A convenient synthesis of 2-oxazolines and 2-benoxazoles with PPh3-DDQ as the dehydrating reagent

Article abstract of DOI:10.1002/cjoc.201190190

2-Oxazolines and 2-benoxazoles were synthesized in high yields from acylamino alcohols and acylaminophenols, respectively, with triphenylphosphine- 2,3-dichloro-5,6-dicyanobenzoquinone (PPh₃-DDQ) as the dehydrating and activating reagent. The synthesis was accomplished under neutral conditions.

Full text of DOI:10.1002/cjoc.201190190

FULL PAPER
A Convenient Synthesis of 2-Oxazolines and 2-Benoxazoles
with PPh3-DDQ as the Dehydrating Reagent
Xu, Quancaia(徐全才)
Li, Zhengning*,a,b(李争宁)
Chen, Huiyingc(陈会英)
a College of Environmental and Chemical Engineering, Dalian University, Dalian, Liaoning 116622, China
b Liaoning Key Laboratory of Bioorganic Chemistry, Dalian University, Dalian, Liaoning 116622, China
c College of Life Science, Dalian Nationalities University, Dalian, Liaoning 116605, China
2-Oxazolines and 2-benoxazoles were synthesized in high yields from acylamino alcohols and acylamino-
phenols, respectively, with triphenylphosphine-2,3-dichloro-5,6-dicyanobenzoquinone (PPh3-DDQ) as the dehy-
drating and activating reagent. The synthesis was accomplished under neutral conditions.
Keywords oxazoline, benzoxazole, synthesis, dehydrative cylization, 2,3-dichloro-5,6-dicyanobenzoquinone,
triphenylphosphine
Introduction
formation by Iranpoor.14 Compared to Mistunobu re-
agent, PPh3-DEAD,15 the PPh3-DDQ combination is
cheaper, more stable, and usually yields cleaner product.
In comparison to SOCl2, DAST, or Deoxo-Fluor reagent,
the PPh3-DDQ combination system is neutral, and thus
acid liable groups in substrates might be tolerated. Herein,
we wish to report our results in detail and to show that the
combination could be extended to the synthesis of ben-
zoxazole.
2-Oxazoline is of great importance in synthetic or-
ganic chemistry, either as a functional group or as a pro-
tecting group to mask the reactive hydroxyl and amino
groups in amino alcohols and carboxylic acids in organic
reactions.1 More importantly, 2-oxazoline derived from
chiral amino alcohols has been used as auxiliary in
asymmetric synthesis and as ligand in asymmetric cataly-
sis in the last two decades.2 It is also of pharmaceutical
interests because this functional group was found in
natural products and some drug-like compounds display-
ing anti-HIV, antimitotic, anti-cancer, and antibiotic ac-
tivities.3 Its hydrolytic property makes it a pro-drug of
acid. In regarding to the wide applications of 2-oxazoline,
it is not surprising that many synthetic methods have been
reported for this kind of compounds. Most of the methods
start from amino alcohols and carboxylic acids or acid
derivatives like ester4,5 and nitrile.6 The intermediate,
N-(2-hydroxyethyl) amide, is converted into 2-oxazoline
via a dehydrative cyclization. In this transformation, it is
necessary to transfer the poor leaving hydroxyl group into
Results and discussion
When N-(2-hydroxyethyl) benzamide (1a) was
added to PPh3-DDQ solution in dichloromethane,
2-phenyloxazoline was formed as judged by TLC, GC
and NMR analyses by comparison with an authentic
sample. Scan of solvents showed that nearly quantitative
yields of oxazoline were obtained in dichloromethane,
toluene, 1,4-dioxane or THF reaction system in 20 min,
but no oxazoline or inferior yield of oxazoline was got
in acetonitrile and ethyl acetate, respectively. In regarding
to the reaction time and the yields, our current
PPh3-DDQ dehydrating reagent is more efficient than
Linclau's isourea protocol,10 which requires 24—48 h at
THF refluxing temperature to get reasonable yields of
2-oxazolines. DDQ in the PPh3-DDQ combination can
be replaced by 7,7,8,8-tetracyanoquinodimethane (TCNQ)
or 1,1,2,2-tetracyanoethene. In the case of PPh3-TCNQ,
clean and nearly quantitative conversion of 1b to 2b
could be furnished in 1 h. However, difficulty in separa-
tion was encountered due to small difference of Rf val-
a good leaving one by the use of SOCl2 or PPh3/CCl4,8 or
7
TsCl/Et3N, followed by an SN2 reaction under basic con-
ditions.9 Recently, dehydrating reagents including car-
bodiimide,10 Et2NSF3
(MeOCH2CH2)2NSF3,11b,11c
11a,11b
2-chloro-4,6-dimeth-oxy-1,3,5-triazine,3b PPh3-DEAD12
were also used for this purpose. The exploration of new
reagents for this transformation, for example, Loughlin's
phosphonium anhydrides, is still an active research
field.3a More recently, we have reported that the PPh3-
DDQ could be used for the synthesis of 2-oxazolines via
a dehydrative cyclization of N-(2-hydroxyethyl) amides
(Eq. 1).13 PPh3-DDQ has been extensively used as the
dehydrating reagent in alcohol functional group trans-
*
E-mail: znli@dl.cn
Received July 18, 2010; revised October 28, 2010; accepted December 27, 2010.
Project supported by National Natural Science Foundation of China (No. 20672016).
Chin. J. Chem. 2011, 29, 925— 932
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
925

Xu, Li & Chen
FULL PAPER
ues between the desired 2b and other product. Using
1,1,2,2-tetracyanoethene, the reaction was relatively
slow. A 45% yield of 2b was obtained in 1 h.
Continued
Yieldb/%
Entry Reaction time
Product
After successfully achieving the dehydrating cycli-
zation above with PPh3-DDQ, we began to employ the
uses of other acylated aminoethanols as substrates. The
results are summarized in Table 1. First, substituted
phenyl ring substrates were tested, and yields above
80% were achieved in 20—120 min (Entries 2—4).
Electron-withdrawing and electron-donating groups at-
tached to phenyl do not influence the reaction too much.
When nitro group exists, 60 min was needed for a com-
plete conversion. The acyl can be extended to cinnamoyl.
As shown in Entry 7, N-(2-hydroxyethyl) trans-
cinnamamide produced the corresponding oxazoline in a
high yield. This is in contrast to the method in literature
in which the reaction could not be applied to cinnama
aldehyde.16 Our system is also effective to ortho-
substituted benzamide (Entry 8), and in this case, 3 h
reaction time was needed, furnishing the product in 90%
yield. Bisoxazoline could be formed from biacylated
amino alcohol (Entry 9).
7
60 min
98
(2g)
8
3 h
90
(2h)
(2i)
(2j)
9
24 h
24 h
97
70
10
When relative inactive alkylacylamino alcohols were
used,17 longer reaction time was necessary to ensure
complete conversion. High yields of desired products
11
24 h
90
Table 1 The synthesis of 2-aryl(alkyl)oxazolinesa
(2k)
(2l)
12
13
24 h
24 h
93
97
Entry Reaction time
Product
(2a)
Yieldb/%
96
(2m)
1
2
20 min
20 min
14
24 h
91
99
99
(2n)
(2b)
a
PPh3/DDQ/acylamino alcohol＝ 1.5/1.5/1.0 (molar ratio), in
dichloromethane, r.t.; b isolated yield.
3
2 h
were obtained in 24 h (Entries 10—14). Cyclopropyl
was tolerated and the corresponding product could be
formed smoothly.
(2c)
(2d)
(2e)
Our effort was then devoted to the stereochemistry of
the reaction. First, stereochemistry for acyl moiety was
studied. Accordingly, amides derived from trans and cis
substituted cyclopropanecarboxylic acid were chosen as
the substrates. Except with trans-2-phenylcyclopropyl-
carboxamide, slight isomerization in cyclopropyl was
observed. Using 2-phenylcyclopropylcarboxamide with a
cis/trans molar ratio of 97.7%/2.3%, a product consisting
of 96.0% cis and 4.0% trans was formed. The use of
trans-2-[2,2-dimethyl-3-(2-methyl-propenyl)-cycloprop-
anecarboxylate (trans/cis＝97.7%/2.3%, molar ratio)
yielded a product with a trans/cis ratio of 93.1%/6.9%,
4
5
20 min
60 min
97
92
6
60 min
82
(2f)
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 925— 932

A Convenient Synthesis of 2-Oxazolines and 2-Benoxazoles with PPh3-DDQ
while using substrate consisting of 98.7% of cis and
The stereochemistry for the amino alcohol moiety
1.3% of trans, the cis/trans ratio in the product was
86.0%/14.0%. The isomerization may be due to a de-
protonation of α-H of acyl and a followed protonation.
was also investigated using chiral amino alcohols. En-
antiopure, optical active oxazolines were obtained in
these cases, as shown in Table 2. The configuration of
Table 2 The synthesis of oxazolines
Entry
1
Substrate
Reaction time
12 h
Product
(2o)
Yielda/%
80
(1o)
2
3
24 h
24 h
73
48
(2p)
(1p)
(1q)
(1r)
(1s)
(1t)
(2q)
4
5
6
24 h
44
93
97
(2r)
(2s)
1 h
1 h
(2t)
7
8
41 h
1 h
68
(2u)
(1u)
1u
2u
88b
9
20 min
90
(2v)
(1v)
10
4 h
66b
(2w)
(1w)
a Unless noted, PPh3/DDQ/acylamino alcohol＝ 1.5/1.5/1.0 (molar ratio), in dichloromethane, r.t.; b toluene as the solvent, reflux.
Chin. J. Chem. 2011, 29, 925— 932
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Xu, Li & Chen
FULL PAPER
carbons attached to the hydroxyl inverted in this process,
as demonstrated by the specific rotation value of the
PPh3-DDQ to the synthesis of benzoxazole, an analogue
of oxazoline, which also has found remarkable bio-
logical activities and significant applications.21 After
consulting the case with DEAD-PPh3,22 and the same
key phosphonium intermediate with PPh3-DEAD and
PPh3-DDQ as the dehydrating and activating reagent, a
possible mechanism using PPh3-DDQ in the synthesis of
benzoxazole is proposed and shown in Scheme 2. The
mechanism is different to that in the formation of oxa-
zoline. In Scheme 2, the oxygen atom of the carbonyl
instead of that of hydroxyl attached the phenyl is acti-
vated by the phosphonium intermediate derived from
PPh3-DDQ, and then a nucleophilic addition of phenol
oxygen to carbonyl and a followed elimination of
triphenylphosphine oxide yield the cyclized product,
benzoxazole. Initially, we supposed that amide could be
formed from carboxylic acid and 2-aminophenol via
dehydration and a followed dehydration might produce
benzoxazole in the presence of excess PPh3-DDQ.
However, almost no desired product was obtained in
acetonitrile or dichloromethane at room temperature.
The use of THF as the solvent generated a 5% yield of
the product only, and change to toluene resulted in a
23% yield, which is still a very low yield (Table 3). We
suspected that the low yields may be due to the slow or
difficult formation of benzoylaminophenol under the
reaction conditions. Accordingly, the amide was used as
the substrate, and benzoxazole was formed in this case.
However, high reaction temperature was needed for get-
ting reasonable yield of the product. As shown in Table
4, good to excellent yields could be obtained for acyl
benzoxazole and for alkyl one in 5—24 h in refluxing
toluene except for 4d (28% yield).
1
products and J value in H NMR (Entries 5—9). For
example, 1s, prepared from (R)-2-phenylglycinol (Alfa,
[α]2D0 －30°, c 0.75, 1 mol/L HCl), afforded 2s with an
[α]2D0 value as 199.5° (c 3.4, CHCl3), which is even
higher than the value reported in literature (162.3°, c 4.7,
CHCl3).18 Substitution of hydroxyl group in alcohol
with halide under the activation of PPh3-DDQ combi-
nation has been reported,19 and the configuration of the
chiral carbon attached to the hydroxyl group inverts in
the process. It has been reported that the mechanism is
very similar to that of Mistunobu reaction, where PPh3
combined with DDQ to generate a phosphonium inter-
mediate which reacted with the alcohol oxygen, acti-
vating it as a leaving group. In the current system, an
intramolecular substitution by the oxygen of the amide
moiety yields the five-membered ring oxazoline and
OPPh3. The process is shown in Scheme 1. With (1S,2R)-
2-benzoylamino-1,2-diphenylethanol as the substrate,
the NMR data of the product can be assigned to a single
oxazoline instead of a mixture of stereoisomers. It has
been reported that in trans 2,4,5-triphenyloxazoline, the
J value between H-4 and H-5 is 7.3 Hz, whereas it is
10.3 Hz in the cis isomer.20 The J value in our sample
between H-4 and H-5 is 7.6 Hz, indicating that the
product is the trans one and its structure is (4R,5R)-
2,4,5-triphenyloxazoline (2w) (Entry 10). This is further
proved by the consistence of 1H and 13C NMR data with
literature ones. Accordingly, there was no change of
configuration for the stereocenter of carbon attached
amino group.
The similarity of PPh3-DEAD and PPh3-DDQ as ac-
tivating and dehydrating reagent promoted us to extend
Scheme 1 Mechanism for the formation of oxazoline with PPh3-DDQ
Scheme 2 A possible mechanism for the formation of benzoxazole using PPh3-DDQ
928
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 925— 932

A Convenient Synthesis of 2-Oxazolines and 2-Benoxazoles with PPh3-DDQ
Table 3 One pot synthesis of benzoxazole from benzoic acid and 2-amino phenol
Entry
Solvent
MeCN
DCM
Reaction time/h
acid∶ aminophenol∶ PPh3∶ DDQ (molar ratio)
Yielda/%
1
2
3
4
5
6
24
24
24
18
23
23
1∶ 1∶ 4∶
1∶ 1∶ 4∶
1∶ 1∶ 4∶
4
4
4
0
trace
5
THF
toluene
toluene
toluene
1∶ 1∶ 2.5∶ 2.5
10
1∶ 1∶ 4∶
1∶ 3∶ 4∶
4
4
22
24
a Isolated yield.
Continued
Yielda/%
Table 4 The synthesis of benzoxazoles
Entry Time/h
Product
9
17
99
76
(4i)
Entry Time/h
Product
(4a)
Yielda/%
97
10
16
1
2
3
4
17
15
24
23
(4j)
a Isolated yield.
92
52
28
Conclusion
(4b)
PPh3-DDQ could be used as an efficient dehydrating
reagent in the synthesis of 2-oxazolines and benzoxa-
zoles from the corresponding 2-aryl or alkylacylamino
alcohols or phenols. The reactions proceed under neutral
conditions, and can produce 2-aryl as well as 2-alkyl
oxazolines or benzoxazoles in high yields in most cases.
(4c)
(4d)
Experimental
Infrared spectra were recorded on a Nicolet 550 FT-－IR
－1
1
5
6
23
16
90
77
spectrometer in nujol, from 4000 cm to 400 cm .
NMR spectra were recorded in CDCl3 on a Varian
Mercury Plus 400 NMR spectrometer operating at 400
(4e)
(4f)
1
MHz, 100 MHz for H NMR and 13C NMR, respec-
tively, or at a Bruker DRX500 spectrometer operating at
500 MHz, 125 MHz for 1H NMR and 13C NMR, respec-
tively. Chemical shifts were referenced internally to
tetramethylsilane (TMS) or CDCl3. Spectral features are
designated as: m＝multiplet, t＝triplet, d＝doublet, s＝
singlet. Low resolution mass spectra (LRMS) were re-
corded on an HP 6890/5973 GC-MS mass spectrometer.
High resolution mass (HRMS) for unreported com-
pounds were recorded on a Micromass GTC Gas Chro-
matography/TOF Mass spectrometer or a UPLC/Q TOF
Mass spectrometer, and spectral data were obtained for
the molecular ion [M]＋, or [M＋H]＋, respectively.
7
8
24
17
81
95
(4g)
(4h)
Chin. J. Chem. 2011, 29, 925— 932
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Xu, Li & Chen
FULL PAPER
(2, [M－1]＋), 196 (5), 182(6), 154 (6), 140 (11), 112 (7),
99 (7), 98(49), 85 (100), 55 (10), 41 (14); HRMS (EI)
calcd for C14H27NO 225.2093, found 225.2082 [M]＋.
2-(2,2,3,3-Tetramethylcyclopropyloxazoline (2n)
Colorless liquid, Rf 0.28 (EtOAc∶petroleum ether＝
Typical procedure for the synthesis of 2-oxzoline
Under an argon atmosphere, PPh3 (0.393 g, 1.50
mmol), DDQ (0.341 g, 1.50 mmol) and DCM (5.0 mL)
were added to a dried Schlenk tube. After the mixture
was stirred at room temperature for 3 min, N-(2-
hydroxyethyl) benzamide (0.165 g, 1.00 mmol) was
added. The color of the mixture turned into yellow and
precipitation occurred. After 20 min, TLC showed the
disappearance of the substrate, and the formation of a
new spot. Then the mixture was washed with aqueous
NaOH solution (5%, 40 mL), and the separated water
layer was extracted with DCM (15 mL×4). The com-
bined organic layer was washed with brine, and dried by
anhydrous Na2SO4. Filtration and evaporation of the
solvent followed by column chromatography separation
(silica gel) using petroleum ether/ethyl acetate (4∶1,
V/V) gave the corresponding 2-phenyl oxazoline (2a) as
1
3∶7, volume ratio); H NMR (CDCl3, 400 MHz) δ:
4.15 (t, J＝9.2 Hz, 2H), 3.83 (t, J＝9.2 Hz, 2H), 1.20 (s,
6H), 1.18 (s, 6H), 1.13 (s, 1H); 13C NMR (CDCl3, 100
MHz) δ: 167.3, 66.0, 54.5, 31.4 (2C), 27.0, 23.5 (2C),
17.7 (2C); IR (KBr) ν: 2919, 1669, 1199, 1125, 103＋8,
－1
951, 903, 751, 595, 501 cm ; LRMS m/z: 167 (2, [M] ),
154 (8), 152 (100), 137 (6), 126 (30), 110 (12), 83 (45),
81 (17), 55 (14), 41 (14); HRMS (EI) calcd for
C14H27NO 225.2093, found 225.2082 [M]＋.
2-trans-(2-Phenylcyclopropyl)oxazoline
(2o)
Colorless liquid, Rf 0.14 (EtOAc∶petroleum ether＝
1
3∶7, volume ratio); H NMR (CDCl3, 400 MHz) δ:
1
7.27 (t, J＝6.8 Hz, 2H), 7.19 (d, J＝6.8 Hz, 1H), 7.11 (d,
J＝6.8 Hz, 2H), 4.25 (t, J＝9.2 Hz, 2H), 3.84 (t, J＝9.2
Hz, 2H), 2.49 (s, br, 1H), 1.94 (t, J＝4.4 Hz, 1H), 1.56 (t,
J＝4.4 Hz, 1H), 1.32—1.30 (m, 1H); 13C NMR (CDCl3,
100 MHz) δ: 168.1, 140.5, 128.4, 126.2, 126.1, 67.4,
54.3, 24.7, 19.6, 16.0; IR (KBr) ν: 2972, 2925, 1656,
1602, 1501,－1407, 1367, 1260, 1172, 1071,＋1038, 984,
colorless liquid (0.156 g, 96%). H NMR (CDCl3, 400
MHz) δ: 7.95 (d, J＝7.2 Hz, 2H), 7.48—7.40 (m, 3H),
4.44 (t, J＝9.6 Hz, 2H), 4.07 (t, J＝9.6 Hz, 2H); 13C
NMR (CDCl3, 100 MHz) δ: 164.5, 131.2, 128.2, 128.0,
127.6, 67.5, 54.8; IR (KBr) ν: 2931, 1651, 1529, 1493,
－1
1456, 1346, 1269, 1201, 1038, 967, 899, 712, 607 cm .
LRMS m/z: 148 (7, [M＋1]＋), 147 (67, [M]＋), 117 (100).
2-(4-Methylbenzoyl)phenyloxazoline (2h) Color-
less solid, m.p. 113 — 115 ℃ , Rf 0.22 (EtOAc ∶
petroleum ether＝3∶7, volume ratio); 1H NMR (CDCl3,
400 MHz) δ: 7.95 (dd, J＝6.6, 2.3 Hz, 1H), 7.64 (d, J＝
8.2 Hz, 2H), 7.60—7.50 (m, 2H), 7.43 (dd, J＝7.0, 1.8
Hz, 1H), 7.22 (d, J＝8.0 Hz, 2H), 4.03 (dd, J＝14.4, 5.0
Hz, 2H), 3.77 (t, J＝9.6 Hz, 2H), 2.41 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ: 196.68, 163.64, 143.57, 140.34,
134.97, 130.97, 129.71, 129.46, 129.07, 128.08, 126.43,
67.83, 55.02, 21.73; IR (KBr) ν: 2911, 2280, 1669, 16－15,
1
917, 749 cm ; LRMS m/z: 188 (16, [M＋1] ), 187 (99,
[M]＋), 172 (7), 158 (23), 144 (23), 132 (33), 116 (61),
115(97), 104 (39), 91 (35), 85 (47), 77 (28), 63 (18), 55
(100); HRMS (EI) calcd for C12H13NO 187.0997, found
187.1006 [M]＋.
2-cis-(2-Phenylcyclopropyl)oxazoline (2p) Color-
less liquid, Rf 0.14 (EtOAc∶petroleum ether＝3∶7,
1
volume ratio); H NMR (CDCl3, 400 MHz) δ: 7.36—
7.20 (m, 4H), 7.21—7.14 (m, 1H), 4.17—4.07 (m, 1H),
3.98—3.89 (m, 1H), 3.74 (td, J＝9.7, 7.8 Hz, 1H), 3.67
—3.60 (m, 1H), 3.55—3.43 (m, 1H), 2.54—2.43 (m,
1H), 2.14—2.06 (m, 1H), 1.66 (dt, J＝6.9, 5.6 Hz, 1H),
1.34 (td, J＝8.4, 5.3 Hz, 1H); 13C NMR (CDCl3, 100
MHz) δ: 165.9, 136.9, 128.6, 127.4, 126.0, 66.8, 53.7,
1
1414, 1199, 1118, 1044＋, 950, 897, 736, 588, 507 cm ;
LRMS m/z: 265 (3, [M] ), 237 (18), 236 (100), 192 (10),
178 (3), 165 (6), 152 (3), 146 (1), 130 (4), 119 (2), 91
(9), 65 (5).
23.6, 16.7, 10.0; IR (KBr) ν: 2919, 1669, 1602, 1508,
2-Benzyloxazoline (2j) Colorless liquid, Rf 0.33
－1
1
1454, 1407, 1179, 1119, 984, 923, 776, 702＋ cm
;
(EtOAc∶petroleum ether＝3∶7, volume ratio); H
LRMS m/z: 188 (15, [M＋1]＋), 187 (90, [M] ), 186
(61), 172 (8), 158 (23), 144 (18), 132 (31), 116 (56),
115(92), 104 (37), 91 (33), 85 (42), 77 (31), 63 (21), 55
(100); HRMS (EI) calcd for C12H13NO 187.0997, found
187.1001 [M]＋.
NMR (CDCl3, 500 MHz) δ: 7.31—7.24 (m, 5H), 4.22 (t,
J＝9.5 Hz, 2H), 3.82 (t, J＝9.5 Hz, 2H), 3.60 (s, 2H);
13C NMR (CDCl3, 125 MHz) δ: 167.0, 135.1, 129.3,
128.8, 126.9, 67.6, 54.3, 34.6; IR (KBr) ν: 3052, 2979,
2932, 2864, 1642, 1582, 1488, 1354, 109＋1, 1071, 977,
－1
2-trans-[2,2-Dimethyl-3-(2-methyl-propenyl)cyclo-
722＋cm ; LRMS m/z: 161 (51, [M＋1] ), 160 (100,
propyl]oxazoline (2q)
Colorless liquid, Rf 0.32
[M] ), 132 (24), 118 (9), 104 (14), 91 (89), 89 (9), 77(8),
65 (22), 51 (9), 39 (8); HRMS (EI) calcd for C10H11NO
161.0841, found 161.0844 [M]＋.
1
(EtOAc∶petroleum ether＝3∶7, volume ratio); H
NMR (400 MHz, CDCl3) δ: 4.89 (d, J＝7.5 Hz, 1H),
4.35—4.12 (m, 2H), 3.92—3.75 (m, 2H), 2.06—1.93 (m,
1H), 1.71 (s, 6H), 1.36 (d, J＝5.3 Hz, 1H), 1.22 (s, 3H),
1.13 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ: 167.87,
135.06, 121.79, 77.48, 77.16, 76.84, 67.22, 54.44, 30.75,
30.15, 26.85, 25.66, 22.15, 21.09, 18.61; IR (KBr) ν:
2979, 2932, 2878, 1656, 1454, 1407－, 1380, 1253, 1193,
2-n-Undecyloxazoline (2l) Colorless liquid, Rf
0.35 (EtOAc∶petroleum ether＝3∶7, volume ratio);
1H NMR (CDCl3, 400 MHz) δ: 4.21 (t, J＝9.4 Hz, 2H),
3.81 (t, J＝9.4 Hz, 2H), 2.26 (t, J＝7.6 Hz, 2H), 1.62
(pent, J＝7.0 Hz, 2H), 1.30—1.26 (m, 16H), 0.88 (t, J＝
6.6 Hz, 3H); 13C NMR (CDCl3, 400 MHz) δ: 168.7, 67.1,
54.3, 31.9, 29.6 (2C), 29.4, 29.3, 29.23, 29.20, 27.9,
25.9, 22.6, 14.1; IR (KBr) ν: 2925,－2858, 1683, 1468,
1
1172, 1125, 1024, 984, 917, 843 cm ; LRMS m/z: 193
(35, [M]＋), 178 (100), 163 (13), 152 (20), 151 (18), 136,
(14) 109 (39), 108 (23), 98 (7), 91 (23), 83 (34), 82 (9),
1
1374, 1233, 1166, 991, 964, 722 cm ; LRMS m/z: 224
930
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 925— 932

A Convenient Synthesis of 2-Oxazolines and 2-Benoxazoles with PPh3-DDQ
－1
81 (26), 67 (14), 53 (14), 41 (23), 39 (15).
1441, 1374, 1239, 1152, 105＋8, 1024, 735 cm ; LRMS
m/z: 196 (14), 195 (100, [M] ), 168 (16), 167 (79), 166
(41), 140 (15), 139 (18), 92 (31), 77 (40), 64 (49), 63
(62), 51 (18).
2-cis-[2,2-Dimethyl-3-(2-methyl-propenyl)cyclo-
propyl]oxazoline (2r)
Colorless liquid, Rf 0.38
1
(EtOAc∶petroleum ether＝3∶7, volume ratio); H
NMR (CDCl3, 400 MHz) δ: 5.30 (d, J＝8.5 Hz, 1H),
4.17 (t, J＝9.1 Hz, 2H), 3.84 (t, J＝9.4 Hz, 2H), 1.80 (t,
J＝8.8 Hz, 1H), 1.75 (s, 3H), 1.70 (s, 3H), 1.64 (d, J＝
8.9 Hz, 1H), 1.20 (s, 3H), 1.19 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ: 166.45, 134.03, 119.17, 66.24,
54.53, 30.12, 28.77, 26.79, 25.92, 24.33, 18.26, 15.81;
IR (KBr) ν: 3409, 2938, 2876, 1656, 1416, 1420, 1380,
1253, 1－185, 1158, 1125, 1071, 1044, 1024, 997, 924,
2-(2,2,3,3-Tetramethylcyclopropyl)benzoxazole
(4j) Colorless solid, m.p. 63 — 64 ℃ , Rf 0.18
1
(EtOAc∶petroleum ether＝3∶97, volume ratio); H
NMR (CDCl3, 500 MHz) δ: 7.64 (dd, J＝6.7, 2.2 Hz,
1H), 7.43 (dd, J＝6.8, 2.1 Hz, 1H), 7.32—7.19 (m, 2H),
1.73 (s, 1H), 1.32 (s, 6H), 1.30 (s, 6H); 13C NMR
(CDCl3, 125 MHz) δ: 166.36, 150.38, 141.89, 123.81,
123.79, 119.26, 109.83, 77.35, 77.10, 76.85, 32.38,
29.05, 23.52, 17.82; IR (KBr) ν: 2901, 1642, 1542, 1421,
＋
1
850 cm ; LRMS m/z: 193 (17, [M] ), 178 (100), 163
(12), 150 (12), 136 (12), 109 (22), 107 (13), 91 (12), 83
(22), 77 (8), 67 (7), 55 (8).
－1
1199, 1038, 970, 890, 742 cm ; LRMS m/z: 216 (18),
215 (80, [M]＋), 200 (100), 184 (38), 174 (68), 158 (71),
146 (14), 133 (47), 120 (12), 108 (8), 93 (12), 91 (11),
81 (16), 77 (22), 55 (14), 41 (23).
(S)-2,4-Diphenyloxazoline (2s) Colorless liquid,
[α]2D0 － 12.3 (c 1.24, CHCl3), Rf 0.70 (EtOAc ∶
petroleum ether＝1∶4, volume ratio); 1H NMR (CDCl3,
400 MHz) δ: 8.05 (d, J＝7.6 Hz, 2H), 7.53—7.42 (m,
3H), 7.38—7.26 (m, 5H), 5.39 (t, J＝8.4 Hz, 1H), 4.81
(t, J＝8.4 Hz, 1H), 4.28 (t, J＝8.4 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) δ: 165.7, 142.3, 131.5, 128.7, 128.4,
128.3, 127.5, 126.7, 74.8, 70.0; IR (KBr) ν: 3069, 3025,
1660, 1614, 1582, 1497, 1480, 1452, 1363, 1314, 1249,
1184, 1－131, 1102, 1094, 1029, 981, 965, 899, 765, 70＋5,
Supporting Information
Supporting information features: copies of some of
oxazolines and benzoxazoles.
Title: NMR spectra of compounds 2c, 2h, 2k, 2m,
2q, 2r, 2u, 2w, 4a—4c, and 4e—4j.
＋
1
References
546 cm ; LRMS m/z: 223 (4, [M] ), 222 (18, [M－1] ),
221 (100), 194 (11), 193 (78), 192 (27), 165 (21), 88
(26), 77 (5), 63 (10), 51 (5). HRMS (EI) calcd for
C15H13NO 223.0997, found 223.1006 [M]＋.
1
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Colorless
liquid, [α]2D0 －19.8 (c 3.98, CHCl3). Rf 0.59 (EtOAc∶
1
petroleum ether＝1∶1, volume ratio). H NMR δ: 7.95
2
(d, J＝7.6 Hz, 2H), 7.47 (t, J＝7.2 Hz, 1H), 7.41 (t, J＝
7.6 Hz, 2H), 4.86 (m, 1H) 4.63—4.55 (m, 1H), 4.15 (dd,
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3
4
Typical procedure for the synthesis of benzoxazole
4a
PPh3 (157 mg, 0.6 mmol), DDQ (137 mg, 0.6 mmol),
and toluene (4.0 mL) were added to a flask, and the mix-
ture was stirred for 3 min, then N-2-benzoaminophenenol
3a (44 mg, 0.2 mmol) was added. The mixture was re-
fluxed for 17 h. after TLC indicted the completion of the
reaction, the mixture was worked-up and separated as
that for oxazoline, yielding 4a as colorless solid, 39 mg
(97%), m.p. 102—103 ℃ (Lit.23 101—103 ℃; lit.24
102 ℃). Rf 0.64 (EtOAc∶petroleum ether＝1∶4,
5
6
1
volume ratio); H NMR (CDCl3, 400 MHz) δ: 8.27 (dd,
J＝6.6, 3.1 Hz, 2H), 7.82—7.75 (m, 1H), 7.63—7.56 (m,
1H), 7.56—7.50 (m, 3H), 7.40—7.32 (m, 2H); 13C
NMR (CDCl3, 100 MHz) δ: 163.08, 150.75, 142.05,
131.63, 128.99, 127.66, 127.12, 125.20, 124.66, 120.04,
110.68; IR (KBr) ν: 3395, 2952, 2851, 1742, 1609, 1555,
Chin. J. Chem. 2011, 29, 925— 932
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
931

Xu, Li & Chen
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 925— 932