New efficient synthesis of 5-ethoxyoxazoles and oxazolo[3,2-c]quinazolines via aza-Wittig reaction

Article abstract of DOI:10.1055/s-0028-1087562

5-Ethoxyoxazoles or 2-acylamino propanoates were synthesized by aza-Wittig reaction of iminophosphorane with acyl chloride in the presence of triethylamine. Reactions of 5-alkoxyoxazole with triphenyphosphine produced iminophosphoranes. A tandem aza-Wittig reaction of iminophosphorane with isocyanate or carbon disulfide generated oxazolo[3,2-c]quinazolines in satisfactory yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087562

LETTER
611
New Efficient Synthesis of 5-Ethoxyoxazoles and Oxazolo[3,2-c]quinazolines
via Aza-Wittig Reaction
S
ynthesis of 5-Eth
i
oxyoxa
a
z
oles and O
n
xazolo[3,2-
c
]quinaz
Y
olines u Huang, Yi-Bo Nie, Ming-Wu Ding*
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Central China Normal University,
Wuhan 430079, P. R. of China
Fax +86(27)67862041; E-mail: mwding@mail.ccnu.edu.cn
Received 23 October 2008
The easily accessible azides 1 reacted with triphenylphos-
Abstract: 5-Ethoxyoxazoles or 2-acylamino propanoates were syn-
thesized by aza-Wittig reaction of iminophosphorane with acyl
chloride in the presence of triethylamine. Reactions of 5-alkoxyox-
azole with triphenyphosphine produced iminophosphoranes. A tan-
phine to create the iminophosphoranes 2, which were al-
lowed to react with acyl chloride in the presence of
triethylamine at room temperature.11 4-Unsubstituted 5-
dem aza-Wittig reaction of iminophosphorane with isocyanate or alkoxyoxazoles 4 were obtained in good yields in case
when R1 group is H (Scheme 1, Table 1). The formation
of 5-alkoxyoxazoles 4 can be rationalized in terms of an
initial aza-Wittig reaction of iminophosphorane 2 with
acyl chloride to give intermediate imidoyl chloride 3,
which undergoes ring closure across the ester carbonyl
oxygen to give 4. The isolated yields of products 4 are re-
carbon disulfide generated oxazolo[3,2-c]quinazolines in satisfac-
tory yields.
Key words: oxazole, oxazolo[3,2-c]quinazoline, aza Wittig reac-
tion, carbodiimide, imidoyl chloride
Although the structure of the first oxazole was reported lated to the substituents of the benzene ring in acyl chlo-
over a century ago, the field of oxazoles continues to hold rides. Better yields are obtained with the meta- or para-
a center stage in organic synthesis. The structural diversi- substituted benzoyl chlorides (4b–g in Table 1), whereas
ty and complexity of naturally occurring oxazoles have moderate isolated yields are obtained with ortho-substi-
generated much interest in the development of mild meth- tuted benzoyl chlorides (4h,i in Table 1). This is probably
ods for their synthesis.1 There are many known methods due to the steric effect of the ortho-substituted benzoyl
for the synthesis of oxazoles, however, only a few were chlorides. When acetyl chloride was utilized, the product
known for the synthesis of 5-alkoxy-oxazoles which were (4a in Table 1) was obtained in moderate yield probably
used as important intermediates for the synthesis of some due to its instability. A CDCl3 sample of 4a was found to
natural products.2 For example, some 5-alkoxyoxazoles decompose after standing at room temperature for several
were prepared from the condensation of diazocarbonyl hours.
compounds with nitriles,3 acylation of ethyl isocyanoace-
tate,4 and cyclodehydration of 2-acylaminoacetates.5
R1
R1
R2COCl
Et3N
Ph3P
The aza-Wittig reactions of iminophosphoranes have re-
ceived increased attention in view of their utility in the
synthesis of nitrogen-containing heterocyclic com-
pounds.6 It has been used by several groups to prepare ox-
azoles. For example, Eguchi and co-workers developed a
general synthesis of a variety of oxazoles by intramolecu-
lar aza-Wittig reaction.7 Molina and co-workers em-
ployed iminophosphoranes derived from a-azidoketones
in their one-step synthesis of oxazole alkaloids.8 Zbiral
and co-workers have also obtained several 5-alkoxy-
oxazoles by this method, albeit in inferior yields.9 Recent-
ly, we are interested in the synthesis of quinazolinones,
N3
COOEt
Ph3P
N
COOEt
2
1
R1
R1
R1
R2
R2
Cl
N
OEt
OEt
+
N
N
R2
OEt
H
O
O
O
O
5
4
3
Scheme 1 Synthesis of 5-ethoxyoxazoles 4 and 2-acylamino pro-
panoates 5 via aza-Wittig reaction
thienopyrimidinones, and imidazolinones via aza-Wittig It is noteworthy that only 2-acylaminopropanoates 5 were
reaction, with the aim of evaluating their fungicidal activ- produced instead if R1 was a methyl group when the reac-
ities.10 Here we wish to report an efficient synthesis of 5- tion was carried out at room temperature (Scheme 1, 5a–
ethoxy substituted oxazoles and oxazolo[3,2-c]quinazo- c in Table 1). In this case the intermediate 3 did not cy-
lines via aza-Wittig reaction.
clize but instead hydrolyzed to give compound 5 during
workup. However, at elevated temperature, 3 cyclized to
give 4-methyl-5-ethoxyoxazoles 4 in 25–34% yields to-
gether with 5 in 33–37% yields (4j–l, 5a–c in Table 1).
Zbiral and co-workers also prepared 2-phenyl-4-methyl-
5-methoxyoxazole in 25% yield starting from methyl 2-
azidopropionate at room temperarature.9 It was obvious
SYNLETT 2009, No. 4, pp 0611–0614
Advanced online publication: 16.02.2009
DOI: 10.1055/s-0028-1087562; Art ID: W17008ST
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x.
2
0
0
9

612
N.-Y. Huang et al.
LETTER
PPh3
N
that the cyclization of intermediate of 3 to 4 was quite sen-
sitive to steric effects of the substituents.
N3
N
N
Ph3P
CS2
OEt
OEt
The obtained 5-alkoxyoxazole 4i was further treated with
triphenylphosphine, and the iminophosphorane 6 was ob-
tained in high yield via Staudinger reaction (Scheme 2).12
O
O
4i
6
ArNCO
Table 1 Synthesis of Compounds 4 and 5
NAr
S
Product
4a
4b
4c
R1
H
R2
Yield (%)
51
C
C
N
N
Me
N
N
OEt
OEt
H
Ph
80
O
O
H
4-ClC6H4
4-FC6H4
4-MeC6H4
4-MeOC6H4
3-ClC6H4
2-FC6H4
2-N3C6H4
Ph
93
7
9
4d
4e
H
94
NAr
N
H
72
S
N
N
4f
H
80
N
OEt
OEt
4g
4h
4i
H
87
O
O
8
H
55
10
H
52
Scheme 2 Synthesis of oxazolo[3,2-c]quinazolines 8 and 10 via
aza-Wittig reaction
4j
Me
Me
Me
Me
Me
Me
25b
28b
Table 2 Synthesis of Compounds 8 and 10
4k
4l
4-MeC6H4
4-ClC6H4
Ph
34b
Product
8a
Ar
Yield (%)
5a
5b
5c
65,a 35b
71,a 37b
75,a 33b
Ph
73
77
83
76
86
4-MeC6H4
4-ClC6H4
8b
3-MeC6H4
4-ClC6H4
4-FC6H4
–
8c
a Carried out at r.t. in CH2Cl2.
b Carried out at 60 °C in MeCN.
8d
10
When solutions of iminophosphoranes 6 in dry methylene
chloride were treated with aromatic isocyanate at room
temperature, the color of the reaction mixture quickly
turned red, and oxazolo[3,2-c]quinazolines 8 were isolat-
ed as red crystalline solids in good yields (Scheme 2,
Table 2).13 Compounds 8 are stable enough when treated
with hydrogen chloride or sodium hydroxide solution at
room temperature. Presumably, the conversion of 6 into 8
involves initial aza-Wittig reaction between the imino-
phosphorane 6 and the isocyanate to give a carbodiimide
7 as a highly reactive intermediate, which easily under-
goes ring closure to give the oxazolo[3,2-c]quinazolines
8. It is noteworthy that the reaction could be easily carried
out at room temperature under mild neutral conditions.
In summary, we have developed an efficient synthesis of
4-unsubstituted 5-ethoxyoxazoles and oxazolo[3,2-
c]quinazolines via aza-Wittig reactions. This method uti-
lizes easily accessible starting materials and allows mild
reaction conditions, straightforward product isolation, and
good yields. The synthetic approach discussed here in
many cases favorably compares with other existing
methods3–5 which either require special reagents or are
carried out under harsh reaction conditions.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Iminophosphoranes 6 also reacted with carbon disulfide
in refluxing acetonitrile to give yellow oxazolo[3,2-
c]quinazolines 10 in good yields (Scheme 2, Table 2).14
The formation of 10 can be viewed as an initial aza-Wittig
reaction between the iminophosphorane 6 and carbon di-
sulfide affording the intermediate isothiocyanate 9 which
undergoes cyclization to give 10.
Acknowledgment
We greatly acknowledge financial support of this work from the
National Natural Science Foundation of China (No. 20772041), and
the Key Project of Chinese Ministry of Education (No. 107082).
Synlett 2009, No. 4, 611–614 © Thieme Stuttgart · New York

LETTER
Synthesis of 5-Ethoxyoxazoles and Oxazolo[3,2-c]quinazolines
613
13C NMR (100 MHz, CDCl3): d = 164.1, 161.7, 159.4,
151.0, 126.9, 126.5, 123.6, 115.5, 115.3, 115.2, 114.9,
References and Notes
(1) (a) Palmer, D. C.; Venkatraman, S. Oxazoles: Synthesis,
Reactions, and Spectroscopy, Part A; John Wiley: New
York, 2003, 1–390. (b) Wasserman, H. H.; McCarthy, K. E.;
Prowse, K. S. Chem. Rev. 1986, 86, 845. (c) Hartner, F. W.
In Comprehensive Heterocyclic Chemistry II, Vol. 3;
Shinkai, I., Ed.; Pergamon: Oxford UK, 1996, 262–318.
(2) Jacobi, P. A.; Lee, K. J. Am. Chem. Soc. 1997, 119, 3409.
(3) (a) Doyle, K. J.; Moody, C. J. Tetrahedron 1994, 50, 3761.
(b) Moody, C. J.; Bagley, M. C. Synlett 1998, 361.
(c) Ducept, P. C.; Marsden, S. P. Synlett 2000, 692.
(4) (a) Huang, W.-S.; Zhang, Y.-X.; Yuan, C.-Y. Synth.
Commun. 1996, 26, 1149. (b) Bossio, R.; Marcaccini, S.;
Pepino, R. Heterocycles 1986, 24, 2003.
(5) (a) Jacobi, P. A.; Kaczmarek, C. S. R.; Udodong, U. E. S.
Tetrahedron 1987, 43, 5475. (b) Nahm, S.; Weinreb, S. M.
Tetrahedron Lett. 1981, 22, 3815. (c) Collins, D. J.;
Hughes, T. C.; Johnson, W. M. Aust. J. Chem. 1996, 49, 463.
(6) (a) Chan, J.; Faul, M. Tetrahedron Lett. 2006, 47, 3361.
(b) Palacios, F.; Herran, E.; Alonso, C.; Rubiales, G.; Lecea,
B.; Ayerbe, M.; Cossio, F. P. J. Org. Chem. 2006, 71, 6020.
(c) Lertpibulpanya, D.; Marsden, S. P.; Rodriguez-Garcia, I.;
Kilner, C. A. Angew. Chem. Int. Ed. 2006, 45, 5000.
(d) Palacios, F.; Alonso, C.; Aparicio, D.; Rubiales, G.;
Santos, J. M. Tetrahedron 2007, 63, 523. (e) Zanatta, N.;
Schneider, J. M. F. M.; Schneider, P. H.; Wouters, A. D.;
Bonacorso, H. G.; Martins, M. A. P.; Wessjohann, L. A.
J. Org. Chem. 2006, 71, 6996.
100.1, 99.7, 67.7, 67.4, 67.2, 13.9, 13.8. MS: m/z (%) = 207
(71) [M+], 178 (45), 151 (36), 134 (17), 123 (100), 107 (25).
Anal. Calcd for C11H10FNO2: C, 63.76; H, 4.86; N, 6.76.
Found: C, 63.50; H, 4.98; N, 6.71.
Compound 4e: white solid, mp 46–47 °C. IR (KBr): 1613,
1503, 1279, 1099, 1046, 1008 cm–1. 1H NMR (400 MHz,
CDCl3): d = 7.81–7.21 (m, 4 H, ArH), 6.18 (s, 1 H, ArH),
4.16 (q, J = 7.2 Hz, 2 H, OCH2), 2.37 (s, 3 H, CH3), 1.45 (t,
J = 7.2 Hz, 3 H, CH3). 13C NMR (100 MHz, CDCl3):
d = 159.4, 152.7, 139.5, 129.3, 129.2, 125.2, 125.0, 124.8,
100.4, 100.1, 67.9, 21.4, 21.2, 14.5, 14.3. MS: m/z (%) = 203
(14) [M+], 174 (5), 147 (13), 119 (100), 91 (20). Anal. Calcd
for C12H13NO2: C, 70.92; H, 6.45; N, 6.89. Found: C, 70.80;
H, 6.60; N, 6.76.
Compound 4f: white solid, mp 51–52 °C. IR (KBr): 1616,
1506, 1254, 1024 cm–1. 1H NMR (400 MHz, CDCl3):
d = 7.84 (d, J = 8.8 Hz, 2 H, ArH), 6.91 (d, J = 8.8 Hz, 2 H,
ArH), 6.15 (s, 1 H, ArH), 4.10 (q, J = 7.2 Hz, 2 H, OCH2),
3.78 (s, 3 H, OCH3), 1.41 (t, J = 7.2 Hz, 3 H, CH3). 13C NMR
(100 MHz, CDCl3): d = 160.3, 159.1, 152.2, 126.5, 120.1,
113.7, 99.9, 67.6, 54.8, 14.1. MS: m/z (%) = 219 (24) [M+],
190 (20), 163 (3), 135 (100), 118 (3), 107 (6). Anal. Calcd
for C12H13NO3: C, 65.74; H, 5.98; N, 6.39. Found: C, 65.67;
H, 6.05; N, 6.44.
Compound 4g: white solid, mp 50–51 °C. IR (KBr): 1601,
1556, 1481, 1282, 1043, 1005 cm–1. 1H NMR (400 MHz,
CDCl3): d = 7.86–7.28 (m, 4 H, ArH), 6.18 (s, 1 H, ArH),
4.13 (q, J = 7.0 Hz, 2 H, OCH2), 1.42 (t, J = 7.0 Hz, 3 H,
CH3). 13C NMR (100 MHz, CDCl3): d = 159.7, 150.6, 134.4,
129.7, 129.0, 124.9, 122.9, 100.6, 67.8, 14.2. MS: m/z
(%) = 223 (19) [M+], 195 (22), 167 (16), 139 (100). Anal.
Calcd for C11H10ClNO2: C, 59.07; H, 4.51; N, 6.26. Found:
C, 59.19; H, 4.70; N, 6.32.
(7) Takeuchi, H.; Yanagida, S.; Ozaki, T.; Hagiwara, S.; Eguchi,
S. J. Org. Chem. 1989, 54, 431.
(8) Molina, P.; Fresneda, P. M.; Almendros, P. Heterocycles
1993, 36, 2255.
(9) Zbiral, E.; Bauer, E.; Stroh, J. Monatsh. Chem. 1971, 102,
168.
(10) (a) Ding, M. W.; Xu, S. Z.; Zhao, J. F. J. Org. Chem. 2004,
69, 8366. (b) Zhao, J. F.; Xie, C.; Xu, S. Z.; Ding, M. W.;
Xiao, W. J. Org. Biomol. Chem. 2006, 4, 130. (c) Yuan,
J. Z.; Fu, B. Q.; Ding, M. W.; Yang, G. F. Eur. J. Org. Chem.
2006, 4170. (d) Ding, M. W.; Fu, B. Q.; Cheng, L. Synthesis
2004, 1067. (e) Li, H. X.; Xie, C.; Ding, M. W.; Liu, Z. M.;
Yang, G. F. Synlett 2007, 2280. (f) Liu, M. G.; Hu, Y. G.;
Ding, M. W. Tetrahedron 2008, 64, 9052.
(11) Oxazoles 4 and 2-Acylaminopropanoates 5
To a stirred solution of azide 1 (1.0 mmol) in CH2Cl2 (10
mL) was added a solution of Ph3P (0.26 g, 1 mmol) in dry
CH2Cl2 (5 mL) at r.t. After the reaction mixture was stirred
for 2 h, acyl chloride (1.0 mmol) and Et3N (0.30 g, 3.0
mmol) were added at r.t., and the color of the solution turned
yellow. After stirring for 4 h, the mixture was filtered to
remove the Et3NHCl, and the filtrate was evaporated under
reduced pressure. The crude product was purified by flash
chromatography (5:1, PE–Et2O) to yield oxazoles 4 or
2-acylaminopropanoates 5.
Compound 4h: white solid, mp 45–46 °C. IR (KBr): 1610,
1497, 1478, 1282, 1229, 1043, 1027 cm–1. 1H NMR (400
MHz, CDCl3): d = 7.91–7.11 (m, 4 H, ArH), 6.27 (s, 1 H,
ArH), 4.16 (q, J = 7.0 Hz, 2 H, OCH2), 1.43 (t, J = 7.0 Hz,
3 H, CH3). 13C NMR (100 MHz, CDCl3): d = 160.4, 159.6,
157.9, 148.3, 130.7, 130.6, 128.1, 123.9, 116.4, 116.2,
115.5, 115.4, 100.4, 67.7, 14.1. MS: m/z (%) = 207 (16)
[M+], 179 (13), 151 (6), 123 (100), 95 (22). Anal. Calcd for
C11H10FNO2: C, 63.76; H, 4.86; N, 6.76. Found: C, 63.70; H,
4.98; N, 6.83.
Compound 4i: light yellow solid, mp 52–54 °C. IR (KBr):
2130 (N3), 1610 (C=O), 1594, 1493, 1304, 1285, 1033, 1005
cm–1. 1H NMR (400 MHz, CDCl3): d = 7.88–7.17 (m, 4 H,
ArH), 6.28 (s, 1 H, ArH), 4.19 (q, J = 7.0 Hz, 2 H, OCH2),
1.47 (t, J = 7.0 Hz, 3 H, CH3). MS: m/z (%) = 230 (50) [M+],
202 (39), 173 (55), 145 (57), 118 (29), 90 (100). Anal. Calcd
for C11H10N4O2: C, 57.39; H, 4.38; N, 24.34. Found: C,
57.45; H, 4.50; N, 24.49.
Compound 4k: light yellow oil. 1H NMR (600 MHz,
CDCl3): d = 7.80–7.21 (m, 4 H, ArH), 4.22 (q, J = 7.0 Hz,
2 H, OCH2), 2.37 (s, 3 H, CH3), 2.11 (s, 3 H, CH3), 1.40 (t,
J = 7.2 Hz, 3 H, CH3). MS: m/z (%) = 217 (5) [M+], 136 (2),
119 (62), 91 (100).
Spectral Data for Some Unreported Compounds
Compound 4c: light yellow solid, mp 60–61 °C. IR (KBr):
1620, 1487, 1282, 1093, 1005 cm–1. 1H NMR (400 MHz,
CDCl3): d = 7.68–7.21 (m, 4 H, ArH), 6.05 (s, 1 H, ArH),
4.00 (q, J = 7.2 Hz, 2 H, OCH2), 1.30 (t, J = 7.0 Hz, 3 H,
CH3). 13C NMR (100 MHz, CDCl3): d = 159.5, 150.9, 134.8,
128.5, 128.4, 126.2, 125.9, 125.7, 100.3, 100.1, 67.6, 14.2,
14.0. MS: m/z (%) = 223 (90) [M+], 195 (73), 167 (23), 139
(100), 111 (64). Anal. Calcd. for C11H10ClNO2: C, 59.07; H,
4.51; N, 6.26. Found: C, 59.01; H, 4.61; N, 6.44.
Compound 4l: white solid, mp 83–85 °C. 1H NMR (600
MHz, CDCl3): d = 7.85–7.37 (m, 4 H, ArH), 4.23 (q, J = 7.2
Hz, 2 H, OCH2), 2.11 (s, 3 H, CH3), 1.40 (t, J = 7.2 Hz, 3 H,
CH3). MS: m/z (%) = 237 (75) [M+], 207 (13), 138 (100),
110 (43). Anal. Calcd for C12H12ClNO2: C, 60.64; H, 5.09;
N, 5.89. Found: C, 60.47; H, 5.24; N, 5.95.
Compound 4d: white solid, mp 52–54 °C. IR (KBr): 1613,
1503, 1282, 1222, 1046, 1008 cm–1. 1H NMR (400 MHz,
CDCl3): d = 7.91–7.07 (m, 4 H, ArH), 6.18 (s, 1 H, ArH),
4.20–4.13 (m, 2 H, OCH2), 1.48–1.43 (m, 3 H, CH3).
Compound 5a: white solid, mp 76–77 °C. IR (KBr): 3347
(NH), 1749 (C=O), 1642, 1528, 1493, 1213, 1181 cm–1. 1H
NMR (400 MHz, CDCl3): d = 7.82–7.42 (m, 5 H, ArH), 6.84
Synlett 2009, No. 4, 611–614 © Thieme Stuttgart · New York

614
N.-Y. Huang et al.
LETTER
(d, J = 6.4 Hz, 1 H, NH), 4.82–4.76 (m, 1 H, NCH), 4.24 (q,
J = 7.0 Hz, 2 H, OCH2), 1.52 (d, J = 6.8 Hz, 3 H, CH3), 1.31
(t, J = 7.2 Hz, 3 H, CH3). 13C NMR (100 MHz, CDCl3):
d = 173.2, 166.7, 133.9, 131.6, 128.5, 127.0, 61.6, 48.5,
18.6, 14.1. MS: m/z (%) = 221 (4) [M+], 148 (66), 105 (100),
77 (24). Anal. Calcd for C12H15NO3: C, 65.14; H, 6.83; N,
6.33. Found: C, 65.33; H, 6.98; N, 6.43.
Compound 5b: white solid, mp 117–118 °C. IR (KBr): 3290
(NH), 1742 (C=O), 1635, 1556, 1203, 1162, 1024 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.72–7.23 (m, 4 H, ArH),
6.75 (d, J = 6.8 Hz, 1 H, NH), 4.82–4.74 (m, 1 H, NCH),
4.24 (q, J = 7.2 Hz, 2 H, OCH2), 2.40 (s, 3 H, CH3), 1.52 (d,
J = 7.2 Hz, 3 H, CH3), 1.31 (t, J = 7.2 Hz, 3 H, CH3).
MS: m/z (%) = 235 (6) [M+], 162 (29), 119 (100), 91 (13).
Anal. Calcd for C13H17NO3: C, 66.36; H, 7.28; N, 5.95.
Found: C, 66.44; H, 7.40; N, 5.99.
Compound 5c: white solid, mp 98–99 °C. IR (KBr): 3293
(NH), 1742, 1626, 1544, 1487, 1216, 1166, 1093, 1017
cm–1. 1H NMR (400 MHz, CDCl3): d = 7.75 (d, J = 8.4 Hz,
2 H, ArH), 7.40 (d, J = 8.4 Hz, 2 H, ArH), 6.84 (br, 1 H, NH),
4.80–4.72 (m, 1 H, NCH), 4.25 (q, J = 7.2 Hz, 2 H, OCH2),
1.52 (d, J = 7.2 Hz, 3 H, CH3), 1.32 (t, J = 7.2 Hz, 3 H, CH3).
MS: m/z (%) = 255 (4) [M+], 182 (68), 139 (100), 111 (14).
Anal. Calcd for C13H17NO3: C, 56.37; H, 5.52; N, 5.48.
Found: C, 56.45; H, 5.78; N, 5.59.
CH3). 13C NMR (150 MHz, CDCl3): d = 157.5, 153.2, 150.8,
147.2, 143.4, 135.5, 129.1, 128.4, 125.6, 123.3, 121.7,
120.4, 102.7, 87.9, 70.5, 14.3. MS: m/z (%) = 305 (53) [M+],
248 (29), 231 (100), 205 (60), 166 (15), 104 (10), 90 (22).
Anal. Calcd for C18H15N3O2: C, 70.81; H, 4.95; N, 13.76.
Found: C, 70.90; H, 4.99; N, 13.91.
Compound 8b: red crystals, mp 105–107 °C. IR (KBr):
1765, 1689, 1639, 1605, 1471, 1442, 1219, 1165 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.62–6.78 (m, 9 H, ArH),
4.34 (q, J = 7.0 Hz, 2 H, OCH2), 2.35 (s, 3 H, CH3), 1.56 (t,
J = 7.0 Hz, 3 H, CH3). 13C NMR (150 MHz, CDCl3):
d = 157.4, 153.6, 150.8, 148.2, 143.6, 137.8, 135.3, 128.1,
125.4, 124.0, 122.2, 121.6, 120.3, 119.8, 102.3, 87.7, 70.3,
21.6, 14.2. MS: m/z (%) = 319 (6) [M+], 291 (100), 262 (13),
248 (46), 235 (28), 91 (5). Anal. Calcd for C19H17N3O2: C,
71.46; H, 5.37; N, 13.16. Found: C, 71.59; H, 5.50; N, 13.20.
Compound 8c: red crystals, mp 157 °C (dec.). IR (KBr):
1642, 1605, 1558, 1530, 1478, 1441, 1308, 1254, 1032
cm–1. 1H NMR (400 MHz, CDCl3): d = 7.64–6.92 (m, 9 H,
ArH), 4.33 (q, J = 7.2 Hz, 2 H, OCH2), 1.56 (t, J = 7.2 Hz,
3 H, CH3). 13C NMR (100 MHz, CDCl3): d = 157.6, 152.8,
150.6, 135.7, 129.9, 128.2, 128.1, 126.1, 125.5, 124.4,
121.7, 121.0, 102.9, 88.0, 70.6, 14.3. MS: m/z (%) = 339
(100) [M+], 311 (68), 265 (88), 255 (81), 230 (53), 192 (10),
125 (24). Anal. Calcd for C18H14ClN3O2: C, 63.63; H, 4.15;
N, 12.37. Found: C, 63.89; H, 4.22; N, 12.51.
(12) Iminophosphorane 6
To a stirred solution of 4i (1.15 g, 5 mmol) in CH2Cl2 (15
mL) was added a solution of Ph3P (1.31 g, 5 mmol) in dry
CH2Cl2 (10 mL). After the reaction mixture was stirred for 2
h, the solvent was removed under reduced pressure, and the
residue was recrystallized from Et2O and EtOH (1:1; v/v) to
give the iminophosphorane 6 (2.22 g, yield 96%); light
yellow crystals; mp 175–177 °C. IR (KBr): 1606, 1468,
1435, 1353, 1271, 1118, 1035cm–1. 1H NMR (400 MHz,
CDCl3): d = 7.86–6.53 (m, 19 H, ArH), 6.23 (s, 1 H, ArH),
4.14 (q, J = 7.0 Hz, 2 H, OCH2), 1.45 (t, J = 7.0 Hz, 3 H,
CH3). MS: m/z (%) = 464 (100) [M+], 435 (65), 380 (92),
277 (18), 261 (10), 201 (11), 183 (16), 145 (16). Anal. Calcd
for C29H25N2O2P: C, 74.99; H, 5.42; N, 6.03. Found: C,
74.77; H, 5.60; N, 6.12.
Compound 8d: red crystals, mp 156 °C (dec.). IR (KBr):
1665, 1644, 1610, 1562, 1485, 1441, 1308, 1207, 1032
cm–1. 1H NMR (400 MHz, CDCl3): d = 7.65–6.89 (m, 9 H,
ArH), 4.36 (q, J = 7.0 Hz, 2 H, OCH2), 1.57 (t, J = 7.0 Hz,
3 H, CH3). 13C NMR (100 MHz, CDCl3): d = 159.1, 157.4,
156.7, 153.7, 144.7, 143.8, 135.4, 125.3, 124.5, 124.5,
121.7, 119.8, 114.8, 114.6, 102.3, 87.6, 70.3, 14.3. MS:
m/z (%) = 323 (32) [M+], 295 (26), 266 (33), 250 (100), 239
(89), 223 (36), 125 (45). Anal. Calcd for C18H14FN3O2: C,
66.87; H, 4.36;N, 13.00. Found: C, 66.73; H, 4.54; N, 13.25.
(14) Oxazolo[3,2-c]quinazoline 10
To a solution of iminophosphorane 6 (0.46 g, 1 mmol) in
MeCN (10 mL) was added CS2 (1.50 g, 20 mmol). The
mixture was heated to reflux for 10 h, the solvent was
evaporated under reduced pressure, and the residue was
recrystallized from EtOH to give oxazolo[3,2-c]quinazoline
10; yellow crystals, mp 138–139 °C. IR (KBr): 1654, 1635,
1484, 1434, 1321, 1298, 1176, 1054 cm–1. 1H NMR (400
MHz, CDCl3): d = 7.94–7.38 (m, 5 H, ArH), 4.47 (q, J = 7.2
Hz, 2 H, OCH2), 1.61 (t, J = 7.2 Hz, 3 H, CH3). 13C NMR
(100 MHz, CDCl3): d = 157.4, 148.4, 138.4, 135.7, 128.2,
126.8, 125.0, 121.5, 115.5, 91.3, 71.0, 14.2. MS: m/z
(%) = 246 (37) [M+], 218 (25), 190 (28), 162 (100), 134 (34).
Anal. Calcd for C12H10N2O2S: C, 58.52; H, 4.09; N, 11.37.
Found: C, 58.59; H, 4.21; N, 11.41.
(13) Oxazolo[3,2-c]quinazolines 8
To a solution of iminophosphorane 6 (0.46 g, 1 mmol) in dry
CH2Cl2 (10 mL) was added aryl isocyanate (1 mmol) under
nitrogen at r.t. The solution turned red immediately. After
stirred for 1 h, the solvent was evaporated under reduced
pressure, and the residue was recrystallized from Et2O and
EtOH (1:1, v/v) to give oxazolo[3,2-c]quinazolines 8 as red
crystals.
Compound 8a: red crystals, mp 151 °C (dec.). IR (KBr):
1764, 1690, 1640, 1560, 1474, 1440, 1307, 1251 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.68–6.94 (m, 10 H, ArH),
4.39 (q, J = 7.0 Hz, 2 H, OCH2), 1.58 (t, J = 7.0 Hz, 3 H,
Synlett 2009, No. 4, 611–614 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.