An efficient potassium cyanide-promoted synthesis of 2-arylbenzoxazoles from [4.3.0]boron heterobicycles

Article abstract of DOI:10.1016/j.tetlet.2010.03.027

The 2-arylbenzoxazoles 3a-f were produced in moderate to excellent yields merely by stirring a potassium cyanide (3 equiv)-containing methanol solution of the borobicyclic compounds 1a-f at room temperature. These compounds were fully characterized spectroscopically [IR, ¹H, and ¹³C NMR and X-ray analysis (3a)] and by elemental analysis. Crown Copyright

Full text of DOI:10.1016/j.tetlet.2010.03.027

Tetrahedron Letters 51 (2010) 2633–2635
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Tetrahedron Letters
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An efficient potassium cyanide-promoted synthesis of 2-arylbenzoxazoles
from [4.3.0]boron heterobicycles
a
a
b
c
Heraclio López-Ruiz a, , Horacio Briseño-Ortega , Susana Rojas-Lima , Rosa Santillán , Norberto Farfán
*
a Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Hidalgo, Carretera Pachuca-Tulancingo Km 4.5, Ciudad Universitaria, 42184 Mineral de la Reforma, Mexico
b Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional Apto. Postal 14-740, 07000 México D.F., Mexico
c Departamento de Química Orgánica, Facultad de Química, Universidad Nacional Autónoma de México, Circuito Escolar, Ciudad Universitaria, 04510, México D.F., Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
The 2-arylbenzoxazoles 3a–f were produced in moderate to excellent yields merely by stirring a
potassium cyanide (3 equiv)-containing methanol solution of the borobicyclic compounds 1a–f at room
temperature. These compounds were fully characterized spectroscopically [IR, 1H, and 13C NMR and X-ray
analysis (3a)] and by elemental analysis.
Received 1 September 2009
Revised 5 March 2010
Accepted 8 March 2010
Available online 15 March 2010
Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
Keywords:
Schiff bases
Boronates
Potassium cyanide
2-Arylbenzoxazoles
NMR
There has been a recent surge in the development of new
benzoxazole syntheses because of their occurrence in a number
of natural products1, and their potential use as cytotoxic agents2,
In continuation of our recent studies involving the boron com-
plexes derived from Schiff bases,23,24 we reacted a methanolic
solution of the very readily available23–26 boron-containing hetero-
cyclic compound 1a (see Scheme 1 for synthesis) with excess
potassium cyanide at room temperature, with the expectation of
obtaining the tetracyclic nitrile 2a (Scheme 1). The only compound
isolated, however, from the reaction mixture was the 2-arylbenz-
oxazole derivative 3a (61 % yield). The 2-arylbenzoxazoles 3b–f
were similarly obtained from compounds 1b–f (See Scheme 2).
The structures of the benzoxazole derivatives were unequivocally
cathepsin
S
inhibitors3, HIV reverse transcriptase inhibitors4,
estrogen receptor agonists5, selective peroxisome proliferator-
activated receptor antagonists6, anticancer agents7, and orexin-1
receptor antagonists.8 They have also found application as herbi-
cides and as fluorescent-whitening agent dyes.9 The methods
which have been used to provide access to benzoxazoles include
(a) conventional thermal- or microwave-accelerated condensa-
tion of 2-aminophenols with carboxylic acid derivatives under
strongly acidic conditions,10 (b) metal-catalyzed cyclization of
2-halo N-acylanilines,11 and (c) oxidative cyclization of the Schiff
bases derived from 2-aminophenols and aldehydes using oxi-
dants
such
as
2,3-dichloro-5,6-dicyano-1,4-benzoquinone
(DDQ),12 PhI(OAc)2,13 NiO2,14 Ba(MnO4)2,15 pyridinium chloro-
chromate (PCC),16 Mn(OAc)3,17 PbO2,18 Pb(OAc)4,19 ThClO4,20
and Pd(OAc)2 (Fig. 1). In addition, oxidative cyclization condi-
21
tions considerably milder than those referred above have been
described for the generation of benzoxaxoles from the Schiff
bases derived from 2-aminophenols.22 Herein, we describe an
exceptionally mild method of generating benzoxazoles from the
boron-containing heterocyclic systems 1a–f.
* Corresponding author. Tel.: +52 7717172000x2209; fax: +52 7717172000x
6502.
E-mail addresses: heraclio@uaeh.edu.mx, heracliol@yahoo.com.mx (H. López-
Ruiz).
Figure 1. X-ray structure of 3a.
0040-4039/$ - see front matter Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.03.027

2634
H. López-Ruiz et al. / Tetrahedron Letters 51 (2010) 2633–2635
H3C
H
H3C
H
CN
O
N
7
7
N
B
3 eq. KCN
N
B
3 eq. KCN
Methanol, 4 h.
O
O
O
Methanol, 4 h.
O
OH
CH3
3a
2a
1a
Scheme 1.
R2
R1
O
R3
R2
7
R3
O
N
3 eq. KCN
N
B
Methanol, 4 h.
O
OH
R1
R1
R2
H
R3
H
H
H
H
H
a
b
c
d
CH3
3a-f
H
H
H
Cl
t-Bu
CH3
1a-f
e
f
H
H
H
H
NO2
Scheme 2.
A crystal suitable for X-ray diffraction was obtained for com-
pound 3a and the molecular structure is shown in Figure 2.28 The
existence of an intramolecular hydrogen bond between the pheno-
lic OH group and benzoxazole N-atom is consistent with the ob-
served N–HO(2) distance (2.66 Å) and the N–H-(O2) angle
(147.7°). The molecular packing reveals that interaction present
at the oxygen (O2) and hydrogen atoms (CH3) forms a dimeric
structure in the solid state (Fig. 2). The H3C-(O2) intermolecular
distance is 3.625 Å and the C(14)–H-(O2) angle is 172.8°, charac-
teristic of a weak intermolecular bond.
In conclusion, an efficient method for the synthesis of 2-aryl-
benzoxazoles has been developed from the [4.3.0] boron heterobi-
cyclic compounds 1a–f containing
a dative N–B bond. This
unprecedented reaction occurs rapidly at room temperature. Com-
pounds 3a–f were fully characterized by 1H and 13C NMR spectros-
copy and by X-ray analysis for 3a.
Acknowledgments
We are indebted to Dr. Joseph M. Muchowski for friendly, help-
ful discussions and to CONACyT for financial support (Grant
J49336-Q).
Figure 2. Dimeric structure for 3a formed by intermolecular hydrogen bonding.
References and notes
established by the usual spectroscopic means27, as well as by an X-
ray crystal structure for compound 3a (Fig. 2, vide infra).28 Thus,
the 1H NMR spectra of these compounds did not possess signals
for H-7 (8.29–8.46, see Scheme 1), but did show a low field absorp-
tion at d 11.2–11.58 typical of an H-bonded hydroxyl group (to the
C@N moiety; see also Fig. 2 below). In addition, the IR spectra
showed absorption bands at 1631–1627 cmꢀ1 (C@N) and 1591–
1557 cmꢀ1 (O–C@N moiety) which are characteristic of the
five-membered ring of benzoxazoles. Furthermore, the Raman
spectrum of compound 3e shows bands expected for both the
C@N (1630 cmꢀ1) and O–C@N (1551 cmꢀ1) groups.
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was purified by crystallization from methanol at 0 °C. The yields are those of
pure compounds. Compound 3a: mp 113–114 °C as a brown solid [lit.29 102 °C]
(yield: 0.22 g, 61%) IR (KBr):
m ;
max 3753, 2958, 1627, 1591, 1547, 751, 714 cmꢀ1
1H NMR (400 MHz, CDCl3):
d
11.58 (s, 1H, OH), 7.99 (dd, 1H, J = 7.6 Hz,
J = 1.4 Hz, H-3), 7.42 (t, 1H, J = 6.5 Hz, H-5), 7.40 (d, 1H, J = 7.7 Hz, H-50), 7.24 (t,
1H, J = 7.7 Hz, H-60), 7.15 (d, 1H, J = 7.3 Hz, H-70), 7.12 (d, 1H, J = 8.4 Hz, H-6),
6.99 (t, 1H, J = 7.5 Hz, H-4), 2.61 (s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d
162.2 (C-20), 158.6 (C-1), 148.8 (C-7a), 139.3 (C-3a), 133.4 (C-5), 129.8 (C-40),
127.0 (C-3), 125.5 (C-70), 125.1 (C-60), 119.5 (C-4), 117.3 (C-6), 110.7 (C-2),
107.9 (C-50), 16.5 (CH3) ppm. Anal. Calcd for C14H11NO2: C, 74.65; H, 4.92; N,
6.22. Found: C, 74.57; H, 4.91; N, 6.48%. For 3b: mp 146–147 °C as a purple
solid [lit.29 140 °C] (yield: 0.25 g, 69%) IR (KBr): mmax 3649, 3153, 1628, 1588,
7. Easmon, J.; Pürstinger, G.; Thies, K.-S.; Heinisch, G.; Hofmann, J. J. Med. Chem.
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1541, 1254, 855, 805, 755, 708 cmꢀ1 1H NMR (400 MHz, CDCl3): d 11.19 (s,
;
1H, OH), 7.95 (dd, 1H, J = 7.8 Hz, J = 1.6 Hz, H-3), 7.66 (d, 1H, J = 1.8 Hz, H-40),
7.48 (d, 1H, J = 8.8 Hz, H-70), 7.43 (ddd, 1H, J = 8.4 Hz, J = 6.9 Hz, J = 1.4 Hz, H-5),
7.31 (dd, 1H, J = 8.5 Hz, J = 2.0 Hz, H-60), 7.09 (dd, 1H, J = 8.4 Hz, J = 0.7 Hz, H-6),
6.98 (td, 1H, J = 7.5 Hz, J = 1.0 Hz, H-4) ppm. 13C NMR (100 MHz, CDCl3): d
164.2 (C-20), 158.9 (C-1), 147.7 (C-7a), 141.1 (C-3a), 134.0 (C-5), 130.5 (C-50),
127.2 (C-3), 125.6 (C-60), 119.7 (C-4), 119.2 (C-40), 117.6 (C-6), 111.3 (C-70),
110.1 (C-2) ppm. Anal. Calcd for C13H8ClNO2: C, 63.56; H, 3.28; N, 5.70. Found:
C, 62.75; H, 3.11; N, 5.41%. For 3c: mp 263–265 °C as a yellow solid (yield:
9. Leaver, I. H.; Milligam, B. Dyes Pigm. 1984, 5, 109–144.
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0.25 g, 67%) IR (KBr): m ;
max 3740, 2962, 2869, 1627, 1557, 1378, 830, 704 cmꢀ1
Anal. Calcd for C17H17NO2: C, 76.38; H, 6.41; N, 5.24. Found: C, 77.00; H, 6.04;
N, 5.33%. Due to insolubility in CDCl3, DMSO-d6, acetone-d6 etc., it was
impossible to obtain NMR data. For 3d: mp 136–137 °C as a orange solid [lit.30
128 °C] (yield: 0.25 g, 71%) IR (KBr): mmax 3648, 2966, 1631, 1590, 1543, 1256,
800, 755, 704 cmꢀ1 1H NMR (400 MHz, CDCl3): d 11.52 (s, 1H, OH), 7.98 (dd,
;
1H, J = 7.8 Hz, J = 1.6 Hz, H-3), 7.48 (d, 1H, J = 0.7 Hz, H-40), 7.44 (d, 1H,
J = 8.4 Hz, H-60), 7.42 (dd, 1H, J = 7.3 Hz, J = 1.4 Hz, H-5), 7.15 (d, 1H, J = 7.6 Hz,
H-70), 7.11 (d, 1H, J = 8.4 Hz, H-6), 6.99 (td, 1H, J = 8.0 Hz, J = 1.8 Hz, H-4), 2.47
(s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d 163.0 (C-20), 158.7 (C-1), 147.4
(C-7a), 140.2 (C-3a), 134.9 (C-50), 133.4 (C-5), 127.0 (C-3), 126.5 (C-70), 119.5
(C-4), 119.2 (C-60), 117.4 (C-6), 110.7 (C-2), 110.0 (C-40), 21.5 (CH3) ppm. Anal.
Calcd for C14H11NO2: C, 74.65; H, 4.92; N, 6.22. Found: C, 74.88; H, 4.79; N, 6.35
%. For 3e: mp 125–126 °C as a pink solid [lit.30 122–124 °C] (yield: 0.21 g, 61%)
IR (KBr): mmax 3527, 3029, 1630, 1587, 1487, 1259, 741, 705 cmꢀ1 1H NMR
;
(400 MHz, CDCl3): d 11.48 (s, 1H, OH), 8.01 (dd, 1H, J = 7.8 Hz, J = 1.6 Hz, H-3),
7.72–7.70 (m, 1H, H-50), 7.60–7.57 (m, 1H, H-60), 7.43 (td, 1H, J = 8.0 Hz,
J = 1.4 Hz, H-5), 7.38–7.35 (m, 2H, H-10, H-40), 7.12 (d, 1H, J = 8.4 Hz, H-6), 7.0
(td, 1H, J = 7.6 Hz, J = 0.9 Hz, H-4) ppm. 13C NMR (100 MHz, CDCl3): d 162.9 (C-
20), 158.8 (C-1), 149.1 (C-7a), 140.0 (C-3a), 133.6 (C-5), 127.1 (C-3), 125.4 (C-
70), 125.0 (C-40), 119.6 (C-4), 119.3 (C-50), 117.4 (C-6), 110.7 (C-60), 110.6 (C-2)
ppm. Anal. Calcd for C13H9NO2: C, 73.92; H, 4.29; N, 6.63. Found: C, 73.76; H,
4.21; N, 6.39%. For 3f: mp 186–189 °C as a yellow solid (yield: 0.34 g, 94%) IR
(KBr): mmax 3736, 3112, 1589, 1542, 757, 706, 546 cmꢀ1 1H NMR (400 MHz,
;
CDCl3): d 10.87 (s, 1H, OH), 8.70 (d, 1H, J = 2.4 Hz, H-70), 8.32 (dd, 1H, J = 2.4 Hz,
J = 8.7 Hz, H-50), 8.04–8.00 (m, 2H, H-40 y H-3), 7.57 (t, 1H, J = 6.8 Hz, H-5), 7.14
(d, 1H, J = 8.2 Hz, H-6), 7.10 (t, 1H, J = 8.3 Hz, H-4) ppm. 13C NMR (100 MHz,
CDCl3): d 167.0 (C-20), 158.7 (C-1), 149.0 (C-7a), 145.9 (C-3a), 145.4 (C-60),
135.5 (C-5), 129.2 (C-40), 121.6 (C-50), 120.6 (C-4), 119.9 (C-3), 118.0 (C-6),
110.8 (C-2), 108.0 (C-70). Anal. Calcd for C13H8N2O4: C, 60.94; H, 3.15; N, 10.93.
Found: C, 60.84; H, 1.04; N, 10.81%.
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28. Crystallographic data (excluding structure factors) for the structures in this
Letter have been deposited with the Cambridge Crystallographic Data Centre as
a Supplementary Publication Numbers, CCDC 713665 No. for 3a Copy of the
data can be obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: +44(0) 1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk].
29. Brewster, K.; Chittenden, R. A.; Harrison, J. M.; Inch, T. D. J. Chem. Soc., Perkin
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J Organomet. Chem. 2007, 692, 2425–2435; (b) Rodríguez, M.; Ochoa, M. E.;
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27. General procedure: In a 100 mL round-bottomed flask containing a magnetic
stirring bar was placed 1 equiv of (1a–f) in 45 mL of methanol, and 3 equiv of
potassium cyanide was added. The resulting solution was stirred at room
temperature for 4 h and the solvent was removed in vacuo. The crude product