermediate
purification. The basic cyclization was performed by refluxing
Reaction route B
As the first synthesis route via the activated carbamate proved
to be challenging when certain functional amines were used, a
second synthesis route was investigated. This route optimizes
the synthesis by Breton et al., who used an activated
2 3
the semicarbazide overnight in a solution of K CO in ethanol.
Although longer reaction times are necessary, this method is
ideal for thermo-sensitive semicarbazides, such as propanol
semicarbazide and tetrahydrofurfuryl semicarbazide.
2
6
intermediate to obtain the semicarbazide in one step.
High yields were again obtained (Table 1) when no competitive
functionalities were present, for example with butyl-, benzyl-
and cyclohexanemethylamine, with yields of 89%, 85% and
As can be seen in Figure 8, the activated intermediate ethyl
phenyl hydrazine-1,2-dicarboxylate (EPHD) is used in the first
4
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 7
Pleas Ge rdeo e nn o Ct ah de j mu si ts mt r ya rgins
View Article Online
DOI: 10.1039/C7GC02027A
Journal Name
ARTICLE
9
5% respectively. The structure was again verified via LC-MS, While the original synthesis routes of Mallakpour and Breton
1 13
HR-MS, H-NMR and C-NMR.
also result in high yields, the syntheses developed in this
Breton et al. already showed that aniline was unreactive project
towards EPHD in solution, which was also confirmed by the avoid the use of chloroformates and solvents and apply
above described method in bulk, even at longer reaction times equimolar amounts, which significantly reduces the E-factor of
of 24 h. It was thus shown to be impossible to synthesize the process. Furthermore, the one-pot process strongly
phenyl urazole without the use of chloroformates. However, in reduces the reaction time, as the reactions are fast,
contrast to the first methodology, propanol urazole could be quantitative and there is no need for intermediate
obtained with a 78 % yield thanks to the use of EPHD. purification
Moreover, also a bis-urazole was obtained starting from
ethylenediamine. The reactive intermediate avoided the
.
Conflicts of interest
overreaction that was observed in reaction route A, leading to
a yield of 92%.
There are no conflicts of interest to declare.
Acknowledgements
Kevin De Bruycker is thanked for fruitful discussions. L.
Vlaminck acknowledges the Special Research Fund (BOF) of
Ghent University for funding of her PhD project.
Figure 9 – Synthesis of EPHD from DPC and EC in bulk.
Phenol recovery
As this synthetic route is based on the use of DPC, the recovery Notes and references
of the produced phenol is of vital importance to underpin its
1
2
. A. Pinner, Eur. J. Inorg. Chem., 1887, 20, 2358.
. T. G. M. Dhar, E. J. Iwanowicz, M. Launay, M. J. B. Maillet, E.
green character. The recuperation of phenol was thus
investigated for both reaction pathways for the example of
octyl-urazole by applying a distillation set-up during the
thermal cyclisation step. In the first reaction pathway, it
concerns two equivalents of phenol, which could be
recuperated in a yield of 83%, while only one equivalent of
phenol is released in the second pathway, which could be
recovered for 92%. The purity of the obtained phenol was
A. Nicolai and D. Potin, Urazole compounds useful as anti-
inflammatory agents, EP 1395259 A2, 2004.
3
. P. D. Boatman, J. Urban, M. Nguyen, M. Qabar and M. Kahn,
Bioorg. Med. Chem. Lett., 2003, 13, 1445.
. K. De Bruycker, S. Billiet, H. A. Houck, S. Chattopadhyay, J. M.
Winne and F. E. Du Prez, Chem. Rev., 2016, 116, 3919.
4
5
1
6
. L. d. L. Freitas, J. Burgert and R. Stadler, Polym. Bull., 1987,
, 431.
. G. B. Butler and A. G. Williams, J. Polym. Sci., Part A: Polym.
1
high, as no other products could be observed in the H-NMR
7
spectrum (Figure S6).
Chem., 1979, 17, 1117.
. B. Saville, Journal of the Chemical Society D: Chemical
Communications, 1971, 12, 635.
. S. Billiet, K. De Bruycker, F. Driessen, H. Goossens, V. Van
Speybroeck, J. M. Winne and F. E. Du Prez, Nat. Chem., 2014,
7
Conclusions
It can be concluded that the synthesis towards more
sustainable urazoles was successful, as two one-pot
isocyanate-free synthesis routes were applied to a wide range
of amines with different R-groups. Depending on the starting
product and desired incorporated functionalities, one
synthesis route is preferred over the other. Via the first
method, urazoles with alkyl or related functionalities were
obtained in high yield. This method shows great advancement
compared to the previously reported synthesis routes, as the
8
6
,
8
9
15.
. S. Vandewalle, S. Billiet, F. Driessen and F. E. Du Prez, ACS
, 766.
0. O. Roling, K. De Bruycker, B. Vonhören, L. Stricker, M.
Macro Lett., 2016,
5
1
Körsgen, H. F. Arlinghaus, B. J. Ravoo and F. E. Du Prez, Angew.
Chem. Int. Ed., 2015, 54, 13126.
1
1. B. Vonhören, O. Roling, K. De Bruycker, R. Calvo, F. E. Du Prez
and B. J. Ravoo, ACS Macro Lett., 2015, , 331.
2. K. De Bruycker, M. Delahaye, P. Cools, J. Winne and F. E. Du
Prez, Macromol. Rapid Commun., 2017, DOI:
0.1002/marc.201700122.
3. M. Basko, M. Bednarek, L. Vlaminck, P. Kubisa and F. E. Du
2
5
reaction route described by Mallakpour et al. showed the
need for solvent (acetone or THF) and reaction times of more
than 10 hours. Furthermore, the scope of the reaction has
been broadened, as this method was previously only applied
to aniline-derivatives. The second synthesis route offers a
solution to prepare functionalized urazoles, as nucleophilic
groups such as an alcohol could be introduced. Furthermore,
also a bis-urazole could be obtained.
4
1
1
1
Prez, Eur. Polym. J., 2017, 89, 230.
4. O. Türünç, S. Billiet, K. De Bruycker, S. Ouardad, J. Winne and
F. E. Du Prez, Eur. Polym. J., 2015, 65, 286.
5. L. Vlaminck, K. De Bruycker, O. Türünç and F. Du Prez, Polym.
Chem., 2016, , 5655.
1
1
7
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Pleas Ge rdeo e nn o Ct ah de j mu si ts mt r ya rgins
Page 6 of 7
View Article Online
DOI: 10.1039/C7GC02027A
ARTICLE
Journal Name
1
6. G. Becker, L. Vlaminck, M. Martinez-Velencoso, F. E. Du Prez
and F. R. Wurm, Polym. Chem., 2017, , 4074.
7. Z. Wang, L. Yuan, N. M. Trenor, L. Vlaminck, S. Billiet, A.
Sarkar, F. E. Du Prez, M. Stefik and C. Tang, Green Chem., 2015,
8
1
17, 3806.
1
8. Z. Wang, Y. Zhang, L. Yuan, J. Hayat, N. M. Trenor, M. E.
Lamm, L. Vlaminck, S. Billiet, F. E. Du Prez, Z. Wang and C. Tang,
ACS Macro Lett., 2016, , 602.
9. R. Cookson, S. Gupte, I. Stevens and C. Watts, Green Chem.,
5
1
1
2
2
2
2
2
1
2
2
4
2
971, 51, 121.
0. G. Zinner and W. Deucker, Arch. Pharm., 1961, 294, 370.
1. T. Curtius, Adv. Synth. Catal., 1894, 50, 275.
2. T. Curtius, Eur. J. Inorg. Chem., 1893, 26, 403.
3. K. Shimada and T. Oe, Anal. Sci., 1990, 6, 461.
4. S. Mallakpour and Z. Rafiee, Synth. Commun., 2007, 37
,
927.
5. S. Mallakpour and Z. Rafiee, Synlett, 2007,
6. G. W. Breton and M. Turlington, Tetrahedron Lett., 2014, 55
661.
7. A. Nilo, M. Allan, B. Brogioni, D. Proietti, V. Cattaneo, S.
8, 1255.
,
Crotti, S. Sokup, H. Zhai, I. Margarit and F. Berti, Bioconjugate
Chem., 2014, 25, 2105.
2
1
2
3
3
8. G. Read and N. R. Richardson, J. Chem. Soc., Perkin Trans. 1,
996, , 167.
9. J. M. Gardlik and L. A. Paquette, Tetrahedron Lett., 1979, 20
2
,
597.
0. F. Jessica, W. Corentin, D. Sylvestre, L. Christian and L. André,
RSC Adv., 2013,
3, 24936.
3
2
3
1. H. Ban, J. Gavrilyuk and C. F. Barbas III, J. Am. Chem. Soc.,
010, 132, 1523.
2. C. F. Barbas III, H. Ban and J. Gavrilyuk, Tyrosine
bioconjugation
WO2011079315, 2011.
3. H. Ban, M. Nagano, J. Gavrilyuk, W. Hakamata, T. Inokuma
and C. F. Barbas III, Bioconjugate Chem., 2013, 24, 520.
4. A. Nilo, M. Allan, B. Brogioni, D. Proietti, V. Cattaneo, S.
through
aqueous
Ene-like
reactions,
3
3
Crotti, S. Sokup, H. Zhai, I. Margarit, F. Berti, Q.-Y. Hu and R.
Adamo, Bioconjugate Chem., 2014, 25, 2105.
3
3
3
3
5. J. Gong, X. Ma and S. Wang, Appl. Catal., A, 2007, 316, 1.
6. A. A. G. Shaikh and S. Sivaram, Ind. Eng. Chem. Res., 1992,
1, 1167.
7. S. Fukuoka, R. Deguchi and M. Tojo, Process for producing
diaryl carbonate, US 5166393 A, 1992.
8. M. Goyal, R. Nagahata, J. i. Sugiyama, M. Asai, M. Ueda and
K. Takeuchi, Catal. Lett., 1998, 54, 29.
9. E. J. Pressman and J. A. King Jr, Method for making aromatic
carbonates, US5284964 A, 1994.
3
3
4
5
4
0. L. A. Paquette and R. F. Doehner Jr, J. Org. Chem., 1980, 45,
105.
1. K. Harada, R. Sugise, K. Kashiwagi and T. Matsuura, Process
for producing aryl carbamates, WO1998035936A1, 2000.
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 7
Green Chemistry
View Article Online
DOI: 10.1039/C7GC02027A
Table of Contents
The synthesis of urazoles in a one-pot, fast, high-yielding fashion without the use of isocyanates or
chloroformates is described.