Selenium-catalyzed oxidative carbonylation of 2-aminobenzyl alcohol to give 1,4-dihydro-2 H -3,1-benzoxazin-2-one

Article abstract of DOI:10.1016/S1872-2067(16)62537-8

An efficient, economical, and phosgene-free approach was developed for the preparation of 1,4-dihydro-2H-3,1-benzoxazin-2-one from 2-aminobenzyl alcohol. In terms of its key features, this reaction uses the cheap and recyclable non-metal selenium as a catalyst instead of the noble metal palladium; carbon monoxide as a carbonylation agent instead of virulent phosgene or one of its derivatives; and oxygen as an oxidant. The selenium-catalyzed oxidative carbonylation reaction of 2-aminobenzyl alcohol proceeded efficiently in a single pot in the presence of triethylamine to afford 1,4-dihydro-2H-3,1-benzoxazin-2-one in 87% yield. Furthermore, the selenium catalyst was readily recovered and recycled, affording a product yield of 80% after five cycles.

Full text of DOI:10.1016/S1872-2067(16)62537-8

Chinese Journal of Catalysis 37 (2016) 2034–2038
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c h n j c
Article
Selenium‐catalyzed oxidative carbonylation of 2‐aminobenzyl
alcohol to give 1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one
Xiaopeng Zhang*, Ping Wang, Xueli Niu, Zhengwei Li, Xuesen Fan, Guisheng Zhang#
Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions,
Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, Henan, China
A R T I C L E I N F O
A B S T R A C T
Article history:
An efficient, economical, and phosgene‐free approach was developed for the preparation of
1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one from 2‐aminobenzyl alcohol. In terms of its key features, this
reaction uses the cheap and recyclable non‐metal selenium as a catalyst instead of the noble metal
palladium; carbon monoxide as a carbonylation agent instead of virulent phosgene or one of its
derivatives; and oxygen as an oxidant. The selenium‐catalyzed oxidative carbonylation reaction of
2‐aminobenzyl alcohol proceeded efficiently in a single pot in the presence of triethylamine to af‐
ford 1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one in 87% yield. Furthermore, the selenium catalyst was
readily recovered and recycled, affording a product yield of 80% after five cycles.
Received 5 July 2016
Accepted 9 August 2016
Published 5 November 2016
Keywords:
Selenium
Oxidative carbonylation
1, 4‐Dihydro‐2H‐3, 1‐benzoxazin‐2‐one
2‐Aminobenzyl alcohol
Phase‐transfer catalysis
© 2016, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
1. Introduction
research efforts have been directed towards the development
of efficient methods for its synthesis. Traditionally, 1,4‐dihy‐
1,4‐Dihydro‐2H‐3,1‐benzoxazin‐2‐one is an important
structural motif that can be found in a wide range of biological‐
ly active compounds. For example, efavirenz, which is a
non‐nucleoside reverse transcriptase inhibitor for the treat‐
ment of HIV infections, consists of a substituted 1,4‐dihydro‐
2H‐3,1‐benzoxazin‐2‐one core [1–3]. Several other compounds
containing this structural motif have been reported to be orally
active nonsteroidal progesterone receptor antagonists, which
could be used for the treatment of hormone‐dependent cancers
[4–6]. 1,4‐Dihydro‐2H‐3,1‐benzoxazin‐2‐one also represents a
useful tool compound in organic synthesis for the preparation
of aza‐ortho‐xylylene via a thermal decarboxylation reaction
[7–9]. In light of the many uses of this compound, considerable
dro‐2H‐3,1‐benzoxazin‐2‐one has been readily prepared by the
reaction of 2‐aminobenzyl alcohol with phosgene [10] or a
suitable alternative such as chloroformate [11], triphosgene
[12], urea [13] or N,N'‐carbonyldiimidazole (CDI) [5]. However,
there are several drawbacks associated with these methods,
including high toxicity, low atom economy and the emission of
the corrosive waste products. Selenium‐ [14,15] and palladi‐
um‐catalyzed [16] reactions have been developed for the prep‐
aration of 1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one by the car‐
bonylation of 2‐nitrobenzyl alcohol with carbon monoxide.
Unfortunately, only one third of the CO consumed during these
reactions is transferred to the product, with the other two
thirds being converted to the greenhouse gas CO2 as a byprod‐
* Corresponding author. Tel: +86‐373‐3326335; Fax: +86‐373‐3325250; E‐mail: zhangxiaopengv@sina.com
# Corresponding author. Tel/Fax: +86‐373‐3325250; E‐mail: zgs@htu.cn
This work was supported by the Program for Changjiang Scholars and Innovative Research Team in University (IRT1061), the Program for Innova‐
tive Research Team in Science and Technology in University of Henan Province (15IRTSTHN003), the Young Backbone Teachers Training Fund of the
Education Department of Henan Province (2013GGJS‐059), and Henan Normal University (2011‐8).
DOI: 10.1016/S1872‐2067(16)62537‐8 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 37, No. 11, November 2016

Xiaopeng Zhang et al. / Chinese Journal of Catalysis 37 (2016) 2034–2038
2035
uct. Furthermore, the expensive palladium catalyst used in this
2.2. Typical procedure for the oxidative carbonylation of
carbonylation reaction increased the overall cost of the trans‐
formation. Palladium‐catalyzed [17] and sulfur‐assisted [18]
reactions have also been developed as alternative processes for
the carbonylation of 2‐aminobenzyl alcohol to give 1,4‐dihy‐
dro‐2H‐3,1‐benzoxazin‐2‐one. However, the application of
these methods had been limited by the high cost of the palla‐
dium catalyst, the requirement for a two‐step procedure or low
product yield. 1,4‐Dihydro‐2H‐3,1‐benzoxazin‐2‐one has also
been prepared by a variety of different methods, including the
direct carbonylation or tandem aza‐Wittig/heterocumulene‐
mediated annulation of 2‐azidobenzyl alcohol [19,20], aminol‐
ysis‐Hofmann rearrangement of phthalides [21], lithium boro‐
hydride reduction of 1,2‐dihydro‐3,1‐benzoxazine‐2,4‐dione
[22] and intramolecular nucleophilic substitution of 2‐(hy‐
droxymethyl)phenyl‐carbamate [23]. However, these process‐
es generally require the use of complex and expensive starting
materials or multi‐step procedures, thereby limiting their prac‐
tical utility. Despite the many achievements listed above, the
development of a green, efficient and cost‐effective approach
for the synthesis of 1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one is
still highly desired. Herein, we report a facile one‐pot proce‐
dure for the synthesis of 1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one
by the selenium‐catalyzed oxidative carbonylation of 2‐amino‐
benzyl alcohol with carbon monoxide (Scheme 1).
2‐aminobenzyl alcohol to give 1,4‐dihydro‐2H‐3,1‐benzoxazin‐
2‐one
2‐Aminobenzyl alcohol (2 mmol), Se (0.2 mmol), Et3N (5
mmol) and THF (5 mL) were added to a 100‐mL autoclave
equipped with a magnetic stirrer. The reactor was then sealed
and flushed three times with a gaseous mixture of CO and O2
(CO:O2 = 4:1). The autoclave was then pressurized with a gas‐
eous mixture of CO and O2 (CO:O2 = 4:1) to 2.5 MPa and heated
in an oil bath at 150 °C with vigorous stirring for 5 h. Upon
completion of the reaction, as determined by thin layer chro‐
matography analysis, the autoclave was cooled to room tem‐
perature and depressurized, followed by stirring for 30 min in
air to allow for the precipitation of the Se. The mixture was
then filtered and the filtrate was concentrated to give a residue,
which was purified by column chromatography (petroleum
ether/ethyl acetate, 3:1) to give 1,4‐dihydro‐2H‐3,1‐benzoxa‐
zin‐2‐one in 87% yield.
Colorless needles; mp 123–124 °C (lit. [14] 118–119 °C); 1H
NMR (400 MHz, CDCl3) δ = 8.36 (s, 1H), 7.28 (d, J = 12.0 Hz, 1H),
7.12 (d, J = 8.0 Hz, 1H), 7.07 (d, J = 8.0 Hz, 1H), 6.85 (d, J = 8.0
Hz, 1H), 5.34 (s, 2H).
3. Results and discussion
2. Experimental
3.1. Preparation of 1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one
2.1. General
It was envisaged that the selenium‐catalyzed oxidative car‐
bonylation of 2‐aminobenzyl alcohol could be conducted in a
one‐pot manner with carbon monoxide and oxygen. In practice,
this reaction proceeded smoothly to give the desired product
1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one and water, together with
a small amount of 1,3‐bis(2‐(hydroxymethyl)phenyl)urea,
suggesting the competitive intermolecular N‐carbonylation of
2‐aminobenzyl alcohol. 2‐Aminobenzyl alcohol reached com‐
plete conversion after 5 h when the reaction was conducted at
150 °C, affording 1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one in 87%
yield (Table 1, entry 2). The outcome of the reaction appeared
to be sensitive to the temperature. For example, the reaction
failed to reach the complete conversion of 2‐aminobenzyl al‐
CO (99.9%), O2 (99.9%) and selenium (99.95%) were pur‐
chased from commercial corporations and used as provided
without further purification. All of the other chemicals were
purchased as the AR grade and were used without further puri‐
fication. 1H NMR spectroscopy was conducted on a Bruker
DPX‐400 spectrometer (Bruker) using CDCl3 as a solvent with
Me4Si as an internal reference standard. Coupling constants (J)
were reported in Hz. Column chromatography was performed
on silica gel (200–300 mesh). The melting point of the product
was determined using a Keyi XT4 apparatus (Beijing, China)
and was uncorrected.
NH
NO
NH
2
chloroformate
2
2
tirphosgene
urea
+ COCl or
OH
2
OH
OH
CDI
R
e
f
s
.
-HCl and/or Refs. 5,10-13
ROH or NH
1
4
-
1
6
3
Refs. 19,20
CO/Pd
NH
N
3
H
2
This work
II
N
O
One-pot manner
OH
OH
CO/O /Se, -H O
or
1. Ph P/CH Cl
2
2
2
3
2
O
2. CO /Toluene
2
LiBH Ref. 22
4
-
R
O
H
H
N
O
NH
OR
O
O
O
O
CH OH
2
O
Scheme 1. Previous and present synthetic approaches to 1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one.

2036
Xiaopeng Zhang et al. / Chinese Journal of Catalysis 37 (2016) 2034–2038
Table 1
Preparation of 1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one under various conditions.
Entry
1
2
3
4
5
6
7
8
t (h)
4
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
T (°C)
150
150
140
160
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
Se (mmol)
0.2
0.2
0.2
0.2
0
Base
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
—
NaOH
K2CO3
NaOAc
C5H5N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N (mmol)
P(CO)/P(O2) (MPa)
2/0.5
Solvent
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
Xa/%
79
100
83
100
0
53
100
34
34
34
43
Yb/%
56
87
66
85
0
5
5
5
5
5
5
5
5
5
5
5
5
1
10
5
5
5
5
5
5
5
5
5
2/0.5
2/0.5
2/0.5
2/0.5
2/0.5
2/0.5
2/0.5
2/0.5
2/0.5
2/0.5
2/0.5
2/0.5
2/0.5
1/0.5
2/1.0
3/0.5
0.1
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
38
86
21
21
21
30
27
39
86
32
86
86
20
20
54
57
64
70
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
45
45
100
68
100
100
32
32
70
75
82
THF
—
2/0.5
2/0.5
2/0.5
2/0.5
2/0.5
2/0.5
Acetone
EtOAc
DMF
CH2Cl2
Toluene
85
Reaction conditions: 2‐aminobenzyl alcohol (2 mmol), base (5 mmol) and solvent (5 mL).
a Conversion of 2‐aminobenzyl alcohol. b Isolated yield of 1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one.
cohol when it was conducted at 140 °C for 5 h (Table 1, entry
3). Increasing the reaction temperature led to an increase in the
conversion of 2‐aminobenzyl alcohol, which reached 100% at
150 °C (Table 1, entry 2). Further increasing the temperature
did not led to any further improvements in the efficiency of the
reaction (Table 1, entry 4). Experimental results indicated that
the selenium catalyst was critical to the success of the current
catalytic system. Notably, the carbonylation reaction did not
proceed in the absence of selenium (Table 1, entry 5). However,
the reaction proceeded smoothly with as little as 0.1 equivalent
of selenium (Table 1, entry 2). Further increasing the selenium
loading failed to lead to further increases in the product yield
(Table 1, entry 7). Strongly alkaline conditions are generally
required for selenium‐catalyzed carbonylation reactions to
promote the formation of the active carbonyl selenide species
(COSe). With this in mind, we proceeded to examine the effects
of several bases on the carbonylation reaction. Although
2‐aminobenzyl alcohol can act as a base, the reaction proceed‐
ed poorly in the absence of an additional base (Table 1, entry
8). Several common bases, including NaOH, K2CO3, NaOAc, pyr‐
idine (C5H5N) and Et3N were tested in the current reaction, and
the results revealed that Et3N gave the best results (Table 1,
entries 2 and 9–12). We subsequently screened several doses
of this base and found that 2.5 equivalents gave the optimum
results (Table 1, entries 2, 13 and 14). We also investigate the
ratio of CO to O2 used in this reaction and found 2 MPa CO to‐
gether with 0.5 MPa O2 gave the best results (Table 1, entries 2
and 15–17). The carbonylation reaction proceed poorly in the
absence of a solvent (Table 1, entry 18), which promoted us to
seek a proper solvent for this reaction. Several common sol‐
vents we screened, including THF, acetone, EtOAc, DMF, CH2Cl2
and toluene, and the results revealed that the reaction per‐
formed most effectively with THF, followed by toluene (Table 1,
entries 2 and 19–23).
3.2. Phase‐transfer catalysis function of selenium catalyst
One remarkable advantage of the current catalytic system is
that the selenium catalyst has all of the functional characteris‐
tics of a phase‐transfer catalyst, in that it cannot only efficiently
catalyze the desired transformation, but can also be readily
recovered from the reaction mixture. We noted that the sele‐
nium powder was generally insoluble in the media prior to the
reaction, making the catalytic system heterogeneous at this
stage in the process. However, during the reaction process, the
selenium dissolved completely to form a homogeneous solu‐
tion, allowing it to efficiently catalyze the carbonylation reac‐
tion. Upon completion of the reaction, the selenium powder
precipitated from the reaction media via an oxidation reaction
in air, allowing for the catalyst to be readily recovered by suc‐
tion filtration. Notably, the recovered selenium could be recy‐
cled without any discernible decrease in its catalytic perfor‐
mance [14,24]. For example, the selenium catalyst gave a
product yield of 80% after five cycles.
3.3. Proposed reaction pathway
A plausible mechanism for the formation of 1,4‐dihydro‐
2H‐3,1‐benzoxazin‐2‐one is shown in Scheme 2. The reaction of
selenium with carbon monoxide in the presence of Et3N would
give the active COSe species A [25,26]. The nucleophilic attack
of 2‐aminobenzyl alcohol to A would generate intermediate B

Xiaopeng Zhang et al. / Chinese Journal of Catalysis 37 (2016) 2034–2038
2037
Se
a low cost, atom economical, one‐pot, phosgene‐free process
for the preparation of 1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one
without the formation of any corrosive waste or carbon diox‐
ide, making this approach a particularly promising alternative
to the existing procedures.
H O
CO
2
O
2
.
H Se
2
Et N
.
COSe Et N
3
3
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We have developed an efficient and economical approach
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2‐aminobenzyl alcohol. The key features of this reaction in‐
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as a catalyst instead of the noble metal palladium; carbon
monoxide as a carbonylation agent instead of virulent phos‐
gene or one of its derivatives; and oxygen as an oxidant. Under
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2‐aminobenzyl alcohol proceeded efficiently in the presence of
triethylamine to afford the desired product 1,4‐dihydro‐2H‐3,1‐
benzoxazin‐2‐one in 87% yield. Overall, this process represents
Graphical Abstract
Chin. J. Catal., 2016, 37: 2034–2038 doi: 10.1016/S1872‐2067(16)62537‐8
Selenium‐catalyzed oxidative carbonylation of 2‐aminobenzyl alcohol to give 1,4‐dihydro‐2H‐3,1‐benzoxazin‐2‐one
Xiaopeng Zhang*, Ping Wang, Xueli Niu, Zhengwei Li, Xuesen Fan, Guisheng Zhang*
Henan Normal University
O
OH
NH2
O2, Et3N
+
CO
Cat. Se
N
O
H
phase-transfer catalysis!
87% yield
one-pot phosgene-free manner!
1,4‐Dihydro‐2H‐3,1‐benzoxazin‐2‐one was prepared in 87% yield via the one‐pot selenium‐catalyzed oxidative carbonylation of
2‐aminobenzyl alcohol. The selenium catalyst was readily recovered and recycled.

2038
Xiaopeng Zhang et al. / Chinese Journal of Catalysis 37 (2016) 2034–2038
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