Oxidation of dihydrazones of diaryl α-diketones to diarylacetylenes using sodium periodate

Article abstract of DOI:10.1246/cl.2010.1279

Oxidation of dihydrazones of α-diketones to acetylene was investigated by using sodium periodate. Further, the described method is also found to be suitable for deprotection of monohydrazones of aldehydes and ketones. The process is mild, efficient, and applicable to both electron-withdrawing and -donating substituents to give good to excellent yields.

Full text of DOI:10.1246/cl.2010.1279

doi:10.1246/cl.2010.1279
Published on the web November 6, 2010
1279
Oxidation of Dihydrazones of Diaryl ¡-Diketones to Diarylacetylenes
Using Sodium Periodate
Balaram S. Takale and Vikas N. Telvekar*
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology,
Matunga, Mumbai 400 019, India
(Received September 22, 2010; CL-100811; E-mail: vn.telvekar@ictmumbai.edu.in)
Oxidation of dihydrazones of ¡-diketones to acetylene was
NNH2
R2
investigated by using sodium periodate. Further, the described
method is also found to be suitable for deprotection of
monohydrazones of aldehydes and ketones. The process is
mild, efficient, and applicable to both electron-withdrawing and
-donating substituents to give good to excellent yields.
NaIO4, Water:EtOAc
room temperature
R1
R1
R2
NNH2
1a−13a
1b−13b
Scheme 1. Benzil dihydrazone oxidation to diphenylacetylene
using NaIO4.
Diarylacetylenes are an important class of organic com-
pounds due to their incorporation in various organic reactions1
as well as wide applications in bioactive molecules,2 natural
products3 and organometallics.4 The most common method for
preparation of diarylacetylene is the Sonogashira coupling
which includes coupling of phenylacetylene with aryl halide
by using metal catalysts like Pd with various ligands,5 Cu,6 and
ZnCl2.7 Numerous palladium complexes have been employed to
catalyze this reaction in recent years, but the limited reusability
of expensive Pd complexes has been a serious problem in
industrial scale. Moreover, the reactions are generally air-
sensitive and also require highly oxophilic phosphine ligands,
while when copper catalysts are used, formation of the Glaser-
type product8 and the explosive nature of copper acetylide
formed in the reaction are of great concern. In addition, amines
such as piperidine, diethylamine, and triethylamine are required
in most Sonogashira reactions and they add to the environmental
burden. Recently, Abele and co-workers reported acetylene-free
coupling of aryl halide with 1-bromo-2-chloroethane, however
the reaction suffers from drawbacks such as formation of
homocoupled product and low yield in the case of heterocyclic
substrates.9 Other methods for synthesis of diphenylacetylene
includes reaction of dihydrazone of benzil with HgO,10 nickel
complexes,11 copper catalysts,12 aryl iodine(III) complexes,13
and alkyl diarylbismuthinates.14 In all these syntheses, there are
detracting experimental limitations, including the use of toxic
metal catalysts, high temperature, or long reaction time, or
organic reagents like aryl iodine(III) salt where an equivalent
amount of aryl iodide is formed as side product which is difficult
to separate from desired product, and by considering all above
facts there is still need to develop a mild, economical, and
efficient method for synthesis of diarylacetylene.
Table 1. Oxidation of dihydrazone to diphenylacetylene
Yield of b Time
Compound R1
R2
/%a
/min
1
2
Ph
Ph
87
90
60
55
4-MeC6H4
4-MeC6H4
3
4-OMeC6H4 4-OMeC6H4
89
60
4
5
4-BrC6H4
4-FC6H4
4-BrC6H4
4-FC6H4
88
87
58
60
6
3-NO2C6H4 3-NO2C6H4
90
60
7
8
9
10
11
12
13
Ph
Ph
Ph
4-NH2C6H4
4-OMeC6H4
4-ClC6H4
Furyl
5-MeFuryl
CH3
91
90
89
90
90
NRb
NRb
50
57
59
56
56
180
180
Furyl
5-MeFuryl
C3H7
C3H7
C3H7
aIsolated yield by using column chromatography. bNR: No
reaction.
Encouraged by this result, we turned our attention toward
various electron-donating and electron-withdrawing substituents
on benzil dihydrazone, and it turned out that the process tolerates
both electron-donating and electron-withdrawing substituents.16
In all the cases desired acetylene was obtained in good yields
(Table 1, compounds 2-9). Under these reaction conditions
heterocyclic dihydrazone also was found to give good yield of
desired diarylacetylene (Table 1, compounds 10 and 11). No
reaction was observed in the case of dihydrazone of dialiphatic
¡-diketone (Table 1, compounds 12 and 13).
Further, this method is applied to monohydrazone of benzil,
however rather than the expected ¡-diazo ketone,17 deprotection
of monohydrazone back to benzil was observed (Scheme 2).
To evaluate further the scope of this method, these reaction
conditions were applied to various hydrazones of aldehydes and
ketones.16 It was observed that electron-donating substituents
give good yield of corresponding carbonyl compound in shorter
reaction time (Table 2, compounds 17, 18, 20 and 21), while
electron-withdrawing substituents give less yield in longer time
(Table 2, compound 22). Hydrazone of aliphatic aldehyde and
ketone also undergo deprotection in comparatively less yield
As part of our ongoing research toward development of
efficient methods using iodine reagents,15 herein we report a
mild and simple method for preparation of diarylacetylene using
sodium periodate.
For our initial study benzil dihydrazone selected as our
model substrate, which was prepared according to a standard
procedure,10 is treated with 2 equivalents of NaIO4 in a biphasic
system (water:EtOAc) at room temperature: rapid evolution of
nitrogen was observed. After completion of the reaction
diphenylacetylene was isolated (Scheme 1).
Chem. Lett. 2010, 39, 1279-1280
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1280
NNH2
R2
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O
NaIO4, Water:EtOAc
room temperature
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R1
R1
R2
14a−24a
14b−24b
6
7
8
9
Scheme 2. Deprotection of monohydrazone using NaIO4.
Table 2. Deprotection of monohydrazone
Yield of b Time
Compound R1
R2
/%a
/min
E. Abele, R. Abele, P. Arsenyan, E. Lukevics, Tetrahedron
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14
15
16
17
18
19
20
21
22
23
24
Ph
Ph
Ph
OCPh
Me
Ph
85
87
87
90
86
89
90
87
76
70
72
45
35
30
35
40
30
25
25
50
60
60
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4-ClC6H4
2-HOC6H4
Ph
Me
Me
H
3,4-(OMe)2C6H3
4-OMeC6H4
4-NO2C6H4
C4H9
H
H
H
CH3
H
C5H11
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aIsolated yield by column chromatography.
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(Table 2, compounds 23 and 24). Though this reaction is
reported utilizing various reagents,18 the above is still an
efficient method due to the mild nature of sodium periodate.
In conclusion, we have shown that wide range of diaryl-
acetylenes was prepared using mild conditions from dihydra-
zones of ¡-diketones using NaIO4. The method is also suitable
for deprotection of monohydrazones to corresponding carbonyl
compound. Both these applications are general, practical,
economical, and efficient.
16 Experimental procedures: Representative procedure for
preparation of diarylacetylene. Synthesis of 1b (Table 1):
NaIO4 (898 mg, 4 mmol) in biphasic system water:EtOAc
(10 mL) was stirred at room temperature for 5 min, then 1a
(500 mg, 2 mmol) was added to the stirred solution. Finally
the reaction mixture was stirred for 1 h and completion of
reaction was confirmed by thin layer chromatography (5%,
hexane:EtOAc). Reaction mixture was then diluted with
water and extracted with CHCl3 (3 © 10 mL), dried with
Na2SO4, filtered, and concentrated in vacuo to isolate crude
residue, which was further subjected to silica gel column
chromatography using mixture of hexane:EtOAc (10:1) to
get final pure product 1b.
VNT thanks DST (India) for financial support under SERC
Fast Track Scheme and BST thanks CSIR (New Delhi) for
providing a fellowship.
References and Notes
Representative procedure for deprotection of mono-
hydrazone. Synthesis of 14b (Table 2): NaIO4 (954 mg,
2.2 mmol) in water:EtOAc (10 mL) was stirred at room
temperature for 5 min, then 14a (500 mg, 2.2 mmol) was
added to the stirred solution. Finally reaction mixture was
stirred for 30 min, and after completion of reaction the
product 14b was isolated as described for 1b. Detailed
experimental procedure and spectral data of all compounds
are given in Supporting Information which is available
electronically on the CSJ-Journal Web site, http://www.
csj.jp/journals/chem-lett/index.html.
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Chem. Lett. 2010, 39, 1279-1280
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/