Efficient indirect electrochemical synthesis of 2-substituted benzoxazoles using sodium iodide as mediator

Article abstract of DOI:10.1002/adsc.201300502

An electrochemical strategy for the effi-cient synthesis of 2-substituted benzoxazoles was de-veloped using a catalytic amount of sodium iodide (Nal) as a redox catalyst in a two-phase buffer system.

Full text of DOI:10.1002/adsc.201300502

FULL PAPERS
DOI: 10.1002/adsc.201300502
Efficient Indirect Electrochemical Synthesis of 2-Substituted
Benzoxazoles using Sodium Iodide as Mediator
Wei-Cui Li,a Cheng-Chu Zeng,a,* Li-Ming Hu,a Hong-Yu Tian,b
and R. Daniel Littlec
a
College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, Peopleꢀs Republic of China
Fax : (+86)-10-6739-6211; phone: (+86)-10-6739-6211; e-mail: zengcc@bjut.edu.cn
Food College, Beijing Technology & Business University, Beijing 100048, Peopleꢀs Republic of China
Department of Chemistry & Biochemistry, University of California, Santa Barbara, California 93106-9510, USA
b
c
Received: June 7, 2013; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300502.
Abstract: An electrochemical strategy for the effi- (NaI) as a redox catalyst in a two-phase buffer
cient synthesis of 2-substituted benzoxazoles was de- system.
veloped using a catalytic amount of sodium iodide
Keywords: electrochemical synthesis; indirect elec-
trolysis; sodium iodide mediator; 2-substituted ben-
zoxazoles
Introduction
of organic compounds. In such a catalytic system, the
stable iodide ion is initially oxidized in situ by the
À
The direct oxidative functionalization of C H bonds mild co-oxidant to form oxidation-active iodine spe-
À
constitutes one of the fundamental, challenging areas cies that further induce C H functionalization of a va-
of investigation in organic chemistry.[1] Since the pres- riety of substrates.[7–10] For example, Ishihara et al. re-
ence of metal impurities can be detrimental in phar- ported that upon treatment with H2O2, quaternary
maceutically important intermediates and final prod- ammonium iodides underwent conversion to the cor-
ucts, much effort has been made to develop metal- responding quaternary ammonium hypoiodite and/or
À
free reactions using organic oxidants or organic cata- iodite species. These substances can activate the a-C
lysts with co-oxidants as opposed to using toxic heavy H bond of the carbonyl group of ketophenols; once
metal oxidants or transition metal catalysts with co- this has been achieved, a subsequent cross-coupling
oxidants.[2] Apart from the common organic oxidants, with a phenolic oxygen atom affords 2-acyl-2,3-dihy-
such as DDQ[3] and TEMPO oxoammonium salts,[4] drobenzofuran derivatives.[7a,b] The oxidizing agents
À
hypervalent organic iodine reagents have been the are also known to activate the a-C H bonds of the
focus of much attention owing to their mild and che- carbonyl group of ketones, aldehydes and 1,3-dicar-
moselective oxidizing properties and their environ- bonyl compounds to facilitate intermolecular or intra-
mentally benign characteristics; significant progress molecular cross-coupling with carboxylic acids and
has been made during the last two decades.[5] Never- give the corresponding a-oxyacylation products.[7c]
theless, the stoichiometric use, poor solubility in Employing the same concept, Wan et al. accomplished
common solvents and potential shock-sensitive nature the direct cross-coupling of ethers and alkenes with
of these hypervalent iodine reagents detract from carboxylic acids to give a-acyloxy ethers[8a] and allylic
their appeal.
It has recently been found that systems consisting and t-BuOOH as the oxidant. In addition to the acti-
esters,[8b] respectively, by using (n-Bu)4NI as a catalyst
À
À
of a catalytic quantity of iodide ion (R4NI or MI) and vation of C H bonds for the formation of a C O
a stoichiometric amount of a co-oxidant[6] (e.g., bond, the catalytic combination has also been used in
H2O2,[7] t-BuOOH,[8] m-CPBA[9] and Oxone[10]) can the formation of C N and C C bonds. Nachtsheim
function in place of toxic heavy metal oxidants and et al. reported that the reaction of benzoxazoles and
hypervalent organic iodine reagents, and these have amines in the presence of a catalytic amount of (n-
been extensively applied to the oxidative conversions Bu)4NI and excess H2O2 or t-BuOOH generated the
À
À
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À
corresponding C N cross-coupling products in good
to excellent yields.[7d] Nearly simultaneously, Yu and
Han found that imidazoACTHNUTRGNEU[GN 1,2-a]pyridines derivatives
could be obtained in moderate to high yields from the
oxidative coupling of 2-aminopyridine with 1,3-dike-
tones or b-keto esters using 10 mol% (n-Bu)4NI as
a catalyst and 2 equiv. of 70% t-BuOOH as a co-oxi-
Scheme 1. Initial optimization of the indirect electrochemi-
cal synthesis of benzoxazole 4a.
.
dant in the presence of 20 mol% BF3 OEt2.[8c] After-
wards, using the same catalytic combination, Zhu acid conditions and at high temperatures,[16] or from
et al. reported that b-keto esters and benzylamines the condensation of 2-aminophenol and aldehydes
generated oxazoles in good yields,[8d] and Loh with subsequent oxidation using an excess of an oxi-
achieved the a-amination of aldehydes.[7e] In addition, dant.[17] Catalytic oxidative synthesis of benzoxazoles
Moran et al. reported that the intramolecular oxida- has also been reported using 4-methoxy-TEMPO as
tive cyclization of d-alkynyl-b-keto esters by using (n- a catalyst and oxygen as a terminal oxidant.[18]
À
Bu)4NI/H2O2 gave a C C coupling product, one that
Herein, we report an efficient electrochemical syn-
thesis of benzoxazoles, using a catalytic amount of
differs from that obtained using PhI/m-CPBA.[7f]
Electrochemistry provides an alternative, environ- sodium iodide as a mediator in a two-phase electrolyt-
À
mentally benign method to achieve the C H function- ic system consisting of a sodium carbonate buffer so-
alization, through direct electron transfer between an lution and dichloromethane (Scheme 1). No addition-
electrode and a substrate (direct electrolysis) or via al supporting electrolyte is required, thereby simplify-
an electrocatalyst playing the role of the electron ing the work-up and isolation process and leading to
transfer agent (indirect electrolysis).[11] In the course a reduction in waste. The process is conveniently car-
of the electrosynthesis, the anode serves as a co-oxi- ried out in an undivided cell. To the best of our
dant that is physically separated from the organic knowledge, this work represents the first example of
layer containing the substrate and is thus easily re- the electrochemical synthesis of these heterocycles
moved. Moreover, no chemical co-oxidant is needed. using iodide as a mediator.
À
We are interested in C H oxidative functionalization,
carried out via an indirect electrolysis and induced by
redox catalysts. In this context, we have developed Results and Discussion
novel redox catalysts based upon the triarylimidazole
scaffold and have achieved the oxidative functionali- To explore these ideas, we selected the Schiff base 3a
À
zation of benzyl C H bonds to afford the correspond- as a model substrate. An indirect anodic oxidation
ing aldehydes, ketones and esters.[11j,12] Recently, we was conducted in a simple beaker-type cell equipped
have also examined the bromide-mediated Knoevena- with an iron plate cathode and a Pt plate anode in the
gel–Michael reaction between tetronic acid and alde- presence of a catalytic amount of sodium iodide as
hydes under constant current electrolysis conditions the redox catalyst and ethanol as the solvent. With
using a catalytic amount of NaBr as a redox catalyst the passage of current, hydrogen gas evolution was
in ethanol solvent and in an undivided cell. Mechanis- observed on the cathode surface. The desired benzox-
tic studies indicated that the oxidation-active bromide azole 4a was isolated in a 64% chemical yield, but
species, generated in situ at the anode, coupled with with a current efficiency of only 23% (entry 1,
ethoxide (an electrochemically generated base, EGB) Table 1). Changing to acetonitrile as the solvent did
generated at the cathode, operated synergistically to not improve the chemical yield or the current efficien-
facilitate the Knoevenagel–Michael reaction.[13]
cy (entry 2, Table 1). Slightly lower yields were ob-
Based upon the significant progress of iodine ion/ tained when (n-Bu)4NI or NaBr were used as redox
co-oxidant induced oxidative transformations and our catalysts (entries 3 and 4, Table 1). Moreover, a glassy
À
studies of electrochemically induced C H functionali- carbon (GC) anode afforded 4a in only 49% (entry 5,
zation, we envisaged that an iodide-catalyzed oxida- Table 1). It should be noted that in these cases, passi-
tive activation could be achieved electrochemically. If vation of the anode occurred. This was first witnessed
so, then external co-oxidants would not be needed by the appearance of a yellow substance on the sur-
and the purification process would be greatly simpli- face of the anode. Passivation necessitated that the re-
fied.
action be interrupted several times in order to reacti-
Benzoxazoles are found extensively in natural prod- vate the anode by washing it with acetone. In addition
ucts and synthetically produced pharmaceuticals; they to these problems, p-bromobenzaldehyde, derived
exhibit a variety of biological activities.[14] Frequently, from the decomposition of 3a, invariably formed as
benzoxazoles are produced through the coupling of 2- a by-product.
aminophenol with carboxylic acid derivatives,[15] in
To avoid passivation of the electrode and decompo-
a process that is usually performed under strongly sition of the starting material, we elected to explore
2
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Efficient Indirect Electrochemical Synthesis of 2-Substituted Benzoxazoles
Table 1. The effects of redox catalyst and solvent on the
electrochemical synthesis of benzoxazole 4a.[a]
Table 2. Effect of the amount of redox catalyst and working
electrode upon the electrochemical synthesis of benz-
AHCTUNGTRENNUNG
oxazole.[a]
Entry Redox
catalyst
Solvent Anode Yield
[%][b,c]
C.E.
[%][d]
Entry Equiv. Organic
Aqueous
phase[c]
Yield C.E.
[%][d] [%][e]
NaI
phase[b]
1
2
3
NaI
NaI
EtOH Pt
CH3CN Pt
EtOH Pt
64
65
55
23
45
20
1
2
3
4
5
6
0.2
1.0
0.5
0.1
none
0.2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
buffer
buffer
buffer
buffer
buffer
H2O (10
mL)
94
94
98
30
trace
82
15
30
31
16
0
(n-
Bu)4NI
NaBr
NaI
4
5
EtOH Pt
EtOH GC
43
49
74
51
31
[a]
Reaction conditions: 1 mmol of Schiff base 3a and
0.2 mmol of redox catalyst in 20 mL of solvent, undivided
cell, current density of 5 mA/cm2, Fe plate cathode.
Isolated yield, using flash chromatography.
p-Bromobenzaldehyde was also isolated.
7[f]
8[f]
0.2
0.2
CH2Cl2
CH2Cl2 (5
mL)
buffer
buffer
91
25
>95 27
[b]
[c]
[d]
[a]
C.E.: current efficiency.
Reaction conditions: 1 mmol of Schiff base 3a, undivided
cell, constant current at 40 mA (current density:
~15 mA/cm2), Pt anode, Fe plate cathode.
10 mL unless indicated otherwise.
Buffer consisting of 10 mL of 0.1M Na2CO3/0.1M
NaHCO3.
Isolated yield, using flash chromatography.
C.E.: current efficiency.
GC anode, Fe plate cathode.
[b]
[c]
mixed solvent systems. A buffered aqueous tert-butyl
alcohol reaction medium was chosen initially since re-
ports have shown that an excellent yield of aldehydes
can be achieved using this solvent combination in
a TEMPO-mediated electrooxidation of primary and
secondary alcohols.[19] However, no reaction occurred
in our case, undoubtedly due to the low solubility of
the starting material 3a in this medium. We then
[d]
[e]
[f]
turned to the use of a two-phase system consisting of at a current density of 16 mA/cm2 proceeded with
an aqueous carbonate buffer (Na2CO3/NaHCO3) and only 23% current efficiency (entry 1, Table 3). In con-
dichloromethane. Under these conditions (undivided trast, excellent (85%) and moderate (51%) efficien-
cell, Pt anode and Fe cathode, constant current at cies could be achieved by reducing the current density
15 mA/cm2), passivation was indeed not observed and to 8 mA/cm2 and 4 mA/cm2, respectively (entries 2
the desired benzoxazole adduct 4a was produced in and 3, Table 3).
an excellent chemical yield (94%), although the cur-
From the results described above we conclude that
rent efficiency did not improve (15%) (entry 1, the optimal reaction conditions call for using a con-
Table 2).
stant current electrolysis at a current density of 8 mA/
Delighted by this result, we then focused upon cm2 and that the chemistry ought to be conducted in
other parameters including the quantity of redox cata- an undivided cell equipped with a GC anode and an
lyst, pH, and the nature of the anode. As shown in iron plate cathode, a 2:1 volume ratio of carbonate
Table 2, excellent yields of 4a were obtained when buffer solution to dichloromethane in which is dis-
1.0 equiv., or when 0.5 equiv. of NaI was used (en- solved 0.2 equiv. of sodium iodide to serve as the
tries 2 and 3), while it decreased to 30% when the redox catalyst.
amount was reduced to 0.1 equiv, (entry 4). Benzoxa-
zole 4a did not form in the absence of NaI (entry 5),
implying that iodide is essential. When the carbonate
buffer solution was replaced by water, a lower yield
(82%) of 4a was obtained indicating that pH also
plays an important role in the chemistry. When the
buffer was employed, the pH value of the buffer solu-
tion did not change during the course of the electroly-
sis (pH was 10.63 before and 10.32 after the electroly-
sis). Finally, it is worth noting that the use of a glassy
carbon (GC) anode also afforded an excellent yield
(entry 7, >95%) when the volume ratio of the buffer
solution to dichloromethane was changed to 2:1
(entry 8).
Table 3. The effects of current density on the electrochemi-
cal synthesis of benzoxazole.[a]
Entry Current density (mA/cm2) Yield [%][b] C.E. [%][c]
1
2
3
16
8
4
>95
>95
>95
23
85
51
[a]
Reaction conditions: GC anode, Fe plate cathode; undi-
vided cell, 1 mmol of Schiff base 3a in 5 mL CH2Cl2,
0.2 mmol of NaI in 10 mL of buffer solution (0.1M
Na2CO3/0.1M NaHCO3 (V:V=8:2), pH 10.5).
Yield determined by H NMR using 1,3,5-trimethoxyben-
zene as the internal standard.
C.E.: current efficiency.
[b]
[c]
1
We next focused upon improving the current effi-
ciency. As indicated in Table 3, the electrolysis of 3a
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Scheme 3. Control experiments.
either electron-donating (3b, 3c) or electron-with-
drawing (3d–3g) substituents was explored. The de-
sired benzoxazoles 4 were generally furnished in good
to excellent yields (70–90%) and moderate current ef-
ficiencies (45–67%). Adducts 4f and 4g did not form
due to the very low solubility of the precursors 3f and
Scheme 2. The indirect electrochemical synthesis of benzox-
azole.
With the optimized conditions in hand, we investi- 3g in dichloromethane (entries 6 and 7, Table 4).
gated the scope of the reaction (Scheme 2 and Next, the Schiff bases derived from o-aminophenol
Table 4). Initially, the Schiff base derived from p-bro- and a variety of substituted benzaldehydes (3h–3k)
mobenzaldehyde and an o-aminophenol bearing were examined. As shown in Table 4, good to excel-
lent yields were obtained. For example, 4h, 4i and 4j
were isolated in 89%, 91% and 79% yields, respec-
tively (entries 8–10). In addition, the electrolysis of 3k
afforded 4k in 89% chemical yield and 71% current
efficiency, suggesting that steric factors do not affect
the reaction (4h vs. 4k).
For comparison and to obtain potentially useful in-
sights pertaining to mechanism, the chemical version
of the reaction was explored. As depicted in
Scheme 3, benzoxazole 4a was obtained in 68% yield
when 1.0 equiv. of molecular iodine was used as the
oxidant, whereas most of the starting 3a was recov-
ered and only 15% of 4a was produced when a catalyt-
ic amount of molecular iodine was utilized. Clearly,
the electrochemical protocol is superior.
On the basis of the results described above, we pro-
pose the following mechanism for the iodide-mediat-
ed electrochemical synthesis of benzoxazoles
(Scheme 4). The sequence begins with an electro-
chemical oxidation of iodide in the buffer layer lead-
ing to the formation of molecular iodine, I2. Evidence
for its presence was visible at the surface of anode.
Furthermore, a characteristic blue color was observed
upon the addition of a few drops of a starch solution
Table 4. Scope of indirect electrochemical synthesis of benz-
ACHTUNGTRENNUNG
oxazoles.[a]
Entry Com- R1
pound
R2
R3
Yield C.E.
[%][b] [%][d]
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
H
CH3
H
Cl
H
NO2
H
H
H
H
H
H
H
4-BrC6H4
4-BrC6H4
95[c]
83
90
78
70
0
83
49
67
45
45
–
CH3 4-BrC6H4
H
Cl
H
4-BrC6H4
4-BrC6H4
4-BrC6H4
NO2 4-BrC6H4
0
89
–
H
H
H
H
4-CH3C6H4
4-CH3OC6H4 91
Ph
54
56
40
71
9
10
11
4j
4k
79
89
2-CH3C6H4
[a]
Reaction conditions: GC anode, Fe plate cathode; undi-
vided cell, 1 mmol of Schiff base 3 in 5 mL CH2Cl2,
0.2 mmol of NaI in 10 mL of buffer solution (0.1M
Na2CO3/0.1M NaHCO3, v/v=8:2, pH 10.5).
[b]
[c]
Isolated yield using flash chromatography.
1
The H NMR yield is nearly quantitative based upon the
use of 1,3,5-trimethoxybenzene as the internal standard.
C.E.: current efficiency.
[d]
Scheme 4. A proposed mechanism for the iodide-mediated electrochemical synthesis of benzoxazoles.
4
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Efficient Indirect Electrochemical Synthesis of 2-Substituted Benzoxazoles
was terminated when the starting material, 3, was consumed
to the reaction medium. Under the basic aqueous re-
as determined by TLC. After electrolysis, extraction was car-
ried out using CH2Cl2 (3ꢂ15 mL); the combined organic
layer was dried over MgSO4. Purified product was obtained
after column chromatography on silica gel using a solvent
mixture of petroleum ether and ethyl acetate (2:1).
action conditions, I2 is known to form HIO whose dis-
À [20]
proportionation leads to hypoiodite, IO2 .
Mean-
while, in the organic layer an intramolecular cycliza-
tion can establish an equilibrium between Schiff base
3 and benzoxazoline 5. Once in the organic layer,
each of the iodine-containing species can serve as an
oxidizing agent toward the benzoxazoline to afford
the benzoxazole adduct, 4. Meanwhile, the reactive
iodine species then are reduced to reform iodide and
re-enter the oxidative cycle.
2-(4-Bromophenyl)benzoxazole (4a):[21] mp 116–1178C;
1H NMR (300 MHz, CDCl3): d=7.36–7.39 (m, 2H), 7.58–
7.60 (m, 1H), 7.68 (d, J=8.7 Hz, 2H), 7.76–7.79 (m, 1H),
8.12 (d, J=8.7 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=
110.6, 120.1, 124.7, 125.4, 126.1, 126.2, 129.0, 132.2, 142.0,
150.7, 162.1; HR-MS (EI): m/z=272.9791, calcd, for
C13H8BrNO (M+): 272.9789.
2-(4-Bromophenyl)-5-methylbenzoxazole (4b):[22] mp
115–1168C; 1H NMR (400 MHz, CDCl3): d=2.49 (s, 3H),
7.16–7.19 (m, 1H), 7.45 (d, J=8.4 Hz, 1H), 7.55 (d, J=
0.8 Hz, 1H), 7.64–7.68 (m, 2H), 8.09–8.12 (m, 2H);
13C NMR (100 MHz, CDCl3): d=21.5, 110.0, 120.0, 126.0,
126.3, 126.5, 128.9, 132.2, 134.6, 142.2, 149.0, 162.2; HR-MS
(EI): m/z=286.9944, calcd. for C14H10BrNO (M+): 286.9946.
2-(4-Bromophenyl)-6-methylbenzoxazole (4c):[23] mp
113–1148C; 1H NMR (400 MHz, CDCl3): d=2.51 (s, 3H),
7.17–7.19 (m, 1H), 7.40 (d, J=0.8 Hz, 1H), 7.63–7.68 (m,
3H), 8.08–8.11 (m, 2H); 13C NMR (100 MHz, CDCl3): d=
21.8, 110.8, 119.4, 125.9, 126.0, 126.3, 128.8, 132.2, 135.9,
139.8, 151.0, 161.6; HR-MS (EI): m/z=286.9943, calcd. for
C14H10BrNO (M+): 286.9946.
Conclusions
In conclusion, we have developed a novel electro-
chemical strategy for the efficient synthesis of 2-sub-
stituted benzoxazoles using an indirect anodic oxida-
tion of a Schiff base. The electrochemical synthesis
was performed under constant current conditions in
a simple undivided cell using a catalytic amount of
NaI as redox catalyst and a two-phase system consist-
ing of buffer/CH2Cl2 as solvent. Following optimiza-
tion of the reaction conditions, the 2-substituted benz-
ACHTUNGTRENNUNGoxazoles were obtained in good-to-excellent yields
2-(4-Bromophenyl)-5-chlorobenzoxazole (4d):[22] mp 136–
and moderate current efficiency. Since the use of
large amounts of supporting electrolyte can be
a major drawback to electroorganic synthesis, it is
noteworthy that in the present instance no additional
supporting electrolyte or oxidant was required since
sodium iodide serves an electrolyte and source of the
oxidant. The application of this chemistry to the syn-
thesis of other heterocycles is underway.
1
1378C; H NMR (400 MHz, CDCl3): d=7.33–7.36 (m, 1H),
7.49–7.52 (m, 1H), 7.67–7.69 (m, 2H), 7.76 (d, J=2.0 Hz,
1H), 8.09–8.11 (m, 2H); 13C NMR (100 MHz, CDCl3): d=
111.3, 120.1, 125.6, 125.7, 126.7, 129.1, 130.3, 132.3, 143.1,
149.3, 163.4; HR-MS (EI): m/z=306.9405, calcd. for
C13H7BrClNO (M+): 306.9400.
2-(4-Bromophenyl)-6-chlorobenzoxazole (4e):[24] mp 117–
1188C; 1H NMR (400 MHz, CDCl3): d=7.35–7.37 (m, H),
7.60 (d, J=1.6 Hz, 1H), 7.68–7.69 (m, 3H), 8.09 (d, J=
8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=111.3, 120.6,
125.5, 125.7, 126.6, 129.0, 131.0, 132.3, 140.8, 150.9, 162.8;
HR-MS (EI): m/z=306.9406, calcd. for C13H7BrClNO (M+):
306.9400.
Experimental Section
Instruments and Reagents
2-(p-Tolyl)benzoxazole (4h):[21] mp 81–828C; 1H NMR
(400 MHz, CDCl3): d=2.44 (s, 3H), 7.28–7.37 (m, 4H),
7.55–7.60 (m, 1H), 7.75–7.79 (m, 1H), 8.16 (d, J=8.0 Hz,
2H); 13C NMR (100 MHz, CDCl3): d=21.6, 110.5, 119.9,
124.4, 124.5, 124.9, 127.6, 129.6, 142.1, 142.2, 150.7, 163.3;
HR-MS (EI): m/z=209.0844, calcd. for C14H11NO (M+):
209.0841.
All melting points were measured with a XT4A Electrother-
mal melting point apparatus and are uncorrected. IR spectra
1
were recorded as KBr pellets. H NMR spectra were record-
1
ed with a Bruker AV 400M spectrometer (400 MHz H fre-
quency). Chemical shifts are given as d values (internal stan-
dard: TMS). Schiff bases 3a–3k were synthesized according
to known procedures.[18] Other chemicals and solvents were
obtained from Beijing Chemicals Co. and used without fur-
ther purification.
2-(4-Methoxyphenyl)benzoxazole (4i):[21] mp 74–758C;
1H NMR (400 MHz, CDCl3): d=3.90 (s, 3H), 7.05 (d, J=
8.8 Hz, 2H), 7.32–7.35 (m, 2H), 7.55–7.58 (m, 1H), 7.73–
7.75 (m, 1H), 8.22 (d, J=8.8 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d=55.4, 110.4, 114.4, 119.6, 119.7, 124.4, 124.6,
129.4, 142.3, 150.7, 162.3, 163.2; HR-MS (EI): m/z=
225.0800, calcd. for C14H11NO2 (M+): 225.0790.
Typical Procedure for the Synthesis of Benzoxazoles
4a–4j by Constant Current Electrolysis
A 50-mL beaker-type cell was equipped with a GC cathode
and a Fe plate anode which were connected to a DC regu-
lated power supply. Schiff base 3 (1 mmol) dissolved in
5 mL CH2Cl2, and NaI (0.2 mmol) dissolved in 10 mL of car-
bonate buffer solution (0.1M Na2CO3/0.1M NaHCO3, v/v=
8:2, pH 10.5) were added to the cell and electrolyzed at
a constant current of 10 mA (~8 mA/cm2). The electrolysis
2-Phenylbenzoxazole (4j):[21] mp 57–588C; 1H NMR
(400 MHz, CDCl3): d=7.34–7.38 (m, 2H), 7.50–7.54 (m,
3H), 7.58–7.60 (m, 1H), 7.76–7.79 (m, 1H), 8.26–8.29 (m,
2H); 13C NMR (100 MHz, CDCl3): d=110.6, 120.0, 124.6,
125.1, 127.2, 127.6, 128.9, 131.5, 142.1, 150.8, 163.0; HR-MS
(EI): m/z=195.0691, calcd. for C13H9NO (M+): 195.0684.
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2-(o-Tolyl)benzoxazole (4k):[25] mp 54–558C; 1H NMR
(400 MHz, CDCl3): d=2.82 (s, 3H), 7.33–7.44 (m, 5H),
7.57–7.62 (m, 1H), 7.79–7.83 (m, 1H), 8.17–8.19 (m, 1H);
13C NMR (100 MHz, CDCl3): d=22.2, 110.5, 120.2, 124.4,
125.0, 126.1, 126.3, 130.0, 130.9, 131.8, 138.9, 142.2, 150.3,
163.4; HRMS (EI): m/z=209.0850, calcd. for C14H11NO
(M+): 209.0841.
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Acknowledgements
This work was supported by Grants from the National Natu-
ral Science Foundation of China (No. 21272021), Beijing
Natural Science Foundation (No. 7112008), the National Key
Technology R&D Program (2011BAD23B01), the National
Basic Research Program of China (No. 2009CB930200) and
a fund to C. C. Zeng, from the Beijing City Education Com-
mittee (KM201010005009). RDL is grateful to the US Na-
tional Science Foundation-supported PIRE-ECCI Program
for fostering our international collaboration.
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8 Efficient Indirect Electrochemical Synthesis of 2-Substituted
Benzoxazoles using Sodium Iodide as Mediator
Adv. Synth. Catal. 2013, 355, 1 – 8
Wei-Cui Li, Cheng-Chu Zeng,* Li-Ming Hu, Hong-Yu Tian,
R. Daniel Little
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