Tetrahedron Letters
Tandem synthesis of highly functionalized N-phosphorylated
sulfonamido-pyrazolone derivatives
⇑
Issa Yavari , Manijeh Nematpour
Department of Chemistry, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction between ketenimine intermediates, generated from terminal alkynes and sulfonyl azides,
diisopropyl azodicarboxylate, and trimethyl or triphenyl phosphite, in N,N-dimethylformamide at room
temperature, affords highly functionalized N-phosphorylated sulfonamido-pyrazolone derivatives in
moderate to good yields.
Received 4 March 2013
Revised 25 June 2013
Accepted 5 July 2013
Available online 13 July 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
N-Phosphorylated pyrazolones
Diisopropyl azodicarboxylate
Sulfonyl azides
Terminal alkynes
Tandem reactions
Heterocyclic compounds occur widely in Nature and are essen-
tial to life. Nitrogen heterocycles are abundant existing in many
natural products such as vitamins, hormones, antibiotics, and alka-
loids.1 The pyrazole ring is a prominent structural motif found in
numerous pharmaceutically active compounds.2 Much effort has
been devoted to prepare this structural unit and a general method
for its synthesis consists of the condensation of hydrazines with
various 1,3-dicarbonyl compounds.3–5 We have previously re-
ported convenient methods for the preparation of functionalized
pyrazole derivatives.6–9 As an extension of these studies, we report
the preparation of highly functionalized N-phosphorylated sulfon-
amido-pyrazolone derivatives.10
Among several methods leading to the generation of keteni-
mines, the copper-catalyzed azide-alkyne cycloaddition reaction
has attracted significant attention because of its mild formation
conditions.11,12 The ketenimine intermediates generated in this
reaction could be trapped by various nucleophiles.13 In this way,
various heterocyclic frameworks were obtained.14–18
In our initial investigations, phenylacetylene (1a), p-toluenesul-
fonyl azide (2a), trimethyl phosphite (4a), and diisopropyl azodi-
carboxylate (5) were selected as the model substrates. Several
catalysts including CuI, CuBr, CuCl, Cu2O, and copper powder were
tested with CuI giving the best results. Among the several solvents
screened, N,N-dimethylformamide (DMF) proved to be the best.
When the reaction was performed in DMF at room temperature
for five hours, it was found that the phosphorylated pyrazolone
6a was obtained in 87% yield (Table 1). Replacement of phosphites
4 with triphenylphosphine led to a complex reaction mixture, and
we were unable to isolate any pyrazolone 6 from this mixture.
Thus, the optimized reaction conditions used were CuI
(10 mol %), alkyne 1 (1 mmol), sulfonyl azide 2 (1.2 mmol), phos-
phite 4 (1 mmol), and azodicarboxylate 5 (1 mmol), in DMF at
room temperature (Scheme 1).
Phenylacetylene readily participates in the coupling to furnish
the corresponding N-phosphorylated sulfonamido-pyrazole deriv-
atives 6 in good yields (Scheme 1). Aliphatic acetylenes served as
Table 1
Optimization of the reaction conditions for the preparation of pyrazolone 6a from
phenylacetylene (1a), p-toluenesulfonyl azide (2a), trimethyl phosphite (4), diiso-
propyl azodicarboxylate (5), and catalyst (10 mol %)
Entry
Catalyst
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Cu2O
Cu2O
Cu2O
CuCl
CuCl
CuCl
CuI
CuI
CuI
CuI
CuBr
CuBr
CuBr
Cu
Cu
Cu
DMF
MeCN
THF
MeCN
THF
DMF
DMF
MeCN
THF
CH2Cl2
DMF
MeCN
THF
8
8
8
8
8
8
5
5
8
8
5
5
8
8
8
8
20
15
15
25
20
45
87
64
57
25
80
55
50
—
DMF
MeCN
THF
—
—
⇑
Corresponding author. Tel.: +98 21 82883465; fax: +98 21 82883455.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.