One-pot tandem synthesis of 2-arylbenzoxazole derivatives via copper-catalyzed C-N and C-O bond formation

Article abstract of DOI:10.1002/adsc.201200164

The reaction of 2-(2-halophenyl)halobenzamides with a series of nitrogen nucleophiles resulted in the formation of benzoxazole derivatives. This procedure involves copper-catalyzed one-pot tandem C-N/C-O coupling reactions. No ligand was used in the reaction, even in the cases of primary or secondary amides, which were used as N-nucleophiles. However, L-proline was used as ligand in the case of N-aromatic heterocycles like indole, imidazole and pyrazole derivatives. Copyright

Full text of DOI:10.1002/adsc.201200164

FULL PAPERS
DOI: 10.1002/adsc.201200164
One-Pot Tandem Synthesis of 2-Arylbenzoxazole Derivatives via
À
À
Copper-Catalyzed C N and C O Bond Formation
Veerababurao Kavala,a Donala Janreddy,a Mustafa J. Raihan,a Chun-Wei Kuo,a
Chintakunta Ramesh,a and Ching-Fa Yaoa,*
a
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei, Taiwan 116, R.O.C.
Fax : (+886)-2-2932-4249; e-mail: cheyaocf@ntnu.edu.tw or cheyaocf@yahoo.com.tw
Received: February 28, 2012; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200164.
Abstract: The reaction of 2-(2-halophenyl)halobenz- However, l-proline was used as ligand in the case of
ACHTUNGTRENNUNGamides with a series of nitrogen nucleophiles result- N-aromatic heterocycles like indole, imidazole and
ed in the formation of benzoxazole derivatives. This pyrazole derivatives.
procedure involves copper-catalyzed one-pot tandem
C N/C O coupling reactions. No ligand was used in Keywords: benzoxazoles; C heteroatom bond for-
the reaction, even in the cases of primary or secon- mation; copper; ligand-free conditions; tandem reac-
dary amides, which were used as N-nucleophiles. tions
À
À
À
Introduction
halo-N-(2-haloaryl)benzamide with amines (primary
or secondary). We expected that the reaction of 2-
À
The copper-catalyzed formation of C heteroatom halo-N-(2-haloaryl)benzamide with an amine in the
bonds has attracted much attention in the recent presence of a copper catalyst would initially produce
times due to the efficiency of the reaction, stability in a 2-(aryl/alkACTHNUTRGNEyNUG lamino)-N-(2-halophenyl)benzamide (I)
air and economic viability.[1] A wide variety of hetero- which would then undergo either an intramolecular
À
cyclic compounds has been synthesized using various C N arylation or a C-O arylation to form dibenzoaze-
À
copper catalysts and employing a tandem one-pot C
pinone (A) or benzoxazole derivtives (B), respective-
heteroatom bond formation strategy.[1,2] In fact, ly (Scheme 1).
tandem one-pot reactions have tremendous advantag-
es over stepwise reactions in that waste production is
minimized, fewer reagents are needed, separation Results and Discussion
processes are simpler and energy, time, and costs are
minimal.[3] Hence, we focused our recent research on To test our hypothesis, we used 2-iodo-N-(2-
tandem one-pot procedures for use in the synthesis of iodophenACTHNUTRGNEUyGN l)benzamide and benzylamine as staring
various heterocyclic compounds.[4] We recently report- materials. In our initial experiment, we treated 2-
ed on a copper-catalyzed one-pot tandem process for iodo-N-(2-iodophenyl)benzamide and benzylamine
the synthesis of sultam-fused triazoles.[5] In a continua- with K2CO3 in DMSO in the presence of copper
tion of this research, we discovered a paper by Fu and iodide as a catalyst at room temperature. Under these
co-workers regarding the reaction of 2-halo-N-(2- conditions, the reaction produced 2-(benzylamino)-N-
halo
ACHTUNGTRENNUNGaryl)benzamide with ethylcyanoacetate or malo- (2-iodophenyl)benzamide (I), which, on heating at
nonitrile to give benzimidazoCATHNUGTRNE[NGU 1,2-b]isoquinolin-11-one 808C, gave a fluorescent product (either A or B). The
derivatives.[6] This reaction involves the copper-cata- 1H NMR spectrum of the product showed a broad sin-
lyzed C-arylation of ethylcyanoacetate, followed by glet at 8.91 for an NH proton, and a doublet at
the nucleophillic addition of the amide group to the 4.63 ppm for two benzylic protons. We assumed that
cyano functionality to generate an aminophenyliso- the splitting of benzylic protons was due to coupling
À
quinoline derivative, which further undergoes a C N between the NH and benzylic protons. This feature is
coupling reaction to give a benzimidazo
A
nolin-11-one moiety. Taking cues from this reaction, since, in the latter case, the signals for these protons
we carried out a detailed study of the reaction of 2- would be expected to be a singlet or a doublet of dou-
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Scheme 1. Hypothesized products from the reaction of 2-iodo-N-(2-iodoaryl)benzamide with a primary amine.
blets. Moreover, we found a signal at 163 ppm in the product produced in our reaction, although the condi-
13C NMR spectrum, which is the characteristic peak tions are different. The result may be accounted for
for a C=N group in benzoxazole derivatives. The by comparing the effect of the ortho-substituent[11] of
structure was confirmed by a single crystal X-ray dif- ring X and Y of the substrate (Scheme 1). As ring X
fraction analysis (Figure 1).
is directly conjugated to a carbonyl moiety, it is more
Although there are several known copper-catalyzed electron deficient than ring Y. As a result, the ortho
cross-coupling reactions for N-arylation[7] as well as substituent effect in ring X is stronger than that in
the generation of 2-arylbenzoxazole derivatives,[8] to ring Y. Hence, the nucleophilic substitution takes
the best of our knowledge, there is no protocol avail- place first at ring X to form I. The presence of a sec-
able for the synthesis of 2-arylbenzoxazole derivatives ondary amine enhances the electron density on ring
bearing an amine or amide functionality in the aryl X, which increases the electron density on the carbon-
ring at an ortho position using a copper catalyst. In yl oxygen due to resonance. An enhancement in elec-
fact, these types of benzoxazole derivatives have been tron density can also be attributed to the delocaliza-
reported to exhibit a variety of biological activities.[9] tion of the nitrogen lone pair of electrons on the
On the other hand, while our manuscript was being amide functionality on the carbonyl oxygen. On the
prepared, Ma and his co-workers documented the re- other hand, the delocalization of the lone pair of elec-
action of 2-bromo-N-(2-bromoaryl)benzamide deriva- trons of the amine nitrogen makes the amine less nu-
tives with various aliphatic amines using a CuCl cata- cleophilic than oxygen. These phenomena may drive
lyst in the presence of K3PO4 in DMSO. From the an- the reaction in the direction of product B.
1
alytical data, i.e., H, 13C NMR and mass spectrum,
Encouraged by the initial results, we focused our at-
they proposed that the product had a dibenzoazepin- tention on optimizing the reaction. In this regard, we
ACHTUNGTRENNUNG
product described by Ma et.al. are identical to the such as CuI, CuBr and CuCl. We found that the reac-
tion was equally efficient with all the copper salts
tested. The effect of solvent on the reaction was also
examined. Toluene, dioxane both resulted in the for-
mation of the expected product, but the yields were
low. In both these cases a considerable amount of the
intermediate 2-(benzylamino)-N-(2-iodophenyl)benz-
AHCTUNGTREGUNaNN mide remained, even after 24 h. A longer reaction
time was needed when CH3CN was used as the sol-
vent. However, using DMSO, the desired product was
obtained in good yield. We then screened some bases,
including K2CO3, NaOAc, Cs2CO3, and K3PO4. When
the reaction was run in the presence of K3PO4, we ob-
tained the intermediate N-arylated product as a major
product, even after 24 h. Moreover, K2CO3 and
Cs2CO3 were found to be the best bases for promot-
ing this reaction (Table 1).
Figure 1. Single crystal X-ray structure of 3aa.[13]
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One-Pot Tandem Synthesis of 2-Arylbenzoxazole Derivatives
Table 1. Optimization of reaction conditions.
Figure 2. Single crystal X-ray structure of 3af.[13]
various primary amines to prepare various 2-(2-alkyl-
AHCTUNGTREGaNNUN minophenyl)benzo[d]oxazoles in moderate to good
yield, we then turned our attention of the use of sec-
ondary amines as nitrogen nucleophiles in the reac-
tion. In this context, we chose 2-iodo-N-(2-iodophen-
[a]
AHCTUNGTREGyNNUN l)benzamide as substrate to couple with various sec-
Reaction conditions: 2-iodo-N-(2-iodophenyl)benzamide
ondary amines including dibutylamine, pyrrolidine, pi-
peridine, morpholine and mono-N-substituted pipera-
zine derivative. It is worthy of note that the reaction
of long-chain dialkylamines resulted in the formation
of the intermediate N-coupled product only. This is
perhaps arising from the steric effect of the bulky
N,N-dibutyl group. The reactions with pyrrolidine and
(0.5 mmol), benzylamine (1 mmol), K2CO3 (2 mmol), CuI
(0.10 mmol), DMSO (3 mL).
Isolated yields.
2-(Benzylamino)-N-(2-iodophenyl)benzamide was isolat-
ed as a side product
[b]
[c]
After optimizing the reaction conditions, we fo- piperidine resulted in the formation of the expected
cused our attention on exploring the generality of this products in good yields. However, the reaction of
methodology with respect to various primary amines morpholine and piperazine derivatives took longer
and substituted 2-iodo-N-(2-iodoaryl)benzamides. We times to furnish their corresponding products
initially investigated the reactions of various primary (Table 3).
amines
with
2-iodo-N-(2-iodophenl)benzamide.
To further extend the scope this methodology, we
Under the optimized reaction conditions, long-chain utilized amides as N-nucleophiles in this reaction. It is
aliphatic amines like dodecylamine produced the cor- interesting to note that the primary amides reacted
responding benzoxazole derivative (3ab) in moderate under the present reaction conditions to furnish the
yield. However, reactions with ethoxyethylamine and desired products in good yields. Moreover, it was nec-
allylamine provided the corresponding products (3ac essary to increase the reaction temperature to 1008C
and 3ad) in good yields. Furthermore, the present re- for the reactions involving secondary amides as cou-
action conditions also applied to the other primary pling partners. Using modified conditions a number of
amines such as furylamine, homoveratrylamine and substituted 2-iodo-N-(2-iodoaryl)benzamides was
tryptamine, which results in the formation of 3ae, 3af, treated with 2-pyrrolidinone to obtain their corre-
and 3ag, respectively. We next studied the reaction sponding 1-[2-(benzo[d]oxazol-2-yl)phenyl]pyrrolidin-
with various substituted 2-iodo-N-(2-iodoaryl)benz- 2-one derivatives in good to moderate yields. In addi-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
electron-withdrawing substituents proceeded smooth- amides possessing six- and seven-membered rings (2-
ly to produce the corresponding benzoxazole deriva- piperidinone, carprolactum). It is noteworthy that 2-
tives with equal ease (Table 2). To ascertain the struc- pyrrolidinone was much more reactive than 2-piperdi-
ture of these derivatives further, we analyzed struc- none and carprolactum. Steric hindrance may be the
ture of one more representative compound (3af) by reason for this reactivity trend. (Table 4).
single crystal X-ray analysis. The crystal structure of
the compound 3af is depicted in Figure 2.
Indole and azaindole structures are important
motifs that are found in many natural products and
After successfully applying our reaction conditions pharmaceuticals. In fact, it was reported that a benzox-
to substituted 2-iodo-N-(2-iodoaryl)benzamides and azole containing an indole moiety has uses as
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Table 2. Scope of the reaction with respect to primary amines.
[a]
[b]
Reaction conditions: amide (0.5 mmol), N-nucleophile (1 mmol), K2CO3 (2 mmol), CuI (0.10 mmol),
DMSO (2 mL) and the reactions were performed at 808C.
Isolated yields.
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One-Pot Tandem Synthesis of 2-Arylbenzoxazole Derivatives
Table 3. Scope of the reaction with respect to secondary amines.
[a]
Reaction conditions: amide (0.5 mmol), N-nucleophile (1 mmol), K2CO3 (2 mmol), CuI (0.10 mmol),
DMSO (2 mL) and the reactions were performed at 808C.
Isolated yields.
Trace of was desired product was formed.
Reaction carried out initially 808C. After formation of the N-arylated product, the temperature rise to
[b]
[c]
[d]
1008C.
[e]
Traces of unidentified products were observed in all the reactions (<5%).
PPARc/d dual agonist.[12] Thus, we intended to install dition of l-proline (30 mol%) as ligand. The results
these moieties in 2-phenylbenzoxazole at the ortho are shown in the Table 5.
position of the phenyl ring. In this regard, we used
To diversify the methodology further, we investigat-
indole and azaindole as nitrogen nucleophiles in the ed the reaction with various azoles such as imidazole,
present reaction. Under the present reaction condi- pyrazole and triazole. Here, we also used l-proline as
tions, the desired product obtained in low yields. We ligand. The reaction with pyrazole gave a moderate
could obtain good yields of the products with the ad- yield of the desired product whereas the reactions
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Table 4. Scope of the reaction with respect to amides.
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One-Pot Tandem Synthesis of 2-Arylbenzoxazole Derivatives
Table 4. (Continued)
[a]
Reaction conditions: amide (0.5 mmol), N-nucleophile (1 mmol), K2CO3 (2 mmol), CuI (0.10 mmol), DMSO
(2 mL) and the reactions were carried out initially 808C. After formation of the N-arylated product, the tempera-
ture was increased to 1008C.
Isolated yields.
[b]
[c]
Traces of unidentified products were observed in all the reactions (<5%).
with imidazole and triazole produced the expected layer was separated, dried over anhydrous MgSO4 and con-
centrated under vacuum to obtain the crude product. The
crude product was further purified by column chromatogra-
phy.
products in 42% and 48%, respectively. The results
are shown in Scheme 2.
General Procedure for Reactions Involving
Secondary Amines and Secondary Amides
Conclusions
In summary, we have reported herein on the synthesis
of 2-arylbenzoxazole derivatives having an amine or
amide functionality in the aryl group at the ortho po-
Copper iodide (20 mol%) and potassium carbonate
(2 mmol) were added to a solution of 2-iodo-N-(2-iodoaryl)-
benzamide (0.5 mmol) and secondary amine or amide
(1 mmol) in DMSO. The reaction mixture then heated at
808C until the 2-iodo-N-(2-iodoaryl)benzamide was com-
pletely converted into the intermediate N-arylated product
as indicated by TLC. After the formation of the intermedi-
ate N-arylated product, the reaction temperature was raised
to 1008C and the reaction continued until completion (for
the times mentioned in Table 3 and Table 4). The reaction
mixture was then extracted with ethyl acetate and the ethyl
acetate solution was washed with brine solution. The organic
layer was separated, dried over anhydrous MgSO4 and con-
centrated under vacuum to obtain the crude product. The
crude product was further purified by column chromatogra-
phy.
À
À
sition through a copper-catalyzed tandem C N/C O
coupling strategy using readily available substrates. A
wide range of nitrogen nucleophiles was investigated
in this reaction, which can be used to produce a varie-
ty of benzoxazole derivatives in moderate to good
yields. This procedure is simple, handy and most of
the reactions were conducted under ligand-free condi-
tions.
Experimental Section
General Procedure for Reactions Involving Primary
Amines and Primary Amides
General Procedure for Reactions Involving N-
Heterocyclic Aromatics (Indole, Azaindole, Pyrazole,
Imidazole and Triazole)
Copper iodide (20 mol%) and potassium carbonate
(2 mmol) were added to a solution of 2-iodo-N-(2-iodoaryl)-
benzamide (0.5 mmol) and a primary amine or amide
(1 mmol) in DMSO. The reaction mixture was then heated
at 808C until the reaction was complete. The reaction mix-
ture was then extracted with ethyl acetate and the ethyl ace-
tate solution was washed with a brine solution. The organic
Copper iodide (15 mol%), l-proline (30 mol%) and potassi-
um carbonate (2 mmol) were added to a solution of 2-iodo-
N-(2-iodoaryl)benzamide (0.5 mmol) and N-hetrocyclic aro-
matics (1 mmol) in DMSO. The reaction mixture then
heated at 808C until the 2-iodo-N-(2-iodoaryl)benzamide
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Table 5. Reaction of indole and azaindole with 2-iodo-N-(2-iodoaryl)benzamides.
[a]
Reaction conditions: amide (0.5 mmol), N-nucleophile (1 mmol), K2CO3 (2 mmol), CuI
(0.15 mmol), DMSO (2 mL) and the reactions were carried out initially 808C. After formation
of the N-arylated product, the temperature was increased to 1008C.
Isolated yields.
[b]
[c]
Traces of unidentified products were observed in all the reactions (<5%).
Scheme 2. Reaction of various azoles with 2-iodo-N-(2-iodoaryl)benzamide. Reaction conditions: (i) 15 mol% CuI/30 mol%
proline, DMSO, K2CO3 (3 equiv.), 80–1008C.
was completely converted into the intermediate N-arylated
product as indicated by TLC. After the formation of the in-
termediate N-arylated product, the reaction temperature
was raised to 1008C and the reaction continued until com-
pletion (for the times mentioned in Table 5). The reaction
mixture was then extracted with ethyl acetate and the ethyl
acetate solution was washed with brine solution. The organic
layer was separated, dried over anhydrous MgSO4 and concen-
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One-Pot Tandem Synthesis of 2-Arylbenzoxazole Derivatives
trated under vacuum to obtain the crude product. The crude
product was further purified by column chromatography.
7.8 Hz, 1H), 7.67–7.65 (m, 1H), 7.56–7.53 (m, 1H), 7.39–
7.29 (m, 3H), 6.91–6.81 (m, 4H), 6.72 (t, J=7.2 Hz, 1H),
3.85 (s, 3H), 3.83 (s, 3H), 3.60 (q, J=7.0 Hz, 2H), 3.04 (t,
J=7.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=163.4,
149.3, 149.2, 148.4, 147.9, 141.9, 132.9, 132.3, 129.3, 124.8,
124.4, 121.1, 119.3, 115.3, 112.5, 111.6, 111.2, 110.4, 108.4,
56.1, 56.0, 45.1, 35.5; MS (EI): m/z (%)=374 (M+, 100);
HR-MS: m/z=374.1627, calcd. for C23H22N2O3 (M+):
374.1630.
Spectral Data of Compounds
2-(Benzo[d]oxazol-2-yl)-N-benzylaniline (3aa): Colorless
1
solid; mp 113–1158C; H NMR (400 MHz, CDCl3): d=8.91
(brs, 1H), 8.12 (d, J=8.0 Hz, 1H), 7.69–7.66 (m, 1H), 7.56–
7.54 (m, 1H), 7.41 (d, J=7.4 Hz, 2H), 7.36–7.24 (m, 6H),
6.76–6.70 (m, 2H), 4.63 (d, J=5.6 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d=163.5, 149.3, 148.5, 141.9, 139.4,
132.9, 129.2, 128.8, 127.2, 127.1, 124.8, 124.4, 119.5, 115.6,
111.7, 110.4, 108.5, 47.2; MS (EI): m/z (%)=300 (M+, 100),
223 (5), 193 (85) 150 (5); HR-MS: m/z=300.1269, calcd. for
C20H16N2O (M+): 300.1263.
2-(Benzo[d]oxazol-2-yl)-N-dodecylaniline (3ab): Colorless
solid; mp 76–788C; 1H NMR (400 MHz, CDCl3): d=8.39
(brs, 1H), 8.13 (dd, J=1.3, 8.0 Hz, 1H), 7.74–7.71 (m, 1H),
7.58–7.54 (m, 1H), 7.41 (d, J=7.4 Hz, 1H), 7.40–7.30 (m,
3H), 6.62 (d, J=8.0 Hz, 1H), 6.74 (t, J=8.0 Hz, 1H), 3.35
(s, 2H), 1.84–1.80 (m, 2H), 1.55–1.52 (m, 2H), 1.30–1.28 (m,
16H), 0.90 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=163.6, 149.3, 148.8, 142.0, 132.9, 129.2, 124.7, 124.3, 119.4,
114.9, 111.1, 110.3, 108.0, 43.3, 32.1, 29.9, 29.8, 29.7, 29.6,
29.4, 27.5, 22.9, 14.3; MS (ESI): m/z (%)=379 (M+H, 100),
211 (40); HR-MS: m/z=379.2770, calcd. for C25H35N2O
(M+H): 379.2749.
N-[2-(1H-Indol-3-yl)ethyl]-2-(benzo[d]oxazol-2-yl)aniline
1
(3ag): Colorless solid; mp 176–1788C; H NMR (400 MHz,
CDCl3): d=8.48 (brs, 1H), 8.11 (dd, J=1.4, 7.9 Hz, 1H),
7.98 (brs, 1H), 7.72 (d, J=7.8 Hz, 1H), 7.65–7.63 (m, 1H),
7.56–7.54 (m, 1H), 7.38–7.29 (m, 4H), 7.24–7.14 (m, 3H),
6.85 (d, J=8.5 Hz, 1H), 6.86 (m, 1H), 3.60 (m, 2H), 3.27 (t,
J=7.12 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=163.5,
149.3, 148.6, 142.0, 136.5, 133.0, 129.2, 127.7, 124.7, 124.3,
122.4, 122.3, 119.6, 119.3, 119.0, 115.2, 113.8, 111.4, 111.2,
110.4, 108.2, 43.9, 25.4; MS (ESI): m/z (%)=376 (M+ +23,
53), 354 (M+ +1, 100), 228 (6), 144 (5).
N-Allyl-2-(benzo[d]oxazol-2-yl)-4-methoxyaniline (3bd):
1
Yellow solid; mp 130–1328C; H NMR (400 MHz, CDCl3):
d=8.20 (brs, 1H), 7.72–7.70 (m, 1H), 7.64 (d, J=3.0 Hz,
1H), 7.58–7.55 (m, 1H), 7.34–7.31 (m, 2H), 7.03 (dd, J=9.2,
3.0 Hz, 1H), 6.74 (d, J=9.2 Hz, 1H), 6.04 (m, 1H), 5.38 (dd,
J=17.2, 1.5 Hz, 1H), 5.21 (dd, J=10.4, 1.5 Hz, 1H), 4.01 (t,
J=4.7 Hz, 2H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3):
d=163.2, 150.2, 149.3, 143.7, 142.0, 135.5, 124.8, 124.5, 121.4,
119.5, 115.9, 113.5, 112.4, 110.4, 108.2, 56.3, 45.6; MS (ESI):
m/z (%)=282 (M+2, 30), 281 (M+H, 100), 280 (10); HR-
MS: m/z=281.1286, calcd. for C17H17N2O2 (M+H):
281.1290.
N-Allyl-2-(6-chlorobenzo[d]oxazol-2-yl)aniline (3cd): Col-
orless solid; mp 112–1148C; 1H NMR (400 MHz, CDCl3):
d=8.42 (brs, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.61 (d, J=
8.4 Hz, 1H), 7.56 (s, 1H), 7.37–7.29 (m, 2H), 6.78–6.72 (m,
2H), 6.07–5.99 (m, 1H), 5.37 (dd, J=17.2, 1.0 Hz, 1H), 5.21
(dd, J=10.2, 1.0 Hz, 1H), 4.03 (t, J=5.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d=164.2, 149.5, 148.5, 140.7, 134.9,
133.2, 130.3, 129.2, 125.1, 119.8, 116.2, 115.6, 111.6, 111.1,
107.2, 45.6; MS (ESI) m/z (%)=285 (M+1, 100), 283 (100),
280 (10); HR-MS: m/z=285.0778, calcd. for C16H14ClN2O
(M+H): 285.0795.
2-(Benzo[d]oxazol-2-yl)-N-(2-ethoxyethyl)aniline
(3ac):
Pale yellow solid; mp 83–858C; 1H NMR (400 MHz,
CDCl3): d=8.58 (brs, 1H), 8.12 (dd, J=7.9, 1.5 Hz, 1H),
7.72–7.69 (m, 1H), 7.56–7.53 (m, 1H), 7.38–7.26 (m, 3H),
6.83 (d, J=8.4 Hz, 1H), 6.73 (t, J=8.4 Hz, 1H), 3.81 (t, J=
8.5 Hz, 2H), 3.65 (q, J=6.9 Hz, 2H), 3.55 (q, J=5.6 Hz,
2H), 1.30 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=163.5, 149.3, 148.6, 142.0, 132.9, 129.2, 124.7, 124.4, 119.4,
115.4, 111.1, 110.3, 108.5, 69.1, 66.8, 43.1, 15.5; MS (ESI): m/
z (%)=305 (M+Na+H), 283 (M+H); HR-MS: m/z=
283.1467, calcd for C17H19N2O2 (M+H): 283.1447.
N-Allyl-2-(benzo[d]oxazol-2-yl)aniline (3ad): Colorless
solid; mp 72–748C; 1H NMR (400 MHz, CDCl3): d=8.56
(brs, 1H), 8.12 (dd, J=7.9, 1.2 Hz, 1H), 7.73–7.71 (m, 1H),
7.58–7.54 (m, 1H), 7.38–7.31 (m, 3H), 6.8–6.74 (m, 2H),
6.11–6. 01 (m, 1H), 5.40 (dd, J=17.2, 1.3 Hz, 1H), 5.24 (dd,
J=13.9, 1.2 Hz, 1H), 4.52 (t, J=5.2 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d=163.5, 149.3, 148.5, 141.9, 135.1,
132.9, 129.2, 124.8, 124.4, 119.4, 116.0, 115.5, 111.5, 110.4,
108.4, 45.6; MS (ESI): m/z (%)=252 (M+2, 15), 251 (M,
100), 237 (5), 210 (10); HR-MS: m/z=251.1196, calcd. for
C16H14N2O (M+): 251.1184.
N-[2-(1H-Indol-3-yl)ethyl]-2-(benzo[d]oxazol-2-yl)-4-me-
1
thoxyaniline (3bg): Yellow solid; mp 195–1978C; H NMR
(400 MHz, CDCl3): d=8.09 (brs, 1H), 7.96 (brs, 1H), 7.67
(d, J=7.8 Hz, 1H), 7.60 (d, J=7.8 Hz, 2H), 7.52–7.51 (m,
1H), 7.34–7.30 (m, 3H), 7.18–7.02 (m, 3H), 7.02–7.00 (m,
1H), 6.80 (d, J=8.92 Hz, 1H), 3.83 (s, 3H), 3.63–3.60 (m,
2H), 3.22 (m, 2H); 13C NMR (100 MHz, CDCl3): d=163.2,
150.0, 149.3, 143.9, 142.1, 136.5, 127.7, 124.7, 124.4, 122.4,
122.2, 121.5, 119.5, 119.4, 119.0, 113.9, 112.8, 112.5, 111.4,
110.3, 108.1, 56.3, 44.4, 25.5; MS: (ESI) m/z (%)=384 (M+
H, 100), 308 (20); HR-MS: m/z=384.1704, calcd. for
C24H22N3O2 (M+H): 384.1712.
N-Benzyl-2-(5-methylbenzo[d]oxazol-2-yl)aniline (3da):
Colorless solid; mp 118–1208C; 1H NMR (400 MHz,
CDCl3): d=8.92 (brs, 1H), 8.12 (d, J=7.5 Hz, 1H), 7.48–
7.42 (m, 4H), 7.35 (t, J=6.2 Hz, 1H), 7.30–7.26 (m, 3H),
7.14 (d, J=6.2 Hz, 1H), 6.76–6.71 (m, 2H), 4.63 (d, J=
5.4 Hz, 2H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
163.6, 148.3, 147.6, 142.1, 139.5, 134.2, 132.8, 129.1, 128.8,
2-(Benzo[d]oxazol-2-yl)-N-(furan-2-ylmethyl)aniline
1
(3ae): Colorless solid; mp 107–1098C; H NMR (400 MHz,
CDCl3): d=8.80 (brs, 1H), 8.13 (d, J=7.4 Hz, 1H), 7.72–
7.70 (m, 1H), 7.57–7.55 (m, 1H), 7.40–7.31 (m, 4H), 6.87 (d,
J=8.4 Hz, 1H), 6.78 (d, J=7.4 Hz, 1H), 6.33 (d, J=15.7 Hz,
2H), 4.59 (d, J=5.7 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d=163.4, 152.9, 149.3, 148.2, 142.0, 141.9, 132.9, 129.2, 124.9,
124.5, 119.5, 115.9, 111.5, 110.6, 110.4, 108.8, 106.9, 40.8; MS
(EI): m/z (%)=313 (M+23, 20), 291 (M,+ 100), 289 (40)
273 (5), 223 (8).
2-(Benzo[d]oxazol-2-yl)-N-(3,4-dimethoxyphenethyl)ani-
line (3af): Colorless solid; mp 151–1538C; 1H NMR
(400 MHz, CDCl3): d=8.42 (brs, 1H), 8.11 (dd, J=1.4,
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Veerababurao Kavala et al.
FULL PAPERS
127.2, 127.1, 125.9, 119.5, 115.6, 111.7, 109.7, 108.8, 47.3,
21.7; MS (ESI): m/z (%)=316 (M+2, 38), 315 (M+1, 100),
313 (12), 217 (5); HR-MS: m/z=315.1473, calcd. for
C21H19N2O (M+H): 315.1497.
142.2, 135.2, 132.5, 132.4, 130.3, 125.3, 124.6, 122.7, 120.7,
120.3, 119.6, 119.3, 116.0, 114.1, 110.6, 52.3, 49.1; MS (EI):
m/z=391 (M+2, 19), 389 (M, 42), 249 (19), 236 (30) 223
(100); HR-MS: m/z= 389.1294, calcd. for C23H20N3OCl
(M+): 389.1295.
2-(Benzo[d]oxazol-2-yl)-N-phenylaniline
(3ah):
Pale
1
N1-[2-(Benzo[d]oxazol-2-yl)phenyl]-N1,N2-dimethyl-
ethane-1,2-diamine (3an): Gummy liquid; 1H NMR
(400 MHz, CDCl3): d=8.46 (brs, 1H), 8.10 (d, J=7.2 Hz,
1H), 7.71–7.69 (m, 1H), 7.56–7.54 (m, 1H), 7.38–7.30 (m,
3H), 6.80 (d, J=8.4 Hz, 1H), 6.74 (t, J=7.4 Hz, 1H), 3.47
(q, J=6.2 Hz, 1H), 2.73 (t, J=6.6 Hz, 2H), 2.39 (s, 6H);
13C NMR (100 MHz, CDCl3): d=163.4, 149.3, 148.5, 141.9,
132.9, 129.2, 124.7, 124.3, 119.4, 115.2, 111.0, 110.3, 108.3,
58.4, 45.8, 41.5; MS (ESI): m/z (%)=304 (M+Na+H), 282
(M+H); HR-MS: m/z=282.1606, calcd. for C17H19N3O
(M+H): 282.1619.
yellow solid; mp 116–1188C; H NMR (400 MHz, CDCl3):
d=10.20 (brs, 1H), 8.18 (d, J=7.8 Hz, 1H), 7.74–7.72 (m,
1H), 7.60–7.58 (m, 1H), 7.40–7.30 (m, 8H), 7.14–7.11 (m,
1H), 6.88 (t, J=7.0 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d=163.0, 149.4, 145.6, 141.7, 141.3, 132.5, 129.6, 129.3, 125.1,
124.6, 123.8, 122.9, 119.6, 117.8, 114.0, 110.5, 110.1; MS (EI):
m/z (%)=286 (M+, 100), 269 (20); HR-MS: m/z=286.1106,
calcd. for C19H14N2O (M+): 286.1100.
2-(Dibutylamino)-N-(2-iodophenyl)benzamide
(3ai):
Gummy liquid; 1H NMR (400 MHz, CDCl3): d=12.8 (brs,
1H), 8.43 (dd, J=8.3, 1.1 Hz, 1H), 8.37 (dd, J=7.9, 1.2 Hz,
1H),), 7.86 (dd,J=8.3, 1.1 Hz, 1H), 7.53–7.49 (m, 1H), 7.39–
7.29 (m, 3H), 6.86–6.82 (m, 1H), 3.08–3.04 (m, 4H), 1.48–
1.41 (m, 4H), 1.26–1.18 (m, 4H), 0.81 (t, J=7.3 Hz, 6H);
13C NMR (100 MHz, CDCl3): d=165.2, 149.4, 141.0, 139.7,
132.5, 131.8, 130.5, 129.0, 125.7, 125.6, 123.9, 123.6, 89.2,
57.3, 28.8, 20.9, 14.1; MS (ESI): m/z (%)=473 (M+Na);
HR-MS: m/z=473.1142, calcd. for C21H27N2OI (M+Na):
473.1066.
N-[2-(Benzo[d]oxazol-2-yl)phenyl]propionamide
(3ao):
Colorless solid; mp 115–1178C; 1H NMR (400 MHz,
CDCl3): d=11.9 (brs, 1H), 8.84 (d, J=8.5 Hz, 1H), 8.22 (dd,
J=8.0, 1.3 Hz, 1H), 7.75–7.73 (m, 1H), 7.61–7.59 (m, 1H),
7.54–7.50 (m, 1H), 7.41–7.38 (m, 2H), 7.18 (t, J=7.8 Hz,
1H), 2.62 (q, J=5.6 Hz, 2H), 1.38 (t, J=7.6 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=173.4, 162.3, 149.4, 141.1,
139.5, 133.0, 128.5, 125.8, 125.1, 122.9, 120.6, 119.8, 112.9,
110.8, 32.0, 9.9; MS (EI): m/z (%)=266 (M+, 41), 237 (100),
210 (73) 181 (7); HR-MS: m/z=266.1051, calcd. for
C16H14N2O2 (M+): 266.1055.
2-[2-(Pyrrolidin-1-yl)phenyl]benzo[d]oxazole
(3aj):
Gummy liquid; 1H NMR (400 MHz, CDCl3): d=7.79–7.76
(m, 1H), 7.73 (dd, J=7.7, 1.7 Hz, 1H), 7.58–7.55 (m, 1H),
7.39–7.31 (m, 3H), 6.92 (d, J=8.4 Hz, 1H), 6.84 (t, J=
7.7 Hz, 1H), 3.19–3.16 (m, 4H), 1.91–1.85 (m, 4H);
13C NMR (100 MHz, CDCl3): d=164.6, 150.6, 149.0, 142.3,
132.8, 131.7, 124.7, 124.4, 120.0, 116.9, 114.6, 113.3, 110.7,
51.1, 25.9; MS (EI): m/z (%)=264 (M+, 100), 235 (15), 195
(17) 157 (82); HR-MS: m/z=264.1267, calcd. for C17H16N2O
(M+): 264.1263.
N-[2-(Benzo[d]oxazol-2-yl)phenyl]cyclopropanecarbox-
amide (3ap): Colorless solid; mp 120–1228C; 1H NMR
(400 MHz, CDCl3): d=12.14 (brs, 1H), 8.85 (d, J=8.6 Hz,
1H), 8.24 (dd, J=1.4, 7.9 Hz, 1H), 7.79–7.77 (m, 1H), 7.64–
7.62 (m, 1H), 7.54–7.50 (m, 1H), 7.42–7.40 (m, 2H), 7.21–
7.17 (m, 1H), 1.88–1.81 (m, 1H), 1.22–1.18 (m, 2H), 1.00–
0.95 (m, 2H); 13C NMR (100 MHz, CDCl3): d=173.2, 162.3,
149.4, 141.1, 139.6, 133.0, 128.5, 125.8, 125.1, 122.7, 120.5,
119.8, 112.6, 110.8, 17.1, 8.5; MS (EI): m/z (%)=278 (M+,
32), 229 (85), 195 (100) 167 (12); HR-MS: m/z=278.1059,
calcd. for C17H14N2O2 (M+): 278.1055.
1-[2-(Benzo[d]oxazol-2-yl)phenyl]pyrrolidin-2-one (3aq):
Colorless solid; mp 142–1448C; 1H NMR (400 MHz,
CDCl3): d=8.28 (d, J=7.8 Hz, 1H), 7.75–7.71 (m, 1H),
7.59–7.52 (m, 2H), 7.53 (td, J=7.7, 1.3 Hz, 1H), 7.38–7.31
(m, 3H), 3.87 (t, J=6.9, 2H), 2.6 (t, J=4.5 Hz, 2H), 2.30 (q,
J=7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=175.9,
160.8, 150.5, 142.3, 138.1, 132.3, 130.9, 129.5, 128.3, 125.5,
125.1, 124.7, 120.5, 110.6, 51.2, 31.7, 19.4; MS (EI): m/z
(%)=278 (M+, 100), 249 ( 10), 235 (12), 221 (18), 171 (24);
HR-MS: m/z=278.1058, calcd. for C17H14N2O2 (M+):
278.1055.
1-[2-(6-Chlorobenzo[d]oxazol-2-yl)phenyl]pyrrolidin-2-
one (3cq): Colorless solid; mp 141–1438C; 1H NMR
(400 MHz, CDCl3): d=8.25 (dd, J=7.9, 1.5 Hz, 1H), 7.64
(d, J=8.5 Hz, 1H), 7.57 (td, J=7.6, 1.6 Hz, 1H), 7.55 (d, J=
1.9 Hz, 1H), 7.48 (td, J=8.2, 1.1 Hz, 1H), 7.38 (dd, J=7.8,
1.0 Hz, 1H), 7.32 (dd, J=8.4, 1.9 Hz, 1H), 3.88 (t, J=
3.4 Hz, 2H), 2.58 (t, J=3.7 Hz, 2H), 2.30 (q, J=3.4 Hz,
2H); 13C NMR (100 MHz, CDCl3): d=175.8, 161.6, 150.7,
141.1, 138.2, 132.6, 131.2, 130.9, 129.4, 128.4, 125.4, 124.6,
121.0, 111.3, 51.1, 31.7, 19.5; MS (EI): m/z (%)=313 (M+
H, 100), 225(10); HR-MS (MALDI): m/z=313.0750, calcd.
for C17H13ClN2O2 (M+H): 313.0743.
2-[2-(Piperidin-1-yl)phenyl]benzo[d]oxazole
(3ak):
Gummy liquid; 1H NMR (400 MHz, CDCl3): d=8.02 (dd
J=7.7, 1.6 Hz, 1H), 7.81–7.77 (m, 1H), 7.61–7.57 (m, 1H),
7.45–7.41 (m, 1H), 7.37–7.32 (m, 2H), 7.12 (d, J=8.2 Hz,
1H), 7.06 (t, J=7.7 Hz, 1H), 2.98 (t, J=5.2 Hz, 4H), 1.75–
1.69 (m, 4H), 1.59–1.53 (m, 2H); 13C NMR (100 MHz,
CDCl3): d=164.1, 153.5, 150.8, 142.2, 132.5, 132.3, 124.9,
124.4, 121.6, 120.2, 120.1, 119.1, 110.6, 53.9, 26.3, 24.5; MS
(EI): m/z (%)=278 (M+, 100), 249 (8), 171 (98) 170 (35);
HR-MS: m/z=278.1417, calcd. for C18H18N2O (M+):
278.1419.
2-(2-Morpholinophenyl)benzo[d]oxazole (3al): Colorless
1
solid; H NMR (400 MHz, CDCl3): d=8.09 (d, J=8.0, 1H),
7.79 (dd, J=5.8, 3.2 Hz, 1H), 7.59 (dd, J=5.9, 3.2 Hz, 1H),
7.47 (t, J=7.8 Hz , 1H), 7.37–7.35 (m, 2H), 7.16–7.13 (m,
2H), 3.88 (t, J=4.4 Hz, 4H), 3.05 (t, J=4.4 Hz, 4H);
13C NMR (100 MHz, CDCl3): d=163.1, 152.2, 150.6, 142.2,
132.5, 132.4, 125.3, 124.6, 122.6, 120.5, 120.3, 119.0, 110.6,
67.3, 52.8; MS (EI): m/z (%)=280 (M+, 100), 249 (15), 221
(24), 195 (29) 173 (20); HR-MS: m/z=280.1208, calcd. for
C17H16N2O2 (M+): 280.1212.
2-{2-[4-(3-chlorophenyl)piperazin-1-yl]phenyl}benzo[d]ox-
azole (3am): Colorless solid; mp 155–1578C; 1H NMR
(400 MHz, CDCl3): d=8.11 (dd, J=7.7, 1.5 Hz, 1H), 7.81–
7.78 (m, 1H), 7.59–7.57 (m, 1H), 7.50–7.47 (m, 1H), 7.37–
7.35 (m, 2H), 7.20–7.14 (m, 3H), 6.92–6.91 (m, 1H), 6.83–
6.80 (m, 2H), 3.38–3.36 (m, 4H), 3.22–3.19 (m, 4H);
13C NMR (100 MHz, CDCl3): d=163.2, 152.6, 152.1, 150.7,
10
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One-Pot Tandem Synthesis of 2-Arylbenzoxazole Derivatives
1-[2-(5-Methylbenzo[d]oxazol-2-yl)phenyl]pyrrolidin-2-
one (3dq): Colorless solid; mp 123–1258C; 1H NMR
(400 MHz, CDCl3): d=8.28 (d, J=7.7 Hz, 1H), 7.58–7.53
(m, 2H), 7.47 (t, J=7.7 Hz, 1H), 7.41 (d, J=8.2 Hz, 1H),
7.38 (d, J=7.7 Hz, 1H), 7.16 (d, J=8.2 Hz, 1H), 3.85 (t, J=
6.9 Hz, 2H), 2.58 (t, J=6.9 Hz, 2H), 2.48 (s, 3H), 2.36–2.26
(m, 2H); 13C NMR (100 MHz, CDCl3): d=175.9, 160.9,
148.8, 142.5, 138.0, 134.6, 132.2, 130.9, 129.5, 128.3, 126.6,
125.2, 120.4, 109.9, 51.1, 31.7, 21.6, 19.4; MS (EI): m/z (%)=
292 (M+, 100), 275 (22), 237 (93), 209 (35); HR-MS: m/z=
292.1211, calcd. for C18H16N2O2 (M+): 292.1212.
1-[2-(6-Bromobenzo[d]oxazol-2-yl)phenyl]pyrrolidin-2-
one (3eq): Colorless solid; mp 152–1548C; 1H NMR
(400 MHz, CDCl3): d=8.25 (dd, J=7.8, 1.4 Hz, 1H), 7.71
(d, J=1.7 Hz, 1H), 7.61–7.56 (m, 2H), 7.50–7.45 (m, 2H),
7.38 (dd, J=7.8, 1.0 Hz, 1H), 3.88 (t, J=6.9 Hz, 2H), 2.58
(t, J=6.9 Hz, 2H), 2.30 (q, J=7.1 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d=175.8, 162.3, 151.0,141.5, 138,.2,
132.7, 130.9, 129.3, 128.4, 128.2, 124.6, 121.4, 118.5, 114.2,
51.1, 31.7, 19.4; MS (EI): m/z (%)=359 (M+2+H, 100),
357 (M+H, 95); HR-MS (MALDI): m/z=357.0244, calcd.
for C17H13BrN2O2 (M+ +H): 357.0238.
(100 MHz, CDCl3): d=171.0, 160.8, 150.6, 142.6, 142.4,
132.7, 130.9, 129.8, 128.2, 125.5, 124.9, 124.7, 120.5, 110.6,
51.8, 33.1, 23.7, 21.4; MS (EI): m/z (%)=292 (M+, 100), 237
(45), 185 (13); HR-MS: m/z=292.1206, calcd. for
C18H16N2O2 (M+): 292.1212.
1-[2-(Benzo[d]oxazol-2-yl)phenyl]azepan-2-one
(3as):
Gummy liquid; 1H NMR (400 MHz, CDCl3): d=8.25 (dd,
J=7.7, 0.9 Hz, 1H), 7.76–7.72 (m, 1H), 7.57–7.53 (m, 2H),
7.49–7.42 (m, 1H), 7.36–7.30 (m, 3H), 4.06–4.00 (m, 1H),
3.52–3.47 (m, 1H), 2.83–2.65 (m, 2H), 1.99–1.76 (m, 6H);
13C NMR (100 MHz, CDCl3): d=176.6, 161.1, 150.6, 144.0,
142.3, 132.5, 130.9, 129.5, 127.8, 125.4, 124.7, 124.6, 120.5,
110.6, 53.4, 37.9, 30.4, 28.8, 23.4; MS (ESI): m/z=329 (M+
Na+H); HR-MS: m/z=329.1283, calcd. for C19H18N2O2Na
(M+): 329.1266.
4-[2-(Benzo[d]oxazol-2-yl)phenyl]thiomorpholin-3-one
1
(3at): Colorless solid; mp 133–1358C; H NMR (400 MHz,
CDCl3): d=8.32 (dd, J=7.8, 1.4 Hz, 1H), 7.75–7.72 (m,
1H), 7.62–7.56 (m, 2H), 7.53–7.49 (m, 1H), 7.39–7.33 (m,
3H), 4.0 (d, J=4.7 Hz, 1H), 3.93 (d, J=5.4 Hz, 1H), 3.68
(d, J=15.9 Hz, 1H), 3.41 (d, J=15.9 Hz, 1H), 3.25 (d, J=
4.6 Hz, 1H), 3.04 (d, J=5.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=167.1, 160.5, 150.5, 142.3, 141.9, 132.7, 130.9,
129.6, 128.7, 125.7, 124.9, 124.8, 120.5, 110.8, 53.2, 31.0, 26.6;
MS (EI): m/z (%)=310 (M+, 62), 260 (50), 237 (100), 236
(23), 210 (16); HR-MS: m/z=310.0771, calcd. for
C17H14N2O2S (M+): 310.0776.
1-[2-(Benzo[d]oxazol-2-yl)-4-bromophenyl]pyrrolidin-2-
1
one (3fq): Pale brown; mp 161–1638C; H NMR (400 MHz,
CDCl3): d=8.43 (d, J=2.3 Hz, 1H), 7.75–7.72 (m, 1H), 7.67
(dd, J=8.4, 2.3 Hz, 1H), 7.56–7.54 (m, 1H), 7.40–7.33 (m,
2H), 7.26 (d, J=7.8 Hz, 1H), 3.85 (t, J=4.4 Hz, 2H), 2.60
(t, J=4.4 Hz, 2H), 2.30 (q, J=4.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d=175.9, 159.4, 150.5, 142.2, 137.1,
135.2, 133.7, 131.1, 126.8, 126.0, 124.9, 121.9, 120.7, 110.8,
50.9, 31.6, 19.5; HR-MS (MALDI): m/z=357.0245, calcd.
for C17H13BrN2O2 (M+ +H): 357.0238.
2-[2-(1H-Indol-1-yl)phenyl]benzo[d]oxazole (3au): Color-
1
less solid; mp 101–1038C; H NMR (400 MHz, CDCl3): d=
8.33 (dd, J=8.7, 1.8 Hz, 1H), 7.70–7.64 (m, 3H), 7.62–7.58
(m, 2H), 7.25–7.08 (m, 7H), 6.55 (d, J=3.3 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=161.4, 150.9, 141.6, 138.6,
137.6, 132.3, 131.9, 129.2, 129.0, 128.3, 125.4, 125.3, 124.6,
122.5, 121.0, 120.3, 110.8, 110.1, 103.7; MS (EI): m/z (%)=
310 (M+, 100), 293 (10), 281 (7) 204 (10); HR-MS: m/z=
310.1100, calcd. for C21H14N2O (M+): 310.1105.
1-[2-(Benzo[d]oxazol-2-yl)-5-fluorophenyl]pyrrolidin-2-
one (3gq): Pale brown solid; mp 198–2008C; 1H NMR
(400 MHz, CDCl3): d=8.27 (dd, J=8.8, 6.1 Hz, 1H), 7.73–
7.70 (m, 1H), 7.55–7.51 (m, 1H), 7.37–7.32 (m, 2H), 7.21–
7.17 (m, 1H), 7.11 (dd, J=9.0, 2.5 Hz, 1H), 3.87 (t, J=
6.9 Hz, 2H), 2.60 (t, J=8.0 Hz, 2H), 2.32 (q, J=7.2 Hz,
2-[2-(1H-PyrroloACTHNUTRGNE[NUG 2,3-b]pyridin-1-yl)phenyl]benzo[d]oxa-
zole (3av): Colorless solid; mp 137–1398C; 1H NMR
(400 MHz, CDCl3): d=8.35 (dd, J=7.8, 1.4 Hz, 1H), 8.12
(dd, J=4.7, 1.5 Hz, 1H), 7.96 (dd, J=7.8, 1.5 Hz, 1H), 7.70–
7.58 (m, 4H), 7.31 (d, J=3.6 Hz, 1H), 7.23–7.11 (m, 3H),
7.02 (dd, J=7.8, 4.7 Hz, 1H), 6.63 (d, J=3.6 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=161.5, 150.7, 148.8, 143.7,
141.7, 137.2, 132.3, 131.6, 129.5, 129.4, 129.0, 128.4, 125.3,
125.2, 124.5, 121.1, 120.3, 116.5, 110.5, 101.7; MS (ESI):
m/z=334 (M+Na+H), 312 (M+H); HR-MS: m/z=
312.1141, calcd. for C20H13N3O (M+): 312.1137.
2H); 13C NMR (100 MHz, CDCl3): d=175.8, 164.6 (d, JC,F
253 Hz), 160.1, 150.5, 142.2, 140.1, 140.0, 132.7 (d, JC,F
=
=
10 Hz), 125.6, 124.7, 121.5 (d, JC,F =3.0 Hz), 120.4, 116.9 (d,
J
C,F =23 Hz), 115.7 (d, JC,F =21 Hz,), 110.6, 50.9, 31.6, 19.4;
MS (EI): m/z (%)=296 (M+, 100), 239 (17), 213 (20), 189
(20), 161 (5); HR-MS: m/z=296.0954, calcd. for
C17H13N2O2F (M+): 296.0961.
1-[2-(Benzo[d]oxazol-2-yl)-4-methoxyphenyl]pyrrolidin-2-
one (3bq): Colorless solid; mp 125–1278C; 1H NMR
(400 MHz, CDCl3): d=7.80 (d, J=2.9 Hz, 1H), 7.74–7.72
(m, 1H), 7.55–7.53 (m, 1H), 7.37–7.32 (m, 2H), 7.26 (d, J=
7.8 Hz, 1H), 7.10 (dd, J=7.7, 3.3 Hz, 1H), 3.91 (s, 3H), 3.83
(t, J=4.4 Hz, 2H), 2.60 (t, J=4.4 Hz, 2H), 2.28 (q, J=
4.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=176.2, 160.7,
159.2, 150.5, 142.3, 130.9, 130.8, 125.9, 125.6, 124.7, 120.5,
118.7, 115.2, 110.6, 56.0, 51.3, 31.6, 19.3; MS (EI): m/z (%)=
308 (M+, 100), 265 (7), 251 (15) 201 (20); HR-MS: m/z=
308.1162, calcd. for C18H16N2O2 (M+): 308.1161.
1-[2-(Benzo[d]oxazol-2-yl)phenyl]piperidin-2-one (3ar):
Colorless solid; mp 139–1418C; 1H NMR (400 MHz,
CDCl3): d=8.35 (dd, J=7.8, 1.5 Hz, 1H), 7.75–7.70 (m,
1H), 7.58 (td, J=7.6, 1.5 Hz, 1H), 7.55–7.53 (m, 1H), 7.49
(td, J=7.6, 1.2 Hz, 1H), 7.36–7.33 (m, 3H), 3.73–3.61 (m,
2H), 2.63–2.51 (m, 2H), 2.13–2.00 (m, 4H); 13C NMR
2-[2-(1H-PyrroloACTHNUTRGNEU[GN 2,3-b]pyridin-1-yl)phenyl]-4,6-dimethyl-
benzo[d]oxazole (3hv): Colorless solid; mp 126–1288C;
1H NMR (400 MHz, CDCl3): d=8.35 (d, J=7.8 Hz, 1H),
8.16 (dd, J=4.7, 1.4 Hz, 1H), 7.97 (dd, J=7.8, 1.5 Hz, 1H),
7.69–7.64 (m, 2H), 7.62–7.57 (m, 1H), 7.26 (d, J=3.5 Hz,
1H), 7.03 (dd, J=7.8, 4.7 Hz, 1H), 6.83 (s, 1H), 6.78 (s,
1H), 6.61 (d, J=3.6 Hz, 1H), 2.35 (s, 3H), 2.33 (s, 3H);
13C NMR (100 MHz, CDCl3): d=159.7, 150.7, 149.1, 143.6,
138.9, 137.0, 135.3, 131.8, 131.2, 130.0, 129.7, 129.5, 128.8,
128.5, 126.3, 125.8, 121.2, 116.4, 107.9, 101.4, 21.8, 16.2; MS
(ESI): m/z=362 (M+Na+H), 340 (M+H); HR-MS: m/z=
340.1467, calcd. for C22H17N3O (M+): 340.1450.
2-[2-(1H-Imidazol-1-yl)phenyl]benzo[d]oxazole
Gummy liquid; H NMR (400 MHz, CDCl3): d=8.26 (d, J=
(3aw):
1
7.4 Hz, 1H), 7.72–7.70 (m, 1H), 7.64–7.59 (m, 3H), 7.45 (d,
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Veerababurao Kavala et al.
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J=3.2 Hz, 1H), 7.41–7.39 (m, 1H), 7.33–7.30 (m, 2H), 7.17
(s, 1H); 7.04 (s, 1H); 13C NMR (100 MHz, CDCl3): d=
160.4, 150.9, 141.6, 138.1, 136.5, 132.2, 131.6, 129.7, 129.3,
128.3, 125.91, 124.9, 124.4, 121.0, 120.6, 110.9; MS (EI): m/z
(%)=262 (M+2, 60), 260 (M+, 100), 232 (10), 221 (5); HR-
MS: m/z=261.0899, calcd. for C16H11N3O (M+): 261.0902.
2-[2-(3-Phenyl-1H-pyrazol-1-yl)phenyl]benzo[d]oxazole
(3ax): Colorless solid; mp 93–958C; 1H NMR (400 MHz,
CDCl3): d=8.16 (dd, J=8.4, 1.5 Hz, 1H), 7.74–7.68 (m,
2H), 7.66–7.64 (m, 3H), 7.72 (d, J=2.5 Hz, 1H), 7.55 (td,
J=9.2, 1.2 Hz, 1H), 7.37–7.25 (m, 6H), 6.71 (d, J=2.4 Hz,
1H); 13C NMR (100 MHz, CDCl3): d=161.6, 153.3, 151.1,
141.8, 139.8, 133.2, 133.2, 132.1, 131.7, 128.7, 128.3, 128.1,
126.6, 126.0, 125.6, 124.7, 123.0, 120.5, 110.9, 104.8; MS
(ESI): m/z=360 (M+Na+H); HR-MS: m/z=360.1162,
calcd. for C22H15N3O (M+Na+H): 360.1113; m/z=
338.1299, calcd. for (M+H): 338.1293.
2-[2-(1H-1,2,4-Triazol-1-yl)phenyl]benzo[d]oxazole (3ay):
Colorless solid; mp 112–1148C; 1H NMR (400 MHz,
CDCl3): d=8.39 (s, 1H), 8.33–8.31 (m, 1H), 8.11 (s, 1H),
7.70–7.67 (m, 3H), 7.60–7.58 (m, 1H), 7.42–7.40 (m, 1H),
7.33–7.31 (m, 2H); 13C NMR (100 MHz, CDCl3): d=159.8,
152.5, 150.7, 145.3, 141.6, 135.9, 132.2, 131.3, 130.2, 128.1,
125.9, 124.9, 124.1, 120.7, 110.8; MS (ESI): m/z (%)=285
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(M+Na+H);
HR-MS:
m/z=285.0776,
calcd.
for
C18H16N4O2 Na (M+): 285.0753.
Acknowledgements
Financial support for this work by the National Science
Council of the Republic of China (NSC 99-2119M-003-003-
MY2) and National Taiwan Normal University (99T3030-2,
99-D, 100-D-06) is gratefully acknowledged.
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[13] CCDC 869088, CCDC 869090, CCDC 869323 and
CCDC 869324 contain the supplementary crystallo-
graphic data for this paper (compounds 3aa, 3af, 3aq
and 3av, respectively). These data can be obtained free
of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
12
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One-Pot Tandem Synthesis of 2-Arylbenzoxazole
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Derivatives via Copper-Catalyzed C N and C O Bond
Formation
Adv. Synth. Catal. 2012, 354, 1 – 13
Veerababurao Kavala, Donala Janreddy, Mustafa J. Raihan,
Chun-Wei Kuo, Chintakunta Ramesh, Ching-Fa Yao*
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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These are not the final page numbers!