Synthesis, microwave-assisted polymerization, and polymer properties of fluorinated 2-phenyl-2-oxazolines: A systematic study

Article abstract of DOI:10.1002/chem.200800671

We present a detailed systematic study of the synthesis and ability of fluorinated 2-phenyl-2-oxazolines to undergo polymerization. The synthesis of these compounds is based on a two-step procedure that gives the desired 2-oxazolines in moderate-to-good yields. All the compounds were fully characterized by IR and NMR (¹H, ¹³C, and ¹⁹F) spectroscopy, mass spectrometry, and elemental analysis. The 2-oxazolines were subsequently used as monomers for living cationic ring-opening polymerization (CROP) with microwave irradiation as the heat source (T= 140°C), nitromethane as the solvent, and methyl tosylate as the initiator. The linear first-order kinetic plots of the polymerizations accompanied by a linear increase of the molecular weight with conversion and low polydispersity index (PDI) values (generally below 1.30) indicate a living polymerization mechanism. The resulting polymerization rates reflect a strong sensitivity to the quantity of fluorine substituents in general and the presence or absence of ortho-fluoro substituents of the phenyl ring in particular. All the polymers were isolated and characterized by size-exclusion chromatography and MALDI-TOF mass spectrometry. Finally, a detailed investigation of selected polymer properties was performed by using differential scanning calorimetry, thermogravimetric analysis, and contact-angle measurements, thus resulting in structure-property relationships. Whereas the thermal properties of the polymers are mostly influenced by the presence of ortho-fluoro substituents, the surface properties are mainly determined by the presence of para- and/or metafluoro substituents.

Full text of DOI:10.1002/chem.200800671

DOI: 10.1002/chem.200800671
Synthesis, Microwave-Assisted Polymerization, and Polymer Properties of
Fluorinated 2-Phenyl-2-oxazolines: A Systematic Study
Matthias Lobert,[a, b] Hanneke M. L. Thijs,[a, b] Tina Erdmenger,[a, b] Rebecca Eckardt,[a, b]
Christoph Ulbricht,[a, b] Richard Hoogenboom,[a, b] and Ulrich S. Schubert*[a, b, c]
Abstract: We present a detailed sys-
tematic study of the synthesis and abili-
ty of fluorinated 2-phenyl-2-oxazolines
to undergo polymerization. The synthe-
sis of these compounds is based on a
two-step procedure that gives the de-
sired 2-oxazolines in moderate-to-good
yields. All the compounds were fully
characterized by IR and NMR (1H, 13C,
and 19F) spectroscopy, mass spectrome-
try, and elemental analysis. The 2-oxa-
zolines were subsequently used as
monomers for living cationic ring-
opening polymerization (CROP) with
microwave irradiation as the heat
source (T=1408C), nitromethane as
the solvent, and methyl tosylate as the
initiator. The linear first-order kinetic
plots of the polymerizations accompa-
nied by a linear increase of the molecu-
lar weight with conversion and low
polydispersity index (PDI) values (gen-
erally below 1.30) indicate a living
polymerization mechanism. The result-
ticular. All the polymers were isolated
and characterized by size-exclusion
chromatography and MALDI-TOF
mass spectrometry. Finally, a detailed
investigation of selected polymer prop-
erties was performed by using differen-
tial scanning calorimetry, thermogravi-
metric analysis, and contact-angle
measurements, thus resulting in struc-
ture–property relationships. Whereas
the thermal properties of the polymers
are mostly influenced by the presence
of ortho-fluoro substituents, the surface
properties are mainly determined by
the presence of para- and/or meta-
fluoro substituents.
ing polymerization rates reflect
a
strong sensitivity to the quantity of flu-
orine substituents in general and the
presence or absence of ortho-fluoro
substituents of the phenyl ring in par-
Keywords: fluorine · oxazolines ·
polymerization · surface energy ·
thermal properties
Introduction
The synthesis of well-defined linear amphiphilic block co-
polymers receives significant scientific interest because such
copolymers can assemble into micellar aggregates, whereby
the exact form of the micelles is defined by the structure of
the copolymer and the solvent. If the copolymer consists of
three[1] or four blocks of very different characters—for ex-
ample, a hydrophilic block and two incompatible hydropho-
bic blocks—the formation of multicompartment micelles is
possible.[1–3] To achieve incompatibility of the hydrophobic
blocks a (aromatic) hydrocarbon block can be combined
with a fluorinated block.[1,3] In addition, a large difference in
polarity and thermal properties of the hydrophobic blocks
can induce segregation.[4] So far, these kind of structures are
mainly based on vinylic monomers, which were polymerized
through anionic or controlled radical mechanisms, such as
atom-transfer radical polymerization (ATRP)[5,6] or reversi-
ble addition–fragmentation chain transfer (RAFT).[7]
[a] Dr. M. Lobert, H. M. L. Thijs, T. Erdmenger, R. Eckardt, C. Ulbricht,
Dr. R. Hoogenboom, Prof. Dr. U. S. Schubert
Laboratory of Macromolecular Chemistry and Nanoscience
Eindhoven University of Technology and Dutch Polymer Institute
(DPI)
P.O. Box 513, 5600 MB Eindhoven (The Netherlands)
E-mail: u.s.schubert@tue.nl
[b] Dr. M. Lobert, H. M. L. Thijs, T. Erdmenger, R. Eckardt, C. Ulbricht,
Dr. R. Hoogenboom, Prof. Dr. U. S. Schubert
Dutch Polymer Institute (DPI)
P.O. Box 902
5600 AX Eindhoven (The Netherlands)
[c] Prof. Dr. U. S. Schubert
Laboratory of Organic and Macromolecular Chemistry
Friedrich-Schiller-Universitꢀt Jena
Humboldtstrasse 10, 07743 Jena (Germany)
Web: www.schubert-group.com
The versatility of 2-oxazolines as monomers in polymeri-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200800671.
zation reactions[8–12] makes them ideal candidates to transfer
10396
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Chem. Eur. J. 2008, 14, 10396 – 10407

FULL PAPER
this concept of multicompartment micelles to polymers
based on living cationic ring-opening polymerizations
(CROPs). (Co)polymers based on 2-oxazolines are of wide
interest in chemical, biochemical, and biomedical re-
search[13–21] and, because their synthetic accessibility could
be optimized by using single-mode microwave reactors,[22–24]
the gate to a broader applicability of 2-oxazoline monomers
was opened. The pressurized microwave conditions lead to a
significant decrease in the polymerization time to only a few
minutes,[22] and additionally enables the polymerization of 2-
phenyl-2-oxazolines substituted with electron-withdrawing
fluoro substituents, as we recently demonstrated.[25,26] Fur-
thermore, di-,[27] tri-,[28] and tetrablock[29] oxazoline copoly-
mers can be synthesized in a controlled manner under mi-
crowave irradiation, thus leading to well-defined multiblock
copolymers in a reasonable time span.
face properties of the polymers, which were investigated by
means of differential scanning calorimetry (DSC), thermog-
ravimetric analysis (TGA), and contact-angle measurements,
respectively. The determined polymer properties are dis-
cussed in relation to the fluorine substitution pattern. This
insight into the thermal and surface properties of the fluori-
nated poly(2-phenyl-2-oxazoline)s will be important for the
design of triblock copolymers that will form multicompart-
ment micelles in future work.
Experimental Section
Materials and instrumentation: Analytical-grade solvents were purchased
from Biosolve Ltd. All chemicals were purchased from Aldrich (Ger-
many), except the fluorinated compounds which were purchased from
Fluorochem (UK). Methyl tosylate and the 2-oxazolines were distilled
prior to use (the latter over barium oxide) and stored under argon. Nitro-
methane, dried over molecular sieves (3 ꢂ), was obtained from Fluka.
The general polymerization mechanism of 2-oxazolines
(Scheme 1) starts with a nucleophilic attack of the lone pair
of the ring nitrogen atom of a monomer onto an electrophil-
ic initiator species, such as methyl tosylate or benzyl bro-
mide.[30,31] The thus-formed intermediate oxazolinium spe-
cies is attacked by a second monomer, thus causing a ring
The polymerizations were performed in capped reaction vials (0.5–2 mL)
in the single-mode microwave reactor Emrys Liberator (Biotage),
equipped with a noninvasive IR sensor (accuracy: 2% for the measure-
ment of the reaction temperatures).
GC measurements were performed utilizing an Interscience Trace GC
with a Trace Column RTX-5 connected to a PAL autosampler. For the
injection of the polymerization mixtures, a special Interscience liner with
additional glass wool was used.
À
rearrangement that leads to the cleavage of the C O bond.
In general, chain-transfer or termination reactions are
absent under appropriate reaction conditions, and hence the
polymerization proceeds in a living manner until all the mo-
nomer is consumed or a terminating agent, such as water, is
added. This process leads to the formation of well-defined
polymers that reveal narrow molecular-weight distributions
with polydispersity index (PDI) values below 1.20.
The obtained polymers feature a polyalkylenimine back-
bone, and their properties are mainly defined by their
amidic side arms, the former 2-substituent of the monomer.
This feature allows direct fine-
Size-exclusion chromatography (SEC) was measured on a Shimadzu SEC
equipped with a system controller SCL-10 Avp, LC-10 AD pump, RID-
10 A refractive-index detector, UV/Vis detector DPD-10 A, PSS ETA-
2010 differential viscometer, degasser DGU-14 A, CTO-10 A column
oven, and two PSS GRAM 10m, 8ꢃ300 mm, 1000/30 ꢂ columns with
N,N-dimethylacetamide (DMA)/LiCl as the eluent (piezo spectroscopic
calibration).
GC–MS measurements were performed on a Shimadzu GC-17 A ma-
chine (column: DB-SMS (equivalent to phenylpolysiloxane/dimethylpoly-
tuning of the properties of oxa-
zoline-based (co)polymers with
various 2-substituents (R).[12,32]
Recently, the scope of mono-
mers was successfully expanded
to fluorinated 2-phenyl-2-oxa-
zolines 1a–c, and 2a,b, thus re-
Scheme 1. Methyl tosylate (TsO)-initiated cationic ring-opening polymerization of 2-substituted 2-oxazolines
(TsOÀ represents the tosylate anion).
vealing a strong relationship be-
tween the presence and amount
of ortho-fluoro substituents at
the phenyl unit with the poly-
merization kinetics.[25] To delve
into the effect of fluorine sub-
stituents, we performed a sys-
tematic study by synthesizing
and polymerizing all the possi-
ble fluorinated 2-phenyl-2-oxa-
zolines (Scheme 2). Herein, we
discuss the polymerization ki-
netics of the fluorinated 2-
phenyl-2-oxazolines.
second part of this contribution
The
Scheme 2. The synthesized monomers. Fox=monofluorophenyl-2-oxazoline (1a–c), DFOx=difluorophenyl-2-
oxazoline (2a–f), TFOx=trifluorophenyl-2-oxazoline (3a–f), TFOx=tetrafluorophenyl-2-oxazoline (4a–c),
focuses on the thermal and sur- PFOx=pentafluorophenyl-2-oxazoline (5).
Chem. Eur. J. 2008, 14, 10396 – 10407
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www.chemeurj.org
10397

U. S. Schubert et al.
siloxane, 5:95), length=30 m, inner diameter=0.25 mm, film thickness=
0.1 mm) connected to an AOC-20i autoinjector and a GC–MS QP5050 A
mass spectrometer. Ionization was managed by electron impact (EI;
70 eV).
OCH2), 6.88 (m, 1H, 5-H), 6.99 (m, 1H, 3-H), 7.06 (bs, 1H, NH),
8.12 ppm (m, 1H, 6-H); 13C NMR (100 MHz, CDCl3): d=41.70/43.61 (2ꢃ
s, NCH2/OCH2), 104.31 (t, 2J(C-3,F-2/4)=26 Hz, C-3), 112.38 (m, C-5),
116.99 (t, 2J(i-CAr,F-2)=12 Hz, i-CAr), 133.80 (m, C-6), 160.94 (dd, 1J
ACHTUNGTRENNUNG
2,F-2)=250 Hz, 3J
ACHTUNGTRENNUNG
Thermogravimetic analyses were performed on a TG 209 F1 Iris by
Netzsch in a nitrogen atmosphere in the range from ambient temperature
to 8008C with a heating rate of 10 KminÀ1. The samples (each 5 mg)
were dried in a vacuum oven at 408C for 24 h prior to use.
(d, 1J
(C-4,F-4)=243 Hz, C-4); 19F NMR (376 MHz, CDCl3): d=À103.55/
À109.05 ppm (2ꢃs, 2F, 4J
ACHTUNGTRENUN(NG F,F)=11 Hz) (F-2/F-4); IR: n˜ =3380/3098
(NH), 3081 (CH), 2975/2950 (CH2), 1648/1490 (C=C), 1616/1525 (C=O),
1266/1253/1187 (CF), 862 (CH), 772/745 cmÀ1 (CCl); MS: m/z (%): 219
(9) [M+], 184 (5) [M+ÀCl], 170 (26) [M+ÀCH2Cl], 141 (100) [M+
ÀC2H5ClN], 113 (25) [M+ÀC3H5ClNO]; elemental analysis (%) calcd for
C9H8NOClF2: C 49.22, H 3.67, N 6.38; found: C 49.22, H 3.80, N 6.24.
DSC was performed on a DSC 204 F1 Phoenix by Netzsch in a nitrogen
atmosphere with a heating rate of 10 KminÀ1 and a cooling rate of
20 KminÀ1. Three heating–cooling cycles were performed and the third
heating run was used for the determination of the glass transition temper-
ature Tg.
N-(2-Chloroethyl)-2-(2,5-difluorophenyl)acid
amide:
Yield:
84%;
1H NMR (400 MHz, CDCl3): d=3.72 (m, 2H, NCH2), 3.81 (m, 2H,
OCH2), 7.13 (m, 3H, NH, 3-H,4-H), 7.76 ppm (m, 1H, 6-H); 13C NMR
(100 MHz, CDCl3): d=41.76/43.45 (2ꢃs, NCH2/OCH2), 117.50 (m, C-4),
Contact-angle measurements were performed on polymer films prepared
by spin-coating of solutions of the polymers in CHCl3 (20 mgmLÀ1) on
precleaned microscopy glass slides at 1000 rpm for 90 s using a WS-400/
500 series spincoater from Laurell Technologies Corporation. An auto-
mated OCA 30 optical contact-angle measuring instrument from Data-
physics was used to determine the contact angles of both diiodomethane
and ethylene glycol as apolar and polar test liquids, respectively, by using
the equation-of-state theory to calculate the surface energy (SE).[33]
118.08 (d, 3J
A
1
4
1
156.41 (dd, J
(C-2,F-2)=226 Hz, J
N
A
5,F-5)=229 Hz, C-5), 162.20 ppm (s, NC=O); 19F NMR (376 MHz,
CDCl3): d=À116.95/À119.30 ppm (2ꢃm, 2ꢃ1F) (F-2/F-5); IR: n˜ =3377/
3121 (NH), 3089 (CH), 2968/2862 (CH2), 1647/1520 (C=O), 1595/1481
(C=C), 1276/1258/1175 (CF), 887/833 (CH), 762/753/691 cmÀ1 (CCl); MS:
m/z (%): 219 (11) [M+], 184 (5) [M+ÀCl], 170 (30) [M+ÀCH2Cl], 141
(100) [M+ÀC2H5ClN], 113 (27) [M+ÀC3H5ClNO]; elemental analysis
(%) calcd for C9H8NOClF2: C 49.22, H 3.67, N 6.38; found: C 49.12, H
3.38, N 6.23.
Elemental analyses were carried out on a EuroVector EuroEA3000 ele-
mental analyzer for CHNS.
All the MALDI experiments were performed on a Voyager-DE PRO Bio-
spectrometry Workstation (Applied Biosystems, Foster City, CA) time-
of-flight mass spectrometer in the linear mode. All the spectra were ob-
tained in the positive-ion mode. Ionization was performed with a 337-nm
pulsed nitrogen laser. Samples were prepared with a multiple-layer spot-
ting technique with 2-(3-(4-tert-butylphenyl)-2-methyl-2-propenylidene)-
malononitrile (DCTB) as the matrix and NaI as the salt, similar to previ-
ous reports.[34] All the data were processed using the Data Explorer soft-
ware package (Applied Biosystems). All the spectra are averaged over
500 laser shots that covered the complete sample area.
N-(2-Chloroethyl)-2-(2,3-difluorophenyl)acid amide:
Yield:
87%;
1H NMR (400 MHz, CDCl3): d=3.74 (t, 2H, 3J
ACHTUNGTERN(NNUG 1-H,2-H)=6 Hz, NCH2),
3.83 (m, 2H, OCH2), 7.03 (bs, 1H, NH), 7.20 (m, 1H, 4-H), 7.31 (m, 1H,
5-H), 7.81 ppm (t, 1H, 4J(H,H)=6.6 Hz, 6-H); 13C NMR (100 MHz,
CDCl3): d=41.79/43.49 (2ꢃs, NCH2/OCH2), 120.50 (d, 3J
(C-6,F-2)=
17.5 Hz, C-6), 122.85 (d, 2J(i-CAr,F-2)=8.5 Hz, i-CAr), 124.59 (m, C-4),
AHCTUNGTRENNUNG
AHCTUNGTRENNUG
2
1
2
126.35 (d, J
G
E
ACHTUNGTRENNUNG(C-
3,F-2)=14.5 Hz, C-3), 150.52 (dd, 1J
G
ACHTUNGTRENNUG
The 1H, 13C, and 19F NMR spectra were recorded on a Varian AM-400
spectrometer in CDCl3 or CD3NO2, and the chemical shifts are given rel-
ative to the residual solvent signal.
14.5 Hz, C-2), 162.49 ppm (s, NC=O); 19F NMR (376 MHz, CDCl3): d=
À137.64/À139.68 ppm (2ꢃm, 2ꢃ1F) (F-2/F-3); IR: n˜ =3302/3268 (NH),
3084 (CH), 2968/2940 (CH2), 1651/1639/1548 (C=O), 1589 (C=C), 1474
(CH), 1267 (CF), 806 (CH), 757/659 (CCl), 724 cmÀ1 (CH2); MS: m/z
(%): 219 (10) [M+], 184 (7) [M+ÀCl], 170 (27) [M+ÀCH2Cl], 141 (100)
[M+ÀC2H5ClN], 113 (27) [M+ÀC3H5ClNO]; elemental analysis (%)
calcd for C9H8NOClF2: C 49.22, H 3.67, N 6.38; found: C 49.50, H 3.39,
N 6.34.
Monomer synthesis
N-(2-Chloroethyl)-2-(fluorophenyl)acid amides: Fluorobenzoic acid chlo-
ride 6 (0.08 mol) and 2-ethylammonium chloride (0.08 mol) were sus-
pended in dry dichloromethane (150 mL) in an argon atmosphere, and
the reaction mixture was cooled to 08C. Triethylamine (0.19 mol) was
added dropwise within 1 h, and the reaction mixture was stirred for an
additional 2 h. Water (50 mL) was added and the aqueous phase was ex-
tracted with dichloromethane (2ꢃ50 mL). The combined organic phases
were washed with water and brine and subsequently dried over MgSO4.
Removing the solvent under vacuum gave 7 as a beige crude product. As
a result of the high purity (>95%) of the crude products, they were con-
verted into the desired oxazolines 2b–5 without further purification. Pu-
rification for the characterizations of 7 was managed by column chroma-
tography (SiO2, eluent: cyclohexane/ethyl acetate (3:1)+2% triethyla-
mine) to yield the amides 7 as colorless solids.
N-(2-Chloroethyl)-2-(2,4,6-trifluorophenyl)acid amide: Yield: 89%;
1H NMR (400 MHz, CDCl3): d=3.72 (m, 2H, NCH2), 3.78 (m, 2H,
OCH2), 6.47 (bs, 1H, NH), 6.72 ppm (m, 2H, 3-H); 13C NMR (100 MHz,
CDCl3): d=41.67/43.47 (2ꢃs, NCH2/OCH2), 101.06 (t, 2J(C-3,F-2/4)=
28 Hz, C-3), 110.42 (t, 2J(i-CAr,F-2)=20 Hz, i-CAr), 159.74 (s, NC=O),
160.59 (dm, 1J(C-2,F-2)=264 Hz, C-2), 163.56 ppm (dt, 1J
ACTHNUTRGENNUG ACHUTGNTREUNNN(G C-4,F-4)=
ACTHNUTRGNEUNG
255 Hz, 3J(C-4,F-2)=15 Hz, C-4); 19F NMR (376 MHz, CDCl3): d=
À103.31 (quin, 1F, 4J
(F-4,F-2)=9 Hz, F-4), À108.50 ppm (t, 2F, 4J
ACHTUNGTRENNUNG(F-2,F-
N-(2-Chloroethyl)-2-(3,4-difluorophenyl)acid
amide:
AHCTUNGTERNG(NNU H,H)=5 Hz, NCH2), 3.81
Yield:
93%;
3
1H NMR (400 MHz, CDCl3): d=3.74 (t, 2H, J
(m, 2H, OCH2), 6.47 (bs, 1H, NH), 7.23 (m, 1H, 5-H), 7.53 (m, 6-H),
7.66 ppm (m, 1H, 2-H); 13C NMR (100 MHz, CDCl3): d=41.79/43.82 (2ꢃ
s, NCH2/OCH2), 116.85/117.51 (2ꢃd, 2J
ACHTUNGTRENNUNG
N-(2-Chloroethyl)-2-(2,3,6-trifluorophenyl)acid amide: Yield: 87%;
(m, C-6), 131.01 (s, i-CAr), 151.42 (dd, 1J
C-3/4), 153.86 (dd, 1J(C,F)=238 Hz, 2J
A
ACHTUNGTRENNUNG
2
1H NMR (400 MHz, CDCl3): d=3.71 (t, 2H, J
C
(m, 2H, OCH2), 6.64 (bs, 1H, NH), 6.89 (tt, 1H, 3J
(5-H,F-3)=3 Hz, 5-H), 7.20 ppm (m, 1H, 4-H); 13C NMR (100 MHz,
CDCl3): d=41.72/43.43 (2ꢃs, NCH2/OCH2), 111.67 (m, C-4), 115.22 (m,
i-CAr), 118.85 (m, C-5), 147.06 (dm, 1J(C,F)=251 Hz)/147.91 (dm, 1J-
(C,F)=263 Hz)/155.01 (dm, 1J
(C,F)=250 Hz) (C-2/C-3/C-6), 159.50 ppm
AHCTUNGTRENNUNG
(5-H,F-6)=10 Hz, 4J-
A
ACHTUNGTRENNUNG
(s, NC=O); 19F NMR (376 MHz, CDCl3): d=À132.20 (m, 1F, F-3)/
À135.98 ppm (m, 1F, F-4); IR: n˜ =3277/3108 (NH), 3082 (CH), 2978/
2920/2884 (CH2), 1604/1509 (C=C), 16385/1559 (C=O), 1281/1207/1186
(CF), 831 (CH), 774/685 cmÀ1 (CCl); MS: m/z (%): 219 (11) [M+], 183
(9) [M+ÀCl], 170 (15) [M+ÀCH2Cl], 141 (100) [M+ÀC2H5ClN], 113 (45)
[M+ÀC3H5ClNO]; elemental analysis (%) calcd for C9H8NOClF2: C
49.22, H 3.67, N 6.38; found: C 49.20, H 3.40, N 6.20.
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
(s, NC=O); 19F NMR (376 MHz, CDCl3): d=À117.37 (m, 1F, F-3),
À135.20/À140.75 ppm (2ꢃm, 2ꢃ1F) (F-2/F-6); IR: n˜ =3302/3245 (NH),
3087 (CH), 2973/2928/2864 (CH2), 1639/1558 (C=O), 1607/1489 (C=C),
1242/1203 (CF), 815 (CH), 703/657 cmÀ1 (CCl); MS: m/z (%): 237 (9)
[M+], 202 (8) [M+ÀCl], 188 (20) [M+ÀCH2Cl], 159 (100) [M+
N-(2-Chloroethyl)-2-(2,4-difluorophenyl)acid
amide:
Yield:
72%;
1H NMR (400 MHz, CDCl3): d=3.73 (m, 2H, NCH2), 3.82 (m, 2H,
10398
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Chem. Eur. J. 2008, 14, 10396 – 10407

Polymerization of Fluorinated 2-Phenyl-2-oxazolines
FULL PAPER
ÀC2H5ClN], 131 (22) [M+ÀC3H5ClNO]; elemental analysis (%) calcd for
(CH2), 1654/1555 (C=O), 1626/1513/1477 (C=C), 1356/1252/1041/1009
(CF), 907 (CH), 707/663 cmÀ1 (CCl); MS: m/z (%): 255 (9) [M+], 220 (6)
[M+ÀCl], 206 (34) [M+ÀCH2Cl], 177 (100) [M+ÀC2H5ClN], 149 (28)
[M+ÀC3H5ClNO]; elemental analysis (%) calcd for C9H6NOClF4: C
42.29, H 2.37, N 5.48; found: C 42.50, H 2.53, N 5.15.
C9H7NOClF3: C 45.49, H 2.97, N 5.89; found: C 45.55, H 2.81, N 5.61.
N-(2-Chloroethyl)-2-(2,4,5-trifluorophenyl)acid amide: Yield: 83%;
1H NMR (400 MHz, CDCl3): d=3.73 (m, 2H, NCH2), 3.82 (m, 2H,
OCH2), 7.02 (m, 1H, 3-H), 7.09 (bs, 1H, NH), 7.95 ppm (m, 1H, 6-H);
13C NMR (100 MHz, CDCl3): d=42.15/43.78 (2ꢃs, NCH2/OCH2), 106.56
N-(2-Chloroethyl)-2-(2,3,5,6-tetrafluorophenyl)acid amide: Yield: 84%;
3
1H NMR (400 MHz, CDCl3): d=3.73 (t, 2H, J
A
2
2
(2d, J(C-3,F-2/4)=21 Hz, C-3), 117.62 (m, i-CAr), 120.23 (d, JACTHNUGRTNEUNG(C-6,F-5)=
(m, 2H, OCH2), 6.56 (bs, 1H, NH), 7.16 ppm (tt, 1H, 3J
AHCTUNGTRENNUNG
1
1
21 Hz, C-6), 147.59 (dm, J
A
ACHTUNGTRNE(NUNG C-4,F-
9.5 Hz, 4J
AHCTUNGTRENNUNG
4)=246 Hz, C-4), 156.21 (dm, 1J
AHCTUNGTRENNUNG
NC=O); 19F NMR (376 MHz, CDCl3): d=À114.45 (s, 1F, F-5), À126.59
(s, 1F, F-4), À140.28 ppm (s, 1F, F-2); IR: n˜ =3355/3056 (NH), 3093
(CH), 2978/2943 (CH2), 1638/1555 (C=O), 1606/1511 (C=C), 1329/1199/
1147 (CF), 906 (CH), 729/662 cmÀ1 (CCl); MS: m/z (%): 237 (9) [M+],
202 (5) [M+ÀCl], 188 (27) [M+ÀCH2Cl], 159 (100) [M+ÀC2H5ClN], 131
(28) [M+ÀC3H5ClNO]; elemental analysis (%) calcd for C9H7NOClF3: C
45.49, H 2.97, N 5.89; found: C 45.74, H 2.91, N 5.68.
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
19F NMR (376 MHz, CDCl3): d=À137.01 (m, 2F)/À141.18 ppm (m, 2F)
(F-2/F-3); IR: n˜ =3289/3246 (NH), 3080 (CH), 2973/2936/2865 (CH2),
1643 (C=O), 1618/1558/1498 (C=C), 1182 (CF), 861 (CH), 709/655 cmÀ1
(CCl); MS: m/z (%): 255 (10) [M+], 220 (8) [M+ÀCl], 206 (30) [M+
ÀCH2Cl], 177 (100) [M+ÀC2H5ClN], 149 (31) M+ÀC3H5ClNO]; elemen-
tal analysis (%) calcd for C9H6NOClF4: C 42.29, H 2.37, N 5.48; found: C
42.49, H 2.59, N 5.30.
N-(2-Chloroethyl)-2-(2,3,5-trifluorophenyl)acid amide: Yield: 85%;
3
1H NMR (400 MHz, CDCl3): d=3.73 (t, 2H, J
G
(m, 2H, OCH2), 7.02 (m, 1H, 6-H), 7.08 ppm (m, 2H, NH/4-H);
13C NMR (100 MHz, CDCl3): d=41.78/43.41 (2ꢃs, NCH2/OCH2), 112.85
(m, C-6), 118.30 (d, 3J(i-CAr,F-2)=10 Hz, i-CAr), 125.73 (m, C-4), 139.86
N-(2-Chloroethyl)-2-(2,3,4,6-tetrafluorophenyl)acid amide: Yield: 89%;
1H NMR (400 MHz, CDCl3): d=3.72 (t, 2H, J
(H,H)=6 Hz, NCH2), 3.80
3
(m, 2H, OCH2), 6.51 (bs, 1H, NH), 6.85 ppm (m, 1H, 5-H); 13C NMR
(dm, 1J
153.30 (dd, 1J
G
E
ACHTUNGTRENUN(NG C,F)=8 Hz)/
(100 MHz, CDCl3): d=41.77/43.25 (2ꢃs, NCH2/OCH2), 101.64 (m, C-5),
N
ACHTUNGTRENNUNG
ACTHNUTRGNEUNG
111.24 (s, i-CAr), 137.27 (dm, 1J(C-6,F-6)=252 Hz, C-6), 149.08 (dm, 1J-
NC=O); 19F NMR (376 MHz, CDCl3): d=À112.92 (s, 1F, F-5), À132.20
(m, 1F, F-3), À144.16 ppm (s, 1F, F-2); IR: n˜ =3327 (NH), 3066 (CH),
2978/2944 (CH2), 1645/1548 (C=O), 1603/1486 (C=C), 1213/1122 (CF),
864 (CH), 756/655 cmÀ1 (CCl); MS: m/z (%): 237 (10) [M+], 202 (6) [M+
ÀCl], 188 (27) [M+ÀCH2Cl], 159 (100) [M+ÀC2H5ClN], 131 (30) [M+
ÀC3H5ClNO]; elemental analysis (%) calcd for C9H7NOClF3: C 45.49, H
2.97, N 5.89; found: C 45.62, H 2.68, N 5.62.
G
(C,F)=256 Hz)/154.17 (dm, 1J
ACHUTGTNRNEUNG ACHTUNGTRENNUNG(C,F)=
AHCTUNGTRENNUNG
U
ACHTUNGTRENNUNG
IR: n˜ =3292 (NH), 3087/3024 (CH), 2977/2944/2857 (CH2), 1644/1555
(C=O), 1505 (C=C), 1462 (CH), 1245/1161 (CF), 850 (CH), 663 cmÀ1
(CCl); MS: m/z (%): 255 (8) [M+], 220 (7) [M+ÀCl], 206 (23) [M+
ÀCH2Cl], 177 (100) [M+ÀC2H5ClN], 149 (20) [M+ÀC3H5ClNO]; ele-
mental analysis (%) calcd for C9H6NOClF4: C 42.29, H 2.37, N 5.48;
found: C 42.13, H 2.64, N 5.22.
N-(2-Chloroethyl)-2-(2,3,4-trifluorophenyl)acid amide: Yield: 83%;
3
1H NMR (400 MHz, CDCl3): d=3.73 (t, 2H, J
G
(m, 2H, OCH2), 6.97 (bs, 1H, NH), 7.08 (m, 1H, 5-H), 7.83 ppm (m, 1H,
6-H); 13C NMR (100 MHz, CDCl3): d=41.82/43.49 (2ꢃs, NCH2/OCH2),
112.91 (dd, 2J(C-5,F-4)=18 Hz, 3J
ACHTUNGTRENNUNG ACHTUNGTRENNUNG
N-(2-Chloroethyl)-2-(pentafluorophenyl)acid
amide: Yield: 88%;
1H NMR (400 MHz, CDCl3): d=3.74 (m, 2H, NCH2), 3.83 (m, 2H,
OCH2), 6.35 ppm (bs, 1H, NH); 13C NMR (100 MHz, CDCl3): d=42.03/
43.24 (2ꢃs, NCH2/OCH2), 111.16 (t, 2J(i-CAr,F-2)=18 Hz, i-CAr), 137.66
C
ACHTUNGTRENNUNG
1
1
17 Hz, C-3), 150.00 (dm, JACTHUNTGRNENUG(C-4,F-4)=252 Hz, C-4), 152.95 (dm, JACHTUNGTRNE(NUGN C-2,F-
2)=257 Hz, C-2), 161.70 ppm (s, NC=O); 19F NMR (376 MHz, CDCl3):
d=À127.64 (m, 1F, F-3), À134.90 (m, 1F, F-4), À159.25 ppm (m, 1F, F-
2); IR: n˜ =3292 (NH), 3078 (CH), 2971/2935/2876 (CH2), 1645/1548 (C=
O), 1608/1508 (C=C), 1281/1095 (CF), 831 (CH), 688/662 cmÀ1 (CCl);
MS: m/z (%): 237 (8) [M+], 202 (7) [M+ÀCl], 188 (22) [M+ÀCH2Cl],
159 (100) [M+ÀC2H5ClN], 131 (24) [M+ÀC3H5ClNO]; elemental analysis
(%) calcd for C9H7NOClF3: C 45.49, H 2.97, N 5.89; found: C 45.76, H
2.66, N 5.56.
(dm, 1J(C,F)=256 Hz)/142.43 (dm, 1J(C,F)=258 Hz)/144.19 (dm, 1J-
ACTHNUTRGENNUG CAHTUNGTRENNUGN
AHCTUNGTRENNUNG
(C,F)=253 Hz) (C-2/C-3/C-4), 157.88 ppm (s, NC=O); 19F NMR
(376 MHz, CDCl3): d=À140.10 (m, 2F, F-2), À149.99 (m, 1F, F-4),
À159.74 ppm (m, 2F, F-3); IR: n˜ =3284/3076 (NH), 3063 (CH), 2967
(CH2), 1654/1553 (C=O), 1519/1486 (C=C), 1332/1254/986 (CF), 663 cmÀ1
(CCl); MS: m/z (%): 273 (9) [M+], 238 (8) [M+ÀCl], 224 (28) [M+
ÀCH2Cl], 195 (100) [M+ÀC2H5ClN], 167 (24) [M+ÀC3H5ClNO]; ele-
mental analysis (%) calcd for C9H5NOClF5: C 39.51, H 1.84, N 5.12;
found: C 39.57, H 1.87, N 5.27.
N-(2-Chloroethyl)-2-(3,4,5-trifluorophenyl)acid amide: Yield: 51%;
3
1H NMR (400 MHz, CDCl3): d=3.73 (t, 2H, J
G
(m, 2H, OCH2), 6.63 (bs, 1H, NH), 7.46 ppm (t, 1H, 3J
2-H); 13C NMR (100 MHz, CDCl3): d=42.14/43.91 (2ꢃs, NCH2/OCH2),
112.05 (m, C-2), 129.70 (d, 3J(i-CAr,F-3)=5 Hz, i-CAr), 141.83 (dt, 1J
(C-
4,F-4)=259 Hz, 2J(C-4,F-3)=14 Hz, C-4), 151.03 (dm, 1J
(C-3,F-3)=
ACHTUNGTREN(NGNU 2-H,F-3)=7 Hz,
Synthesis of the fluorinated 2-phenyl-2-oxazolines
Method A (2c, 2e, 2 f): Acid amide 7 (65 mmol) was dissolved in THF
(35 mL) at ambient temperature, and this solution was added dropwise
within 30 min to an aqueous potassium hydroxide solution (25%). After
stirring for an additional 24 h, the organic phase was separated, diethyl
ether (150 mL) was added, and the organic phase was washed with water
(4ꢃ) and brine (2ꢃ). After drying over MgSO4 and removing the solvent
under vacuum, a beige crude product was obtained. Further purification
was carried out by column chromatography (SiO2, eluent: cyclohexane/
ethylacetate (3:1)+2% NEt3) to yield the desired oxazolines as colorless
solids.
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
253 Hz, C-3), 164.33 ppm (s, NC=O); 19F NMR (376 MHz, CDCl3): d=
À132.04 (m, 2F, F-3), À154.54 ppm (m, 1F, F-4); IR: n˜ =3303 (NH),
3075/2978 (CH), 2928/2843 (CH2), 1642/1557 (C=O), 1618/1514 (C=C),
1434 (CH), 1232 (CF), 878 (CH), 674/661 cmÀ1 (CCl); MS: m/z (%): 237
(10) [M+], 202 (5) [M+ÀCl], 188 (16) [M+ÀCH2Cl], 159 (100) [M+
ÀC2H5ClN], 131 (37) [M+ÀC3H5ClNO]; elemental analysis (%) calcd for
C9H7NOClF3: C 45.49, H 2.97, N 5.89; found: C 45.36, H 3.30, N 5.67.
N-(2-Chloroethyl)-2-(2,3,4,5-tetrafluorophenyl)acid amide: Yield: 39%;
Method B (2b, 5): Acid amide 7 (15 mmol) was dissolved in dry THF
(60 mL) and heated to 358C in an argon atmosphere. At this tempera-
ture, potassium tert-butoxide (23 mmol) was added portionwise within
5 min. The reaction was stopped after 1 h by adding the mixture to water
(50 mL). The aqueous phase was extracted with dichloromethane (2ꢃ
50 mL) and the combined organic phases were washed with water and
brine. After drying over MgSO4 and removing the solvent under vacuum,
a yellowish crude product was obtained. Purification was managed by
sublimation (458C, 8ꢃ10À3 Torr) to yield the desired oxazolines as color-
less waxy solids.
3
1H NMR (400 MHz, CDCl3): d=3.72 (t, 2H, J
A
(m, 2H, OCH2), 7.02 (bs, 1H, NH), 7.72 ppm (m, 1H, 6-H); 13C NMR
(100 MHz, CDCl3): d=42.09/43.45 (2ꢃs, NCH2/OCH2), 113.00 (d, 2J
(C-
6,F-5)=21 Hz, C-6), 117.17 (s, i-CAr), 140.76 (dm, 1J
(C,F)=256 Hz)/
142.82 (dm, 1J(C,F)=261 Hz) (C-3/C-4), 146.31 (ddm, 1J
(C,F)=248 Hz,
2J(C,F)=11 Hz)/147.39 (ddm, 1J(C,F)=250 Hz, 2J
(C,F)=10 Hz) (C-2/C-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
5), 160.74 ppm (s, NC=O); 19F NMR (376 MHz, CDCl3): d=À136.65 (m,
1F, F-4), À139.37 (m, 1F, F-5), À148.73 (m, 1F, F-3), À153.83 ppm (t, 1F,
3J
ACHTUNGTRENNUNG(F-2,F-3)=20 Hz, F-2); IR: n˜ =3345/3056 (NH), 3063 (CH), 2978/2940
Chem. Eur. J. 2008, 14, 10396 – 10407
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10399

U. S. Schubert et al.
Method C (2d, 3a–f, 4a–c): Acid amide 7 (20 mmol) and [18]crown-6
(1 mmol) were dissolved in dry THF (60 mL) in an argon atmosphere.
Potassium hydroxide (60 mmol) was added portionwise at room tempera-
ture. The reaction was stopped after 1 h by adding the mixture to water
(100 mL). The aqueous phase was extracted with diethyl ether (2ꢃ
50 mL), and the combined organic phases were washed with water (4ꢃ)
and brine (2ꢃ). After drying over MgSO4 and removing the solvent
under vacuum, a slightly yellow crude product was obtained. Further pu-
rification was performed by column chromatography (SiO2, eluent: cyclo-
hexane/ethylacetate (3:1)+2% NEt3) for 2d, 3b, and 3d–f; sublimation
(508C, 1ꢃ10À2 Torr) for 3a and 4a–c; and distillation (588C, 1.2ꢃ10À2
Torr) for 3c.
141 (15) [M+ÀC2H4N], 126 (14) [M+ÀC2H3NO], 113 (13) [M+
ÀC3H4NO]; elemental analysis (%) calcd for C9H7NOF2: C 59.02, H
3.85, N 7.65; found: C 58.97, H 3.78, N 7.56.
2-(2,4,6-Trifluorophenyl)-2-oxazoline (3a): Yield: 79%; 1H NMR
3
(400 MHz, CDCl3): d=4.11 (t, 2H, J
A
3J(H,H)=9.5 Hz, OCH2), 6.74 ppm (t, 2H, 3J
ACTHNUGTRENNUGN ACHTUNGTRENNNUG
AHCTUNGTRENNUNG
1
3
1
161.63 (dd, JACTHNUTRGENN(GU C-2,F-2)=258 Hz, JAHCTUNGTRENN(UGN C-2,F-4)=16 Hz, C-2), 161.79 (dd, J-
ACHUTNGRENNUG AHCTUNGTRNE(NUGN C-4,F-2)=8 Hz, C-4), 165.27 ppm (s, N=CO);
(C-4,F-4)=266 Hz, 2J
4
19F NMR (376 MHz, CDCl3): d=À103.26 (q, 1F, J
ACHTUNGTREN(NUNG F-4,F-2)=8 Hz, F-4),
À105.23 ppm (m, 2F, 4J
ACHTUNGTRENUN(NG F-2,F-4)=8 Hz, F-2); IR: n˜ =3040 (CH), 2988/
2-(3,4-Difluorophenyl)-2-oxazoline (2c): Yield: 80%; 1H NMR
2959/2918/2888 (CH2), 1637 (C=N), 1616/1598 (C=C), 1439 (CH), 1256/
1043 (CO), 1179/1130 (CF), 870/847 cmÀ1 (CH); MS: m/z (%): 201 (52)
[M+], 171 (100) [M+ÀCH2O], 159 (15) [M+ÀC2H4N], 131 (11) [M+
ÀC3H4NO]; elemental analysis (%) calcd for C9H6NOF3: C 53.74, H
3.01, N 6.96; found: C 53.96, H 2.84, N 6.78.
3
(400 MHz, CDCl3): d=4.05 (t, 2H, J
(H,H)=9.5 Hz, NCH2), 4.43 (t, 2H,
3J
ACHTUNGTRENNUNG(H,H)=9.5 Hz, OCH2), 7.18 (m, 1H, 5-H), 7.70 (m, 1H, 6-H), 7.76 ppm
(m, 1H,2-H); 13C NMR (100 MHz, CDCl3): d=54.80 (s, NCH2), 67.75 (s,
OCH2), 117.05 (2ꢃm, C-2, C-5), 124.50 (m, C-6), 124.71 (s, i-CAr), 149.83
(dd, 1J
ACHTUNGTRENNUNG ACHTUNGTRENNUNG ACTUHNGTRENNUGN
(C,F)=248 Hz, 2J(C,F’)=13 Hz, C-2/3), 152.16 (dd, 1J
2-(2,4,5-Trifluorophenyl)-2-oxazoline (3b): Yield: 77%; 1H NMR
254 Hz, 2J
ACHTUNGTRENNUNG
(400 MHz, CDCl3): d=4.10 (t, 2H, 3J
ACHTUNGTRENNUNG
3J
ACHTUNGTRENNUNG
(376 MHz, CDCl3): d=À133.10 (m, 1F)/À137.07 ppm (m, 1F) (F-3/F-4);
IR: n˜ =3066/3050 (CH), 2985/2945/2916/2889 (CH2), 1652 (C=N), 1605/
1515 (C=C), 1436 (CH), 1366/1185 (CF), 1280/1063 (CO), 831 (CH),
721 cmÀ1 (CH2); MS: m/z (%): 183 (56) [M+], 153 (100) [M+ÀCH2O],
141 (14) [M+ÀC2H4N], 126 (12) [M+ÀC2H3NO], 113 (35) [M+
ÀC3H4NO]; elemental analysis (%) calcd for C9H7NOF2: C 59.02, H
3.85, N 7.65; found: C 58.92, H 3.56, N 7.44.
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
d=À110.16 (m, 1F, F-5), À127.93 (m, 1F, F-4), À141.84 ppm (m, 1F, F-
2); IR: n˜ =3038/3016 (CH), 2986/2890 (CH2), 1642 (C=N), 1626/1515 (C=
C), 1438 (CH), 1364/1141 (CF), 1238/1034 (CO), 899/806 (CH), 727 cmÀ1
(CH2); MS: m/z (%): 201 (35) [M+], 171 (100) [M+ÀCH2O], 159 (20)
[M+ÀC2H4N], 131 (20) [M+ÀC3H4NO]; elemental analysis (%) calcd for
C9H6NOF3: C 53.74, H 3.01, N 6.96; found: C 54.15, H 2.96, N 6.86.
2-(2,3-Difluorophenyl)-2-oxazoline (2d): Yield: 80%; 1H NMR
3
(400 MHz, CDCl3): d=4.11 (t, 2H, J
N
3J
ACHTUNGTRENNUNG(H,H)=9.5 Hz, OCH2), 7.11 (m, 1H, 4-H), 7.27 (m, 1H, 5-H) 7.63 ppm
(dt, 1H, 3J(6-H,5-H)=8 Hz, 4J(6-H,F-2)=1.5 Hz, 6-H); 13C NMR
A
A
(100 MHz, CDCl3): d=55.00 (s, NCH2), 67.11 (s, OCH2), 117.89 (d, 2J(i-
3
2-(2,3,6-Trifluorophenyl)-2-oxazoline (3c): Yield: 71%; 1H NMR
CAr,F-2)=7.5 Hz, i-CAr), 119.57 (d, J
(C-6,F-2)=17.5 Hz, C-6), 123.82 (m,
2
1
3
C-4), 125.37 (d, J
A
ACHTUNGTRENNUNG
(400 MHz, CDCl3): d=4.10 (t, 2H, J
N
2J(C-3,F-2)=14.5 Hz, C-3), 150.52 (dd, 1J
A
R
ACHTUNGTRENNUNG
3J
13C NMR (100 MHz, CDCl3): d=55.13 (s, NCH2), 67.65 (s, OCH2),
108.85 (dd, 2J(i-CAr,F-2)=2J(i-CAr,F-6)=14 Hz, i-CAr), 111.44 (dm, 2J
(C-
5,F-6)=24 Hz, C-5), 119.01 (m, C-4), 147.18 (dm, 1J
(C-3,F-3)=246 Hz,
C-3), 149.08 (dm, 1J(C-2,F-2)=259 Hz, C-2), 156.22 (dm, 1J
(C-9,F-9)=
266 Hz, C-9), 156.41 (t, 3J(C-3,F-5)=3J
(C-3,F-9)=4 Hz, C-3), 161.79 (dd,
1J(C-7,F-7)=266 Hz, 2J
(C-7,F-5)=8 Hz, C-7), 165.27 ppm (s, N=CO);
AHCTUNGTREGNUN(N H,H)=9.5 Hz, OCH2), 6.89 (m, 1H, 4-H), 7.22 ppm (m, 1H, 5-H);
3)=14.5 Hz, C-2), 162.49 ppm (s, N=CO); 19F NMR (376 MHz, CDCl3):
d=À135.40/À137.10 ppm (2ꢃm, 2ꢃ1F) (F-2/F-3); IR: n˜ =3030 (CH),
2986/2956/2913/2885 (CH2), 1643 (C=N), 1586/1492 (C=C), 1479 (CH),
1278/1079 (CO), 1226/1137 (CF), 800 (CH), 730 cmÀ1 (CH2); MS: m/z
(%): 183 (45) [M+], 153 (100) [M+ÀCH2O], 141 (9) [M+ÀC2H4N], 126
(13) [M+ÀC2H3NO], 113 (19) [M+ÀC3H4NO]; elemental analysis (%)
calcd for C9H7NOF2: C 59.02, H 3.85, N 7.65; found: C 59.17, H 3.78, N
7.48.
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
19F NMR (376 MHz, CDCl3): d=À114.14 (m, 1F, F-3), À132.04 (m, 1F,
F-2), À141.37 ppm (s, 1F, F-6); IR: n˜ =3080 (CH), 2984/2911/2886 (CH2),
1664/1635 (C=N), 1602/1492 (C=C), 1265/1017 (CO), 1176/1111 (CF),
848/814 cmÀ1 (CH); MS: m/z (%): 201 (49) [M+], 171 (100) [M+
ÀCH2O], 159 (12) [M+ÀC2H4N], 131 (18) [M+ÀC3H4NO]; elemental
analysis (%) calcd for C9H6NOF3: C 53.74, H 3.01, N 6.96; found: C
53.66, H 3.07, N 7.06.
2-(2,5-Difluorophenyl)-2-oxazoline (2e): Yield: 54%; 1H NMR
3
(400 MHz, CDCl3): d=4.11 (t, 2H, J
G
3J
ACHTUNGTRENNUNG(H,H)=9.5 Hz, OCH2), 6.92 (m, 2H, 3-H/4-H), 7.56 ppm (m, 1H, 6-H);
13C NMR (100 MHz, CDCl3): d=55.35 (s, NCH2), 67.30 (s, OCH2),
117.13 (m, i-CAr), 117.25, (m, C-3), 117.95 (m, C-6), 119.40 (m, C-4),
157.25 (dd, 1J
ACHTUNGTRENNUNG ACHTUNGTRENNUGN
(C-5,F-5)=255 Hz, 4J(C-5,F-2)=2 Hz, C-5), 158.07 (dd, 1J-
2-(2,3,5-Trifluorophenyl)-2-oxazoline (3d): Yield: 77%; 1H NMR
(C-2,F-2)=243 Hz, 4J
ACHTUNGTRENNUNG(C-2,F-5)=2 Hz, C-5), 160.30 ppm (m, N=CO);
3
(400 MHz, CDCl3): d=4.13 (t, 2H, J
N
19F NMR (376 MHz, CDCl3): d=À115.50/À118.46 ppm (2ꢃm, F-2/F-5);
IR: n˜ =3125/3088/3043 (CH), 2985/2943/2912/2888 (CH2), 1649 (C=N),
1596/1502/1493 (C=C), 1437 (CH), 1266/1043 (CO), 1222/1176 (CF), 888/
827 (CH), 737 cmÀ1 (CH2); MS: m/z (%): 183 (41) [M+], 153 (100) [M+
ÀCH2O], 141 (9) [M+ÀC2H4N], 126 (11) [M+ÀC2H3NO], 113 (18) [M+
ÀC3H4NO]; elemental analysis (%) calcd for C9H7NOF2: C 59.02, H
3.85, N 7.65; found: C 58.87, H 4.00, N 7.58.
3J
ACHTUNGTREN(NUNG H,H)=9.6 Hz, OCH2), 7.05 (m, 1H, 4-H), 7.38 ppm (m, 1H, 6-H);
13C NMR (100 MHz, CDCl3): d=55.31 (s, NCH2), 67.53 (s, OCH2),
2
2
3
108.11 (2d, J(C-4,F-3/5)=21 Hz, C-4), 112.00 (dd, J
(C-6,F-2)=4 Hz, C-6), 118.42 (m, i-CAr), 146.43 (dm, 1J
151.02 (dm, 1J(C,F)=240 Hz)/156.91 (dm, 1J
(C,F)=247 Hz) (C-2/C-3/C-
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
5), 159.72 ppm (m, N=CO); 19F NMR (376 MHz, CDCl3): d=À114.69
(m, 1F, F-5), À131.79 (m, 1F, F-3), À140.00 ppm (m, 1F, F-2); IR: n˜ =
3094/3035 (CH), 2917/2889 (CH2), 1638 (C=N), 1603/1496 (C=C), 1458
(CH), 1248/1020 (CO), 1174/1109 (CF), 873/827 cmÀ1 (CH); MS: m/z
(%): 201 (62) [M+], 171 (100) [M+ÀCH2O], 159 (13) [M+ÀC2H4N], 131
(29) [M+ÀC3H4NO]; elemental analysis (%) calcd for C9H6NOF3: C
53.74, H 3.01, N 6.96; found: C 53.82, H 2.86, N 6.72.
2-(2,4-Difluorophenyl)-2-oxazoline (2 f): Yield:
75%;
1H NMR
(400 MHz, CDCl3): d=4.08 (t, 2H, 3J
AHCTUNGTRENNUNG
2H, 3J
ACHTUNGTRENNUNG(2-H,1-H)=9.5 Hz, OCH2), 6.89 (m, 2H, 3-H,5-H) 7.87 ppm (m,
1H, 6-H); 13C NMR (100 MHz, CDCl3): d=55.16 (s, NCH2), 67.14 (s,
2
OCH2), 105.00 (t, J(C-3,F-2/4)=26 Hz, C-3), 111.47 (m, C-5), 112.55 (m,
3
3
2
2-(2,3,4-Trifluorophenyl)-2-oxazoline (3e): Yield: 77%; 1H NMR
i-CAr), 132.38 (dd, J
A
G
ACHTUNGTRENNUNG
(C,F-2)=6 Hz, N=CO), 161.84 (dd, 1J
13 Hz, C-2), 164.63 ppm (dd, J
G
G
(400 MHz, CDCl3): d=4.11 (t, 2H, 3J
ACHTUNGTRENNUNG
1
3
(C-4,F-4)=255 Hz, J
U
3J
ACHTUNGTRENNUNG
4); 19F NMR (376 MHz, CDCl3): d=À104.70 ppm (m, 2F, F-2/F-4); IR:
n˜ =3062 (CH), 2985/2958/2913/2886 (CH2), 1642 (C=N), 1611/1592/1505
(C=C), 1428 (CH), 1201/1110 (CF), 1264/1048 (CO), 865/857 (CH),
733 cmÀ1 (CH2); MS: m/z (%): 183 (50) [M+], 153 (100) [M+ÀCH2O],
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
G
N
ACHTUNGTRENNUG
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Chem. Eur. J. 2008, 14, 10396 – 10407

Polymerization of Fluorinated 2-Phenyl-2-oxazolines
FULL PAPER
4 Hz, C-2), 159.88 ppm (s, N=CO); 19F NMR (376 MHz, CDCl3): d=
À128.91/À130.24 (2ꢃm, 2ꢃ1F, F-3/F-4), À159.15 ppm (m, 1F, F-2); IR:
n˜ =3054/3008/2989 (CH), 2940/2919/2880 (CH2), 1650 (C=N), 1611/1509/
1493 (C=C), 1262/1032 (CO), 1132/1107 (CF), 838 cmÀ1 (CH); MS: m/z
(%): 201 (66) [M+], 171 (100) [M+ÀCH2O], 159 (19) [M+ÀC2H4N], 131
(25) [M+ÀC3H4NO]; elemental analysis (%) calcd for C9H6NOF3: C
53.74, H 3.01, N 6.96; found: C 53.90, H 2.67, N 6.66.
2-(2,3,4,5,6-Pentafluorophenyl)-2-oxazoline (5): Yield: 43%; 1H NMR
3
(400 MHz, CDCl3): d=4.14 (t, 2H, J
U
(H,H)=9.5 Hz, OCH2); 13C NMR (100 MHz, CDCl3): d=53.36 (s,
ACHTUNGTRENNUNG
G
AHCTUNGTRENNUNG
19F NMR (376 MHz, CDCl3): d=À136.89 (m, 2F, F-2), À149.88 (m, 1F,
F-4), À160.91 ppm (m, 2F, F-3); IR: n˜ =2989/2964/2948/2921/2895 (CH2),
1680 (C=N), 1655/1524 (C=C), 1488 (CH), 1359/980/954 (CF), 1207/
1076 cmÀ1 (CO); MS: m/z (%): 237 (31) [M+], 207 (100) [M+ÀCH2O],
195 (9) [M+ÀC2H4N], 181 (8) [M+ÀC2H4NO], 167 (12) [M+ÀC3H4NO];
elemental analysis (%) calcd for C9H4NOF5: C 45.59, H 1.70, N 5.91;
found: C 45.18, H 1.51, N 5.56.
2-(3,4,5-Trifluorophenyl)-2-oxazoline (3 f): Yield: 68%; 1H NMR
3
(400 MHz, CDCl3): d=4.06 (t, 2H, J
A
3J(H,H)=9.5 Hz, OCH2), 7.58 ppm (t, 1H, 3J
ACHTUNGTRENNUNG ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
Microwave-assisted polymerization of 2-oxazolines: The microwave vials
were heated to 1058C, allowed to cool to room temperature, and filled
with argon prior to use. For each polymerization, stock solutions
(c(Ox)=1.4m) were prepared with a monomer/initiator (MeOTs) ratio
ACHTUNGTRENNUNG
(F-3,F-4)=12 Hz, 3J
E
1F, F-4); IR: n˜ =3039/2987 (CH), 2966/2943/2919/2888 (CH2), 1651 (C=
N), 1609/1527 (C=C), 1432 (CH), 1239/1042 (CO), 1203 (CF), 899/881
(CH), 713 cmÀ1 (CH2); MS: m/z (%): 201 (80) [M+], 171 (100) [M+
ÀCH2O], 159 (19) [M+ÀC2H4N], 131 (43) [M+ÀC3H4NO]; elemental
analysis (%) calcd for C9H6NOF3: C 53.74, H 3.01, N 6.96; found: C
53.87, H 2.65, N 6.67.
of [Ox]/ACTHUNRTGNEUNG[MeOTs]=60:1 and divided over the different reaction vials (de-
pending on the amount of solution, the volume varied between 750 and
900 mL). After microwave irradiation for predefined times, the polymeri-
zation mixtures were quenched by the automated addition of water
(50 mL; on the Emrys Liberator). The polymerization mixtures were di-
luted once with CHCl3 to homogenize the solution, and the resulting mix-
tures were analyzed by GC and SEC to investigate the polymerization ki-
netics.
2-(2,3,4,5-Tetrafluorophenyl)-2-oxazoline (4a): Yield: 61%; 1H NMR
(400 MHz, CDCl3): d=4.12 (t, 2H, 3J
ACHTUNGTRENNUNG
3J
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
4/C-5), 159.08 ppm (s, N=CO); 19F NMR (376 MHz, CDCl3): d=À134.88
Results and Discussion
(m, 1F, F-4), À138.40 (m, 1F, F-5), À150.20 (m, 1F, F-3), À154.00 ppm (t,
1F, 3J
ACHTUNGTRENNUNG(F-2,F-3)=20 Hz, F-2); IR: n˜3039 (CH), 2991/2960/2943/2920/2891
Synthesis: The synthesis of the monofluorinated oxazolines
1a–c and the difluorinated oxazoline 2a was performed by
reaction of the corresponding fluorobenzonitriles with 2-
(CH2), 1643 (C=N), 1623/1524 (C=C), 1479 (CH), 1266/1082 (CO), 1191/
1150 (CF), 804 cmÀ1 (CH); MS: m/z (%): 219 (43) [M+], 189 (100) [M+
ÀCH2O], 177 (12) [M+ÀC2H4N], 149 (18) [M+ÀC3H4NO]; elemental
analysis (%) calcd for C9H5NOF4: C 49.33, H 2.30, N 6.39; found: C
49.40, H 2.10, N 6.27.
ethanolamine in the presence of ZnACTHNUTRGNEUNG(OAc)2 as a Lewis acid
catalyst to yield the desired oxazolines, as recently report-
ed.[25,26] To avoid undesired side reactions, such as nucleo-
philic substitution reactions of the para- or ortho-fluoro sub-
stituents of the benzonitriles, all other di-, tri-, tetra-, and
pentafluoro-substituted 2-phenyl-2-oxazolines 2b–f, 3a–f,
4a–c, and 5 were synthesized according to the two-step pro-
cedure outlined in Scheme 3.
Starting from acid chlorides 6 one can obtain amides 7
through a modified one-step reaction with the hydrochloride
salt of chloroethylamine in moderate-to-good yields (2 f, 3 f,
4a: 40–72%; 2b–e, 3a–e, 4b,c, 5: 80–90%).[25,35] Finally, the
desired oxazolines can be obtained by the elimination of hy-
drogen chloride by using different kind of bases, such as
KOH or potassium tert-butoxide, respectively. The difluoro-
substituted 2-phenyl-2-oxazolines could be synthesized by
performing the reaction over 24 h with KOH as the base in
2-(2,3,4,6-Tetrafluorophenyl)-2-oxazoline (4b): Yield: 65%; 1H NMR
(400 MHz, CDCl3): d=4.11 (t, 2H, 3J
ACHTUNGTRENNUNG
3J
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
(376 MHz, CDCl3): d=À111.72 (m, 1F)/À127.63 (m, 1F)/À129.36 (m,
1F)/À163.93 ppm (m, 1F) (F-2/F-3/F-4/F-6); IR: n˜ =3046/3010 (CH),
2923/2896 (CH2), 1651/1638 (C=N), 1613/1514 (C=C), 1474 (CH), 1270/
1058 (CO), 1206/1164 (CF), 842 cmÀ1 (CH); MS: m/z (%): 219 (35) [M+],
189 (100) [M+ÀCH2O], 177 (10) [M+ÀC2H4N], 149 (11) [M+ÀC3H4NO];
elemental analysis (%) calcd for C9H5NOF4: C 49.33, H 2.30, N 6.39;
found: C 49.05, H 2.02, N 6.06.
2-(2,3,5,6-Tetrafluorophenyl)-2-oxazoline (4c): Yield: 73%; 1H NMR
(400 MHz, CDCl3): d=4.14 (t, 2H, 3J
ACHTUNGTRENNUNG
3J
N
ACHTUNGTRENNUNG
2
3
108.02 (dt, J
144.89 (dm, 1J
(dm, (C,F)=252 Hz)
1J
G
ACHTUNGTRNE(NUNG C-4,F-2)=10 Hz, C-4), 110.01 (s, i-CAr),
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
155.66 ppm (s, N=CO); 19F NMR
(376 MHz, CDCl3): d=À 137.96 (s,
2F)/À137.99 ppm (s, 2F) (F-2/F-3);
IR: n˜ =3028 (CH), 2921/2888 (CH2),
1635 (C=N), 1610 (C=C), 1492 (CH),
1273/1001 (CO), 1185/1174 (CF),
885 cmÀ1 (CH); MS: m/z (%): 219 (31)
[M+], 189 (100) [M+ÀCH2O], 177 (7)
[M+ÀC2H4N],
149
(16)
[M+
ÀC3H4NO]; elemental analysis (%)
calcd for C9H5NOF4: C 49.33, H 2.30,
N 6.39; found: C 49.29, H 2.40, N 6.27.
Scheme 3. Two-step synthesis of 2-fluorophenyl-2-oxazolines 2b–5.
Chem. Eur. J. 2008, 14, 10396 – 10407
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10401

U. S. Schubert et al.
THF at room temperature (2c,e,f: 54–80% yield). Potassi-
um tert-butoxide was required as the base for the synthesis
of 5, produced in a yield of 43%, and led to a higher yield
of 86% being obtained for 2b, instead of the yield of 66%
that was obtained under the previously described conditions.
However, the reaction conditions for the other fluorophenyl
oxazolines turned out to be optimal with KOH as the base,
[18]crown-6 as a phase-transfer catalyst, and THF as the sol-
vent at room temperature to give the oxazolines 2d, 3a–f,
and 4a–c after a reaction of 2 h in moderate-to-good yields
(54–80%). These mild reaction conditions were accompa-
nied by minor side-product formation and hence easier pu-
rification. These optimized conditions represent a general
route for the successful synthesis of such kind of oxazolines.
methane at 1408C with methyl tosylate as the initiator and
microwave irradiation as the heat source. Stock solutions
were prepared that contained solvent, monomer, and initia-
tor with a ratio of [monomer]/[initiator]=60:1. The initial
monomer concentration [M]0 was in all cases [M]0 =1.4m.
Between five and seven vials were prepared, and the poly-
merizations were performed for different reaction times.
The reactions were quenched after the desired time by the
addition of water, and the monomer conversion, represented
as lnACHTUNTRGNE(NUG M0/Mt), was monitored by GC, whereas the molecular
weights and PDI values were investigated by SEC.
In all cases, the first-order kinetic plots of monomer con-
sumption with respect to the reaction time revealed a linear
relationship (Figures 1–3, left), thus demonstrating a con-
stant amount of propagating species. All the monomers
could be polymerized to full conversion in less than 3 h at
1408C under microwave irradiation, except for 2-(3,4,5-tri-
fluorophenyl)-2-oxazoline (3,4,5-TFOx; 3 f), which only
Polymerization: All the new monomers and the nonfluori-
nated analogue 2-phenyl-2-oxazoline (PhOx) were polymer-
ized through cationic ring-opening polymerization in nitro-
Figure 1. Polymerization of the 2-difluorophenyl-2-oxazolines 2a–f and PhOx as a reference. Left: first-order kinetics; right: number-average molecular
weight Mn against conversion. lin. regr.=linear regression.
Figure 2. Polymerization of the 2-trifluorophenyl-2-oxazolines 3a–f and PhOx as a reference. Left: first-order kinetics; right: number-average molecular
weight Mn against conversion.
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Chem. Eur. J. 2008, 14, 10396 – 10407

Polymerization of Fluorinated 2-Phenyl-2-oxazolines
FULL PAPER
Figure 3. Polymerization of the 2-tetrafluorophenyl-2-oxazolines 4a–c and 2-pentafluorophenyl-2-oxazoline 5 and PhOx as a reference. Left: first-order
kinetics; right: number-average molecular weight Mn against conversion.
reached 15% conversion within 1 h, and 2-(2,3,4,5,6-penta-
fluorophenyl)-2-oxazoline (2,3,4,5,6-PFOx; 5), which
reached full conversion within 7 h. Surprisingly, most of the
fluorinated aromatic monomers revealed faster polymeri-
zations than the unsubstituted PhOx, even though the elec-
tron-withdrawing effect of the fluorine atoms was expected
to lead to a decreased reaction speed and hence longer reac-
tion times. The effect of the fluorine substitution pattern on
the polymerization rate will be discussed later.
Subsequent SEC analysis resulted in constantly increasing
molecular weights with conversion during all the polymeri-
zations (Figures 1–3, right). The Mn values correlated in a
reasonably linear way to the monomer conversion, thus
demonstrating a living polymerization behavior. Discrepan-
cies with the theoretical Mn value might be related to the oc-
currence of some chain-transfer reactions and to the utilized
polystyrene standards. However, the PDI values of all the
oxazoline polymers are below 1.30 at <90% conversion,
Figure 4. MALDI-TOF mass spectrum of polymer polyACTHUNTGRNEUNG(3a).
thus indicating that the polymerizations take place in a
living manner. The higher PDI values for conversions great-
er than 90% are presumably caused by the high viscosity of
the polymerization mixture and therefore the hindered dif-
fusion of the last monomer units to the reaction centers.
Nonetheless, the polymerizations of 2b, 3a,c, and 4b,c re-
vealed low PDI= values of 1.2 at <99% conversion. Fur-
thermore, all the polymers could be characterized by
MALDI-TOF mass-spectrometric analysis. The spectrum of
ization rates than the corresponding 2-alkyl-2-oxazolines as
a result of the +M effect of the phenyl substituent onto the
oxazoline ring. The positive charge of the oxazolinium ring
of the growing species is partially compensated by resonance
with the aromatic system, thus lowering its electrophilicity
and hence causing a slower chain growth. For example,
PhOx polymerizes three times more slowely than 2-alkyl-2-
oxazolines such as 2-ethyl-2-oxazoline.[22] As a consequence,
it is expected that the polymerization of 2-phenyl-2-oxazo-
lines substituted with electron-withdrawing groups such as
fluorine exhibit even slower polymerization rates. Surpris-
ingly, only the polymerization rates for 2a,c, 3 f, and 5 are
significantly lower than for PhOx, thus representing the
monomers with a predominantly negative impact on the
+M effect.
polyACHTUNGTRENNUNG(3a) features a monomodal mass distribution and equi-
distant peaks with a difference of D=201 Da according to
the mass of one monomer unit (Figure 4). The spectra of the
other polymers were similar with equidistant peaks of D=
165 (1a–c), 183 (2a–f), 201 (3a–f), 219 (4a–c), and 237 Da
(5), respectively (see Figures S1–S19 in the Supporting In-
formation).
From the slopes of the first-order kinetic plots (Figures 1–
3, left), the corresponding polymerization rates were deter-
mined (Table 1). 2-Aryl-2-oxazolines feature lower polymer-
Chem. Eur. J. 2008, 14, 10396 – 10407
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10403

U. S. Schubert et al.
Table 1. Polymerization rates kP [ꢃ10À3 LmolÀ1 sÀ1] of PhOx and the fluorinated 2-aromatic-2-oxazoline mo-
nomer library in nitromethane at 1408C.
the pentafluoro monomer 5. In
this case, the electron-with-
drawing effect of the meta- and/
Oxazolines with no
Mono-ortho-fluoro oxazolines
Di-ortho-fluoro oxazolines
ortho-fluoro substituents
or
para-fluoro
substituents
Monomer
kP
Monomer
kP
Monomer
2,6-DFOx
2,4,6-TFOx
2,3,6-TFOx
2,3,4,6-TFOx
2,3,5,6-TFOx
2,3,4,5,6-PFOx
kP
overcompensates for the posi-
tive effect of the ortho-difluoro
substitution. This destabilizing
effect is even more pronounced
for the trifluoro oxazoline lack-
ing any ortho substituents 3,4,5-
TFOx (3 f), which only be poly-
merized at <25% of monomer
conversion (degree of polymeri-
PhOx
m-Fox
p-Fox
3,5-DFOx
3,4-DFOx
3,4,5-TFOx
35.8
29.3
26.7
14.8
14.2
5.5
o-Fox
1a
2d
2e
2 f
3b
3d
3e
4a
173.1
102.4
103.9
96.4
57.1
46.5
2b
3a
3c
4b
4c
5
382.4
103.5
134.1
64.2
41.7
7.3
1b
1c
2a
2c
3 f
2,3-DFOx
2,5-DFOx
2,4-DFOx
2,4,5-TFOx
2,3,5-TFOx
2,3,4-TFOx
2,3,4,5-TFOx
68.9
29.4
zation
(DP)ꢀ15)
within
However, the polymerization rates for all other monomers
containing one or two ortho-fluoro substituents are higher
or similar to PhOx. As recently discussed in detail, ortho-
fluoro substituents have two positive effects on the rate of
the polymerization of such oxazolines.[25] First, the coplanar-
ity of the oxazoline and the phenyl rings is repealed, thus re-
sulting in a higher nucleophilicity of the monomer; second,
the ortho-fluoro substituent stabilizes the cationic reaction
center—the tetra-coordinated nitrogen atom—during the
polymerization by donation of electron density through
space. Both effects overcompensate for the negative elec-
tron-withdrawing effect of the fluorine substituent(s) and
contribute to a significant acceleration of the polymeri-
zation. This behavior is especially noticeable from the poly-
merization rates of the ortho-difluoro oxazoline 2b, oxazo-
lines 1a and 2d,e,f containing one ortho-fluoro substituent,
and even the trifluoro oxazolines 3a,c containing two ortho-
fluoro substituents. Whereas 2-(2,6-difluorophenyl)-2-oxazo-
line (o-DFOx; 2b) polymerizes ten times faster than PhOx
and even three times faster
16 hours. It is noteworthy that o-DFOx (2b) is the fastest 2-
oxazoline monomer in the living cationic ring-opening poly-
merization to date.
Polymer properties: All synthesized polymers (DPꢀ60)
were characterized by thermogravimetric analysis (TGA),
differential scanning calorimetry (DSC), and contact-angle
measurements to investigate selected thermal and surface
properties, respectively. Before the analysis, the end samples
of the polymerization kinetic experiments were precipitated
in cold diethyl ether, isolated by filtration, and dried for
24 h at 408C and 1 mbar prior to use.
The thermal stability of the library of oxazoline polymers
was determined by TGA in a temperature range of 25–
8008C. All the heating curves are depicted in the Supporting
Information (Figure S24–S27), and the results are summar-
ized in Figure 5 and Table S1 in the Supporting Information.
All the polymers are stable up to at least 2928C (i.e., 2b)
but the range of temperatures over 5% degradation is
than 2-n-alkyl-2-oxazolines,[25,36]
the other monomers polymerize
three to five times faster than
the unsubstituted PhOx ana-
logue. The trifluoro oxazolines
with one ortho-fluoro substitu-
ent 3b,d,e and even the tetra-
fluoro oxazolines 4a–c polymer-
ize slightly faster or at a compa-
rable rate to PhOx. Here, the
positive effects of the ortho-
fluoro substituents balance the
negative electron-withdrawing
effect of the meta- and/or para-
fluoro substituents. As men-
tioned previously, only the
monomers without any ortho-
fluoro substituents have signifi-
cantly slower polymerization
rates. PhOx polymerizes ap-
proximately two times faster
than the difluoro monomers
Figure 5. Thermostability of the polymers of the fluorophenyl oxazolines 2a–f, 3a–f, 4a–c, 5, and PhOx deter-
2a,c and five times faster than mined by TGA.
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Chem. Eur. J. 2008, 14, 10396 – 10407

Polymerization of Fluorinated 2-Phenyl-2-oxazolines
FULL PAPER
broad up to 3728C for the most stable polyoxazoline 2,4,6-
TFOx (3a). All the fluorinated oxazoline polymers degrade
in one step, and the temperatures of the inflection point
range from 361 to 4498C, comparable to the properties of
polymers based on 2-alkyl-2-oxazolines.[27] A more detailed
look into the inflection temperatures reveals a significant in-
fluence of the substitution pattern. All the polymers with
two ortho-fluoro substituents (2a, 3a,c, 4b,c, and 5) reveal
significantly higher inflection temperatures relative to the
analogue polymers with or without any ortho-fluoro sub-
stituents. Furthermore, the latter are even less thermally
stable than PhOx, as indicated by lower inflection tempera-
tures.
above 1208C in such cases reflect the limited rotational free-
dom of the phenyl rings carrying two ortho-fluoro substitu-
ents, thus culminating for the sterically most demanding ox-
azolines 3a and 5 in maximal Tg values of 133 and 1358C,
respectively, which is approaching the highest reported
Tg value of 1398C for poly(2-oxazoline)s bearing very bulky
adamantyl side groups. The high Tg values of the polymers
with ortho-fluoro substituents is most likely because of the
À
presence of attractive C F···C=O interactions, which de-
crease the chain mobility and thus increase the Tg value.[39,40]
These attractive interactions are also evidenced by the fact
that the Tg value for polystyrene (Tg =1008C), which has no
heteroatoms to form such attractive interactions, only slight-
ly increases when fluoro substituents are introduced, that is,
The DSC measurements (see Figures S20–S23 in the Sup-
porting Information for the corresponding graphs) led to the
conclusion that all the polymers exhibit one glass transition
temperature Tg, but no melting point could be observed in
any case. The glass transition temperature characterizes the
chain mobility of a polymer, which means that a high
Tg value represents a low chain mobility.[37] It is known that
polymers based on aromatic 2-oxazolines, such as PhOx,
feature glass-transition temperatures of Tg =103[32] or
1058C,[12] which are significantly higher than the Tg values of
2-methyl- or 2-ethyl-2-oxazolines (between 60 and
808C)[12,38] because of the influence of the rigid aromatic
phenyl ring. The Tg values of the present fluorinated poly-
mer library are comparable to PhOx or higher (see Figure 6
and Table S1 in the Supporting Information). The polymers
with two ortho-fluoro substituents on the phenyl ring (2a,
3a,c, 4b,c, and 5) revealed significantly higher Tg values
than the other copolymers. These observed Tg values of
poly(pentafluorophenyl)styrene and polyACHTNUTRGNEUNG(4-fluoro)styrene
have Tg values of 106 and 1088C, respectively.[41] The ex-
tremely low Tg value for 3,4,5-TFOx (3 f) of around 608C
can be explained by the short length of the polymer chain,
which is only DPꢀ15 as discussed before.
To characterize the surface properties of the present oxa-
zoline polymer library, the oxazolines were spin-coated onto
glass slides and the contact angles were measured for two
different test liquids, namely, diiodomethane and ethylene
glycol. Next, the polymer films were annealed by leaving
them overnight in an oven at 1408C, which is higher than
the corresponding Tg value. The surface energies (see
Figure 7 and Table S1 in the Supporting Information) were
calculated from the resulting contact angles. Unfortunately,
not all polymers formed perfect homogenous clear films on
the glass slide by spin-coating. The polymers based on the
trifluoro oxazolines 3e and 3 f and the tetrafluoro mono-
mers 4a–c formed films that
featured slightly opaque parts.
Hence, the surface properties
were determined from the clear
parts.
All the obtained surface en-
ergies are lower than the sur-
face energy of the unfluorinat-
ed PhOx (42.6 mNmÀ1); over-
all, the presence of fluorine
substituents on the phenyl ring
led to lower surface energies as
expected for fluorine-based
polymers. However, the surface
energy does not continuously
decrease with increasing fluo-
rine substitution, although the
tetrafluoro oxazoline polymer
of 4b and the pentafluoro oxa-
zoline polymer of 5 represent
the polymers with the lowest
surface energies of 25.7 mNmÀ1
after annealing.
In general, annealing led to
significantly lower surface ener-
gies relative to the untreated
Figure 6. Glass-transition temperatures Tg of the polymers based on the fluorophenyl oxazolines 2a–f, 3a–f,
4a–c, 5, and PhOx determined by DSC.
Chem. Eur. J. 2008, 14, 10396 – 10407
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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U. S. Schubert et al.
In conclusion, the presence
of a para-fluoro substituent is
sufficient for a reasonable re-
duction of the surface energy,
although the minimal surface
energy is obtained for the pen-
tafluoro oxazoline 5.
Conclusions and Outlook
The synthesis and polymeri-
zation of all possible fluorinat-
ed 2-phenyl-2-oxazolines was
successfully performed and se-
lected polymer properties were
analyzed in detail. All the mon-
omers could be polymerized
through a living cationic ring-
opening polymerization with
microwave irradiation as the
heat source. The fluoro-substi-
tuted
2-phenyl-2-oxazolines
Figure 7. Surface energies (SEs) of the polymers of the fluorophenyl oxazolines 2a–f, 3a–f, 4a–c, 5, and PhOx
before and after annealing (16 h, 1408C).
containing one or two ortho-
fluoro substituents polymerize
faster than the parent unsubsti-
tuted 2-phenyl-2-oxazoline for
polymer films. As a result of the heat-induced flexibility of
the polymer side chain, the optimal arrangement of the
fluoro-substituted phenyl rings of the polymers is enabled
during the annealing step. Therefore, the outer fluorine sub-
stituents can orient directly toward the air surface, thus re-
sulting in lower surface energy values. This behavior be-
comes obvious by a detailed look at the substitution pattern
of the polymers with the lowest surface energies beside 4b
and 5, which are in fact 1c (1ꢃp), 2c (1ꢃp, 1ꢃm), 3a (1ꢃp,
2ꢃo), 3b (1ꢃp, 1ꢃm, 1ꢃo), and 4a (1ꢃp, 2ꢃm, 1ꢃo) with
surface energies between 27–29 mNmÀ1. All these polymers
carry a para-fluoro substituent that causes an efficient de-
crease of the corresponding surface energy. The importance
of especially the para-fluoro substituent in lowering the sur-
face energy is further confirmed by a detailed look onto the
surface energies of the polymers based on the tetrafluoro
oxazolines, in which 4c, without a para-fluoro substituent,
displays a significantly higher surface energy than 4a,b. This
trend is further supported by the the fact that the highest
surface energy (40 mNmÀ1; not considering PhOx) was ob-
tained for the fluorinated polymer 2b, which is substituted
with two ortho-fluoro substituents that cannot be readily ori-
ented towards the surface. The surface energy values of the
remaining oxazolines span the range between the penta-
fluoro-substituted oxazoline and PhOx. The relatively high
surface energy for 3,4,5-TFOx 3 f (34 mNmÀ1) with two
meta- and one para-fluorine substituents is not understood
at the moment, but might be related to the short polymer
chain length.
two reasons: First, the interaction of the cationic reaction
center of N+ with the ortho-fluoro substituent overcompen-
sates for the negative electron-withdrawing effect; second,
the nucleophilic character of the monomers are increased
because of the nonplanarity of the oxazoline ring and the
phenyl substituent. The lack of ortho-fluoro substituents sig-
nificantly decreases the polymerization rates for the difluoro
monomers 2a,c and the trifluoro monomer 3 f.
The different substitution patterns were found to have a
remarkable influence on the polymer properties as well. The
thermal stability and the glass-transition temperatures were
found to increase in the presence of ortho-fluoro substitu-
À
ents, which is attributed to attractive C F···C=O interactions
that decrease the chain mobility, thus increasing the glass-
transition temperatures. Furthermore, these interactions
seem to stabilize the amidic side chains, thus resulting in
higher decomposition temperatures. In contrast to the ther-
mal properties, the surface energy of the fluorinated aromat-
ic poly(2-oxazoline)s was found to be mostly dependent on
the presence of para-fluoro substituents; that is, the surface
energy decreases when para substituents are present, which
can be understood by the easier orientation of such para
substituents toward the surface without exposing the polar
polymer backbone to the surface.
Within this oxazoline library, especially the polymers of
3a, 4b, and 5, which feature both a high Tg value and a low
surface energy, there might be useful candidates for the for-
mation of multicompartment micelles once integrated into
an amphiphilic triblock copolymeric structure. Therefore,
future investigations will focus on the synthesis of well-de-
10406
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Chem. Eur. J. 2008, 14, 10396 – 10407

Polymerization of Fluorinated 2-Phenyl-2-oxazolines
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Received: April 9, 2008
Published online: September 26, 2008
Chem. Eur. J. 2008, 14, 10396 – 10407
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10407