Synthesis and Liquid Crystal Properties of New Fluorinated Isoxazoles

Article abstract of DOI:10.1080/15421406.2015.1030972

New fluorinated LC 3,5-diarylisoxazolines and 3,5-diarylisoxazoles have been synthesized and their thermal properties reported. Isoxazolines were synthesized using [3+2] 1,3-dipolar cycloaddition from nitrile oxide and alkenes with subsequent MnO₂

Full text of DOI:10.1080/15421406.2015.1030972

This article was downloaded by: [FU Berlin]
On: 07 July 2015, At: 10:23
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: 5 Howick Place, London, SW1P 1WG
Molecular Crystals and Liquid Crystals
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gmcl20
Synthesis and Liquid Crystal Properties
of New Fluorinated Isoxazoles
L. D. Lopesa & A. A. Merloa
a Chemistry Institute, Universidade Federal do Rio Grande do Sul,
Porto Alegre, Brazil
Published online: 06 Jul 2015.
Click for updates
To cite this article: L. D. Lopes & A. A. Merlo (2015) Synthesis and Liquid Crystal Properties
of New Fluorinated Isoxazoles, Molecular Crystals and Liquid Crystals, 612:1, 149-157, DOI:
10.1080/15421406.2015.1030972
To link to this article: http://dx.doi.org/10.1080/15421406.2015.1030972
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Mol. Cryst. Liq. Cryst., Vol. 612: pp. 149–157, 2015
Copyright © Taylor & Francis Group, LLC
ISSN: 1542-1406 print/1563-5287 online
DOI: 10.1080/15421406.2015.1030972
Synthesis and Liquid Crystal Properties of New
Fluorinated Isoxazoles
L. D. LOPES AND A. A. MERLO∗
Chemistry Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre,
Brazil
New fluorinated LC 3,5-diarylisoxazolines and 3,5-diarylisoxazoles have been syn-
thesized and their thermal properties reported. Isoxazolines were synthesized using
[3+2] 1,3-dipolar cycloaddition from nitrile oxide and alkenes with subsequent MnO2-
oxidation yielded the corresponding isoxazoles. The title compounds obtained were
1
characterized by H and 13C NMR, differential scanning calorimetry (DSC), elemen-
tal analysis and polarized optical microscopy (POM). The final compounds are com-
posed by terminal flexible hydrogenated alkyl chains or semiperfluoroalkyl chains. 3,5-
diarylisoxazoline composed of alkyl chains is not LC, whereas when composed of one
or two semiperfluoroalkyl chains it displays SmA mesophase. For 3,5-diarylisoxazoles
a second mesophase SmC was also observed.
Keywords Isoxazolines; isoxazoles; fluorinated; [3+2] cycloaddition; MnO2
oxidation.
Introduction
The incorporation of 5-membered heterocyclic rings, such as 1,3,4-oxadiazole, tetrazole,
thiophene, isoxazoline, isoxazole and others, into molecular structures leads to considerable
changes on molecular and mesomorphic properties [1]. In the world of 5-membered hete-
rocyclic rings, isoxazoles are found in many natural and pharmaceutical products [2a–b].
Beyond well-known medicinal properties, isoxazolines and isoxazoles are interesting inter-
mediates in organic synthesis [2c–d], and play an important role in the synthesis of novel
liquid crystalline materials [2e–f]. The isoxazole ring incorporates a strong dipole moment
and this polar effect favors the increasing of molecular anisotropic polarizability. Conse-
quently, it induces the formation of stable mesophase with enantiotropic behavior [3]. The
special features concerning the chemical nature of isoxazoles can be greatly improved with
the installation of fluorine atoms at peripheral region of diarylisoxazoles represented by
semiperfluoroalkyl chains or connected directly into the aryl groups. The combination of
different characteristics, as small size, high polarity, great stability (due to the high strength
of the C F bond) and low polarizability has stimulated the study of fluorine influence
on the control of the liquid crystalline properties. The important attributes of the fluorine
∗Address correspondence to A. A. Merlo, Chemistry Institute, Universidade Federal do Rio
Grande do Sul, Porto Alegre, Brazil. E-mail: aloir.merlo@ufrgs.br
Color versions of one or more of the figures in the article can be found online at
www.tandfonline.com/gmcl.
[615]/149

150/[616]
L. D. Lopes and A. A. Merlo
Figure 1. Synthesis of isoxazolines by [3+2] 1,3-dipolar cycloaddition followed by MnO2-oxidation
reaction.
substituent ensure that significant modifications are frequently encountered in respect of
melting point, mesophase morphology and transition temperatures [4].
Herein we are describing the synthesis and characterization of new liquid crystals
based on fluorinated isoxazoles. Isoxazoles were obtained in two steps transformation -
[3+2] 1,3-dipolar cycloaddition of nitrile oxide with alkene to access the key intermediate
isoxazolines. MnO2-oxidation reaction of isoxazolines renders the corresponding isoxa-
zoles. This synthetic methodology has been largely used by us in the preparation of new LC
materials [5] and its main attribute is the high regioselectivity in favor of 3,5-disubstituted
isoxazolines [6].
In the strategy depicted briefly in Figure 1, the oxime is the precursor for the active
nitrile oxide which acts as 1,3-dipolar component for cycloaddition and alkene is the dipo-
larophile for [3+2] 1,3-dipolar cycloaddition. The key intermediate 3,5-diarylisoxazoline
is subsequently oxidized using MnO2 to reach the final isoxazole [5].
Results
Classical synthetic methodologies were employed in the preparation of the oximes
and alkenes, as we can see in the Scheme 1. The synthetic route started from 4-
hydroxybenzaldehyde (1), which was alkylated [7] to obtain the compounds 2a and 2b,
Aldehydes 2a and 2b were precursors for the oximes 3a and 3b as well as the alkenes
4a and 4b. Aldehydes 2a and 2b were composed of terminal segments of flexible alkyl
chain (hydrogenated chain) and semiperfluoroalkyl chain, respectively. Wittig olefination
was employed to synthesize the alkenes 4a-b [8], and the oximes 3a-b were obtained by
a well-established procedure in the literature [9]. It is important to highlight that alkenes
and oximes are originated from the same chemical precursors. With the appropriate alkenes
and oximes synthesized in good yields, the [3+2] 1,3-dipolar cycloadditions were carried
out using a 5% aqueous NaOCl solution as oxidizing agent, to form the 3,5-disubstituted
isoxazolines in high regioselectivity.
To accomplish the final synthesis of title compounds, the oxidation step using activated
MnO2, that present low toxicity, low cost, ease of handling and the absence of hazardous
additives/byproducts [10], led to the isoxazoles 6a, 6b and 6c in 55%, 43% and 67% yields,
respectively, as outlined in the Figure 2.

Synthesis/Properties of Fluorinated Isoxazoles
[617]/151
Scheme 1. Synthetic routes to obtain the alkenes, oximes and isoxazolines (i) to form prod-
uct 2a: n-dodecyl bromide, K2CO3, TBAB, butanone, reflux, 18h; (ii) to form product 2b: 3-
(perfluorooctyl)propyl iodide, K2CO3, DMF, 60◦C, 18h; (iii) NH2OH.HCl, EtOH, NaOAc, H2O,
reflux, 1h; (iv) methyltriphenylphosphonium bromide, NaH, THF, room temperature, 24h; (v) NaOCl
5%, CH2Cl2, 30 min.
The chemical structures of all final compounds synthesized were characterized by
1H and 13C NMR and elemental analysis. Thermal and liquid crystalline properties were
investigated by POM and DSC. LC samples were first filtered from DCM solution to remove
dusty, paper fibers, etc and after analyzed by POM and DSC. The transitional properties are
tabulated in Table 1. As we can see, the isoxazolines containing semiperfluoroalkyl chains
displayed liquid-crystalline behavior. The compound 5a only showed the existence of two
different crystalline forms, while the isoxazoline 5b with two semiperfluoroalkyl chains
showed monotropic SmA mesophase. Isoxazoline 5c, having two mixed flexible segments
formed by hydrogenated alkyl chain and semiperfluoroalkyl chain, presented enantiotropic
SmA mesophase with a greater transition temperature range than 5b. Here we can see a
Figure 2. Oxidation reaction used to synthesize the isoxazoles 6a, 6b and 6c.

152/[618]
L. D. Lopes and A. A. Merlo
Table 1. Transition temperatures (◦C) and enthalpy values (kJ/mol) for the isoxazolines
5a-c and isoxazoles 6a-c
LC
Transition temperatures (◦C)
ꢀH (kJ/mol)
5a
5b
5c
6a
6b
6c
Cr1 102.3 Cr2 105.1 I
Cr1 49.8 Cr2 38.1 I
I (150.7) SmA∗ 136.2 Cr
Cr 111.6 SmA 135.7 I
I (2.5) SmA∗ 43.1 Cr
Cr 28.0 SmA 5.4 I
Cr 104.0 SmC 148.9 I
Cr 186.8 SmC 203.2 SmA 213.1 I
Cr 116.0 SmC 172.9 SmA 199.3 I
Cr 65.7 SmC 8.8 I
Cr 42.7 SmC 3.3 SmA 1.7 I
Cr 31.0 SmC 0.8 SmA 6.7 I
Cr, Cr1 and Cr2 = Crystal phases; SmA = Smectic A phase; SmC = Smectic C phase; I = Isotropic
phase; ∗Monotropic behavior.
clear effect of segregation exerted by fluorine atoms presented in the carbon backbone.
All the isoxazoles 6a-c displayed the existence of liquid crystalline properties, exhibiting
enantiotropic mesophases. For compound 6a a SmC was observed as previously reported
in the literature [11]. The new isoxazoles 6b and 6c displayed two smectic mesophases.
Upon cooling from isotropic state, samples 6b and 6c entered to SmA phase followed by
a second transition to the SmC mesophase as evidenced clearly by the textures observed
using POM analysis. DSC curves of those samples also corroborated for the assignment of
this second transition between mesophases. Mesophase range and enthalpy values for 5b-c
and 6a-c are definitely a manifestation of influence of fluorine atom on transition properties
of the compounds reported here [4c, 12, 13]. Incompatibility of totally flexible alkyl chain,
rigid anisometric core and less flexible semiperfluorinated alkyl chain are responsible for
the formation of positional ordered liquid-crystalline phases [14] as observed in Table 1.
Figure 3. DSC curve for the LC compound 6c upon second heating and cooling at a rate of
10 ◦Cmin−1
.

Synthesis/Properties of Fluorinated Isoxazoles
[619]/153
Figure 4. Optical textures observed in the mesophases A) SmC and B) SmA obtained upon cooling
from isotropic phase of the isoxazoles 6b and 6c.
In the Figure 3 the DSC curve for the isoxazole 6c is shown, where it is possible to
observe the peaks associated to the phase transitions. Considering the enantiotropic behavior
of the samples in this study, there are three peaks upon heating (the sample passes from
crystal phase to smectic C phase, then to smectic A phase, and finally reaches the isotropic
phase). Upon cooling, sample 6c enters to SmA mesophase at 198.9◦C from isotropic state
and at 172.1◦C a second transition to SmC is seen. At 108.4◦C the crystallization of sample
6c from SmC mesophase to crystal phase occurs.
All mesophases were identified according to their textures observed by optical mi-
croscopy (see Figure 4). Once the isotropic liquid is cooled, a focal-conic texture appears
in the smectic A phase for the compounds 6b and 6c. Cooling down, a Schlieren and a
broken focal-conic textures allow us to identify smectic C phase for the LC 6b and 6c,
respectively.
Conclusion
We have synthesized new 3,5-diarylisoxazolines and 3,5-diarylisoxazoles 5a-c and 6a-c,
respectively using an efficient and regioselective synthetic route. 5a and 6a are composed
by terminal flexible hydrogenated alkyl chain in both sides of the rigid core. 5b and 6b have
terminal flexible semiperfluoroalkyl chains in both sides and 5c and 6c are composed by
terminal flexible alkyl chains from one side and to the other side by terminal segments of

154/[620]
L. D. Lopes and A. A. Merlo
semiperfluoroalkyl chains. Isoxazoline 5a did not show liquid crystalline behavior, whereas
isoxazole 6a showed only mesophase SmC. The isoxazolines 5b and 5c presented SmA
mesophases, monotropic and enantiotropic, respectively. Conversion to more anisotropic
isoxazoles 6b and 6c stable mesophases arose. By comparison with the isoxazole 6a
that presented mesophase SmC, the incorporation of fluorine atoms modified the thermal
behavior, favoring also the formation of SmA mesophase for the compounds 6b and 6c.
Calamitic isoxazole 6c, that has only one side with polyfluorinated chain, showed the
lowest transition temperatures and the greatest mesophase range. Improved mesophase
range of the 6c compared to the isoxazoles 6b with two polyfluorinated chains is a clearly
segregation effect induced by the two different flexible chains in their polar character. The
combination of better conjugation of isoxazole ring and polar effect of semiperfluorinated
alkyl chain induce the formation of structured layer mesophase by means of segregation
effect. As expected, fluorinated alkyl chain induced the formation of orthogonal mesophase
by means of segregation effect. Therefore, this research contributed to a better understanding
of the structure-property relationship in molecules such as 3,5-disubstituted isoxazoles
containing long fluorinated chains and facilitates the design of new and more complex
compounds.
Experimental
General
The melting point and textures of the samples were determined using an Olympus BX 41
polarizing microscope in conjunction with a Mettler Toledo FP-90 controller and HT84
heating stage. The transition temperatures and enthalpies were determined using a TA
Instruments DSC Q20 differential scanning calorimeter, the heating and cooling rate was
10 ◦Cmin−1. 1H NMR and 13C NMR spectra were recorded at Varian 300 MHz and Bruker
Avance 400 MHz instruments. Chemical shifts are given in parts per million (δ) and they
are referenced to tetramethylsilane (TMS).
Alkylation Reactions
The products 2a and 2b were prepared from 4-hydroxybenzaldehyde (1) following previ-
ously reported procedures [7].
Synthesis of Aldoximes
The oximes 3a and 3b were synthesized from the corresponding benzaldehyde by treatment
with a hydroxylamine hydrochloride solution according to literature procedures [9].
Synthesis of Alkenes
To prepare the alkenes 4a and 4b the Wittig reaction was used according to the procedure
described in the reference [8].
Procedure for the 1,3-dipolar Cycloaddition Reactions
To a solution of alkene (1.0 mmol) and oxime (1.0 mmol) in dichloromethane (4 mL)
at room temperature, was added dropwise a 5% aqueous sodium hypochlorite solution

Synthesis/Properties of Fluorinated Isoxazoles
[621]/155
(3.0 mL, 2.0 mmol). After the completed addition, the reaction mixture was stirred for
30 min. The CH2Cl2 was evaporated in vacuum and water was added to the reaction
mixture to filter and wash the product. Isoxazolines 5a-c were recrystallized from ethanol
and filtered off and dried.
3,5-bis[4-(dodecyloxy)phenyl]isoxazoline (5a): White solid; Yield: 68%; mp Cr1
102.3◦C Cr2 105.1◦C I; 1H NMR (400 MHz, CDCl3) δ = 7.64 (m, 2H), 7.32 (m, 2H), 6.92
(m, 4H), 5.67 (dd, 1H, Jcis = 10.7 Hz, Jtrans = 8.6 Hz), 3.98 (m, 4H), 3.72 (dd, 1H, Jgem
= 16.5 Hz, Jcis = 10.8 Hz), 3.32 (dd, 1H, Jgem = 16.5 Hz, Jtrans = 8.6 Hz), 1.80 (m, 4H),
1.46 (m, 4H), 1.30 (m, 32H), 0.90 (t, 6H, J = 6.7 Hz); 13C NMR (101 MHz, CDCl3) δ =
160.7, 159.1, 155.9, 132.7, 128.2, 127.4, 121.9, 114.7, 82.2, 68.1, 68.1, 43.2, 31.9, 29.7,
29.7, 29.6, 29.6, 29.4, 29.4, 29.4, 29.3, 29.2, 26.0, 26.0, 22.7, 14.1; C39H61NO3: calcd. C
79.14, H 10.39, N 2.37; found C 79.27, H 10.69, N 2.33.
3,5-bis[4-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoroundecyloxy)phen-
yl]isoxazoline (5b): White solid; Yield: 42%; Transition temperatures: I (150.7◦C)
SmA 136.2◦C Cr; 1H NMR (300 MHz, CDCl3) δ = 7.66 (m, 2H), 7.35 (m,
2H), 6.94 (m, 4H), 5.69 (dd, 1H, Jcis = 10.7 Hz, Jtrans = 8.5 Hz), 4.11 (t, 2H,
J = 5.9 Hz), 4.07 (t, 2H, J = 5.9 Hz), 3.73 (dd, 1H, Jgem = 16.5 Hz, Jcis = 10.8 Hz), 3.31
(dd, 1H, Jgem = 16.5 Hz, Jtrans = 8.5 Hz), 2.34 (m, 4H), 2.14 (m, 4H); 13C NMR (75 MHz,
CDCl3) δ = 160.0, 158.6, 155.6, 133.4, 128.2, 127.3, 122.6, 114.7, 114.7, 82.1, 66.5, 43.1,
28.0 (t, CH2-CF2, J = 22.3 Hz), 20.6; C37H23F34NO3: calcd. C 37.80, H 1.97, N 1.19;
found C 37.97, H 2.09, N 1.20.
5-[4-(dodecyloxy)phenyl]-3-[4-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafl-
uoroundecyloxy)phenyl]isoxazoline (5c): White solid; Yield: 67%; Transition tempera-
1
tures: Cr 111.6◦C SmA 135.7◦C I; H NMR (300 MHz, CDCl3) δ = 7.63 (m, 2H), 7.30
(m, 2H), 6.90 (m, 4H), 5.65 (dd, 1H, Jcis = 10.7 Hz, Jtrans = 8.6 Hz), 4.07 (t, 2H, J =
5.8 Hz), 3.94 (t, 2H, J = 6.6 Hz), 3.69 (dd, 1H, Jgem = 16.6 Hz, Jcis = 10.8 Hz), 3.29 (dd,
1H, Jgem = 16.6 Hz, Jtrans = 8.6 Hz), 2.33 (m, 2H), 2.13 (m, 2H), 1.77 (m, 2H), 1.42 (m,
2H), 1.28 (m, 16H), 0.88 (t, 3H, J = 6.7 Hz); 13C NMR (101 MHz, CDCl3) δ = 160.0,
159.2, 155.7, 132.6, 128.3, 127.4, 122.6, 114.7, 114.6, 82.3, 68.1, 66.4, 43.1, 31.9, 29.7,
29.6, 29.6, 29.6, 29.4, 29.4, 29.2, 27.9 (t, CH2-CF2, J = 22.4 Hz), 26.0, 22.7, 20.5, 14.1;
C38H42F17NO3: calcd. C 51.65, H 4.79, N 1.58; found C 51.82, H 4.96, N 1.55.
Procedure for the Oxidation Reactions
To a flask adapted with a Dean-Stark were added 3,5-disubstituted isoxazoline (1.0 mmol),
toluene (35 ml) and MnO2 (18.0 mmol). The mixture was heated under reflux. Reactions
were monitored by thin-layer chromatography. After observing that all the isoxazoline was
consumed, it was filtered over celite, washed with CH2Cl2 and concentrated in vacuum to
give the solid which were purified by recrystallization in ethanol.
3,5-bis[4-(dodecyloxy)phenyl]isoxazole (6a): White solid; Yield: 55%; Transition
temperatures: Cr 104.0◦C SmC 148.9◦C I; 1H NMR (300 MHz, CDCl3) δ = 7.76 (m, 4H),
6.97 (m, 4H), 6.63 (s, 1H), 4.01 (t, 4H, J = 6.5 Hz), 1.81 (m, 4H), 1.45 (m, 4H), 1.27 (m,
32H), 0.88 (t, 6H, J = 6.7 Hz); 13C NMR (75 MHz, CDCl3) δ = 170.2, 162.5, 160.7, 160.6,
128.1, 127.3, 121.7, 120.3, 114.9, 114.8, 95.8, 68.2, 68.2, 31.9, 29.6, 29.6, 29.5, 29.5, 29.3,
29.3, 29.3, 29.2, 29.2, 26.0, 26.0, 22.6, 14.0; C39H59NO3: calcd. C 79.41, H 10.08, N 2.37;
found C 79.86, H 10.77, N 2.46.
3,5-bis[4-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoroundecyloxy)phen-
yl]isoxazole (6b): White solid; Yield: 43%; Transition temperatures: Cr 186.8◦C SmC
1
203.2◦C SmA 213.1◦C I; H NMR (300 MHz, C2D2Cl4, 120◦C) δ = 7.80 (t, 4H, J =

156/[622]
L. D. Lopes and A. A. Merlo
8.2 Hz), 7.04 (d, 4H, J = 8.3 Hz), 6.64 (s, 1H), 4.17 (t, 4H, J = 5.5 Hz), 2.39 (m, 4H),
2.18 (m, 4H).
5-[4-(dodecyloxy)phenyl]-3-[4-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafl-
uoroundecyloxy)phenyl]isoxazole (6c): White solid; Yield: 67%; Transition tempera-
1
tures: Cr 116.0◦C SmC 172.9◦C SmA 199.3◦C I; H NMR (400 MHz, CDCl3) δ = 7.82
(d, 2H, J = 8.6 Hz), 7.77 (d, 2H, J = 8.6 Hz), 7.01 (d, 4H, J = 8.0 Hz), 6.67 (s, 1H), 4.12
(t, 2H, J = 5.7 Hz), 4.03 (t, 2H, J = 6.4 Hz), 2.34 (m, 2H), 2.16 (m, 2H), 1.82 (m, 2H),
1.49 (m, 2H), 1.29 (m, 16H), 0.90 (t, 3H, J = 6.6 Hz); 13C NMR (75 MHz, CDCl3) δ =
170.3, 162.4, 160.7, 159.9, 128.2, 127.3, 122.4, 120.2, 114.9, 114.8, 95.7, 68.2, 66.4, 31.9,
29.6, 29.5, 29.3, 29.3, 29.3, 29.1, 28.0 (t, CH2-CF2, J = 22.5 Hz), 25.9, 22.6, 20.6, 13.9;
C38H40F17NO3: calcd. C 51.76, H 4.57, N 1.59; found C 51.48, H 4.49, N 1.51.
Acknowledgments
The authors gratefully acknowledge the INCT-Cata´lise, Fapergs-Edital PqG 2012 and Edital
01/12-PPG-Qu´ımica-UFRGS. L. D. Lopes thanks Capes agency for her fellowship.
References
[1] a) Shanker, G., & Tschierske, C. (2011). Tetrahedron, 67, 8635. b) Vasconcelos, U. B., & Merlo
A. A. (2006). Synthesis, 1141. c) Campbell, N. L., Duffy, W. L., Thomas, G. I., Wild, J. H.,
Kelly, S. M., Bartle, K., O’Neill, M., Minter, V., & Tuffin, R. P. (2002). J. Mater. Chem., 12,
2706. d) Santos, D. R., Oliveira, A. G. S., Coelho, R. L., Begnini, I. M., Magnago, R. F., &
Silva, L. (2008). Arkivoc, XVII, 157. e) Tariq, M., Hameed, S., Bechtold, I. H., Bortoluzzi, A.
J., & Merlo, A. A. (2013). J. Mat. Chem. C., 1, 5583.
[2] a) Zeng, L.-F., Zhang, H.-S., Wang, Y.-H., Sanchez, T., Zheng, Y.-T., Neamati, N., & Long,
Y-Q. (2008). Bioorg. Med. Chem. Lett., 18, 4521. b) Zhu, S., Shi, S., & Gerritz, S. W. (2011).
Tetrahedron Lett., 52, 4001. c) Fuller, A. A., Chen, B., Minter, A. R., & Mapp, A. K. (2005).
J. Am. Chem. Soc., 127, 5376. d) Dieter Muri, D., & Carreira, E. M. (2009). J. Org. Chem.
74, 8695. e) Kuo, H-M., Shao-Ling Tsai, S-L., Lee, G-H., Sheu, H-S., & Lai, C. K. (2013).
Tetrahedron, 69, 618. f) Brown, D. H., & Styring, P. (2003). Liq. Cryst., 30, 23.
[3] a) Tavares, A., Schneider, P. H., & Merlo, A. A. (2009). Eur. J. Org. Chem., 2009, 889. b) Haino,
T., Tanaka, M., Ideta, K., Kubo, K., Mori, A., & Fukazawa, Y. (2004). Tetrahedron Lett., 45,
2277. c) Serrano, J. L., Iglesias, R., & Sierra, T. (1997). Liq. Cryst., 22, 37.
[4] a) Hird, M. (2007). Chem. Soc. Rev., 36, 2070. b) Hunter, L., & O’Hagan, D. (2008). Org.
Biomol. Chem., 6, 2843. c) Schneider, J. M. F. M., Sales, E. S., Livotto, P. R., Schneider, P. H.,
& Merlo, A. A. (2014). J. Braz. Chem. Soc., 25, 1493. d) Al-Maharik, N., Kirsch, P., Slawin,
A. M. Z., & O’Hagan, D. (2014). Tetrahedron, 70, 4626. e) Kirsch, P., Binder, W., Hahn, A.,
Ja¨hrling, K., Lenges, M., Lietzau, L., Maillard, D., Meyer, V., Poetsch, E., Ruhl, A., Unger, G.,
& Fro¨hlich, R. (2008). Eur. J. Org. Chem., 2008, 3479.
[5] a) Vilela, G. D., da Rosa, R. R., Schneider, P. H., Bechtold, I. H., Eccher, J., & Merlo, A.
A. (2011). Tetrahedron Lett., 52, 6569. b) Ritter, O. M. S., Giacomelli, F. C., Passo, J. A., da
Silveira, N. P., & Merlo, A. A. (2006). Polym. Bull., 56, 549.
[6] a) Gonc¸alves, R. S. B., Dos Santos, M., Bernadat, G., Bonnet-Delpon, D., & Crousse, B. (2013).
Beilstein J. Org. Chem., 9, 2387. b) Jeddeloh, M. R., Holden, J. B., Nouri, D. H., & Kurth, M.
J. (2007). J. Comb. Chem., 9, 1041.
[7] a) Hersmis, M. C., Spiering, A. J. H., Waterval, R. J. M., Meuldijk, J., Vekemans, J. A. J. M.,
Hulshof, L. A. (2001). Org. Process Res. Dev., 5, 54. b) Kapla´nek, R., Havl´ık, M.,Kra´l, V.,
Marta´sek, P., & Br´ıza, T. (2010). Synthetic Commun., 40, 247.
[8] Simoni, D., Grisolia, G., Giannini, G., Roberti, M., Rondanin, R., Piccagli, L., Baruchello, R.,
Rossi, M., Romagnoli, R., Invidiata, F. P., Grimaudo, S., Jung, M. K., Hamel, E., Gebbia, N.,

Synthesis/Properties of Fluorinated Isoxazoles
[623]/157
Crosta, L., Abbadessa, V., Di Cristina, A., Dusonchet, L., Meli, M., & Tolomeo, M. (2005). J.
Med. Chem., 48, 723.
[9] Ritter, O. M. S., Giacomelli, F. C., Passo, J. A., Silveira, N. P., & Merlo, A. A. (2006).
Polym.Bull., 56, 549.
[10] Taylor, R. J. K., Reid, M., Foot, J., & Raw, S. A. (2005). Acc. Chem. Res., 38, 851.
[11] Kuo, H., Tsai, S., Lee, G., Sheu, H., & Lai, C. K. (2013). Tetrahedron, 69, 618.
[12] Ho¨pken, J., Pugh, C., Richtering, W., & Mo¨ller, M. (1998). Makromol. Chem., 189, 911.
[13] Peer, K. (2004). Modern Fluoroorganic Chemistry, WILEY-VCH Verlag GmbH & Co. KGaA:
Weinheim.
[14] Tschierske, C. (1998). J. Mater. Chem., 8, 1485.