Nitro-group-directed selective dealkylation

Article abstract of DOI:10.1080/00397910802633439

Nitro-substituted phenolic ethers were successfully selectively dealkylated. The directing effect of the nitro group is supported by the excellent regioselectivities and good yields. These reactions demonstrate that the complexation of AlCl3 with the phenolic nitro group is stronger than with the phenolic ether alone. The mechanism for the selective dealkylation directed by the nitro group is proposed.

Full text of DOI:10.1080/00397910802633439

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Nitro-Group–Directed Selective
Dealkylation
Xiujie Ji a , Bowen Cheng a , Jun Song a , Chao Liu b
& Yufei Wang c
a Tianjin Municipal Key Laboratory of Fiber
Modification and Functional Fiber, School of
Material Science and Chemical Engineering, Tianjin
Polytechnic University, Tianjin, China
b School of Materials Science and Engineering, Hebei
University of Technology, Tianjin, China
c School of Chemical Engineering, Dalian University
of Technology, Dalian, China
Available online: 27 Apr 2009
To cite this article: Xiujie Ji, Bowen Cheng, Jun Song, Chao Liu & Yufei Wang
(2009): Nitro-Group–Directed Selective Dealkylation, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 39:11,
2053-2057
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Synthetic Communications1, 39: 2053–2057, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802633439
Nitro-Group–Directed Selective Dealkylation
Xiujie Ji,1 Bowen Cheng,1 Jun Song,1 Chao Liu,2 and Yufei Wang3
1Tianjin Municipal Key Laboratory of Fiber Modification and Functional
Fiber, School of Material Science and Chemical Engineering,
Tianjin Polytechnic University, Tianjin, China
2School of Materials Science and Engineering, Hebei University of
Technology, Tianjin, China
3School of Chemical Engineering, Dalian University of Technology,
Dalian, China
Abstract: Nitro-substituted phenolic ethers were successfully selectively dealky-
lated. The directing effect of the nitro group is supported by the excellent regio-
selectivities and good yields. These reactions demonstrate that the complexation
of AlCl3 with the phenolic nitro group is stronger than with the phenolic ether
alone. The mechanism for the selective dealkylation directed by the nitro group
is proposed.
Keywords: AlCl3, complexation, nitro group, selective dealkylation
It has long been found that heteroatoms with lone pairs can complex with
Lewis acids. Stable complexes are often obtained when the heteroatoms
are nitrogen and oxygen.[1] Nitro is a fundamental functional group in
organic chemistry. We have reported that AlCl3 coordinates more
strongly to the oxygen in the nitro group and in the neigh‘boring ester
group than it does to an isolated phenolic ester.[2] We believe that this
directing effect of the nitro group can be taken advantage of in organic
synthesis such as selective dealkylation. To prove further the existence
Received October 12, 2008.
Address correspondence to Bowen Cheng, Tianjin Municipal Key Laboratory
of Fiber Modification and Functional Fiber, School of Material Science and
Chemical Engineering, Tianjin Polytechnic University, Tianjin 300160, China.
E-mail: bowen15@tjpu.edu.cn
2053

2054
X. Ji et al.
Table 1. Selective dealkylation of 1,4-dialkoxy-2-nitrobenzene using AlCl3
AlCl3 Temp. Time Yield
(%)a
Entry Product
R
(eq.)
(ꢀC)
(h)
Mp (ꢀC)
1
2
3
4
5
2a
2b
2c
2d
2e
Bn
1.0
1.0
2.0
1.5
1.5
0
0
60
60
60
0.5
87
96
93
87
96
154–156 (156–158[4]
)
i-Pr
Me
Et
1.5
2.5
1.5
1.0
42–44 (42–44[5]
74–75 (78–79[6]
)
)
80–82 (81–81.5[7]
Yellow oil
)
n-Bu
aYield of isolated product.
of this effect as well as to use this effect in organic synthesis prompted us
to carry out the following research.
The substrates, 1,4-dialkoxy-2-nitrobenzene and 1,5-dialkoxy-2-
nitrobenzene, were made by dialkylation of the hydroquinone and
resorcinol using the corresponding alkyl halides under basic condition
followed by nitration using Cu(NO3)2 and Ac2O.[3] Substrates were
treated with AlCl3 in anhydrous chloroform. Dialkylated nitro hydro-
quinones and dialkylated nitro resorcinols were all successfully and
selectively dealkylated in good yields and at good reaction rates
(Tables 1 and 2).
Table 2. Selective dealkylation of 1,5-dialkoxy-2-nitrobenzene using AlCl3
AlCl3 Temp.
(ꢀC)
Yield
Time (h) (%)a
Entry Product
R
(eq.)
Mp (ꢀC)
6
7
8
9
10
4a
4b
4c
4d
4e
Bn
1.0
1.0
1.5
1.5
1.5
0
0
60
60
60
0.5
1.0
1.5
1.5
1.0
90
94
93
93
96
94–96 (96–97[8])
44 (44[9])
i-Pr
Me
Et
92 (95[10]
)
)
76–78 (79[11]
n-Bu
43–44 (43–44[12]
)

Nitro-Group–Directed Selective Dealkylation
2055
The AlCl3 use ranged from 1 to 2 eq. For selective dealkylation of
benzyl and isopropyl groups, the reaction temperatures were 0ꢀC and
60ꢀC for methyl and primary alkyl groups. These results suggest that
the nitro oxygen and the ether oxygen both complex with AlCl3. This
makes the alkyl group susceptible to attack by a chloride anion to form
RX (Scheme 1). We carried out gas chromatography–mass spectrometric
(GC-MS) and GC anlysis and found that BnCl was formed in 81% yield.
This type of deprotection has been catalyzed by trifluroaceticacid
(TFA),[3] LiCl,[13] and LiI[14] under harsh conditions (e.g., in refluxing
quinoline).[14]
From the result listed in Tables 1 and 2, we can see that the ben-
zyl cation is the most stable one and the dealkylation is the fastest.
The secondary group (isopropyl) is the second fastest. The primary
alkyl group and methyl group are roughly at the same dealkylation
rate because the methyl group is less hindered but the primary cation
is more stabilized. Accordingly, the following mechanism is proposed
(Scheme 1).
Most of the dealkylated compounds such as 4-methoxy-2-nitrophe-
nol are useful intermediates for dye stuffs,[14] calcium ion indicators,[15]
antibacterial and antitumor medications,[16] anti-inflammatories, and
allergy inhibitors.[17]
In conclusion, we have provided evidence that the complexation of
AlCl3 with the phenolic nitro group is stronger than that with the pheno-
lic ether alone. This type of complexation has led to an efficient and
convenient selective dealkylation of dialkylated nitrohydroqinone and
nitroresorcinol.
All the products are fully characterized spectroscopically, and their
infrared (IR; 3250–3430 cmꢁ1) and 1H NMR (10–10.5 ppm) spectra
display typical intramolecular hydrogen bonding.
Scheme 1. Proposed reaction mechanism of selective dealkylation using AlCl3.

2056
X. Ji et al.
EXPERIMENTAL
Typical Procedure of Selective Dealkylation
The substrate 1 (1 mmol) was dissolved in anhydrous chloroform (30 mL)
and cooled to 0ꢀC. After aluminum chloride (1.0 to 2.0 eq) was added in
portions within 5 min, the reaction was kept at 0ꢀC or refluxed (as indi-
cated in Tables 1 and 2). Upon addition of AlCl3, the reaction solution
became red. Thin-layer chromatography (TLC) monitored the reaction.
When the substrate disappeared, the reaction was cooled to rt, and
reaction mixture was treated with 10% aq. HCl, extracted with dichloro-
methane (40 mL ꢂ 3), dried with Na2SO4, and concentrated. The residue
was purified by crystallization or flash-column chromatography.
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