Convenient syntheses of 2-alkyl(Aryl)-4,5-diphenyloxazoles and 2-alkyl(Aryl)-4-phepyloxazoles

Article abstract of DOI:10.1055/s-1998-6093

The synthetic methods to prepare 2-alkyl(aryl)-4,5-diphenyloxazoles and 2-alkyl(aryl)-4-phenyloxazoles were improved on the basis of a mechanistic study of oxazole formation from α-hydroxy ketones (carboxylic esters of benzoin and phenacyl alcohols). By these methods, seven trisubstituted oxazoles and twelve disubstituted oxazoles of the title compounds were prepared.

Full text of DOI:10.1055/s-1998-6093

SYNTHESIS
Papers
1298
Convenient Syntheses of 2-Alkyl(Aryl)-4,5-diphenyloxazoles and 2-Alkyl(Aryl)-4-
phenyloxazoles
Weiwei Pei, Shaohui Li, Xiaoping Nie, Yiwei Li, Jian Pei, Bingzi Chen, Jie Wu, Xiulin Ye*
Department of Chemistry, Peking University, Beijing 100871, People’s Republic of China
Fax: +86(1)62751708
Received 20 October 1997; revised 19 January 1998
Abstract: The synthetic methods to prepare 2-alkyl(aryl)-4,5-
diphenyloxazoles and 2-alkyl(aryl)-4-phenyloxazoles were im-
proved on the basis of a mechanistic study of oxazole formation
from α-hydroxy ketones (carboxylic esters of benzoin and phenacyl
alcohols). By these methods, seven trisubstituted oxazoles and
twelve disubstituted oxazoles of the title compounds were prepared.
Key words: benzoin carboxylate, phenacyl carboxylate, di- and
trisubstituted oxazoles, mechanism of oxazole formation
In the past three decades, oxazoles have proved quite use-
Scheme l
ful in medicine owing to their curative properties, for ex-
ample, anti-platelet coagulant,1, 2 anti-articular rheuma-
gave 4,5-diphenyloxazole in 55% yield.17 If xylene was
tism,3 skeletal muscle relaxant4 and depressors5–8 of al-
used to remove water by azeotropic distillation, the yield
dose reductases, blood sugar and blood lipid, etc.
increased to 83%.
Moreover, since the synthesis of pyridoxine9 had been ac-
complished by the Diels–Alder reaction of 5-ethoxy-4-
methyloxazole with but-2-ene-1,4-diol, oxazoles have
been found very useful in organic synthesis.10–14
However, when route C was repeated, the results obtained
in our experiments were compared with those recorded in
the literature and some errors were revealed (see Table 2).
We wanted to design synthetic routes for some natural
products from 5-aryl-4-phenyloxazole or 2-aryl-4-phenyl-
oxazole, but the preparative procedures in the literature
were not satisfactory for either of the diaryloxazoles.
Thus, a mechanism for the formation of oxazoles from
α-hydroxy ketones was suggested according to the exper-
imental evidence, and the synthetic procedures were im-
proved on the basis of this mechanism. Nineteen oxazoles
were prepared in acceptable yields.
The benzil obtained was possibly formed in the following
reaction (Scheme 2).
Scheme 2
Three methods have been reported in the literature for the
preparation of 4,5-diphenyloxazoles from benzoin
(Scheme 1).15–17
Thus, the melting point of benzoin formate is now correct-
ed from 68°C to 73.0–74.5°C according to our investiga-
tion. The purified benzoin formate was subjected to reflux
in formamide to give 4,5-diphenyloxazole in 52% yield.
Firstly, the routes A and B were repeated and the results
are shown in Table 1.
There is a problem with the mechanism of 4,5-diphenyl-
oxazole formation by this route, whether the formyl group
in the -O–CHO moiety (mechanism I) or the formyl group
in the -N-CHO moiety (mechanism II) takes part in the
Because route A gave a very low yield of 4,5-diphenylox-
azole, no further investigation of this route was made. Ac-
cording to route B, refluxing benzoin in excess formamide
Table 1. Preparation of 4,5-Diphenyloxazole from Benzoin
Route
Intermediatea
mp (°C)
4,5-Diphenyloxazole
Yield (%)
Found
bp (°C)/mbar or mp (°C)
Yield (%)
Found
Found
Lit.
Lit.
Found
Lit.
Lit.
A
B
64.5–66.0
–
66–6716
–
67
–
7416
–
170–172/2.66
171–174/2.66
42–44
132/6.66×10–2 15
121/1.33×10–2 17
4417
33b
83
7015
5517
a Route A: PhCOCHClPh; route B: –.
b The product obtained in 33% yield was indeed a mixture of the oxazole (4%) and a byproduct, benzil (29%).

SYNTHESIS
September 1998
1299
Table 2. The Reaction Results of Benzoin with Thionyl Chloride in Formic Acid
Lit.17
Experiment
I
II
0–5°C
III
Temperature
r.t.
91
68
–
r.t.
–10–0°C
90
Yield (%)
91
90
mp (°C)
52–68
67–82
67–84
Column Chromatography
two components:
three components:
(1) benzoin (70%) colorless (1) benzoin (20%), colorless needles, mp 134–136°C, identified
needles, mp 132–134°C
(2) benzil (30%), yellow
needles, mp 92–93.5°C
by IR, 1H NMR, MS.
(2) benzil (19%), yellow needles, mp 94–96°C.
(3) benzoin formate (46%), colorless needles, mp 73.0–74.5°C,
identified by IR, 1H NMR, MS, elemental analysis.
Table 3. Reaction of 1a–h and Formamide
1, 2
Starting Esters 1a–h
Oxazoles 2a–h
mp (°C)
Yield (%)
52 (83)a
bp (°C)/mbar or mp (°C)
171–174/2.66
168–170/2.66
152–155/2.66
160–162/2.66
–
a
b
c
d
e
f
H
73.0–74.5
80.0–82.0
58.0–60.0
79.5–81.0
106.0–108.0
122.0–122.5
142.0–144.0
114.0–115.0
Me
87
Et
85
CH(CH3)2
CH=CH2
Ph
82
38
90
m.p. 116–117
m.p. 124–125
m.p. 107–110
g
h
3,4-CH2O2C6H3
3,4-(MeO)2C6H3
70
74
a Yield when xylene was used to remove water by azeotropic distillation.
Scheme 3
cyclization process and forms the C-2 of the oxazole
(Scheme 3).
H atom of formamide used for ring closure. This means that
mechanism I shown in Scheme 3 should be involved in the
formation of oxazoles from benzoin esters. However, when
benzoin itself was used to react with formamide, a process
similar to mechanism II should be in operation.
To solve this problem, the reaction between eight carbox-
ylic esters of benzoin and formamide in the presence of
sulfuric acid were carried out and the results are listed in
Table 3.
It is difficult to obtain 5-aryl-4-phenyloxazoles by a similar
procedure to that used for preparing 4,5-diphenyloxazole
from ordinary benzoin, because unsymmetrical benzoins
usually consist of two equilibrated isomers (Scheme 4).
The results demonstrated that the substituent attached to C-
2 of the oxazole ring was adopted from the R group of the
carboxylic component of the benzoin ester rather than the

SYNTHESIS
Papers
1300
ence of sulfuric acid or in refluxing acetic acid, few
products were obtained. Many trial experiments were
carried out at elevated temperature and/or in the pres-
ence of catalysts. Eventually, it was found that the reac-
tion ran smoothly in boiling xylene with boron trifluor-
ide–diethyl ether complex as catalyst and 2,4-diphenyl-
oxazole was obtained as the only product in 85% yield
(Scheme 7).19
Scheme 4
Our attention was therefore turned to the preparation
of 2-aryl-4-phenyloxazoles. The method provided by
Strzybny18 for the preparation of 5-methyl-2,4-diphenyl-
oxazole could be used to synthesize oxazoles having two
aryl groups substituted at the 2- and 4-positions (Scheme
5).
Scheme 7
Scheme 5
When the preparation was carried out on a larger scale, it
was found that the reaction became very time consuming
and gave lower yields. Further modification was carried
out by fusing the reactants at 140°C in the presence of
boron trifluoride–diethyl ether complex without any sol-
vent. The reaction time could be shortened from more
than 20 to 4–9 hours and the yield had no obvious change
even for large scale preparation. By this further improved
method, eight 2-aryl-4-phenyloxazoles 4e–l and four
2-alkyl-4-phenyloxazoles 4a–d were obtained from phen-
acyl carboxylates 3a–l with yield ranging from 20 to 90%.
It is noted that the esters at the aryl ring having electron-
By analogy phenacyl benzoate was used instead of
α-methylphenacyl benzoate to react with ammonium ace-
tate in boiling acetic acid; 2,4-diphenyloxazole and 2,4-
diphenylimidazole were separated from the mixture
formed each in about 40% yield (Scheme 6).
On the basis of the mechanistic assumption, we speculat-
ed that when acetamide instead of ammonium acetate was
used as the nitrogen source of the oxazoles, the formation
of imidazoles might be avoided, because ammonium ace-
tate is liable to decompose to ammonia and acetic acid,
while acetamide is not.
Unexpectedly, when acetamide was used to react with donating substituents gave higher yield than those having
phenacyl benzoate under similar conditions in the pres- electron-withdrawing substituents (Table 4).
Scheme 6
Table 4. Yield of 2-Aryl(or Alkyl)-4-phenyloxazoles 4a–l
Alkyl
4
Yield (%)
Aryl
4
Yield (%)
Aryl
4
Yield (%)
Me
Et
Pr
a
b
c
60
60
65
63
4-AcNHC6H4
3,4,5-(MeO)3C6H2
4-HOC6H4
e
f
g
h
90
83
73
66
3-ClC6H4
i
43
53
30
20
3-NO2C6H4
4-NO2C6H4
3,5-(NO2)2C6H9
j
k
l
Bu
d
4-BrC6H4

SYNTHESIS
September 1998
1301
Mps and bps were not corrected. IR spectra were obtained using a
75 IR spectrophotometer, H NMR were recorded in CDCl3 on an
ARX-400 NMR instrument unless otherwise stated, and chemical
shifts are reported in δ units downfield from TMS. MS analyses were
carried out on a VG-ZAB-HS mass spectrometer. Reagents and sol-
vents were purified in the usual way.
1H NMR: δ = 5.92 [dd, 1H, 3J = 10.4 Hz, 2J = 1.3 Hz, CH=CH2(cis)],
6.27 (dd, 1H, 3J = 17.3, 10.4 Hz, -CH=CH2), 6.52 [dd, 1H, 3J = 17.3
Hz, J = 1.3 Hz, CH=CH2(trans)], 6.94 (s, 1H, >CH-O), 7.36–7.97
1
2
(m, 10H, Ph-H).
+
MS (EI): m/z (%) = 266 (M· ), 161 (M – PhCO)+, 105 (PhC≡O+,100).
Anal. calcd for C17H14O3: C, 76.67; H, 5.30. Found: C, 76.76; H, 5.53.
Benzoin Benzoate (1f): 92%; colorless needles; mp 122–122.5°C
(125°C24).
Preparation of Benzoin Carboxylates:
Benzoin Formate (1a):
1H NMR: δ = 6.65 (s, 1H, -OC-H), 6.81–7.70 (m, 15H, Ph-H).
A mixture of benzoin (10.60 g, 0.05 mol) and formic acid (46.00 g,
1.0 mol) was stirred vigorously at 0 °C, and then, when all the benzoin
had dissolved, SOCl2 (142.80 g, 1.2 mol) was added dropwise, the
solution was poured into ice-water (100 g) with stirring to settle the
resultant as aggregated solids. A yellow precipitate was obtained in
90% (91%17) yield and which melted at 67–84°C (68°C17). After pu-
rification by a chromatographic column (silica gel H, CH2Cl2), the
following three components were separated.
Benzoin 3,4-Methylenedioxybenzoate (1g): 89%; colorless needles;
mp 142–144°C.
IR: ν = 1700, 1440, 1250, 760, 695 cm–1.
1H NMR: δ = 6.02 (s, 2H, -OCH2O–), 6.78-6.88 (m, 3H, Ar-H), 7.04
(s, 1H, -OC-H), 7.32-8.05 (m, 10H, Ph-H).
+
MS (EI): m/z (%) = 360 (M· ), 255 (M - PhCO)+,149 (ArC≡O+, 100).
Anal. calcd for C22H16O5: C, 73.32; H, 4.48. Found: C, 73.33; H, 4.68.
(1) Benzoin Formate: 46%; colorless needles; mp 73.0–74.5°C
(68°C17).
Benzoin 3,4-Dimethoxybenzoate (1h): 85%; colorless needles; mp
114–115°C.
IR: ν = 2940, 1725, 1685, 1150, 755, 695 cm–1.
1H NMR: δ = 6.99 (s, 1H, -OCH), 7.26-7.99 (m, 10H, Ph-H), 8.23 (s,
1H, HCOO-).
IR: ν = 2960, 1690, 1280, 760, 695 cm–1.
1H NMR: δ = 3.89 (s, 3H, -OCH3), 3.91 (s, 3H, -OCH3), 6.82–6.92
(m, 3H, Ar-H), 7.07 (s, 1H, -OC-H), 7.30-8.06 (m, 10H, Ph-H).
+
MS (EI): m/z (%) = 240 (M· ), 195 (M–OOCH),+ 105 [(PhC≡O)+,
+
MS (EI): m/z (%) = 376 (M· ), 165 (ArC≡O+, 100), 105 (Ph≡O+).
100], 77(Ph)+.
Anal. calcd for C23H20O5: C, 73.39; H, 5.36. Found: C, 73.20; H, 5.42.
Anal. calcd for C15H12O3: C, 74.99; H, 5.03. Found: C, 75.29; H, 4.75.
4,5-Diphenyloxazole (2a) and 2-Substituted 4,5-Diphenyloxazoles
2b–h:
4,5-Diphenyloxazole (2a):
(2) Benzil: 19%; yellow needles; mp 94–96°C (94–95°C20).
+
MS (EI): m/z (%) = 210 (M· ), 105 [(PhC≡O)+, 100].
A mixture of benzoin (5.30 g, 0.025 mol), formamide (20 mL), xylene
(80 mL) and concd H2SO4 (2 mL) was heated with stirring for 14 h at
reflux temperature, so as to remove water formed in the reaction by
azeotropic distillation. After cooling to r.t., a suitable amount of water
was added to the mixture. The organic layer was separated, washed,
dried (MgSO4), and then distilled under reduced pressure. The pale
yellow liquid product, 4,5-diphenyloxazole soon solidified; yield:
83% (55%17); mp 42–44°C (44°C20); bp 171–174°C/2.66 mbar
(121°C/1.33 × 10–2 mbar17).
(3) Benzoin (Recovered Reactant): 20%; mp 134–136°C (137 °C21).
Benzoin Acetate (1b):22
Concd H2SO4 (2 mL) was added dropwise to a mixture of benzoin
(21.2 g, 0.1 mol), glacial HOAc (20 mL) and Ac2O (20 mL) with
stirring. Then the reactants were heated and stirred for 1 h at 80–
85°C. After cooling, the solution was added dropwise to ice-water
with vigorous stirring for 1 h. The yellow solid formed was filtered
and washed with ice-water. Recrystallization (EtOH) gave colorless
needles of benzoin acetate in 88% (86–90%22) yield; mp 80-82 °C
(81.5–82.5 °C22).
IR: ν = 1600,1520, 1445, 1200, 960, 760, 700 cm–1.
1H NMR: δ = 7.30-7.73 (m, 10H, Ph-H), 7.94 (s, 1H, Oxaz-H).
+
MS (EI): m/z (%) = 221 (M· ), 193 (M - CO)+, 105 (PhC≡O+, 100).
2-Substituted 4,5-Diphenyloxazoles 2b–h; General Procedure:
Concd H2SO4 (1 mL) was added dropwise to a mixture of benzoin
carboxylate (0.01 mol) and formamide (100 mL) while stirring. The
solution was heated for 1 h at 110°C and a further 2 h at 140–150°C.
After cooling to r.t., a suitable amount of water was added to the so-
lution. The organic layer was separated and the aqueous layer was
extracted with benzene. The combined organic layer was dried
(MgSO4), and then the solvent was removed by distillation to afford
the crude product. The product was vacuum distilled and purified by
recrystallization of the solidified mass from 95% EtOH.
Benzoin Carboxylates (Except Formate and Acetate):
General Procedure:
A mixture of benzoin (10.60 g, 0.05 mol), RCOCl (0.1 mol) and
RCOOH (0.15 mol) was refluxed for 30 min, when the solution was
cooled to r.t., the acyl chloride in excess was decomposed with a suit-
able amount of water. The pale yellow crude product obtained was
recrystallized (95% EtOH) to give the pure product.
Benzoin Propanoate (1c): 99% (88%23); colorless needles; mp 58–
60°C (53°C23).
2-Methyl-4,5-diphenyloxazole (2b): 87%; pale yellow liquid; bp 168–
170°C/2.66 mbar (210–213°C/24 mbar25).
Benzoin Isobutyrate (1d): ~100%; colorless needles; mp 79.5–81°C.
IR: ν = 2970, 1720, 1685, 1600, 1450, 1330, 1190, 1150, 960, 930,
760, 700 cm–1.
IR: ν = 3070, 1590, 1510, 1440, 765, 695 cm–1.
1H NMR: δ = 2.53 (s, 3H, -CH3), 7.26–7.64 (m, 10H, Ph-H).
1H NMR: δ = 1.21 (d, 3H, J = 6.99 Hz, -CH3), 1.27 (d, 3H, J = 6.99
Hz, -CH3), 2.71 (m, 1H, J = 6.99 Hz, CHCOO), 6.84 (s, 1H,
COOCH), 7.35-7.95 (m, 10H, Ph-H).
+
MS (EI): m/z (%) = 235 (M· , 100), 207(M–CO)+.
Anal. calcd for C16H13NO: C, 81.67; H, 5.57; N, 5.95. Found: C,
81.60; H, 5.50; N, 5.94.
+
MS (EI): m/z (%) = 282 (M· ), 177 (M – PhCO)+, 105 (PhC≡O+, 100).
2-Ethyl-4,5-diphenyloxazole (2c): 85%; (63%26); pale yellow liquid;
bp 152-155°C/2.66 mbar (119–120°C/5.32 × 10–1 mbar26).
IR: ν = 2960, 1590, 1440, 1210, 765, 595 cm–1.
Anal. calcd for C18H18O3: C, 76.57; H, 6.43. Found: C, 76.48; H, 6.37.
Benzoin Acrylate (1e): 98%; colorless needles; mp 106–108°C.
IR: ν = 3080, 1720, 1680, 1405, 1285, 1255, 1200, 1060, 965, 760,
700 cm–1.
1H NMR: δ = 1.42 (t, 3H, J = 7.60 Hz, -CH3), 2.88 (q, 2H, J = 7.60
Hz, -CH2-), 7.24-7.65 (m, 10H, Ph-H)
+
MS (EI): m/z (%) = 249 (M· , 100).

SYNTHESIS
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1302
Anal. calcd for C17H15NO: C, 81.90; H, 6.06; N, 5.62. Found: C,
81.93; H, 6.01; N, 5.65.
Phenacyl Butanoate (3c): 67%; colorless liquid; bp 159–161°C/
3.99 mbar.
IR: ν = 2970, 1740, 1700, 1600, 1450, 1430, 1370, 1230, 1165, 965,
2-Isopropyl-4,5-diphenyloxazole (2d): 82.5% (61%26); pale yellow
liquid; bp 160–162°C/2.66 mbar (141°C/5.32 × 10–1 mbar, mp
58°C26).
750, 690 cm–1.
1H NMR: δ = 1.01 (t, 3H, J = 7.43 Hz, CH3), 1.75 (m, 2H, J = 7.43,
7.40 Hz, -C-CH2-C), 2.48 (t, 2H, J = 7.40 Hz, -CH2COO-), 5.35 (s,
2H, -OCH2CO-), 7.47–7.93 (m, 5H, Ph-H).
IR: ν = 2960, 1580, 1440, 1210, 765, 695 cm–1.
1H NMR: δ = 1.43 [d, 6H, J = 6.40 Hz, C(CH3)2], 3.10 (m, 1H, J =
6.40 Hz, -CH-), 7.24-7.65 (m, 10H, Ph-H).
+
MS (EI): m/z (%) = 206 (M· ), 105 (PhC≡O+, 100).
Anal. calcd for C12H14O3: C, 69.88; H, 6.84. Found: C, 69.63; H, 6.88.
+
MS (EI): m/z (%) = 263 (M· , 100).
Phenacyl Pentanoate (3d): 86%; colorless liquid; bp 150–153°C/
3.99 mbar.
4,5-Diphenyl-2-vinyloxazole (2e): 38% (37%27); pale yellow liquid
(obtained by column separation); (bp 175°C/2.66 × 10–1 mbar, mp
76–77.5°C27).
IR: ν = 2970, 1740, 1700, 1600, 1450, 1430, 1370, 1230, 1165, 965,
755, 690 cm–1.
IR: ν = 1600, 1420, 1200, 765, 695 cm–1.
1H NMR: δ = 5.50–6.80 (m, 3H, -CH=CH2), 7.25–7.75 (m, 10H, Ph-
H).
1H NMR: δ = 0.94 (t, 3H, J = 7.36 Hz, -CH3), 1.42 (m, 2H, J = 5.72,
7.36 Hz, -CH2CH3), 1.70 (m, 2H, J = 7.58, 5.72 Hz, -CH2CH2CH3),
2.50 (t, 2H, J = 7.58 Hz, -CH2COO-), 5.35 (s, 2H, -OCH2CO-), 7.47–
7.93 (m, 5H, Ph-H).
+
MS (EI): m/z (%) = 220 (M· ), 178 [PhCOCH2OC(OH)+CH2], 105
2,4,5-Triphenyloxazole (2f): 90% (93%25); colorless needles; mp
116–117°C (116°C25).
(PhC≡O+, 100).
IR: ν = 1590, 1450,1220, 765, 695 cm–1.
1H NMR: δ = 7.25–8.25 (m, 15H, Ph-H).
Anal. calcd for C13H16O3: C, 70.89; H, 7.32. Found: C, 70.71; H, 7.20.
+
Phenacyl p-Acetamidobenzoate (3e): 96%; colorless plate crystals;
mp 177–179°C.
MS (EI): m/z (%) = 297 (M· , 100).
Anal. calcd for C21H15NO: C, 84.82; H, 5.09; N, 4.71. Found: C,
84.85; H, 5.04; N, 4.75.
IR: ν = 3360, 1700, 1680, 1600, 1520, 1400, 1370, 1280, 1220, 1120,
1000, 950, 760, 680 cm–1.
1H NMR (DMSO): δ = 2.10 (s, 3H, -CH3), 5.72 (s, 2H, -CH2-), 7.57–
8.02 (m, 9H, Ar-H), 10.36 (s, 1H, -NH-).
2-(3,4-Methylenedioxyphenyl)-4,5-diphenyloxazole (2g): 70%; color-
less needles; mp 124–125°C.
+
MS (EI): m/z (%) = 297 (M· ), 162 (ArC≡O+), 105 (PhC≡O+, 100).
IR: ν = 2920, 1600, 1480, 1240, 1040, 760, 730, 690 cm–1.
1H NMR: δ = 6.02 (s, 2H, -OCH2O-), 6.83-6.94 (m, 3H, Ar-H), 7.30–
7.77 (m, 10H, Ph-H).
Anal. calcd for C17H15NO4: C, 68.67; H, 5.09; N, 4.71. Found: C,
68.68; H, 5.13; N, 4.60.
+
MS (EI): m/z (%) = 341 (M· , 100).
Phenacyl 3,4,5-Trimethoxybenzoate (3f): 87%; colorless needles; mp
117.5–118.5°C.
Anal. calcd for C22H15NO3: C, 77.40; H, 4.43; N, 4.10. Found: C,
77.23; H, 4.58; N, 3.82.
IR: ν = 2950, 1720, 1690, 1595, 1505, 1420, 1340, 1215, 1130, 750,
680 cm–1.
1H NMR: δ = 3.93 [s, 9H, 3(-OCH3)], 5.58 (s, 2H, -CH2-), 7.41–7.99
2-(3,4-Dimethoxyphenyl)-4,5-diphenyloxazole (2h): 74%; colorless
needles; mp 107–110°C.
(m, 7H, Ar-H).
IR: ν = 1600, 1460, 1250, 1030, 735, 730, 690 cm–1.
1H NMR: δ = 3.95 (s, 3H, -OCH3), 3.99 (s, 3H, -OCH3), 6.74-6.99 (m,
3H, Ar-H), 7.32-7.79 (m, 10H, Ph-H).
+
MS (EI): m/z (%) = 330 (M· ), 195 (ArC≡O+, 100), 105 (PhC≡O+).
Anal. calcd for C18H18O6: C, 65.44; H, 5.49. Found: C, 65.48; H, 5.80.
+
MS (EI): m/z (%) = 357 (M· , 100).
Phenacyl p-Hydroxybenzoate (3g): 82% (91%30); colorless needles;
mp 181–182°C (178°C30).
Anal. calcd for C23H19NO3: C, 77.28; H, 5.36; N, 3.92. Found: C,
77.45; H, 5.24; N, 3.66.
1H NMR: δ = 5.66 (s, 2H, -CH2-), 6.95-8.06 (m, 9H, Ar-H), 9.24 (s,
1H, -OH).
Phenacyl Carboxylates 3a–l; General Procedure:
Phenacyl p-Bromobenzoate (3h): 96% (70%31); colorless needles;
mp 83–84°C (88°C31).
A mixture of RCOOH or ArCOOH (0.1 mol), Na2CO3 (5.30 g,
0.05 mol) and water (100 mL) was stirred and heated until all the solid
dissolved. After cooling for several minutes, phenacyl bromide
(19.90 g, 0.1 mol) and EtOH (200 mL) were added. The solution was
heated gently to boiling and refluxed for 2 h, then cooled until crystals
separated. The crystals were filtered, washed with 70% EtOH. Re-
crystallization (70% EtOH) gave a colorless solid. For the ester of
lower fatty acid, extraction and distillation were required in order to
obtain pure product.
1H NMR: δ = 5.58 (s, 2H, -CH2-), 7.51–7.63 (m, 5H, Ph-H), 7.94–
8.01 (m, 4H, Ar-H).
Phenacyl 3-Chlorobenzoate (3i): 92% (98%30); colorless needles; mp
120–122°C (116.4°C30).
1H NMR: δ = 5.60 (s, 2H, -CH2-), 7.42–8.13 (m, 9H, Ar-H).
+
MS (EI): m/z (%) = 274 (M· ), 139 (ArC≡O+), 105 (PhC≡O+, 100).
Phenacyl Acetate (3a): 78% (82.5%28); colorless plate crystals; mp
47–48°C (48–49°C28).
Phenacyl 3-Nitrobenzoate (3j): 89% (86%30); pale yellow prisms; mp
106–108°C (104.5°C30).
1H NMR: δ = 2.32 (s, 3H, -CH3), 5.43 (s, 2H, -CH2-), 7.55–8.01 (m,
5H, Ph-H).
1H NMR: δ = 5.67 (s, 2H, -CH2-), 7.53–8.98 (m, 9H, Ar-H).
MS (EI): m/z (%) = 255 (M – HCHO).+, 150 (ArC≡O+), 105 (PhC≡O+,
100).
Phenacyl Propanoate (3b): 84% (95%29); colorless liquid; bp 135–
136°C/2.66 mbar (26°C29).
Phenacyl p-Nitrobenzoate (3k): 85% (69%31); pale yellow needles;
mp 124-125°C (129°C29).
1H NMR: δ = 1.22 (t, 3H, J = 7.57 Hz, -CH3), 2.53 (q, 2H, J = 7.57
Hz, -CH2COO-), 5.35 (s, 2H, -OCH2CO-), 7.47–7.92 (m, 5H, Ph-H).
1H NMR: δ = 5.65 (s, 2H, -CH2-), 7.51–7.98 (m, 5H, Ph-H), 8.32 (s,
4H, Ar-H).
+
MS (EI): m/z (%) = 192 (M· ), 105 (PhC≡O+, 100).

SYNTHESIS
September 1998
1303
Phenacyl 3,5-Dinitrobenzoate (3l): 84%; pale yellow granular crys-
tals; mp 137.5–139°C.
Anal. calcd for C17H14N2O2: C, 73.37; H, 5.07; N, 10.07. Found: C,
73.31; H, 5.24; N, 10.22.
IR: ν = 3100, 1740, 1700, 1540, 1350, 1280, 1230, 1170, 970, 965,
725 cm–1.
4-Phenyl-2-(3,4,5-trimethoxyphenyl)oxazole (4f): 83%; colorless
needles; mp 133–135°C.
1H NMR: δ = 5.73 (s, 2H, -CH2-), 7.21–7.97 (m, 5H, Ph-H), 9.26 (s,
3H, Ar-H).
IR: ν = 1600, 1560, 1420, 1360, 1240, 1135, 995, 960, 740 cm–1.
1H NMR: δ = 3.92 (s, 3H, 4-OCH3), 3.98 [s, 6H, 3,5-di(-OCH3)],
7.27-7.85 (m, 7H, Ar-H), 7.96 (s, 1H, Oxaz-H).
MS (EI): m/z (%) = 311 (M.+, 100), 296 (M–CH3)+, 268 (M–
CH3CO)+.
MS (EI): m/z (%) = 195 (ArC≡O+), 105 (PhC≡O+), 77(Ph+, 100).
Anal. calcd for C15H10N2O7: C, 54.55; H, 3.05; N, 8.48. Found: C,
54.42; H, 3.32; N, 8.25.
2-Aryl(or 2-Alkyl)-4-phenyloxazoles 4a–l; General Procedure:
A mixture of the phenacyl carboxylate (0.05 mol), acetamide (14.8 g,
Anal. calcd For C18H17NO4: C, 69.44; H, 5.50; N, 4.50. Found: C,
69.44; H, 5.54; N, 4.50.
•
0.25 mol) and 47% BF3 Et2O (2.5 mL) was heated gently to 140°C
and reacted at this temperature until no ester was detected by TLC.
The solution was cooled, and then 50 mL water was added. The aque-
ous layer was extracted with Et2O or CH2Cl2. The combined organic
layer was dried (anhyd MgSO4), filtered and the solvent removed to
afford the crude product. Recrystallization (95% EtOH) gave a color-
less or pale yellow solid (or distillation in vacuo gave a colorless liq-
uid).
2-(p-Hydroxyphenyl)-4-phenyloxazole (4g): 73%; colorless needles;
mp 205–206°C.
IR: ν = 3080, 2600, 1620, 1510, 1450, 1280, 1250, 830, 740, 690 cm–1.
1H NMR (DMSO): δ = 6.93–7.90 (m, 9H, Ph-H), 8.63 (s, 1H, Oxaz-
H), 10.20 (s, 1H, -OH).
MS (EI): m/z (%) = 237 (M.+, 100), 209 (M–CO)+.
Anal. calcd for C15H11NO2: C, 75.94; H, 4.67; N, 5.90. Found: C,
75.78; H, 4.77; N, 5.89.
2-Methyl-4-phenyloxazole (4a): 60%; colorless plate crystals; mp 44–
46°C.
2-(p-Bromophenyl)-4-phenyloxazole (4h): 66%; colorless needles;
mp 142–143°C.
IR: ν = 3100, 2920, 1585, 1440, 1070, 920, 755, 690 cm–1.
1H NMR: δ = 2.52 (s, 3H, -CH3), 7.30-7.72 (m, 5H, Ph-H), 7.81 (s,
1H, Oxaz-H).
IR: ν = 3130, 1600, 1480, 1080, 830, 760, 730, 690 cm–1.
1H NMR: δ = 7.34-8.01 (m, 10H, Ph-H and Oxaz-H).
MS (EI): m/z (%) = 299 (M.+, 100), 271 (M–CO)+, 220 (M–Br)+.
Anal. calcd for C15H10BrNO: C, 60.02; H, 3.35; N, 4.66. Found: C,
59.94; H, 3.31; N, 4.54.
MS (EI): m/z (%) = 159 (M.+, 100), 131 (M–CO)+, 103 (PhCN)+.
Anal. calcd for C10H9NO: C, 75.45; H, 5.70; N, 8.80. Found: C,
75.28; H, 5.90; N, 8.76.
2-Ethyl-4-phenyloxazole (4b): 60%; colorless liquid; bp 104.5–
105°C/2.00 mbar.
2-(m-Chlorophenyl)-4-phenyloxazole (4i): 43%; colorless needles;
mp 106–108°C.
IR: ν = 3000, 1580, 1460, 1100, 1080, 940, 740, 640 cm–1.
1H NMR: δ = 1.37 (t, 3H, J = 7.65 Hz, -CH3), 2.82 (q, 2H, J = 7.65 Hz,
-CH2-), 7.28–7.72 (m, 5H, Ph-H), 7.80 (s, 1H, Oxaz-H).
MS (EI): m/z (%) = 173 (M.+, 100), 145 (M–CO)+.
Anal. calcd for C11H11NO: C, 76.28; H, 6.40; N, 8.09. Found: C,
76.10; H, 6.95; N, 7.70.
IR: ν = 3130, 3080, 1550, 1480, 1060, 765, 730, 690 cm–1.
1H NMR: δ = 7.34–8.13 (m, 9H, Ar-H), 7.99 (s, 1H, Oxaz-H).
MS (EI): m/z (%) = 255 (M.+, 100), 227 (M–CO)+.
Anal. calcd for C15H10ClNO: C, 70.46; H, 3.94; N, 5.48; Cl, 13.87.
Found: C, 70.56; H, 4.16; N, 5.50; Cl, 14.07.
2-(m-Nitrophenyl)-4-phenyloxazole (4j): 53%, yellow needles, mp
188–189.5°C.
4-Phenyl-2-propyloxazole (4c): 65%; colorless liquid; bp 119–120°C/
2.66 mbar.
IR: ν = 3160, 3080, 1520, 1350, 1110, 980, 750, 710 cm–1.
1H NMR (DMSO): δ = 7.38–8.74 (m, 9H, Ar-H), 8.86 (s, 1H, Oxaz-H).
MS (EI): m/z (%) = 266 (M.+, 100), 238 (M–CO)+.
Anal. calcd for C15H10N2O3: C, 67.67; H, 3.79; N, 10.52. Found: C,
67.59; H, 3.96; N, 10.74.
IR: ν = 2970, 1570, 1450, 1110, 1090, 1065, 945, 740, 695 cm–1.
1H NMR: δ = 1.02 (t, 3H, J = 7.40 Hz, -CH3), 1.84 (m, 2H, J = 7.40,
7.40 Hz, -CH2CH3), 2.81 (t, 2H, J = 7.40 Hz, Oxaz-CH2-), 7.26–7.73
(m, 5H, Ph-H), 7.82 (s, 1H, Oxaz-H).
MS (EI): m/z (%) = 187 (M.+, 100).
Anal. calcd for C12H13NO: C, 76.97; H, 7.00; N, 7.48. Found: C,
76.71; H, 6.88; N, 7.44.
2-(p-Nitrophenyl)-4-phenyloxazole (4k): 30%; yellow plate crystals;
mp 155–156°C.
IR: ν = 3120, 1520, 1350, 860, 760, 720, 690 cm–1.
1H NMR: δ = 7.38–8.37 (m, 9H, Ph-H), 8.07 (s, 1H, Oxaz-H).
MS (EI): m/z (%) = 266 (M.+, 100), 238 (M–CO)+, 220 (M–NO2)+.
Anal. calcd for C15H10N2O3: C, 67.67; H, 3.79; N, 10.52. Found: C,
67.13; H, 3.89; N, 10.48.
2-Butyl-4-phenyloxazole (4d): 63%; colorless liquid; bp 130–132°C/
2.66 mbar.
IR: ν = 2970, 1570, 1450, 1110, 1065, 945, 740, 695 cm–1.
1H NMR: δ = 0.96 (t, 3H, J = 7.36 Hz, -CH3), 1.43 (m, 2H, J = 7.36,
7.56 Hz, -CH2CH3), 1.80 (m, 2H, J = 7.56, 7.66 Hz, -CH2CH2CH3),
2.83 (t, 2H, J = 7.66 Hz, Oxaz-CH2-), 7.26–7.73 (m, 5H, Ph-H), 7.81
(s, 1H, Oxaz-H).
2-(3,5-Dinitrophenyl)-4-phenyloxazole (4l): 20%; yellow powder
solid; mp 279.5–281.5°C (dec.).
MS (EI): m/z (%) = 201 (M.+, 100), 186, 172, 159, 130, 104, 90.
Anal. calcd for C13H15NO: C, 77.58; H, 7.51; N, 6.96. Found: C,
77.44; H, 7.50; N, 6.87.
IR: ν = 3100, 1540, 1340, 760, 720 cm–1.
1H NMR (DMSO): δ = 7.40–9.03 (m, 8H, Ar-H), 8.88 (s, 1H, Oxaz-
H).
MS (EI): m/z (%) = 311 (M.+), 283, 265, 90 (100).
Anal. calcd for C15H9N3O5: C, 57.88; H, 2.91; N, 13.50. Found: C,
57.83; H, 3.11; N, 13.80.
2-(p-Acetamidophenyl)-4-phenyloxazole (4e): 90%; colorless nee-
dles; mp 196–197.5°C.
IR: ν = 3280, 1660, 1600, 1530, 1500, 1400, 1370, 1320, 840, 740,
690 cm–1.
1H NMR (CD3OD): δ = 2.15 (s, 3H, -CH3), 7.33-8.04 (m, 9H, Ar-H),
8.27 (s, 1H, Oxaz-H).
We are grateful for the financial support of the National Natural Sci-
ence Foundation of China.
MS (EI): m/z (%) = 278 (M.+, 100), 236, 208.

SYNTHESIS
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