TBHP-promoted and iodide-catalyzed synthesis of anhydrides via cross dehydrogenative coupling (CDC) of aldehydes

Article abstract of DOI:10.1016/j.tetlet.2016.02.036

We have successfully developed a transition metal free green methodology for the synthesis of carboxylic anhydrides from aldehydes via CDC pathway and have also demonstrated the reaction mechanism. The developed method has also been successfully applied for the synthesis of amides.

Full text of DOI:10.1016/j.tetlet.2016.02.036

Tetrahedron Letters 57 (2016) 1325–1327
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
TBHP-promoted and iodide-catalyzed synthesis of anhydrides
via cross dehydrogenative coupling (CDC) of aldehydes
Raju Singha a,b, Munmun Ghosh a, Yasin Nuree a, Jayanta K. Ray a,
⇑
a Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721302, India
b Department of Chemistry, Panskura Banamali College, Panskura R. S. 721152, India
a r t i c l e i n f o
a b s t r a c t
Article history:
We have successfully developed a transition metal free green methodology for the synthesis of carboxylic
anhydrides from aldehydes via CDC pathway and have also demonstrated the reaction mechanism. The
developed method has also been successfully applied for the synthesis of amides.
Ó 2016 Elsevier Ltd. All rights reserved.
Received 4 January 2016
Revised 9 February 2016
Accepted 9 February 2016
Available online 11 February 2016
Keywords:
TBHP
Iodide
Aldehyde
CDC
Anhydride
Carboxylic anhydrides are an important class of organic com-
pounds used as the precursor for the synthesis of esters and
amides,1 and are also used in peptide synthesis.2 Because of such
importance, various methods have been developed for their syn-
thesis. In most of the cases, the carboxylic anhydrides have been
prepared by reacting the corresponding carboxylic acids with any
one of dehydrating coupling agents such as thionyl or sulfonyl
chloride,3,4 phosgene,5 phosphoranes,6 isocyanates,7 1,3,5-triazi-
nes,8 and carbodiimides.9 Other approaches involve the reaction
of acid salts with a powerful acylating agents such as acid chlorides
or acid anhydrides.10 All the above mentioned methods have their
corresponding advantages along with some drawbacks such as
instability, toxicity, solubility, and volatility of the reagents.
Recently Stephenson and co-workers have reported a photore-
dox catalyzed synthesis of symmetrical anhydrides from the corre-
sponding carboxylic acid in presence of Ru(bpy)3Cl2 catalyst.11
Very recently Patel and his co-workers have reported a CuO
nanoparticle-catalyzed synthesis of carboxylic anhydrides from
the corresponding aldehydes.12 In spite of a number of advantages,
both the methods involve heterogeneous transition metal catalysts
which are difficult to separate from the products. Thus we
intended to develop a transition metal free green methodology
for the synthesis of carboxylic anhydrides.
Wan and co-workers had previously reported a metal free
method for the synthesis of tert-butyl perester from the corre-
sponding aldehyde in presence of TBAI catalyst in aqueous medium
(Scheme 1).13 From this Letter we observed that, the electron-
deficient arylaldehydes gave excellent yields whereas the electron-rich
arylaldehydes gave poor yields (for e.g., anisaldehyde gave only
52% yield) and they also avoided di- and tri-methoxybenzaldehy-
des as the substrate. While reinvestigating the same reaction with
anisaldehyde in water, we observed that a significant amount of
anisic acid was formed along with the normal perester product
and formation of trace amounts of a new product was observed
in TLC. We then performed the reaction in dry acetonitrile solvent
with TBHP (5–6 M in decane) and isolated and characterized the
new product as p-anisic anhydride. Then we screened the reaction
conditions to maximize the yield of carboxylic anhydride and the
results are shown in Table 1.
Initially we used the same reaction condition suggested by
Wan’s group: anisaldehyde (1 mmol), TBHP (3 mmol), TBAI
(20 mol %) and stirred at 40 °C for 24 h resulting in the formation
of a trace amount of anhydride along with a large amount of acid.
Then we reduced the amount of TBHP (2 mmol) and TBAI (5 mol %)
in dry acetonitrile and isolated the desired anhydride in 28% of
yield. The yield increased on increasing the temperature to 70 °C.
However, on further raising the temperature 90 °C, the yield
decreased (Table 1, entries 2–5). TBAB resulted only in 9% of the
anhydride whereas TBAC failed to give any such product (Table 1,
entries 6–7). DMSO and DMF were also tested as solvent leading to
no fruitful result. The yield decreased on increasing the amount of
⇑
Corresponding author. Tel.: +91 03222 283326; fax: +91 03222 283352.
E-mail address: jkray@chem.iitkgp.ernet.in (J.K. Ray).
http://dx.doi.org/10.1016/j.tetlet.2016.02.036
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.

1326
R. Singha et al. / Tetrahedron Letters 57 (2016) 1325–1327
Path A
Previous work
CHO
O
O
+
OOH
HO
n-Bu4N
+
+
20 mol% TBAI
O
O
O
O
HO
1/2 I2
n-Bu4NI
H2O, 40 oC, 24h
R
R
R
H2O
+
OO
HOO
n-Bu4N
O
Present work
CHO
HO
+
O
O
TBAI (5 mol%)
But
O
tBuOH
HO
O
OO
O
O
MeCN, 70 oC, 30 min.
O
R
R
Ar
O
Ar
H
Ar
1
A
2
Scheme 1. Previous work and present work.
O
O
O
Ar
O
Ar
O
TBAI (20 mol %) and TBHP (3 equiv) (Table 1, entry 10). The reac-
tion was also found to fail in absence of TBAI (entry 11). Thus
the screened reaction conditions are substrate (1 mmol), TBAI
2
O
O
O
B
-
Ar
O
Ar
O
O
3
(17.5 mg), acetonitrile (3 mL), TBHP in decane (5–6 M) (400 lL)
and heated at 70 °C for 30 min.
Ar
Ar
H
A
1
OH
With the confirmed product-structure and standard reaction
condition in hand we were curious to understand the mechanism
of formation of anhydride from aldehyde. Wan’s group showed
that the peresters were formed via radical pathway and they also
trapped the carboxylate intermediate by radical scavenger TEMPO.
Thus, we primarily thought that probably the perester bond breaks
and forms carboxyl radical (B) which couples with the acyl radical
(A) generated from the aldehyde by the tert-butoxylradical to
afford the anhydride 3 (Scheme 2, path 1). To examine this mech-
anism we first synthesized the corresponding perester derivative
and heated it with 3,4-dimethoxybenzaldehyde in the presence
of TBHP and TBAI; however only the normal 3,4 dimethoxybenzoic
anhydride was formed and no crossover product was observed
(Scheme 3, Eq. 1).
Then we anticipated that probably the corresponding carboxylic
acid formed by the oxidation of aldehyde participated in the reac-
tion. The tert-butoxyl radical abstracts hydrogen from carboxylic
acid to form the carboxyl radical (B) which then couples with acyl
radical (A) to afford the product 3 (Scheme 2, path B). To examine
this mechanism, we performed a controlled experiment (Scheme 3,
Eq. 2). When anisaldehyde (1 mmol) and o-anisic acid (1 mmol)
were heated under the standard reaction conditions, we got the
crossover product 4 in 23% yield along with normal perester pro-
duct and trace amount of p-anisic anhydride. This experiment
proved that the reaction followed path B mechanism.
Path B
+
O
2
2 HO
2 HO
2 n-Bu4N
2 n-Bu4N
OOH
2
+
I2
2 n-Bu4NI
O
O
H2O
+
HO
Ar
+
+
H
Ar
But
O
But
O
tBuOH
tBuOH
O
O
O
O
Ar
H
Ar
O
Ar
HO
Ar
A
1
B
O
O
Ar
O
Ar
3
Scheme 2. Plausible mechanism.
O
O
tBu
O
CHO
OMe
O
O
OMe
OMe
eq.1
TBHP, TBAI
70 oC, 30 min
O
+
Table 1
+ 3b
Screening of the reaction conditionsa
MeO
MeO
Y = 71%
2a
Y = 0%
OMe
O
O
CHO
O
O
CHO
Catalyst
O
HO
O
COOH
O
TBHP, TBAI
70 oC, 30 min
eq.2
MeO
+ 3a
solvent, heat
+
MeO
OMe
MeO
MeO
1a
OMe
3a
Y = 18%
OMe
4, Y = 23%
Entry
Catalyst
Solvent
Temp (°C)
Time (h)
Yieldb (%)
Scheme 3. Controlled experiments.
c
1
2
3
4
5
6
7
8
TBAI
TBAI
TBAI
TBAI
TBAI
TBAB
TBAC
TBAI
TBAI
TBAI
—
H2O
40
40
50
70
90
70
70
70
70
70
70
24
24
6
Trace
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
DMSO
CH3CN
CH3CN
28
33
37
35
9
After establishing the reaction mechanism and getting the
standard reaction conditions we employed it on different aryl
aldehydes and the results are shown in Table 2.14,15 We used
different aryl and hetero-arylaldehydes having a range of electron
withdrawing and donating functional groups and observed that
only the electron-rich arylaldehydes resulted in the formation of
the desired anhydrides (Table 2, entries 3a–3h) whereas the elec-
tron-poor arylaldehydes such as 4-nitrobenzaldehyde, 4-chloroben-
zaldehyde, 2-naphthaldehyde afforded mainly the normal perester
product. Benzaldehyde produced trace amount of anhydride
which was observed in TLC of the crude reaction mixture however,
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0
0
0
9
10
11
32c
0
a
Reaction conditions: Anisaldehyde (1 mmol), TBAI (5 mol %), acetonitrile
(3 mL), TBHP in decane (5–6 M) (2 equiv), heat.
b
Isolated yield.
TBAI (20 mol %) and TBHP (3 equiv).
c

R. Singha et al. / Tetrahedron Letters 57 (2016) 1325–1327
1327
Table 2
and got the corresponding amides in moderate yields. The overall
yields of the amides were slightly greater than the corresponding
anhydrides because some amount of anhydrides were hydrolyzed
during the normal work up process.
We have successfully characterized and optimized the forma-
tion of carboxylic anhydride as another product of perester synthe-
sis reaction reported previously by Wan’s group and have proved
the general applicability of the method employing a series of elec-
tron rich arylaldehydes. Formation of the anhydride has initially
been proposed through the intermediacy of carboxyl radical and
has been further confirmed through controlled experiments. The
method has also been extended for the one pot synthesis of a num-
ber of aryl amides.
Substrate scope examinationa
O
O
CHO
TBHP, TBAI
MeCN, 70 oC, 30 min
Ar
O
Ar
Ar
1a-i
3a-i
O
O
O
O
O
O
MeO
OMe
OMe
O
O
O
MeO
OMe
MeO
OMe
MeO
OMe
O
OMe
OMe
O
OMe
3a, Y = 37%
3b, Y = 75%
3c, Y = 37%
O
O
O
O
O
OMe
O
O
MeS
SMe
Acknowledgements
OMe
3e, Y = 80%
OMe
OMe
3f, Y = 30%
3d, Y = 24%
O
O
O
O
O
We would like to thank Department of Science and Technology
(DST), New Delhi, India and R.S. thanks Council of Scientific and
Industrial Research (CSIR), New Delhi, India for the financial
support.
O
O
O
O
S
S
MeO
OMe
3i, Y = trace
3h, Y = 31%
3g, Y = 51%
a
Reaction conditions: Arylaldehyde (1 mmol), TBAI (5 mol %), acetonitrile (3 mL),
Supplementary data
TBHP in decane (5–6 M) (2 equiv), 70 °C for 30 min.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.02.
036.
O
1. TBHP, TBAI
CHO
MeCN, 70 oC, 30 min
N
H
Ar
Ar
4a-f
References and notes
2.
10 min
H2N
1. (a) Ogliaruso, M. A.; Wolfe, J. F. Synthesis of Carboxylic Acids, Esters, and Their
Derivatives; Wiley: New York, NY, 1991. p 198; (b) Ogliaruso, M. A.; Wolfe, J. F.;
Tarbell, D. S. Acc. Chem. Res. 1969, 2, 296.
O
O
O
O
MeO
MeO
MeO
MeO
N
2. Rebek, J.; Feitler, D. J. Am. Chem. Soc. 1974, 96, 1606.
N
H
N
H
N
H
H
3. Kazemi, F.; Sharghi, H.; Nasseri, M. A. Synthesis 2004, 2, 205.
4. (a) Edwards, D. J. Chem. Soc., Perkin Trans. 1 1966, 19, 1734; (b) Fife, W. K.;
Zhang, Z. D. Tetrahedron Lett. 1986, 27, 4937; (c) Kazemi, F.; Kiasat, A. R.
Phosphorus, Sulfur Silicon Relat. Elem. 2003, 178, 2287; (d) Kazemi, F.; Kiasat, A.
R.; Mombaini, B. Synth. Commun. 2007, 37, 3219.
MeO
MeO
OMe
4a, Y = 53%
4b, Y = 65%
4d, Y = 48%
4c, Y = 49%
5. (a) Rinderknecht, H.; Ma, V. Helv. Chim. Acta 1964, 47, 162; (b) Kocz, R.;
Roestamadji, J.; Mobashery, S. J. Org. Chem. 1994, 59, 2913.
6. (a) Mestres, R.; Palomo, C. Synthesis 1981, 3, 218; (b) Kawamura, Y.; Sato, Y.;
Horie, T.; Tsukayama, M. Tetrahedron Lett. 1997, 38, 7893.
7. Keshavamurthy, K. S.; Vankar, Y. D.; Dhar, D. N. Synthesis 1982, 6, 506.
8. Kaminski, Z. J.; Kolesinska, B.; Marcinkowska, M. Synth. Commun. 2004, 34,
3349.
Scheme 4. One pot synthesis of amides. Reaction conditions: Arylaldehyde
(1 mmol), TBAI (5 mol %), acetonitrile (3 mL), TBHP in decane (5–6 M) (2 equiv),
70 °C for 30 min then tert-butyl amine (2 mmol) was added and stirred at 70 °C for
10 min. Isolated yield.
9. (a) Rammler, D. H.; Khorana, H. G. J. Am. Chem. Soc. 1963, 85, 1977; (b) Hata, T.;
Tajima, K.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 1968, 41, 2746; (c) Stadler, A.;
Kappe, C. O. Tetrahedron 2001, 57, 3915; (d) Clarke, P. A.; Kayaleh, N. E.; Smith,
M. A.; Baker, J. R.; Bird, S. J.; Chan, C. J. Org. Chem. 2002, 67, 5226.
10. (a) Ferris, A. F.; Emmons, W. D. J. Am. Chem. Soc. 1953, 75, 232; (b) Rambacher,
P.; Make, S. Angew. Chem., Int. Ed. Engl. 1968, 7, 465; (c) Fakuoka, S.; Takimoto,
S.; Katsuki, T.; Yamaguchi, M. Tetrahedron Lett. 1987, 28, 4711; (d) Lu, Y. L.; Jwo,
J. J. J. Mol. Catal. A: Chem. 2001, 170, 57; (e) Hajipour, A. R.; Mazloumi, G. Synth.
Commun. 2002, 32, 23.
11. Konieczynska, M. D.; Dai, C.; Stephenson, C. R. J. Org. Biomol. Chem. 2012, 10,
4509.
12. Khatun, N.; Santra, S. K.; Banerjee, A.; Patel, B. K. Eur. J. Org. Chem. 2015, 1309.
13. Wei, W.; Zhang, C.; Xu, Y.; Wan, X. Chem. Commun. 2011, 10827.
14. General reaction procedure: Aryl aldehyde (1 mmol) and tetrabutylammonium
hydrolyzed to acid during the workup procedure. It is also important
to mention that steric effect had no significant role on the reactivity
of the aromatic aldehydes and thus o-anisaldehyde gave the excel-
lent yield 80% (entry 3e). The heteroaryl thiophene-2-aldehyde also
produced the corresponding anhydride in 31% yield. Electron defi-
cient aryl aldehydes such as 4-nitrobenzaldehyde, 4-chlorobenzalde-
hyde, and 2-naphthaldehyde failed to give the corresponding
anhydrides. Finally the yields of the reactions were moderate to good
due to the formation of normal perester product in each case.
To explain the applicability of the reaction on only electron-rich
arylaldehydes we recapitulated the reaction mechanism. We found
that the acyl radical intermediate (Scheme 2, Path A and Path B)
can give both perester and anhydride; however the carboxyl radi-
cal intermediate (Scheme 2, B) promote only the anhydride forma-
tion path. Thus it can be concluded that greater the stability of
carboxyl radical, higher the chance of anhydride formation.
After synthesizing a number of anhydrides successfully, we
applied the reaction for the one pot synthesis of amides from alde-
hydes via anhydride. After completion of the anhydride formation,
we added tert-butyl amine in the same reaction mixture and
allowed to continue the reaction for another ten minutes for one
pot amide formation (Scheme 4). We used different aldehydes
iodide (TBAI) 19 mg were taken in
acetonitrile was added to it. Then tert-butyl hydrogenperoxide in decane (5–
6 M) (400 L) was added and the reaction mixture was stirred at 70 °C for
a round bottomed flask and 5 mL of
l
30 min. After completion of the reaction mixture was cooled to room
temperature, diluted with saturated solution of sodium thiosulphate and
extracted with ethyl acetate (3 Â 20 mL). The combined organic layer was
washed with brine, dried over anhydrous Na2SO4, evaporated under reduced
pressure. Then the crude product was purified by column chromatography
using silica gel (60–120 mesh) and hexane/EtOAc as eluent.
15. Spectral data for the representative compound 3a: White solid. 1H NMR
(400 MHz, Chloroform-d) d: 8.09 (d, J = 8.9 Hz, 2H), 6.98 (d, J = 9.0 Hz, 2H),
3.89 (s, 3H). 13C NMR (101 MHz, Chloroform-d) d: 164.7, 162.4, 132.9, 121.4,
114.3, 55.7.