Expeditious preparation of isoxazoles from Δ2-isoxazolines as advanced intermediates for functional materials

Article abstract of DOI:10.1016/j.tetlet.2011.09.122

A collection of isoxazoles derivatives has been efficiently synthesized in three steps. The oximation reaction of aldehydes followed by nitrile oxide [3+2] 1,3-dipolar cycloaddition and MnO₂-oxidation reaction furnished the title compounds which were purified by simple filtration on celite.

Full text of DOI:10.1016/j.tetlet.2011.09.122

Tetrahedron Letters 52 (2011) 6569–6572
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Expeditious preparation of isoxazoles from
intermediates for functional materials
D
2-isoxazolines as advanced
Guilherme D. Vilela a, Rafaela R. da Rosa a, Paulo H. Schneider a, Ivan H. Bechtold b, Juliana Eccher b,
Aloir A. Merlo a,
⇑
a Instituto de Química, UFRGS, Av. Bento Gonçalves, 9500, Porto Alegre, RS 91501970, Brazil
b Departamento de Física, UFSC, Florianópolis, SC, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 July 2011
Revised 22 September 2011
Accepted 26 September 2011
Available online 1 October 2011
A collection of isoxazoles derivatives has been efficiently synthesized in three steps. The oximation reac-
tion of aldehydes followed by nitrile oxide [3+2] 1,3-dipolar cycloaddition and MnO2-oxidation reaction
furnished the title compounds which were purified by simple filtration on celiteÒ.
Ó 2011 Elsevier Ltd. All rights reserved.
The Letter is dedicated to Professor Hugo
Gallardo on the occasion of his 60th
birthday and his contribution for liquid
crystals research in Brazil.
Keywords:
Isoxazolines–isoxazoles
Liquid crystals
MnO2 oxidation
Nitrile oxide [3+2] cycloaddition
1. Introduction
Nucleosides and nucleotides chemistry are another example of
the exploration of isoxazolines/isoxazole core as substitutes for the
Isoxazolines and isoxazoles are important 5-membered hetero-
cycles widely spread out in many compounds with biological and
technological properties. These related ‘cousin’ heterocycles are
also present in a series of important compounds with well known
medicinal properties. For instance, Lee-878, a nitrofuranyl isoxazo-
line is a potent inhibitor against Mycobacterium tuberculosis.1 The
outstanding in vitro activity of this compound led the Lee group
to explore the isoxazolinic core as a privileged structure with
anti-tuberculosis activity.2,3
furanose ring in nucleoside analogues.4 These structural modifica-
tions originated a new class of uracils tethered to isoxazolines5 and
isoxazoles6, which showed potential antiviral and anticancer
activity.
Isoxazolines and isoxazoles are substructures also present in
many anti-inflammatory drugs, antibacterials,7 in orally bioavail-
able factor Xa inhibitors,8 and display in vitro antiprotozoal activ-
ities.9 These small molecules act as activators of the cystic fibrosis
transmembrane conductance regulator protein (CFTR), in the treat-
ment of lethal genetic disease cystic fibrosis (CF). This disease is
caused by mutations of the CFTR protein.10 Beyond their broad
spectra of biological activity, isoxazolines and isoxazoles are inter-
esting intermediates in organic synthesis,11 and play an important
role in the synthesis of novel liquid-crystalline (LC) materials.12
From the synthetic point of view there are different approaches
to prepare disubstituted isoxazoles. Condensation of 1,3-dicarbonyl
compounds with hydroxylamine,13 Michael addition of hydroxyl-
O
N
O
NO2
N
N
Bn
Lee-878
amine hydrochloride to
(chalcones) followed by cyclization,14 nucleophilic addition of N-hy-
droxyl-4-toluenesulfonamide to
,b-unsatd. Aldehydes/ketones15
a,b-insaturated carbonyl compounds
a
are representative methods. Besides improvements, many
procedures, have some inherent limitations such as low yields,
⇑
Corresponding author. Tel.: +55 51 33087316; fax: +55 51 33087304.
E-mail address: aloir@iq.ufrgs.br (A.A. Merlo).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.09.122

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G. D. Vilela et al. / Tetrahedron Letters 52 (2011) 6569–6572
co-products from side reactions, and both regioisomers are fre-
quently isolated. Other strategies of preparation of regioisomeric
isoxazoles in moderate yields are possible and involves the thermol-
ysis of haloazidoalkenes and 2-halo-2H-azirines,16 reaction of al-
kynes with ammonium cerium(IV) nitrate [(NH4)2Ce(NO3)6,
CAN(IV)] in acetone,17 diazotization of b-ketoesters followed by
the addition of triethylamine and clorooxime.18 More recently, Lar-
ock’s group reported a three-step approach to synthesize isoxazoles
involving an electrophilic cyclization of the ynone O-methyl
oxime.19
The use of [3+2] 1,3-dipolar cycloaddition of nitrile oxides to al-
kynes constitutes an important alternative to prepare isoxazoles in
solution or by combinatorial synthesis on solid support.20 In fact,
many nitrile oxides react with alkynes, with few exceptions,21
leading often to a mixture of regioisomeric products, with low
yields. To overcome this trouble Sharpless and co-workers re-
ported that nitrile oxides react with alkynes at appreciable rates
at room temperature in a highly selective manner and with good
yields when copper(I) catalyst was added.22 The performance of
this procedure was also applied later in the synthesis of liquid crys-
tals by Gallardo et al.23 Although some alkynes are commercially
available, the synthesis of mono-substituted alkynes can take
two or more steps. In this sense, alkyne synthons can serve to alle-
viate the issues related on both alkyne preparation and cycloaddi-
tion regioselectivity.24
In our search for new LC molecules we have demonstrated the
versatility of the [3+2] 1,3-dipolar cycloaddition as a suitable
methodology to access a variety of 3,5-disubstituted isoxazoline
liquid crystals.25 Our previous results showed that the introduction
of an isoxazoline ring flanked by aromatic rings or polar groups
opened a route to prepare useful intermediates in the liquid crys-
tals field, from themselves or their parent compounds isoxazoles.
During the course of our investigation about isoxazolines, as a
molecular kit for LC, we selected one of them and subjected it to
a MnO2-mediated oxidation process. We found that this reagent
can easily oxidize 3,5-diarylisoxazoline to the corresponding
3,5-diarylisoxazole yielding LC materials with a large enantiotropic
nematic mesophase.26
The mixture was heated under reflux for 40 min, concentrated
and left in the freezer overnight to give pure products as white sol-
ids. Next, using the [3+2] 1,3-dipolar cycloaddition reaction were
prepared the key isoxazolines 3–13, 25a–b, and 26a–b containing
suitable groups for chemical transformations. These compounds
were synthesized starting with the 1,3-dipolar component nitrile
oxide, which was obtained in situ by reacting the aldoxime deriv-
atives with NCS in pyridine28, followed by the addition of a solu-
tion of different acceptors 2, at room temperature for 4 h. The
low yields observed in some examples are related with the low sol-
ubility of some oximes. The preparation of these isoxazolines
derivatives provided us with an entry of a new class of precursors
for high-performance liquid crystals materials.
With the valuable target intermediates 3,5-diarylisoxazolines
synthesized, we focused our attention toward the transformation
of them to isoxazoles through the oxidation protocol using acti-
vated
and 2.
c
ÀMnO2 reagent.29 The results are presented in Tables 1
In order to determine the best reaction condition on the
oxidation step, several other reagents were also tested30 and the
best results were obtained using activated MnO2 oxidant in a
Dean–Stark apparatus. By simple filtration and remotion of the
solvent the final isoxazoles were synthesized in good to excellent
yields.
All halogenated compounds synthesized are versatile building
blocks that may be incorporated into low molar mass mesogenic
structures for potential use on optical applications. The bromine
atom at para position of the benzene ring offers the possibility to
carry out a palladium-catalyzed cross-coupling reaction, which
would lead to a very broad range of compounds with interesting
properties in the field of organic materials.31
For example, compounds 23b and 24b could be valuable inter-
mediates in the synthesis of bent core liquid crystals.32 They are
synthesized according to Scheme 2 where the delivery of free phe-
nol 23b is accomplished by the remotion of t-butyl group in AcOH/
HBr medium. The alkylation of 23b yields LC 23c.
In order to extend the scope of our methodology, aliphatic
aldoximes were also used as precursors for the nitrile oxides. The
data collected in Table 3 show that the preparation of 3-alkyl-5-
arylisoxazoline 25a–b and 26a–b and the corresponding isoxazoles
27a–b and 28a–b is an attractive alternative to obtain advanced
synthetic intermediates in the field of functional materials.
In fact, as can be seen from the results presented until now, the
preparation of isoxazoles from isoxazolines constitutes of an
alternative very efficient, fast, and clean method to reach useful
intermediates in areas such as OEM and functional materials. Some
Herein we wish to report a facile and efficient synthesis of a
collection of 3,5-disubstituted isoxazoles liquid crystals from isox-
azolines, using the couple nitrile oxide [3+2] 1,3-dipolar cycloaddi-
tion/MnO2-oxidation reactions.
In addition, halogenated variants of these core motifs open to us
an avenue to be explored as starting materials for palladium-cata-
lyzed reactions. So, the preparation of small molecular organic
intermediate with potential technological applications, such as or-
ganic light-emitting diodes (OLEDs), organic field-effect transistors
(OFETs) and liquid crystal displays (LCDs) can be achieved once it is
an important task in the field of organic electronic materials-
OEM.27
Table 1
Thermal data (°C) and yield (%) of the isoxazolines 3a–d, 4–13
Entry
X
Y
Yield (%)
Mp (°C)
3a
3b
3c
3d
4
5
6
7
8
Br
Br
Br
Br
Cl
Me
Br
Cl
Me
Br
OC7H15
OC8H17
OC9H19
OC10H21
OC8H17
OC8H17
Br
Br
Br
NO2
NO2
53
75
54
52
43
30
34
14
93
42
19
14
57
20
119.8
115.8
113.3
111.8
109.5
94.8
123.2
120.0
142.5
132.0
140.5
122.0
122.0
143.0
2. Results and discussion
Scheme 1 outlines the preparation of a general collection of
isoxazolines and isoxazoles in a short and efficient sequence. Thus,
aliphatic and aromatic aldehydes 1 were first converted into aldox-
imes by treatment with a hydroxylamine hydrochloride solution.
9
10
11
12
13
Cl
1.NH2OH.HCl,
H2O/EtOH,
R
O
H
R'
R
R'
3. MnO2,
C6H6
Me
tButO
tButO
NO2
Br
NO2
R
Na2CO3,
N
O
N
O
2. NCS, py, DCM,
Isoxazoles
1
Isoxazolines
p-XC6H4CH=CH2 (2)
O
N
X = Br, Cl, Me, t-ButO
Y
X
Scheme 1. Synthesis of isoxazoles from isoxazolines by [3+2] 1,3-dipolar cycload-
dition followed by MnO2-oxidation reaction.

G. D. Vilela et al. / Tetrahedron Letters 52 (2011) 6569–6572
6571
Table 2
Transition temperaturesa (°C) and yield (%) of the isoxazoles 14a–d, 15–24b
O-
O-
+
Mn
.
MnO2
C6H6
O
N
+ Mn
O
N
O
Entry
X
Y
Yield (%)
Physical appearance
O
N
O
MnO2
Ar
Ar
14a
14b
14c
14d
15
16
17
18
19
20
21
22
23a
24a
Br
Br
Br
Br
Cl
Me
Br
Cl
Me
Br
OC7H15
OC8H17
OC9H19
OC10H21
OC8H17
OC8H17
Br
Br
Br
NO2
NO2
99
98
50
97
70
90
94
47
67
62
66
70
95
95
Cr 109.3 CrE 128.0 SmA 191.3 I
Cr 93.0 CrE 129.0 SmA 191.0 I
Cr 108.6 CrE 126.0 SmA 184.5 I
Cr 99.0 CrE 128.0 SmA 186.0 I
Cr 115.5 CrA 180.0 N 184.0 I
Cr 105.9 N 132.2 I
Cr 214.4 I
Cr 200.0 I
Cr 210.0 I
Cr 224.8 I
Cr 222.2 I
Ar
Ar
Ar
Ar
6
II
H
I
.
Association
step
III
MnO(OH)
MnO2 or
.
III
MnO(OH)
O-
Dissociation
step
+
Mn
Ar
O
N
O
N
O
MnO2 + MnO
+ H2O
+
Ar
Ar
Ar
Cl
17
III
Me
t-ButO
t-ButO
NO2
Br
NO2
Cr 182.5 I
Cr 157.8 I
Cr 181.0 I
Scheme 3. Stepwise reaction sequence for the manganese dioxide oxidation of
isoxazoline 6.
O
N
Also, the nature of mesophase is dependent on the terminal group
attached in the para position of benzene ring if we compare 14d,
15, and 16.34 As expected all isoxazolines in Tables 1 and 3 are
not liquid crystals considering that they are not completely conju-
gate and planar.
X
Y
a
Data obtained by polarizing optical microscopy, POM; Cr = crystal phase;
CrE = Crystal E phase; SmA = Smectic A phase and I = Isotropic phase.
The 3-alkyl-5-arylisoxazoles 27a–b and 28a–b are other precur-
sors for obtaining new low molar mass liquid crystal.35 These new
precursors have the benzene ring substituted by short and medium
alkyl chain at C-3 position of the isoxazole ring. The properties
could be tailored by changing the molecular shape. A detailed
synthetic study of preparation of the new compounds from these
isoxazoles is now in progress and will be reported soon.
O
N
a
Y
RO
23a R
= t-But, Y = Br
23b R = H, Y = Br
a. AcOH, HBr, MeOH
(99%, mp 205.5 oC for 23b
98%, mp 241.0 oC for 24b)
b
23c R
=OC8H17, Y = Br
The mechanistic proposal for the formation of 3,5-disubstituted
isoxazoles from 3,5-disubstuted isoxazolines with activated man-
ganese dioxide is shown in Scheme 3. The mechanism of oxidation
of benzyl alcohol with manganese dioxide has been studied by
Goldman.36 According to his studies, the rate-determining step in
the oxidation of benzyl alcohols with activated manganese dioxide
24a R
24b R = H, Y = NO2
= t-But, Y = NO2
b. RBr, CH3CN, K2CO3, (84%)
(Cr 98.8 CrE 119.5 SmA 191.0 I)
a
Scheme 2. Preparation of phenols 23b and 24b by deprotection reaction of 23a and
24a and the corresponding alkylated 23c.
involves the cleavage of the
a-CH bond, and that the assumed
Table 3
adsorption step is reversible. More recently, Srivastava et al. re-
ported the conversion of 4,5-dihydro-1,2,4-oxadiazoles to 1,2,4-
oxadiazoles by an oxidation process mediated by MnO2 and NaOCl
reagents.37 The mechanism of this transformation was discussed
by the authors. Similar mechanism should be considered for the
oxidation of 3,5-disubstituted isoxazolines to 3,5-disubstituted
isoxazoles as exemplified by 6 to 17 (Scheme 3). Initially, 6 inter-
acts reversibly at the surface of manganese dioxide via coordina-
tion between N and MnO2 forming the complex I (to activate the
Thermal data (°C) and yield (%) of the isoxazolines 25a,b–26a,b and isoxazoles 27a,b–
28a,b, respectively
Entry
R
X
Yield (%)
Mp (°C)
a
a
a
a
25a
25b
26a
26b
C4H9
C4H9
C7H15
C7H15
Br
Me
Br
25
44
87
49
Me
O
O
N
N
R
Ha-iminic hydrogen), which undergoes oxidation via hydrogen-
X
X
27a
27b
28a
28b
C4H9
C4H9
C7H15
C7H15
Br
Me
Br
48
89
70
72
48.3
a
76.0
55.5
atom transfer from I to another equivalent of MnO2 to form the sta-
ble radical II. Abstraction of a hydrogen radical from C-3 generates
III, which then is dissociated delivering the isoxazole 17 and the
inorganic species (MnO2, MnO, and H2O).
In summary, we have synthesized a collection of isoxazoles
which are rapidly accessed by two efficient methodologies—the
nitrile oxide [3+2] 1,3-dipolar cycloaddition followed by MnO2-
oxidation reaction. The final isoxazoles are valuable building
blocks which may be transformed into potential materials in
OEM or functional materials.
Me
R
a
Viscous liquid at room temperature.
of them 14a–d, 15, 16, and 23c are liquid crystals itself. The crystal
E phase founded in these compounds makes them very promising
candidates for their application in the field of OFETs. It is interest-
ing to see that exchanging the terminal groups in 14a–d to 23c
does not modify the nature of the mesophase. We anticipated that
the optical texture of the liquid crystalline A phase of compound
14a, viewed between crossed polarisers (see SI) on cooling, is
transferred to the smectic E phase, and then to the crystalline state.
This paramorphosis phenomenon is important to control the short-
range spatial order present in the smectic phases on cooling.33
3. Experimental section
3.1. Synthesis
4-n-Alkyloxybenzadehyde and the corresponding oximes were
prepared according to Refs. 25,26. The general procedure for the
preparation of 3,5-disubstituted isoxazolines is described as fol-
lows: To a solution of alkene (4.25 mmol) in CH2Cl2 (10 ml), at
0 °C and under inert atmosphere, were added NCS (4.67 mmol)

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G. D. Vilela et al. / Tetrahedron Letters 52 (2011) 6569–6572
9. Patrick, D. A.; Bakunov, S. A.; Bakunova, S. M.; Kumar, E. V. K. S.; Lombardy, R. J.;
and pyridine (6.37 mmol).
A solution of aldehyde oxime
Jones, S. K.; Bridges, A. S.; Zhirnov, O.; Hall, J. E.; Wenzler, T.; Brun, R.; Tidwell,
R. R. J. Med. Chem. 2007, 50, 2468–2485.
10. Sammelson, R. E.; Ma, T.; Galietta, L. J. V.; Verkman, A. S.; Kurtha, M. J. Bioorg.
Med. Chem. Lett. 2003, 13, 2509–2512.
11. (a) Kozikowski, A. P. Acc. Chem. Res. 1984, 17, 410–416; (b) Fader, L. D.; Carreira,
E. M. Org. Lett. 2004, 66, 2485–2488; (c) Jiang, D.; Chen, Y. J. Org. Chem. 2008,
73, 9181–9183.
(4.25 mmol) in CH2Cl2 (12 ml) was added dropwise and stirred
for 4 h at room temperature. The mixture was washed with HCl
1 M (3 Â 20 ml), brine, (2 Â 20 ml) and dried over anhydrous
Na2SO4. Removal of CH2Cl2 afforded the crude product, which
was recrystallized from ethanol to give the pure product as a white
solid or isolated by column chromatography using a mixture of
EtOAc/hexane (1:9).
General procedure for the oxidation reaction. To a flask adapted
with
(1.2 mmol), benzene (25 ml), and
was heated under reflux for 10 hours. After that, it was filtered over
celite and concentrated in vacuum to give a pale white solid which
was purified by recrystallization in ethanol. Data for 14a. Yield:
99%; mp 109.3 °C; 1H NMR (300 MHz, CDCl3) d 7.76 (d, 2H,
J = 8.4 Hz, Ar), 7.68 (d, 2H, J = 8.7 Hz, Ar), 7.60 (d, 2H, J = 8.4 Hz,
Ar), 6.97 (d, 2H, J = 8.4 Hz, Ar), 6.76 (s, 1H), 4.00 (t, 2H, J = 6.4 Hz,
OCH2CH2), 1.81 (m, 2H, OCH2CH2), 1.5–1.3 (m, 8H, (CH2)4), 0.90
(t, 3H, J = 6.4 Hz, CH3); 13C NMR (75.5 Hz, CDCl3) d 169.0, 162.7,
160.7, 132.2, 128.1, 127.3, 127.2, 126.4, 124.4, 121.1, 114.8, 97.6,
68.1, 31.8, 29.2, 29.0, 26.0, 22.6; Elem. Anal. Calcd for C22H24NO2Br:
C, 63.77; H, 5.84; N, 3.38. Found: C, 63.63; H, 5.63; N, 3.42.
12. (a) da Silva, L.; Gallardo, H.; Magnago, R. F.; Begnini, I. M. Mol. Cryst. Liq. Cryst.
2005, 432, 1–13; (b) Gallardo, H.; Zucco, C.; da Silva, L. Mol. Cryst. Liq. Cryst.
2002, 373, 181–190; (c) Barbera, J.; Cativiela, C.; Serrano, J. L.; Zurbano, M. M.
Liq. Cryst. 1992, 11, 887–897; (d) Brown, D. H.; Styring, P. Liq. Cryst. 2003, 30,
23–30; (e) Bezborodov, V. S.; Kauhanka, N. N.; Lapanik, V. I.; Lee, C. J. Liq. Cryst.
2003, 30, 579–583.
a
Dean-Stark were added 3,5-disubstituted isoxazoline
-MnO2 (6 mmol). The mixture
c
13. Bandiera, T.; Grunanger, P.; Marinone, A. F. J. Heterocycl. Chem. 1992, 29, 1423–
1428.
14. Kidwai, M.; Kukreja, S.; Thakur, R. Lett. Org. Chem. 2006, 3, 135–139.
15. Tang, S.; He, J.; Sun, Y.-Q.; He, L.; She, X. Org. Lett. 2009, 11, 3982–3985.
16. Pinho e Melo, T. M. V. D.; Lopes, C. S. J.; Rocha Gonsalves, A. M. A.; Storr, R. C.
Synthesis 2002, 5, 605–608.
17. Itoh, K.; Takahashi, S.; Ueki, T.; Sugiyama, T.; Takahashi, T. T.; Horiuchi, C. A.
Tetrahedron Lett. 2002, 43, 7035–7037.
18. Pruitt, J. R.; Pinto, D. J.; Estrella, M. J.; Bostrom, L. L.; Knabb, R. M.; Wong, P. C.;
Wright, M. R.; Wexler, R. R. Bioorg. Med. Chem. Lett. 2000, 10, 685–689.
19. Waldo, J. P.; Larock, R. C. Org. Lett. 2005, 7, 5203–5205.
20. Tanaka, M.; Haino, T.; Ideta, K.; Kubo, K.; Mori, A.; Fukazawa, Y. Tetrahedron
2007, 63, 652–665.
21. For highly regioselective 1,3-dipolar cycloadditions using alkynliodonium salts
please see: Stang, P. J.; Murch, P. Tetrahedron Lett. 1997, 38, 8793–8794.
22. Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.; Sharpless, K.
B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210–216.
Acknowledgments
23. Vieira, A. A.; Bryk, F. R.; Conte, G.; Bortoluzzi, A. J.; Gallardo, H. Tetrahedron Lett.
2009, 50, 905–908.
A.A.M. thanks CNPq, PROCAD/CAPES, INCT-Catálise. R.R.R. is an
undergraduate student and thanks FAPERGS-UFRGS for her
fellowship.
24. Dadiboyena, S.; Xu, J.; Hamme, A. T. Tetrahedron Lett. 2007, 48, 1295–1298.
25. (a) Passo, J. A.; Vilela, G. D.; Schneider, P. H.; Ritter, O. M. S.; Merlo, A. A. Liq.
Cryst. 2008, 35, 833–840; (b) Ritter, O. M. S.; Giacomelli, F. C.; Passo, J. A.;
Silveira, N. P.; Merlo, A. A. Polym. Bull. 2006, 56, 549–561.
26. Tavares, A.; Schneider, P. H.; Merlo, A. A. Eur. J. Org. Chem. 2009, 889–897.
27. (a) Aldred, M. P.; Vlachos, P.; Dong, D. W.; Kitney, S. P.; Tsoi, W. C.; O’Neill, M.;
Kelly, S. M. Liq. Cryst. 2005, 32, 951–965; (b) Carrasco-Orozco, M.; Tsoil, W. C.;
O’Neill, M.; Aldred, M. P.; Vlachos, P.; Kelly, S. M. Adv. Mat. 2006, 18, 1754–
1758; (c) Zafiropoulos, N. A.; Choi, E.-J.; Dingemans, T.; Wenbin Lin, W.;
Samulski, E. T. Chem. Mater. 2008, 20, 3821–3831; (d) Shimizu, Y.; Oikawa, K.;
Nakayama, K.; Guillon, D. J. Mat. Chem. 2007, 17, 4223.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.09.122.
28. (a) Liu, K.-C.; Shelton, B. R.; Howe, R. K. J. Org. Chem. 1980, 45, 3916–3918; (b)
Das, B.; Holla, H.; Mahender, G.; Banerjee, J.; Reddy, M. R. Tetrahedron Lett.
2004, 45, 7347–7350.
References and notes
29. Barco, A.; Benetti, S.; Pollini, G. P.; Baraldi, P. G. Synthesis 1977, 837; For review,
see please (a) Fatiadi, A. J. Synthesis 1976, 65–104; (b) Taylor, R. J. K.; Reid, M.;
Foot, J.; Raw, S. A. Acc. Chem. Res. 2005, 38, 851–869.
30. Li, R.; Wu, W. T.; Wu, G. L.; Fan, Y.; Wu, L. M. Chinese Chem. Lett. 2007, 18, 788–
790.
1. Tangallapally, R. P.; Yendapally, R.; Daniels, A. J.; Lee, R. E. B.; Lee, R. E. Curr. Top.
Med. Chem. 2007, 7, 509–526.
2. Rakesh; Sun, D.; Lee, R. B.; Tangallapally, R. P.; Lee, R. E. Eur. J. Med. Chem. 2009,
44, 460–472.
3. Tangallapally, R. P.; Sun, D.; Rakesh; Budha, N.; Lee, R. E. B.; Lenaerts, A. J. M.;
Meibohm, B.; Lee, R. E. Bioorg. Med. Chem. Lett. 2007, 17, 6638–6642.
4. (a) Merino, P. Curr. Med. Chem: Anti-infective Agents 2002, 1, 389–411; (b) Cao,
J.; Huang, X. J. Comb. Chem. 2008, 10, 526–533; (c) Quadrelli, P.; Mella, M.;
Carosso, S.; Bovio, B.; Caramella, P. Eur. J. Org. Chem. 2007, 6003–6015.
5. (a) Romeo, G.; Iannazzo, D.; Piperno, A.; Romeo, R.; Saglimbeni, M.; Chiacchio,
M. A.; Balestrieri, E.; Macchi, B.; Mastino, A. Bioorg. Med. Chem. 2006, 14, 3818–
3824; (b) Adams, D. R.; Boyd, A. S. F.; Ferguson, R.; Grierson, D. S.; Monneret, C.
Nucleosides Nucleotides 1998, 17, 1053–1075; (c) Adams, D. R.; Perez, C.;
Maillard, M.; Florent, J. C.; Evers, M.; Henin, Y.; Litvak, S.; Litvak, L.; Monneret,
C.; Grierson, D. S. J. Med. Chem. 1997, 40, 1550–1558.
6. (a) Lee, Y. S.; Kim, B. H. Bioorg. Med. Chem. Lett. 2002, 12, 1395–1397; (b) Kim, S.
J.; Lee, Y. S.; Kim, B. H. Nucleic Acids Res. Suppl. 2002, 2, 3–4.
7. (a) Jeddeloh, M. R.; Holden, J. B.; Nouri, D. H.; Kurth, M. J. J. Comb. Chem. 2007, 9,
1041–1045; (b) Habeeb, A. G.; Praveen Rao, P. N.; Knaus, E. E. J. Med. Chem.
2001, 44, 2921–2927.
31. Hird, M.; Toyne, K. J. Liq. Cryst. 1993, 14, 741–761.
32. (a) Semmler, K. J. K.; Dingemans, T. J.; Samulski, E. T. Liq. Cryst. 1998, 24, 799–
803; Cai, R.; Samulski, E. T. Liq. Cryst. 1991, 9, 617–637; (b) Ros, M. B.; Serrano,
J. L.; Fuente, M. R.; Folcia, C. L. J. Mater. Chem. 2005, 15, 5093–5098; (c)
Yelamaggad, C. V.; Shashikala, I. S.; Quan, Li. Q. Chem. Mater. 2007, 19, 6561–
6568; (d) Bruce, D. C.; Heyns, K.; Vill, V. Liq. Cryst. 1997, 23, 813–819; (e) Pelzl,
G.; Wirth, I.; Weissflog, W. Liq. Cryst. 2001, 28, 969–972; (f) Bates, M. A. Chem.
Phys. Lett. 2007, 437, 189–192.
33. (a) Vlachos, P.; Mansoor, B.; Adred, M. P.; O’Neill, M.; Kelly, S. M. Chem.
Commun. 2005, 2921–2923; (b) Funahashi, M.; Hanna, J.-I. Appl. Phys. Lett.
1998, 73, 3733–3735.
34. Han, J.; Chang, X.-Y.; Zhu, L.-R.; Wang, Y.-M.; Meng, J.-B.; Lai, S.-W.; Chui, S. S.-
Y. Liq. Cryst. 2008, 35, 1379–1394.
35. Kauhanka, U. M.; Kauhanka, M. M. Liq. Cryst. 2006, 33, 121–127.
36. Goldman, I. M. J. Org. Chem. 1969, 34, 3289–3295.
37. Srivastava, R. M.; Lima, A. A.; Viana, O. S.; Silva, M. J. C.; Catanho, M. T. J. A.;
Morais, J. O. F. Bioorg. Med. Chem. 2003, 11, 1821–1827.
8. (a) Lam, P. Y. S.; Adams, J. J.; Clark, C. G.; Calhoun, W. J.; Luettgen, J. M.; Knabb,
R. M.; Wexler, R. R. Bioorg.Med. Chem. Lett. 2003, 13, 1795–1799; (b) Pruitt, J. R.;
Pinto, D. J.; Estrella, M. J.; Bostrom, L. L.; Knabb, R. M.; Wong, P. C.; Wright, M.
R.; Wexler, R. R. Bioorg. Med. Chem. Lett. 2000, 10, 685–689.