Synthesis of cinnamic acid-derived 4,5-dihydrooxazoles

Article abstract of DOI:10.2478/s11696-013-0405-x

A range of cinnamic units containing 4,5-dihydrooxazoles was prepared using two different synthetic routes. The first method was based on the transformation of substituted cinnamic or benzoic acids to 2-styryl-4,5- dihydrooxazoles. Several derivatives con

Full text of DOI:10.2478/s11696-013-0405-x

Chemical Papers 67 (11) 1424–1432 (2013)
DOI: 10.2478/s11696-013-0405-x
ORIGINAL PAPER
Synthesis of cinnamic acid-derived 4,5-dihydrooxazoles
Juraj Kronek*, Tomáš Nedelčev, Marcel Mikulec, Angela Kleinová, Jozef Lustoň
Polymer Institute, Slovak Academy of Sciences, Centre of Excellence-GLYCOMED,
Dúbravská cesta 9, 845 41 Bratislava, Slovakia
Received 17 April 2012; Revised 13 September 2012; Accepted 18 September 2012
Dedicated to Professor Štefan Toma on the occasion of his 75th birthday
A range of cinnamic units containing 4,5-dihydrooxazoles was prepared using two different syn-
thetic routes. The first method was based on the transformation of substituted cinnamic or benzoic
acids to 2-styryl-4,5-dihydrooxazoles. Several derivatives containing phenolic groups were prepared
in this manner. The second approach consisted of a reaction between the 4,5-dihydrooxazole moiety
and double bond-containing compounds. These compounds contain two or more reactive centres
capable of providing polymerisations and also organic reactions.
c
ꢀ 2013 Institute of Chemistry, Slovak Academy of Sciences
Keywords: cinnamic acid derivatives, 4,5-dihydrooxazole, conjugated unsaturated bond, 2-
oxazolines
Introduction
2006; Nagarathinam et al., 2008). The cyclodimerisa-
tion of unsaturated compounds was used in syntheses
of organic compounds (K¨onig et al., 1996) or for pho-
tocrosslinking of unsaturated polymers (Rabek, 1987;
Nagarathinam & Vittal, 2006). Irradiation of poly-
meric unsaturated anhydrides derived from cinnamic
acids leads to the formation of an insoluble poly-
mer (Pinther et al., 1992) which indicates the course
of a photocrosslinking process. Micelle crosslinking
can be achieved by (2 + 2) cycloaddition reaction of
co-polymer-containing amphiphilic comonomers and
comonomers bearing a cinnamic chromophore with
light (λ > 270 nm) (Szczubialka et al., 1999). The
crosslinking was rapid and was concluded in several
minutes. In this case, irradiation of the micelle solu-
tion resulted in a decrease in the polymer absorption
band around 280 nm.
4,5-Dihydrooxazoles, also known as 2-oxazolines,
are members of a large family of cyclic imino ethers.
4,5-Dihydrooxazoles react with different functional
groups in ring-saving reactions as well as in ring-
opening reactions (Kronek et al., 1998a). Formation
of the 4,5-dihydrooxazole ring can occur in several
ways (Kronek et al., 1998b). The most common way
Polymers which contain unsaturated bonds play
an important role in polymer chemistry where they
can be involved in radical or photochemical pro-
cesses. Radical reactions include radical polymerisa-
tion, grafting, or crosslinking. Photoreactions proceed-
ing subsequent to irradiation can be divided into a
reversible trans/cis photoisomerisation, a photocycli-
sation, (2 + 2) photodimerisation, or a photoreduc-
tion (Rabek, 1987). E/Z isomerisations of azo com-
pounds (Suginome, 1995) and alkenes, especially 1,2-
diphenylethenes (stilbene)s and derivatives of cin-
namic acids (Saltiel et al., 1995), are well known. The
mechanism of the photoisomerisation of stilbenes has
been the subject of extensive study over the last few
decades. Stilbene undergoes isomerisation from the
stable trans-form to the Z-form upon irradiation at
280–320 nm. This photoreaction proceeds via the low-
est triplet state (1t∗) of stilbene (Saltiel & Sun, 1989;
Papper & Likhtenshtein, 2001). Stilbenes and deriva-
tives of cinnamic acids can also provide photoinitiated
(2 + 2) cycloaddition, both in solution (Kaupp, 1995),
and in solid state (Cohen et al., 1964; Bertmer et al.,
*Corresponding author, e-mail: upolkron@savba.sk

J. Kronek et al./Chemical Papers 67 (11) 1424–1432 (2013)
1425
is the dehydration of N-(2-hydroxyethyl)amides using
thionyl chloride, sulphuric acid, or Lewis acids or de-
hydrohalogenation of N-(2-haloethyl)amides using a
base such as alkali hydroxides or alkali alkanoates.
4,5-Dihydrooxazoles-containing compounds can also
be prepared from nitriles in the reaction with oxirane,
ethylene glycol, or 2-aminoethanol.
observed that, in the AIBN-initiated polymerisa-
tion, the polyreaction proceeded through the unsat-
urated bond while perchloric acid initiated polyreac-
tion yields poly(N-methacroylethyleneimine). There-
fore, polymerisation conditions can vary, hence poly-
mers with different properties can be achieved.
The aim of this work was the preparation of 4,5-
dihydrooxazole derivatives containing a conjugated
unsaturated bond and another reactive group in
one molecule. Two synthetic routes were employed.
These molecules with three reaction centres represent
monomers of ABC types and can provide three dif-
ferent polymerisation reactions such as radical poly-
merization, cationic polymerization, or polyaddition
reactions. The spectral properties of the compounds
thus prepared were also studied.
Synthesis of unsaturated 4,5-dihydrooxazoles can
be performed in a variety of ways. The simplest com-
pounds with the end-double bond and 4-dihydro-
oxazole structural unit were prepared by the con-
densation of 2-methyl- or 2-ethyl-4,5-dihydrooxazole
with paraformaldehyde. In the case of the reac-
tion of 2-ethyl-4,5-dihydrooxazole with paraformalde-
hyde, the resulting 2-(1,1-bis(hydroxymethyl)alkyl)-
4,5-dihydrooxazole can be thermally dehydrated to
the required product (Frump, 1971). Another ap-
proach was reported by de Benneville and Luskin
(1958) who synthesised the required compounds by
condensation of methyl methacrylate with an aminoal-
cohol; subsequently, after thermal treatment, they ob-
tained 2-isopropenyl-4,5-dihydrooxazole. Condensa-
tion of the methylene group with acidic protons in the
alkyl side-group can also be achieved with aromatic
aldehydes (Wehrmeister, 1962). Reactions result in the
formation of 2-phenylethenyl-4,5-dihydrooxazoles. In
another paper, the condensation of aromatic dialde-
hydes with 2-alkyl-4,5-dihydrooxazoles was described
(Lustoň et al., 1999a). This reaction leads to the
formation of alkadienes with two 4,5-dihydrooxazole
groups on both sides of the chain. Hydrolysis of the
unsaturated bis(4,5-dihydrooxazole) formed provides
p- or m-phenylenediacrylic acids with high yields and
represents an alternative route to the Perkin or Kno-
evenagel methods. Another way is preparation of the
allyl group containing 4,5-dihydrooxazoles under con-
ditions of phase transfer catalysis (PTC) (Luston
et al., 1999b). The reactions of a different hydroxyl
group-containing 4,5-dihydrooxazoles with allyl bro-
mide were performed in a mixture of organic solvent
(chloroform, dichloromethane, toluene) and aqueous
sodium hydroxide at ambient temperature in the pres-
ence of a catalyst (tetrabutylammonium hydrogen sul-
phate, tetrabutylammonium bromide).
Experimental
General
All chemicals were purchased from Sigma–Aldrich
(Germany). N,N-dimethylformamide (DMF) was pu-
rified by distillation over P2O5. The solvents used for
spectroscopic measurements were of photochemical or
HPLC grade. The syntheses of 4-(4,5-dihydrooxazol-
2-yl)phenol, 3-(4,5-dihydrooxazol-2-yl)phenol, and 2-
(4,5-dihydrooxazol-2-yl)phenol were described previ-
ously (Lustoň et al., 2006).
The 1H NMR (400 MHz) and 13C NMR (100 MHz)
spectra of all the compounds were recorded at am-
bient temperature using a Varian VXR-400 (Varian,
USA). Tetramethylsilane (TMS) was used as an in-
ternal standard for 1H NMR spectra. The chemi-
cal shift is given in δ relative to the internal stan-
dard. 13C NMR spectra were measured with an auto-
matic chemical shifts calibration. The FTIR spectra
were recorded with an IR spectrophotometer, NICO-
LET 8700TM
(Thermo Scientific, USA), with 64 scans
and resolution of 4 cm−1. All the compounds were
measured in KBr pellets. The UV-VIS spectra of
all derivatives were conducted with a UV-VIS spec-
trophotometer (Shimadzu 1650 PC, Japan) in various
solutions of spectroscopic grade at a concentration of
5 × 10−5 mol L−1. The resolution of the UV-VIS spec-
trophotometer was 0.2 nm. All melting points were
measured using a Kofler hot stage (VEB Analytik,
Germany) and were used uncorrected. Elemental anal-
yses were performed on a FLASH 2000 Organic ele-
mental analyser (CHNS-O) (Thermo Fisher Scientific,
USA).
The presence of an unsaturated bond together
with 4,5-dihydrooxazole group in the molecule of a
monomer makes several types of polymerisation pos-
sible. The first is the cationic ring-opening polymerisa-
tion of the heterocyclic group. The second is the rad-
ical polymerisation and the third is the anionic poly-
merisation (Tomalia et al., 1980). This means that,
depending on the polymerisation conditions, different
polymers can be obtained from the same monomer.
Thus, Kagiya and Matsuda (1972) performed poly-
merisation of 2-isopropenyl-4,5-dihydrooxazole initi-
General procedure for preparation of cin-
namoyl chlorides (IIa–IIe)
ated by 2,2ꢀ
-azobis(2-methylpropionitrile), 2-(azo(1-
4-Acetoxycinnamic acid (Ia–Ie; 0.029 mol) was dis-
solved in thionyl chloride (21 mL, 0.29 mol) in a
100 mL round-bottom flask equipped with a mag-
cyano-1-methylethyl))-2-methylpropane nitrile (azo-
bisisbutyronitrile, AIBN) or perchloric acid. They

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J. Kronek et al./Chemical Papers 67 (11) 1424–1432 (2013)
netic stirring rod and condenser. The reaction mixture
was stirred under reflux for 24 h. Next, the excess of
thionyl chloride was removed under reduced pressure.
Yellowish solids of chlorides (IIa-IIe) were obtained.
der reduced pressure. The yellowish crude solid so ob-
tained was recrystallised from ethyl acetate and light
yellow crystals of 4,5-dihydrooxazole (IVa–IVe) were
obtained.
General procedure for preparation of amides
(IIIa–IIIe)
General procedure for the reaction of (4,5-
dihydrooxazolyl)phenols with methyl 4-((E)-
3-chloro-3-oxo-1-propenyl)benzoate (IIe)
2-Chloroethylamine hydrochloride (1.74 g, 0.015
mol) was dissolved in 2 M aqueous KOH (14 mL, 0.03
mol) in a 250 mL round-bottom flask equipped with
a magnetic stirring rod and dropping funnel. The so-
lution of a chloride (IIa–IIe, 0.015 mol) in chloroform
(60 mL) was added dropwise for 30 min under cooling
in an ice-bath. The reaction mixture was vigorously
stirred for 3 h, then the organic and aqueous layers
were separated. The aqueous layer was extracted with
chloroform (3 × 15 mL). The organic layers thus col-
lected were washed with water and dried over sodium
sulphate. After removal of the solvent, a light yellow
solid of amides (IIIa–IIIe) was obtained. The product
was recrystallised from ethanol.
(4,5-Dihydrooxazol-2-yl)phenols (Va–Vb; 0.85 g,
0.005 mol) and triethylamine (0.51 mol, 0.70 mol,
0.005 mol) were dissolved in dry DMF (10 mL) and
stirred in an ice-bath. A solution of IIe (1.12 g, 0.005
mol) in DMF (3 mL) was added dropwise for 30 min,
then the reaction mixture was stirred in an ice bath
for 5 h. Next, the reaction mixture was poured onto
ice (50 mL). The white crystals of ester (VIa–VIb)
formed were crystallised from ethyl acetate.
Results and discussion
Compounds containing 4,5-dihydrooxazole, conju-
gated unsaturated bond and another functionality
represent multi-functional compounds of ABC type
with significant importance in polymer chemistry,
photochemistry, and optoelectronics. The design of
the molecule makes the polymerisation reactions on
2-oxazoline or double bonds possible and the third
group remains untreated. Both types of polymerisa-
tion species give controlled polymerisation; this means
that the size, polydispersity, and properties of the
General procedure for preparation of 4,5-
dihydrooxazoles (IVa–IVe)
Amide (IIIa–IIIe, 0.014 mol) was dissolved in 1 M
methanolic KOH (25 mL) in a 100 mL round bottom
flask. The reaction mixture was stirred under reflux for
3 h. After cooling, the inorganic salt thus formed was
removed by filtration and methanol was removed un-
Table 1. Data characterising newly prepared compounds
wi(calc.)/%
wi(found)/%
Yield
M.p.
Compound
Formula
Mr
C
H
N
%
93
78
31
90
80
97
40
91
51
48
◦C
IIIb
IIIc
IIId
IIIe
IVb
IVc
IVd
IVe
VIa
VIb
C13H14ClNO3
C13H14ClNO3
C13H14ClNO3
Cb13H14ClNO3
C11H11NO2
C11H11NO2
C11H11NO2
C12H11NO3
C19H15NO5
C19H15NO5
267.71
267.71
267.71
267.71
189.22
189.22
189.22
217.22
337.33
337.33
58.32
57.91
58.32
57.95
58.32
57.89
58.32
57.91
69.83
69.66
69.83
69.58
69.83
69.33
66.35
66.03
67.65
68.06
67.65
67.84
5.27
5.38
5.27
5.34
5.27
5.23
5.27
5.18
5.86
6.00
5.86
5.94
5.86
5.98
5.10
5.18
4.48
4.82
4.48
4.86
5.23
5.18
5.23
5.12
5.23
5.12
5.23
4.98
7.40
7.23
7.40
7.13
7.40
7.56
6.45
6.25
4.15
3.97
4.15
3.89
105–110
102–105
158–170
114–116
165–167
229–231
185–186
> 300
147
173–176

J. Kronek et al./Chemical Papers 67 (11) 1424–1432 (2013)
1427
Fig. 1. Synthesis of 4,5-dihydrooxazoles I–V: i) thionyl chloride; ii) 2-chloroethanamine hydrochloride, KOH; iii) KOH, MeOH.
polymers formed can be controlled during the poly-
merisation process. In addition, monomers and poly-
mers containing double bonds provide photochemical
reactions such as (2 + 2) cycloaddition or E/Z iso-
merisation (Rabek, 1987).
Several 4,5-dihydrooxazoles containing a conju-
gated unsaturated bond and another group were pre-
pared by two different approaches (Table 1). Syn-
thesis of the derivatives containing phenolic or ben-
zoic groups entailed the commercially available hy-
droxycinnamic acids or substituted cinnamic acid pre-
pared by the Knoevenagel reaction of the substi-
tuted aromatic aldehydes with malonic acid. The sec-
ond approach concerned the esterification of x-(4,5-
dihydrooxazol-2-yl)phenols (x = 2, 3, 4) with chloride
of 4-methoxycarbonyl cinnamic acid.
The multi-functional compounds containing three
different functional groups (IVb–IVd) were prepared
by the reactions depicted in Fig. 1. II contains a phe-
nolic group known as a possible photoacid, which is
able to create the ionic complexes (Kronek et al.,
2002). II can also be used as a fluorescent probe or
photo- and pH-sensitive modifier.
IVb was prepared from 4-acetoxyxycinnamic acid
(Ib) according to the scheme in Fig. 1. Synthesis con-
sisted of the reaction of carboxylic acid Ib with thionyl
chloride, the reaction of IIb with 2-chloroethylamine
hydrochloride under Schotten–Baumann conditions
and the dehydrohalogenation of IIIb with a strong
base to give the required 4,5-dihydrooxazole IVb. The
fact that cyclisation and deprotection occurred simul-
taneously represents an advantage.
IVa represents a simple model of a compound
containing a conjugated unsaturated bond and 4,5-
dihydrooxazole ring. IVa was prepared by two-step
synthesis from cinnamoyl chloride (IIa) including
a reaction with 2-chloroethylamine hydrochloride in
the presence of a base and a cyclisation step with
KOH (Fig. 1). IVa was also prepared using the re-
action of cinnamoyl chloride with 2-aminoethanol in
dichloromethane and aqueous NaOH under Schotten–
Baumann conditions and cyclisation with mesyl chlo-
ride in the presence of triethylamine (Beutler, 2005). A
An analogous procedure was used for the synthe-
sis of meta-derivative IVc and ortho-derivative IVd. In
the case of IVd, deprotection of the phenolic group oc-
curred during the amidation step. In this step a lower
yield due to the increased solubility of the deprotected
amide in water during isolation was achieved.
The more common procedure via esterification of
the starting carboxylic acid, amidation reaction with
2-aminoethanol, and cyclisation with thionyl chloride
could not be used due to the side reactions of 2-
aminoethanol with methyl 4-hydroxycinnamate (Lus-
further possibility is the reaction of N-(2-hydroxyethyl) ton et al., 2001). In this case, the side Michael addition
cinnamamide using a triphenylphosphine–2,3-dichloro- of 2-aminoethanol to the unsaturated bond is the par-
5,6-dicyanobenzoquinone (PPh3–DCQ) system (Xu &
Li, 2009). The structure of IVa was confirmed by NMR
spectroscopy and compared with the results in the lit-
erature.
allel reaction of the amidation reaction (Fig. 2).
1
The structures of IVb–IVd were confirmed by H
NMR and 13C NMR spectroscopy. In the spectrum of
II, two triplets with δ 3.84 and 4.25 were assigned to

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J. Kronek et al./Chemical Papers 67 (11) 1424–1432 (2013)
Fig. 2. Michael addition of 2-aminoethanol to methyl 4-hydroxycinnamate as side reaction to amidation of the ester with 2-
aminoethanol: i) 2-aminoethanol.
Fig. 3. Synthesis of compounds VIa, VIb: i) triethylamine, DMF.
the protons of the 4,5-dihydrooxazole cycle and two
signals with δ 6.48 and 7.21 to the unsaturated bond.
Two doublets with δ 6.77 and 7.44 were assigned to
the aromatic protons. The singlet with δ 10.13 was
assigned to a phenolic proton. The interaction con-
stants (1J) calculated for the protons of the unsatu-
rated bond are equal to 16.2 Hz and 16.4 Hz, respec-
tively, which are typical values of E-isomers.
Table 2. UV-VIS and FTIR absorbance bands of compounds
IVa–IVe and VIa, VIb
FTIRa
cm−1
UV-VISb
nm
UV-VISc
nm
Compound
IVa
IVb
IVc
IVd
IVe
VIa
VIb
1651
1652
1655
1648
1625
1635
1632
280
312
282
322, 279
293
289
4.23
4.41
4.41
1
Similar H NMR spectra were obtained for meta-
3.93, 4.11
4.85
derivative IVc and ortho-derivative IVd. The chemical
shifts of protons on the 4,5-dihydrooxazole ring are al-
most the same for all the isomers while the protons of
the aromatic ring are strongly influenced by the posi-
tion of the electron-donor group. The chemical shifts
of the phenolic protons depend on the position of the
OH group on the aromatic ring due to the mesomeric
effect that can be applied.
4.92
4.89
290
—
a) Data for ν(C N), b) data for λmax (π–π*) and measured
—
in ethanol (c = 5 × 10−5 M), c) data for log εmax; λmax
–
wavelength of the absorbance maximum, εmax – extinction co-
efficient of absorbance maximum.
The synthesis of IVe started with 4-(methoxycarbo-
nyl)cinnamic acid (Ie) and consisted of the stan-
dard procedures for the preparation of the 4,5-
dihydrooxazole ring (Fig. 1). The structure of IVe
the E-isomer. The signal of the carboxyl group is low-
field shifted to δ 13.05 in comparison with the phe-
nolic proton in benzoic acid (δ 12.35) (Wu et al.,
2010). This indicates that the electron-withdrawing
4,5-dihydrooxazole ring increases the acidity of the
carboxylic group. A further possible explanation of
the enhanced acidity of hydrogen of the carboxylic
group posits the formation of a hydrogen bond with a
4,5-dihydrooxazole ring.
1
was confirmed by NMR spectroscopy. In the H NMR
spectrum of IVe, two triplets with δ 3.90 and 4.35
are assigned to the protons of the 4,5-dihydrooxazole
group and two bands with δ 6.90 and 7.40 to the
unsaturated bond. The value of the interaction con-
stant (J = 16.0 Hz) indicates that derivative IVe is
As stated above, another approach for the prepa-

J. Kronek et al./Chemical Papers 67 (11) 1424–1432 (2013)
Table 3. Chemical shifts (δ) of IVb in different solvents
1429
Chemical shifta/δ
Solvent
H-1
H-2
H-3
H-4
H-5
H-6
OH
THF-d8
DMSO-d6
CD3OD
6.73
6.77
6.80
6.92
7.35
7.46
7.33
7.58
7.23
7.21
7.40
7.82
6.44
6.50
6.43
6.79
3.85
3.85
3.91
4.20
4.21
4.25
4.38
4.98
8.71
9.81
–
CD3COOD
–
a) For atom numbering see Fig. 1.
Table 4. Dependence of wavelength of the longest absorption maximum (λabs) and decadic logarithm of extinction coefficient
(log εmax) of IVb on the dielectric constant (ε) of solvent used
Solvent
λabs/nm
log εmax
εa
Toluene
Chloroform
Ethyl Acetate
THF
Ethanol
Methanol
DMF
308
309
308
309
312
312
312
314
4.27
4.37
4.36
4.35
4.45
4.40
4.36
4.37
2.4
5.5
6.0
7.5
24.3
33.0
38.3
47.2
DMSO
a) Dielectric constants measured at 25◦C.
ration of functional 4,5-dihydrooxazoles is based on
the esterification reaction of cinnamic acid derivatives
and functional 4,5-dihydrooxazoles. In this manner,
IIe reacted with 4,5-dihydrooxazole VIa or VIb in the
presence of an equimolar amount of triethyl amine
(Fig. 3). Surprisingly, the yields of esterifications were
relatively low in both cases (51 % and 48 %, respec-
tively). The ortho-isomer does not provide a reaction
with IIe this can be ascribed to the existence of the hy-
drogen bond between phenolic hydrogen and nitrogen
of 4,5-dihydrooxazole (Langer et al., 2005).
The presence of two polar groups in the molecule
connected by a conjugated system significantly influ-
ences the properties of all groups in the molecule of
such compounds. The dependence of the 1H NMR
spectrum of IVb on a solvent polarity can be seen
1
in Table 2. The H NMR spectrum was measured in
four different solvents of different polarities. The high-
est change in chemical shift (∆δ) is approximately 0.2
for aromatic protons, but more than δ 1 for phenolic
proton. In the case of deuterated acetic acid, protona-
tion of an oxazoline ring causes higher changes in ∆δ
of methylene protons near to the protonated nitrogen
atom (Table 3).
All the prepared compounds were characterised
by UV-VIS spectroscopy. In all cases, the absorption
maximum can be found in the range of 297–325 nm
and can be assigned to the π–π∗ transition of the E-
isomer (Fig. 4). These values correspond to the wave-
lengths of the absorption maxima of stilbene and cin-
namoyl derivatives (Creed et al., 2001; Kwasniewski et
al., 2001). The shape of the spectrum and the wave-
length of the absorption maximum depend on the
Fig. 4. UV-VIS spectra of compounds IVa–IVd (a) and IVa,
IVe, VIb (b) measured in ethanol at concentration of
5 × 10−5 mol L−1
.

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J. Kronek et al./Chemical Papers 67 (11) 1424–1432 (2013)
Table 5. Spectral data of newly prepared compounds
Compound
Spectral data
1H NMR (DMSO-d6, 400 MHz), δ: 2.28 (s, 3H, CH3COO), 3.51–3.56 (m, 2H, N—CH2), 3.68 (t, 2H, J = 5.8 Hz,
IIIb
—
—
CH2Cl), 6.64 (d, 1H, J = 15.9 Hz, CH—CO), 7.18 (d, 2H, J = 8.2 Hz, H-ar), 7.46 (d, 1H, J = 15.8 Hz, Ph—CH ),
—
—
7.61 (d, 2H, J = 8.2 Hz, H-ar), 8.37 (bp, 1H, CONH)
13C-NMR (DMSO-d6, 100 MHz), δ: 20.8, 40.9, 43.4, 121.9, 122.4, 128.7, 132.5, 138.2, 151.3, 165.2, 169.0
IIIc
1H NMR (DMSO-d6, 400 MHz), δ: 2.29 (s, 3H, CH3COO), 3.51 (t, 2H, N—CH2), 3.68 (t, 2H, CH2Cl), 6.63 (d, 1H,
—
—
—
CH–CO), 7.15 (d, 1H, H-ar), 7.34 (s, 1H, H-ar), 7.44 (d, 1H, Ph—CH ), 7.46–7.48 (m, 2H, H-ar), 8.37 (t, 1H,
—
CONH)
13C NMR (DMSO-d6, 100 MHz), δ: 20.9, 41.0, 43.5, 120.7, 122.9, 123.0, 125.2, 130.1, 136.5, 138.2, 151.0, 165.1,
169.2
IIId
1H NMR (DMSO-d6, 400 MHz), δ: 2.04 (s, 3H, CH3), 3.48 (q, 2H, J = 7.6 Hz, CH2N), 3.66 (t, 2H, J = 7.7 Hz,
—
CH2Cl), 6.71 (d, 1H, J = 15.6 Hz, CH ), 6.81 (t, 1H, J = 7.1 Hz, H-ar,), 6.88 (d, 2H, J = 8.2 Hz, H-ar,), 7.16 (t,
—
—
—
1H, J = 7.5 Hz, H-ar), 7.41 (d, 1H, J = 7.6 Hz, H-ar), 7.63 (d, 1H, J = 15.8 Hz, CH ), 8.43 (bs, 1H, NH)
13C NMR (DMSO-d6, 100 MHz), δ: 20.7, 40.9, 43.4, 116.1, 119.2, 121.1, 121.4, 128.3, 130.4, 135.0, 156.4, 165.9,
169.8
IIIe
IVb
IVc
1H NMR (DMSO-d6, 400 MHz), δ: 3.50 (q, 2H, J = 5.9 Hz, N—CH2), 3.67 (t, 2H, J = 6.1 Hz, ClCH2), 3.83 (s,
—
—
3H, OCH3), 6.78 (d, 1H, J = 15.9 Hz, —CH ), 7.48 (d, 1H, J = 15.9 Hz, —CH ), 7.68 (d, 2H, J = 8.2 Hz, H-ar),
—
—
7.95 (d, 2H, J = 8.2 Hz, H-ar), 8.81 (bp, 1H, CONH)
13C NMR (DMSO-d6, 100 MHz), δ: 43.7, 46.2, 54.9, 127.1, 130.5, 132.4, 132.7, 140.5, 142.1, 167.6, 168.5
1H-NMR (DMSO-d6, 400 MHz), δ: 3.84 (t, 2H, J = 9.2 Hz, N—CH2), 4.25 (t, 2H, J = 9.4 Hz, CH2O), 6.48 (d, 1H,
—
—
—
J = 16.4 Hz, CH—CO), 6.77 (d, 2H, J = 8.5 Hz, H-ar), 7.21 (d, 1H, J = 16.2 Hz, Ph—CH ), 7.44 (d, 2H, J =
—
8.0 Hz, H-ar), 10.13 (s, 1H, ArOH)
13C-NMR (DMSO-d6, 100 MHz), δ: 54.4, 66.5, 111.5, 115.8, 125.6, 129.2, 139.2, 159.4, 163.2
1H NMR (DMSO-d6, 400 MHz), δ: 2.29 (s, 3H, CH3COO), 3.51 (t, 2H, N—CH2), 3.68 (t, 2H, CH2Cl), 6.63 (d, 1H,
—
—
—
CH—CO), 7.15 (d, 1H, H-ar), 7.34 (s, 1H, H-ar), 7.44 (d, 1H, Ph—CH ), 7.46–7.48 (m, 2H, H-ar), 8.37 (t, 1H,
—
CONH)
13C NMR (DMSO-d6, 100 MHz), δ: 20.9, 41.0, 43.5, 120.7, 122.9, 123.0, 125.2, 130.1, 136.5, 138.2, 151.0, 165.1,
169.2
IVd
IVe
VIa
1H NMR (DMSO-d6, 400 MHz), δ: 3.84 (t, 2H, J = 9.1 Hz, CH2N), 4.27 (t, 2H, J = 9.6 Hz, CH2O), 6.72 (d, 1H,
—
J = 16.6 Hz, CH ), 6.80 (t, 1H, J = 7.1 Hz, H-ar), 6.95 (d, 1H, J = 8.2 Hz, H-ar), 7.17 (t, 1H, J = 7.7 Hz, H-ar),
—
—
7.51–7.55 (m, 2H, CH CH, H-ar), 10.04 (bs, 1H, OH)
—
13C NMR (DMSO-d6, 100 MHz), δ: 54.4, 66.5, 114.5, 116.0, 119.3, 121.5, 127.9, 130.5, 134.6, 156.0, 163.3
1H NMR (DMSO-d6, 400 MHz), δ: 3.90 (t, 2H, J = 9.4 Hz, N—CH2), 4.35 (t, 2H, J = 9.5 Hz, OCH2), 6.90 (d, 1H,
—
—
—
J = 16.5 Hz, —CH ), 7.40 (d, 1H, J = 16.5 Hz, —CH ), 7.75 (d, 2H, J = 8.5 Hz, H-ar), 7.95 (d, 2H, J = 8.5 Hz,
—
H-ar), 13.05 (s, 1H, COOH)
13C NMR (DMSO-d6, 100 MHz), δ: 54.7, 67.5, 117.8, 127.6, 129.7, 131.2, 138.0, 139.1, 162.7, 166.9
1H NMR (CDCl3, 400 MHz), δ: 3.92 (s, 3H, OCH3), 4.18 (t, 2H, J = 9.5 Hz, N—CH2), 4.45 (t, 2H, J = 9.5 Hz,
—
OCH2), 6.72 (d, 1H, J = 16.0 Hz, —CH ), 7.25 (d, 2H, J = 8.8 Hz, H-ar), 7.65 (d, 2H, J = 8.5 Hz, H-ar), 7.90 (d,
—
—
—
1H, J = 16.0 Hz, —CH ), 8.00 (d, 2H, J = 8.5 Hz, H-ar), 8.10 (d, 2H, J = 8.5 Hz, H-ar)
13C NMR (CDCl3, 100 MHz), δ: 52.5, 55.2, 68.0, 119.6, 121.7, 125.8, 128.4, 129.7, 130.4, 132.0, 138.4, 145.5, 153.1,
163.9, 164.8, 166.5
VIb
1H NMR (CDCl3, 400 MHz), δ: 3.95 (s, 3H, OCH3), 4.10 (t, 2H, J = 9.5 Hz, NCH2), 4.45 (t, 2H, J = 9.5 Hz,
—
OCH2), 6.70 (d, 1H, J = 16.5 Hz, —CH ), 7.35 (d, 2H, J = 8.0 Hz, H-ar), 7.45 (t, 1H, J = 8.0 Hz, H-ar), 7.65 (d,
—
—
—
2H, J = 8.0 Hz, H-ar), 7.75 (s, 1H, H-ar), 7.85 (d, 1H, J = 7.5 Hz, H-ar), 7.90 (d, 1H, J = 16.0 Hz, —CH ), 8.10
(d, 2H, J = 8.5 Hz, H-ar)
13C NMR (CDCl3, 100 MHz), δ: 52.1, 55.0, 68.0, 119.5, 121.6, 124.7, 125.7, 128.4, 129.7, 129.8, 130.4, 132.1, 138.3,
145.7, 150.7, 164.0, 164.6, 166.5
functional groups on the aromatic rings (Fig. 4, Ta-
ble 2). The phenolic group is an electron-donor and
shifts the absorption maximum to the higher wave-
lengths while the electron-acceptor carboxylic and
methoxycarbonyl groups shift the absorption maxi-
mum to lower values.
The solvatochromic properties of IVb were also
proved by UV-VIS spectra. The measurements were

J. Kronek et al./Chemical Papers 67 (11) 1424–1432 (2013)
1431
carried out at ambient temperature in solvents with
different polarities (water, ethanol, methanol, ethyl
acetate, toluene, chloroform, DMF, DMSO, and tetra-
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hydrofuran) at the concentration of 5 × 10−5 mol L−1
.
The UV-VIS spectra were batochromically shifted
with a higher dielectric constant of the solvent used
(Table 4).
Specral data of newly prepared compounds are
given in Table 5.
K¨onig, B., Leue, S., Horn, C., Caudan, A., Desvergne, J. P., &
Bouas-Laurent, H. (1996). Synthesis of medium size macro-
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Conclusions
4,5-Dihydrooxazoles containing an unsaturated
bond and another functional group have possible ap-
plications in different organic, photochemical, and
polymerisation processes. For their preparation, two
different synthetic approaches were employed. The
first represents formation of the 4,5-dihydrooxazole
ring as the last step of a synthesis beginning from
an aromatic carboxylic acid including protection
and deprotection of the other functional groups.
Three derivatives were prepared from hydroxycin-
namic acids, including protection of their phenolic
groups. The second approach is based on the reac-
tion of 4,5-dihydrooxazole derivatives containing a hy-
droxyl group with cinnamoyl chlorides. These two ap-
proaches can be utilised in a wide spectrum of cin-
namoyl moiety containing 4,5-dihydrooxazole deriva-
tives and can also be used for the introduction of fur-
ther reactive centres to the molecule.
Kronek, J., Lustoň, J., & B¨ohme, F. (1998b). Syntéza 2-
oxazolínov ako účinných činidiel
v organickej syntéze a
monomérov pre makromolekulovú chémiu. Chemické Listy,
92, 175–185. (in Slovak)
Kronek, J., Lustoň, & J., B¨ohme, J. (2002). New materials
with high π conjugation by reaction of 2-oxazoline contain-
ing phenols with polyamidines and inorganic base. Macro-
molecular Symposia, 187, 427–436. DOI: 10.1002/1521-
3900(200209)187:1<427::aid-masy427>3.0.CO;2-9.
Kwasniewski., S. P., Fran¸cois, J. P., & Deleuze, M. S. (2001).
Temperature effects on the UV–Vis electronic spectrum of
trans-stilbene. International Journal of Quantum Chem-
istry, 85, 557–568. DOI: 10.1002/qua.10016.
Langer, V., Koóš, M., Gyepesová, D., Sládkovičová, M., Lus-
toň, J.,
& Kronek, J. (2005). Three isomeric forms of
hydroxyphenyl-2-oxazoline: 2-(2-hydroxyphenyl)-2-oxazoline,
2-(3-hydroxyphenyl)-2-oxazoline and 2-(4-hydroxyphenyl)-2-
oxazoline. Acta Crystallographica Section C, 61, o602–o606.
DOI: 10.1107/s0108270105027812.
Lustoň, J., Kronek, J., B¨ohme, J., & Komber, H. (1999a).
Synthesis of bis-2-oxazolines containing inner unsaturation
and their hydrolysis to phenylenediacrylic acids. Designed
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Acknowledgements. The authors wish to express their
thanks to the Agency of the Ministry of Education and the Slo-
vak Academy of Sciences for the financial support received in
project no. 2/0151/12. The research was performed within the
frame of the Centre of Excellence GLYCOMED.
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oxazolines containing allyl groups by phase transfer catal-
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cieties, September 3–6, 2001. Banská Bystrica, Slovakia: Slo-
vak Chemical Society.
Lustoň, J., Kronek, J., & B¨ohme, F. (2006). Synthesis and poly-
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homopolyaddition of AB type hydroxyphenyl substituted 2-
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