Copper-catalyzed oxidation of arene-fused cyclic amines to cyclic imides

Article abstract of DOI:10.1039/c3cc45869e

A novel copper-catalyzed oxidation of arene-fused cyclic amines to the corresponding cyclic imides has been developed. The reaction can be used to synthesize 1,3-disubstituted TPD in high yields.

Full text of DOI:10.1039/c3cc45869e

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Copper-catalyzed oxidation of arene-fused cyclic amines to cyclic imides
Xiaoyu Yana, Kun Fanga, Hailan Liua, Chanjuan Xi*a,b
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
DOI: 10.1039/b000000x
The imide functional group, which consists of two acyl groups
30 bound to nitrogen, is a key component in various chemical
reactions and plays a huge role in modern organic synthesis.
Among them, areneꢀfused cyclic imides play vital role in
5
A novel copper-catalyzed oxidation of arene-fused cyclic
amines to the corresponding cyclic imides has been
developed. The reaction can be used to synthesize 1,3-
disubstituted TPD in high yields.
pharmaceuticals,7a
fungicides,7b
polymers,7c
organic
semiconductors, and organic photovoltaics.7dꢀ7f Some selections
35 are shown in Scheme 2.
Oxidation reactions are one of the fundamental functional group
10 transformation reactions in organic synthesis.1 Catalytic oxidative
transformation of ubiquitously present C–H bonds to polar
functional groups (e.g., C–O, C–N bonds) and molecular
Owing to the widespread occurrence of this structural motif,
efficient means for the chemical synthesis of imides is of
continuing interest. Traditionally, the syntheses of imides have
relied primarily on the heating dicarboxylic acids (or anhydrides)
40 with an amine, and acylation of an amide.8 Recently, a
straightforward synthesis of imides is via the oxidation of
amides.9 However, in contrast to the plethora of methods
available for the oxidation of amines,4,5 procedures for the
oxidation of amines to imides were, until recently, rather limited.6
45 Herein, we describe a copperꢀcatalyzed direct oxidation of areneꢀ
fused cyclic amines to afford areneꢀfused cyclic imides. To the
best of our knowledge, this is the first example of metalꢀcatalyzed
oxidation of cyclic amines to imides under mild conditions.
Initially, we used Nꢀbutylisoindoline10 1a as the starting
50 material to study the oxidation reaction. In the preliminary
experiment, the oxidation reaction of Nꢀbutylisoindoline was
skeletons is
a straightforward and versatile approach to
constructing complex molecules.2,3 Amines are desirable starting
15 materials to prepare other chemicals because they are abundant
and inexpensive chemicals. Oxidation of amines can afford a
large number of organic compounds.4,5 For examples, oxidation
can occur on nitrogen atom to afford amine oxides,4cꢀ4d
hydrazines,4eꢀ4g azo compounds,4fꢀ4m and nitro compounds
20 (Scheme 1, aꢀd).4nꢀ4p The oxidation can also occur on vicinal
carbon atom to afford imines,5aꢀ5g nitriles,5hꢀ5l and amides
(Scheme 1, eꢀg).5mꢀ5p However, to the best of our knowledge,
there is no efficient method for direct oxidation of amines to
imides.6
o
examined in acetonitrile at 50 C in the presence of 10 mol %
CuCl and 10 equivlants of TBHP (tertꢀbutyl hydroperoxide).
Phthalimide 2a was formed in 54% yield (Table 1, entry 1). We
55 then examined the effect of different solvents, such as
dimethylformamide (DMF), dioxane, toluene, 1,2ꢀdichloroethane
(DCE), and dichloromethane (entries 2ꢀ6), and we found the yield
increased to 82% in dichloromethane (entry 6). Temperature
screening experiments (entries 6ꢀ8) revealed that the best reaction
o
60 temperature is at 50 C (entry 6). When 5 equivalents of TBHP
25
Scheme 1 Amine oxidation reaction
were used, the yield of 2a decreased to 54% (entry 9).
Furthermore, the effect of other copper salts was also examined.
Cu(OAc)2, CuCl2, CuBr, and CuI as catalyst gave product 2a in
77%, 74%, 66%, and 25% yields, respectively (entries 10ꢀ13).
65 We also checked FeCl3 as catalyst and 2a was obtained in 48%
yield (entry 14).
On the basis of these results, the optimal condition involved
the following parameters: CuCl as catalyst, TBHP (10 eq) as
oxidant, dichloromethane as solvent, and reaction temperature at
70 50 °C. Under the optimized condition, a study on the substrate
scope was carried out, and the results are summarized in Table 2.
A
series of Nꢀsubstituted isoindolines were oxidized to
phthalimides in morderate to high yields (Table 2, entries 1ꢀ10).
Scheme 2 Examples of areneꢀfused cyclic imides
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NꢀAlkyl isoindolines 1a-1c were converted to phthalimide 2a-2c
in 68ꢀ73% isolated yield (entries 1ꢀ3). NꢀAllylꢀ, Nꢀbenzylꢀ and Nꢀ
bispropargylamines,12 were conveniently converted into 1,3ꢀ
disubstituted TPD (Scheme 3). The yields are moderate to high
methyloxycarbonylmethylisoindolines 1d-1f were converted to 35 depending on the substituent of TPD. The structure of 4a was
phthalimide 2d-2f in 40ꢀ48% isolated yield (entries 4ꢀ6). It is
noteworthy that oxidation of Nꢀbenzylisoindoline 1e, which has
two different types of benzyl, afforded cyclic imide 2e. No
formation of Nꢀbenzoylisoindolinꢀ1ꢀone was observed. NꢀAryl
isoindolines 1g-1j were converted to phthalimide 2g-2j in 30ꢀ
47% isolated yield (entries 7ꢀ10). 5ꢀChloroisoindoline 1k
also confirmed by XRD analysis.‡
5
Table 2 Scope of copperꢀcatalyzed amine oxidationa
10 afforded the corresponding phthalimide 2k in 48% yield (entry
11). Besides isoindolines, naphthaleneꢀfused piperidine 1l can
also proceeded, and the corresponding imide 2l was isolated in
75% yield (entry 12). In the case of Nꢀallylꢀ, benzylꢀ , aryl, and
methyloxycarbonylmethyl substituted isoindolines, ringꢀopen and
15 degradative byproducts were detected by GCꢀMS.
Table 1 Optimization of reactiona
aReaction condition: isoindoline 0.4 mmol, catalyst 10 mol%, solvent 1
mL, TBHP (70% in water) 4 mmol, sealed tube, 24 h. bGC yield, isolated
20 yield are given in parentheses. c2 mmol TBHP was used.
Scheme 3 Copper catalyzed amine oxidation to afford TPD
Thieno[3,4ꢀc]pyrroleꢀ4,6ꢀdione (TPD) unit, which has an
imide group fused with thiophene ring, has become an important
25 building block in organic solar cells and organic fieldꢀeffect
transistors.11 The most common pathway toward TPD unit
involves condensation of an amine with thiophene anhydride,7f
which possesses two drawbacks: (i) 3,4ꢀthiophenedicarboxylic
acid is a relatively expensive starting material, (ii) the reaction
30 needs more steps especially for preparation of 1,3ꢀdisubstituted
aReaction condition: amine 0.4 mmol, catalyst 10 mol%, solvent 1 mL,
40 TBHP (70% in water) 4 mmol, sealed tube, 24 h. bisolated yield. c5 mmol
scale. d10 mmol scale.
We also investigated the oxidation reaction of acyclic amine
under the standard condition. When amine 5 was used as
substrate, only amide 6 was obtained in 74% isolated yield
TPD. In our reaction, 5,6ꢀdihydrothieno[3,4ꢀc]pyrroles 3, which 45 without observation of the desire imide (Scheme 4).13 Although
are easily prepared by zirconoceneꢀmediated cyclization of
| Journal Name, [year], [vol], 00–00
we must await for further investigations to elucidate the reaction
2
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Scheme 4 Copperꢀcatalyzed oxidation of acyclic amine
5
In conclusion, we have developed an efficient methodology for
the synthesis of areneꢀfused cyclic imides via copperꢀcatalyzed
oxidation of cyclic amine. The reaction proceeded with high
selectivity. This reaction can be used to synthesize 1,3ꢀ
disubstituted TPD in high yields. Further investigations are still in
75
10 progress in this area.
This work was supported by the National Key Basic Research
Program of China (973 program) (2012CB933402) and National
Natural Science Foundation of China (21032004 and 21272132).
80
6
7
Notes and references
85
15 aKey Laboratory of Bioorganic Phosphorus Chemistry & Chemical
Biology (Ministry of Education), Department of Chemistry, Tsinghua
University, Beijing 100084, China; E-mail: cjxi@tsinghua.edu.cn
bState Key Laboratory of Elemento-Organic Chemistry, Nankai
University, Tianjin 300071, China
90
20 †Electronic Supplementary Information (ESI) available: Experimental
1
procedures, full characterization including H NMR and 13C NMR data
and spectra for all compounds. Xꢀray structure of 4a. See
DOI: 10.1039/b000000x/
‡CCDC 952362.
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4
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