Synthesis of polymerizable vinyltriazoles: Development of an optimized one-pot strategy starting from 4-bromobutyne

Article abstract of DOI:10.1039/c3gc37066f

The development and implementation of a safe and scalable process for the preparation of isomeric vinyl-1,2,3-triazoles under mild conditions are described. Key aspects of the route reside in a one-pot click-elimination procedure in aqueous media leading to simple work-up and purification steps with increased overall yields.

Full text of DOI:10.1039/c3gc37066f

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Synthesis of polymerizable vinyltriazoles: development
of an optimized one-pot strategy starting from
4-bromobutyne†
Cite this: Green Chem., 2013, 15, 1138
Received 18th December 2012,
Accepted 21st February 2013
DOI: 10.1039/c3gc37066f
A. Praud, O. Bootzeek and Y. Blache*
www.rsc.org/greenchem
The development and implementation of a safe and scalable available alkynes, yields remain poor, in particular for the
process for the preparation of isomeric vinyl-1,2,3-triazoles under 5-vinyl-(1H)-1,2,3-triazoles (Fig. 1).
mild conditions are described. Key aspects of the route reside in a
As a part of our studies aimed at the elaboration of environ-
one-pot click-elimination procedure in aqueous media leading to mentally friendly antifouling coatings, here we are interested
simple work-up and purification steps with increased overall in the preparation of natural product-derived (1H)-1,2,3-tria-
yields.
zoles possessing potent and non-toxic antibiofilm properties
in view of the preparation of original polymers derived from
these bioactive heterocycles.7–9 For this purpose, low price,
easily accessible large amounts of polymerizable bio-inspired
triazole monomers are needed in a “green” approach in order
to assess the most ecofriendly route to the final coatings.
Considering these elements, and in order to improve the
preparation of such monomers, we report here an original syn-
thesis of isomeric substituted 5-vinyl-(1H)-1,2,3-triazole and
4-vinyl-(1H)-1,2,3-triazole monomers that would be amenable
to scale up, by means of a simple one-pot procedure from the
commercially available 4-bromobutyne (Fig. 2).
In practice, we postulated that an elimination process from
the intermediary bromo derivatives should be favored since
the resulting vinyl compounds are conjugated with the triazolic
ring. The first step of this work was to validate the concept of
this one pot click-elimination process. For this purpose, com-
pound 2 was prepared by reacting 4-bromobutyne and azide 19
in EtOH/H2O in the presence of CuSO4·5H2O as a catalyst.
Without further addition of base (entry 1), 2 was isolated in
95% yield and characterized by 1H-NMR, 13C-NMR and mass
spectra. For the elimination step, we postulated that the use of
sodium hydroxide should permit the simplest work-up process
through a simple extraction with ethyl acetate (Scheme 1).
Parameters of temperature, nature and concentration of
sodium hydroxide were examined (Table 1) under different
entries. The appropriate azide (0.4 mmol) was added to a solu-
tion of H2O/EtOH (2 mL/2 mL) containing CuSO4–5H2O
(0.01 eq.), 4-bromobutyne (1.5 eq.) and sodium ascorbate
(0.03 eq.). The resulting mixture was stirred for 12 hours at RT.
The base (appropriate concentration, see entries 2–14) was
added and the resulting mixture was stirred at the appropriate
temperature for 8 hours. The resulting solution was extracted
3 times with ethylacetate. The organic layers were then dried
4-Vinyl and 5-vinyl-(1H)-1,2,3-triazoles represent interesting
classes of heterocyclic compounds and have received increas-
ing attention in the field of polymer sciences, since it has been
shown that 4-vinyl and 5-vinyl polymerizable monomers are
valuable building blocks for the construction of well-defined
macromolecules.1–3 However, until recently, preparation of
such monomers occurred only through multistep procedures,
and the remaining challenge of this class of monomers resides
in a simple and low-cost synthetic accessibility to large
amounts with high degrees of functionalization. Three main
multistep approaches using catalyzed azide–alkyne cycloaddi-
tions have been developed to date. The “Wittig approach” is
based on a three-step procedure using propargyl alcohol as a
starting material, which is converted to an aldehyde as a key
intermediary for the Wittig step, allowing obtention of the
vinyl derivatives in 60–75% yield.4 The “vinylacetylene
approach”, in which the starting materials are trimethylsilyl-
acetylene and vinyl bromide, is a two-step methodology where
the crucial intermediary trimethylsilylvinylacetylene was
obtained in 67% yield and the desired 4-vinyltriazole in the
range of 44% from commercially available vinyl bromide. In
addition, this methodology could not be applied to 5-vinyltria-
zoles.3,5 In the “two steps click-elimination approach”, the
starting material is but-3-yn-1-ol, and the vinyl group is intro-
duced by means of an elimination process from a mesylated
intermediary leading to 4-vinyl and 5-vinyl derivatives.6
However, when regarding the total yields from commercially
Université de Toulon, MAPIEM, EA 4323, 83957 La Garde, France.
E-mail: blache@univ-tln.fr
†Electronic supplementary information (ESI) available: Experimental procedure
and structural data. See DOI: 10.1039/c3gc37066f
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Scheme 1 Preparation of 2 and/or 3 through the one-pot “click-elimination”
process.
Table 1 Effect of reaction conditions on the preparation of 3 through the one-
pot “click-elimination” process
Compound 3
yield (%)
Compound 2
yield (%)
Entrya
Base
Temp.
1
2
3
4
5
6
7
8
—
NaOH
25 °C
25 °C
45 °C
60 °C
100 °C
0
60
82
70
75
0
95
30
Traces
—
—
85
80
—
—
5 eq.
NaOH
DBU
1 eq.
2.5 eq.
7 eq.
10 eq.
2.0 eq.
5 eq.
10 eq.
5 eq.
5
45 °C
92
99
53
66
74
11
84
9
10
11
12
13
14
25
45 °C
Traces
Traces
67
NEt3
LiOH
45 °C
45 °C
5 eq.
—
a All reactions were conducted with 1.5 eq. of bromobutyne and yields
were calculated from 1 eq. of azide.
over Na2SO4 and concentrated in vacuo. Purification by flash
chromatography (silica gel (Si60 15–40 μm), n-hexane/ethyl
acetate (70/30)) gave the vinyl derivatives. In entries 2–5, the
effect of temperature was first attempted using five equivalents
of a base. At room temperature (25 °C), the conversion of com-
pound 2 was incomplete and the desired vinyl derivative 310
was obtained in 60% yield admixed with the bromo-derivative
2 (30% yield). At a temperature of 45 °C a good conversion of
the intermediary brominated species to the vinyl derivative
was observed (82% from azide). Augmentation to 60 °C and
100 °C led to lower yields (70 and 75% respectively), and no
bromoderivative 3 was recovered, indicating a probable degra-
dation of compounds at these high temperatures. Finally, the
temperature of 45 °C was selected for the following experi-
ments. In entries 6–9, we examined variations of the base con-
centration (1.0, 2.5, 7.0, and 10 equivalents of NaOH). The
conversion rate was very low with 1 and 2.5 eq. and a conver-
sion of 92% and 99% was observed with higher concen-
trations. From these experiments, the good compromise
finally appeared to be a temperature of 45 °C, and the concen-
tration of 5 equivalents of sodium hydroxide should be rec-
ommended to ensure mild conditions of the elimination
Fig. 1 Wittig, vinyl acetylene and two-steps click elimination processes.
Fig. 2 Proposed one-pot two steps strategy for the preparation of 5-vinyl and
4-vinyl targeted triazoles.
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process. In entries 10–12, the nature of the base was investi- improvement of the elimination step was found. Finally, the
gated by using 2.0, 5.0, and 10 equivalents of 1,8-diazabicyclo- use of triethylamine (entry 13) did not allow better yields (11%
[5,4,0]undec-7-ene (DBU) which was the base used in the pre- of conversion), while replacement of sodium hydroxide by
viously described two-step click-elimination approach.6 No lithium hydroxide (entry 14) led to a similar result (84%).
The scope of the reaction was tested with two other azido
compounds showing efficiency of the procedure with yields up
to 85% for 4 and 5 (Table 2).
Table 2 Preparation of 4-vinyl-(1H)-1,2,3-triazoles
Then, we were curious to apply our methodology to the syn-
thesis of the isomeric 5-vinyl-(1H)-1,2,3-triazoles. In this case
too, treatment of bromobutyne in dioxane with the appropriate
azide in the presence of catalytic amounts of Cp*RuCl(PPh3)2
followed by basic treatment led to the formation of the desired
5-vinyl derivative 4. Reactions were conducted at 45 °C using a
concentration of 5 eq. of base. DBU and sodium hydroxide
Azide
Triazole
Yielda (%)
88
ref. 8
ref. 6
86
were tested (Table 3).
A solution of appropriate azide
(0.4 mmol, purity monitored by 1H-NMR), alkyne (1 eq.) in
dioxane (0.5 mL) was added under argon to 3.5 mL of dioxane
containing a catalytic amount of Cp*RuCl(PPh3)2 (0.02 eq.).
The resulting mixture was stirred for 12 hours at 60 °C under
argon atmosphere. After cooling, an appropriate base (NaOH,
entry 3 or DBU, entry 11) was added and the resulting mixture
was stirred at 45 °C for 8 hours. The resulting solution was
extracted 3 times with ethylacetate. The organic layers were
then dried over Na2SO4 and concentrated in vacuo. Purification
by flash chromatography (silica gel (Si60 15–40 μm), n-hexane/
ethyl acetate (70/30)) gave the vinyl derivatives. Results were
unambiguous: using NaOH, compound 6 was obtained in 97%
yield, while the use of DBU led to compound 6 in only 56%
yield. For the two other derivatives 7 and 8, despite the fact
that yields remain in the same scale as in the previously
described method,6 the main interest resides in the one-pot
procedure which affords a simpler process.
a Conditions of entry 3 (5 eq. of NaOH), yield calculated from azide.
Table 3 Preparation of 5-vinyl-(1H)-1,2,3-triazoles
Azide
Triazole
Yielda,b (%)
97a
56b
All these results indicate that this new process affords a
more sustainable synthetic route to 4-vinyltriazoles and 5-vinyl-
triazoles and should have a great interest for scale-up develop-
ment in a “greener” concept. In this way, Table 4 summarizes
the improvement of the preparation of such monomers in
terms of pot, atom and step economy (PASE: a concept which
combines as many transformations as possible into a single
reaction vessel, without need for work-up and isolation of
intermediate compounds).11 Clearly, the three previously
described methods implement organic solvents, additional
carbon sources, catalysts, and finally organic bases to proceed
with the elimination step. In the present methodology, the use
62a
NTc
NT
59a
a Conditions of entry 3 (5 eq. of NaOH), yield calculated from azide.
b Conditions of entry 11 (5 eq. of DBU), yield calculated from azide.
c NT: not tested.
of the combination H2O–NaOH offers
a
pot economy
Table 4 Comparison of the different methods showing the green process of the present methodology
Starting materiala
Solventsb
Reactantsb
Potsc
Stepsc
Applicability
Propargyl alcohol
Trimethylsilylacetylene
But-3-yn-1-ol
DMSO, THF
THF
MeP+(PPh3)2, Br−, IBX, NaH
TBAF, PdCl2(PPh)3, vinylbromide, NEt3
CH3SO2Cl, DBU, NaI
3
2
3
1
3
2
4
2
4-Vinyl
4-Vinyl
4 and 5-Vinyl
4 and 5-Vinyl
DMFd
4-Bromobutyne
H2O
NaOHe
a Carbon source of triazole ring. b The click step is not included since the reactants are the same for all methods. c Whole process including the
click step. d Alternatively DME. e Alternatively DBU.
1140 | Green Chem., 2013, 15, 1138–1141
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(reduction of solvents used in synthesis and work-up) and a
step economy is realized (reduction of the amount of reagents
by reducing the number of steps). The atom economy (FW
product/FW of all reagents used) has been increased on
average by 30% to 83% (31% to 83% when compared to the
previously described two-steps click-elimination process and
the present process; only NaOH is used without an additional
source of carbon and/or other elements).
In conclusion, we have described a new process for easy
preparation of 4-vinyl and 5-vinyltriazoles from 4-bromo-
butyne. Interest in the process focused on the one-pot “click-
elimination” methodology. This procedure provides a new sig-
nificant “greening” synthesis of vinyltriazoles with improve-
ments in terms of yields, and operability when compared to
previous methodologies. In particular, the use of a mineral
base leads to an easier work-up process for further purifi-
cations and permits a facile scale-up of the methodology for a
large diversity of azido compounds, while an organic base
such as DBU remains usable, especially for substrates that are
sensitive to hard mineral bases.
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