Preparation of 2-(1-chloroalkyl)-4,5-dimethyloxazoles and (E)2-alkenyl-4,5-dimethyloxazoles

Article abstract of DOI:10.1055/s-2006-942351

2-(1-Chloroalkyl)-4,5-dimethyloxazoles were prepared in 84-91% yields by simultaneous reduction and regioselective chlorination of the corresponding unstable N-oxides with POCl₃ or SOCl₂. Dehydrochlorination of 2-(1-chloroalkyl)-4,5-

Full text of DOI:10.1055/s-2006-942351

PAPER
1763
Preparation of 2-(1-Chloroalkyl)-4,5-dimethyloxazoles and (E)-2-Alkenyl-4,5-
dimethyloxazoles
2
-(1-Chloroalkyl)-
u
4,5-dimethyl
a
oxazoles and (
E
)-
Z
2-Alkenyl-4,5-
h
dimethyloxaz
a
oles ng,a–c Peng-Fei Yan,c Guo-Lin Zhang*a
a
Chengdu Institute of Biology, The Chinese Academy of Sciences, Chengdu 610041, P. R. of China
Fax +86(28)85225401; E-mail: zhanggl@cib.ac.cn
b
c
Graduate School of the Chinese Academy of Sciences, Beijing 100039, P. R. of China
College of Chemical Engineering and Material of Heilongjiang University, Haerbin 150080, P. R. of China
Received 9 November 2005; revised 12 January 2006
Table 1 Synthesis of 3a–h
R
Abstract: 2-(1-Chloroalkyl)-4,5-dimethyloxazoles were prepared
in 84–91% yields by simultaneous reduction and regioselective
chlorination of the corresponding unstable N-oxides with POCl3 or
SOCl2. Dehydrochlorination of 2-(1-chloroalkyl)-4,5-dimethylox-
azoles with potassium hydroxide afforded (E)-2-alkenyl-4,5-di-
methyloxazoles in 71–90% yields.
Products
3a
Isolated yield (%)a
94 (91)
Phenyl
4-Methoxyphenyl
3,4-Dimethoxyphenyl
3,4,5-Trimethoxyphenyl
4-Chlorophenyl
4-Bromophenyl
4-Nitrophenyl
3b
88 (85)
Key words: oxazole, chlorination, regioselectivity, dehydrochlori-
nation
3c
86 (83)
3d
83 (80)
3e
89 (86)
Oxazoles have attracted great interest due to their occur-
rence as subunits of various biologically active natural
products and some drug molecules, as well as their appli-
cations as valuable precursors in many useful synthetic
transformations.1,2 There are some synthetic methods for
2,4,5-trisubstituted oxazoles,3,4 but there is no report on
the synthesis of 2-(1-chloroalkyl)-4,5-dimethyloxazoles 5
and (E)-2-alkenyl-4,5-dimethyloxazoles 6. Here, we re-
port a practical and convenient synthesis of 5 and 6.
3f
79 (78)
3g
91 (89)
Furan-2-yl
3h
85 (84)
a The numbers in parentheses are the yields obtained when SOCl2 was
used.
According to the procedure reported,5,6 several 4-chlo-
romethyl-2-aryl-5-methyloxazoles 3 were prepared from
the N-oxides 2 with POCl3 or SOCl2 in chloroform at re-
flux (Scheme 1, Table 1). Compounds 2 could be ob-
tained by condensation of aromatic aldehyde and 2,3-
butanedione monooxime 1 in acetic acid saturated by an-
hydrous hydrochloride gas.5,6
efficiency of the reaction, compounds 5a–f were synthe-
sized. Dehydrochlorination of 5b–f with potassium hy-
droxide afforded 6b–f (Table 2). The structure of 5b was
determined by 2D NMR experiments (Figure 1).
R
O
O
b
a
N+
HON
–O
1
4a–f
O
O
O
b
a
R
R
N+
1
N
1
O
HON
–O
R'
Cl
R
O
5
4
2
2
5
4
c
3a–h
2a–h
1
3N
5a–f
Cl
3 N
Scheme 1 Reagents and conditions: (a) anhyd HCl (g), ArCHO,
AcOH; (b) POCl3 (or SOCl2), CHCl3, reflux.
6b–f
Scheme 2 Reagents and conditions: (a) anhyd HCl (g), RCH2CHO,
AcOH; (b) POCl3 or SOCl2, CHCl3, reflux; (c) KOH, C2H5OH, ref-
lux.
While attempting to prepare 2-alkyl-4-chloromethyl-5-
methyloxazoles following the above-mentioned proce-
dure, we observed the chlorination of the corresponding
N-oxides by POCl3 or SOCl2 at 2-methylene rather than
4-methyl (Scheme 2) position. This phenomenon may be
due to the activity difference between 2-methylene and
4-methyl (Scheme 2) groups. To investigate the scope and
In conclusion, a simple and efficient procedure to synthe-
size 2-(1-chloroalkyl)-4,5-dimethyloxazoles and (E)-2-
alkenyl-4,5-dimethyloxazoles was developed.
SYNTHESIS 2006, No. 11, pp 1763–1766
x
x.
x
x
.
2
0
0
6
Advanced online publication: 05.05.2006
DOI: 10.1055/s-2006-942351; Art ID: F19305SS
© Georg Thieme Verlag Stuttgart · New York

1764
H. Zhang et al.
PAPER
Et2O (2 × 10 mL), then dissolved in H2O (20 mL) and concd
NH4OH (20 mL). This solution was extracted with CHCl3. The
combined organic layer was washed with H2O and brine, and dried
over MgSO4. The solvent was removed in vacuo to give the unstable
N-oxides. To a solution of the unstable N-oxides (4 mmol) in CHCl3
(20 mL) was added dropwise POCl3 or SOCl2 (0.4 mL, 5 mmol).
The mixture was stirred at reflux for 0.5 h, then cooled to r.t., and
washed with H2O (3 × 20 mL). The combined aqueous layer was re-
extracted with CHCl3 (2 × 30 mL). The combined organic layer was
dried over MgSO4, and the solvent was removed in vacuo to give
the crude products, which were purified by column chromatography
or by recrystallization.
Table 2 Synthesis of 5a–f and 6b–f
Isolated yield (%)a
O
Y
Y
N
Chlorophenylmethyl
1-Chloro-2-phenylethyl
1-Chloropropyl
2-Chloropropan-2-yl
1-Chloropentyl
1-Chlorooctyl
Styryl
5a
5b
5c
5d
5e
5f
88 (86)
91 (88)
87 (81)
90
Synthesis of 6b–f; General Procedure
87
The mixture of 5b–f (2.0 mmol) in anhyd EtOH (20 mL) and anhyd
KOH (2.2 mmol) was stirred at reflux for 2 h and then cooled to r.t.
The solvent was removed in vacuo to give the residue, which was
washed with Et2O (3 × 20 mL). The combined organic layer was
washed with H2O and dried over MgSO4. Then the solvent was re-
moved in vacuo to give the crude products, which were purified by
column chromatography.
84
6b
6c
6d
6e
6f
90
Propenyl
73
Isopropenyl
71
Pentenyl
80
4-Chloromethyl-5-methyl-2-phenyloxazole (3a)
Yield: 0.78 g (94%); colorless columnar crystals [PE–acetone,
30:1]; mp 77.8–78.3 °C.
Octenyl
87
a The numbers in parentheses are the yields obtained when SOCl2 was
used.
IR (KBr): 2924, 1633, 1558, 1490, 1448, 1259, 1112, 1063, 774,
700 cm–1.
1H NMR (600 MHz, CDCl3): d = 2.43 (s, 3 H), 4.56 (s, 2 H), 7.26
(t, J = 7.8 Hz, 1 H), 7.30 (t, J = 7.2 Hz, 2 H), 7.42 (d, J = 7.5 Hz, 2
H).
1
I3C NMR (150 MHz, CDCl3): d = 160.1, 146.6, 132.9, 130.3, 128.7,
H
H
H
O
CH3
3''
2''
1'
H
1''
2
5
127.2, 126.2, 37.3, 10.4.
2'
4''
N
Cl
ESI–MS (+ve mode): m/z (%) = 230 (82) [M + Na]+, 246 (15) [M +
4
3
CH3
H
6''
K]+.
5''
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C11H11ClNO:
208.0524; found: 208.0521.
1
O
H
2''
H
CH3
1'
2
4-Choromethyl-2-(4-methoxyphenyl)-5-methyloxazole (3b)
Yield: 0.83 g (88%); colorless cubic crystals [PE–acetone, 30:1];
mp 83.9–84.2 °C.
3''
5''
H
5
2'
4''
N
Cl
1''
4
3
6''
CH3
H
IR (KBr): 2964, 1617, 1590, 1499, 1447, 1251, 1165, 1024, 832,
740, 698 cm–1.
1H NMR (600 MHz, CDCl3): d = 2.40 (s, 3 H), 3.85 (s, 3 H), 4.54
(s, 2 H), 6.94 (d, J = 8.8 Hz, 2 H), 7.93 (d, J = 8.6 Hz, 2 H).
H
Figure 1 Major HMBC (→) and NOESY (↔) correlations in com-
pound 5b.
I3C NMR (150 MHz, CDCl3): d = 161.2, 160.2, 145.9, 132.6, 127.8,
120.1, 114.1, 55.4, 37.4, 10.3.
ESI–MS (+ve mode): m/z (%) = 238 (70) [M + H]+, 260 (10) [M +
All starting compounds were used as received from commercial
sources without further purification. Petroleum ether (PE) used had
the boiling range 60–90 °C. Melting points were determined on a
XRC-1 micromelting point apparatus and are uncorrected. Column
chromatography was carried out on silica gel (200–300 mesh,
Qingdao Haiyang Chemical Co. Ltd.). NMR spectra were recorded
on a Bruker Avance 600 spectrometer with TMS as internal stan-
dard. MS spectra measurements were carried out on a Finnigan
LCQDECA mass spectrometer (ESI–MS) and a BioTOF-Q mass
spectrometer (HR–ESI–MS). IR spectra were recorded on a Perkin-
Elmer spectrum one FT-IR spectrometer (KBr disc).
Na]+.
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C12H13ClNO2:
238.0635; found: 238.0629.
4-Chloromethyl-2-(3,4-dimethoxyphenyl)-5-methyloxazole (3c)
Yield: 0.92 g (86%); colorless needles [PE–acetone, 20:1]; mp
113.8–114.3 °C.
IR (KBr): 2962, 1607, 1568, 1513, 1463, 1251, 1138, 1023, 858,
770, 714 cm–1.
1H NMR (600 MHz, CDCl3): d = 2.42 (s, 3 H), 3.93 (s, 3 H), 3.97
(s, 3 H), 4.54 (s, 2 H), 6.91 (d, J = 8.3 Hz, 1 H), 7.52 (d, J = 1.7 Hz,
1 H), 7.57 (dd, J = 1.7, 8.3 Hz, 1 H).
I3C NMR (150 MHz, CDCl3): d = 160.1, 150.9, 149.1, 146.1, 132.6,
120.2, 119.4, 111.0, 109.0, 56.0, 37.4, 10.4.
Synthesis of 3a–h and 5a–f; General Procedure
A solution of 2,3-butanedione monooxime7 (0.40 g, 5.0 mmol) and
aldehyde (5.3 mmol) in AcOH (20 mL) was cooled to 0–5 °C. An-
hyd HCl (g) was bubbled into the reaction mixture for 0.5 h. The
mixture was stirred at the same temperature for 0.5 h and diluted
with Et2O (40 mL). The precipitate was filtered and washed with
Synthesis 2006, No. 11, 1763–1766 © Thieme Stuttgart · New York

PAPER
2-(1-Chloroalkyl)-4,5-dimethyloxazoles and (E)-2-Alkenyl-4,5-dimethyloxazoles
1765
ESI–MS (+ve mode): m/z (%) = 268 (71) [M + H]+, 290 (60) [M +
4-Chloromethyl-2-(furan-2-yl)-5-methyloxazole (3h)
Yield: 0.67 g (85%); colorless needles [PE–acetone, 40:1]; mp 43–
45 °C.
Na]+.
HR–MS (ESI, +ve mode): m/z [M + H]+ calcd for C13H15ClNO3:
268.0739; found: 268.0735.
IR (KBr): 3106, 2970, 1634, 1620, 1546, 1495, 1436, 1305, 1264,
1157, 1025, 954, 893, 764, 774, 747, 706 cm–1.
4-Chloromethyl-2-(3,4,5-trimethoxyphenyl)-5-methyloxazole
(3d)
Yield: 0.98 g (83%); colorless cubic crystals [PE–acetone, 15:1];
mp 113.9–114.6 °C.
1H NMR (600 MHz, CDCl3): d = 2.42 (s, 3 H), 4.53 (s, 2 H), 6.53
(dd, J = 1.7, 3.4 Hz, 1 H), 6.98 (d, J = 3.4 Hz, 1 H), 7.54 (t, J = 0.8
Hz, 1 H).
13C NMR (150 MHz, CDCl3): d = 152.7, 146.1, 144.3, 142.6, 132.7,
111.8, 111.2, 37.0, 10.3.
IR (KBr): 2924, 1630, 1560, 1502, 1418, 1241, 1127, 1004, 747,
779, 714 cm–1.
1H NMR (600 MHz, CDCl3): d = 2.44 (s, 3 H), 3.90 (s, 3 H), 3.94
(s, 6 H), 4.56 (s, 2 H), 7.25 (s, 2 H).
I3C NMR (150 MHz, CDCl3): d = 159.9, 153.5, 146.5, 140.0, 132.9,
122.6, 103.4, 61.0, 56.3, 37.3, 10.4.
ESI–MS (+ve mode): m/z (%) = 220 (75) [M + Na]+, 162 (79) [M –
Cl]+.
HRMS (ESI, +ve mode): m/z [M + Na]+ calcd for C9H8ClNO2Na:
220.0138; found: 220.0136.
ESI–MS (+ve mode): m/z (%) = 298 (84) [M + H]+, 320 (72) [M +
2-(Phenylchloromethyl)-4,5-dimethyloxazole (5a)
Yield: 0.78 g (88%); colorless oil.
Na]+, 337 (15) [M + K]+.
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C14H17ClNO4:
298.0841; found: 298.0834.
IR (KBr): 2928, 2852, 1625, 1559, 1490, 1441, 1254, 1110, 1030,
770, 690 cm–1.
1H NMR (600 MHz, CDCl3): d = 2.36 (s, 3 H), 2.38 (s, 3 H), 6.21
(s, 1 H), 7.28 (d, J = 7.8 Hz, 2 H), 7.30 (t, J = 7.3 Hz, 1 H), 7.33 (t,
J = 7.6 Hz, 2 H).
I3C NMR (150 MHz, CDCl3): d = 159.4, 138.7, 136.2, 129.7, 128.3,
127.6, 126.2, 62.8, 12.1, 10.3.
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C12H13ClNO:
222.0618; found: 222.0612.
4-Chloromethyl-2-(4-chlorophenyl)-5-methyloxazole (3e)
Yield: 0.86 g (89%); colorless cubic crystals [PE–acetone, 30:1];
mp 92.3–92.9 °C.
IR (KBr): 2962, 1634, 1605, 1549, 1485, 1260, 1118, 1090, 834,
716, 691 cm–1.
1H NMR (600 MHz, CDCl3): d = 2.42 (s, 3 H), 4.54 (s, 2 H), 7.41
(d, J = 8.5 Hz, 2 H), 7.93 (d, J = 8.5 Hz, 2 H).
I3C NMR (150 MHz, CDCl3): d = 159.1, 146.8, 136.4, 133.1, 129.0,
127.4, 125.7, 37.1, 10.4.
2-(1-Chloro-2-phenylethyl)-4,5-dimethyloxazole (5b)
Yield: 0.86 g (91%); yellow oil.
ESI–MS (+ve mode): m/z (%) = 243 (74) [M + H]+, 265 (20) [M +
IR (KBr): 2965, 1630, 1551, 1497, 1443, 1260, 1110, 1060, 771,
710 cm–1.
Na]+.
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C11H10Cl2NO:
243.0134; found: 243.0125.
1H NMR (600 MHz, CDCl3): d = 2.06 (s, 3 H), 2.34 (s, 3 H), 3.39
(dd, J = 7.1, 14.1 Hz, 1 H), 3.58 (dd, J = 8.2, 14.1 Hz, 1 H), 5.05 (t,
J = 7.6 Hz, 1 H), 7.20 (d, J = 7.4 Hz, 2 H), 7.24 (t, J = 7.1 Hz, 1 H),
7.28 (t, J = 7.5 Hz, 2 H).
I3C NMR (150 MHz, CDCl3): d = 158.4, 144.4, 136.5, 131.2, 129.3,
128.6, 127.2, 53.8, 42.2, 11.1, 10.0.
2-(4-Bromophenyl)-4-chloromethyl-5-methyloxazole (3f)
Yield: 0.91 g (79%); colorless cubic crystals [PE–acetone, 20:1];
mp 57–58 °C.
IR (KBr): 2970, 1633, 1599, 1481, 1402, 1258, 1117, 1006, 843,
718, 700 cm–1.
1H NMR (600 MHz, CDCl3): d = 2.44 (s, 3 H), 4.53 (s, 2 H), 7.57
(d, J = 8.5 Hz, 2 H), 7.87 (d, J = 8.5 Hz, 2 H).
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C13H15ClNO:
236.0837; found: 236.0831.
2-(1-Chloropentyl)-4,5-dimethyloxazole (5c)
Yield: 0.60 g (87%); colorless oil.
IR (KBr): 2967, 2862, 1667, 1455, 1384 cm–1.
13C NMR (150 MHz, CDCl3): d = 159.3, 146.6, 133.2, 132.0, 127.8,
126.1, 124.7, 37.4, 10.7.
ESI–MS (+ve mode): m/z (%) = 286 (80) [M + H]+, 308 (24) [M +
1H NMR (600 MHz, CDCl3): d = 1.05 (t, J = 7.3 Hz, 3 H), 2.04 (s,
3 H), 2.18 (s, 3 H), 2.20 (m, 2 H), 4.79 (t, J = 7.1 Hz, 1 H).
Na]+.
I3C NMR (150 MHz, CDCl3): d = 159.2, 144.2, 130.9, 55.0, 37.3,
4-Chloromethyl-5-methyl-2-(4-nitrophenyl)oxazole (3g)
Yield: 0.92 g (91%); yellow columnar crystals [PE–acetone, 25:1];
mp 107.4–107.9 °C.
13.7, 10.1, 9.9.
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C8H13ClNO:
174.0686; found: 174.0683.
IR (KBr): 3088, 2975, 2925, 1629, 1603, 1561, 1520, 1485, 1353,
1333, 1108, 1063, 864, 852, 710 cm–1.
1H NMR (600 MHz, CDCl3): d = 2.48 (s, 3 H), 4.57 (s, 2 H), 8.18
(d, J = 8.6 Hz, 2 H), 8.31 (d, J = 8.6 Hz, 2 H).
13C NMR (150 MHz, CDCl3): d = 157.9, 148.6, 148.3, 134.1, 132.6,
126.9, 124.2, 36.8, 10.5.
2-(2-Chloropropan-2-yl)-4,5-dimethyloxazole (5d)
Yield: 0.64 g (90%), colorless oil.
IR (KBr): 2957, 2868, 1661, 1445, 1380 cm–1.
1H NMR (600 MHz, CDCl3): d = 1.98 (s, 6 H), 2.20 (s, 3 H), 2.39
(s, 3 H).
I3C NMR (150 MHz, CDCl3): d = 167.4, 145.8, 130.8, 58.2, 29.3,
10.1.
ESI–MS (+ve mode): m/z (%) = 253 (85) [M + H]+.
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C11H10ClN2O3:
253.0312; found: 253.0316.
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C8H13ClNO:
174.0686; found: 174.0683.
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H. Zhang et al.
PAPER
2-(1-Chloropentyl)-4,5-dimethyloxazole (5e)
Yield: 0.70 g (87%); colorless oil.
I3C NMR (150 MHz, CDCl3): d = 156.8, 145.8, 139.6, 126.7, 119.3,
22.5, 11.7, 10.1.
IR (KBr): 2959, 2874, 1645, 1455, 1196 cm–1.
HRMS (ESI, +ve mode): m/z: [M + H]+ calcd for C8H12NO:
138.0934; found: 138.0906.
1H NMR (600 MHz, CDCl3): d = 0.92 (t, J = 7.1 Hz, 3 H), 1.24–1.56
(m, 6 H), 2.08 (s, 3 H), 2.27 (s, 3 H), 4.86 (t, J = 5.1 Hz, 1 H).
I3C NMR (150 MHz, CDCl3): d = 159.4, 144.3, 130.9, 53.5, 35.8,
28.6, 21.9, 13.9, 11.0, 10.0.
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C10H17ClNO:
202.1017; found: 202.1015.
(E)-4,5-Dimethyl-2-pentenyloxazole (6e)
Yield: 0.26 g (80%); yellow oil.
IR (KBr): 3028, 2962, 2853, 1660, 1439, 1105 cm–1.
1H NMR (600 MHz, CDCl3): d = 0.93 (t, J = 6.0 Hz, 3 H), 1.42 (m,
2 H), 1.90 (m, 2 H), 2.15 (s, 3 H), 2.39 (s, 3 H), 6.12 (dt, J = 7.1,
15.9 Hz, 1 H), 6.46 (d, J = 15.9 Hz, 1 H).
I3C NMR (150 MHz, CDCl3): d = 159.8, 138.1, 131.5, 130.0, 126.7,
36.2, 21.5, 14.1, 9.9.
2-(1-Chlorooctyl)-4,5-dimethyloxazole (5f)
Yield: 0.82 g (84%); colorless oil.
IR (KBr): 2982, 2857, 1669, 1450, 1378 cm–1.
1H NMR (600 MHz, CDCl3): d = 0.89 (t, J = 6.7 Hz, 3 H), 1.20–1.54
(m, 12 H), 2.08 (s, 3 H), 2.26 (s, 3 H), 4.85 (t, J = 5.1 Hz, 1 H).
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C10H16NO:
166.1213; found: 166.1216.
I3C NMR (150 MHz, CDCl3): d = 160.4, 144.8, 131.0, 53.5, 38.3,
(E)-4,5-Dimethyl-2-octenyloxazole (6f)
Yield: 0.36 g (87%); yellow oil.
IR (KBr): 3034, 2958, 2872, 1644, 1455, 1094 cm–1.
1H NMR (600 MHz, CDCl3): d = 0.89 (t, J = 6.2 Hz, 3 H), 1.29–1.98
(m, 10 H), 2.10 (s, 3 H), 2.31 (s, 3 H), 6.12 (dt, J = 7.2, 16.1 Hz, 1
H), 6.58 (d, J = 16.1 Hz, 1 H).
I3C NMR (150 MHz, CDCl3): d = 156.3, 139.3, 130.6, 126.1, 123.8,
35.6, 30.7, 29.6, 29.0, 23.5, 15.1, 10.0, 9.6.
31.6, 29.0, 28.8, 25.2, 23.6, 14.3, 10.1, 9.8.
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C13H23ClNO:
244.1466; found: 244.1461.
(E)-4,5-Dimethyl-2-styryloxazole (6b)
Yield: 0.36 g (90%); white solid.
IR (KBr): 3025, 2963, 16370, 1550, 1493, 1440, 1260, 1110, 1060
cm–1.
1H NMR (600 MHz, CDCl3): d = 2.08 (s, 3 H), 2.26 (s, 3 H), 6.90
(d, J = 16.2 Hz, 1 H), 6.98 (d, J = 16.2 Hz, 1 H), 7.18 (t, J = 7.6 Hz,
2 H), 7.28 (t, J = 7.3 Hz, 1 H), 7.37 (d, J = 7.8 Hz, 2 H).
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C13H22NO:
208.1712; found: 208.1702.
I3C NMR (150 MHz, CDCl3): d = 155.1, 139.6, 136.2, 133.8, 128.8,
127.8, 126.9, 124.9, 124.1, 11.3, 10.7.
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Kronenthal, D. R.; Singh, J.; Pansegrau, P. D.; Mueller, R.
H. Tetrahedron Lett. 1992, 33, 7835.
(4) (a) Williams, D. R.; McClymont, E. L. Tetrahedron Lett.
1993, 34, 7705. (b) Lee, J. C.; Choi, H. J.; Lee, Y. C.
Tetrahedron Lett. 2003, 44, 123. (c) Cai, X. H.; Yang, H. J.;
Zhang, G. J. Synthesis 2005, 1569.
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C13H14NO:
200.1062; found: 200.1068.
(E)-4,5-Dimethyl-2-propenyloxazole (6c)
Yield: 0.20 g (73%); light-yellow oil.
IR (KBr): 3052, 2980, 2831, 16651, 1441, 1380 cm–1.
1H NMR (600 MHz, CDCl3): d = 1.78 (d, J = 15.6 Hz, 3 H), 2.12 (s,
3 H), 2.41 (s, 3 H), 6.10 (dq, J = 6.9, 16.2 Hz, 1 H), 6.42 (d, J = 16.2
Hz, 1 H).
I3C NMR (150 MHz, CDCl3): d = 158.8, 142.3, 131.3, 131.0, 130.0,
15.1, 9.8.
HRMS (ESI, +ve mode): m/z [M + H]+ calcd for C8H12NO:
138.0934; found: 138.0975.
4,5-Dimethyl-2-isopropenyloxazole (6d)
Yield: 0.19 g (71%); light-yellow oil.
IR (KBr): 3075, 2928, 2830, 1668, 1440, 1375, 1118 cm–1.
1H NMR (600 MHz, CDCl3): d = 1.76 (s, 3 H), 2.10 (s, 3 H), 2.31
(s, 3 H), 4.93 (d, J = 7.1 Hz, 1 H), 5.31 (d, J = 7.1 Hz, 1 H).
(5) Daw, A. B.; Garret, J. E.; Christopher, J. R.; Athony, J. S. J.
Med. Chem. 2001, 44, 2061.
(6) Goto, Y.; Yamazaki, M.; Hamana, M. Chem. Pharm. Bull.
1971, 19, 2050.
(7) Semon, W. L.; Damerell, V. R. Org. Synth., Coll. Vol. II;
Wiley: New York, 1943, 204.
Synthesis 2006, No. 11, 1763–1766 © Thieme Stuttgart · New York