Synthesis of 4-oxazolinephenylboronic acid and heterobiaryl oxazolines via a Suzuki reaction

Article abstract of DOI:10.3184/030823409X431355

An efficient synthesis of 4-oxazolinephenylboronic acid from 4-bromobenzoic acid is reported. The title compound couples with heteroaryl halides in presence of Pd(PPh₃)₄ and Na₂CO₃ in aqueous toluene to give het

Full text of DOI:10.3184/030823409X431355

JOURNAL OF CHEMICAL RESEARCH 2009
APRILꢋꢀꢈꢌꢎ±207
RESEARCH PAPER 205
Synthesis of 4-oxazolinephenylboronic acid and heterobiaryl oxazolines
via a Suzuki reaction
Samir Ghosha, A.Sanjeev Kumara, G.N.Mehtab, R.Soundararajana* and Subhabrata Sena
aChemical Research and Development Department, Pfizer Ltd, Mumbai-400705, India
bChemistry Section, Applied Sciences and Humanities Department, SVNIT, Surat-395 007, India
An efficient synthesis of 4-oxazolinephenylboronic acid from 4-bromobenzoic acid is reported. The title compound
couples with heteroaryl halides in presence of Pd(PPh3)4 and Na2CO3 in aqueous toluene to give heterobiaryl oxazolines.
Keywords: 4-oxazolinephenylboronic acid, Suzuki-coupling, biaryl, heteroaryl halides, palladium catalyst
Heterocyclic compounds such as oxazolines are of interest
to organic chemists, because they are present in various
biologicallyactivenaturalproducts.1 Furthermore,theoptically
active heterocyclic compounds have been successfully used in
asymmetric synthesis as chiral templates or ligands.
was heated with under optimal reaction conditions (5 mol%
Pd (PPh3)4, 3 equiv. of 1M aq. Na2CO3 solution in toluene
at 90°C for the time indicated in Table 1. The coupling
reactions for reactive monohalides 4a–i proceed in moderate
WRꢀH[FHOOHQWꢀ\LHOGVꢀꢄꢎꢎ±ꢏꢌꢍꢉꢋꢀZLWKꢀPLQLPDOꢀZRUNꢊXSꢁ
The Suzuki reaction is a powerful tool for the construction
RIꢀ&±&ꢀERQGVꢀLQꢀWKHꢀV\QWKHVLVꢀRIꢀKHWHURELDU\OꢀR[D]ROLQHVꢁ2-3
As a result of the developments in this area, there are
increasing demands for boronic acid products. In the
process of preparing a variety of boronic acids, we needed
a method to prepare 4-oxazolinephenylboronic acid 3.
Oxazolinephenylboronic acids are typically prepared from
2-, 3- and 4- bromooxazolines using nBuli and triisopropyl
ERUDWHꢀ DWꢀ ±ꢂꢃ°C. The bromooxazolines4 are prepared from
commercially available 2-, 3- and 4- bromobenzoic acids
using thionyl chloride and 2-amino-2-methyl propane-1-ol
under mild conditions.
The heteroaryl halides shown in Table 1 demonstrate the
scope of the reaction. Under the reaction conditions, 2- and
3-bromopyridines (entries a and b) gave the corresponding
heterobiaryl oxazoline in 82% and 90% yield respectively.5
4-Bromopyridine hydrochloride (entry c) also underwent
the reaction and the coupling product was an off-white
solid obtained in 85% yield. As expected, 3-bromoquinoline
(entry d) gave the desired product within 1 h. In the case of
entries e and f under the same conditions the observed yield
was 65% and 60% respectively. However, in the case of
entry f, a detosylated coupled product was observed. Though
bromopyrimidines are more reactive than the analogous
bromopyridines, the observed yield was less. In case of
S-excessive hetero aromatic compounds (entries g, h and i),
the observed yield was 75%, 80% and 55% respectively.
Table 1 showed that all reactions are fast and proceed with
moderate yield except for the chloro substituted moiety.
The cross-coupling of 3- and 2-oxazolinephenylboronic
acids 6 and 8 with selected heteroaryl halides 4g and
4i were also examined (Scheme 2). Similar to the 4-
oxazolinephenylboronic acid 3, 3-oxazolinephenylboronic
acid 6 gave the corresponding heterobiaryl oxazolines 7g
and 7i in the same yield as earlier. On the other hand, 2-
oxazolinephenylboronic acid 8 was only partially converted
to the corresponding heterobiaryl oxazolines 9g (30%) and 9i
(20%) using the standard conditions. This may be due to steric
constraints.
However, there is no exact procedure for the synthesis
of these oxazolinephenylboronic acids. We describe
here
a practical method for the preparation of 4-
oxazolinephenylboronic 3 acid and its Suzuki coupling
reactions with heteroaryl halides under optimal conditions
WRꢀ SUHSDUHꢀ KHWHURELDU\Oꢄ±ꢅ±ꢆ±ꢇ±ꢆ±ꢈ±ꢉR[D]ROLQHVꢁ7KHꢀ WLWOHꢀ
compound was prepared from 4-bromooxazoline 2 by reacting
LWꢀZLWKꢀQꢊ%X/LꢀDQGꢀWULLVRSURS\OꢀERUDWHꢀLQꢀ7+)ꢀDWꢀ±ꢂꢃ°C. This
easy preparation and the economical starting material make
this method potentially useful for the large-scale synthesis
of 4-oxazolinephenylboronic acid 3. In the case of 4- and
ꢇꢊR[D]ROLQHSKHQ\OERURQLFꢀ DFLGꢋꢀ WKHꢀ \LHOGꢀ ZDVꢀ aꢂꢌ±ꢃꢌꢍꢁꢀ
On the other hand, 2-oxazolinephenylboronic acid the yield
was considerably lower at ~30% possibly because of steric
hindrance.
With 4-oxazolinephenylboronic acid in hand, several
Suzuki coupling reactions were carried out. However with 3-
and 2-oxazolinephenylboronic acids only two reactions were
performed. Scheme 1 also gives general conditions for the
cross-coupling reactions of 4-oxazolinephenylboronic acid 3
with some readily accessible heteroaryl halides 4. In a typical
example an equimolar amount of boronic acid 3 and halide 4
In conclusion, we have developed a practical method
from readily available starting materials, for preparation of
4-oxazolinephenylboronic acid under optimal conditions.
The title compound reacts with the different heteroaryl halides
under optimal Suzuki condition to afford the heterobiaryl
oxazolines in fair to good yields.
Ar
HO
OH
Br
B
Br
n-Buli / THF
Pd(PPh3)4, Na2CO3
Toluene, H2O, 90°C
SOCl2/ CCl4, DMF(cat)
ArX
+
Tri isopropyl borate
2-amino-2-methyl propane-1-ol / DCM
SOCl2/DCM
N
O
COOH
N
O
N
O
3
4
5
1
2
Scheme 1
* Correspondent. E-mail: soundara1959@yahoo.com

206 JOURNAL OF CHEMICAL RESEARCH 2009
Table 1 Coupling reactions of 4-oxazolinephenylboronic acid 3 with heteroaryl halides 4
Entry
Ar–X
Time/h
Yield/%
a
b
c
d
e
f
g
h
i
2-Bromopyridine
2
1
1
1
1
4
1
1
2
82
90
85
80
65
60
75
80
55
3-Bromopyridine
4-Bromopyridine
3-Bromoquinoline
5-Bromopyrimidine
4-Chloro-7-tosyl-7H-pyrrolo [2, 3-d] pyrimidine
2-Bromothiophene
3-Bromothiophene
3-Bromofuran
3-Oxazolinephenylboronic acid (6): Preparative procedure was the
same as for compound 3, to give a yellow solid, 70% yield, PꢁSꢁꢀꢐꢅꢌ±
HO
Ar
B
Pd(PPh3)4, Na2CO3
Toluene, H2O, 90°C
1
OH
145°C, H NMR (400 MHz,DMSO-d6) G 8.23 (s, 1H), 8.16 (s, 2H),
7.85 (m, J = 7.2 Hz, 1H), 7.80 (m, J = 8 Hz, 1H), 7.37 (m, J = 7.2 Hz,
1H), 4.03 (s, 2H), 1.24 (s, 6H), 13C NMR (DMSO-d6) G 161.3, 137.4,
134.1, 129.8, 129.7, 128.0, 127.2, 78.7, 67.8, 28.7; ESIMS: m/z Calcd
[M +]: 219; Found: 220 [M + H +]; HRMS (ESI): m/z Calcd [M +]:
219.0447; Found: 220.0426 [M + H +].
ArX
+
N
O
N
O
2-Oxazolinephenylboronic acid (8): Preparative procedure was
the same as for compound 3. Compound 8ꢀZDVꢀSXUL¿HGꢀE\ꢀFROXPQꢀ
chromatography (silica, 4:6 hexane/EtOAc) as an eluent; Rf = 0.1,
ꢇꢌꢍꢀ\LHOGꢋꢀZKLWHꢀVROLGꢋꢀPꢁSꢁꢀꢐꢐꢎ±ꢐꢈꢌ°C, 1H NMR (400 MHz,DMSO-
d6) G 8.04 (d, J = 8 Hz, 1H), 8.01 (s, 2H), 7.53 (m, J = 7.6 Hz, 1H),
7.40 (m, J = 8 Hz, 1H), 7.31 (m, J = 7.6 Hz, 1H), 4.11 (s, 2H), 1.29
(s, 6H), 13C NMR (DMSO-d6) G 160.2, 137.3, 135.5, 130.2, 129.9,
128.8, 128.5, 78.9, 68.0, 27.8; ESIMS: m/z Calcd [M +]: 219; Found:
220 [M + H +]; HRMS (ESI): m/z Calcd [M +]: 219.0447; Found:
220.0128 [M + H +].
ArX
4g
Reaction/time
Product/yield
OH
OH
7g
7i
)
(70%
(50 %)
1h
2h
3-B
2-B
6
,
i
4
OH
OH
4g
4i
9g
9i
1h
2h
(30%)
(20%)
8,
Typical procedure for Suzuki coupling
Pd (PPh3)4 (5 mol%) was added to
a degassed solution of
Scheme 2
oxazolinephenylboronic acid 3 (1.0 equiv) and heteroaryl halides
(1.0 equiv) in 1M sodium carbonate solution (1.4 mL) and toluene
(10 vol.). The mixture was heated at 90°C under N2 for the time
indicated in Table 1 (reaction progress was monitored by TLC).
After cooling to r.t., the solution was diluted with ethyl acetate,
washed with H2O and brine, dried over anhydrous MgSO4 and
FRQFHQWUDWHGꢀXQGHUꢀUHGXFHGꢀSUHVVXUHꢁꢀ7KHꢀFRQFHQWUDWHꢀZDVꢀSXUL¿HGꢀ
by silica gel column chromatography to give the coupling products.
Experimental
All solvents and reagents were purchased from the suppliers and
XVHGꢀ ZLWKRXWꢀ IXUWKHUꢀ SXUL¿FDWLRQꢁꢀ $OOꢀ QRQꢊDTXHRXVꢀ UHDFWLRQVꢀ ZHUHꢀ
performed in dry glassware under an atmosphere of dry nitrogen.
Organic solutions were concentrated under reduced pressure.
TLC was performed on Merck precoated Silica-gel 60F254 plates.
1H and 13C NMR spectra were recorded in DMSO-d6 and CDCl3
at 400 MHz, on a Varian Gemini 400 MHz FT NMR spectrometer.
The chemical shifts were reported in G ppm relative to TMS.
The mass spectra were recorded on Shimadzu LCMS-QP 800 LC-
MS and AB-4000 Q-trap LC-MS/MS. Melting points were obtained
by using the open capillary method and are uncorrected.
Spectral data for new compounds prepared as above
2-(4-(4, 4-dimethyl-4, 5-dihydrooxazol-2-yl)phenyl)pyridine (5a):
3XUL¿FDWLRQꢀE\ꢀFROXPQꢀFKURPDWRJUDSK\ꢀꢄVLOLFDꢋꢀꢐꢀꢒꢀꢐꢀKH[DQHꢆ(W2$Fꢉꢀ
DVꢀ DQꢀ HOXHQWꢓꢀ 5Iꢀ ꢀ ꢌꢁꢅꢋꢀ ꢃꢈꢍꢀ \LHOGꢋꢀ ZKLWHꢀ VROLGꢋꢀ PꢁSꢁꢀ ꢂꢈ±ꢂꢎ°C,
1H NMR (400 MHz,DMSO-d6) G 8.91 (d, J = 3.2 Hz, 1H), 8.63 (d,
J = 8.4 Hz, 2H), 8.12 (m, J = 4.8 Hz, 1H), 7.87 (d, J = 8.4 Hz, 2H),
7.71 (m, J = 8 Hz, 1H), 7.46 (m, J = 8.2 Hz, 1H), 4.07 (s, 2H), 1.26
(s, 6H), 13C NMR (DMSO-d6) G 160.9, 158.0, 149.4, 140.3, 135.6,
129.8, 129.5 128.5, 126.3, 124.5 78.8, 68.0, 27.8; ESIMS: m/z Calcd
[M +]: 252; Found: 253 [M + H +]; HRMS (ESI): m/z Calcd [M +]:
252.3110; Found: 253.3240 [M + H +].
4-Oxazolinephenylboronic acid (3)
4-Bromooxazoline 24 (10 g, 39.37 m.mol) was dissolved in dry THF
ꢄꢎꢌꢀP/ꢉꢀDQGꢀFRROHGꢀWRꢀ±ꢂꢃ°C under N2. After the internal temperature
UHDFKHGꢀ±ꢂꢃ°C, n-BuLi (1.6M in hexane, 60 mL, 98.42 m.mol) was
added dropwise under N2 over 30 min; a yellow solid precipitated.
The reaction mixture was stirred at the same temperature for 1 h.
At the same temperature neat triisopropyl borate (14.8 g, 78.74
mmol) was added to the reaction mixture. The solids dissolved and
a brown homogeneous solution was observed. The reaction mixture
ZDVꢀ ZDUPHGꢀ WRꢀ íꢐꢎ°C and stirred at this temperature for 1 h.
The reaction was monitored by TLC until there was no starting
material present. The reaction mixture was then quenched with an
ice-cold solution of 2 N HCl (50 mL). The reaction mixture was
warmed to 30°C and stirred at the same temperature for another 1 h.
The reaction mixture was diluted with water (30 mL) and extracted
with methyl t-butylether (MTBE) (50 mL). The organic layer was
removed and the aqueous layer was washed with MTBE (30 mL).
7KHꢀDTXHRXVꢀOD\HUꢀZDVꢀEDVL¿HGꢀZLWKꢀꢐꢌꢍꢀDTꢁꢀ1D+&23 solution to
make pH~ 6 and extracted with ethyl acetate (2 u 50 mL). The ethyl
acetate layer was dried over MgSO4 and concentrated under reduced
pressure. The residue was dissolved in heptanes (50 mL) and the
solvent distilled off to give a yellow solid. The solid was triturated
ZLWKꢀ KHSWDQHVꢀ ꢄꢎꢌꢀ P/ꢉꢀ DQGꢀ ¿OWHUHGꢀ WRꢀ JLYHꢀ Dꢀ SXUHꢀ \HOORZꢀ VROLGꢀ 39
ꢄꢑꢁꢏꢀJꢉꢀZLWKꢀꢃꢌꢍꢀ\LHOGꢋꢀPꢁSꢁꢀꢐꢐꢈ±ꢐꢐꢎ°C, 1H NMR (400 MHz,DMSO-
d6) G 8.22 (s, 2H), 7.82 (d, J = 7.4 Hz, 2H), 7.77 (d, J = 7.2 Hz, 2H),
4.06 (s, 2H), 1.24 (s, 6H), 13C NMR (DMSO-d6) G 28.3, 67.3, 78.2,
126.0, 128.3, 132.2, 134.2, 160.6; ESIMS: m/z Calcd [M +]: 219;
Found: 220 [M + H +]; HRMS (ESI): m/z Calcd [M +]: 219.0447;
Found: 220.0627 [M + H +].
3-(4-(4, 4-dimethyl-4, 5-dihydrooxazol-2-yl) phenyl) pyridine (5b):
3XUL¿FDWLRQꢀE\ꢀFROXPQꢀFKURPDWRJUDSK\ꢀꢄVLOLFDꢋꢀꢐꢒꢐꢀKH[DQHꢆ(W2$FꢉꢀDVꢀ
DQꢀHOXHQWꢓꢀ5Iꢀ ꢀꢌꢁꢅꢋꢀꢏꢌꢍꢀ\LHOGꢋꢀRIIꢀZKLWHꢀVROLGꢋꢀPꢁSꢁꢀꢃꢂ±ꢏꢈ°C, 1H NMR
(400 MHz,DMSO-d6) G 8.86 (d, J = 2 Hz, 1H), 8.53 (d, J = 4.4 Hz,
1H), 8.08 (m, J = 8.4 Hz, 1H), 7.89 (d, J = 8.4 Hz, 2H), 7.78 (d,
J = 8 Hz, 2H), 7.62 (m, J = 8.4 Hz, 1H), 4.09 (s, 2H), 1.27 (s, 6H),
13C NMR (DMSO-d6) G 160.8, 149.5, 148.0, 140.1, 135.0, 134.7,
132.6, 131.9 129.2, 127.4, 78.9, 67.9, 28.6; ESIMS: m/z Calcd
[M +]: 252; Found: 253 [M + H +]; HRMS (ESI): m/z Calcd [M +]:
252.3110; Found: 253.3282 [M + H +].
4-(4-(4, 4-dimethyl-4, 5-dihydrooxazol-2-yl) phenyl) pyridine (5c):
3XUL¿FDWLRQꢀE\ꢀFROXPQꢀFKURPDWRJUDSK\ꢀꢄVLOLFDꢋꢀꢐꢒꢐꢀKH[DQHꢆ(W2$Fꢉꢀ
DVꢀ DQꢀ HOXHQWꢓꢀ 5Iꢀ ꢀ ꢌꢁꢅꢋꢀ ꢃꢎꢍꢀ \LHOGꢋꢀ ZKLWHꢀ VROLGꢋꢀ PꢁSꢁꢀ ꢐꢇꢃ±ꢐꢅꢅ°C,
1H NMR (400 MHz,DMSO-d6) G 8.61 (m, J = 6 Hz, 2H), 7.92 (m,
J = 8.4 Hz, 4H), 7.71 (m, J = 4.8 Hz, 2H), 4.07 (s, 2H), 1.23 (s, 6H),
13C NMR (DMSO-d6) G 160.6, 150.8, 146.3, 140.1, 132.0, 129.0,
127.4 121.7, 78.9, 67.9, 28.2; ESIMS: m/z Calcd [M +]: 252; Found:
253 [M + H +]; HRMS (ESI): m/z Calcd [M +]: 252.3110; Found:
253.3189 [M + H +].
3-(4-(4, 4-dimethyl-4, 5-dihydrooxazol-2-yl) phenyl) quinoline
(5dꢉꢒꢀ 3XUL¿FDWLRQꢀ E\ꢀ FROXPQꢀ FKURPDWRJUDSK\ꢀ ꢄVLOLFDꢋꢀ ꢐꢒꢐꢀ KH[DQHꢆ
(W2$FꢉꢀDVꢀDQꢀHOXHQWꢓꢀ5Iꢀ ꢀꢌꢁꢎꢋꢀꢃꢌꢍꢀ\LHOGꢋꢀRIIꢀZKLWHꢀVROLGꢋꢀPꢁSꢁꢀꢏꢌ±
95°C, 1H NMR (400 MHz,DMSO-d6) G 9.23 (s,1H), 8.67 (s, 1H),
8.02 (m, J = 6 Hz, 1H), 7.93 (s, 2H), 7.88 (d, J = 8 Hz, 1H), 7.76

JOURNAL OF CHEMICAL RESEARCH 2009 207
(m, J = 7.2 Hz, 2H), 7.61 (m, J = 6.8 Hz, 2H), 4.07 (s, 2H), 1.24
(s, 6H), 13C NMR (DMSO-d6) G 160.7, 149.6, 147.5, 140.0, 133.8,
132.5, 131.9 130.3, 129.2, 128.9, 128.0, 127.6, 127.3, 78.9, 67.9,
28.8; ESIMS: m/z Calcd [M +]: 304; Found: 305 [M + H +]; HRMS
(ESI): m/z Calcd [M +]: 304.3856; Found: 304.3740 [M +].
6H), 13C NMR (DMSO-d6) G 160.6, 142.7, 134.4, 129.9, 129.1,
128.9, 128.5 127.2, 126.7, 124.6 78.9, 67.9, 28.6; ESIMS: m/z Calcd
[M +]: 257; Found: 258 [M + H +]; HRMS (ESI): m/z Calcd [M +]:
257.3507; Found: 258.0916 [M + H +].
2-(3-(furan-3-yl) phenyl)-4, 4-dimethyl-4, 5-dihydrooxazole (7i):
3XUL¿FDWLRQꢀE\ꢀFROXPQꢀFKURPDWRJUDSK\ꢀꢄVLOLFDꢋꢀꢂꢒꢇꢀKH[DQHꢆ(W2$Fꢉꢀ
as an eluent; Rf = 0.6, 50% yield, brown liquid, 1H NMR (400
MHz,CDCl3) G 8.21 (s, 1H), 7.94 (d, J = 7.76 Hz, 1H), 7.74 (m,
J = 6.8 Hz, 2H), 7.49 (m, J = 10 Hz, 3H), 4.15 (s, 2H), 1.42 (s, 6H),
13C NMR (CDCl3) G 162.0, 140.5, 140.4, 132.3, 130.0, 129.6, 128.9
127.4, 127.0, 120.0, 114.9, 79.2, 67.6, 29.7; ESIMS: m/z Calcd
[M +]: 241; Found: 242 [M + H +]; HRMS (ESI): m/z Calcd [M +]:
241.2851; Found: 242.2751 [M + H +].
5-(4-(4, 4-dimethyl-4, 5-dihydrooxazol-2-yl) phenyl) pyrimidine
(5eꢉꢒꢀ 3XUL¿FDWLRQꢀ E\ꢀ FROXPQꢀ FKURPDWRJUDSK\ꢀ ꢄVLOLFDꢋꢀ ꢐꢒꢐꢀ KH[DQHꢆ
(W2$FꢉꢀDVꢀDQꢀHOXHQWꢓꢀ5Iꢀ ꢀꢌꢁꢅꢋꢀꢑꢎꢍꢀ\LHOGꢋꢀRIIꢀZKLWHꢀVROLGꢋꢀPꢁSꢁꢀꢐꢐꢎ±
1
117 °C, H NMR (400 MHz,DMSO-d6) G 9.15 (d, J = 11.2 Hz, 3H),
7.91 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 4.06 (s, 2H), 1.22 (s,
6H), 13C NMR (DMSO-d6) G 160.5, 158.1, 155.3, 136.8, 132.7,131.9,
131.8 127.5, 78.9, 67.9, 28.6; ESIMS: m/z Calcd [M +]: 253; Found:
254 [M + H +]; HRMS (ESI): m/z Calcd [M +]: 253.2991; Found:
254.2752 [M + H +].
4, 4-dimethyl-2-(2-(thiophen-2-yl) phenyl)-4, 5-dihydrooxazole
(9gꢉꢒꢀ 3XUL¿FDWLRQꢀ E\ꢀ FROXPQꢀ FKURPDWRJUDSK\ꢀ ꢄVLOLFDꢋꢀ ꢂꢒꢇꢀ KH[DQHꢆ
(W2$FꢉꢀDVꢀDQꢀHOXHQWꢓꢀ5Iꢀ ꢀꢌꢁꢑꢋꢀꢇꢌꢍꢀ\LHOGꢋꢀRIIꢀZKLWHꢀVROLGꢋꢀPꢁSꢁꢀꢈꢐꢏ±
4-(4-(4, 4-dimethyl-4, 5-dihydrooxazol-2-yl) phenyl)-7H-pyrrolo
[2, 3-d] pyrimidine (5fꢉꢒꢀ 3XUL¿FDWLRQꢀ E\ꢀ FROXPQꢀ FKURPDWRJUDSK\ꢀ
(silica, 1:1 hexane/EtOAc) as an eluent; Rf = 0.7, 60% yield, white
VROLGꢋꢀ PꢁSꢁꢀ ꢐꢏꢎ±ꢐꢏꢃ°C, 1H NMR (400 MHz,DMSO-d6) G 9.12
(s, 1H), 8.26 (m, J = 8.8 Hz, 2H), 8.15 (m, J = 8 Hz, 2H), 7.55 (d,
J = 8.4 Hz, 1H), 7.31 (d, J = 4 Hz, 1H), 4.20 (s, 2H), 1.29 (s, 6H),
13C NMR (DMSO-d6) G 160.4, 158.2,152.0, 151.2, 136.3, 132.4,
131.8, 130.5 127.8, 114.3, 103.4 78.8, 67.7, 28.5; ESIMS: m/z Calcd
[M +]: 292; Found: 293 [M + H +]; HRMS (ESI): m/z Calcd [M +]:
292.3351; Found: 293.3201 [M + H +].
4, 4-dimethyl-2-(4-(thiophen-2-yl) phenyl)-4, 5-dihydrooxazole
(5gꢉꢒꢀ 3XUL¿FDWLRQꢀ E\ꢀ FROXPQꢀ FKURPDWRJUDSK\ꢀ ꢄVLOLFDꢋꢀ ꢂꢒꢇꢓꢀ KH[DQHꢆ
(W2$FꢉꢀDVꢀDQꢀHOXHQWꢓꢀ5Iꢀ ꢀꢌꢁꢑꢋꢀꢂꢎꢍꢀ\LHOGꢋꢀ\HOORZꢀVROLGꢋꢀPꢁSꢁꢀꢂꢎ±
77°C, 1H NMR (400 MHz,DMSO-d6) G 7.80 (d, J = 8.4 Hz, 2H),
7.69 (d, J = 8 Hz, 2H), 7.57 (m, J = 7.2 Hz, 2H), 7.11 (m, J = 8.8 Hz,
1H), 4.04 (s, 2H), 1.22 (s, 6H), 13C NMR (DMSO-d6) G 160.6, 142.7,
136.7, 129.3, 129.0, 127.3, 126.9 125.7, 125.3, 78.8, 67.9, 28.7;
ESIMS: m/z Calcd [M +]: 257; Found: 258 [M + H +]; HRMS (ESI):
m/z Calcd [M +]: 257.3507; Found: 258.2326 [M + H +].
1
223°C, H NMR (400 MHz,DMSO-d6) G 7.63 (m, J = 8.4 Hz, 1H),
7.48 (m, J = 7.6 Hz, 2H), 7.21 (m, J = 7.6 Hz, 1H), 6.92 (t, J = 7.2
Hz, 1H), 6.56 (m, 1H), 6.29 (m, J = 7.2 Hz, 1H), 4.42 (s, 2H), 1.59
(s, 6H), 13C NMR (DMSO-d6) G 160.3, 144.0, 133.2, 131.5, 131.2,
130.7, 129.3 128.1, 127.7, 126.0, 123.2, 79.8, 67.9, 28.3; ESIMS: m/z
Calcd [M +]: 257; Found: 258 [M + H +]; HRMS (ESI): m/z Calcd
[M +]: 257.3507; Found: 258.3216 [M + H +].
2-(2-(furan-3-yl) phenyl)-4, 4-dimethyl-4, 5-dihydrooxazole (9i):
3XUL¿FDWLRQꢀE\ꢀFROXPQꢀFKURPDWRJUDSK\ꢀꢄVLOLFDꢋꢀꢂꢒꢇꢀKH[DQHꢆ(W2$Fꢉꢀ
as an eluent; Rf = 0.6, 20% yield, colourless liquid, 1H NMR
(400 MHz, DMSO-d6) G 7.81 (d, J = 8.2 Hz, 1H), 7.72 (m, J = 7.4 Hz,
2H), 7.69 (m, J = 7.6 Hz, 1H), 7.60 (s, 1H), 7.56 (m, 1H), 6.61 (d,
1H), 4.06 (s, 2H), 1.28 (s, 6H), 13C NMR (DMSO-d6) G 160.8, 146.3,
144.0, 133.0, 131.7, 129.2, 128.1 127.8, 127.7, 126.2, 108.4, 79.8,
67.9, 29.3; ESIMS: m/z Calcd [M +]: 241; Found: 242 [M + H +];
HRMS (ESI): m/z Calcd [M +]: 241.2851; Found: 242.2831
[M + H +].
4, 4-dimethyl-2-(4-(thiophen-3-yl) phenyl)-4, 5-dihydrooxazole
(5hꢉꢒꢀ 3XUL¿FDWLRQꢀ E\ꢀ FROXPQꢀ FKURPDWRJUDSK\ꢀ ꢄVLOLFDꢋꢀ ꢂꢒꢇꢀ KH[DQHꢆ
(W2$FꢉꢀDVꢀDQꢀHOXHQWꢓꢀ5Iꢀ ꢀꢌꢁꢑꢋꢀꢃꢌꢍꢀ\LHOGꢋꢀ\HOORZꢀVROLGꢋꢀPꢁSꢁꢀꢃꢌ±
84°C, 1H NMR (400 MHz,DMSO-d6) G 7.71 (d, J = 8.2 Hz, 2H),
7.51 (d, J = 7.4 Hz, 2H), 7.46 (s, 1H), 7.30 (d, J = 8.8 Hz, 1H), 7.08
(d, J = 8.4 Hz, 1H), 4.05 (s, 2H), 1.27 (s, 6H), 13C NMR (DMSO-
d6) G 160.5, 142.4, 139.8, 130.3, 128.5, 126.7, 125.8 124.8, 122.5,
78.9, 67.8, 27.9; ESIMS: m/z Calcd [M +]: 257; Found: 258 [M +
H +]; HRMS (ESI): m/z Calcd [M +]: 257.3507; Found: 258.2816
[M + H +].
We are grateful to Indian Association for Cultivation Sciences,
-DGDYSXUꢀ 3¿]HUꢀ /WGꢀ DQGꢀ 691,7ꢋꢀ 6XUDWꢋꢀ ,QGLDꢀ IRUꢀ DQDO\WLFDOꢀ
support.
Received 9 January 2009; accepted 17 February 2009
Paper 09/0380 doi: 10.3184/030823409X431355
Published online: 29 April 2009
2-(4-(furan-3-yl) phenyl)-4, 4-dimethyl-4, 5-dihydrooxazole (5i):
3XUL¿FDWLRQꢀE\ꢀFROXPQꢀFKURPDWRJUDSK\ꢀꢄVLOLFDꢋꢀꢂꢒꢇꢀKH[DQHꢆ(W2$Fꢉꢀ
as an eluent; Rf = 0.6, 55% yield, brown liquid, 1H NMR (400
MHz,DMSO-d6) G 7.89 (d, J = 8.4 Hz, 2H), 7.61 (s, 1H), 7.56 (d,
J = 7.4 Hz, 2H), 6.58 (m, J = 8.8 Hz, 2H), 4.08 (s, 2H), 1.23 (s, 6H),
13C NMR (DMSO-d6) G 159.8, 142.7, 141.4, 136.0, 129.7, 128.8,
127.7 125.9, 108.6, 78.7, 67.9, 28.2; ESIMS: m/z Calcd [M +]: 241;
Found: 242 [M + H +]; HRMS (ESI): m/z Calcd [M +]: 241.2851;
Found: 242.1102 [M + H +].
4,4-dimethyl-2-(3-(thiophen-2-yl)phenyl)-4,5-dihydrooxazole
(7gꢉꢒꢀ 3XUL¿FDWLRQꢀ E\ꢀ FROXPQꢀ FKURPDWRJUDSK\ꢀ ꢄVLOLFDꢋꢀ ꢂꢒꢇꢀ KH[DQHꢆ
EtOAc) as an eluent; Rf = 0.6, 70% yield, brown liquid, 1H NMR
(400 MHz,DMSO-d6) G 7.98 (t, J = 1.6 Hz, 1H), 7.79 (m, J = 6.4 Hz,
1H), 7.70 (m, J = 8 Hz, 1H), 7.53 (m, J = 7.6 Hz, 2H), 7.46 (m,
J = 7.6 Hz, 1H), 7.10 (m, J = 5.2 Hz, 1H), 4.06 (s, 2H), 1.22 (s,
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