Hydrotrope promoted in situ azidonation followed by copper catalyzed regioselective synthesis of β-hydroxytriazoles

Article abstract of DOI:10.1007/s11164-017-2871-1

Abstract: The rapid method for the synthesis of organic azides was achieved by employing azide acceptors such as halides, epoxides and pseudohalides like diazonium salts and aryl boronic acids in hydrotropic media. In extension, the sequential multicomponent reaction of epoxides, azide and alkynes using copper catalysis has been discussed. The reaction proceeds via the in situ generation of azido-alcohol followed by synthesis of chiral β-hydroxytriazoles. This [3?+?2] cycloaddition reaction of azide and alkyne using copper catalysis serves as a green and efficient protocol in “Click Chemistry”. The nucleophilic addition of azide to epoxide and alkyne-azide cycloaddition is the two simultaneous regioselective click reactions observed in the proposed method. Graphical Abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-017-2871-1

Res Chem Intermed
DOI 10.1007/s11164-017-2871-1
Hydrotrope promoted in situ azidonation followed
by copper catalyzed regioselective synthesis of
b-hydroxytriazoles
1
1
Amol Patil
•
Rajashri Salunkhe
Received: 18 May 2016 / Accepted: 17 January 2017
Ó Springer Science+Business Media Dordrecht 2017
Abstract The rapid method for the synthesis of organic azides was achieved by
employing azide acceptors such as halides, epoxides and pseudohalides like diazonium
salts and aryl boronic acids in hydrotropic media. In extension, the sequential multi-
component reaction of epoxides, azide and alkynes using copper catalysis has been
discussed. The reaction proceeds via the in situ generation of azido-alcohol followed by
synthesis of chiral b-hydroxytriazoles. This [3 ? 2] cycloaddition reaction of azide and
alkyne using copper catalysis serves as a green and efficient protocol in ‘‘Click Chem-
istry’’. The nucleophilic addition of azide to epoxide and alkyne-azide cycloaddition is
the two simultaneous regioselective click reactions observed in the proposed method.
Graphical Abstract
Keywords Hydrotrope Á b-Hydroxytriazoles Á One-pot synthesis Á Click chemistry
&
Rajashri Salunkhe
rsschem1@gmail.com
1
Department of Chemistry, Shivaji University, Kolhapur, MS 416004, India
123

A. Patil, R. Salunkhe
Introduction
The principles of green chemistry include the designing and implementation of
novel sustainable methodologies which have minimal impact on the environment.
Owing to this, the areas of research have been defined by the scientific community
and a myriad of efforts has been undertaken for the same [1–4]. One of such
approach is to use water as a reaction medium. The barrier of solubilization of
organic reactants in aqueous medium is overcome by using green additives like
hydrotropes; which increases the water solubility dramatically up to 200-fold.
Hydrotropes are short chain amphiphiles structurally resembling surfactants but the
mode of action is based on critical aggregation concentration (cac) of hydrotrope
[
5–7]. The salient structural characteristic of hydrotropes includes an anionic group
and hydrophobic aromatic ring. The amphiphilic molecular structure of the
hydrotrope dramatically increases the solubility of sparingly soluble organic
molecules in water. Hydrotropic solutions precipitate the solute on dilution with
water, which permits the recovery of the hydrotropic solution for re-use.
Azides are the important intermediates in organic chemistry [8, 9]. They serve as
one of the most promising ways to introduce a nitrogen substituent of a triazole ring,
which is undeniably a crucial part in ‘‘Click Chemistry’’. They give excellent
cycloaddition reactions with alkynes due to the presence of a 1,3-dipole in the
structure. Several different methodologies have been reported for the synthesis of
organic azides; even though they are free from green efforts [10–13]. Therefore,
there is a need for environmentally friendly protocols for the synthesis of organic
azides and thus, now a day, the strategy of in situ synthesis of azides is employed.
Transition metal-catalysis constitutes a broad spectrum of research in organic
transformations. Among them, copper has greatly contributed to the development of
C–C, C–N, C–S and C–O bonds in coupling reactions [14–18]. Copper catalyzed
azide–alkyne cycloaddition (CuAAC) reactions have extensive applications in
triazole chemistry. Very robust, inexpensive, virtually quantitative and orthogonal
?
ligation properties of Cu made them successful catalytic systems in synthetic
?
chemistry. Cu catalysts require a reducing agent like ascorbic acid for activation.
2
?
Therefore, Cu catalysts, due to their high activity, found more applications than
?
Cu catalysts [19, 20].
2
The appliance of copper catalysts to other areas of organic chemistry was
pursued concurrently with the development of click reactions [21, 22]. The Huisgen
1
,3-dipolar cycloaddition of alkynes and azides is regarded as the ‘cream of the
crop’ of concerted reactions [23]. In the realm of ‘Click Chemistry’, a plethora of
methods has been developed a long time ago. Among them transition metals,
preferably copper catalysts, were found to be more effective. Depending upon
substrates, the azide-alkyne 1,3-dipolar cycloaddition reaction can be successful
using copper in solid phase systems, ruthenium, gold catalysis, and nano-catalysis
[
24, 25]. The immobilization of copper on high surface area supports allows the
stability and reactivity as well as recycling purpose of the catalyst [26]. Although a
reduced dicopper core showed high reactivity in the synthesis of 1,2,3-triazoles, this
left serious drawbacks like the use of hazardous organic solvents, high temperature
1
23

Hydrotrope promoted in situ azidonation followed by…
and a long reaction time [27]. In order to overcome the shortcomings, the bio-
catalytic system was used to synthesize chiral hydroxytriazoles [28]. Most of the
supported catalysts [29, 30] failed to give good regioselectivity of the reaction.
Several members of the 1,2,3-triazole family have been confirmed to be potent anti-
bacterial, anti-HIV and anti-allergic agents [31–35]. The triazole chemistry is
widely explored due to its numerous applications in the agrochemicals, dyes, and
pharmaceuticals [36, 37]. Moreover, these molecules act as nano-carriers in
biological systems [38] as well as having synthetic equivalence in peptides,
oligosaccharides and dendrimer synthesis [39–41].
As a part of our interest in the utility of hydrotropic solution for organic
transformations [42–44], we planned to design a green methodology for the
synthesis of organo-azides. For this purpose, we have used a variety of azide
acceptors such as alkyl halides, diazonium salts, boronic acids and epoxides. In
extension, one-pot syntheses of b-hydroxytriazoles were carried out from epoxides,
sodium azide and alkynes, via the in situ formation of 2-azidoalcohols and further
cycloaddition with alkynes.
Results and discussion
In an inception study, we investigated the template reaction of sodium azide and
benzyl chloride (1a) in aqueous medium. The reaction gave the corresponding
product benzyl azide (5a) in moderate yield (70%). Inspired by this positive result,
we sought to develop methodology by employing an aqueous hydrotropic solution
(
50% NaPTS) as reaction medium. To our delight, the hydrotropic solution gave
good conversion of reactants and offers product 5a in excellent yield (93%). After
this, we screened several hydrotropes like sodium xylene sulphonate, sodium
cumene sulphonate, sodium salisylate and sodium p-toluene sulphonate (NaPTS);
and tried to find out the best suitable reaction medium for the model reaction. We
observed that 50% aqueous solution of NaPTS was found to be the best reaction
medium among screened hydrotropes and offered good product yield at room
temperature (Table 1, entry 2). Decrease in concentration of NaPTS decreases the
product yield (Table 1, entries 5–6).
Thereafter, we subjected various substrates susceptible to the azidonation
reaction, and the outcomes are listed in Table 2. Alkyl halides (1) such as butyl
bromide, octyl bromide and ethyl bromide gave good yields (Table 2, entries 2–4).
Aryl azides were successfully synthesized by using diazonium salts (2) and boronic
acids (3). It was observed that both activated and deactivated diazonium compounds
as well as boronic acids were tolerated well to give azides in good yields (Table 2,
entries 5–12). The ring opening reaction of epoxides (4) with sodium azide occurs in
a regioselective manner. Cyclohexene oxide was treated with sodium azide to give
the corresponding trans-b-azido alcohol (7b) in good yield (Table 2, entry 14).
Styrene oxide gave exclusively primary alcohol (7a) instead of secondary alcohol
(
8). Here, the nucleophilic attack of azide was observed at sterically crowded
benzylic carbon instead of less substituted b-carbon. In this case the electronic
factor dominates over the steric factor (Table 2, entry 13). The striking feature of
123

A. Patil, R. Salunkhe
Table 1 Screening of hydrotropes
NaN3
Cl
N3
water/
hydrotropic solution
a
Entry
Solvent
Water
Time
min)
Yield
(%)
(
1
2
3
4
5
6
a
60
10
10
10
10
10
70
93
84
80
79
86
Sodium p-toluene sulphonate (50% NaPTS)
Sodium p-xylene sulphonate (50% NaXS)
Sodium cumene sulphonate (50% NaCS)
Sodium p-toluene sulphonate (10% NaPTS)
Sodium p-toluene sulphonate (30% NaPTS)
Yields by GC
this reaction was the introduction of the chiral center in the product molecule. The
azidonation of epichlorohydrin not only displaces chlorine but also opens the
epoxide ring offering a bis-azido compound (7c). Here, the reactivity of azide
towards the ring opening reaction and substitution reaction of chlorine remains
unchanged (Table 2, entry 15) (CAUTION: Ethyl azide and bis-azide are likely to
be explosive and dangerous if isolated).
Synthesis of b-hydroxy triazoles from epoxides
We next sought to exploit the principle of in situ generation of toxic organo-azides
for the synthesis of b-hydroxytriazoles from epoxides, sodium azide and alkynes.
For this purpose styrene oxide, sodium azide and phenyl acetylene were chosen as
reaction partners and the effect of various copper catalysts was examined (Table 3).
Initially, the model reaction of styrene oxide with sodium azide was carried out in
5
0% NaPTS solution for the generation of 1,2-azidol as discussed earlier (Table 2,
entry 13). Thereafter, phenyl acetylene was added to the same reaction mixture
without catalyst, which does not give product formation. Subsequently, the addition
of 10 mol % CuSO4 catalyst gave formation of product 10a with 40% yield
(
in click chemistry gave 87% product yield (Table 3, entry 3). Encouraged by this
Table 3, entry 2). Furthermore, CuSO ? Sodium ascorbate, a classical condition
4
?
2?
positive result, we switched over to screening of different Cu and Cu catalysts
without use of sodium ascorbate. Among tested copper sources, CuI showed high
activity for the cycloaddition reaction (Table 3, entry 10). NMR studies confirm the
formation of exclusively the product 10a instead of product 11 [26]. The calculated
atom economy for the model reaction is 92.33%.
With the promising results in hand, we explored the scope of various alkynes for
the sequential cycloaddition reaction, and the results are summarized in Table 4.
1
23

Hydrotrope promoted in situ azidonation followed by…
a
Table 2 Synthesis of azides from epoxides, halides and pseudo-halides
O
N3
R
1-3
X
OH
R
4
R
7
or
aq. NaPTS solution
RT
aq. NaPTS solution
RT
NaN3
R
N3
-6
OH
5
N3
R
X= Br, Cl, N BF , B(OH)
8
2
4
2
Entry
1
Reactants
Product
Time
Yield
b
(
min)
(%)
Cl
N3
10
93
1
a
5a
5b
5c
2
3
Br
N
3
10
10
90
89
1
b
Br
N
3
1
c
4
5
Br
N
5d
3
10
5
90
94
1
d
+
-
N3
N2 BF4
6
a
2
a
+
-
N3
N2 BF4
6
7
8
5
5
93
94
91
6
b
2
b
+
-
N3
N3
N2 BF4
MeO
MeO
6
c
2
c
+
-
N2 BF4
10
O N
2
O N
2
6
d
2
d
+
-
N3
N2 BF4
9
10
94
HOOC
HOOC
6
e
2
e
123

A. Patil, R. Salunkhe
Table 2 continued
Entry
Reactants
Product
Time
Yield
b
(
min)
(%)
B(OH)2
N3
1
0
1
15
86
83
3
a
6a
6b
B(OH)2
N3
1
15
3
b
O N
B(OH)2
O
O N
N3
2
2
1
2
3
25
20
80
91
3
f
6f
N3
1
OH
(
96:4)
4
a
7a
OH
O
O
1
4
15
20
95
4
b
N
3
7
b
OH
5c
93
Cl
N3
N3
1
4
c
7c
a
Reaction conditions: 1 mmol of alkyl halides/diazonium salt/boronic acid/epoxide and 1.2 mmol of
NaN in 5 mL 50% NaPTS
Yields by GC. Value in parenthesis refers to isomers formed determined by GC analysis
3
b
c
3
Reaction condition: 1 mmol of epichlorohydrin, and 2.4 mmol of NaN in 5 mL 50% NaPTS
Aromatic alkyne like 4-methyl phenylacetylene offers excellent yield of the
corresponding b-hydroxytriazole (Table 4, entry 2). Moreover, aliphatic alkynes
tolerated well and gave corresponding triazoles in high yield. Two simultaneous
regioselectivities were observed for the ring opening reaction of epoxide with
sodium azide and in the 1,3-cycloaddition reaction of in situ generated azide with
alkynes. Among 1,4- and 1,5-disubstituted triazoles, the 1,4-addition product
1
predominates. H-NMR spectrum confirmed the formation of chiral product and the
methylene protons adjacent to chiral carbon became diastereotopic protons.
In the light of the results obtained, we extended this methodology by subjecting
cyclohexene oxide and epichlorohydrin for the azidonation and subsequent
cycloaddition reaction with alkynes. Azidonation of cyclohexene oxide follows a
2
S
path and gave exclusively trans isomers, which is confirmed by coupling
N
1
constant measurement in H-NMR spectroscopy. The amount of trans isomer
formed of product 2-(4-phenyl-1H-1,2,3-triazol-1-yl)cyclohexanol over cis-isomer
1
in the ratio 89:11. D O exchange analysis in H-NMR confirmed the formation of
2
1
23

Hydrotrope promoted in situ azidonation followed by…
a
Table 3 Optimization of reaction conditions for the synthesis of b-hydroxytriazole
OH
N
N
O
N
10a
Catalyst
+
N
N
+
NaN3
+
5
0 % NaPTS
N
OH
rt
9a
4a
11
b
Entry
Catalyst (mol %)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
None
24
4
n r
40
70
35
38
41
48
88
80
92
88
92
91
Cu(II) sulfate (10)
CuSO
4
? Na-ascorbate
3.5
4.5
4.5
4
Cu(II) bromide (10)
Cu(II) chloride (10)
Cu(II) iodide (10)
Cu(I) acetate (10)
Cu(I) bromide (10)
Cu(I) chloride (10)
Cu(I) iodide (10)
Cu(I) iodide (5)
6
4
4
1
1
1
1
a
0
1
2
3
3
3
Cu(I) iodide (15)
Cu(I) iodide (20)
3
3
All reactions were run with epoxide (1 mmol), sodium azide (1.2 mmol), phenyl acetylene (1 mmol)
and catalyst in 5 mL 50% NaPTS solution at room temperature
b
Isolated yields
n r: no reaction
the hydroxy derivative. Furthermore, epichlorohydrin gave structurally complex bis-
triazoles confirming the reactivity of azide towards both nucleophilic displacements
of chlorine as well as in ring opening of epoxide. Because of the symmetrical
arrangement of the molecule, chirality is not observed for the product which is
1
confirmed by H-NMR spectroscopy.
Experimental
Epoxides, alkyl halides, boronic acids, alkynes and sodium p-toluene sulphonate
were obtained from Alfa Aesar and Sigma Aldrich Company and used as received.
Diazonium salts were prepared following the literature procedure [45]. Infrared
spectra were obtained on a Perkin Elmer FT-IR spectrometer. NMR spectra were
1
13
recorded on a Bruker AC (300 MHz for H NMR and 75 MHz for C NMR)
spectrometer using CDCl and/or DMSO-d as solvent and tetramethylsilane (TMS)
3
6
123

A. Patil, R. Salunkhe
a
Table 4 CuI catalyzed synthesis of b-hydroxytriazoles from epoxides
OH R2
R1
O
CuI
+
NaN3
+
R3
N
R1
R2
50 % NaPTS
rt
N
4
9
R3
10
N
b
Entry
1
Epoxide
Alkyne
Product
Time Yield
(h)
(%)
c
(
Ratio)
OH
N
3
92
N
N
9
a
(
(
(
(
(
96:4)
1
0a
OH
2
3
4
5
6
N
N
2.5
93
N
9
b
96:4)
1
0b
OH
O
N
N
4
83
O
H
N
OH
94:6)
9
c
4
a
1
0c
OH
N
N
4.5
81
Br
N
Br
94:6)
9
d
1
0d
OH
N
N
4
80
Et N
2
N
NEt2
96:4)
9
e
1
0e
OH
N
N
3.5
90
N
9
f
(96:4)
1
0f
1
23

Hydrotrope promoted in situ azidonation followed by…
Table 4 continued
b
Entry
Epoxide
Alkyne
Product
Time Yield
(h)
(%)
c
(
Ratio)
OH
N
7
2.5
2.5
3
88
N
N
9
a
1
0g
OH
O
8
9
N
N
90
86
N
4
b
9b
1
0h
OH
N
N
N
9
f
1
0i
N
N
N
N
N
N
OH
N
N
1
1
1
0
1
2
4
82
80
82
9
a
1
0j
N
N
OH
N
N
O
Cl
4.5
4.5
9
b
4
c
10k
OH
N
N
N
N
N
N
9
f
1
0l
a
All reaction were run with epoxide (1 mmol), sodium azide (1.2 mmol), acetylene (1 mmol) and CuI
10 mol %) in 5 ml 50% NaPTS solution at room temperature
(
b
Isolated yields
c
Ratio of 1,4: 1,5 disubstituted triazole
as an internal standard. Melting points were determined with DBK melting point
apparatus and are uncorrected. Elemental analyses were performed on the EURO
EA3000 vector model. GC and MS were recorded on a Shimadzu QP2010.
123

A. Patil, R. Salunkhe
Experimental procedure for the synthesis of organic azides
Sodium azide (1.2 mmol) and alkyl halide/diazonium salt/aryl boronic acid/epoxide
1 mmol) were stirred in 5 mL 50% aq. NaPTS solution at room temperature. The
(
progress of reaction was monitored by gas chromatography until total conversion of
starting materials. The reaction mixture was extracted with EtOAc (3 9 5 mL), the
organic layer was dried over anhydrous Na SO , and the solvent was removed in
2
4
vacuo to afford corresponding organic azide.
Experimental procedure for the synthesis of b-hydroxytriazoles
Epoxide (1 mmol), sodium azide (1.2 mmol) and the alkyne (1 mmol) were added
to a suspension of CuI (10 mol %) in 50% aq. NaPTS solution. The reaction
mixture was stirred at room temperature for an appropriate time, and the progress of
the reaction was monitored by TLC until total conversion of starting materials. The
reaction mixture was extracted with EtOAc (3 9 5 mL); the organic layer was dried
over anhydrous Na SO , and the solvent was removed in vacuo. The resulting
2
4
residue was purified by column chromatography to afford corresponding b-
hydroxytriazole.
Spectral data of representative compounds
1
1
-(Azidomethyl)benzene (5a) Viscous oil; H NMR (300 MHz, CDCl , d ppm):
3
1
.40 (s, 2H), 7.29 (d, J = 8.7 Hz, 3H), 7.82 (d, J = 8.1 Hz, 2 H); C NMR
3
2
(
Calcd for C H N : C, 63.14; H, 5.30; N, 31.56. Found: C, 63.26; H, 5.27; N, 31.47.
75 MHz, CDCl , d ppm): 21.5 (CH ), 127.5, 129.8, 139.0, 143.9 (C–CH ); Anal.
3
2
2
7
7 3
MS (m/z): 133 (M?).
-
1
4
-Azidobenzoic acid (6e) Pale yellow solid; mp = 182–184 °C; IR (KBr, cm ):
1
2404–3412 (br, COOH), 2108 (N ), 1681 (C=O); H NMR (300 MHz, DMSO-d6, d
ppm): 7.01 (d, J = 6.6 Hz, 2H), 7.93 (d, J = 8.4 Hz, 2H), Peak for acidic proton
3
1
3
(
COOH) was not observed in PMR spectrum; C NMR (75 MHz, DMSO-d6, d ppm):
18.8, 127.6, 131.5, 144.2 (C–N ), 167.2 (C=O); Anal. Calcd for C H N O : C, 51.54;
H, 3.09; N, 25.76. Found: C, 51.42; H, 3.15; N, 25.67. MS (m/z): 163 (M?).
1
3
7 5 3 2
-
1
2
-Azidocyclohexanol (7b) White solid, mp = 121–123 °C; IR (KBr, cm ): 3409
1
(br, O–H), 2928 (C–H), 2105 (N ); H NMR (300 MHz, CDCl , d ppm): 0.92 (t,
J = 7.2 Hz, 2H), 1.37 (q, J = 7.2 Hz, 2H), 1.63 (s, 1H), 2.69 (d, J = 9.9 Hz, 1H), 3.41
3
3
1
3
(
ppm): 13.7, 22.2, 25.1, 31.3, 53.9 (C–N ), 68.5 (C–OH); Anal. Calcd for C H N O: C,
d, J = 7.2 Hz, 1H), 4.40–4.58 (m, 2H), 7.59 (s, 1H); C NMR (75 MHz, CDCl , d
3
3
6 11 3
5
1.05; H, 7.85; N, 29.77. Found: C, 50.96; H, 7.90; N, 29.73. MS (m/z): 141 (M?).
2
1
1
-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanol (10a) White solid, mp = 133–
-1
35 °C; IR (KBr, cm ): 3378 (br, O–H), 3093 (=C–H), 2929 (C–H), 2100 (N=N–N),
1
604 (C=C); H NMR (300 MHz, DMSO-d6, d ppm): 4.05 (dd, J = 11.7, 4.5 Hz,
1
23

Hydrotrope promoted in situ azidonation followed by…
1
H), 4.34 (t, J = 9.3 Hz, 1H), 5.80 (q, J = 4.5 Hz, 1H), 7.27–7.41 (m, 9H), 7.83 (d,
1
3
J = 7.5 Hz, 2H), 8.65 (s, 1H). C NMR (75 MHz, DMSO-d6, d ppm): 68.4 (CH2),
7
1
5
1.5 (CH), 125.5, 130.3, 132.0, 132.2, 132.8, 133.2, 133.6, 133.7, 134.0, 135.5, 141.8,
51.6. Anal. Calcd for C H N O: C, 72.43; H, 5.70; N, 15.84. Found: C, 72.56; H,
.75; N, 15.74. MS (m/z): 265 (M?).
1
6 15 3
2
-Phenyl-2-(4-p-tolyl-1H-1,2,3-triazol-1-yl)ethanol (10b) White solid, mp =
-1
1
51–153 °C; IR (KBr, cm ): 3404 (br, O–H), 3094 (=C–H), 2930 (C–H), 2100
1
(N=N–N), 1621 (C=C); H NMR (300 MHz, CDCl , d ppm): 2.38 (s, 3H), 4.24 (d,
J = 11.1 Hz, 1H), 4.62–4.70 (m, 1H), 5.69 (d, J = 4.8 Hz, 1H), 7.21–7.41 (m, 8H),
3
1
3
7
.69 (d, J = 7.5 Hz, 3H); C NMR (75 MHz, CDCl , d ppm): 21.3 (CH ), 65.2
3
3
(CH ), 67.3 (CH), 125.6, 127.1, 128.7, 128.9, 129.0, 129.2, 129.5, 136.0, 138.2; Anal.
Calcd for C H N O: C, 73.10; H, 6.13; N, 15.04. Found: C, 73.46; H, 5.95; N,
2
1
7 17 3
1
5.18. MS (m/z): 279 (M?).
2
-(4-Phenyl-1H-1,2,3-triazol-1-yl)cyclohexanol (10g) Pale yellow solid, mp =
1
1
70–172 °C; H NMR (300 MHz, DMSO d6, d ppm): 1.37–2.00 (m, 8H), 3.73–3.83
(
m, 1H), 4.19–4.28 (m, 1H), 5.02 (d, 1H, J = 5.7 Hz, OH exchangeable with D O),
2
7
.32 (t, J = 7.5 Hz,, 1H), 7.44 (t, J = 7.5 Hz, 2H), 7.83–7.86 (m, 2H), 8.59 (s, 1H);
C NMR (75 MHz, DMSO d6, d ppm): 24.3, 24.9, 32.4, 35.2, 66.4 (CH–N), 71.8
1
3
(
CH–OH), 121.0, 125.4, 128.0, 129.3, 131.6, 146.1; Anal. Calcd for C H N O: C,
14 17 3
6
9.11; H, 7.04; N, 17.27. Found: C, 69.26; H, 6.93; N, 17.20. MS (m/z): 243 (M?).
,3-Bis-(4-phenyl-1H-1,2,3-triazol-1-yl)propan-2-ol (10j) White solid, mp =
1
2
5
1
31–233 °C; H NMR (300 MHz, DMSO-d6, d ppm): 4.44 (s, 3H), 4.60 (s, 2H),
.81 (s, 1H, OH), 7.30–7.39 (m, 6H), 7.83 (s, 4H), 8.46 (s, 2H). C NMR (75 MHz,
1
3
DMSO-d6, d ppm): 53.4 (CH ), 68.6 (CH–OH), 122.3, 125.5, 128.0, 128.9, 130.9,
2
1
46.9. Anal. Calcd for C H N O: C, 65.88; H, 5.24; N, 24.26. Found: C, 65.79; H,
19 18 6
5
.20; N, 24.32. MS (m/z): 346 (M?).
1
,3-Bis-(4-p-tolyl-1H-1,2,3-triazol-1-yl)propan-2-ol (10k) White solid, mp =
-
1
2
42–244 °C; IR (KBr, cm ): 3348 (br, O–H), 3108 (=C–H), 2920 (C–H), 2100
1
(
(
(
N=N–N), 1634 (C=C); H NMR (300 MHz, DMSO d6, d ppm): 2.30 (s, 6H), 4.37
d, J = 13.2 Hz, 3H), 4.52 (s, 2H), 4.79 (s, 1H, OH exchangeable with D O), 7.15
3
d, J = 6 Hz, 4H), 7.65 (d, J = 6 Hz, 4H), 8.16 (s, 2H); C NMR (75 MHz,
2
1
DMSO d6, d ppm): 21.3 (CH ), 53.3 (CH ), 68.6 (CH–OH), 121.7, 125.4, 128.0,
3
2
129.5, 137.5, 147.0; Anal. Calcd for C H N O: C, 67.36; H, 5.92; N, 22.44.
21 22 6
Found: C, 67.34; H, 5.99; N, 22.38. MS (m/z): 374 (M?).
Conclusions
We have developed an efficient method for the synthesis of organic azides using
simple starting materials. The method was effectively extended for three component
sequential MCR involving epoxides, azide and alkynes leading to the generation of
123

A. Patil, R. Salunkhe
b-hydroxytriazoles based on the click chemistry approach. The reaction proceeds
via the in situ generation of b-hydroxyazide, which undergoes smooth [3 ? 2]
cycloaddition reaction with terminal alkynes with high atom economy. The
additive- and base-free approach follows two simultaneous ‘clicks’ employing
hydrotropic solutions with their green characters. We are privileged to claim that the
developed method is a good alternative to the complex catalytic as well as solvent-
systems in organic synthesis in the near future.
Acknowledgements The authors thank UGC, New Delhi for financial assistance [F. No. 41-310/2012
(SR)].
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