Synthesis of 2,5-Diaminoquinones by one-pot copper-catalyzed aerobic oxidation of hydroquinones and addition reaction of amines

Article abstract of DOI:10.1002/adsc.200900347

The aerobic oxidation of various hydroquinones was achieved by using copper nanoparticles entrapped in aluminum oxyhydroxide [Cu/ AlO(OH)] at room temperature. Furthermore, 2,5diamino-1,4-benzoquinones were synthesized directly from hydroquinone and amines by a one-pot procedure consisting of the copper-catalyzed aerobic oxidation of hydroquinones and the double addition of amines to the resulting quinones.

Full text of DOI:10.1002/adsc.200900347

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DOI: 10.1002/adsc.200900347
Synthesis of 2,5-Diaminoquinones by One-Pot Copper-Catalyzed
Aerobic Oxidation of Hydroquinones and Addition Reaction of
Amines
Sungjin Kim,a Daehwan Kim,a and Jaiwook Parka,*
a
Department of Chemistry, Pohang University of Science and Technology (POSTECH), San 31 Hyojadong, Pohang,
Kyeongbuk 790-784, Republic of Korea
Fax : (+82)-54-279-3399; e-mail: pjw@postech.ac.kr
Received: May 19, 2009; Revised: September 3, 2009; Published online: October 28, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900347.
Abstract: The aerobic oxidation of various hydro-
quinones was achieved by using copper nanoparti-
cles entrapped in aluminum oxyhydroxide [Cu/
AlO(OH)] at room temperature. Furthermore, 2,5-
diamino-1,4-benzoquinones were synthesized direct-
ly from hydroquinone and amines by a one-pot pro-
cedure consisting of the copper-catalyzed aerobic
oxidation of hydroquinones and the double addition
of amines to the resulting quinones.
benzoquinone for the oxidation of intermediate hy-
droquinones (Scheme 1).[6] Therefore, a stoichiometric
amount of oxidants such as copper salts is used to im-
prove the yields.[6b] This method, however, still suffers
from low reactivity of primary amines, and requires
six equivalents of amines to complete the addition re-
actions. Recently, a direct synthesis of diaminoqui-
nones from hydroquinone, which accompany the oxi-
dation of hydroquinone by electrochemical reac-
tions,[7] or enzymatic reactions,[8] has been reported.
However, the direct synthetic methods require re-
stricted reaction conditions, including reaction tem-
perature, solvent, electrolytes, and pH. Besides, more
than five equivalents of amines are used for the direct
synthesis.
Keywords: aerobic oxidation; 2,5-diaminobenzoqui-
nones; catalysis; conjugate addition; copper
There are several catalyst systems for the aerobic
Quinones are valuable and versatile compounds in oxidation of hydroquinone derivatives: CuSO4/
ACTHNUTRGNEUNG
nature and in organic synthesis.[1] In particular, amino- Al2O3,[9] Fe(III)-EDTA,[10] dinuclear copper com-
quinones have been studied for pigments and pharma- plex,[11] platinum complex,[12] NPV6Mo6/C,[13] and
ceuticals.[2,3] Recently, 2,5-diamino-1,4-benzoquinones polymer-incarcerated gold nanoparticles (PI Au).[14]
were reported as potent drug candidates for Alzheim- However, they often suffer from high reaction tem-
erꢀs disease.[4]
perature, low recyclability, and limited substrate
The addition of amines to p-benzoquinone is a scope. Recently, Kobayashi and co-workers have re-
usual procedure for the preparation of 2,5-diamino- ported a notable catalyst system consisting of poly-
1,4-benzoquinones.[5] However, the yields are general- mer-incarcerated platinum nanoparticles (PI Pt),[15]
ly low due to the consumption of two-thirds of the p- which can oxidize even electron-difficient hydroqui-
Scheme 1. Synthesis of 2,5-diamino-1,4-benzoquinones from 1,4-benzoquinone and amines.
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Scheme 2. Direct synthesis of 2,5-diamino-1,4-benzoquinones using 1 under an oxygen atmosphere.
nones at room temperature. Meanwhile, we have de- trate of the reaction mixture under the conditions of
veloped heterogeneous copper catalyst [Cu/ entry 1 after 1 h was monitored for 24 h and analyzed
a
AlO(OH), 1] that is prepared from readily available by ICP-MS. Further oxidation was not observed in
reagents through a simple procedure and shows a the filtrate, although a tiny amount of copper species
high activity in the (3+2)Huisgen cycloaddition of was present.[20]
alkynes and azides.[16,17] Herein, we report that the
The scope of our catalyst system was investigated
copper catalyst 1 is highly active and recyclable for under the conditions of the entry 1 of Table 1
the aerobic oxidation of a wide range of hydroqui- (Table 2). Mono- and disubstituted hydroquinones
nones. Furthermore, our catalyst is effective for the were transformed successfully into the corresponding
direct synthesis of 2,5-diamino-1,4-benzoquinones quinones in high yields in 1–4 h (Table 2, entries 1–8),
from amines and hydroquinones under ambient con- except those having carbonyl groups (Table 2, en-
ditions (Scheme 2).
tries 11 and 12). Methoxy-substituted hydroquinones
The activity of 1 was compared with those of com- were oxidized faster than halide-substituted ones
mercial copper catalysts in the aerobic oxidation of (Table 2, entries 5–8). The oxidation of pyrocatechol
hydroquinone (Table 1). Remarkably, our catalyst 1 was not possible with our catalyst (Table 2, entry 9).
(3 mol% of Cu) showed a distinct activity to give p- However, 3,5-di-tert-butylcatechol was transformed
benzoquinone in almost quantitative yield in 3 h at into 3,5-di-tert-butyl-1,2-benzoquinone in quantitative
room temperature under an oxygen atmosphere (1 yield although the reaction rate was much slower than
atm),[18] while commercial copper catalysts such as that of hydroquinone (Table 2, entry 10). We tested
CuO, CuO nanopowder, CuO/Al2O3, Cu2O, the recyclability of 1 in the oxidation of methylhydro-
CuCl2·2H2O, and CuCl were not active under these quinone (Table 3). The solid catalyst was recovered
conditions. The oxidation did not proceed in the ab- by decanting the product solution. Although initial
sence of 1 (Table 1, entry 8). To check the leaching- rates decreased slightly in reuse,[21] the oxidation
out of catalytic species during the oxidation,[19] the fil- using 3 mol% of Cu was completed within 2 h even in
the fifth use.
Then, we investigated the activity of 1 for the syn-
Table 1. Activities of Cu/AlO(OH) (1) and commercial Cu
catalysts for the aerobic oxidation of hydroquinone.[a]
thesis of 2,5-diamino-1,4-benzoquinones from hydro-
quinone and amines by a one-pot procedure, which
requires continuous oxidation of the intermediate hy-
droquinones formed from the reaction of quinones
with amines (Scheme 2). 2,5-Diamino-1,4-benzoqui-
nones were obtained as the major products in high
yields in the reaction of hydroquinone with various
amines (Table 4).[22] Primary amines (Table 4, en-
tries 1–4) as well as secondary amines (Table 4, en-
tries 5–7) were reacted successfully with hydroqui-
none. In all cases, only two equivalents of amines
were enough to complete the reaction, except for the
case of benzylamine. Under the conditions of the oxi-
dation, benzylamine was consumed in side reactions,
and the corresponding diaminobenzoquinone was ob-
Entry
Catalyst [mol% of Cu]
Time [h]
Yield[b] [%]
1
2
3
4
5
6
7
8
1 [3]
CuO [100]
3
3
3
3
3
3
3
24
96
0
<1
<1
0
<1
0
0
CuO nanopowder [100]
CuO/Al2O3 [6]
Cu2O [100]
CuCl2·2 H2O [100]
CuCl [100]
none
[a]
The reaction was performed on 0.50 mmol of hydroqui-
none in 3.0 mL of toluene with a copper catalyst at 258C
under O2 (1 atm).
[b]
Determined by GC with an internal standard.
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Synthesis of 2,5-Diaminoquinones by One-Pot Copper-Catalyzed Aerobic Oxidation
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Table 2. Oxidation of hydroquinones and catechols using 1.[a]
Entry
1
Substrate
Product
Time [h]
Yield[b] [%]
96
3
2
2
3
99
4
2
2
99[c]
4
5
99
95[c]
6
7
1
3
94[c]
99
8
9
3
98[c]
24[d]
0
10
11
24[d]
99[c]
24[d]
24[d]
0
0
12
[a]
The reaction was performed on 0.50 mmol of substrate in 3.0 mL of toluene with 1 (3.0 mol% of Cu) at 258C under O2
(1 atm).
[b]
[c]
[d]
Determined by GC with an internal standard.
Isolation yield.
5.0 mol% of Cu was used.
Table 3. Recycling test for 1.[a]
tained only in 72% yield by using four equivalents of
benzylamine (Table 4, entry 2). Notably, 2-methylazir-
idine did not suffer from ring-opening or polymeri-
zation during the coupling reaction (Table 4, entry 7).
It is also notable that memoquin, a potent drug candi-
date for Alzheimerꢀs disease, was obtained in 71%
isolated yield by our catalytic method. In a conven-
tional synthesis employing 1,4-benzoquinone and N1-
ethyl-N1-(2-methoxybenzyl)hexane-1,6-diamine, the
Reuse
1
2
3
4
5
Yield[b] [%]
>99
>99
>99
>99
>99
[a]
After washing the catalyst with toluene (3.0 mL) three
times, methylhydroquinone was added for reuse.
Determined by GC.
[b]
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Table 4. Direct coupling between hydroquinone and various amines using 1.[a]
Entry
1
Substrate
Time [h]
14
Product
Yield[b] [%]
88
2[c]
24
72
3
4
6
6
90
83
5
6
6
6
96 (92)[d]
85
7
6
89
71
8
24
[a]
The reaction was performed on 1.0 mmol of hydroquinone and 2.0 mmol of amine dissolved in 3.0 mL of ethyl acetate
with 1 (3.0 mol% of Cu) at 258C under O2 (1 atm).
Isolation yield.
Two equivalents of benzylamine were added after 12 h.
The number in parenthesis is the yield in the third use.
[b]
[c]
[d]
yield is only 17% (Table 4, entry 8).[4a] The recyclabili-
In conclusion, we have demonstrated an efficient
ty of our catalyst 1 was also tested in the coupling re- aerobic oxidation of various hydroquinones at room
action of piperidine; the catalyst can be reused at temperature, which is catalyzed by a recyclable
least three times without significant loss of activity copper catalyst. Furthermore, the copper catalyst has
(Table 4, entry 5).
been applied successfully for the synthesis of 2,5-di-
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Synthesis of 2,5-Diaminoquinones by One-Pot Copper-Catalyzed Aerobic Oxidation
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purified by column chromatography to give memoquin;
yield: 450 mg (71%).
ACHTUNGTRENNUNGamino-1,4-benzoquinones directly from hydroqui-
nones and two equivalents of amines in a one-pot
procedure.
Acknowledgements
Experimental Section
We are grateful for the financial supports from Korea Re-
search Foundation (KRF-2008-314-C00203), and the Korean
Ministry of Education through the BK21 project for our
graduate program.
Synthetic Procedure for Catalyst 1 [Cu/AlO(OH)]
CuCl2·2H2O (400 mg, 2.3 mmol), Pluronic P123 (4.0 g)
[EO20PO70EO20 (EO=ethylene oxide, PO=propylene
oxide], AlACHTUNGTRENNUNG(O-sec-Bu)3 (9.1 g, 37 mmol) and absolute ethanol
(8.0 g) were placed in a 100-mL flask equipped with a con-
denser. The reaction mixture was heated at 1608C for 3 h.
To the resulting suspension, water (3 mL) was added slowly
to form a bluish gel. After cooling to room temperature, the
bluish gel was filtered, washed with acetone, and dried at
1208C for 2 h to give 1 as greenish powder; yield: 3.7 g
(4.0 wt% of Cu). The copper content was estimated by ICP
analysis.
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Aerobic Oxidation of Hydroquinone at Room
Temperature
Catalyst 1 (22 mg, 3.0 mol% of Cu) was added to a mixture
of hydroquinone (55 mg, 0.50 mmol) and toluene (3 mL),
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(3 mL), and the reaction mixture was stirred at room tem-
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washed with toluene three times. The reaction was repeated
by adding toluene (3 mL) and methylhydroquinone (62 mg,
0.50 mmol).
Coupling Reaction between Hydroquinone and
Amines
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a solution of hydroquinone (110 mg, 1.0 mmol) and piperi-
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stirred at room temperature for 6 h under an O2 balloon.
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purified by column chromatography to give 2,5-dipiperidi-
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[21] See Supporting Information.
[22] The oxidation of hydroquinone was faster in toluene
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