Selective syntheses of benzoxazoles and N-(2-hydroxyaryl)pyrrolidin-2-ones from the corresponding cyclopropyl amides with PPh3/CX4

Article abstract of DOI:10.1016/j.tet.2005.11.077

Benzoxazoles 2 can be smoothly synthesized by treatment of starting materials of N-(2-hydroxyaryl) cyclopropyl amides 1 with PPh₃/ CCl₄ in acetonitrile in good yields. When PPh₃/CBr ₄/MS 4 ? was used in the reac

Full text of DOI:10.1016/j.tet.2005.11.077

Tetrahedron 62 (2006) 2420–2427
Selective syntheses of benzoxazoles and
N-(2-hydroxyaryl)pyrrolidin-2-ones from the corresponding
cyclopropyl amides with PPh3/CX4
*
Yong-Hua Yang and Min Shi
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received 27 October 2005; revised 10 November 2005; accepted 11 November 2005
Available online 9 January 2006
Abstract—Benzoxazoles 2 can be smoothly synthesized by treatment of starting materials of N-(2-hydroxyaryl) cyclopropyl amides 1 with
˚
PPh3/CCl4 in acetonitrile in good yields. When PPh3/CBr4/MS 4 A was used in the reaction system, the corresponding ring-expanding
products 3 were obtained in moderate to good yields in acetonitrile at 80 8C. Using DCE as a solvent in this reaction, the corresponding
2-(3-chloropropyl)benzoxazoles 5 were obtained as major products.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Recently, we reported a new preparation method for
N-substituted pyrrolidin-2-ones from cyclopropyl amides
in good yields in the presence of 2.0 equiv of PPh3 and
1.0 equiv of CBr4.4 As it is well known, lactam rings are of
important structures in a number of biologically and
pharmaceutically active compounds as well as some
alkaloids such as cotinine or mannolactam having lactam
structures.5 Among these lactam compounds, pyrrolidi-
nones are often found in natural products and a variety of
pharmacologically active compounds, for example, con-
vultamides,6 enzyme inhibitors7 and various drugs.8 There-
fore, in order to extend the scope and limitations of this
interesting ring-expanding reaction, we next carried out
the reaction of N-(2-hydroxyphenyl)cyclopropyl amide 1a
in the presence of PPh3/CBr4 under the same reaction
conditions. As shown in Scheme 1, N-(2-hydroxyphenyl)-
pyrrolidin-2-one 3a as a ring-expanding product was
It is well known that triphenylphosphine in the combination
with a tetrahalomethane provides reagents that have
manifold uses and are finding increasing application in
preparative chemistry for halogenation, dehydration, and
P–N linking reactions.1 Of more general importance is
tertiary phosphane/tetrachloromethane system, as chlorinat-
ing and dehydrating agent for sensitive substrates to the
aggressive and readily hydrolyzed acid chlorides such
as PCl5, P(O)Cl3, thionyl chloride and sulfonyl chloride.
A great advantage can also be seen in the ability to the
demands made by the various donor strengths of the
substituents chosen for attachment to the phosphorus atom.2
However, there are few reports about changing the halogen
atom in the reaction by use of tetrahalomethane in the
combination with tertiary phosphane system.1a,3
H
N
4 PPh3, 2 CBr4
MeCN, 60 oC
O
OH
1a
O
N
N
+
+
N
Br
O
O
OH
3a, 42%
4a, 32%
2a, Trace
Scheme 1. Reaction of N-(2-hydroxyphenyl) cyclopropyl amide 1a with PPh3/CBr4.
Keywords: Cyclopropyl amide; Benzoxazole; Triphenylphosphine; Tetrahalomethane; Cyclopropane; Ring-expanding reaction; Ring-opening reaction;
Pyrrolidin-2-one.
*
Corresponding author. Fax: C86 21 64166128; e-mail: mshi@pub.sioc.ac.cn
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.11.077

Y.-H. Yang, M. Shi / Tetrahedron 62 (2006) 2420–2427
2421
obtained in 42% yield along with a trace of benzoxazole
product 2a and 32% of 2-(3-bromopropyl)benzoxazole 4a,
which was determined as a ring-opening product of 2a by
BrK (see Supporting information for spectroscopic data).
However, for substrate 3e bearing an electron-withdrawing
fluoro group on the benzene ring, the reaction became
sluggish and some of the starting materials (amide 1e) can
be recovered even if the reaction time was prolonged to
3 days (Table 2, entry 5). Using 1f as substrate, no reaction
occurred (Table 2, entry 6). As for aliphatic cyclopropyl
amide 1g, a L-2-amino-3-phenylpropanol derivative, the
corresponding ring-expanding as well as brominated
product 3g was formed in 72% yield under identical
conditions (Table 2, entry 7).
This result intrigued us to explore the precious reaction
conditions to prepare benzoxazole products and N-(2-
hydroxyaryl)pyrrolidin-2-one derivatives selectively from
N-(2-hydroxyaryl) cyclopropyl amide 1 since highly
selective synthesis beginning from the same starting
materials is a formidable challenge in organic synthesis.9
˚
Table 2. Ring-expanding reaction of 1 with PPh3/CBr4/MS 4 A in MeCN
OH
OH
4 PPh3, 2 CBr4, 4
Å MS
2. Results and discussion
O
O
N
H
MeCN, 80 oC, 10 h
R
N
R
After trial and error, we found that the dehydration reaction
proceeded smoothly to give the desired benzoxazole
product 2a in 88% yield as a sole product in acetonitrile
at 60 8C with 4.0 equiv of PPh3 and 2.0 equiv of CCl4
without ring-expanding product 3a and ring-opening
product 4a (Table 1, entry 1). Moreover, the above
reaction conditions were found to be quite general. Other
N-(2-hydroxyaryl) cyclopropyl amides 1a–g bearing
a variety of substituted phenyl groups as well as
cyclopropanecarboxylic acid (3-hydroxynaphthalen-2-yl)
amide 1f also underwent the dehydration and cyclization
to give the corresponding benzoxazoles 2, as a sole product,
in excellent yields under the same reaction conditions
within 2 h (Table 1, entries 2–6).
3
1
Entry
R
Yield (%)a
3
1
2
3
4
5
6
1a, H
3a, 87
3b, 77
3c, 50
3d, 88
1b, Me
1c, OMe
1d, Cl
1e, F
3e, 51 (26)b
NR
OH
O
1f,
N
H
7
Ph
Ph
O
O
1g,
HO
3g, 72
Br
N
N
H
Table 1. Intramolecular dehydration reaction of 1 with PPh3/CBr4
a Isolated yields.
O
N
OH
4 PPh3, 2 CCl4
b The reaction time was prolonged to 3 days, the yield in bracket is the
recovered yield of starting materials 1e.
O
MeCN, 60 oC, 2 h
R
R
N
H
2
1
The structures of benzoxazole products 2 and pyrrolidin-
2-ones 3 were determined by NMR spectroscopic data,
microanalyses and HRMS (see Supporting information).
Entry
R
Yield (%)a
2
1
2
3
4
5
6
1a, H
2a, 88
2b, 96
2c, 95
2d, 97
2e, 85
2f, 96
The similar reaction was also investigated using 1,2-
dichloroethane (DCE) instead of acetonitrile as a solvent.
We found that N-(2-hydroxyaryl) cyclopropyl amides 1a–1f
could surprisingly undergo dehydration and subsequent
chloride displacement to afford the corresponding 2-(3-
chloropropyl)benzoxazole products 5a–5f in moderate to
good yields along with 2-cyclopropylbenzoxazoles 2 as
minor constituents during a prolonged reaction time
(Table 3, entries 1–6). The structure of 5d was further
determined by X-ray diffraction. The ORTEP draw of 5d is
shown in Figure 1.10 The control experiment showed that
after a prolonged reaction time, 2-(3-chloropropyl)benz-
oxazole product 5a can be obtained from the corresponding
2-(3-bromopropyl)benzoxazole 4a in 88% yield when the
reaction was carried out in DCE, in addition, no reaction
occurred when 2a was treated with PPh3 in DCE under
identical conditions (Scheme 2). Therefore, we believe that
products 5 were formed through the corresponding products
4 when DCE, containing Cl atom, was used as a solvent.
Namely, although ClK, generated from PPh3 and DCE,11
cannot trigger the ring-opening reaction of benzoxazole
products 2 bearing a cyclopropyl ring to take place
presumably due to its weak nucleophilicity, nucleophilic
displacement of bromo atom in compounds 4 by chloro
1b, Me
1c, OMe
1d, Cl
1e, F
OH
O
1f,
N
H
a Isolated yields.
Interestingly, we found that when CBr4 was utilized to
replace CCl4 for this reaction, the corresponding ring-
expanding product 3a was formed in 87% yield in
acetonitrile after the reaction solution was stirred for 10 h
at 80 8C in the presence of molecular sieves 4 A (100 mg for
0.3 mmol) (Table 2, entry 1). It should be noted that
˚
molecular sieves 4 A was necessary for this reaction
because three products were formed in the absence of MS
˚
4 A (Scheme 1). Next, under these optimized reaction
conditions, the ring-expanding reactions of other substrates
˚
˚
were also investigated in the presence of PPh3/CBr4/MS 4 A
in acetonitrile. The results are summarized in Table 2. The
corresponding 1-(2-hydroxyphenyl)pyrrolidin-2-ones 3
were obtained in good yields for a variety of N-(2-
hydroxyaryl) cyclopropyl amides 1 (Table 2, entries 2–4).

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Y.-H. Yang, M. Shi / Tetrahedron 62 (2006) 2420–2427
Table 3. Reaction of 1 with PPh3/CBr4 in DCE
OH
O
N
O
4 PPh3, 2 CBr4
O
+
Cl
DCE, 60 oC
R
R
N
H
N
R
2
1
5
Entry
R
Time (days)
Yield (%)a
Yield (%)a
2
5
1
2
3
4
5
6
1a, H
1b, Me
1c, OMe
1d, Cl
1e, F
3
3
4
3
5
5
2a, Trace
2b, Trace
2c, Trace
2d, Trace
2e, 17
5a, 79
5b, 64
5c, 89
5d, 84
5e, 69
5f, 73
2f, 20
OH
O
1f,
N
H
a Isolated yields.
and dihalogenmethylene ylid 8. Next, the intermediate A is
formed by the reaction of N-(2-hydroxyaryl) cyclopropyl
amide 1 with dihalogentriphenylphosphorane 7 to release a
dihalogenmethyltriphenylphosphonium salt 9 as white pre-
cipitates, which is dissolved after the solution was heated.1f,g
Thus, the corresponding N-substituted formimidoyl halogen
B is formed along with the generation of triphenylphosphine
oxide. When CCl4 is used in the reaction, intramolecular
ring-closure smoothly takes place to give the corresponding
benzoxazoles bearing cyclopropyl group 2. On the other
hand, if CBr4 is subjected into the reaction instead of CCl4,
the subsequent ring-opening process of N-substituted
formimidoyl halogen B takes place, because of the
comparatively stronger nucleophilicity of BrK than ClK, to
give another formimidoyl halogen C, which gives the ring-
closure product 4 through intramolecuar substitution of Br
atom by the phenolic OH group on the ortho position (path
a). If the Br atom in formimidoyl halogen C is substituted by
OH group of ambient H2O in the reaction system, the
corresponding pyrrolidin-2-one 3 can be obtained through
intermediate D (path b). Though it is difficult to explain the
Figure 1. ORTEP drawing of 5d.
PPh3, 60 oC, 3 days
ClCH2CH2Cl
O
no reaction
N
2a
PPh3, 60 oC, 3 days
ClCH2CH2Cl, 88%
O
N
O
Cl
Br
N
4a
5a
˚
Scheme 2. Control experiment of the formation of 5a.
exact role of molecular sieves 4 A at present stage,
˚
experiment results indicate that molecular sieves 4 A prevent
the intramolecuar substitution of Br atom by the phenolic
OH group on the ortho position and alternatively,
intermolecular attack by ambient H2O in reaction system
takes place to give the corresponding pyrrolidin-2-one
product 3.
atom could occur to give the corresponding chlorinated
products 5 at 60 8C.
Based on the above results and previous literature on the
reaction of amide with PPh3/CX412 as well as our studies on
the mechanism in the transformation of cyclopropyl amides
to N-substituted pyrrolidin-2-ones in which we confirmed
that the ring-expanding reaction proceeded through 4-bromo-
3. Conclusion
butyramide intermediate 6 as shown in Scheme 3,4
a
plausible reaction mechanism is proposed in Scheme 4. At
first, triphenylphosphine reacts with carbon tetrahalide to
give the corresponding dihalogentriphenylphosphorane 7
We succeeded in the preparation of intramolecular
dehydration product benzoxazoles bearing cyclopropyl
group 2 from the N-(2-hydroxyaryl) cyclopropyl amide 1
with PPh3/CCl4. When CBr4 was used instead of CCl4 in
the reaction, 1-(2-hydroxyaryl)pyrrolidin-2-ones 3 can be
obtained in moderate to good yield in the presence of
O
O
2 PPh3, CBr4
Br
NH
MeCN, 60 oC, 10 h, 94%
N
˚
molecular sieves 4 A. Using DCE as a solvent for the
C6H5
C6H5
reaction, the corresponding 2-(3-chloropropyl)benz-
oxazoles 5 were obtained as major products. Efforts are
underway to elucidate the mechanistic details and to extend
the scope of this reaction.
6
Scheme 3. Ring-closure reaction of 4-bromo-N-phenyl-butyramide 6 with
PPh3/CBr4.

Y.-H. Yang, M. Shi / Tetrahedron 62 (2006) 2420–2427
2423
+
Ph PX
3
Ph P CX
3
2 Ph P
CX
4
+
2
2
3
7
8
Ph
X
Ph
Ph
P
Ph
OH
Ph
O
P
OH
Ph
X
O
- Ph3PCHX2X (9)
- Ph3P=O
X
R
N
H
R
N
1
A
OH
OH
X
path a
HBr
O
N
X = Br
N
X
X
R
N
X
R
B
R
4
C
X = Cl
path b
H2O
HCl
O
OH
HBr
H
OH
O
O
N
R
N
R
N
R
2
3
Br
D
Scheme 4. A possible reaction mechanism.
4. Experimental
chromatography to give the corresponding benzoxazole
product.
4.1. General methods
4.4. General procedure for the synthesis of
N-(2-hydroxyphenyl)pyrrolidin-2-one from
N-(2-hydroxyaryl) cyclopropyl amide
1H and 13C NMR spectra were recorded at 300 and 75 MHz,
respectively. Mass spectra were recorded by EI and MALDI
methods, and HRMS was measured on Kratos Analytical
Concept mass spectrometer (EI), Bruker FT mass spectro-
meter (ESI), and IonSpec 4.7 T FTMS (MALDI). Organic
solvents used were dried by standard methods when
necessary. Commercially obtained reagents were used
without further purification. All reactions were monitored
by TLC with Yinlong GF254 silica gel coated plates. Flash
column chromatography was carried out using 300–400
mesh silica gel at increased pressure.
˚
Molecular sieves 4 A (100 mg) was put into a glass vessel
and the vessel was flame-dried under reduced pressure.
Then, N-(2-hydroxyaryl) cyclopropyl amide (0.3 mmol),
PPh3 (314 mg, 1.2 mmol) and CBr4 (200 mg, 0.6 mmol) and
acetonitrile (3.0 mL) were added successively. Kept the
reaction system at 80 8C for necessary time. After filtration,
the solvent was evaporated and the residue was dissolved
in CH2Cl2 (50 mL), washed with H2O (50 mL!2), and
dried over anhydrous MgSO4. The solvent was removed
under reduced pressure and the residue was purified by a
silica gel column chromatography to give the corresponding
pyrrolidin-2-one product.
4.2. General procedure for the preparation of
N-(2-hydroxyaryl) cyclopropyl amide
Added dropwise cyclopropanecarbonyl chloride (261 mg,
2.5 mmol, 228 mL) to the mixture of 2-aminophenol
(2.5 mmol) and pyridine (3.0 mmol) in ethyl acetate
(EtOAc) (20 mL) at room temperature. After stirring for
another 2 h, the reaction mixture was washed with 10% HCl
(50 mL!2) and dried over anhydrous MgSO4. The corre-
sponding pure N-(2-hydroxyaryl) cyclopropyl amide can be
obtained through a short column chromatography (SiO2).
4.5. General procedure for the synthesis of 2-(3-
chloropropyl)benzoxazole from N-(2-hydroxyaryl)
cyclopropyl amide
A mixture of N-(2-hydroxyaryl) cyclopropyl amide
(0.3 mmol), PPh3 (314 mg, 1.2 mmol) and CBr4 (200 mg,
0.6 mmol) was dissolved in DCE (3.0 mL). Then the
reaction system was heated to 60 8C. The solvent was
evaporated after the necessary reaction time, which can be
monitored by 1H NMR spectroscopy. The residue was
dissolved in CH2Cl2 (50 mL), washed with H2O (50 mL!
2), and dried over anhydrous MgSO4. The solvent was
removed under reduced pressure and the residue was
purified by a silica gel column chromatography to give the
corresponding 2-(3-chloropropyl)benzoxazole product.
4.3. General procedure for the synthesis of benzoxazole
from N-(2-hydroxyaryl) cyclopropyl amide
A mixture of N-(2-hydroxyaryl) cyclopropyl amide
(0.3 mmol), PPh3 (314 mg, 1.2 mmol) and CCl4 (92 mg,
58 mL, 0.6 mmol) was dissolved in acetonitrile (3.0 mL).
The solvent was evaporated after the reaction system was
heated at 60 8C for 2 h. The residue was dissolved in CH2Cl2
(50 mL), washed with H2O (50 mL!2), and dried over
anhydrous MgSO4. The solvent was removed under reduced
pressure and the residue was purified by a silica gel column
4.5.1. Cyclopropanecarboxylic acid (2-hydroxyphenyl)-
amide (1a). This compound was obtained as a white solid,
yield: 92%, mp 125–126 8C. IR (CH2Cl2): n 1098, 1136,

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Y.-H. Yang, M. Shi / Tetrahedron 62 (2006) 2420–2427
1178, 1200, 1247, 1311, 1384, 1455, 1498, 1533, 1601,
1656, 1753, 3285 cmK1 1H NMR (300 MHz, CDCl3,
CD3SOCD3): d 7.5, 14.2, 108.1 (d, JC–FZ27.2 Hz), 109.4
(d, JC–FZ23.1 Hz), 115.3 (d, JC–FZ9.0 Hz), 127.4 (d,
JC–FZ11.3 Hz), 143.3, 154.8 (d, JC–FZ230.8 Hz), 172.4;
MS (EI) m/z: 195 (MC, 14), 177 (2), 154 (1), 127 (19), 109
(1), 98 (5), 69 (100), 41 (43); HRMS (EI) Calcd for
(C10H10FNO2)C: 195.0696, found: 195.0699.
;
TMS): d 0.91–0.95 (m, 2H, CH2), 1.12–1.15 (m, 2H,
CH2), 1.62–1.70 (m, 1H, CH), 6.83–6.88 (m, 1H, Ar),
6.99–7.02 (m, 2H, Ar), 7.26–7.27 (m, 1H, Ar), 7.84 (br, 1H,
NH), 9.01 (br, 1H, OH); 13C NMR (75 MHz, CDCl3, TMS):
d 8.8, 15.3, 119.8, 120.3, 122.0, 125.8, 127.0, 148.7, 174.2;
MS (EI) m/z: 177 (MC, 51), 159 (4), 133 (1), 120 (1), 109
(100), 80 (14), 69 (93), 41 (54). Anal. Calcd for C10H11NO2:
C, 67.78; H, 6.25; N, 7.90%. Found: C, 67.51; H, 6.25;
N, 7.83%.
4.5.6. Cyclopropanecarboxylic acid (3-hydroxynaph-
thalen-2-yl)amide (1f). This compound was obtained as a
white solid, yield: 66%, mp 180–182 8C. IR (CH2Cl2): n
1234, 1304, 1434, 1505, 1536, 1626, 3257 cmK1; 1H NMR
(300 MHz, CDCl3, TMS): d 0.98–1.04 (m, 2H, CH2),
1.20–1.28 (m, 2H, CH2), 1.79–1.86 (m, 1H, CH), 7.26 (d,
JZ8.7 Hz, 1H, Ar), 7.39 (dt, JZ1.2, 3.6 Hz, 1H, Ar), 7.53
(dt, JZ1.5, 6.9 Hz, 1H, Ar), 7.69 (d, JZ1.2 Hz, 1H, Ar),
7.80 (t, JZ9.0 Hz, 2H, Ar), 7.94 (br, 1H, NH), 8.78 (br, 1H,
OH); 13C NMR (75 MHz, CDCl3, TMS): d 9.0, 15.3, 117.1,
119.1, 121.6, 123.7, 126.9, 128.16, 128.2, 128.7, 129.0,
148.1, 174.5; MS (EI) m/z: 227 (MC, 25), 209 (3), 180 (1),
159 (100), 149 (2), 130 (19), 103 (10), 69 (43), 41 (42);
HRMS (ESI) Calcd for (C14H13NO2CNa)C: 250.0838,
found: 250.0841.
4.5.2. Cyclopropanecarboxylic acid (2-hydroxy-5-
methylphenyl)amide (1b). This compound was obtained
as a white solid, yield: 86%, mp 110–112 8C. IR (CH2Cl2): n
1215, 1242, 1273, 1316, 1383, 1439, 1505, 1537, 1602,
1
1653, 3284 cmK1; H NMR (300 MHz, CDCl3, TMS): d
0.86–0.92 (m, 2H, CH2), 1.08–1.13 (m, 2H, CH2), 1.60–1.65
(m, 1H, CH), 2.22 (s, 3H, CH3), 6.85 (s, 1H, Ar), 6.88 (s, 2H,
Ar), 8.00 (br, 1H, NH), 8.87 (br, 1H, OH); 13C NMR
(75 MHz, CDCl3, TMS): d 8.6, 15.2, 20.3, 119.3, 122.4,
125.4, 127.5, 129.8, 146.1, 174.1; MS (EI) m/z: 191 (MC,
40), 172 (1), 160 (3), 132 (1), 123 (100), 106 (3), 69 (26), 41
(18). Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85; N,
7.32%. Found: C, 68.89; H, 6.79; N, 7.07%.
4.5.7. Cyclopropanecarboxylic acid (1-benzyl-2-
hydroxyethyl)amide (1g). This compound was obtained
as a white solid, yield: 91%, mp 113–115 8C. IR (CH2Cl2): n
1036, 1250, 1455, 1497, 1542, 1645, 3290, 3649 cmK1; 1H
NMR (300 MHz, CDCl3, TMS): d 0.70–0.76 (m, 2H, CH2),
0.93–0.97 (m, 2H, CH2), 1.26–1.36 (m, 1H, CH), 2.88 (d,
JZ6.9 Hz, 2H, CH2), 3.34 (br, 1H, OH), 3.57–3.71 (m, 2H,
CH2), 4.11–4.19 (m, 1H, CH), 6.10 (br, 1H, NH), 7.21–7.33
(m, 5H, Ar); 13C NMR (75 MHz, CDCl3, TMS): d 7.3, 7.4,
14.7, 37.0, 53.0, 63.9, 126.6, 128.6, 129.2, 137.7, 174.4; MS
(EI) m/z: 219 (MC, 1), 188 (3), 168 (1), 128 (39), 91 (32), 69
(100), 41 (41). Anal. Calcd for C13H17NO2: C, 71.21; H,
7.81; N, 6.39%. Found: C, 71.08; H, 7.65; N, 6.32%.
4.5.3. Cyclopropanecarboxylic acid (2-hydroxy-5-
methoxyphenyl)amide (1c). This compound was obtained
as a white solid, yield: 87%, mp 124–126 8C. IR (CH2Cl2): n
1039, 1102, 1151, 1198, 1219, 1273, 1307, 1376, 1431, 1453,
1
1508, 1540, 1600, 1650, 3182 cmK1; H NMR (300 MHz,
CDCl3, TMS): d 0.86–0.89 (m, 2H, CH2), 1.08–1.13 (m, 2H,
CH2), 1.60–1.65 (m, 1H, CH), 3.69 (s, 3H, OCH3), 6.64 (d,
JZ7.2 Hz, 1H, Ar), 6.79 (s, 1H, Ar), 6.88 (d, JZ7.2 Hz, 1H,
Ar), 8.28 (br, 1H, NH), 8.46 (br, 1H, OH); 13C NMR
(75 MHz, CDCl3, TMS): d 8.6, 15.2, 55.7, 107.3, 112.0,
119.4, 126.4, 141, 8, 153.3, 174.1; MS (EI) m/z: 207 (MC,
19), 185 (10), 174 (4), 149 (6), 139 (100), 124 (6), 110 (9), 69
(58), 41 (64). Anal. Calcd for C11H13NO3: C, 63.76; H, 6.32;
N, 6.76%. Found: C, 63.47; H, 6.25; N, 6.59%.
4.5.8. 2-Cyclopropylbenzooxazole (2a). This compound
1
was obtained as a pale oil,13 yield: 42 mg, 88%. H NMR
(300 MHz, CDCl3, TMS): d 1.13–1.21 (m, 2H, CH2),
1.25–1.30 (m, 2H, CH2), 2.16–2.25 (m, 1H, CH), 7.21–7.30
(m, 2H, Ar), 7.41–7.43 (m, 1H, Ar), 7.59–7.62 (m, 1H, Ar);
13C NMR (75 MHz, CDCl3, TMS): d 9.1, 9.2, 109.9, 118.9,
123.9, 124.0, 141.5, 150.3, 168.5.
4.5.4. Cyclopropanecarboxylic acid (5-chloro-2-
hydroxyphenyl)amide (1d). This compound was obtained
as a white solid, yield: 85%, mp 178–180 8C. IR (CH2Cl2): n
1204, 1268, 1371, 1426, 1542, 1589, 1655, 3016 cmK1; 1H
NMR (300 MHz, CDCl3, TMS): d 0.94–1.00 (m, 2H, CH2),
1.14–1.19 (m, 2H, CH2), 1.59–1.65 (m, 1H, CH), 6.91–6.95
(m, 1H, Ar), 7.06–7.09 (m, 2H, Ar), 7.65 (br, 1H, NH), 8.83
(s, 1H, OH); 13C NMR (75 MHz, CD3COCD3): d 7.0, 14.0,
116.8, 120.2, 123.0, 123.5, 127.7, 145.6, 172.8; MS (EI)
m/z: 213 (16), 211 (MC, 50), 193 (5), 167 (1), 154 (1), 145
(15), 143 (44), 114 (11), 99 (2), 69 (100), 41 (37). Anal.
Calcd for C10H10ClNO2: C, 56.75; H, 4.76; N, 6.62%.
Found: C, 57.11; H, 4.72; N, 6.62%.
4.5.9. 2-Cyclopropyl-5-methylbenzooxazole (2b). This
compound was obtained as a pale oil, yield: 50 mg, 96%.
IR (CH2Cl2): n 1029, 1044, 1083, 1158, 1180, 1260, 1456,
1483, 1576, 1615, 2856, 2924, 3015 cmK1 1H NMR
;
(300 MHz, CDCl3, TMS): d 1.10–1.19 (m, 2H, CH2),
1.22–1.28 (m, 2H, CH2), 2.13–2.22 (m, 1H, CH), 2.43 (s,
3H, CH3), 7.04 (dd, JZ8.4, 1.5 Hz, 1H, Ar), 7.28 (d, JZ
8.4 Hz, 1H, Ar), 7.38 (d, JZ1.5 Hz, 1H, Ar); 13C NMR
(75 MHz, CDCl3, TMS): d 9.0, 9.3, 21.4, 109.3, 118.9,
124.8, 133.7, 141.7, 148.6, 168.6; MS (EI) m/z: 173 (MC,
100), 158 (8), 154 (1), 147 (43), 144 (11), 130 (5), 117 (3),
106 (5), 78 (14); HRMS (MALDI) Calcd for (C11H11NOC
H)C: 174.0913, found: 174.0906.
4.5.5. Cyclopropanecarboxylic acid (5-fluoro-2-hydroxy-
phenyl)amide (1e). This compound was obtained as a white
solid, yield: 76%, mp 165–167 8C. IR (CH2Cl2): n 1134,
1190, 1212, 1261, 1311, 1443, 1534, 1620, 1655 cmK1; 1H
NMR (300 MHz, CD3COCD3): d 0.80–0.88 (m, 2H, CH2),
0.90–1.03 (m, 2H, CH2), 1.98–2.03 (m, 1H, CH), 3.34 (br,
2H, OH, NH), 6.66–6.73 (m, 1H, Ar), 6.84–6.89 (m, 1H,
Ar), 7.65–7.69 (m, 1H, Ar); 13C NMR (75 MHz,
4.5.10. 2-Cyclopropyl-5-methoxybenzooxazole (2c). This
compound was obtained as a pale oil, yield: 54 mg, 95%.
IR (CH2Cl2): n 1028, 1153, 1174, 1195, 1288, 1441, 1483,
1
1574, 1615, 2834, 2939, 3011 cmK1; H NMR (300 MHz,

Y.-H. Yang, M. Shi / Tetrahedron 62 (2006) 2420–2427
2425
CDCl3, TMS): d 1.11–1.16 (m, 2H, CH2), 1.22–1.27 (m, 2H,
CH2), 2.12–2.20 (m, 1H, CH), 3.82 (s, 3H, OCH3), 6.83 (dd,
JZ2.7, 8.7 Hz, 1H, Ar), 7.10 (d, JZ2.7 Hz, 1H, Ar), 7.29
(d, JZ8.7 Hz, 1H, Ar); 13C NMR (75 MHz, CDCl3, TMS):
d 9.0, 9.2, 55.7, 102.3, 109.9, 111.9, 142.3, 144.9, 156.9,
169.3; MS (EI) m/z: 189 (MC, 100), 174 (57), 163 (26), 146
(6), 107 (57), 79 (75), 63 (13), 51 (43); HRMS (MALDI)
Calcd for (C11H11NO2CH)C: 190.0863, found: 190.0868.
4.5.15. 1-(2-Hydroxy-5-methylphenyl)pyrrolidin-2-one
(3b). This compound was obtained as a white solid, yield:
44 mg, 77%, mp 177–179 8C. IR (CH2Cl2): n 1106, 1135,
1186, 1261, 1308, 1420, 1439, 1461, 1510, 1601, 1656,
1
2851, 2922 cmK1; H NMR (300 MHz, CDCl3, TMS): d
2.24 (tt, JZ8.1, 6.6 Hz, 2H, CH2), 2.27 (s, 3H, CH3), 2.64 (t,
JZ8.1 Hz, 2H, CH2), 3.93 (t, JZ6.6 Hz, 2H, CH2), 6.85 (d,
JZ0.6 Hz, 1H, Ar), 6.92–6.99 (m, 2H, Ar), 8.32 (s, 1H,
OH); 13C NMR (75 MHz, CDCl3, TMS): d 19.4, 20.5, 32.1,
50.7, 120.3, 121.6, 127.2, 128.2, 129.8, 147.7, 176.0; MS
(EI) m/z: 191 (MC, 69), 174 (2), 162 (3), 148 (4), 136 (100),
120 (2), 109 (37), 91 (12), 77 (16). Anal. Calcd for
C11H13NO2: C, 69.09; H, 6.85; N, 7.32%. Found: C, 68.83;
H, 6.64; N, 7.07%.
4.5.11. 5-Chloro-2-cyclopropylbenzooxazole (2d). This
compound was obtained as a white solid, yield: 56 mg, 97%,
mp 70–72 8C. IR (CH2Cl2): n 1028, 1047, 1291, 1343, 1456,
1
1571, 1607, 2924, 3049, 3094 cmK1; H NMR (300 MHz,
CDCl3, TMS): d 1.15–1.22 (m, 2H, CH2), 1.23–1.30 (m, 2H,
CH2), 2.14–2.32 (m, 1H, CH), 7.20 (dd, JZ1.8, 8.7 Hz, 1H,
Ar), 7.32 (d, JZ8.7 Hz, 1H, Ar), 7.56 (d, JZ1.8 Hz, 1H,
Ar); 13C NMR (75 MHz, CDCl3, TMS): d 9.3, 9.4, 110.6,
118.9, 124.1, 129.4, 142.7, 148.9, 170.0; MS (EI) m/z: 195
(31), 193 (MC, 100), 178 (8), 169 (18), 167 (63), 130 (14),
112 (4), 102 (12), 63 (53), 41 (19). Anal. Calcd for
C10H8ClNO: C, 62.03; H, 4.16; N, 7.23%. Found: C, 62.09;
H, 4.27; N, 7.15%.
4.5.16. 1-(2-Hydroxy-5-methoxyphenyl)pyrrolidin-2-one
(3c). This compound was obtained as a white solid,
yield: 31 mg, 50%, mp 83–85 8C. IR (CH2Cl2): n 1038,
1176, 1212, 1261, 1416, 1461, 1509, 1612, 1662, 2959,
3919 cmK1; 1H NMR (300 MHz, CDCl3, TMS): d 2.29 (tt,
JZ8.1, 6.6 Hz, 2H, CH2), 2.69 (t, JZ8.1 Hz, 2H, CH2),
3.77 (s, 3H, OCH3), 3.95 (t, JZ6.6 Hz, 2H, CH2), 6.61 (d,
JZ3.0 Hz, 1H, Ar), 6.76 (dd, JZ9.0, 3.0 Hz, 1H, Ar), 7.00
(d, JZ9.0 Hz, 1H, Ar), 7.97 (s, 1H, OH); 13C NMR
(75 MHz, CDCl3, TMS): d 19.4, 32.2, 50.8, 55.8, 107.4,
112.45, 121.2, 128.2, 143.9, 153.4, 176.0; MS (EI) m/z: 207
(MC, 100), 192 (9), 179 (3), 164 (10), 152 (78), 136 (11),
125 (14), 69 (9); HRMS (EI) Calcd for (C11H13NO3)C:
207.0895, found: 207.0908.
4.5.12. 2-Cyclopropyl-5-fluorobenzooxazole (2e). This
compound was obtained as a white solid, yield: 45 mg,
85%, mp 63–65 8C. IR (CH2Cl2): n 1031, 1103, 1136, 1151,
1174, 1265, 1293, 1339, 1350, 1441, 1466, 1481, 1570,
1
1615, 2851, 2922, 3012, 3034 cmK1; H NMR (300 MHz,
CDCl3, TMS): d 1.15–1.22 (m, 2H, CH2), 1.23–1.30 (m, 2H,
CH2), 2.15–2.24 (m, 1H, CH), 6.93–7.00 (m, 1H, Ar),
7.26–7.36 (m, 2H, Ar); 13C NMR (75 MHz, CDCl3, TMS):
4.5.17. 1-(5-Chloro-2-hydroxy-phenyl)pyrrolidin-2-one
(3d). This compound was obtained as a white solid,
yield: 56 mg, 88%, mp 213–215 8C. IR (CH2Cl2): n 1024,
1117, 1191, 1282, 1302, 1418, 1464, 1504, 1657, 2852,
2924 cmK1; 1H NMR (300 MHz, CDCl3, TMS): d 2.31 (tt,
JZ7.8, 6.9 Hz, 2H, CH2), 2.71 (t, JZ7.8 Hz, 2H, CH2),
3.95 (t, JZ6.9 Hz, 2H, CH2), 6.99 (d, JZ8.4 Hz, 1H, Ar),
7.04 (d, JZ2.4 Hz, 1H, Ar), 7.14 (d, JZ2.4, 8.4 Hz, 1H,
Ar), 8.57 (s, 1H, OH); 13C NMR (75 MHz, CDCl3, TMS): d
19.5, 32.2, 50.9, 121.0, 121.9, 125.1, 127.5, 148.8, 176.5;
MS (EI) m/z: 213 (18), 211 (MC, 64), 194 (2), 183 (4), 169
(2), 156 (100), 148 (3), 129 (23), 93 (16). Anal. Calcd for
C10H10ClNO2: C, 56.75; H, 4.76; N, 6.62%. Found: C,
56.62; H, 4.52; N, 6.41%.
d 9.3, 9.4, 105.5 (d, JC–FZ25.7 Hz), 110.1 (d, JC–F
9.8 Hz), 111.3 (d, JC–FZ25.7 Hz), 142.4 (d, JC–F
Z
Z
13.2 Hz), 146.7, 159.9 (d, JC–FZ238.1 Hz), 170.5; MS
(EI) m/z: 177 (MC, 100), 162 (9), 151 (67), 122 (5), 109 (7),
82 (26), 63 (14), 41 (16); HRMS (EI) Calcd for C10H8FNO:
177.0590, found: 177.0576.
4.5.13. 2-Cyclopropylnaphtho[2,3-d]oxazole (2f). This
compound was obtained as a pale yellow oil, yield:
60 mg, 96%. IR (CH2Cl2): n 1005, 1027, 1099, 1161,
1198, 1236, 1261, 1274, 1372, 1569, 1591, 1641, 2924,
1
3013, 3064 cmK1; H NMR (300 MHz, CDCl3, TMS): d
1.15–1.21 (m, 2H, CH2), 1.25–1.34 (m, 2H, CH2), 1.29–2.35
(m, 1H, CH), 7.47–7.64 (m, 3H, Ar), 7.69 (d, JZ8.7 Hz, 1H,
Ar), 7.92 (d, JZ8.4 Hz, 1H, Ar), 8.45 (dd, JZ8.1, 0.3 Hz,
1H, Ar); 13C NMR (75 MHz, CDCl3, TMS): d 9.0, 9.5,
110.5, 121.9, 124.7, 124.9, 126.0, 126.6, 128.4, 130.9,
136.6, 147.4, 167.5; MS (EI) m/z: 209 (MC, 100), 192 (3),
180 (19), 153 (6), 140 (6), 128 (5), 114 (22), 88 (10), 63
(10); HRMS (ESI) Calcd for (C14H12NOCNa)C: 210.0913,
found: 210.0915.
4.5.18. 1-(5-Fluoro-2-hydroxyphenyl)pyrrolidin-2-one
(3e). This compound was obtained as a white solid, yield:
30 mg, 51%, mp 158–160 8C. IR (CH2Cl2): n 1178, 1270,
1419, 1445, 1519, 1622, 1663, 2962, 3103 cmK1; 1H NMR
(300 MHz, CDCl3, TMS): d 2.30 (tt, JZ7.8, 6.9 Hz, 2H,
CH2), 2.69 (t, JZ7.8 Hz, 2H, CH2), 3.93 (t, JZ6.9 Hz, 2H,
CH2), 6.76–6.80 (m, 1H, Ar), 6.86–6.92 (m, 1H, Ar), 6.98–
7.03 (m, 1H, Ar), 8.29 (s, 1H, OH); 13C NMR (75 MHz,
CDCl3, TMS): d 19.4, 32.2, 50.8, 107.9 (JC–FZ25.8 Hz),
114.1 (JC–FZ22.3 Hz), 121.4 (JC–FZ9.2 Hz), 128.2, 146.1,
156.4 (JC–FZ237.6 Hz), 176.4; MS (EI) m/z: 195 (MC, 57),
174 (12), 149 (28), 140 (100), 129 (25), 113 (51), 91 (60), 57
(52); HRMS (EI) Calcd for (C10H10FNO2)C: 195.0696,
found: 195.0692.
4.5.14. 1-(2-Hydroxyphenyl)pyrrolidin-2-one (3a). This
compound was obtained as a white solid,14 yield: 44 mg,
87%, mp 136–138 8C; 1H NMR (300 MHz, CDCl3, TMS): d
2.28 (tt, JZ8.1, 7.2 Hz, 2H, CH2), 2.68 (t, JZ8.1 Hz, 2H,
CH2), 3.96 (t, JZ7.2 Hz, 2H, CH2), 6.92 (dt, JZ0.6, 7.5 Hz,
1H, Ar), 7.06 (dd, JZ0.6, 8.4 Hz, 2H, Ar), 7.18 (dt, JZ0.9,
7.8 Hz, 1H, Ar), 8.58 (s, 1H, OH); 13C NMR (75 MHz,
CDCl3, TMS): d 19.5, 32.2, 50.9, 109.7, 120.5, 120.7, 121.2,
127.7, 150.1, 176.2.
4.5.19. 1-(1-Benzyl-2-hydroxyethyl)pyrrolidin-2-one
(3g). This compound was obtained as a pale red oil, yield:
61 mg, 72%. IR (CH2Cl2): n 1290, 1462, 1495, 1658, 1729,

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Y.-H. Yang, M. Shi / Tetrahedron 62 (2006) 2420–2427
1
2854, 2922 cmK1; H NMR (300 MHz, CDCl3, TMS): d
1.89–1.99 (m, 2H, CH2), 2.29–2.38 (m, 2H, CH2), 2.98 (d,
JZ7.8 Hz, 2H, CH2), 3.32 (t, JZ6.9 Hz, 2H, CH2), 3.57 (d,
JZ7.5 Hz, 2H, CH2), 4.47 (tt, JZ7.8, 7.5 Hz, 1H, CH),
7.20–7.32 (m, 5H, Ar); 13C NMR (75 MHz, CDCl3,
TMS): d 18.4, 31.2, 33.3, 36.8, 44.7, 54.3, 126.7, 128.5,
128.7, 136.9, 175.3; MS (MALDI) m/z: 284 [(MC3)C,
100], 282 [(MC1)C, 100]; HRMS (MALDI) Calcd for
(C13H16BrNOCH)C: 282.0488, found: 282.0494.
148 (14), 107 (19), 79 (25); HRMS (EI) Calcd for
(C11H12NO2Cl)C: 225.0557, found: 225.0545.
4.5.24. 5-Chloro-2-(3-chloropropyl)benzooxazole (5d).
This compound was obtained as a white solid, yield:
58 mg, 84%, mp 47–49 8C. IR (CH2Cl2): n 1055, 1145,
1161, 1257, 1428, 1452, 1568, 1609, 2962 cmK1; 1H NMR
(300 MHz, CDCl3, TMS): d 2.37 (tt, JZ7.2, 6.0 Hz, 2H,
CH2), 3.14 (t, JZ7.2 Hz, 2H, CH2), 3.71 (t, JZ6.0 Hz, 2H,
CH2), 7.29 (dd, JZ8.7, 2.4 Hz, 1H, Ar), 7.41 (d, JZ8.7 Hz,
1H, Ar), 7.65 (d, JZ2.4 Hz, 1H, Ar); 13C NMR (75 MHz,
CDCl3, TMS): d 25.7, 29.1, 43.7, 111.1, 119.7, 125.0, 129.7,
142.3, 149.4, 167.2; MS (EI) m/z: 233 (1), 231 (7), 229 (11,
MC), 194 (7), 180 (9), 167 (100), 138 (6), 127 (5), 102 (10),
63 (26); HRMS (EI) Calcd for (C10H9NOCl2)C: 229.0061,
found: 229.0077.
4.5.20. 2-(3-Bromopropyl)benzooxazole (4a). This com-
pound was obtained as a pale oil, yield: 23 mg, 32%. IR
(CH2Cl2): n 1003, 1104, 1155, 1167, 1243, 1455, 1572,
1615, 2853, 2924, 2956 cmK1; 1H NMR (300 MHz, CDCl3,
TMS): d 2.46 (tt, JZ7.2, 6.3 Hz, 2H, CH2), 3.14 (t, JZ
7.2 Hz, 2H, CH2), 3.58 (t, JZ6.3 Hz, 2H, CH2), 7.30–7.34
(m, 2H, Ar), 7.48–7.51 (m, 1H, Ar), 7.66–7.69 (m, 1H, Ar);
13C NMR (75 MHz, CDCl3, TMS): d 26.9, 29.3, 32.3,
110.3, 119.6, 124.2, 124.7, 141.1, 150.7, 165.5; MS (EI)
m/z: 241 (6), 239 (MC, 6), 183 (19), 149 (30), 133 (100),
104 (14), 77 (19), 41 (26). Anal. Calcd for C10H10NOBr: C,
50.02; H, 4.20; N, 5.83%. Found: C, 50.14; H, 4.38; N,
5.73%.
4.5.25. 2-(3-Chloropropyl)-5-fluorobenzooxazole (5e).
This compound was obtained as a pale oil, yield: 44 mg,
69%. IR (CH2Cl2): n 1131, 1167, 1249, 1276, 1299, 1440,
1478, 1572, 2926, 2961 cmK1; 1H NMR (300 MHz, CDCl3,
TMS): d 2.37 (tt, JZ7.2, 6.0 Hz, 2H, CH2), 3.13 (t, JZ
7.2 Hz, 2H, CH2), 3.71 (t, JZ6.0 Hz, 2H, CH2), 7.01–7.08
(m, 1H, Ar), 7.34–7.44 (m, 2H, Ar); 13C NMR (75 MHz,
CDCl3, TMS): d 25.8, 29.1, 43.7, 106.1 (d, JC–FZ25.7 Hz),
110.6 (d, JC–FZ9.7 Hz), 112.2 (d, JC–FZ25.7 Hz), 142.1,
147.1, 159.9 (d, JC–FZ238.7 Hz), 167.6; MS (EI) m/z: 215
(4), 213 (9, MC), 178 (5), 164 (8), 151 (100), 122 (7), 111
(5), 95 (5), 82 (9); HRMS (EI) Calcd for (C10H9ClFNO)C:
213.0357, found: 213.0343.
4.5.21. 2-(3-Chloropropyl)benzooxazole (5a). This com-
pound was obtained as a pale oil, yield: 46 mg, 79%. IR
(CH2Cl2): n 1003, 1104, 1143, 1169, 1242, 1277, 1298,
1456, 1573, 1615, 2926, 2961 cmK1; H NMR (300 MHz,
1
CDCl3, TMS): d 2.37 (tt, JZ7.2, 6.6 Hz, 2H, CH2), 3.13
(t, JZ7.2 Hz, 2H, CH2), 3.71 (t, JZ6.6 Hz, 2H, CH2),
7.27–7.33 (m, 2H, Ar), 7.46–7.50 (m, 1H, Ar), 7.66–7.69
(m, 1H, Ar); 13C NMR (75 MHz, CDCl3, TMS): d 25.6,
29.2, 43.7, 110.26, 119.5, 124.1, 124.6, 141.1, 150.7, 165.6;
MS (EI) m/z: 197 (5), 195 (MC, 11), 183 (16), 160 (6), 133
(100), 109 (28), 97 (13), 57 (17); HRMS (EI) Calcd for
(C10H10NOCl)C: 195.0451, found: 195.0447.
4.5.26. 2-(3-Chloropropyl)naphtho[2,3-d]oxazole (5f).
This compound was obtained as a pale oil, yield: 54 mg,
73%. IR (CH2Cl2): n 1005, 1226, 1274, 1300, 1373, 1445,
1567, 1589, 2924, 2959 cmK1; 1H NMR (300 MHz, CDCl3,
TMS): d 2.42 (tt, JZ7.2, 6.6 Hz, 2H, CH2), 3.22 (t, JZ
7.2 Hz, 2H, CH2), 3.74 (t, JZ6.6 Hz, 2H, CH2), 7.49–7.55
(m, 1H, Ar), 7.62–7.67 (m, 2H, Ar), 7.76 (d, JZ9.0 Hz, 1H,
Ar), 7.95 (d, JZ8.1 Hz, 1H, Ar), 8.46 (d, JZ8.1 Hz, 1H,
Ar); 13C NMR (75 MHz, CDCl3, TMS): d 26.0, 29.7, 43.9,
110.7, 121.9, 125.2, 125.5, 126.3, 126.9, 128.5, 131.0,
136.4, 147.9, 164.7; MS (EI) m/z: 247 (11), 245 (MC, 32),
209 (47), 196 (6), 183 (100), 154 (8), 140 (4), 127 (11), 114
(20); HRMS (EI) Calcd for (C14H12ClNO)C: 245.0607,
found: 245.0596.
4.5.22. 2-(3-Chloropropyl)-5-methylbenzooxazole (5b).
This compound was obtained as a pale oil, yield: 40 mg,
64%. IR (CH2Cl2): n 1119, 1146, 1177, 1261, 1297, 1430,
1444, 1482, 1574, 2924, 2960 cmK1; H NMR (300 MHz,
1
CDCl3, TMS): d 2.36 (tt, JZ7.2, 6.6 Hz, 2H, CH2), 2.45 (s,
3H, CH3), 3.10 (t, JZ7.2 Hz, 2H, CH2), 3.69 (t, JZ6.6 Hz,
2H, CH2), 7.11 (dd, JZ8.4, 0.9 Hz, 1H, Ar), 7.35 (d, JZ
8.4 Hz, 1H, Ar), 7.45 (d, JZ0.9 Hz, 1H, Ar); 13C NMR
(75 MHz, CDCl3, TMS): d 21.4, 25.7, 29.2, 43.7, 109.6,
119.5, 125.6, 133.9, 141.3, 148.9, 165.7; MS (EI) m/z: 211
(5), 209 (MC, 11), 183 (2), 174 (6), 160 (12), 147 (100), 106
(14), 78 (26); HRMS (EI) Calcd for (C11H12NOCl)C:
209.0607, found: 209.0621.
Acknowledgements
We thank the State Key Project of Basic Research (Project
973) (No. G2000048007), Shanghai Municipal Committee
of Science and Technology, and the National Natural
Science Foundation of China for financial support
(20472096, 203900502, and 20272069).
4.5.23. 2-(3-Chloropropyl)-5-methoxybenzooxazole (5c).
This compound was obtained as a colorless oil, yield:
56 mg, 89%. IR (CH2Cl2): n 1027, 1152, 1196, 1284, 1341,
1441, 1483, 1574, 1615, 2835, 2959, 2999 cmK1; 1H NMR
(300 MHz, CDCl3, TMS): d 2.35 (tt, JZ7.2, 6.0 Hz, 2H,
CH2), 3.09 (t, JZ7.2 Hz, 2H, CH2), 3.70 (t, JZ6.0 Hz, 2H,
CH2), 3.84 (s, 3H, OCH3), 6.89 (dd, JZ8.7, 2.7 Hz, 1H, Ar),
7.16 (d, JZ2.7 Hz, 1H, Ar), 7.35 (d, JZ8.7 Hz, 1H, Ar);
13C NMR (75 MHz, CDCl3, TMS): d 25.7, 29.2, 43.7, 55.8,
102.7, 110.3, 112.9, 141.9, 145.3, 157.0, 166.4; MS (EI)
m/z: 227 (11), 225 (MC, 40), 189 (7), 176 (31), 163 (100),
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2005.11.
077. The X-ray crystal data of 5d is included in Supporting
information. This material is available free of charge via
the Internet.

Y.-H. Yang, M. Shi / Tetrahedron 62 (2006) 2420–2427
2427
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¨
¨
Chem. Soc. Rev. 1974, 3, 87–137. (f) Tomoskozi, I.; Gruber, L.;
Radics, L. Tetrahedron Lett. 1975, 16, 2473–2476. (g) Aneja, R.;
Davies, A. P.; Knaggs, J. A. Tetrahedron Lett. 1974, 15, 67–70.
2. (a) Friederang, A. W.; Tarbell, D. S. J. Org. Chem. 1968, 33,
3797–3800. (b) Castrol, B.; Chapleur, Y.; Gross, B.; Selve, C.
Tetrahedron Lett. 1972, 13, 5001–5004. (c) Downie, I. M.;
Lee, J. B.; Matough, M. F. S. J. Chem. Soc., Chem. Commun.
1968, 1350–1351. (d) Boigegrain, R.; Castrol, B.; Selve, C.
Tetrahedron Lett. 1975, 16, 2529–2530. (e) Appel, R.;
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406–409.
10. The crystal data of 5d has been deposited in CCDC with
number 283183. Empirical formula: C10H9NOCl2; formula
weight: 230.08; crystal size: 0.508!0.472!0.080; crystal
color, habit: colorless, prismatic; crystal system: monoclinic;
˚
lattice type: primitive; lattice parameters: aZ5.4568(8) A,
˚
˚
bZ25.949(4) A, cZ7.5903(11) A, aZ908, bZ25.949(4)8,
3
˚
gZ908, VZ1048.2(3) A ; space group: P2(1)/c; ZZ4;
3. Tamura, K.; Mizukami, H.; Maeda, K.; Watanabe, H.;
Uneyama, K. J. Org. Chem. 1993, 58, 32–35.
4. Yang, Y.-H.; Shi, M. J. Org. Chem. 2005, 70, 8645–8648.
DcalcdZ1.458 g/cm3; F000Z472; R1Z0.0511, wR2Z0.1176.
Diffractometer: Rigaku AFC7R.
´
5. (a) Milewska, M. J.; Bytner, T.; Połonski, T. Synthesis 1996,
11. Wada, M.; Higashizaki, S.; Tsuboi, A. J. Chem. Res. Miniprint
1985, 467–490.
1485–1488. (b) Neurath, G. B. In Nicotine Related Alkaloids;
Gorrod, J. W., Ed.; Chapman: London, 1993; p 61. (c)
Cook, G. R.; Beholz, L. G.; Stille, J. R. J. Org. Chem. 1994, 59,
3575–3584.
12. Wasserman, H. H.; Vinick, F. J. J. Org. Chem. 1973, 38,
2407–2408.
13. de Raadt, A.; Griengl, H.; Petsch, M.; Plachota, P.; Schoo, N.;
Braunegg, G.; Weber, H.; Kopper, I.; Kreiner, M.; Zeiser, A.
Tetrahedron: Asymmetry 1996, 7, 473–490.
6. Zhang, H.-P.; Shigemori, H.; Ishibashi, M.; Kosaka, T.;
Pettit, G. R.; Kamano, Y.; Kobayashi, J. Tetrahedron 1994, 50,
10201–10206.
14. Reppe, V. W. Justus Liebigs Ann. Chem. 1955, 596, 206.