3
reduction (Cu+2 to Cu+1) by Na Ascorbate exhibits a band in
the range of 300-400 nm (absorption at 331 nm, Figure 2)
which is attributed to a metal-to-ligand charge transfer
transition32.
Cu(I) complex with ligand. The Cu(I) catalyst first interact
with terminal alkyne to form a complex A and then reacts
with a second Cu(I) to generate a copper-acetylide complex
B. The complex thus formed react with an azide to produce
After developing the optimized reaction conditions, the
scope of this method further explored for the synthesis of
regioselective 1,4-disubstituted triazole via 1,3-dipolar
cycloadditions reaction. In this context, different derivatives
of 3-azidocoumarin (2a-e) (electron donating and
withdrawing group) and terminal alkyne (1a-c) were taken to
prepare the corresponding 1,4-disubstituted triazole under the
optimized reaction conditions (Table 2). To further widen the
scope of the study common substrates were also tested (Table
S2). Analysis of the results showed that most of the substrates
produced the expected triazole products with excellent
conversion. Attractive attributes of the present methodology
are that the click reaction is performed using water as a
versatile solvent at ambient temperature, devoid of unwanted
products, and recycling for five consecutive runs without
appreciable loss in yield % of the desired product.
complex
metallacycle D, which gets transformed into copper triazolide
after reductive elimination. Complex undergoes
protonolysis, providing the desired 1,4-disubstituted triazole
and regenerating the Cu(I).
Catalytic performance where toxic copper metal involved is
another side of concern from environmental concern which
can be sorted out by recycling of catalyst. Since CuSO4.
5H2O, L-phenylalanine, and Na ascorbate are all soluble in
H2O so it was thought useful to recycle the aqueous filtrate as
such without further addition of these reagents in consecutive
cycles. This theory led to positive results up to five runs.
Slight decrease in %yield of desired products (Figure S3)
may be due to loss of Cu(I) in water during workup process.
B
via intermolecular cyclization leads to
E
D
Absorbance and Fluorescence Analyses of 1,4-
disubstituted Triazoles (3a-o)
Conclusion
In conclusion, we have demonstrated a simple efficient and
versatile protocol for regioselective synthesis of a variety of 1,
4-disubstituted triazoles from diversely substituted azide and
various terminal alkyne under organic solution free conditions
using L-phenylalanine as an additive. Ligands plays a key role
and enforced hydrophobicity of water for the reaction. This
environmental friendly protocol opens-up new door for
achieving target compounds under mild conditions (less time,
ambient temperature (40 °C)) to tackle future synthetic
experiments and have a broad spectrum impact on biological
and material sciences as L-phenylalanine is cheap, easily
available, and biocompatible reagent.
Figure S4 a shows the absorption spectra of coumarin
triazoles (3a-o) (1 × 10-5 M in DMSO solution). Absorption at
around 300 nm is attributed to the π-π* transition, which
arises from the extension of conjugation by triazole ring
formation33. A bathochromic shift in absorption is observed in
the case of 6-bromo, 7-hydroxy, 5, 6-benzo and 8-methoxy
substituted triazoles, which consistent with previous reports8.
The bands around 410 nm in 7-hydroxy and 8-methoxy
derivatives, is assigned to the n-π* transition.
3-azidocoumarin derivatives (2a-e) are nonfluorescent
because of the presence of three electron-rich azido group at
the
Experimental
3rd position but after clicking with different terminal alkynes
(1a-c), fluorescence turn on is observed due to the formation
of five-membered triazole ring which extends the conjugation.
It is observed that the fluorescence intensity and position vary
by the presence of certain functional groups in the coumarin
scaffold. Triazoles containing the -OH functional group (3b,
3g, 3l) at the 7th position on the coumarin moiety produces a
strong emission band with maximum intensity due to the
expansion of conjugation by increasing its electron density. In
contrast, triazoles containing a 6-Br group (3c, 3h, 3m)
produce a weak emission band due to first the electron
withdrawing nature of bromine and second its heavy atom
effect34.
Typical procedure for the synthesis of 1,4-
disubstituted 1,2,3-Triazoles (3a-o)
3-azidocoumarin (1 mmol, 0.1871 g) and phenylacetylene
(1.1 mmol) were taken in a round bottom flask. Then
CuSO4·5H2O (2.49 mg, 1 mol%), sodium ascorbate (9.9 mg,
5 mol%), L-phenylalanine (2 mol%, 3.3 mg) in H2O (5.0 mL)
were added into it. The resultant mixture was ultrasonicated
for the time mentioned in Table 2 at 40 °C. Progress of
reaction was monitored by TLC. After completion of the
reaction, resultant mixture was extracted with ethyl acetate
(3x10 mL) and dried over Na2SO4 and concentrated under
reduced pressure. Removal of the solvent yielded a residue,
which was purified by a flash column chromatography over
silica gel (80-200 mesh) and eluted with n-Hexane:EtOAc
(3:1) to furnish desired products.
Mechanism
The plausible mechanism of the Cu(I)-catalyzed azide-alkyne
35, 36
cycloaddition reaction2,
for the formation of 3a is
proposed as depicted in Figure S2. The Cu(II) salt is first
reduced to Cu(I) by the reducing agent and then forming a