Syntheses of new benzoxazole derivatives

Article abstract of DOI:10.1002/jhet.623

2-(Arylidene)cyanomethylbenzoxazoles have been prepared in water from benzoxazole-2-ylacetonitriles. Using multi-component reactions, a variety of heterocycles containing benzoxazole and nitrile functionality has been prepared.

Full text of DOI:10.1002/jhet.623

1126
Syntheses of New Benzoxazole Derivatives
Chiraz Youssef,a Hamed Ben Ammar,a,b Mohamed Belhouchet,
Vol 48
a
*
Kassem Beydoun,c Ridha Ben Salem,a Henri Doucet,c* and Pierre H. Dixneufc
a
´
Laboratoires de Chimie Organique Physique et de l’Etat Solide, Faculte des Sciences de Sfax,
3038 Sfax, Tunisia
b
c
´
´
`
`
Laboratoire de Chimie Organique Appliquee, Faculte des Sciences de Gabes, 6072 Gabes, Tunisia
´
´
Catalyse et Organometalliques UMR 6226: CNRS-Universite de Rennes 1, Sciences Chimiques de Rennes,
Campus de Beaulieu, 35042 Rennes, France
*E-mail: hamed_benammar@yahoo.fr or henri.doucet@univ-rennes1.fr
Received June 17, 2010
DOI 10.1002/jhet.623
Published online 7 June 2011 in Wiley Online Library (wileyonlinelibrary.com).
2-(Arylidene)cyanomethylbenzoxazoles have been prepared in water from benzoxazole-2-ylacetoni-
triles. Using multi-component reactions, a variety of heterocycles containing benzoxazole and nitrile
functionality has been prepared.
J. Heterocyclic Chem., 48, 1126 (2011).
complete reduction of the nitrile groups into primary
amines [21], thus these catalysts offer to nitrile contain-
ing heterocycles new applications as polydentate ligands
with mixed coordinating-basic properties. These new
catalytic transformations motivate that the benzoxazole
syntheses can be revisited adopting greener processes.
The arylidene benzoxazole synthesis usually results
from the classical Knoevenagel condensation which is
currently performed in organic solvents, in the presence
of a catalyst such as amines [22], Lewis acids [23], or
even ionic liquids [24]. Recently, 2-benzoxazolyl aceto-
nitrile was reacted with aromatic aldehydes in the pres-
ence of a catalytic amount of benzyldimethylamine to
open an easy route to a,b-unsaturated a-oxazolines con-
taining a nitrile function [16].
INTRODUCTION
Molecules containing the benzoxazole moiety constitute
a large family of heterocycles offering a range of biological
and pharmacological activities [1–4] such as anti-tumoral
[5,6], anticancer [7], antiviral [8,9], or antimicrobial
[10,11] properties. They also lead to industrial applications
in the field of textiles [12], dyes [13], and pigments [14].
Benzoxazoles offer a versatile reactivity and can be
used as starting materials in heterocyclic compound syn-
theses, especially those containing an activated methylene
group that can take part in condensation reactions [15]. In
addition, the arylidene benzoxazoles containing an acti-
vated methylene linked to the reactive nitrile group, are
frequently used in organic synthesis [16], as reactive pre-
cursors. They are currently used for their analgesic [17],
insecticide, fungicide and nematicide [18] properties and
as topo-isomerase I inhibitor [19,20].
The interest, especially for environmental reasons and
costs, of decreasing the use of organic solvents in syn-
thesis and to develop new processes such as multi-com-
ponent reactions (MCR) led us to adapt the previous
synthesis of 2-benzoxazolyl acetonitrile for the
Recently, new soluble metal catalysts have been
revealed as powerful hydrogenation catalysts for the
C
V
2011 HeteroCorporation

September 2011
Syntheses of New Benzoxazole Derivatives
1127
Scheme 1. Synthesis of benoxazoles 3a–g.
1
production of a,b-unsaturated a-oxazolines in water for
the production of polycyclic benzoxazole derivatives.
We now report the preparation of a variety benzoxa-
zole containing heterocycles from a,b-unsaturated a-
oxazolines and their one pot MCR synthesis directly
from 2-benzoxazolyl acetonitrile, an aromatic aldehyde
and an activated nitrile.
5 and 6 were confirmed by infrared (IR), H-NMR, 13C-
1
NMR, and high-resolution mass spectroscopy. H-NMR
spectra of 5a–g present a characteristic singlet at d
4.61–4.73 ppm (pyrido proton). For compounds 6a–g,
this typical pyrido proton was observed as a singlet at
1
d ¼ 5.09–5.38 ppm in H-NMR.
After the preparation of compounds 5 via heterocycles
3, the synthesis of heterocycles 5 has been attempted by
a one-pot three-components reaction directly from 1a or
1b, the arylaldehyde 2 and malononitrile 4 without the
isolation of the intermediate 3 (method B) (Scheme 3).
In each case, the heterocycles 5b (68%), 5e (63%), and
5f (70%) were obtained in better yields than by the two
step reaction (method A) for which 51, 45, 53% yields
were obtained, respectively. Similarly, the benzoxazole
1 was reacted with half an equivalent of the arylalde-
hyde 2 in dry ethanol in the presence of AcONH4 and
piperidine at reflux for 2 h. The heterocycles 6 were
directly obtained in better 52–75% yields than in the
two step procedure (method A 30–63%). Thus, the
direct three-component reaction has an obvious advant-
age with respect to the two steps reaction for the sim-
plicity and yields.
RESULTS AND DISCUSSION
The synthesis of 2-benzoxazolyl acetonitriles 1a and 1b
has first been performed using the literature process [25].
These benzoxazoles are insoluble in water, but the addition
of K2CO3 increases their water solubility and catalyses the
condensation with a variety of aromatic aldehydes 2a–f.
The reaction was completed at room temperature for less
than 10 minutes. The derivatives 3a–g were obtained in
good yields (81–95%) (Scheme 1). The 1H-NMR spectrum
showed the presence of only one stereoisomer with a sin-
glet at 8.26–8.31 for the CH¼¼C proton.
The X-ray diffraction study of compound 3g con-
firmed the product structure. It showed that the flat ben-
zoxazole and phenyl moieties are not coplanar to each
other. It established that the cyano group and benzoxa-
zole nitrogen are in the cisoid positions (Fig. 1).
These 2-arylidene cyanomethylbenzoxazoles 3 were
used as starting materials for the access to new polycy-
clic heterocycles containing the benzoxazole moiety
(Scheme 2). Heating of the derivatives 3 at 50ꢀC for 30
min with malononitrile 4 in dry ethanol in the presence
of piperidine, gave 5b, 5e, and 5f in 45–53% (method
A) [26,27]. Similarly, the 2-benzoxazolyl acetonitrile 1
on reaction with the benzoxazoles 3 led to heterocycles
6 in up to 63% yields. The structures of the compounds
Figure 1. ORTEP of derivative 3g.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1128
C. Youssef, H. Ben Ammar, M. Belhouchet, K. Beydoun, R. Ben Salem, H. Doucer,
and P. H. Dixneuf
Vol 48
Scheme 2. Synthesis of heterocycles 5 and 6 using method A.
EXPERIMENTAL
CONCLUSION
1H and 13C-NMR spectra were recorded on a AC 300 FT
Bruker instrument (1H: 300 MHz, 13C: 75 MHz) and refer-
enced internally to tetramethylsilane. IR spectra were recorded
with a Perkin Elmer 298 spectrometer.
Preparation of 2-(arylidene)cyanomethylbenzoxazoles
3. To a stirred solution of 2-cyanomethylbenzoxazole 1a (0.158
g, 1 mmol) and K2CO3 (0.069 g, 0.5 mmol) in water (10 mL), the
appropriate aldehyde 2 (1 mmol) was added. The reaction mixture
was stirred at room temperature for 2–10 min during which time
yellow crystals appeared. The crystalline product was filtered,
washed with ethanol, dried and recrystallized in the appropriate
solvent. The crystals were filtrated and dried under vacuum to
give the derivatives 3a–g in 81–95% yields.
The above syntheses show a direct access to a vari-
ety of benzoxazole derivatives containing nitrile func-
tionalities via reaction in water. Multicomponent reac-
tions using aldehydes, benzoxazole acetonitriles and
for some reactions malononitrile has been found to
give good yields of heterocycles 5 and 6. These sub-
strates offer potential especially in catalytic hydrogen-
ation of the nitrile functionalities for the preparation
of amine derivatives that we are now exploring. The
use of a chiral base, through organocatalysis, might
also allow to control the stereogenic centre of these
products [28].
Scheme 3. Synthesis of heterocycles 5 and 6 using method B.
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Syntheses of New Benzoxazole Derivatives
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thylbenzoxazole 3 (1 mmol) was added and the mixture was
stirred at 50ꢀC for 30 min. The formed crystalline product was fil-
tered, washed with ethanol, and recrystallized from the appropri-
ate solvent.
Spectroscopic data of products 3a–3g. The nucleus were
numbered as in the X-ray structure (ORTEP) of 3g (Fig 1).
IR of compounds 3. m(cmꢁ1): 2230–2223 (CN), 1588–1574
(C¼¼N), 1513–1502 (C¼¼C).
(E)-2-(Benzoxazole-2-yl)-3-phenylacrylonitrile: 3a [29]. Yield:
85% Recrystallization in ethanol.
Synthesis of heterocycles 5 via method B (Scheme 3). To a solu-
tion of 2-cyanomethylbenzoxazole 1a (0.158 g, 1 mmol), ammo-
nium acetate (0.5 mmol) and piperidine (0.5 mL) in absolute ethanol
(10 mL), the appropriate aldehyde 2 (1 mmol) and malononitrile 4
(0.066 g, 1 mmol) were added. The reaction was stirred under reflux
for 2 h. The formed crystalline products 5 were filtered, washed
with ethanol, and recrystallized from the appropriate solvent.
Synthesis of heterocycles 6 via method B (Scheme 3). To a so-
lution of 2-cyanomethylbenzoxazole 1a (0.316 g, 2 mmol),
ammonium acetate (0.5 mmol) and piperidine (0.5 mL) in
absolute ethanol (10 mL), the appropriate aldehyde 2 (1
mmol) was added. The reaction was stirred at reflux from 2 h.
The formed crystals of heterocycles 6 were filtered, washed
with ethanol and recrystallized from the appropriate solvent.
4-Amino-2-(4-chlorophenyl)-7-methyl-2H-9-oxa-4a-aza-flu-
orene-1,3-dicarbonitrile: 5b. Method A: Yield: 51%, Method B:
Yield: 68%, Recrystallization in ethanol/dioxane.
1H-NMR (CDCl3, 300 MHz): d 7.36–7.41 (m, 2H, CHar),
7.43–7.60 (m, 4H, CHar), 7.77–7.82 (m, 1H, CHar), 8.03–8.06
(m, 2H, CHar), 8.32 (s, 1H, CH¼¼C).
(E)-2-(Benzoxazole-2-yl)-3-(4-chlorophenyl)acrylonitrile: 3b
[29]. Yield: 81% Recrystallization in ethanol.
1H-NMR (CDCl3, 300MHz): d 7.37–7.45 (m, 2H, CHar),
7.49–7.52 (m, 2H, CHar), 7.55–7.62 (m, 1H, CHar), 7.78–7.83
(m, 1H, CHar), 7.98–8.01 (m, 2H, CHar), 8.26 (s, 1H, CH¼¼C).
(E)-2-(Benzoxazole-2-yl)-3-(4-methoxyphenyl)acrylonitrile: 3c
[29]. Yield: 92% Recrystallization in ethanol/dioxane.
1H-NMR (CDCl3, 300 MHz): d 3.90 (s, 3H, OCH3), 7.10–
7.12 (m, 1H, CHar), 7.39–7.46 (m, 3H, CHar), 7.55–7.69 (m,
2H, CHar), 7.79–7.82 (m, 3H, CHar), 8.31 (s, 1H, CH¼¼C).
(E)-2-(Benzoxazole-2-yl)-3-(3-chlorophenyl)acrylonitrile: 3d. Yield:
93% Recrystallization in ethanol/dioxane.
1H-NMR (CDCl3, 300 MHz): d 7.36–7.49 (m, 5H, CHar),
7.51–7.63 (m, 1H, CHar), 7.79–7.85 (m, 1H, CHar), 8.29–8.34
(m, 1H, CHar), 8.69 (s, 1H, CH¼¼C). 13C-NMR (CDCl3, 75
MHz): d 102.5 (C9), 114.4 (C10), 110.8, 120.9, 125.4 and
126.6 (C1, C4, C5 and C6), 127.5, 129.6, 130.3 and 133.2 (C13,
C15, C16 and C17), 130.4 (C14), 136.0 and 141.6 (C5 and C6)
and 150.8 (C11), 144.9 (C12), 158.4 (C8).
1H-NMR (DMSO, 300 MHz): d 2.35 (s, 3H), 4.68 (s, 1H),
6.55 (s, 2H), 7.02 (d, J ¼ 8.1 Hz, 1H), 7.33 (d, J ¼ 8.1 Hz,
1H), 7.39 (d, J ¼ 8.4 Hz, 2H), 7.42 (d, J ¼ 8.4 Hz, 2H), 7.57
(s, 1H). 13C-NMR (DMSO, 75 MHz): d 39.9, 60.1, 64.4,
110.4, 113.2, 116.6, 119.2, 124.3, 124.6, 127.4, 128.8, 129.5,
130.5, 132.3, 142.7, 146.3, 147.6, 156.6. MS (m/z) 383.0670
(MþNa).
4-Amino-2-(3-methoxyphenyl)-2H-9-oxa-4a-aza-fluorene-
1,3-dicarbonitrile: 5e. Method A: Yield: 45%, Method B:
Yield: 63%, Recrystallization in dioxane.
(E)-2-(Benzoxazole-2-yl)-3-(3-methoxyphenyl)acrylonitrile:
3e. Yield: 95% Recrystallization in ethanol/dioxane.
1H-NMR (CDCl3, 300 MHz): d 3.90 (s, 3H, OCH3), 7.09–
7.12 (m, 1H, CHar), 7.37–7.46 (m, 3H, CHar), 7.55–7.60 (m, 2H,
CHar), 7.68 (s, 1H, CHar), 7.79–7.82 (m, 1H, CHar), 8.29 (s, 1H,
CH¼¼C). 13C-NMR (CDCl3, 75 MHz): d 55.5 (OCH3), 99.4
(C9), 115.0 (C10), 110.7, 119.7, 125.3 and 126.3 ( C1, C4, C5 and
C6), 113.9; 120.7, 123.8 and 130.5 (C13, C14, C15 and C17),
133.3, 141.6 and 149.4 (C2, C3, C12 and C16), 150.7 (C11), 160.0
(C8).
1H-NMR (DMSO, 300 MHz): d 3.75 (s, 3H, OMe), 4.63 (s,
1H, H-pyrido), 6.50–6.55 (m, 2H), 6.80–7.00 (m, 4H), 7.10–7.35
(m, 3H), 7.48 (d, J ¼ 6.8 Hz, 1H), 7.70 (d, J ¼ 6.8 Hz, 1H). 13C-
NMR (DMSO, 75 MHz): d 55.1, 60.3, 64.7, 110.3, 112.5, 113.1,
113.4, 116.7, 119.2, 119.6, 124.2, 124.5, 125.3, 127.4, 129.9,
145.2, 146.2, 147.4, 156.4, 159.5. MS (m/z) 365.1006 (MþNa).
4-Amino-2-(3-nitrophenyl)-2H-9-oxa-4a-aza-fluorene-1,3-
dicarbonitrile: 5f. Method A: Yield: 53%, Method B: Yield:
70%, Recrystallization in dioxane.
(E)-2-(Benzoxazole-2-yl)-3-(3-nitrophenyl)acrylonitrile: 3f. Yield:
88% Recrystallization in ethanol.
1H-NMR (DMSO, 500 MHz): d 5.00 (s, 1H), 6.67 (s, 2H),
7.20–7.30 (m, 2H), 7.49 (d, J ¼ 7.3 Hz, 1H), 7.71 (t, J ¼ 8.0
Hz, 1H), 7.76 (d, J ¼ 8.0 Hz, 1H), 7.95 (d, J ¼ 8.0 Hz, 1H),
8.19 (d, J ¼ 8.0 Hz, 1H), 8.30 (s, 1H). 13C-NMR (DMSO, 125
MHz): d 40.7, 59.9, 64.0, 110.8, 113.6, 117.0, 119.6, 122.6,
123.2, 124.8, 125.0, 127.9, 130.9, 135.0, 146.3, 146.8, 148.4,
148.6, 157.3. MS (m/z) 380.0756 (MþNa).
1H-NMR (CDCl3, 300 MHz): d: 7.38–7.53 (m, 4H, CHar),
7.55–7.58 (m, 1H, CHar), 7.60–7.64 (m, 1H, CHar), 7.80–7.84
(m, 1H, CHar), 8.31–8.34 (m, 1H, CHar), 8.71 (s, 1H, CH¼¼C).
13C-NMR (CDCl3, 75 MHz): d: 102.5 (C9), 114.4 (C10), 110.9,
120.9, 125.4 and 126.6 (C1, C4, C5 and C6), 127.6, 129.6, 130.4
and 133.3 (C13, C15, C16 and C17), 130.4 (C14), 136.0 and 141.6
(C5 and C6) and 150.8 (C11), 145.0 (C12), 158.4 (C8).
(E)-2-(6-Methylbenzoxazol-2-yl)-3-phenylacrylonitrile: 3g. Yield:
85% Recrystallization in ethanol.
4-Amino-3-benzoxazol-2-yl-2-phenyl-2H-9-oxa-4a-aza-fluo-
rene-1-carbonitrile: 6a. Method A: Yield: 30%, Method B:
Yield: 52%, Recrystallization in dioxane.
1H-NMR (CDCl3, 300 MHz): d 2.43 (s, 3H, CH3), 7.16 (d,
1H, J ¼ 8.1 Hz, CHar), 7.39 (d, 1H, J ¼ 8.4 Hz, CHar), 7.47–
7.51 (m, 4H, CHar), 7.97–8.00 (m, 2H, CHar), 8.18 (s, 1H,
CH¼¼C).
1H-NMR (DMSO, 300 MHz): d 5.10 (s, 1H, H-pyrido), 7.21
(t, 2H, J ¼ 7.8 Hz), 7.26–7.38 (m, 4H), 7.43 (d, 2H, J ¼ 8.2
Hz), 7.53 (d, 1H, J ¼ 8.2 Hz), 7.54 (d, 1H, J ¼ 8.2 Hz), 7.59
(d, 1H, J ¼ 8.2 Hz), 7.84 (d, 1H, J ¼ 8.2 Hz), 7.90 (s, 2H).
13C-NMR (DMSO, 75 MHz): d 30.6, 61.7, 78.7, 109.8, 110.5,
113.1, 117.0, 117.4, 123.3, 124.4, 124.5, 124.6, 126.7, 127.1,
127.4, 128.7, 141.0, 144.7, 145.2, 146.5, 148.1, 156.1, 164.1.
MS (m/z) 427.1165 (MþNa).
13C-NMR (CDCl3, 75 MHz): d 21.5 (C7), 99.4 (C9), 115.0
(C10), 110.1, 120.4 and 127.4 (C1, C4 and C5), 135.2 and
141.8 (C2 and C3), 129.4, 130.6, 132.8 (C13, C14, C15, C16 and
C17), 132.1 and 148.5 (C6 and C12), 148.9 (C11), 158.9 (C8).
Synthesis of heterocycles 5 and 6 via method A (Scheme
2). To a solution of 2-cyanomethylbenzoxazole 1a (0.158 g, 1
mmol) or malononitrile 4 (1 mmol) and piperidine (0.2 mL) in
absolute ethanol (10 mL), the appropriate 2-arylidene cyanome-
4-Amino-3-benzoxazol-2-yl-2-(4-methoxyphenyl)-2H-9-oxa-
4a-aza-fluorene-1-carbonitrile: 6c. Method A: Yield: 45%,
Method B: Yield: 65%, Recrystallization in DMF.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1130
C. Youssef, H. Ben Ammar, M. Belhouchet, K. Beydoun, R. Ben Salem, H. Doucer,
and P. H. Dixneuf
Vol 48
Table 1
1H-NMR (CDCl3, 300MHz): d 3.68 (s, 3H, OCH3), 5.10 (s,
1H, H-pyrido), 6.77 (d, 1H, J ¼ 8.1 Hz, CHar), 6.91–6.97 (m,
2H, CHar), 7.19–7.33 (m, 5H, CHar), 7.50–7.58 (m, 3H, CHar),
7.81 (d, 1H, J ¼ 7.8 Hz, CHar), 7.88 (brs, 2H, NH2). 13C-
NMR (CDCl3, 75 MHz) : d : 39.7, 54.8, 61.3, 78.4, 109.8,
110.4, 111.8, 112.9, 113.0, 117.4, 118.8, 123.2, 124.4, 124.5,
129.8, 116.9, 127.3, 140.9, 144.7, 146.5, 146.6, 148.0, 156.1,
159.3, 164.0. MS (m/z) 457.1270 (MþNa).
X-ray data for 3g [30].
Crystal data
Formula: C12H17N2O
Fw ¼ 260.29
F(000) ¼ 544
Calculated density:
1.306 g.cmꢁ3
Crystal system: monoclinic
Linear absorption
factor: l(MoKa) ¼
0.08 mmꢁ1
4-Amino-3-benzoxazol-2-yl-2-(3-nitrophenyl)-2H-9-oxa-4a-aza-
fluorene-1-carbonitrile: 6f. Method A: Yield: 57%, Method B:
Yield: 72%, Recrystallization in dioxane.
Space group: P21/c
˚
Morphology: block
Color: yellow
Crystal size (mm3):
0.32 ꢂ 0.22 ꢂ 0.15
a ¼ 11.0508(8) A
1H-NMR (CDCl3, 300 MHz): d 5.38 (s, 1H, H-pyrido), 7.16–
7.37 (m, 4H, CHar), 7.46–7.64 (m, 4H, CHar), 7.84 (d, 1H, J ¼
7.8 Hz, CHar), 7.94–7.98 (m, 3H, ANH2 and CHar), 8.06 (d, 1H,
J ¼ 8.10 Hz, CHar), 8.24 (s, 1H, CHar8). 13C-NMR (CDCl3, 75
MHz) : d : 39.7, 61.3, 77.4, 109.7, 110.4, 111.8, 112.9, 113.0,
117.9, 118.9, 123.2, 124.3, 124.5, 130.2, 116.9, 127.3, 140.6,
144.6, 146.7, 148.0, 156.3, 159.3, 163.7. MS (m/z) 472.1018
(MþNa).
˚
b ¼ 12.0159(10) A
˚
c ¼ 10.0074(9) A
b ¼ 94.761(5)ꢀ
3
˚
V ¼ 1324.25 (19) A ; Z ¼ 4
Data collection
Temperature 296(2) K
Diffractometer: Bruker
APEX-II area detector
Rint ¼ 0.033
Absorption correction:
multi-scan SADABS [33],
Tmin ¼ 0.978, Tmax ¼ 0.988
Number of scanned reflections:
15413
4-Amino-3-benzoxazol-2-yl-2-(3-methylphenyl)-2H-9-oxa-
4a-aza-fluorene-1-carbonitrile : 6h. Method A: Yield: 57%,
Method B: Yield: 71%, Recrystallization in dioxane.
Monochromator:
graphite plate
1H-NMR (DMSO, 300 MHz): d 7.88 (s, 2H), 7.84 (d, 1H, J
¼ 8.2 Hz), 7.56 (d, 1H, J ¼ 8.2 Hz), 7.49 (d, 1H, J ¼ 8.2
Hz), 7.46 (d, 1H, J ¼ 8.2 Hz), 7.36–7.15 (m, 6H), 7.11 (t, 1H,
J ¼ 7.8 Hz), 7.06 (t, 1H, J ¼ 7.8 Hz), 2.63 (s, 3H). 13C-NMR
(DMSO, 75 MHz): d 18.5, 35.1, 61.7, 79.3, 109.7, 110.4,
112.9, 116.9, 117.4, 123.2, 124.2, 124.3, 124.5, 126.7, 126.9,
127.4, 127.9, 129.9, 133.8, 140.9, 144.4, 144.6, 146.4, 147.9,
155.7, 164.1. MS (m/z) 441.1325 (MþNa).
Wavelength: MoKa
Number of independent
reflections: 4986
˚
¼ 0.71073 A
Scan mode: x/y
Number of observed reflections
(I > 2r(I)): 2755
Number of refined
y range: 2.5–33.2ꢀ
parameters: 181
Measurement area:
ꢁ16 ꢃ h ꢃ 16;
ꢁ18 ꢃ k ꢃ 17; ꢁ15 ꢃ l ꢃ 14
X-ray structure determination of benzoxazole 3g [30]. A
single crystal of the compound 3g with approximate dimen-
sions 0.32 ꢂ 0.22 ꢂ 0.15 mm3 was selected for lattice param-
eter determination and collection of intensity at 293(2) K,
using a Bruker APEX-II area-detector diffractometer with
Structure determination
Structure determination:
SHELXS97 [31]
Structure refinement
SHELXL97 [32]
wR2/R1: 0.141/0.052
˚
graphite monochromated MoKa radiation (k ¼ 0.71073 A).
Goodness-of-fit, S, on F2: S ¼ 1.02
Intensities were collected by x-2y scan technique. The struc-
ture was solved by direct methods (SHELXS-97) [31] and
refined with full-matrix least-squares technique (SHELXL-97)
[32]. The positions of all remaining non-H atoms were
obtained from successive Fourier syntheses. The positions of
hydrogen atoms for aromatic rings were calculated using ideal-
ized geometry. The parameters of the crystal, data collection,
and refinement are given in Table 1.
Final Fourierꢁr3esidual: min
ꢁ3
˚
˚
(ꢁ0.20 eA ), max (0.24 eA
)
1H-NMR (CDCl3, 300 MHz): d 3.68 (s, 3H, OCH3), 5.09 (s,
1H, H-pyrido), 6.75–6.78 (m, 1H, CHar), 6.91–6.96 (m, 2H,
CHar), 7.15–7.35 (m, 5H, CHar), 7.49–7.57 (m, 3H, CHar),
7.80–7.82 (m, 1H, CHar), 7.87 (brs, 2H, ANH2). 13C-NMR
(CDCl3, 75 MHz): d 39.7, 54.8, 61.3, 78.4, 109.8, 110.49,
111.8, 112.9, 113.0, 117.9, 118.9, 123.2, 124.3, 124.5, 129.8,
116.9, 127.3, 140.6, 144.6, 146.7, 148.0, 156.3, 159.3, 164.0.
4-Amino-3-benzoxazol-2-yl-2-(3-chlorophenyl)-2H-9-oxa-4a-aza-
fluorene-1-carbonitrile: 6d. Method A: Yield: 63%, Method B:
Yield: 75%, Recrystallization in dioxane.
REFERENCES AND NOTES
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Syntheses of New Benzoxazole Derivatives
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DOI 10.1002/jhet