Synthesis of bis- and trisoxazole derivatives via Suzuki-Miyaura cross-coupling reaction and van Leusen oxazole synthesis

Article abstract of DOI:10.1055/s-2007-990865

Both C₂- and C₃-symmetric oxazole derivatives are synthesized via the Suzuki-Miyaura cross-coupling and van Leusen oxazole synthesis. Here, bis- and triscarboxaldehydes were obtained via the Suzuki-Miyaura cross-coupling and further treated withp-toluenesulfonylmethyl isocyanide (TosMIC) in the presence of potassium carbonate as a base and methanol as a solvent to deliver the corresponding oxazole derivatives. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-990865

PAPER
3653
Synthesis of Bis- and Trisoxazole Derivatives via Suzuki–Miyaura
Cross-Coupling Reaction and van Leusen Oxazole Synthesis
Synthesis of
B
a
is- and Tris
m
oxazole
D
erivative
basivarao Kotha,* Vrajesh R. Shah
Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai 400 076, India
Fax +91(22)25723480; E-mail: srk@chem.iitb.ac.in
Received 20 August 2007; revised 5 September 2007
example, VX-4977 (7) acts as an IMPHD antagonist while
phthaloxazolins 8 and 9 are the oxazole-triene antibiotics
isolated from streptomyces sp. KO-7888 and streptomy-
ces sp. OM-5714.8,9 Also, nucleophilic substitution to 1,3-
Abstract: Both C2- and C3-symmetric oxazole derivatives are syn-
thesized via the Suzuki–Miyaura cross-coupling and van Leusen
oxazole synthesis. Here, bis- and triscarboxaldehydes were ob-
tained via the Suzuki–Miyaura cross-coupling and further treated
with p-toluenesulfonylmethyl isocyanide (TosMIC) in the presence oxazole ring followed by ring opening and recyclization
of potassium carbonate as a base and methanol as a solvent to deliv-
can provide other heterocyclic rings such as pyrrole, pyri-
er the corresponding oxazole derivatives.
midine, and imidazole.
Key words: bisoxazole, Suzuki–Miyaura cross-coupling, trisox-
Because of its presence in a wide range of biologically im-
azole, TosMIC
portant molecules, various methods have been reported
for the synthesis of functionalized 1,3-oxazole deriva-
tives.1,10–12 Among these, Gabriel–Robinson synthesis via
1,3-Oxazole moiety is an important structural element
the dehydration of 2-acylaminoketones is an important
present in various natural products isolated from marine
method for the preparation of a wide range of 2,5-disub-
sources. These products were either 2,5-disubstituted or
stituted and 2,4,5-trisubstituted oxazoles.13 In 1968,
2,4,5-trisubstituted oxazole derivatives.1 Annuloline (1) is
Schöllkopf and co-workers used metalated methyl isocy-
an alkaloidal pigment2 isolated from the roots of Lolium
anide to prepare oxazole derivatives with substitution at 5-
multiflorim and a natural constituent of Halfordia sclerox-
position.14 Various isocyanide derivatives like ethyl iso-
yla, the quaternary alkaloid N-methylhalfordine3 (2) con-
cyanoacetate, methyl isocyanoacetate were exploited by
tain 2,5-disubstituted oxazoles (Figure 1). The mold
different groups towards the synthesis 5-substituted ox-
metabolite pimprinine4 (3), a fermentation product of
azole derivatives as well as 5-(aminomethyl) oxazoles.15
Streptomyces pimprina and pimprinethine5 (4) isolated
However, in 1972, van Leusen and co-workers16 reported
from Sterptoverticillum olivoreticute contain 2,5-disubsti-
a nontoxic isocyanide derivative, p-toluenesulfonylmeth-
tuted oxazole moieties. Other natural products are tex-
yl isocyanide (TosMIC, 10) as a precursor to 5-substituted
oxazoles from the corresponding aldehydes or acyl chlo-
rides under mild reaction conditions. Various groups ex-
ploited TosMIC to synthesize a variety of oxazole
amine (5) and texaline (6),6 isolated from plants of Amyris
texana. However, 5-monosubstituted oxazole derivatives
were also isolated from Streptomyces strains, having bio-
logical activity ranging from herbicidal to antitumor. For
N
MeO
N
Me
O
Me
OH
MeO
O
N
O
1
X
OMe
2
Me
OH
N
N
R
O
O
O
O
NR1
X
3 R = Me; R1 = H
4 R = Et; R1 = H
5 X = CH
6 X = N
N
O
H
H
O
MeO
N
N
O
N
O
H
O
O
R
N
O
OH
8
9
cis
trans
H2N
7
R = H, OH
Figure 1 Biologically active 2,5-disubstituted and 5-substituted oxazole derivatives
SYNTHESIS 2007, No. 23, pp 3653–3658
x
x.
x
x
.
2
0
0
7
Advanced online publication: 31.10.2007
DOI: 10.1055/s-2007-990865; Art ID: Z20407SS
© Georg Thieme Verlag Stuttgart · New York

3654
S. Kotha, V. R. Shah
PAPER
Het
R
derivatives. In this regard, Sasaki and co-workers pre-
pared bisoxazole derivatives having substitution at 4-po-
sition and dioxazolo[3]2metacylcophane derivatives using
TosMIC.17 Recently, Vedejs and co-workers18 reported
the two-step iterative process for the synthesis of the oli-
gooxazole telomestatin using TosMIC as a oxazole pre-
cursor. Also, TosMIC equivalents were reported by
Kulkarni and Ganesan for solid-phase combinatorial
synthesis19 as well as solution-phase parallel synthesis20
of 5-aryloxazole from the aryl aldehydes. Recently, Bar-
rett and co-workers have developed a ROMPgel TosMIC
reagent for the oxazole synthesis from the aryl aldehydes
with minimal purification.21 Herein, we report the synthe-
Het
Het
R
R
13 R = I
14 R = Br
11 Het = 2-thiophene
12 Het = 2-furan
Figure 2
sis of bis- and trisoxazole derivatives via the combination ic acid (17). Towards this goal, when 16 was coupled un-
of Suzuki–Miyaura22 cross-coupling and van Leusen ox- der cross-coupling condition with boronic acid 17, the
azole synthesis.
cross-coupling product 15 was isolated in 76% yield
(Scheme 1). However, the same trialdehyde can also be
obtained from the corresponding tribromide 14 via the
known literature procedure.24 When this trialdehyde de-
rivative was treated with TosMIC (10) in the presence of
K2CO3 in refluxing methanol, the corresponding C3-sym-
metric oxazole derivative 18 was obtained in 60% isolated
yield (Scheme 1). The formation of the oxazole derivative
18 was confirmed from the 1H NMR and 13C NMR spec-
tral data. Disappearance of the peak at d = 10 and appear-
Recently, we have reported the synthesis of oligoaryl/-
heteroaryl C3-symmetric molecules via the Suzuki–
Miyaura cross-coupling as a key step. Furan- and
thiophene-containing star-shaped molecules (e.g. 11 and
12, Figure 2) were also prepared under similar reaction
conditions from the corresponding aromatic bromide as
well as iodide (13 or 14).23 However, incorporation of het-
erocycles such as oxazole, imidazole, or isoxazole is not a
trivial exercise because of the nonavailability of the corre-
sponding boronic acids or difficulty involved in their
preparation. So, as an alternative to this we thought of ex-
ploring TosMIC as an oxazole precursor.
1
ance of two new singlets at d = 7.97 and 7.43 in the H
NMR spectra, three peaks at d = 151.3, 150.7 and 121.9 in
the 13C NMR spectra, and mass peak at 508.1672 (m/z
calcd for C33H22N3O3 [M + H]+: 508.1661) confirmed the
formation of the C3-symmetric oxazole derivative 18.
To realize our strategy, the corresponding C3-symmetric
aldehyde derivative is required. This trialdehyde can be
prepared via the Suzuki–Miyaura cross-coupling between
1,3,5-tribromobenzene (16) with 4-formylbenzeneboron-
Having synthesized the C3-symmetric trisoxazole deriva-
tive 18, we thought of generalizing this methodology to
CHO
B(OH)2
Br
Pd(PPh3)4
aq Na2CO3
+
THF–toluene (1:1)
reflux
Br
Br
CHO
(76%)
OHC
16
17
15
CHO
K2CO3, MeOH
reflux
(60%)
TosMIC (10)
N
O
O
N
O
18
N
Scheme 1
Synthesis 2007, No. 23, 3653–3658 © Thieme Stuttgart · New York

PAPER
Synthesis of Bis- and Trisoxazole Derivatives
3655
N
O
CHO
CH2Br
IBX
TosMIC
DMSO
r.t.
K2CO3, MeOH
reflux
O
OHC
CHO
BrH2C
CH2Br
N
(57%)
19
(82%)
20
21
O
N
Scheme 2
prepare other C3-symmetric and C2-symmetric oxazole zeneboronic acid (17) under cross-coupling conditions to
derivatives. In this connection, 1,3,5-benzenetricarboxal- provide the dicarboxaldehyde 24 in 42% yield (Scheme 5,
dehyde (19) was prepared via the known literature proce- Route A). The second route includes the coupling be-
dure in 57% yield from the corresponding 1,3,5- tween 1,4-benzenediboronic acid (30) with 4-bromoben-
tris(bromomethyl)benzene (20) via IBX oxidation zaldehyde (28) to provide the cross-coupling product 24
(Scheme 2).25 When tricarboxaldehyde derivative 19 was in 32% yield (Scheme 5, Route B).
treated with TosMIC (10) under the above-mentioned
conditions, the trisoxazole derivative 21 was obtained in
82% yield.
Br
B(OH)2
CHO
28
17
Pd(PPh3)4
Pd(PPh3)4
Next, we focused our attention on the synthesis of C2-
symmetric bisoxazole derivatives. In this regard, treat-
ment of terephthaladehyde (22; n = 1, Scheme 3) with 10,
provided 1,4-bis(oxazol-5-yl)benzene (25; n = 1,
Scheme 3) in 75% yield.
aq Na2CO3
THF–toluene (1:1)
reflux
aq Na2CO3
THF–toluene (1:1)
reflux
3
Br
B(OH)2
CHO
(32%)
(42%)
24
30
29
Route A
Route B
Scheme 5
N
O
CHO
CHO
When 24 was treated with TosMIC (10), the bisoxazole 27
(n = 3, Scheme 3) was obtained in 62% yield. However,
bisoxazole 27 was not soluble in common solvents, so the
spectral analysis could not be performed for this com-
pound.
10
n
K2CO3, MeOH
reflux
n
O
n = 1 22
2 23
n = 1 25 (75%)
2 26 (69%)
Anthracene was found to be a very good chromophore for
fluorescence studies. Therefore, the preparation of 9,10-
bis(oxazol-5-yl) anthracene (31) was undertaken. To-
wards this end, the corresponding 9,10-anthracenedicar-
boxaldehyde (32) was prepared via the literature
procedure.26 Reaction of dicarbaldehyde 32 with TosMIC
(10) in methanol in the presence of potassium carbonate
under reflux condition provided the bisoxazole derivative
31 in 38% yield (Scheme 6).
N
3 24
3 27 (62%)
Scheme 3
4,4¢-Biphenyldicarboxaldehyde (23) was prepared via the
cross-coupling reaction of 4-bromobenzaldehyde (28)
with 4-formylbenzeneboronic acid (17) in 88% yield
(Scheme 4). Treatment of 23 with 10 delivered the corre-
sponding bisoxazole derivative 26 (n = 2, Scheme 3) in
69% isolated yield.
N
O
CHO
CHO
10
Br
17
K2CO3, MeOH
reflux
Pd(PPh3)4
aq Na2CO3
THF–toluene (1:1)
CHO
32
(38%)
O
N
reflux
CHO
31
(88%)
28
CHO
23
Scheme 6
Scheme 4
Having synthesized linear bisoxazole derivatives, we di-
rected our attention for the synthesis of angular bisoxazole
derivatives. In this connection, treatment of o-phthalalde-
hyde (33) and isophthalaldehyde (34) with 10 under the
same reaction conditions provided the 1,2-bis(oxazol-5-
Along the same line, 4,4¢¢-p-terphenyldicarboxaldehyde
(24) was prepared by two different pathways via the Su-
zuki–Miyaura cross-coupling reaction. In the first route,
1,4-dibromobenzene (29) was treated with 4-formylben-
Synthesis 2007, No. 23, 3653–3658 © Thieme Stuttgart · New York

3656
S. Kotha, V. R. Shah
PAPER
4-formylbenzeneboronic acid (17; 69.0 mg, 0.46 mmol), and THF–
toluene (1:1, 4 mL), and the mixture was degassed for 20 min. To
this degassed solution, Pd(PPh3)4 (15.5 mg, 5 mol%) was added and
the resulting mixture was heated to reflux (80 °C). At the conclu-
sion of the reaction (TLC monitoring, 8 h), H2O (5 mL) was added
and the mixture extracted with CH2Cl2 (3 × 20 mL). The combined
organic layers were washed with H2O (20 mL), brine (20 mL), and
dried (Na2SO4). Evaporation of the solvent gave the crude product
which was purified by a silica gel column chromatography. Elution
of the column with 2% EtOAc–PE mixture gave the desired product
23 (52.0 mg, 88%) as a white solid; mp 148–151 °C (Lit.28 mp 140–
142 °C).
O
N
CHO
10
K2CO3, MeOH
reflux
O
CHO
35
33
N
(22%)
Scheme 7
N
O
CHO
10
4,4¢¢-p-Terphenyldicarboxaldehyde (24)
K2CO3, MeOH
reflux
Route A: A 2-necked RB flask was charged with 1,4-dibromoben-
zene (29; 60.0 mg, 0.25 mmol), Na2CO3 (108.0 mg, 1.00 mmol) in
H2O (1 mL), 4-formylbenzeneboronic acid (17; 114.2 mg, 0.76
mmol), and THF–toluene (1:1, 4 mL), and the mixture was de-
gassed for 20 min. To this degassed solution was added Pd(PPh3)4
(30 mg, 10 mol%) and the resulting mixture was heated to reflux
(80 °C). At the conclusion of the reaction (TLC monitoring, 2.5 h),
H2O (5 mL) was added and the mixture extracted with CH2Cl2 (3 ×
20 mL). The combined organic layers were washed with H2O (20
mL), brine (20 mL) and dried (Na2SO4). Evaporation of the solvent
gave crude product which was purified by silica gel column chro-
matography. Elution of the column with 5% EtOAc–PE mixture
gave the desired product 24 (33.0 mg, 42%) as a white solid; mp
208–212 °C (Lit.28 mp 211–213 °C).
O
CHO
34
(86%)
N
36
Scheme 8
yl)benzene (35) and 1,3-bis(oxazol-5-yl)benzene (36) in
22% and 86% yields, respectively (Schemes 7 and 8).
In summary, various bis- and trisoxazole derivatives were
synthesized by using the combination of Suzuki–Miyaura
cross-coupling reaction and van Leusen oxazole synthe-
sis. The biscarboxaldehydes 23, 24 were synthesized via
the Suzuki–Miyaura cross-coupling reaction. Treatment
of C2- and C3-carboxaldehydes with TosMIC (10) gave
the corresponding oxazole derivatives.
Route B: A 2-necked RB flask was charged with 1,4-benzenedibo-
ronic acid (30; 90.0 mg, 0.54 mmol), Na2CO3 (58.0 mg, 0.54 mmol)
in H2O (1 mL), 4-bromobenzaldehyde (28; 50.0 mg, 0.27 mmol),
and THF–toluene (1:1, 4 mL), and the mixture was degassed for 20
min. To this degassed solution was added Pd(PPh3)4 (15.5 mg, 5
mol%) and the resulting mixture was heated to reflux (80 °C). At
the conclusion of the reaction (TLC monitoring, 7 h), H2O (5 mL)
was added and the mixture extracted with CH2Cl2 (3 × 20 mL). The
combined organic layers were washed with H2O (20 mL), brine (20
mL) and dried (Na2SO4). Evaporation of the solvent gave crude
product which was purified by a silica gel column chromatography.
Elution of the column with 4% EtOAc–PE mixture gave the desired
product 24 (25.0 mg, 32%) as a white solid; mp 206–209 °C.
Analytical TLC was performed on (10 × 5 cm) glass plate coated
with silica gel G or GF 254 (containing 13% CaSO4 as a binder). Vi-
sualization of the spots on TLC plate was achieved either by expo-
sure to I2 vapor or UV light. Column chromatography was
performed using silica gel (100–200 mesh) and the column was usu-
ally eluted with EtOAc and petroleum ether (PE; bp 60–80 °C) mix-
ture. Melting points are uncorrected. 1H NMR and 13C NMR
spectral data were recorded on Varian VXR 300 and Varian VXR
400 spectrometers using TMS as an internal standard and CDCl3 as
solvent. The coupling constants (J) are given in Hertz (Hz). HRMS
data were recorded on Q-ToF micromass machine.
Formation of Oxazoles from Aldehydes; General Procedure
In a 2-necked RB flask were added the appropriate aldehyde (1.0
equiv), TosMIC (10; 1.0 equiv for each formyl group), K2CO3 (2.5
equiv for each formyl group), and MeOH (4 mL), and the mixture
was heated to reflux (70 °C, oil bath temperature). At the conclusion
of reaction (TLC monitoring), MeOH was removed under reduced
pressure and the residue was loaded on the silica gel column. Elu-
tion of the column with appropriate EtOAc–PE mixture gave the de-
sired oxazole derivatives.
1,3,5-Benzenetricarboxaldehyde (19)25 and 9,10-anthracenedicar-
boxaldehyde (32)26 were prepared via the reported literature proce-
dures.
C3-Symmetric Aldehyde 15
A 2-necked round-bottomed (RB) flask was charged with 1,3,5-tri-
bromobenzene (40 mg, 0.13 mmol), 4-formylbenzeneboronic acid
(17; 113.5 mg, 0.76 mmol), THF–toluene (1:1, 4 mL), and Na2CO3
(81 mg, 0.76 mmol) in H2O (1 mL), and the mixture was degassed
for 20 min. To this degassed solution was added Pd(PPh3)4 (22 mg,
15 mol%) and the resulting mixture was heated to reflux (80 °C). At
the conclusion of the reaction (TLC monitoring, 16 h), H2O (5 mL)
was added and the mixture extracted with CH2Cl2 (3 × 20 mL). The
combined organic layers were washed with H2O (20 mL), brine (20
mL), and dried (Na2SO4). Evaporation of the solvent gave the crude
product which was purified by a silica gel column chromatography.
Elution of the column with 15% EtOAc–PE mixture gave the de-
sired product 15 (37.5 mg, 76%) as a white solid; mp 228–230 °C
(Lit.27 mp 230–234 °C).
Trisoxazole Derivative 18
Trialdehyde 15 (20.0 mg, 0.05 mmol), TosMIC (10; 30.0 mg, 0.15
mmol), and K2CO3 (40.0 mg, 0.38 mmol) in MeOH (4 mL) were
treated as described in the general procedure. The crude product
was loaded on a silica gel column. Elution of the column with 40%
EtOAc–PE mixture gave the desired product 18 (15.4 mg, 60%);
yellow solid; mp 138–144 °C (dec.).
1H NMR (400 MHz, CDCl3): d = 7.43 (s, 3 H), 7.81–7.76 (m, 12 H),
7.83 (s, 3 H), 7.97 (s, 3 H).
13C NMR (100.5 MHz, CDCl3): d = 121.9, 125.0, 125.2, 127.3,
127.9, 141.0, 141.8, 150.7, 151.3.
4,4′-Biphenyldicarboxaldehyde (23)
A 2-necked RB flask was charged with 4-bromobenzaldehyde (28;
50.0 mg, 0.27 mmol), Na2CO3 (57.0 mg, 0.54 mmol) in H2O (1 mL),
HRMS (Q-ToF): m/z calcd for C33H22N3O3 [M + H]+: 508.1661;
found: 508.1672.
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PAPER
Synthesis of Bis- and Trisoxazole Derivatives
3657
Trisoxazole Derivative 21
13C NMR (100.5 MHz, CDCl3): d = 124.7, 126.1, 126.9, 128.5,
1,3,5-Benzenetricarboxaldehyde (20; 15.0 mg, 0.09 mmol),
TosMIC (10; 54.0 mg, 0.27 mmol), and K2CO3 (96.0 mg, 0.67
mmol) in MeOH (4 mL) were treated as described in the general
procedure. The crude product was loaded on the silica gel column.
Elution of the column with 60% EtOAc–PE mixture gave the de-
sired product 21 (21.0 mg, 81%); white solid; mp 271–274 °C
(dec.).
1H NMR (400 MHz, DMSO-d6): d = 7.85 (s, 3 H), 8.03 (s, 3 H),
8.46 (s, 3 H).
13C NMR (100.5 MHz, DMSO-d6): d = 119.1, 123.4, 129.1, 149.4,
152.1.
131.4, 147.5, 152.3.
HRMS (Q-ToF): m/z calcd for C20H13N2O2 [M + H]+: 313.0977;
found: 313.0981.
1,2-Bis(oxazol-5-yl)benzene (35)
o-Phthalaldehyde (33; 50.0 mg, 0.37 mmol), TosMIC (10; 145.0
mg, 0.74 mmol), and K2CO3 (248.0 mg, 1.79 mmol) in MeOH (4
mL) were treated as described in the general procedure. The crude
product was purified by a silica gel column chromatography. Elu-
tion of the column with 10% EtOAc–PE mixture gave the desired
product 35 (18.0 mg, 23%) as a thick liquid.
1H NMR (400 MHz, CDCl3): d = 6.92 (s, 2 H), 7.47–7.51 (m, 2 H),
7.60–7.65 (m, 2 H), 7.92 (s, 2 H).
13C NMR (100.5 MHz, CDCl3): d = 124.5, 126.3, 129.6, 129.7,
150.1, 150.9.
HRMS (Q-ToF): m/z calcd for C15H10N3O3 [M + H]+: 280.0722;
found: 280.0721.
1,4-Bis(oxazol-5-yl)benzene (25)
Terephthalaldehyde (22; 50.0 mg, 0.37 mmol), TosMIC (10; 145.0
mg, 0.74 mmol), and K2CO3 (248.0 mg, 1.79 mmol) in MeOH (4
mL) were treated as described in the general procedure. The crude
product was loaded on a silica gel column. Elution of the column
with 20% EtOAc–PE mixture gave the desired product 25 (59.5 mg,
75%); white solid; mp 184–188 °C (dec.).
1H NMR (400 MHz, CDCl3): d = 7.42 (s, 2 H), 7.72 (s, 4 H), 7.95
(s, 2 H).
13C NMR (100.5 MHz, CDCl3): d = 122.3, 125.0, 127.9, 150.8,
151.1.
HRMS (Q-ToF): m/z calcd for C12H9N2O2 [M + H]+: 213.0664;
found: 213.0668.
1,3-Bis(oxazol-5-yl)benzene (36)
Isophthalaldehyde (34; 50.0 mg, 0.37 mmol), TosMIC (10; 145.0
mg, 0.74 mmol), and K2CO3 (248.0 mg, 1.79 mmol) in MeOH (4
mL) were treated as described in the general procedure. The crude
product was purified by a silica gel column chromatography. Elu-
tion of the column with 20% EtOAc–PE gave the desired product
36 (68.0 mg, 86%) as a white solid; mp 159–162 °C.
1H NMR (400 MHz, CDCl3): d = 7.42 (s, 2 H), 7.48 (t, J = 8.0 Hz,
4 H), 7.60 (dd, J = 1.6 Hz, 8.0 Hz, 2 H), 7.91 (t, J = 2.0 Hz, 1 H),
7.94 (s, 2 H).
HRMS (Q-ToF): m/z calcd for C12H9N2O2 [M + H]+: 213.0664;
found: 213.0670.
4,4¢-Bis(oxazol-5-yl)biphenyl (26)
13C NMR (100.5 MHz, CDCl3): d = 120.2, 122.3, 124.5, 128.6,
Dialdehyde 23 (40 mg, 0.19 mmol), TosMIC (10; 75 mg, 0.38
mmol), and K2CO3 (131.4 mg, 0.95 mmol) in MeOH (4 mL) were
treated as described in the general procedure. The crude product
was loaded on a silica gel column. Elution of the column with
EtOAc gave the desired product 26 (44.0 mg, 69%); yellow crystal-
line solid; mp 266–270 °C (dec.).
129.7, 150.8, 150.9.
HRMS (Q-ToF): m/z calcd for C12H9N2O2 [M + H]+: 213.0664;
found: 213.0665.
Acknowledgment
1H NMR (400 MHz, DMSO-d6): d = 7.77 (s, 2 H), 7.81–7.88 (m, 8
H), 8.48 (s, 2 H).
13C NMR (75.4 MHz, DMSO-d6): d = 122.3, 124.6, 126.7, 127.1,
139.0, 150.1, 151.9.
We are thankful to DST (NSTI), New Delhi and CSIR, New Delhi
for the financial support. V.R.S. thanks CSIR, New Delhi for the
award of a research fellowship.
HRMS (Q-ToF): m/z calcd for C18H13N2O2 [M + H]+: 289.0977;
found: 289.0980.
References
(1) Brown, D. J. Chemistry of Heterocyclic Compounds,
Oxazoles: Synthesis, Reactions and Spectroscopy; Palmer,
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Part A, 1–390.
(2) Axelrod, B.; Belzile, J. R. J. Org. Chem. 1958, 23, 919.
(3) Crow, W. D.; Hodgkin, J. H. Tetrahedron Lett. 1963, 4, 85.
(4) Joshi, B. S.; Taylor, W. I.; Bhate, D. S.; Karmkar, S. S.
Tetrahedron 1963, 16, 1437.
4,4¢¢-Bis(oxazol-5-yl)-p-terphenyl (27)
Dialdehyde 24 (30 mg, 0.11 mmol), TosMIC (10; 57 mg, 0.21
mmol), and K2CO3 (72.0 mg, 0.52 mmol) in MeOH (4 mL) were
treated as described in the general procedure. The crude product
was loaded on a silica gel column. Elution of the column with
EtOAc gave the desired product 27 (26.0 mg, 62%); yellow crystal-
line solid. Since the product was not soluble in commonly used sol-
vents, it was not possible to obtain spectral data; mp >198 °C (dec.).
(5) Koyama, Y.; Yokose, K.; Dolby, L. J. Agric. Biol. Chem.
1981, 45, 1285.
9,10-Bis(oxazol-5-yl)anthracene (31)
(6) Dominguez, X. A.; de la Fuente, G.; Gonzalez, A. G.; Reina,
M.; Timon, I. Heterocycles 1988, 27, 35.
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9,10-Anthracenedicarboxaldehyde (32; 50.0 mg, 0.21 mmol),
TosMIC (10; 83.5 mg, 0.43 mmol), and K2CO3 (148.0 mg, 1.06
mmol) in MeOH (4 mL) were treated as described in the general
procedure. The crude product was purified by a silica gel column
chromatography. Elution of the column with 8% EtOAc–PE mix-
ture gave the desired product 31 (25.0 mg, 38%); greenish-yellow
solid; mp 260–266 °C (dec.).
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1H NMR (400 MHz, CDCl3): d = 7.48 (s, 2 H), 7.50–7.54 (m, 4 H),
7.85–7.89 (m, 4 H), 8.27 (s, 2 H).
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