Cu(I) catalyzed synthesis of anhydrides from aldehydes via CDC-pathway at ambient temperature

Article abstract of DOI:10.1016/j.tetlet.2016.02.066

A one-pot simple and concise methodology has been developed for synthesizing aromatic carboxylic anhydrides starting from easily accessible aromatic aldehydes using cuprous chloride as the catalyst and TBHP as the oxidant in DMSO solvent to garner moderate to good yields via radical pathway in short and convenient reaction time at room temperature.

Full text of DOI:10.1016/j.tetlet.2016.02.066

Tetrahedron Letters xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Cu(I) catalyzed synthesis of anhydrides from aldehydes via
CDC-pathway at ambient temperature
⇑
Yasin Nuree, Raju Singha, Munmun Ghosh, Pronay Roy, Jayanta K. Ray
Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721302, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A one-pot simple and concise methodology has been developed for synthesizing aromatic carboxylic
anhydrides starting from easily accessible aromatic aldehydes using cuprous chloride as the catalyst
and TBHP as the oxidant in DMSO solvent to garner moderate to good yields via radical pathway in short
and convenient reaction time at room temperature.
Received 24 January 2016
Revised 14 February 2016
Accepted 17 February 2016
Available online xxxx
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
One-pot synthesis
Aromatic aldehydes
Carboxylic anhydrides
CDC pathway
Radical mechanism
Ambient temperature
The controlled transformation of prevalent but inert C–H bonds
to other functional groups has earned an exigent theme in syn-
thetic organic chemistry for its ample implications for the forma-
tion of a diverse array of C–C and C–X (X = heteroatom) bonds
from less expensive and more readily available substrates. In the
last 30 years, C–H bond activation at transition-metal centers has
been explored particularly under mild conditions and with some
desired selectivity.1 The two most popular approaches are chela-
tion assisted C–H bond functionalization and the cross dehydro-
genative coupling (CDC).1 The CDC approach is attractive because
it does not require substrate pre-functionalization and it is atom
economic. As evident from the literature, CDC has been widely
investigated for the formation of C–C bonds albeit the concept
has rarely been explored regarding C–O bond formation.2 The rel-
evance of C–O bonds in organic chemistry has resulted in the
emergence of various transition metal based methodologies via
C–H bond activation.3 In this regard the carboxylic acid derivatives
have been the common target. A number of CDC based approaches
employing expensive metal catalysts such as Ru, Rh, Ir, and Pd have
been developed.4 Cu-catalyzed cross-dehydrogenative coupling
(CDC) methodologies have also been developed based on the
oxidative activation of sp2 C–H bonds adjacent to an oxygen atom.5
Recently, a copper-catalyzed synthesis of methyl esters from aro-
matic aldehydes in the presence of tert-butylhydrogen peroxide
(TBHP) was reported via a radical reaction mechanism.6a But,
only few methods are available in the literature for the
synthesis of anhydrides of aromatic carboxylic acids. Therefore,
the development of simple and efficient methodology towards
the synthesis of anhydrides is highly covetable.
a
Carboxylic anhydrides are a very important class of organic
compounds used as versatile functional reagents for various types
of reactions such as the condensation reaction of free carboxylic
acids and alcohols,7a condensation reactions with silyl esters,7b
chemoselective esterification reactions,7c asymmetric esterifica-
tions,7d chemoselective lactonization,7e,f lactonization of silyl
esters.7g Naphthalenetetracarboxylic dianhydrides (Fig. 1, 1) are
used as the precursor to naphthalenediimides (NDIs) which have
different uses in material science and artificial photosynthesis.8
Organic acid anhydrides are rarely found in nature because of the
reactivity of the functional group. Cantharidin (Fig. 1, 2), a type
of terpenoid, is a naturally occurring carboxylic anhydride secreted
by many species of blister beetle, and most notably by the Spanish
fly, Lytta vesicatoria.9 Maleic anhydride (Fig. 1, 3) moiety is present
in tautomycin (Fig. 1, 4) occurs naturally in shellfish and is ema-
nated by the bacterium streptomyces spiroverticillatus.10
Although anhydrides are very important for the organic che-
mists and not abundant in nature, synthesis is the only way to have
these compounds. In the literature, very few methods are available
for the synthesis of carboxylic anhydrides. So, the synthesis of
anhydrides from easily available starting materials in a simple
and convenient way should be of great importance.
⇑
Corresponding author. Tel.: +91 322 228 2252; fax: +91 322 228 3326.
E-mail address: jkray@chem.iitkgp.ernet.in (J.K. Ray).
http://dx.doi.org/10.1016/j.tetlet.2016.02.066
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Nuree, Y.; et al. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.02.066

2
Y. Nuree et al. / Tetrahedron Letters xxx (2016) xxx–xxx
Table 2
O
O
O
O
Exploration of substrate scopea,b
O
H3C
O
O
O
H
O
O
O
O
tBuOOH (3 equiv.)
CuCl (6 mol%),
DMSO,
O
O
H3C
O
O
O
O
1
room temp.
2
3
R
R
R
1h
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
H
O
OH
O
OH
O
Me
Me
O
OH
O
O
6a
Me
Me
O
O
Me
Me
6c
6b
(82%)
4
(75%)
(75%)
O
O
O
O
Me
O
O
O
Me
O
O
O
6f
O
O
Me
Me
Figure 1. Structure of some industrially important and naturally occurring bioac-
O
O
Me
Me
O
O
tive anhydrides.
O
O
Me
6e
(51%)
6d Me
O
Me
O
(42%)
Me
O
(85%)
O
O
O
Table 1
O
O
O
Me
Me
S
S
Screening of the reaction condition
Me
Me
S
S
O
O
6h
(77%)
O
6g
(90%)
O
6i
CHO
O
O
(65%)
Catalyst, Oxidant
O
a
Reaction conditions: Arylaldehyde (1 mmol), CuCl (6 mol %), TBHP in toluene
Solvent, Additive
Room Temp.
(3 equiv), 2 ml DMSO, stirred at room temperature for 1 h.
MeO
OMe
b
Isolated yield.
OMe
5a
6a
Entry
Catalyst (mol %)
Oxidant (equiv)
Solvent
Yielda (%)
Herein, we are reporting a novel method for the synthesis of
anhydrides of aromatic carboxylic acids through copper-catalyzed
CDC based approach from aromatic aldehydes at room
temperature.
Recently, our lab has designed a short, convenient and efficient
methodology for the synthesis of dibenzopyranones by aryl C–H
activation by cross dehydrogenative coupling based approach
using low-cost CuCl and TBHP oxidant from 2-arylbenzaldehyde
at room temperature.14 When we tried to accomplish the reaction
with the aromatic aldehydes, we obtained the corresponding
anhydrides.
With this observation, we started our investigation by reaction
of anisaldehyde (5a) taking cuprous chloride as catalyst, TBHP as
oxidant, pyridine as additive in DMSO solvent at room tempera-
ture, which resulted the desired anhydride in 46% yield. Then we
screened the additive, solvent, catalyst and the oxidant in order
to find the optimized reaction conditions (Table 1). Firstly, we
changed the additive. We found the reaction to give better result
in the absence of any additive. Next, the solvents were screened,
which indicated DMSO as the best one. Then we replaced the cat-
alyst CuCl by other catalysts (CuI, Cu(OAc)2, CuBr) and CuCl was
found to be the most efficient catalyst. Then we varied the oxidants
as well as its amounts. TBHP in 3 equiv amount was found to be the
most effective oxidant for our purpose. Finally, we screened the
amount of the catalyst, 6 mol % CuCl was found to be the most
promising for our reaction in the presence of 3 equiv TBHP (80%
in toluene) in DMSO solvent giving 82% yield (Table 1, entry 20)
after 1 h of stirring at room temperature. We have also used CuCl2
1
2
3
4
5
6
7
8
CuCl (10)
CuCl (10)
CuCl (10)
CuCl (10)
CuCl (10)
CuCl (10)
CuCl (10)
CuCl (10)
CuI (10)
Cu(OAc)2 (10)
CuBr (10)
CuCl (10)
CuCl (10)
CuCl (10)
CuCl (10)
CuCl (10)
CuCl (10)
CuCl (10)
CuCl (30)
CuCl (6)
TBHP (3)b,c
TBHP (3)d
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)e
H2O2 (3)
m-CPBA (3)
TBHP (1)
TBHP (5)
TBHP (3)f
TBHP (3)g
TBHP (3)
TBHP (3)h
TBHP (3)
TBHP (3)
DMSO
DMSO
DMSO
CH2Cl2
C6H6
46
N.R
78
Trace
Trace
70
Trace
18
Trace
29
43
82
Trace
34
40
52
60
12
49
82
N.R.
38
CH3CN
DMF
Dioxane
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
9
10
11
12
13
14
15
16
17
18
19
20
21
22
—
CuCl2 (10)
The bold values indicate conditions with highest yields.
a
Isolated yield.
80% TBHP in H2O (entry 1–11).
Pyridine additive.
Et3N additive.
80% TBHP in toluene (entry 12–21).
45 min reaction time.
1.5 h reaction time.
b
c
d
e
f
g
h
Optimized reaction conditions: the substrate 5a (1 mmol), CuCl (6 mol %), TBHP
(3 equiv), 2 ml DMSO, stirred at room temperature for 1 h.
Classically anhydrides are prepared by dehydrating carboxylic
acids in the presence of dehydrating agents like phosgene,11a thio-
nyl chloride,11b and reacting acylating agents with carboxylates.11c
Recently metal catalyzed routes which include Pd-catalyzed12 and
nano CuO-catalyzed13 methodologies, for the synthesis of anhy-
drides have also been developed. All these procedures require
either high temperature or costly metal catalyst or both. Therefore,
a mild and efficient methodology comprising easily available start-
ing materials at room temperature is highly desirable.
Me
Me
O
O
H
O
CuCl (6 mol%), TBHP (3 equiv.)
DMSO, 1 h, rt
N
Me
Me
Me
Me
+
Me
N
Me
O
Me
O
O
8
Me
7
5a
(78%)
Scheme 1. Trapping of intermediate.
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Y. Nuree et al. / Tetrahedron Letters xxx (2016) xxx–xxx
3
O
H
O
H
O
O
O
CuCl (6 mol%), TBHP (3 equiv.)
6a
6d
+
+
+
Me
Me
Me
DMSO, 1 h, rt
O
O
O
(25%)
(15%)
6j
(24%)
O
O
O
Me
Me
Me
5d
5a
Scheme 2. Cross-over experiment.
tBuOOH
Cu(I)
tBuO + OH
From the identification of trapped intermediate, it might be
proposed that anhydrides were formed as the result of combina-
tion of an acyl radical with a carboxyl radical which was produced
from another aldehyde molecule. As both acyl and carboxyl radi-
cals are involved in the reaction, three different products should
be obtained if the reaction is carried out with a mixture of two dif-
ferent aldehydes. In order to validate our proposal, we performed
the reaction taking a mixture of both anisaldehyde (5a) and 3,4-
dimethoxybanzaldehyde (5d) as the substrates. We obtained the
cross product 6j along with the products 6a and 6d (Scheme 2).
Hence, it can be concluded that the reaction proceeds through an
intermolecular pathway involving both acyl and carboxyl radicals,
otherwise we would not get the cross product 6j.
So, we may hypothesize that the reaction plausibly proceeds
through the intermolecular radical pathways as shown in
Scheme 3.6 First, t-butyloxy radical is generated (Path I, Scheme 3)
from TBHP in the presence of Cu(I) catalyst which becomes Cu(II)
which again converts back to Cu(I) with the help of TBHP (Path
II, Scheme 3). TBHP produces t-butylperoxy radical (tBuOOÅ) in
the later path (Path II, Scheme 3). t-Butyloxy radical generates acyl
radical (ArCOÅ) from the aldehydes (Path A, Scheme 3). Next, the
acyl radical combines with t-butylperoxy radical (tBuOOÅ) to give
a per-ester, I (Path A, Scheme 3). Then I undergoes homolytic O–
O cleavage to yield the carboxyl radical II. Finally, I and II combine
to produce the desired anhydride (Path C, Scheme 3).
Path I
Cu(II)
Path II
tBuOOH + OH
tBuOO
H2O + tBuOO
tBuO
O
O
C
A.
B.
ArCHO
O
Ar
C
Ar
O
tBu
- tBuOH
I
O
C
O
C
I
O
O
Cleavage
O
tBuO
+
Ar
O
Ar
O
tBu
II
O
O
O
C
O
C
II
C.
Ar
Ar
O
III
Ar
Ar
O
I
Scheme 3. Plausible reaction mechanism.
Conclusions
as the catalyst which gave 38% yield. In the absence of the catalyst,
the desired product was not obtained. So, the optimized reaction
conditions are the aromatic aldehydes (1 mmol), CuCl (6 mol %),
TBHP (3 equiv), DMSO solvent (2 ml) stirred at room temperature
for 1 h.
In conclusion, we have developed an easy and efficient method-
ology for the synthesis anhydrides starting from commercially
available aromatic aldehydes using low-cost Cu(I) catalyst and
TBHP as oxidant at room temperature with satisfactory yields.16
We have also explored the plausible reaction pathway in our labo-
ratory. We hope our methodology will find application in the syn-
thesis of anhydrides having promising synthetic, material as well
as pharmaceutical applicability.
Having the satisfactory conditions in our hand, we investigated
the scope of the reaction utilizing different aromatic aldehydes
(5a–5i). As observed in Table 2, we have used both benzaldehyde
derivatives as well as naphthaldehyde derivatives and all the alde-
hydes with electron donating groups produced the respective
anhydrides in satisfactory yields whereas the aldehydes with elec-
tron withdrawing groups gave the desired product in trace
amounts and produced mainly the corresponding carboxylic acids.
The observation with aldehydes having electron withdrawing
groups could be attributed to the fact that anhydrides with elec-
tron withdrawing groups are more readily hydrolyzed than the
anhydrides with electron donating groups. The substrate 5e gave
lower yield possibly due to the steric factor. The methylthio deriva-
tive of benzaldehyde (5h) and thiofene-2-carbaldehyde (5i) also
gave satisfactory yields (Table 2, 6h, 6i).
Acknowledgments
Yasin Nuree thanks IIT Kharagpur for the fellowship and the
Department of Science and Technology (DST), Ministry of Human
Resource Development (MHRD), India for providing funds for the
project.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.02.
066.
In order to get the proper pathways for our methodology we
have carried out two different reactions as shown in Schemes 115
-
and 2. We tried to trap the intermediate formed during the reac-
tion using 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) (7)
under the optimized reaction conditions (Scheme 1). We did not
obtain 6a, but we got 8 as the only product which was formed as
a result of trapping of the acyl radical generated in situ under
the reaction conditions, by TEMPO. This indicates the reaction
mechanism involves a radical intermediate, namely an acyl radical.
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16. General procedure for the synthesis of anhydrides (6a–6i): In a two necked
round-bottomed flask, 1 mmol aromatic aldehyde and 6 mol % CuCl were taken
and 2 ml distilled DMSO was added to it under Ar-atmosphere. Then 3 mmol
TBHP (0.34 ml 80% TBHP in toluene) was added dropwise to the above mixture
under stirring condition. The reaction mixture was then allowed to stir for 1 h
at room temperature. Progress of the reaction was monitored through TLC.
After the completion of the reaction, the product was purified through column
chromatography after a quick work up. In every case, the column was washed
with 1% triethylamine in eluent.
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